What are lymph nodes and where are they located in the body. How do lymph nodes filter lymph fluid and fight infections. What is the connection between lymph nodes and cancer detection. How do doctors examine lymph nodes to diagnose diseases.

What Are Lymph Nodes and Their Function?

Lymph nodes are small, bean-shaped structures that play a crucial role in the body’s immune system. They act as filters for lymph fluid, which contains waste products, bacteria, viruses, and other harmful substances. Lymph nodes contain white blood cells called lymphocytes that help fight infections and diseases.

The primary functions of lymph nodes include:

• Filtering lymph fluid to remove harmful substances
• Trapping and destroying bacteria, viruses, and other pathogens
• Producing and storing lymphocytes and other immune cells
• Initiating immune responses to fight infections
• Serving as an early warning system for detecting cancer spread

Where Are Lymph Nodes Located in the Body?

Lymph nodes are distributed throughout the body in specific locations. The major groups of lymph nodes are found in the following areas:

• Neck (cervical lymph nodes)
• Armpits (axillary lymph nodes)
• Groin (inguinal lymph nodes)
• Chest (mediastinal lymph nodes)
• Abdomen (mesenteric lymph nodes)

Each group of lymph nodes drains lymph fluid from specific regions of the body. For example, cervical lymph nodes drain fluid from the head and neck, while axillary lymph nodes drain the upper limbs and chest.

How Many Lymph Nodes Are in the Human Body?

The human body contains approximately 600 lymph nodes. However, the exact number can vary from person to person. Some of the largest clusters of lymph nodes are found in the neck, armpits, and groin areas.

The Lymphatic System: An Overview

The lymphatic system is a network of vessels, tissues, and organs that works alongside the circulatory system to maintain fluid balance and support immune function. Key components of the lymphatic system include:

• Lymph vessels
• Lymph nodes
• Lymphoid organs (spleen, thymus, tonsils)
• Lymph fluid

Lymph fluid is a clear, colorless liquid that contains white blood cells, proteins, and other substances. It circulates through the lymphatic vessels, passing through lymph nodes where it is filtered and cleansed before returning to the bloodstream.

How Do Lymph Nodes Filter Lymph Fluid?

The filtering process in lymph nodes is a complex and efficient mechanism. Here’s how it works:

1. Lymph fluid enters the lymph node through afferent lymphatic vessels.
2. The fluid passes through a network of sinuses within the node.
3. Specialized cells in the node, including macrophages and dendritic cells, capture and process foreign particles, bacteria, and other harmful substances.
4. Lymphocytes in the node examine these processed substances and initiate immune responses if necessary.
5. Filtered lymph fluid exits the node through efferent lymphatic vessels.

This filtering process helps remove harmful substances from the lymph fluid before it returns to the bloodstream, protecting the body from infections and diseases.

Can Lymph Nodes Become Enlarged?

Yes, lymph nodes can become enlarged or swollen in response to various conditions. This swelling, known as lymphadenopathy, is often a sign that the immune system is actively fighting an infection or disease. Common causes of swollen lymph nodes include:

• Viral or bacterial infections
• Immune system disorders
• Certain medications
• Cancer

While swollen lymph nodes are usually not a cause for concern, persistent or widespread swelling should be evaluated by a healthcare professional.

The Role of Lymph Nodes in Cancer Detection and Treatment

Lymph nodes play a crucial role in cancer detection, staging, and treatment. Cancer cells can spread from their original site to nearby lymph nodes through the lymphatic system, a process known as lymphatic metastasis.

Doctors use various methods to examine lymph nodes for cancer involvement:

• Physical examination: Feeling for enlarged or hard lymph nodes
• Imaging studies: CT scans, MRI, or PET scans to visualize lymph nodes
• Sentinel lymph node biopsy: Removing and examining the first lymph node(s) where cancer is likely to spread
• Lymph node dissection: Surgically removing and examining multiple lymph nodes

The presence or absence of cancer cells in lymph nodes helps determine the stage of cancer and guides treatment decisions. In some cases, such as in lymphomas, cancer may originate in the lymph nodes themselves.

How Do Doctors Use Lymph Nodes to Stage Cancer?

Cancer staging often involves evaluating lymph nodes. The TNM staging system, widely used for many types of cancer, includes a specific component for lymph node involvement:

• N0: No cancer in nearby lymph nodes
• N1, N2, N3: Increasing levels of lymph node involvement

The more lymph nodes affected by cancer, the higher the stage and potentially the more aggressive the treatment needed.

Lymph Node Disorders and Diseases

While lymph nodes are crucial for maintaining health, they can also be affected by various disorders and diseases. Some common lymph node-related conditions include:

Lymphadenitis

Lymphadenitis is the inflammation of lymph nodes, usually due to infection. It can be acute (short-term) or chronic (long-term). Symptoms may include swollen, tender lymph nodes and fever.

Lymphoma

Lymphoma is a type of cancer that originates in the lymphatic system. There are two main types:

• Hodgkin lymphoma
• Non-Hodgkin lymphoma

Symptoms can include swollen lymph nodes, fever, night sweats, and unexplained weight loss.

Lymphedema

Lymphedema is a condition characterized by swelling in the arms or legs due to a blockage in the lymphatic system. It can be primary (inherited) or secondary (caused by damage to lymph nodes, often from cancer treatment).

Maintaining Lymph Node Health

While you can’t directly control your lymph nodes, you can support overall lymphatic system health through lifestyle choices:

• Stay hydrated to help lymph fluid flow smoothly
• Exercise regularly to promote lymph circulation
• Maintain a healthy diet rich in fruits, vegetables, and lean proteins
• Practice good hygiene to prevent infections
• Manage stress through relaxation techniques

These habits can help support your lymphatic system and overall immune function.

Advanced Research and Future Directions in Lymph Node Studies

Ongoing research in lymph node biology and function is opening new avenues for disease diagnosis and treatment. Some exciting areas of study include:

Lymph Node Mapping in Cancer

Researchers are developing more precise techniques for mapping lymphatic drainage patterns. This could lead to more accurate cancer staging and targeted treatments.

Immunotherapy and Lymph Nodes

Scientists are exploring ways to harness the immune functions of lymph nodes to enhance cancer immunotherapy treatments. This could potentially improve the body’s ability to fight cancer cells.

Artificial Lymph Nodes

Bioengineers are working on creating artificial lymph nodes. These could potentially be used to boost immune responses in individuals with compromised lymphatic systems.

Lymphatic System Imaging

New imaging techniques are being developed to visualize the lymphatic system in greater detail. This could aid in the early detection of lymphatic disorders and cancers.

As our understanding of lymph nodes and the lymphatic system continues to grow, we can expect to see advancements in diagnostic techniques, treatment strategies, and overall patient care.

In conclusion, lymph nodes are vital components of our immune system, playing crucial roles in fighting infections and detecting the spread of cancer. Their complex structure and function make them essential subjects of study in both health and disease. As research progresses, our ability to leverage the lymphatic system for improved health outcomes will undoubtedly expand, offering hope for better treatments and prevention strategies in the future.

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What are lymph nodes?

Lymph nodes (or lymph glands) are small lumps of tissue that contain white blood cells, which fight infection. They are part of the body’s immune system and filter lymph fluid, which is composed of fluid and waste products from body tissues. They help fight infections, and also play an important role in cancer diagnosis, treatment and the chance of recovery or recurrence.

Where are lymph nodes located?

Lymph nodes are located throughout the body, including the neck, armpits, groin, around the gut, and between the lungs. Lymph nodes drain lymph fluid from nearby organs or areas of the body.

How do lymph nodes filter lymph fluid?

Lymph fluid is carried to the lymph nodes by lymphatic vessels. The lymph nodes filter out harmful substances and waste products. They also contain immune cells called lymphocytes that destroy cancer cells and bacteria.

The filtered fluid is then returned to the blood circulation.

If you have an infection or cancer, a lymph node may become swollen. If you are concerned about your lymph nodes, speak to your doctor.

Lymph nodes are located throughout the body. They drain lymph fluid from nearby organs or areas of the body.

How are lymph nodes and cancer related?

Sometimes cancer can start in the lymph nodes (such as in lymphoma), but some others types of cancer can also spread from one part of the body to another through lymph nodes.

If a person has cancer, doctors examine lymph nodes carefully to see whether or not they are affected by cancer. They can do this by:

• feeling all the nodes in the body
• getting scans, for example a CT scan
• removing nodes near the cancer, then examining them under a microscope
• taking a biopsy of the lymph nodes near the cancer, then examining them under a microscope

This is done to see if the cancer has spread or not. This helps doctors work out the best treatment for the cancer.

Having swollen lymph nodes is only very rarely a sign of cancer. Lymph nodes may be swollen due to infection or inflammation. Swollen lymph nodes may be in the neck, under the arm or anywhere else there are lymph nodes. They can swell up to several centimetres and may stay swollen for weeks after the infection has cleared up.

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Last reviewed: January 2021

Histopathology of the Lymph Nodes

Abstract

Lymph nodes function as filters of tissues and tissue fluids and are sites of origin and production of lymphocytes for normal physiological functions. As part of this normal function, they react to both endogenous and exogenous substances with a variety of specific morphological and functional responses. Lesions can be both proliferative and nonproliferative, and can be treatment-related or not. The histological evaluation of lymph nodes is necessary in order to understand the immunotoxic effects of chemicals with the resulting data providing an important component of human risk assessment. It is the challenge of the toxicologic pathologist to interpret the pathology data within the complete clinical evaluation of the entire animal. Daily insults, ageing and toxins can alter the normal histology and primary function of lymph nodes. Therefore it is important to distinguish and differentiate lesions that occur naturally during normal development and ageing from those that are induced by xenobiotics. To achieve this goal, comparison with strain- age- and sex-matched controls is crucial.

Keywords: Lymph node, immunotoxic, xenobiotic, hyperplasia, angiectasis, lymphoma

Introduction

The lymph nodes are organized lymphoid organs that contain lymphocytes within a fine reticular stroma. The structures within a lymph node include the capsule, subcapsular sinus, cortex (B cell zone with follicles and germinal centers), paracortex (T cell zone), medullary sinuses, medullary cords and hilus. In order to ensure that all of these components are evaluated, particular attention should be paid to tissue collection and orientation. Lymph nodes should routinely be examined grossly and microscopically since they may reflect lesions in organs and tissues they drain. Moreover, special attention should be given to lymph nodes that are more likely to be exposed to a test compound (Haley et al., 2005; Ruehl-Fehlert et al., 2005). The bronchial and mediastinal lymph nodes should be examined for compounds administered via inhalation whereas orally administered compounds would most likely affect the mandibular (superficial cervical) and mesenteric lymph nodes. For dermal or subcutaneous exposures, the most proximal draining peripheral node or nodes (auricular, axillary, inguinal and popliteal) should be examined.

The range of normal histological findings within groups of lymph nodes due to normal immune functions should also be considered. For example, sinus histiocytosis is a normal finding in mesenteric lymph nodes and the macrophages may contain endogenous pigment (hemosiderin, lipofuscin) or exogenous pigments reflecting antigen uptake from the digestive tract. The mandibular lymph nodes are exposed to antigens from the oropharyngeal region and will typically have well-developed secondary follicles and considerable numbers of plasma cells within the medullary cords. For systemic effects of compounds, examination of lymph nodes distal to the site of application may provide additional information. Unless draining a site of application, the popliteal and axillary lymph nodes are often not stimulated and can give information on the resting state of the lymph node. However these lymph nodes can be highly variable, small and difficult to adequately sample. It is also useful to have knowledge of the regions drained by specific nodes for determining the origin of metastatic neoplasms. Detailed information on the location of specific lymph nodes and patterns of lymphatic drainage in the rat are described by Tilney (1971) and Sainte-Marie et al. (1982). Information on anatomy and nomenclature of murine lymph nodes is provided by Van den Broeck et al. (2006). Finally, a careful and detailed examination of the lymph nodes may give valuable clues to the possible mechanism of action of the test material. For a thorough description of the normal structure, function and histology of the lymph node, refer to the article by Willard-Mack (2006). For detailed information on the enhanced histopathological evaluation of the lymph node, refer to the article by Elmore (2006). The following figures and descriptions illustrate and discuss some of the typical lesions observed in lymph nodes.

Lymphoid Necrosis

Lymphoid necrosis may either be focal, multifocal or diffuse within a lymph node and there can be differences in the presence and severity of lymphoid necrosis between lymph nodes in the same animal, depending on the inciting factor and the effectiveness of the immune response. Lymphocyte necrosis is characterized by cell swelling with chromatin clumping, karyorrhexis or karyolysis and in more severe lesions, abundant eosinophilic cellular debris (). Necrosis is frequently accompanied by inflammatory cells including neutrophils and phagocytic macrophages with intracytoplasmic cellular debris (). This form of necrosis should be distinguished from apoptosis in which there is individual cell death characterized by cell shrinkage, nuclear pyknosis and fragmentation with apoptotic bodies and tingible body macrophages. This type of cell death normally occurs within the germinal centers of secondary follicles where it is an important homeostatic mechanism. Apoptosis can also be produced by a variety of injurious stimuli when given at low doses, but these same stimuli may be capable of producing necrosis at higher doses. Examples are heat, irradiation, hypoxia and cytotoxic cancer drugs (i.e., cyclophosphamide). Dexamethasone, a glucocorticoid, can also cause lymphocyte apoptosis in the lymph node, but the thymus is the more sensitive organ (Elmore, 2006).

Figures 1A–E are from the mandibular lymph node of a male cynomolgus monkey that received a test article in a four week oral gavage study with a 4-week recovery period. Figures 1A–C illustrate lymphoid necrosis within the cortex and regions of the paracortex and medulla. The areas of necrosis are eosinophilic at low magnifications (Figures 1A–B). At higher magnification (Figure 1C) the loss of lymphocytes can be seen in conjunction with eosinophilic cellular debris and dark pyknotic nuclear debris. Macrophages are the predominant inflammatory cells in this region. Figure 1D and the higher magnification in Figure 1E are from a different region of the same lymph node with a more robust inflammatory response, predominately neutrophils. Figures 1F and 1G are low and high magnifications of the mediastinal lymph node from a 90-day-old female F344 rat that was treated with a high dose of urethane. There is moderate lymphoid depletion, characterized by a decrease in the number and size of follicles with few to no germinal centers as well as depletion of paracortical lymphocytes. With a depletion of paracortical lymphocytes, the stromal cells may become more prominent, as illustrated by the arrow in Figure 1G. Photomicrographs 1A–E are courtesy of Drs. Hans Harleman and Kathryn Bowenkamp.

Lymphoid depletion or atrophy is the sequela to chronic necrosis or apoptosis. It can occur in any lymph node and there can be differences in the presence and severity of lymphoid depletion between lymph nodes in the same animal. Lymphoid depletion is typically characterized by a decrease in the number and size of follicles with few to no germinal centers and/or depletion of paracortical lymphocytes (). With a depletion of paracortical lymphocytes, the stromal cells may become more prominent ().

Massive necrosis of the lymph nodes is uncommon and may be induced by obstruction of the blood flow (infarction). This lesion is characterized by diffuse coagulation necrosis with loss of cell nuclei but, early on, with well preserved cell outlines. Caseous necrosis is also an uncommon lesion but can be produced by infection with tuberculosis organisms and fungi in nonhuman primates. It can also be seen in the centers of rapidly growing neoplasms. Grossly, there is semisolid, gray to pale yellow tissue. Microscopically, there is an amorphous mass of granular eosinophilic material with no cell outlines as well as no identifiable nuclei.

Lymphatic Sinus Ectasia

Lymphatic sinus ectasia can involve both the medullary and subcapsular sinuses. Diffuse sinus ectasia is typically associated with lymphoid atrophy. This lesion can be found in control animals, especially in the mesenteric and mediastinal lymph nodes of ageing mice. is an example of medullary sinus ectasia. This lesion is characterized by the presence of dilated or cystic sinuses lined by lymphendothelium and filled with pale eosinophilic/amphophilic material (presumably lymph) that has a delicate lacy appearance (). A few lymphocytes, plasma cells and macrophages can be found admixed with the lymph.

This is an example of medullary sinus ectasia from a control 2-year-old female F344 rat. The low magnification image shows a large ectatic medullary sinus (Figure 2A). At higher magnification the lymphendothelium lining the sinus can be visualized (arrow, Figure 2B). The pale eosinophilic lymph that fills the dilated sinus has a delicate lacy appearance (Figure 2B). A few lymphocytes, plasma cells and macrophages can sometimes be found admixed with the lymph.

Synonymous names for this lesion are lymphangiectasia, lymphatic cysts, cystic lymphatic ectasia and sinus dilatation. A group of pathologists that are associated with the National Toxicology Program were surveyed for the preferred terminology for this lesion. The 2 favored terms were “lymphatic sinus ectasia” and “lymphangiectasia.” Lymphatic sinus ectasia more clearly defines the lesion location.

Vascular Lesions

When defining vascular lesions in the lymph node, various terminologies can be used, each with a very specific definition. Angiectasis is defined in Dorland’s Medical Dictionary as “abnormal, usually gross dilatation and often lengthening of a blood vessel or lymphatic” and its synonyms are hemangiectasis, hemangiectasia, vasodilation and vasodilatation. In the lymph node, blood vessel angiectasis is characterized by the dilatation and congestion of thin veins within the cortex, medulla, capsule, hilus or surrounding connective tissue. Angiectasis is most often seen in the mesenteric lymph nodes of rats and mice, including the B6C3F1 strain and may or may not be accompanied by hemorrhage (Ward et al., 1999). This lesion can be distinguished from a hematoma by the presence of endothelial lining cells and from early hemangioma by the absence of large neoplastic endothelial cells.

Intrasinusoidal erythrocytes (sinus erythrocytosis) can result from a lymph node draining a region of hemorrhage. This can also be an artifact that results from euthanasia or tissue dissection during necropsy, especially in the bronchial or mediastinal lymph nodes. The trimming and sectioning of lymph node tissue can also dislodge erythrocytes from congested blood vessels, which can then appear in the sinusoids or in the perinodal region (). Lymph nodes draining sites of hemorrhage can also have intrasinusoidal erythrocytes but, depending on chronicity, they can be accompanied by variable numbers of hemosiderin-laden macrophages, erythrophagocytosis and inflammatory cells ().

Figures 3A and 3B are images of the bronchial lymph node of a control 3-month-old Sprague–Dawley rat. The trimming and sectioning of this tissue dislodged erythrocytes from congested blood vessels which then appeared in the sinusoids (Figure 3A, short arrow and Figure 3B) and in the perinodal region (Figure 3A, long arrow). Figures 3C and 3D are images of the mediastinal lymph node from a 3-month-old Wistar rat with a lesion of pulmonary hemorrhage. In this case the chronic nature of the lesion is indicated by the presence of erythrophagocytosis and hemosiderin-laden macrophages (Figure 3D). Figures 3E–H are images of lymph nodes from mice with dilated vascular spaces filled with red blood cells. In this case it is difficult to differentiate lymph node angiectasis from moderate to marked sinus erythrocytosis because dilated and blood filled lymphatic vessels can resemble dilated blood vessels. They are both lined by flattened cells and both occur throughout the lymph node. Evaluation of the other organ systems for congestion and a survey for regions of hemorrhage in the drainage field could help to more clearly define this lesion. Figures 3I–L are images of the mesenteric lymph node from a 24-month-old male B6C3F1 mouse treated with a high dose of N-methylolacrylamide. This lymph node has a range of lesions that includes nodal and perinodal angiectasia with congestion (Figures 3I–K), sinus erythrocytosis (Figures 3I–J), perinodal vascular proliferation with angiectasis and congestion (Figure 3K) and hemorrhage within the nodal parenchyma (Figure 3L). Figures 3M–P are images of the mesenteric lymph nodes from two 24-month-old male B6C3F1 mice that were treated with a high dose of methylimidazole. There are blood-filled vascular spaces (blood vessels and/or lymphatics) throughout both of the lymph nodes. There are also congested arterioles in the surrounding tissue of one lymph node (Figure 3M) and perivascular hemorrhage associated with an arteriole in the perinodal adipose tissue of the other lymph node (Figures 3O–P). Figures 3E and 3F photomicrographs are courtesy of Drs. C. Frith and J. Ward. Figures 3G and 3H photomicrographs are courtesy of Dr. Michael Leach.

Lesions of lymph node vascular angiectasis can be difficult to differentiate from moderate to marked sinus erythrocytosis because dilated blood vessels can resemble dilated and blood-filled lymphatic vessels. Both are lined by flattened cells and both occur throughout the lymph node. In trying to resolve this issue, a more holistic diagnostic approach could be taken. For example, evaluation of the other organ systems for congestion could rule in/out blood vessel congestion as a possible diagnosis. A survey for regions of hemorrhage in the drainage field for the node could help to rule in/out sinus erythrocytosis. are examples of blood-filled vascular spaces that would require this type of holistic approach to more clearly define the lesion.

A wide range of vascular lesions in treated animals can include sinus congestion, sinus erythrocytosis, nodal and perinodal angiectasia with congestion, hemorrhage within the nodal parenchyma, perinodal vascular proliferation, and perivascular hemorrhage (). The diagnosis of treatment-related vascular lesions in the lymph node should be made with consideration of the animal’s overall health status and the presence or absence of vascular lesions in other organs and tissues. A survey of lesion terminology for the two lymph nodes in was obtained from a group of pathologists. Without any prior knowledge of treatment-related lesions and pathogenesis of the lymph node lesions in these mice, there was disagreement as to the most appropriate terminology. Sinus erythrocytosis and congestion emerged as the two favored terms. However, most agreed that information on other organs, potential areas of hemorrhage in the drainage field and time from death to necropsy were needed in order to make an accurate diagnosis.

Telangiectasia and angiomatosis are two terms that would not typically be used to define the lesions of vascular ectasia in the rodent lymph node because in human medicine they are terms that define neoplastic lesions. Telangiectasia is defined as “an abnormal dilatation of capillary vessels and arterioles that often forms an angioma” and angiomatosis is defined as “a diseased state of the vessels with the formation of multiple angiomas. ” An angioma is considered a tumor that is made up of chiefly blood or lymph vessels. However, when blood-filled vessels are present in the lymph node, it is important to distinguish them from vascular tumors such as hemangiomas and hemangiosarcomas.

Pigment

Pigment is a common finding within the cytoplasm of sinusoid macrophages in both control and treated animals. The most common pigments are hemosiderin and ceroid/lipofusin. Hemosiderin is an iron-containing golden brown granular material and macrophages containing this pigment are most likely found within the medullary cords and lymphatic sinuses of nodes with sinus erythrocytosis. Lipofuscin is also a golden brown, finely granular pigment but it is derived chiefly from the breakdown products of lipids, usually those derived from cell membranes. Ceroid is a variant of lipofuscin that is acid-fast and autofluorescent. The numbers of hemosiderin- or ceroid/lipofuscin-laden macrophages can be increased with associated macrophage hyperplasia in nodes draining various lesions (inflammatory, necrotic, neoplastic, etc. ). These pigments are difficult to distinguish from each other with a conventional hematoxylin and eosin stain. In order to differentiate the two, an iron stain (Perl’s iron stain, Prussian blue reaction) can be used to stain hemosiderin blue. A variety of stains and methods can be used to identify ceroid/lipofuscin including Sudan Black B, Schmorl’s reaction, Oil red O, carbol lipofuscin stain, Periodic acid-Schiff, Ziehl-Neelsen acid fast stain, autofluorescence or the lysosomal acid phosphatase and esterase stains. Melanin is another endogenous pigment that can be found within lymph nodes. This is a normal finding in black-skinned mice and is not considered a lesion. For positive identification of melanin, Schmorl’s method can be used which stains the melanin granules blue-green. DOPA-oxidase is an enzyme histochemical method that can also be used and is very specific for melanin.

A variety of inhaled, ingested, injected, and topically applied chemicals can induce sinus histiocytosis in associated lymph nodes with macrophages that contain inert or insoluble pigmented test substance (Goginpath et al. , 1987). Tail tattoo pigment, which is inert and non-polarizable, can sometimes be found as aggregates of scattered brown/black material in the lymph nodes adjacent to the tattoo. Regional lymph nodes draining test article application sites should always be inspected for the presence of exogenous pigments () but the parent compound, or its metabolite, can sometimes localize in specific tissues in the body ().

Figures 4A and 4B are low and high images of a mediastinal lymph node from a male F344 rat treated with 2.5 mg of nickel oxide. Note the minimal scattered aggregates of brown/black pigment and associated lymphoid hyperplasia. Figures 4C–F are from a 2-year-old female F344 rat that received a high dose of 2,4 diaminophenol 2 HCL. The pancreatic lymph node contains a finely granular brown pigment (Figures 4C–D) that was negative for iron. This material was presumed to be the parent compound or its metabolite. The same pigment was present in the lamina propria of the duodenum (Figures 4E–F). Figures 4G–I are images of the bronchial lymph node from a 2-year-old female F344 rat that received a low dose of molybdenum trioxide. Although the red blood cells are difficult to see in these images, there is sinus erythrocytosis, erythrophagocytosis and intra-histiocytic accumulations of a golden brown globular pigment consistent with hemosiderin.

Amyloidosis

With the light microscope and hematoxylin and eosin stain, amyloid appears as amorphous, eosinophilic and hyalinized extracellular material. With large accumulations, amyloid will encroach on adjacent tissue causing pressure atrophy. Congo red is the most common stain used to evaluate amyloid, imparting an apple-green birefringence when polarized. Amyloidosis occurs in a number of strains of mice and other rodents, but is not seen in the lymph nodes of rats. Amyloidosis occurs in a low incidence in most mouse strains but in CD1 mice, there appears to be a genetic predisposition (Frith and Chandra, 1991). Lymph node amyloidosis is more prevalent in female CD1 mice and the degree of amyloidosis increases with age with 20–30% of the lymph nodes affected by 24 months of age. In these mice, amyloid deposition occurs in a variety of tissues, including the lymph node. The mesenteric lymph node is most commonly affected and amyloid predominately accumulates within the subcapsular sinuses with progressive extension into the paracortical areas of the lymph node (). Early lesions typically occur in the periphery of the node.

These are images of lymph node amyloidosis in CD1 mice. The mesenteric lymph node is most commonly affected in this strain of mouse and amyloid predominately accumulates within the subcapsular sinuses (Figure 5A, arrows). Figures 5B and 5C illustrate the characteristic homogenous, amorphous, eosinophilic and extracellular nature of the amyloid with progressive extension into the paracortical areas of the lymph node. Figure 5D illustrates the pale eosinophilic nature of the amyloid when stained with Congo red. Photomicrographs 5A–C are courtesy of Dr. Michael Leach. Photomicrograph 5D is courtesy of Drs. C. Frith and J. Ward.

Lymphadenitis

Inflammatory cells can be found in lymph nodes draining sites of inflammation, necrosis, neoplasia, etc. or they can be the result of the administration of an irritating test compound. Inflammatory cells can also be present within a lymph node in response to primary lymphocyte necrosis. The type of lymphadenitis can vary depending on the inciting factor (foreign body, bacteria, etc.) and the response can vary from acute to granulomatous (). In acute lymphadenitis, neutrophils and immature myeloid cells can be found within the sinuses and medullary cords. Lymphoid hyperplasia or atrophy may also occur in association with nodal inflammation. Inflammatory infiltrates should be distinguished from conditions of extramedullary hematopoiesis (EMH) () and granulocytic leukemia.

With EMH, there is typically a mixture of megakaryocytes and other hematopoietic elements whereas granulocytic leukemia will have high numbers of immature myeloid cells with multiple organ involvement. The term “chronic lymphadenitis” and “granulomatous lymphadenitis” should be reserved for lymph nodes with chronic abscesses or granulomatous lesions that partially or completely efface the normal nodal architecture as opposed to increased numbers of histiocytes within the subcapsular and medullary sinuses (sinus histiocytosis) (). Abscesses may be acute or chronic and are characterized by a central region of necrosis associated with predominately neutrophils. In the later stages, they are surrounded by variable amounts of granulation tissue which can progress to fibrous connective tissue (). Pyogranulomatous lymphadenitis is characterized by an abundance of neutrophils and macrophages partially or completely effacing the normal nodal architecture.

Lymphocyte Hyperplasia

The description of reactive hyperplastic lesions, including lymphocyte hyperplasia, in rodent lymph nodes has been described (Ward, 1990). In normal rodents, lymphocyte hyperplasia may be evident to varying degrees depending on the location of the lymph node, health status of the animal, age of the animal, and plane of section of the node. Mesenteric lymph nodes, in particular, may show a wide variation in degree of reactive lymphocyte hyperplasia between animals due to stimulation by antigens in the intestinal tract. If an increase in lymphocytes is suspected to be treatment-related, then this potential for variability underscores the need to compare with control tissues. If a treatment-related effect is suspected, then enhanced histopathology may be performed to more clearly define the nature and degree of this lesion (Elmore, 2006).

Lymphocyte hyperplasia can involve both the B-cell-rich follicles and the T-cell-rich paracortex and can be indicative of a humeral or cell-mediated response, respectively (). Lymphoid hyperplasia is generally a reactive or immune response and is not considered to be a preneoplastic lesion in the lymph node. Stimulated (reactive) follicles, also called secondary follicles, are usually larger than the unstimulated primary follicles and will have a paler staining germinal center with large lymphoblasts and increased numbers of apoptotic lymphocytes and tingible body macrophages. The mantle zone surrounding the germinal center is composed of small to medium-sized darker staining B lymphocytes. Hyperplastic follicles are identified by an increase in number and size of follicles and conversion to secondary follicles. Hyperplasia of the paracortex is characterized by an increase in the cell density and, depending on the degree of hyperplasia, an increase in the paracortical area.

Figures 7A and 7B illustrate lymphoid hyperplasia with a follicular pattern in a mandibular lymph node from a 22-month-old C57bl/6 mouse. At low magnification (Figure 7A) it is difficult to determine if this is a case of lymphocyte proliferation or follicular lymphoma. However, at higher magnification (Figure 7B), the heterogeneous nature of the lymphocyte proliferation indicates hyperplasia rather than neoplasia. There are paler staining B lymphoblasts (Figure 7B, long arrow) within the follicular germinal centers interspersed with and surrounded by the smaller, more mature lymphocytes (Figure 7B, short arrow). For comparison, the mandibular lymph node from a female B6C3F1 mouse with lymphoma is depicted in Figure 7C. At higher magnification (Figure 7D) the homogeneous nature of the neoplastic lymphocytes is illustrated.

Plasma Cell Hyperplasia

Plasma cells are usually increased in number in response to antigenic stimulation that requires antibody production. Therefore B cell hyperplasia can occur simultaneously with plasma cell hyperplasia. Marked plasma cell hyperplasia, or plasmacytosis, is a common finding in rodents, particularly in the submandibular lymph nodes. The medullary cords normally contain plasma cells and their precursors as the dominant cell types and these cords are the primary sites of plasma cell hyperplasia. In cases of marked plasma cell hyperplasia the node can be greatly enlarged, composed almost entirely of plasma cells, exhibit partial effacement of normal nodal architecture, and can be difficult to differentiate from neoplasia. Findings that support hyperplasia are a lack of cortical and capsular infiltration, atypical plasma cells and metastases (). Depending on the degree and chronicity of antigenic stimulation, some plasma cells may contain Russell’s bodies. Plasma cell precursors (immunoblasts or plasmablasts) may also be present among the more mature plasma cells.

This is a peripancreatic lymph node from a 15-month-old C57bl/6 mouse with marked plasma cell hyperplasia involving the medullary and paracortical regions. Although there is marked infiltration of the medullary and paracortical regions by this population of plasma cells, the intact nature of the follicles (Figure 8B, arrows) and the uniform and differentiated cytomorphology of the plasma cells (Figure 8C) indicate that this is plasma cell hyperplasia rather than neoplasia.

Macrophage Hyperplasia

Macrophage hyperplasia usually results from proliferation of resident sinusoidal macrophages () but can also be seen as aggregates of macrophages within any region of the lymph node. Macrophage aggregates can be peripherally located around the paracortex () or within the cortical, paracortical and medullary regions (). Macrophage hyperplasia can also be a feature of lymph nodes that drain a site of test article application (). Specific patterns (intrasinusoidal, cortical, paracortical, medullary) of macrophage hyperplasia in the same node within a dose group would be consistent with a treatment-related effect.

Figure 9A is an example of a mesenteric lymph node from a female B6C3F1 mouse that was treated with a high dose of 4,4′-thiobis-(6-T-butyl-M-cresol). Note the proliferation of sinusoidal macrophages (sinus histiocytosis). However, aggregates of macrophages can also be seen within any region of the lymph node. Figures 9B–D are images of a lymph node from of a male B6C3F1 mouse treated with sodium dichromate dihydrate that illustrate macrophage aggregates peripherally located around the paracortex (arrows). Figures 9E–G are images of a lymph node from a 2-year-old F344 rat with macrophage aggregates within the cortical, paracortical and medullary regions. Figures 9H–I are images of the mesenteric lymph node from a 90-day-old male F344 rat in a subchronic elmiron study. These images illustrate a proliferation of macrophages with vacuolated cytoplasm within the medullary region. These types of hyperplasia can be a feature of lymph nodes that drain a site of test article application. Specific patterns of macrophage hyperplasia in the same node within a dose group would be consistent with a treatment related effect. Inhalation studies with particulates may result in increased accumulations of macrophages within regional draining lymph nodes. An inhalation study of talc resulted in accumulations of macrophages, most containing talc particles, in the peribronchial lymphoid tissue of the lung and in the bronchial (Figures 9J and 9K) and mediastinal lymph nodes of a 2-year-old male F344 rat. Polarization of the bronchial lymph node revealed short linear fragments of talc within the macrophage cytoplasm (Figures 9L and 9M).

Proliferation (hyperplasia) of resident macrophages can easily be confused with increased numbers of intrasinusoidal macrophages that enter through the efferent lymphatics draining an area with high numbers of macrophages. Comparison of the lesions within the lymph node with the organs and tissues that that particular node drains helps to differentiate the two. Mesenteric lymph nodes are constantly stimulated by intra-intestinal antigens and can therefore have large numbers of intrasinusoidal macrophages as well as multifocal aggregates of macrophages within the cortex and paracortex. Also, there can be considerable individual variation among animals. Comparison of a group of treated animals with control animals would help to determine if this is a treatment-related finding. Special attention should be given to lymph nodes associated with the route of administration of a test compound. For inhalation studies, bronchial and mediastinal lymph nodes should be examined and orally administered compounds may result in lesions in the submandibular and mesenteric lymph nodes. Prior knowledge of the physical and chemical properties of the test compound may help to identify phagocytized test article material. For example, insoluble particulate matter may be seen as intracytoplasmic refractile material when polarized ().

When histiocytes occur as aggregates within the sinusoids, the common term for this finding is “sinus histiocytosis.” When aggregates of histiocytes occur within the lymph node parenchyma, the terms “granulomatous inflammation,” “granulomatous lymphadenitis,” “histiocyte aggregates/infiltrates,” and “macrophage aggregates/infiltrates” have been used interchangeably. However, the degree of macrophage accumulation should help to determine if the term “granulomatous” is used. If there are histiocyte aggregates with a minimal to mild severity grade, then histiocyte or macrophage aggregates/infiltrates would be appropriate. If the severity is moderate or marked with partial or complete effacement of nodal architecture, then the term “granulomatous” would be more appropriate.

Extramedullary Hematopoiesis

Although the spleen is the principle site of extramedullary hematopoiesis (EMH) in the rodent, it can sometimes be present in the lymph node. EMH is typically a physiological response to a dramatic loss or increased need for additional blood cells from conditions such as hemorrhage or severe inflammation. It is characterized by a mixture of myelocytic, erythrocytic and megakaryocytic cells and is primarily present in the medullary cords ().

These images illustrate various types of EMH present in rodent lymph nodes. Figure 10A is an image of the mesenteric lymph node of a control male B6C3F1 mouse. Sinus erythocytosis can be seen in this low magnification image. The presence of megakaryocytes (arrows) indicates that EMH is also present. This may be in response to chronic blood loss in the body and the need for additional platelets. Figures 10B and 10C are images of the mesenteric lymph node from a 24-month-old male B6C3F1 mouse that was treated with a high dose of N-methylolacrylamide. In addition to sinus erythrocytosis, the arrow in Figure 10B and the arrowheads in Figure 10C indicate megakaryocytes within the sinuses. The medullary cords are filled with myeloid precursors, indicative of granulopoiesis (Figure 10C, arrow). Figures 10D and 10E are images of the mesenteric lymph node of a 24-month-old male B6C3F1 mouse from a control group. In addition to megakaryocytes, there are myeloid and erythroid precursors within the medullary cords and sinuses.

Lymphoma and MCL

There are a variety of subclassifications of lymphoma including small lymphocyte, lymphoblastic, plasma cell, immunoblastic, follicular center and marginal zone lymphomas. A consensus system for classification of mouse lymphoid neoplasms according to their histopathologic and genetic features has been proposed as a way to model human hematopoietic diseases in mice (Morse et al., 2002). However, discussion and description of each type is beyond the scope of this paper.

Lymphoma is the most common primary neoplasm arising in lymph nodes and, in the F344 rat, must be distinguished from mononuclear cell leukemia (MCL). In the B6C3F1 mouse, lymphomas often arise in mesenteric lymph nodes, spleen and Peyer’s patches (Ward et al., 1999). Lymphoma typically consists of monomorphic sheets of neoplastic lymphocytes (). Lymphocyte apoptosis is a common feature of lymphoma giving the lymph node a “starry sky” appearance at low magnification (). At higher magnification tingible body macrophages are visualized with intracytoplasmic apoptotic bodies, which represent nuclear debris (). General diagnostic features of lymphoid neoplasia include the size of the lymph node, the loss of normal architecture, the presence of a monomorphic population of lymphocytes, capsular invasion and perinodal fat invasion (). It should be noted that lymphoid tissue is a common finding within the perinodal fat and should not be considered neoplastic invasion without other features of lymphoma present in the node.

Lymphosarcoma typically consists of monomorphic sheets of neoplastic lymphocytes as depicted in this lymph node from a TGAC (FVB/N) hemizygous mouse (Figure 11A). Lymphocyte apoptosis is a common feature of lymphosarcoma giving the lymph node a “starry sky” appearance at low magnification (Figure 11B). At higher magnification tingible body macrophages are visualized with intracytoplasmic apoptotic bodies (nuclear debris) (Figure 11C, arrows). General diagnostic features of lymphoid neoplasia include the size of the lymph node, the loss of normal architecture, the presence of a monomorphic population of lymphocytes, capsular invasion and perinodal fat invasion. However, these can also be features of MCL. Figures 11D–H are images of a lymph node from a F344 rat and illustrate a case of MCL with capsular invasion (Figure 11D and 11E), perinodal fat invasion (Figure 11F) and a monomorphic population of neoplastic lymphocytes (Figure 11G). Diffuse splenic red pulp involvement is the primary feature of MCL and will help to differentiate MCL from lymphosarcoma. The presence of leukemia in other tissues such as lung (Figure 11H), liver and kidney is a common feature of advanced MCL.

The diagnostic features of lymphoma can also be features of MCL. However, the cytoplasm of MCL cells may have a characteristic eosinophilic granular appearance with a hematoxylin and eosin stain or show almost no staining and the nuclear staining can range from pale to densely basophilic. Diffuse splenic red pulp involvement is the primary feature of MCL and will help to differentiate MCL from lymphoma. The presence of leukemia in other tissues such as lung (), liver and kidney is a common feature of advanced MCL. For more detailed information on MCL, refer to the paper by Suttie (2006).

Metastatic Lesions

Metastatic lesions in lymph nodes can arise from neoplastic blood-born emboli from tumors that are not in close proximity to the node. Metastatic neoplasias can also be found in the lymph nodes draining the region affected by the tumor. Therefore, if metastatic neoplasia is found within a lymph node and the primary tumor has not yet been identified, the location of the primary tumor may be found by evaluating tissues within the lymphatic draining field of that particular node. Although not an exhaustive list, lists several lymph nodes and corresponding metastases in the F344 rat based on anatomic location and draining field (Stefanski et al., 1990). Detailed information on the location of specific lymph nodes and patterns of lymphatic drainage in the rat and mouse have been described (Tilney, 1971; Sainte-Marie et al., 1982; Van den Broeck et al., 2006). The photomicrographs and descriptions for – illustrate and discuss various metastatic lesions in rodent lymph nodes.

Metastatic lesions can sometimes be found in the lymph node that drains a region affected by neoplasia. Figures 12A and 12B illustrate a mandibular lymph node from a F344 rat with effacement of approximately 80% of the normal node architecture by a large metastatic lesion. There is compression of the remaining normal lymphoid tissue to the left of the mass (arrows). At higher magnification, islands and trabeculae of neoplastic squamous epithelial cells are evident with eosinophilic keratin production (Figure 12C, arrow). Figure 12D shows the primary site of this neoplasm, the maxillary gingiva, which is a region drained by the mandibular lymph node.

Figures 17A and 17B show a lymph node from a female B6C3F1 mouse with sheets of round cells effacing the normal node architecture. Evaluation of the cells at the periphery of the lesion reveal neoplastic cells with classic features of plasma cells (eccentric nucleus and prominent golgi apparatus) (Figure 17C). Plasma cell tumors can be primary neoplasms of the lymph nodes or can be metastatic lesions. In the mouse, prolonged adjuvant stimulation can result in the development of plasma cell tumors within the peritoneum (Potter and Robertson, 1960; McIntire and Princler, 1969). Tumors of plasma cells result from the monoclonal proliferation of B cells.

Table 1

Lymph nodes and corresponding metastases.

Lymphadenopathy: Differential Diagnosis and Evaluation

ROBERT FERRER, M.D., M.P.H., University of Texas Health Sciences Center at San Antonio, San Antonio, Texas

Am Fam Physician. 1998 Oct 15;58(6):1313-1320.

Although the finding of lymphadenopathy sometimes raises fears about serious illness, it is, in patients seen in primary care settings, usually a result of benign infectious causes. Most patients can be diagnosed on the basis of a careful history and physical examination. Localized adenopathy should prompt a search for an adjacent precipitating lesion and an examination of other nodal areas to rule out generalized lymphadenopathy. In general, lymph nodes greater than 1 cm in diameter are considered to be abnormal. Supraclavicular nodes are the most worrisome for malignancy. A three- to four-week period of observation is prudent in patients with localized nodes and a benign clinical picture. Generalized adenopathy should always prompt further clinical investigation. When a node biopsy is indicated, excisional biopsy of the most abnormal node will best enable the pathologist to determine a diagnosis.

The cause of lymphadenopathy is often obvious: for example, the child who presents with a sore throat, tender cervical nodes and a positive rapid strep test, or the patient who presents with an infection of the hand and axillary lymphadenopathy. In other cases, the diagnosis is less clear. Lymphadenopathy may be the only clinical finding or one of several nonspecific findings, and the discovery of swollen lymph nodes will often raise the specter of serious illness such as lymphoma, acquired immunodeficiency syndrome or metastatic cancer. The physician’s task is to efficiently differentiate the few patients with serious illness from the many with self-limited disease. This article reviews the evaluation of patients with a central clinical finding of lymphadenopathy, emphasizing the identification of patients with serious illness.

Definition

The body has approximately 600 lymph nodes, but only those in the submandibular, axillary or inguinal regions may normally be palpable in healthy people.1 Lymphadenopathy refers to nodes that are abnormal in either size, consistency or number. There are various classifications of lymphadenopathy, but a simple and clinically useful system is to classify lymphadenopathy as “generalized” if lymph nodes are enlarged in two or more noncontiguous areas or “localized” if only one area is involved. Distinguishing between localized and generalized lymphadenopathy is important in formulating a differential diagnosis. In primary care patients with unexplained lymphadenopathy, approximately three fourths of patients will present with localized lymphadenopathy and one fourth with generalized lymphadenopathy (Figure 1).2,3

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FIGURE 1.

Presentation of lymphadenopathy by anatomic site (in percentages).

FIGURE 1.

Presentation of lymphadenopathy by anatomic site (in percentages).

Epidemiology

Our understanding of the epidemiology of lymphadenopathy in family practice is limited by the scarcity of relevant literature. Only one study4 provides reliable population-based estimates. Findings from this Dutch study revealed a 0.6 percent annual incidence of unexplained lymphadenopathy in the general population. Of 2,556 patients in the study who presented with unexplained lymphadenopathy to their family physicians, 256 (10 percent) were referred to a subspecialist and 82 (3.2 percent) required a biopsy, but only 29 (1.1 percent) had a malignancy.

This low prevalence of malignancy is supported by the results of two case series2,3 from family practice departments in the United States, in which none of 80 patients and three of 238 patients with unexplained lymphadenopathy were diagnosed with malignancy. In contrast, the prevalence of malignancy in lymph node biopsies performed in referral centers is 40 to 60 percent,5 a statistic that has made its way into many textbooks (e.g., “In those more than 30 years of age, however, lymphadenopathy is due to a benign process only 40 percent of the time”6). Such assertions overestimate the probability of malignancy in patients with lymphadenopathy because they exclude the 97 percent of patients with lymphadenopathy who do not undergo a biopsy. In primary care settings, patients 40 years of age and older with unexplained lymphadenopathy have about a 4 percent risk of cancer versus a 0.4 percent risk in patients younger than age 40.4

Diagnostic Approach to Lymphadenopathy

The algorithm in Figure 2 provides a diagnostic framework for the evaluation of lymphadenopathy. The algorithm emphasizes that a careful history and physical examination are the core of the evaluation. In most cases, a careful history and physical examination will identify a readily diagnosable cause of the lymphadenopathy, such as upper respiratory tract infection, pharyngitis, periodontal disease, conjunctivitis, lymphadenitis, tinea, insect bites, recent immunization, cat-scratch disease or dermatitis, and no further assessment is necessary (see the “diagnostic” branch of the algorithm).

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FIGURE 2.

Algorithm for the evaluation of a patient with lymphadenopathy. (HIV = human immunodeficiency virus; CBC = complete blood count; PPD = purified protein derivative; RPR = rapid plasma reagin; ANA = antinuclear antibody; HBsAg = hepatitis B surface antigen)

FIGURE 2.

Algorithm for the evaluation of a patient with lymphadenopathy. (HIV = human immunodeficiency virus; CBC = complete blood count; PPD = purified protein derivative; RPR = rapid plasma reagin; ANA = antinuclear antibody; HBsAg = hepatitis B surface antigen)

In other cases, a definitive diagnosis cannot be made on the basis of the history and physical examination alone; however, the clinical evaluation may strongly suggest a particular cause. Confirmatory testing should be performed in order to correctly identify the patient’s illness (see the “suggestive” branch of the algorithm).

A subset of patients will either have unexplained lymphadenopathy after the initial clinical evaluation or have a presumptive diagnosis that is made in the “diagnostic” or “suggestive” branches of the algorithm and is not confirmed by test results or by the clinical course. In patients with unexplained localized lymphadenopathy and a reassuring clinical picture, a three- to four-week period of observation is appropriate before biopsy. Patients with localized lymphadenopathy and a worrisome clinical picture or patients with generalized lymphadenopathy will need further diagnostic evaluation that often includes biopsy (see the “unexplained” branch of the algorithm). Fine-needle aspiration is occasionally considered an alternative to excisional biopsy but often yields a high number of nondiagnostic results because of the small amount of tissue obtained and the inability to examine the architecture of the gland.7 In addition, there may be some risk of sinus tract formation, depending on the underlying pathology.8

History

The physician should consider four key points when compiling a patient’s history.1  First, are there localizing symptoms or signs to suggest infection or neoplasm in a specific site? Second, are there constitutional symptoms such as fever, weight loss, fatigue or night sweats to suggest disorders such as tuberculosis, lymphoma, collagen vascular diseases, unrecognized infection or malignancy? Third, are there epidemiologic clues (Table 1) such as occupational exposures, recent travel or high-risk behaviors that suggest specific disorders? Fourth, is the patient taking a medication that may cause lymphadenopathy? Some medications are known to specifically cause lymphadenopathy (e.g., phenytoin [Dilantin]), while others, such as cephalosporins, penicillins or sulfonamides, are more likely to cause a serum sickness-like syndrome with fever, arthralgias and rash in addition to lymphadenopathy (Table 2).

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TABLE 1

Epidemiologic Clues to the Diagnosis of Lymphadenopathy

TABLE 1

Epidemiologic Clues to the Diagnosis of Lymphadenopathy

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TABLE 2

Medications That May Cause Lymphadenopathy

TABLE 2

Medications That May Cause Lymphadenopathy

Physical Examination

When lymphadenopathy is localized, the clinician should examine the region drained by the nodes for evidence of infection, skin lesions or tumors (Table 3). Other nodal sites should also be carefully examined to exclude the possibility of generalized rather than localized lymphadenopathy. This is an important aspect of the examination, as a study of primary care physicians found that generalized lymphadenopathy was identified in only 17 percent of the patients in whom it was present.9 Careful palpation of the submandibular, anterior and posterior cervical, supraclavicular, axillary and inguinal nodes can be accomplished in a short time and will identify patients with generalized lymphadenopathy.

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TABLE 3

Lymph Node Groups: Location, Lymphatic Drainage and Selected Differential Diagnosis

TABLE 3

Lymph Node Groups: Location, Lymphatic Drainage and Selected Differential Diagnosis

If lymph nodes are detected, the following five characteristics should be noted and described:

Size. Nodes are generally considered to be normal if they are up to 1 cm in diameter; however, some authors suggest that epitrochlear nodes larger than 0.5 cm or inguinal nodes larger than 1.5 cm should be considered abnormal.7,8 Little information exists to suggest that a specific diagnosis can be based on node size. However, in one series10 of 213 adults with unexplained lymphadenopathy, no patient with a lymph node smaller than 1 cm² (1 cm × 1 cm) had cancer, while cancer was present in 8 percent of those with nodes from 1 cm² to 2.25 cm² (1 cm × 1 cm to 1.5 cm × 1.5 cm) in size, and in 38 percent of those with nodes larger than 2.25 cm² (1.5 cm × 1.5 cm). In children, lymph nodes larger than 2 cm in diameter (along with an abnormal chest radiograph and the absence of ear, nose and throat symptoms) were predictive of granulomatous diseases (i.e., tuberculosis, cat-scratch disease or sarcoidosis) or cancer (predominantly lymphomas).11 These studies were performed in referral centers, and conclusions may not apply in primary care settings.

Pain/Tenderness. When a lymph node rapidly increases in size, its capsule stretches and causes pain. Pain is usually the result of an inflammatory process or suppuration, but pain may also result from hemorrhage into the necrotic center of a malignant node. The presence or absence of tenderness does not reliably differentiate benign from malignant nodes.4

Consistency. Stony-hard nodes are typically a sign of cancer, usually metastatic. Very firm, rubbery nodes suggest lymphoma. Softer nodes are the result of infections or inflammatory conditions. Suppurant nodes may be fluctuant. The term “shotty” refers to small nodes that feel like buckshot under the skin, as found in the cervical nodes of children with viral illnesses.

Matting. A group of nodes that feels connected and seems to move as a unit is said to be “matted.” Nodes that are matted can be either benign (e.g., tuberculosis, sarcoidosis or lymphogranuloma venereum) or malignant (e.g., metastatic carcinoma or lymphomas).

Location. The anatomic location of localized adenopathy will sometimes be helpful in narrowing the differential diagnosis. For example, cat-scratch disease typically causes cervical or axillary adenopathy, infectious mononucleosis causes cervical adenopathy and a number of sexually transmitted diseases are associated with inguinal adenopathy (Table 4).

Supraclavicular lymphadenopathy has the highest risk of malignancy, estimated as 90 percent in patients older than 40 years and 25 percent in those younger than age 40.4 Having the patient perform a Valsalva’s maneuver during palpation of the supraclavicular fossae increases the chance of detecting a node. Lymphadenopathy of the right supraclavicular node is associated with cancer in the mediastinum, lungs or esophagus. The left supraclavicular (Virchow’s) node receives lymphatic flow from the thorax and abdomen, and may signal pathology in the testes, ovaries, kidneys, pancreas, prostate, stomach or gallbladder. Although rarely present, a paraumbilical (Sister Joseph’s) node may be a sign of an abdominal or pelvic neoplasm.12

In patients with generalized lymphadenopathy, the physical examination should focus on searching for signs of systemic illness. The most helpful findings are rash, mucous membrane lesions, hepatomegaly, splenomegaly or arthritis (Table 4). Splenomegaly and lymphadenopathy occur concurrently in many conditions, including mononucleosis-type syndromes, lymphocytic leukemia, lymphoma and sarcoidosis.

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TABLE 4

Evaluation of Suspected Causes of Lymphadenopathy

TABLE 4

Evaluation of Suspected Causes of Lymphadenopathy

Clinical Evaluation for Algorithm’s ‘Suggestive’ Branch

Laboratory tests that may be useful in confirming the cause of lymphadenopathy are listed in Table 4. The presence of certain characteristic clinical syndromes may help the physician determine a suspected cause of lymphadenopathy.

Mononucleosis-Type Syndromes

Patients with these syndromes present with lymphadenopathy, fatigue, malaise, fever and an increased atypical lymphocyte count. Mononucleosis is most commonly due to Epstein-Barr virus infection. The presence of the typical syndrome and positive results on a heterophilic antibody test (Monospot test) confirms the diagnosis. The most common cause of heterophil-negative mononucleosis is early Epstein-Barr virus infection. False-negative results on heterophilic antibody tests are especially common in patients younger than four years of age. Epstein-Barr virus infection may be confirmed by repeating the Monospot test in seven to 10 days. Rarely is it necessary to confirm the diagnosis with IgM viral capsid antigen or early antigen antibody titers.

If Epstein-Barr virus antibodies are absent, other causes of the mononucleosis syndrome should be considered. These include toxoplasmosis, cytomegalovirus infection, streptococcal pharyngitis, hepatitis B infection and acute human immunodeficiency virus (HIV) infection. Acute infections with cytomegalovirus and Toxoplasma may be identified with IgM serology for those organisms.

Ulceroglandular Syndrome

This syndrome is defined by the presence of a skin lesion with associated regional lymphadenopathy. The classic cause is tularemia, acquired by contact with an infected rabbit or tick; more common causes include streptococcal infection (e.g., impetigo), cat-scratch disease and Lyme disease.

Oculoglandular Syndrome

This syndrome involves the combination of conjunctivitis and associated preauricular nodes. Common causes include viral kerato-conjunctivitis and cat-scratch disease resulting from an ocular lesion.

HIV Infection

Enlargement of the lymph nodes that persists for at least three months in at least two extrainguinal sites is defined as persistent generalized lymphadenopathy and is common in patients in the early stages of HIV infection. Other causes of generalized lymphadenopathy in HIV-infected patients include Kaposi’s sarcoma, cytomegalovirus infection, toxoplasmosis, tuberculosis, cryptococcosis, syphilis and lymphoma.

Unexplained Lymphadenopathy

When, after the initial evaluation and after exploration of the “diagnostic” and “suggestive” branches of the algorithm (Figure 2), a cause for the lymphadenopathy remains unexplained, the physician must decide whether to pursue a specific diagnosis. The decision will depend primarily on the clinical setting as determined by the patient’s age, the duration of the lymphadenopathy and the characteristics and location of the nodes.

Generalized Lymphadenopathy

Because generalized lymphadenopathy almost always indicates that a significant systemic disease is present, the clinician should consider the diseases listed in Table 4 and proceed with specific testing as indicated. If a diagnosis cannot be made, the clinician should obtain a biopsy of the node. The diagnostic yield of the biopsy can be maximized by obtaining an excisional biopsy of the largest and most abnormal node (which is not necessarily the most accessible node). If possible, the physician should not select inguinal and axillary nodes for biopsy, since they frequently show only reactive hyperplasia.

Localized Lymphadenopathy

If the lymphadenopathy is localized, the decision about when to biopsy is more difficult. Patients with a benign clinical history, an unremarkable physical examination and no constitutional symptoms should be reexamined in three to four weeks to see if the lymph nodes have regressed or disappeared. Patients with unexplained localized lymphadenopathy who have constitutional symptoms or signs, risk factors for malignancy or lymphadenopathy that persists for three to four weeks should undergo a biopsy. Biopsy should be avoided in patients with probable viral illness because lymph node pathology in these patients may sometimes simulate lymphoma and lead to a false-positive diagnosis of malignancy.

Initial Management

Many patients worry about the cause of their abnormal lymph nodes. To adequately address their fears, the physician should ask the patient about his or her concerns and respond to questions about specific diagnoses. When biopsy is deferred, the physician should explain to the patient the rationale for waiting. Patients should be cautioned to remain alert for the reappearance of the nodes because lymphomatous nodes have been known to temporarily regress.

Final Comment

In most patients, lymphadenopathy has a readily diagnosable infectious cause. A diagnosis of less obvious causes can often be made after considering the patient’s age, the duration of the lymphadenopathy and whether localizing signs or symptoms, constitutional signs or epidemiologic clues are present. When the cause of the lymphadenopathy remains unexplained, a three- to four-week observation period is appropriate when the clinical setting indicates a high probability of benign disease.

Inguinal Lymph Node Dissection

Overview

What is inguinal lymph node dissection?

“Inguinal” refers to the groin, that part of the body where the legs meet the lower abdomen. “Dissection” refers to the cutting and separating apart of tissue. Therefore inguinal lymph node dissection is the surgical removal of lymph nodes from the groin.

Other names for this procedure are groin dissection or lymphadenectomy.

What are inguinal lymph nodes?

Inguinal lymph nodes are lymph nodes located in the groin. Other lymph nodes are found in the armpits, neck, behind the ears, and under the chin.

All lymph nodes are part of the lymphatic system, which includes lymph fluid, lymph vessels, bone marrow, and organs such as the thymus, adenoid, tonsil, and spleen. Lymphatic structures are part of the body’s immune system, making and transporting cells that fight against infections and other diseases.

Lymph nodes are small oval-shaped structures that produce disease-fighting cells, and also act as filters for lymph vessels, a network of thin tubes that collect and circulate lymph fluid throughout the body.

There is a chain of about 10 superficial (close to the surface of the skin) inguinal lymph nodes located in the upper inner thigh. These nodes drain into three to five deep inguinal lymph nodes in the connective tissue of the upper thigh. From there, lymph fluid drains into other lymph nodes in the pelvis.

When is inguinal lymph node dissection needed?

Cancer cells may travel in lymph fluid from the point where a cancer starts into lymph nodes. In the case of inguinal lymph nodes, they may receive cells from cancers of the penis, vulva, anus, and the skin on the arms and trunk of the body. If inguinal lymph nodes become cancerous, they can then spread cancer to the pelvic lymph nodes they flow into.

In the early stages of cancer, inguinal lymph nodes cannot be felt by hand. If large lymph nodes or a lump in the groin are detected, this could be an indication of a more advanced stage of cancer.

Inguinal lymph node dissection is used to diagnose, treat, and prevent the spread of cancer to the inguinal lymph nodes, as follows:

• To see if cancer is present in the lymph nodes of the groin: A surgical procedure called a sentinel lymph node biopsy (SLNB) removes the first lymph node in a chain or group of lymph nodes that a particular cancer is most likely to spread to. Because the lymphatic system drains in a predictable pattern, the fluid from a particular area of the body will flow to specific lymph nodes. It is presumed that if the “sentinel” lymph node is free of disease, then other nodes around it will also be cancer-free. This is confirmed when the removed node is examined and tested in a laboratory. Test results help the doctor determine if cancer is present. If it is present, laboratory results help determine the stage of cancer, a treatment plan, and the long-term outlook of the disease.
• To remove lymph nodes that may be cancerous.
• To remove lymph nodes with a high chance of becoming cancerous.
• To reduce the chance that cancer which is currently under control will come back in the future.
• To remove cancer that remains in the lymph nodes following treatments such as radiation or chemotherapy.
• To help doctors form a plan to treat cancer.

Procedure Details

How is inguinal lymph node dissection done?

1. The patient is placed under general anesthesia in a hospital operating room.
2. The surgeon cuts into the groin and removes lymph nodes that may be cancerous. This could involve only superficial nodes or both superficial and deep nodes, depending on the patient’s particular case.
3. A skin flap is created to cover the cut, tubes are put in place to drain excess fluid, and the cut is closed with stitches or staples.
4. A bag is attached to the end of the tube to collect any fluid drainage, which could last for several weeks.
5. All tissue removed is sent to a laboratory for testing to see if cancer cells are present. If yes, the important factors to consider are the type of cancer, the number of lymph nodes removed versus the number with cancer cells, and whether the cancer has spread beyond the lymph node. These factors help determine the stage of the disease, and possible treatments and outlook.

Risks / Benefits

What are possible complications of inguinal lymph node dissection?

The rate of complications following inguinal lymph node surgery can be quite high, with a direct correlation between the number and depth of the lymph nodes removed, and the occurrence of complications. The most common complications are:

• Infection at the site of the incision, an early complication and the one seen most often. A risk factor for developing infection is obesity. Signs of infection include pain, redness, pus, discharges or fever.
• Swelling (seroma) at the site of the incision due to fluid buildup.
• Swelling (lymphedema) of the lower legs, usually as a long-term complication.
• Deep vein blood clots.
• Poor wound-healing.
• Tissue death.

Studies are being done to reduce the number of surgical complications, which mainly are the result of bleeding and fluid accumulation due to damage done to blood and lymph vessels at or near the surgical site. Efforts at improvement include identifying nodal disease as soon as possible so that treatment can begin before extensive surgery is needed; changes in surgical technique; increased efforts at preserving as much tissue as possible, and a move toward less invasive surgery.

Recovery and Outlook

What can be expected following inguinal lymph node dissection?

• The drainage bag will remain in place until the amount of fluid being drained slows to a targeted amount, or until the doctor decides the bag is safe to remove.
• The patient may remain in the hospital for 10 to 14 days, although this can vary by patient.
• Attempts to walk are encouraged as soon as possible in order to avoid blood clots, although doing so may increase the amount of lymph fluid being drained.
• Driving a motor vehicle is discouraged for at least four to six weeks after surgery.

Lymph nodes: Histology | Kenhub

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Lymph node (histological slide)

The presence of foreign organisms within the blood stream can trigger a massive cascade of events that will disrupt many homeostatic microenvironments within the body. Therefore, the immune system carries out detailed surveillance of the blood in order to detect these pathogens. One method of screening takes place at the level of the lymph nodes. These are secondary lymphoid organs that are widely distributed throughout the body. Apart from its role in immune regulation, the lymphatic system is also important for immune regulation and fat absorption.

Between 400 and 450 lymph nodes are scattered throughout the average human body. They are found along the lymphatic vessels, which carry fluid from the interstitial space into the main circulation. They are particularly abundant in the cervical, axillary, inguinal, perihilar, and intra-abdominal areas. These locations are vulnerable points of entry of pathogens into the host’s intrinsic environment. As a result, it is important that surveillance is maximized in these areas. This article will review the embryology and gross anatomy of lymph nodes. However, the primary focus will be on the histological composition of these structures as well as clinically relevant points regarding lymph node function.

Gross anatomy

At approximately 0.1 by 2.5 cm, the lymph node is a relatively small glandular structure that resembles a kidney-bean. It has a convexed surface that is penetrated by afferent lymph vessels. On the opposing side, there is a concavity that is penetrated by the supplying artery, vein and nerve and also allows exit of efferent lymphatic vessels. This concavity is known as the hilum of the lymph node. They are suspended in loose connective tissue that follows the large vasculature.

Active lymph node. Stain: hematoxylin and eosin. Medium magnification.

Histological architecture

Lymph nodes are encapsulated by dense connective tissue comprised of elastin and collagen fibres along with interspersed fibroblasts. The convexed surface of the lymph node is pierced by numerous afferent lymph vessels. They extend to the deeper areas of the lymph node by way of the trabecular extensions of the cortex. As the trabeculae penetrate the lymph node, they continue as reticulin fibrils (type III collagen) that offer additional structural support to the gland.

Trabeculae (histological slide)

Cross sectional analysis of a lymph node reveals that it is subdivided into three regions:

Outer cortex

The outermost layer is the cortex. It is made up of a subcapsular sinus, cortical sinus and lymphoid nodules. The subcapsular sinus is the first space that lymph fluid from the afferent channels enters within the node. The fluid then travels from here to the cortical sinuses; which are branches of the subcapsular sinus. The cortical sinuses are also known as trabecular sinuses because they travel along the trabecular network within the lymph node.

Cortex (histological slide)

The endothelium of the trabecular sinuses are perforated by dendritic processes as well as reticulin fibres. Antigen presenting cells (APCs), circulating antigen, and lymphocytes flowing within the lymph can access the lymphatic tissue within the nodes through the disrupted endothelium. The cortical layer also has relatively large aggregates of helper T – lymphocytes and rapidly dividing B – lymphocytes in the peripheral part of the lymph nodes. Although both T cells and B cells are present in the cortex, B cells are more abundant than T cells are in this region. These lymphoid nodules are situated around the branched, interlacing extensions of the follicular dendritic cells (FDCs). The nodules may or may not have a germinal centre depending on if it is a primary or secondary follicle.

Primary follicle (histological slide)

Histological staining of lymph node samples are strongly influenced by the amount of antigen the cells of the lymph node are exposed to. Additionally, the number of cells within the node as well as the distinct separation of the cords is also influenced by antigenic exposure. As a result, the primary follicle is comprised of small dormant lymphocytes throughout, while the secondary follicle has a heterogeneous collection of large B lymphocytes that have already been activated by inciting antigens. Primary follicles absorb less histological stains then secondary follicles. This is likely due to fewer cells in the primary follicle when compared to the secondary follicle.

Secondary follicle (histological slide)

The germinal centre can be further subdivided into a dark zone, light zone and a mantle zone. Each zone facilitates different aspects of B cell affinity maturation. In the peripherally aspect of the germinal centre, quiescent B cells are found in the mantle zone. These cells are characterized by intense basophilic staining, small cytoplasmic volume and a heterochromatic nucleus. Other cells in the mantle zone include follicular dendritic cells as well as the occasional helper T lymphocyte and macrophages. The fate of B cells in the mantle zone can go one of two ways. These cells either remain in the lymph node and mature into antibody secreting plasma cells and remain in the lymph node, or they transform into memory B cells that re-enter the systemic circulation.

Germinal center (histological slide)

The other two zones of the germinal centre are the light zone and dark zone. The light zone contains centrocytes that interact with follicular dendritic cells that express intact antigen on their surface. Centrocytes with high affinity binding to the follicular dendritic cell antigen will persist, while those with weak binding undergoes apoptosis. While resident macrophages help to clean up apoptotic B cells, helper T cells support the remaining B cells and foster the class switching phase of the cellular maturity.

Centrocytes (histological slide)

In the dark zone of the germinal centre, the centroblasts are highly mitotic and have a strong likelihood of producing mutated antibodies. These are the source cells for the light zone.

Centroblasts (histological slide)

Paracortex

Deep to the cortical layer is the paracortex. Its margins blend with the superficial cortex and deep medulla. The principal distinguishing features are the absence of lymphoid nodules and the large number of T lymphocytes (both cluster of differentiation 4 and 8 positive T cells [CD4+ and CD8+]) within the stroma of the paracortex.

Paracortex (histological slide)

The paracortex also has unique venules known as high endothelial venules (HEVs). Most of the lymphocytes that enter the lymph node do so via these channels. They are made up of cuboidal endothelium that is fitted apically with integrins and glycoproteins. Both these surface markers allow unimpeded passage of lymphocytes (i.e. diapedesis) from the percolating blood into the lymph node. These specialized vessels are also present in the mucosa associated lymphatic tissue distributed throughout the gastrointestinal tract. However, they are at their highest level of development within the lymph nodes.

Medulla

The deepest layer of the lymph node is the medulla. It is subdivided functionally and histologically into two other regions; which are the medullary cords and sinuses. The cords are populated by plasma cells, as well as B – cells and T – cells. The cells are arranged in cord-like projections extending centrally from the paracortex.

Medulla (histological slide)

Interlacing between the cords are distended areas lined by discontinuous endothelium. The luminal surface of the sinuses also contains a vast network of reticular cell processes. They act as the final point of filtration of circulating lymph. The medullary sinuses are the terminal continuations of the peripherally located cortical sinuses. They eventually culminate at the hilum of the lymph node to form efferent lymphatic vessels.

Medullary sinuses (histological slide)

Lymph vessels are lined by a single layer of squamous endothelium. They are fitted with valves that promotes unidirectional flow of lymph from the afferent lymph vessels to the lymph node and then to the efferent lymph vessels. The afferent lymph channels bring lymph with either free floating or complement bound antigen into the subcapsular space. Of note, the subcapsular space extends around the entire lymph node except at the hilum. The lymph then flows through the cortical sinuses.

Efferent lymphatic vessels (histological slide)

Blood Supply

The arterial supply of the lymph nodes is derived from the vessels they encircle within their respective regions. For example, the axillary lymph nodes are perfused by arterial branches of the axillary artery. Each lymphatic artery gains access to the node by way of the hilum. As the vessel penetrates this area, it gives off a myriad of straight branches within the medulla that also arborize to supply areas that are distal to the vessels.

Hilum of the lymph node (histological slide)

In the cortex, the straight arteries branch off into arterioles that form tightly packed anastomosing networks. The capillaries are more commonly seen around the germinal centres, where there are usually less arterioles. Capillaries also become more numerous when there is antigenic stimulation of the lymph node. The arterioles and capillaries then return to similarly numerous anastomosing networks of venules and veins. They tend to follow the course of the arteries and arterioles in the opposite direction. Eventually the veins leave the node via the same point of entrance of the arteries (the hilum).

Embryology

A few weeks after the initiation of cardiovascular development (third week of gestation), the lymphatic system begins to take shape (sixth week of gestation). Numerous studies dating from 1995 to 2002 identified vascular endothelial growth factor receptor 3 (VEGFR 3), vascular endothelial growth factor C (VEGF C) and prospero homebox 1 (PROX1) as integral components in the development of lymphatic vessels. While VEGFR 3 and VEGF C are essential for vascular differentiation from mesenchyme, the presence of PROX1 is imperative for lymphatic endothelial cell differentiation. Definitive confirmation of the venous derivative theory postulated in 1902 was recently confirmed in 2007.

One theory proposed that outpouchings of the venous endothelium (i.e. diverticulae) result in the formation of lymphatic sacs. Another school of thought proposes that the lymphatic system, like the rest of the vascular network, originates from cells arising from the mesenchymal layer and develops separately from the veins. The former theory, proposed in 1909, is the most widely accepted concept.

The lymph sacs develop adjacent to the primitive venous network. The lymph sacs identified at the early stage of development are paired (jugular and posterior lymph sacs) and unpaired lymph sacs (retroperitoneal and cisterna chyli). Jugular lymphatic sacs form around the superior cardinal veins (precursors to the jugular veins). There are axillary lymphatic sacs that develop around the right subclavian vein. On the left side, the thoracic duct forms on either side of the left brachiocephalic vein. There are also lumbar and iliac sacs forming caudally. The lumbo-iliac, jugular and axillary sacs are bilateral structures.

Cisterna chyli

The deep cervical nodes are the first to develop from its lymphatic sac. It is followed by the axillary, parasternal, and mediastinal lymph nodes; which also arise from their respective lymphatic sacs. The retroperitoneal, lumbo-iliac and inguinal nodes are derived from the lumbo-iliac lymphatic sacs. The differentiation from sac to nodes occurs when the sacs are invaded and segmented by adjacent mesenchymal cells.

Axillary lymph nodes

The mesenchyme also forms the lymph node capsule and connective tissue stroma. More specifically, it gives rise to the fibroblastic reticular cells that produce the connective tissue stroma as well as its extracellular matrix. Eventually lymphoid tissue inducer cells that promote the development of lymphoid tissue within the lymph node are formed. There is subsequent invasion of the lymph nodes by thymic lymphocytes either shortly before, or during the antenatal period,. These T lymphocytes tend to migrate into the deeper cortex while the B lymphocytes migrate to the outer cortex of the lymphatic nodules.

Clinical significance

Lymphadenopathy

Certain groups of lymph nodes are responsible for draining lymph from particular regions of the body. For example, lymphatic fluid from the lower limbs and perineal area will drain to the inguinal lymph nodes. Keep in mind that this lymph may contain pathogenic antigen from potential invaders. This antigenic stimulation can result in local enlargement of lymph nodes draining that particular region. The antigenic stimulation may also lead to changes not only in the size of the nodes, but also their consistency. This process is known as lymphadenopathy; it is also applicable to any disease process that affects the reticuloendothelial system. Lymph node enlargement is considered significant based on how large the nodes get. A general rule of thumb states that any enlargement greater than 1 cm of more than one lymph node is considered lymphadenopathy. However, some clinicians say that enlargement should be related to the region the nodes are located in. In other words:

• Cervical lymph nodes greater than 2 cm are considered significant
• Axillary lymph nodes greater than 1 cm are considered significant
• Inguinal lymph nodes greater than 1.5 cm are considered significant

Lymphadenopathy can be further classified as local or generalized. If swollen nodes are only seen in one region (i.e. cervical or axillary) then it is local. But if swollen nodes are found in more than one areas (i.e. epitrochlear and cervical) then it is generalized. Typically, swollen lymph nodes are reflective of self-limiting viral or bacterial infections in children. However, there are other non-benign conditions that may also result in lymphadenopathy. Furthermore, in adults, it is unlikely for lymph nodes to be found in a quiescent state as past exposure may incite long standing morphological changes within the nodes. Therefore it is important to differentiate between an ongoing disease process and a past exposure. Nevertheless, the swollen glands should not be ignored.

Lymphadenopathy should not be confused with lymphadenitis. The latter refers to an acute inflammatory process within the lymph node. While this condition also presents with lymph node enlargement, it is characterized by painful, indurated lymph nodes. This is in contrast to lymphadenopathy where the lymph nodes are painless on palpation and are not erythematous.

Clinicians can use clues from lymph node enlargement to determine where the underlying insult is occurring. Palpating lymph nodes is a clinical skill that is relatively easy to master and should not be neglected. Palpation of lymph nodes is particularly important during the general examination of a patient, as well as during examination of specific systems such as the respiratory system and abdominal exam. Common areas to palpate include the epitrochlear, axillary, cervical, pre and postauricular, occipital, submandibular and submental nodes. Inguinal nodes may also be palpated but the popliteal nodes are difficult to appreciate. In addition to the size and location of the nodes, the clinician should also note whether or not these nodes are tender, indurated and febrile as this points to a clinical diagnosis of lymphadenitis. Lymph nodes that are immobile, clumped together, and firm are more than likely (but not exclusively) a sign of malignancy than those that were described earlier.

The list of aetiological factors leading to lymphadenopathy is quite eclectic. The can be generally classified based on whether or not the lymphadenopathy is generalized (systemic) or regional (localized). Below is a truncated list of the causes of lymphadenopathy:

• 
  Generalized
  
  • Infections
    • Viral
    • Bacterial
    • Parasitic

  • Autoimmune & Hypersensitivity disorders
    • Systemic lupus erythematosus
    • Drug reactions

  • Storage disorders
  • Neoplasms

• 
  Regional (specifically those that are palpable)
  • Cervical
    • Upper respiratory tract infections
    • Infectious mononucleosis
    • Leukaemias
    • Lymphomas

  • Submaxillary and Submental
  • Occipital
    • Tinea capitis
    • Rubella
    • Roseola

  • Pre-auricular
    • Cutaneous infection
    • Catscratch disease

  • Supraclavicular
  • Axillary
    • Immunization reaction
    • Non-neoplastic lesions of the breast
    • Mastitis
    • Brucellosis
    • Lymphoma

  • Inguinal
    • Insect bites
    • Sexually transmitted infections

Lymphadenectomy

In cases where lymphadenopathy is believed to be a result of a non-benign process, then surgical excision of the node may be warranted. Lymphadenectomy is a diagnostic and therapeutic approach to managing patients with malignancies. It is often done in addition to removing a primary tumor. Recall that a hallmark feature of cancers is their ability to metastasize. If these malignant cells gain access to the circulating lymph then they can spread throughout the body and become lodged in the lymph nodes. This will result in the formation of a secondary site from which these nodes can spread. Therefore, clinicians use this information as a part of staging the malignancy. The stage of the malignancy also influences the mode of treatment that would be best for the patient.

Lymphedema

An interesting complication of lymphadenectomy is lymphedema. This is a disorder of the lymphatic system characterized by swelling of the limbs as a result of disrupted lymphatic pathways. While it is a complication of lymph node resection, it may also occur outside of surgical intervention.

The process is subdivided aetiologically into primary and secondary lymphedema. Primary lymphedema is a result of hypoplastic lymphatic channels. It is an uncommon cause of the disease that can be seen in patients as young as 2 years old. There are also associations with lymphedema and other genetic disorders such as Turner syndrome. More commonly, the cause of lymphedema is secondary to obstruction or destruction of the lymphatic channels. Surgery and radiation therapy are the most common iatrogenic causes of lymphedema. Traumatic injury to the lymph nodes or vessels has also been implicated in the process. Parasitic infections (filariasis) and metastatic obstruction are also other prominent causes.

Sources

References:

• 
  Bailey, R. and Weiss, L. (1975). Light and electron microscopic studies of postcapillary venules in developing human fetal lymph nodes. American Journal of Anatomy, 143(1), pp.43-57.
• 
  Butler, M., Isogai, S. and Weinstein, B. (2009). Lymphatic development. Birth Defects Research Part C: Embryo Today: Reviews, 87(3), pp.222-231.
• 
  Dhar, A. (2017). Lymphadenitis – Dermatologic Disorders – MSD Manual Professional Edition. [online] MSD Manual Professional Edition. Available at: http://www.msdmanuals.com/professional/dermatologic-disorders/bacterial-skin-infections/lymphadenitis [Accessed 12 Sep. 2017].
• 
  Douketis, J. (2017). Lymphadenopathy – Cardiovascular Disorders – MSD Manual Professional Edition. [online] MSD Manual Professional Edition. Available at: http://www.msdmanuals.com/professional/cardiovascular-disorders/lymphatic-disorders/lymphadenopathy [Accessed 12 Sep. 2017].
• 
  Gray, H. and Standring, S. (2009). Gray’s anatomy. 40th ed. [Edinburgh u.a.]: Churchill Livingstone Elsevier.
• 
  Kanwar, V. and Sills, R. (2017). Lymphadenopathy: Background, Pathophysiology, Epidemiology. [online] Emedicine.medscape.com. Available at: http://emedicine.medscape.com/article/956340-overview#a4 [Accessed 12 Sep. 2017].
• 
  Kumar, V., Abbas, A. and Aster, J. (2015). Robbins and Cotran pathologic basis of disease. 9th ed. Philadelphia, PA: Elsevier Saunders.
• 
  Mescher, A. and Junqueira, L. (2013). Junqueira’s Basic Histology. 13th ed. McGaw-Hill.
• 
  James D. Douketis, MD (2017). Lymphedema – Cardiovascular Disorders – MSD Manual Professional Edition. [online] Available at: http://www.msdmanuals.com/professional/cardiovascular-disorders/lymphatic-disorders/lymphedema [Accessed 12 Sep. 2017].
• 
  Pansky, B. (1982). Review of medical embryology. New York: Macmillan.
• 
  Vondenhoff, M., van de Pavert, S., Dillard, M., Greuter, M., Goverse, G., Oliver, G. and Mebius, R. (2008). Lymph sacs are not required for the initiation of lymph node formation. Development, 136(1), pp.29-34.

Author, review and layout:

• Lorenzo Crumbie
• Uruj Zehra
• Adrian Rad

Illustrators:

• Lymph node (histological slide) – Smart In Media
• Cisterna chyli – Begoña Rodriguez
• Axillary lymph nodes – Begoña Rodriguez
• Trabeculae (histological slide) – Smart In Media
• Cortex (histological slide) – Smart In Media
• Primary follicle (histological slide) – Smart In Media
• Secondary follicle (histological slide) – Smart In Media
• Germinal center (histological slide) – Smart In Media
• Centrocytes (histological slide) – Smart In Media
• Centroblasts (histological slide) – Smart In Media
• Paracortex (histological slide) – Smart In Media
• Medulla (histological slide) – Smart In Media
• Medullary sinuses (histological slide) – Smart In Media
• Efferent lymphatic vessels (histological slide) – Smart In Media
• Hilum of the lymph node (histological slide) – Smart In Media

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Lymphoscintigraphy

Lymphoscintigraphy helps evaluate your body’s lymphatic system for disease using small amounts of radioactive materials called radiotracers that are typically injected into the bloodstream, inhaled, swallowed, or in the case of lymphoscintigraphy, injected into the skin. The radiotracer travels through the area being examined and gives off energy in the form of gamma rays which are detected by a special camera and a computer to create images of the inside of your body. Because it is able to pinpoint molecular activity within the body, lymphoscintigraphy offers the potential to identify lymphatic disease in its earliest stages.

Tell your doctor if there’s a possibility you are pregnant or if you are breastfeeding. Discuss any recent illnesses, medical conditions, allergies and medications you’re taking, including vitamins and herbal supplements. Your doctor will instruct you on how to prepare. Leave jewelry at home and wear loose, comfortable clothing. You may be asked to wear a gown.

What is Lymphoscintigraphy?

Lymphoscintigraphy is a special type of nuclear medicine imaging that provides pictures called scintigrams of the lymphatic system.

Nuclear medicine uses small amounts of radioactive material called radiotracers. Doctors use nuclear medicine to diagnose, evaluate, and treat various diseases. These include cancer, heart disease, gastrointestinal, endocrine, or neurological disorders, and other conditions. Nuclear medicine exams pinpoint molecular activity. This gives them the potential to find disease in its earliest stages. They can also show whether you are responding to treatment.

Nuclear medicine is noninvasive. Except for intravenous injections, it is usually painless. These tests use radioactive materials called radiopharmaceuticals or radiotracers to help diagnose and assess medical conditions.

Radiotracers are molecules linked to, or “labeled” with, a small amount of radioactive material. They accumulate in tumors or regions of inflammation. They can also bind to specific proteins in the body. The most common radiotracer is F-18 fluorodeoxyglucose (FDG), a molecule similar to glucose. Cancer cells are more metabolically active and may absorb glucose at a higher rate. This higher rate can be seen on PET scans. This allows your doctor to detect disease before it may be seen on other imaging tests. FDG is just one of many radiotracers in use or in development.

You will usually receive the radiotracer in an injection. Or you may swallow it or inhale it as a gas, depending on the exam. It accumulates in the area under examination. A special camera detects gamma ray emissions from the radiotracer. The camera and a computer produce pictures and supply molecular information.

The lymphatic system is a network of small channels similar to blood vessels that circulate the fluid (called lymph) and cells (lymphocytes) of the immune system throughout the body. Lymph nodes, which act like a filter for foreign bodies such as germs, viruses and pollen, are located along this network.

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What are some common uses of the procedure?

Physicians perform lymphoscintigraphy to:

• identify the sentinel lymph node, or the first node to receive the lymph drainage from a tumor.
• plan a biopsy or surgery that will help assess the stage of cancer and create a treatment plan.
• identify points of blockage in the lymphatic system, such as lymph flow in an arm or leg, or lymphedema.

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How should I prepare?

You may wear a gown during the exam or be allowed to wear your own clothing.

Women should always tell their doctor and technologist if they are pregnant or breastfeeding. See the Safety in X-ray, Interventional Radiology and Nuclear Medicine Procedures page for more information about pregnancy and breastfeeding related to nuclear medicine imaging.

Tell the doctor and your exam technologist about any medications you are taking, including vitamins and herbal supplements. List any allergies, recent illnesses, and other medical conditions.

Leave jewelry and accessories at home or remove them prior to the exam. These objects may interfere with the procedure.

Your doctor will tell you how to prepare for your specific exam.

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What does the equipment look like?

Nuclear medicine uses a special gamma camera and single-photon emission-computed tomography (SPECT) imaging techniques.

The gamma camera records the energy emissions from the radiotracer in your body and converts it into an image. The gamma camera itself does not emit any radiation. It has radiation detectors called gamma camera heads. These are encased in metal and plastic, often shaped like a box, and attached to a round, donut-shaped gantry. The patient lies on an exam table that slides in between two parallel gamma camera heads, above and beneath the patient. Sometimes, the doctor will orient the gamma camera heads at a 90-degree angle over the patient’s body.

In SPECT, the gamma camera heads rotate around the patient’s body to produce detailed, three-dimensional images.

A computer creates the images using the data from the gamma camera.

A probe is a small hand-held device resembling a microphone. It measures the amount of radiotracer in an area of your body.

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How does the procedure work?

Ordinary x-ray exams pass x-rays through the body to create an image. Nuclear medicine uses radioactive materials called radiopharmaceuticals or radiotracers. Your doctor typically injects this material into your bloodstream. Or you may swallow it or inhale it as a gas. The material accumulates in the area under examination, where it gives off gamma rays. Special cameras detect this energy and, with the help of a computer, create pictures that detail how your organs and tissues look and function.

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How is the procedure performed?

Doctors perform nuclear medicine exams on outpatients and hospitalized patients.

You will lie on an exam table. If necessary, a nurse or technologist will insert an intravenous (IV) catheter into a vein in your hand or arm.

The radiotracer will be injected just beneath the skin, or sometimes deeper, using a very small needle.

Immediately after the injection, the gamma camera will take a series of images of the area of the body being studied.

When imaging begins, the camera or scanner will take a series of images. The camera may rotate around you or stay in one position. You may need to change positions in between images. While the camera is taking pictures, you will need to remain still for brief periods. In some cases, the camera may move very close to your body. This is necessary to obtain the best quality images. Tell the technologist if you have a fear of closed spaces before your exam begins.

The type of study you are having will determine the location of your injection and the number of scans performed.

• Melanoma cancer patients — Two to five doses of radiotracer are injected into the skin or other tissue surrounding the site of the melanoma. Images may be taken of the arms and underarms, legs and groins, or head, neck and chest, or other areas, depending on the site of the melanoma. Your skin will be marked to show where your lymph nodes are located. Imaging for this procedure usually takes about one to two hours, but may take up to three to four hours.
• Breast cancer — The radiotracer may be injected in multiple sites near the tumor and/or around the areola, or nipple. The breast, chest and underarm regions will be imaged. Imaging usually is completed within 30 minutes to one hour, but may take up to two or more hours.
• Leg or arm swelling (edema) — The radiotracer is injected between the first and second fingers or toes of each hand or foot. Both the swollen and healthy arm or leg will be imaged so that the two sides can be compared. Depending on the degree of lymphatic obstruction and the cause, imaging may take 30 minutes to several hours.

For some procedures, you may also be asked to exercise lightly for about 10 minutes—walking for leg exams or doing handgrip or lifting exercises for arm exams. Additional images are taken once you complete these exercises.

After the exam, you may need to wait until the technologist determines if more images are needed. Sometimes, the technologist takes more images to clarify or better visualize certain areas or structures. The need for more images does not necessarily mean there was a problem with the exam or that something is abnormal. It should not cause you concern.

If you have an intravenous (IV) line for the procedure, your technologist will usually remove it. The technologist will leave it in place if you are to have another procedure that same day that requires an IV line.

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What will I experience during and after the procedure?

Except for intravenous injections, most nuclear medicine procedures are painless. Reports of significant discomfort or side effects are rare.

No anesthesia is needed for a scintigram unless a lymph node biopsy is performed in the operating room following the procedure.

You will feel a slight pin prick when the technologist inserts the needle into your vein for the intravenous line. You may feel a cold sensation moving up your arm during the radiotracer injection. Generally, there are no other side effects.

For lymphoscintigraphy or sentinel node studies, the radiotracer is not injected intravenously, but rather near the tumor site.

It is important to remain still during the exam. Nuclear imaging causes no pain. However, having to remain still or in one position for long periods may cause discomfort

Unless your doctor tells you otherwise, you may resume your normal activities after your exam. A technologist, nurse, or doctor will provide you with any necessary special instructions before you leave.

The small amount of radiotracer in your body will lose its radioactivity over time through the natural process of radioactive decay. It may also pass out of your body through your urine or stool during the first few hours or days after the test. Drink plenty of water to help flush the material out of your body.

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Who interprets the results and how do I get them?

A radiologist or other doctor specially trained in nuclear medicine will interpret the images and send a report to your referring physician.

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What are the benefits vs. risks?

Benefits

• This nuclear medicine test has essentially replaced the more complex procedure formerly used to assess the lymphatic system as well as to determine the spread of cancer to lymph nodes (lymphangiography).
• Lymphoscinitigraphy allows for a less extensive surgery to be performed which has fewer side effects and a lower morbidity rate compared to more radical surgery (axillary lymph node dissection).
• Nuclear medicine exams provide unique information that is often unattainable using other imaging procedures. This information may include details on the function and anatomy of body structures.
• Nuclear medicine supplies the most useful diagnostic or treatment information for many diseases.
• A nuclear medicine scan is less expensive and may yield more precise information than exploratory surgery.

 

Risks

• Because nuclear medicine exams use only a small dose of radiotracer, they have a relatively low radiation exposure. This is acceptable for diagnostic exams. Thus, the potential benefits of an exam outweigh the very low radiation risk.
• Doctors have been using nuclear medicine diagnostic procedures for more than six decades. There are no known long-term adverse effects from such low-dose exposure.
• Your doctor always weighs the benefits of nuclear medicine treatment against any risks. Your doctor will discuss the significant risks prior to treatment and give you an opportunity to ask questions.
• Allergic reactions to radiotracers are extremely rare and usually mild. Always tell the nuclear medicine personnel about any allergies you may have. Describe any problems you may have had during previous nuclear medicine exams.
• The radiotracer injection may cause slight pain and redness. This should rapidly resolve.
• Women should always tell their doctor and radiology technologist if there is any possibility that they are pregnant, or they are breastfeeding. See the Safety in X-ray, Interventional Radiology and Nuclear Medicine Procedures page for more information about pregnancy, breastfeeding and nuclear medicine exams.

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What are the limitations of Lymphoscintigraphy?

Nuclear medicine procedures can be time consuming. It can take several hours to days for the radiotracer to accumulate in the area of interest. Plus, imaging may take up to several hours to perform. In some cases, newer equipment can substantially shorten the procedure time.

The image resolution of nuclear medicine images may not be as high as that of CT or MRI. However, nuclear medicine scans are more sensitive for a variety of indications. The functional information they yield is often unobtainable using other imaging techniques.

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This page was reviewed on January, 16, 2020

Multi-factorial considerations for intra-thoracic lymph node evaluations of healthy cats on computed tomographic images | BMC Veterinary Research

Intra-thoracic lymph nodes could be clearly detected only on post-contrast enhanced CT images. Without enhancement of contrast medium, the inability to distinguish between lymph nodes and surrounding soft tissues in the feline thorax could be accounted as a limitation. Therefore, the contrast-enhanced technique could be applied to the CT procedure to ensure a greater degree of precision in the images. Although use of an intravenous contrast medium was routinely followed in CT scan to improve image quality and facilitate the differentiation between normal and pathological tissue [16], all intra-thoracic lymph nodes remained undetectable in kittens. This might be due to several reasons, such as the smaller size of the lymph node, lesser fat accumulation in the mediastinum or adjacent structures that affects the evidence of lymph node boundary, and the presence of an enlarged, thymus-suspected soft tissue structure that might later obscure the smaller lymph nodes. In dogs, progressive involution of thymus could be found between the ages of 6 and 23 months [17]. However, the degeneration time of the thymus in cats had not been reported. Considering this, the oldest cat presenting with a thymus-suspected structure was aged 12 months. However, this was not conclusive and further studies are needed.

BW and BCS were described as factors that effected to a feasibility of lymph node detection in the previous studies [12, 13]. In addition to the higher BW in male cats, the BW and BCS were significantly greater in gonadectomized cats than those of both intact genders. The results of this study were similar to that of a previously published investigation [18]. The gained BW in gonadectomized cats was caused by hormonal variations, which subsequently increased food intake [19,20,21]. The greatest average BW and BCS, specifically in senile cats, was assumed to affect the feasibility of detecting intra-thoracic lymph nodes considering the clear fat-lymph node demarcation. In dogs, the surrounding fat formed a well-defined boundary to the lymph node [12]. However, the statistical differences could not be visualized when comparing the feasibility to detect lymph nodes and the factors associated with BW or BCS in this study. In contrast, the feasibility of detection was significantly correlated to the size of the lymph nodes. Therefore, a larger lymph node size was associated with an ease of detection, which was consistent with the outcomes of a previous report [12].

Juvenile and mature cats revealed fewer lymph nodes on the CT images. With regard to the BCS, senile cats typically presented with higher BC and BCS. Besides, the larger dimensions of lymph nodes, especially at the cranial mediastinal and tracheobronchial areas, were detected in this group. This could be attributed to the fat accumulation at the hilus of the lymph node [13]. Loss of the evidence of nodal hilus on diagnostics imaging was associated with neoplastic infiltration in multiple species [22, 23]. However, the disappearance of the fat accumulation at the nodal hilus in present study might be due to the small size of most lymph nodes. Currently, there are no studies that have reported the relationship between hilus of lymph node and dimensions of the lymph node. Therefore, it was assumed that a higher BCS in cats was associated with a greater degree of fat deposition at the hilar region of lymph nodes as seen in some cats of this study. However, the relationship between either BCS or the accumulation of fat at the hilus and a dimension of lymph nodes should be further investigated.

The maximal width of lymph node on transverse CT image, a primary axis of CT diagnosis in veterinary medicine, was utilized to statistically observe several aspects in present study. The mean ± SD of the widest of sternal lymph node, cranial mediastinal lymph node, and tracheobronchial lymph nodes were 3.93 ± 0.74 mm, 4.02 ± 0.65 mm, and 3.51 ± 0.62 mm, respectively. Previously, a report had quantitatively assessed the tracheobronchial and sternal lymph nodes after inoculation with Aelurostrongylus abstrusus (A. abstrusus) in 6 cats [24]. The results showed that the mean ± SD of pre-inoculated dimensions of intra-thoracic lymph nodes were similar to that of our results. Subsequently, after infection at 48 and 81 days, moderate lymphadenopathy due to the reactive hyperplasia was detected through thoracic radiographs and post-contrast enhanced CT image with an increased CT attenuation of the affected lymph nodes. Previous studies reported that CT attenuation of normal intra-thoracic lymph node at pre- and post-contrast enhancement were 7.3–60 and 8–263 HU, respectively [4, 14]. Whereas, the CT attenuation at post-contrast CT image were ranging form 15.75–143.40 HU. Therefore, the estimated attenuation number of intra-thoracic lymph nodes at pre- and post-contrast enhancement should be 7.3–60 and 8–263 HU. Recently, Smith et al. (2019) reported that the size of presumptively normal intra-thoracic lymph nodes was not affected by age, weight and sex [4]. However, that study was performed in adult cats whose ages began from 1.75 years. At that age, a similar result was observed, implying that lymph node size in G2 and G3 was not significantly different. A comparison between studies showed that the mean widths of sternal, cranial mediastinal, and tracheobronchial lymph nodes in the previous study were 3.0, 2.1 and 2.4 mm, respectively, which were smaller than our results. This might be due to the difference in age ranges between studies; the previous study was conducted in cats whose age range was between 1.75 and 21 years (median = 7.5 years), whereas in the present study, the cats’ age ranged from 4 months to 11 years (median = 2 years). The smaller size of lymph nodes in previous study might be due to age-related replacement of immune cell by connective tissue [25].

Although sex is not a factor on lymph node size, gonadectomized male cats have a longer lymph node than those of the spayed females in the previous study [4]. Considering the sex, male cats were significantly heavier than female cats. Therefore, body size might affect the lymph node size, both in the previous and the present study. Last but not least, present study was evaluated the effect of gonadectomy on the lymph node size. Although it has been reported that gonadectomy causes a decrease in androgens in post-pubertal male mice due to its effect on the lymphoid organs by increasing immune cells [26]; the different sizes of lymph nodes between intact and gonadectomized cats could not be detected in our study. The discrepancy between studies might be due to the inter-species difference or a smaller population size in the present study. Therefore, prospective study with a larger population and control protocol might be further required.

The resolution of the CT image is a crucial goal for diagnostic quality. Detectability of anatomical structures, especially low-contrast organs, is related to several factors such as radiation dose requiring a combination of tube current and tube voltage, slice thickness, and pitch [27,28,29]. Radiation dose is the main factor required for the creation of a qualified image due to quantum detection at the image detector [27]. To create a valuable diagnostic CT image, higher signal-to-noise ratio (SNR) is desirable to produce a greater image quality. To achieve a higher level of SNR, radiation dose must be increased to reduce image noise [30]. There are several factors contributing to image noise of a CT image. For example: a lower kVp setting causes a greater photoelectric effect [28, 31]. Despite this, it can increase the contrast of the image and enhance visualization [28]; this effect on the attenuation of a photon in the object tissue, called photon starvation effect, can increase noise [27].

It is well known that slice thickness in also counted as a factor of image quality that contributes to the noise of an image [32]. Slice thickness is one of the factors that can influence the interpretation precision on CT images [27, 30]. Generally, slice thickness should be as low as possible to reduce partial volume effect (PVE) that is the effect of a thicker slice causing the less perceptibility of the smaller anatomical structures [33]. Despite decreasing PVE, too thin a slice could increase the image noise [32]. To conquer that problem, an increased radiation dose with an increased tube current can be used to increase SNR [28], however, it would result in a higher dose delivery to the patient.

The previous report unveiled that 1.5–2.0% of cancers may be related to the CT radiation [34]; the scanning technique in clinical practice must be optimized to achieve the diagnostic task with a higher imaging quality and lower delivered radiation dose following the concept of as low as reasonable achievable (ALARA). In addition, the scan range should reportedly be as small as possible due to the related total radiation dose delivered [27]. It is well known that dose-length product (DLP) is the total radiation dose absorbed by the patient with the relationship to number of slices and the scanning length as: DLP = CTDI × T × N where CTDI: CT dose index, T: slice thickness and N: number of slices [35]. It has been reported that a tube current has a linear relationship with slice thickness. When the slice thickness is increased, the higher radiation dose that produces the adequate number of photons to produce the image must be increased to reduce noise and increase the SNR [32]. From present study, slice thickness at 0.625 mm provided the highest detection score of the normal, intra-thoracic lymph nodes. Similar result was reported in a previous study with human participants, which suggested that the interpretation of CT images of children required a smaller slice thickness than that of the adults [36] to conquer with PVE. However, at the similar setting of mA, thinner slices of CT images can increase noise [32] and degrade image quality. In dogs, the recommended CT slice interval to examine the tracheobronchial lymph node was 1.0–1.5 mm [37], which was consistent with the results of the present study. In the retrospective CT study on feline lymph node the slice thickness was setup only at 1.5 mm [4]. Since the significant difference between the feasibility to detect feline intra-thoracic lymph nodes at the slice thicknesses of 0.625 and 1.250 mm could not be identified, the appropriate slice thickness for CT examination to enhance detectability with higher SNR of feline thorax should be 1.250 mm. At this CT thickness, the radiation risk to animals is reduced considerably, while ensuring a good SNR of CT image that would be suitable for data management.

In addition to the slice thickness at 1.250 mm, the present study was conducted under the automatic exposure control (AEC). AEC is the tube current modulation at the longitudinal (z) axis and angular (x-y) axes that can decrease dose delivery to the patient. Besides, this study was performed at 0.969 of pitch. A higher pitch can decrease motion artifact [27] that can enhance image resolution. In addition to the detectability and size of the intra-thoracic lymph nodes of cats in this study, a variety of exposure settings on the low contrast detectability (LCD) and dose delivery should be further investigated to optimize scanning techniques for higher image quality along with ALARA concept.

Despite the variation of the age groups, the small sample size with a limited breed of cats could be considered as a major limitation of this study. Due to the regulation of animal use for scientific research, the appropriate number of cats, which were screened to be a good representative in according to the inclusion criteria, was agreed and designed. Therefore, at this sample size, presented information could be applied and enlighten for clinical usage. In addition, bronchoscopy and coproscopy were not performed in this study because no incidence of the lung parasite in the area of this study was reported. Besides, all of the enrolled cats were indoor cats, which regularly underwent health checks and were updated with all preventive medicine. Moreover, according to the policy of animal use, additional invasive procedures such as tissue biopsy or necropsy to validate the anatomical tissue type could not be done for both intra-thoracic lymph nodes and suspected thymus. Further prospective studies with a larger study population, along with the validation to examine the gross anatomy of the feline thorax would be necessary.

Lymphatic marking with sentinel node biopsy

This information explains how lymphatic marking with sentinel node biopsy is performed at Memorial Sloan Kettering (MSK).

You may be prescribed this procedure if you have breast cancer or melanoma. It will help your doctor understand if cancer cells have spread to the lymph nodes.

to come back to the beginning

Information on the lymphatic system

The lymphatic system has 2 main functions:

• helps fight infections;
• promotes the outflow of fluid from different parts of the body.

The lymphatic system consists of lymph nodes, lymphatic vessels and lymphatic fluid (see Figures 1 and 2).

Figure 1. Lymphatic system in the breast

• Lymph nodes are small bean-shaped formations located along the lymphatic vessels. They filter the lymphatic fluid, trapping bacteria, viruses, cancer cells and metabolic products. A sentinel lymph node (also called a sentinel lymph node) is the first lymph node that cancer cells spread to.
• Lymphatic vessels are tiny tubes (similar to blood vessels) that carry lymphatic fluid to and from the lymph nodes.

• Lymphatic fluid is a clear fluid that travels through the lymphatic system. It carries cells that help fight infections and other diseases.

Figure 2. Lymphatic system of other parts of the body

to come back to the beginning

Lymphatic marking

Lymphatic Marking is the first step in a sentinel node biopsy.It is done to find the signal node. Lymphatic marking may be done the day before the sentinel node biopsy.

The location for the lymphatic marking procedure is listed on the reminder you received.

During pegging procedure

During the procedure, you will need to lie on a reclining chair for about 20 minutes. While you are in the chair, your doctor or nurse will inject a small amount of radioactive fluid under your skin under the areola of the affected breast.You may feel a tingling sensation or burning sensation during the injection.

After injection, you will need to massage the area around the injection site for 10 minutes. This is necessary for the radioactive liquid to enter the signaling unit (s). The technician will then measure the level of radioactivity in the breast, armpit and thigh on the affected side and check how much fluid has been absorbed. This can be done in 2 ways:

• The technician can use a small handheld device called the Neoprobe;

The

• can put you in a large full-body medical imaging machine.

Both methods are equally effective. The doctor or nurse / nurse will tell you what to expect.

After pegging procedure

If you are scheduled for a sentinel biopsy on the day of your stripping procedure, you will be taken to the biopsy area.

If you are scheduled for a sentinel biopsy on a different day from your stripping procedure, you will go home after the procedure.

Breastfeeding

Refrain from breastfeeding for 24 hours after lymphatic tracing.You can express milk, but do not feed your baby. You can discard this milk or store it for 24 hours.

After 24 hours, you can resume breastfeeding or feed your baby previously expressed milk.

If you have questions, talk to your radiologist.

to come back to the beginning

Sentinel lymph node biopsy

Before biopsy

Sentinel biopsy is a surgical procedure.A sentinel biopsy is often done during breast surgery or melanoma surgery.

If you are scheduled for a sentinel biopsy as a separate surgery, read the resource Preparing for Surgery. It explains how to prepare for a biopsy. Your nurse will give you this material at your appointment. You can also find it online.

During biopsy procedure

Before the procedure, you will receive anesthesia (medication that will make you fall asleep).

When you are asleep, your surgeon will inject you a small amount of blue dye near the cancer site. This dye will travel through the lymphatic vessels to the lymph nodes. It will color the signal nodes blue.

Your surgeon then uses a Neoprobe (a small handheld device) to measure the radiation from the fluid injected during the lymphatic marking procedure. Having found the area where the signal nodes are located, he will make an incision (surgical incision).It will find blue signal nodes and remove them. The nodes will be sent to the pathology department and examined for cancer cells.

If sentinel nodes contain cancer cells, you may need to remove more lymph nodes. This is called axillary lymph node removal. The surgeon will discuss this with you in more detail if necessary.

After biopsy procedure

You may go home on the day of your biopsy, or you may need to stay in the hospital.It depends on the number of operations performed to you. The doctor or nurse / nurse will tell you what to expect.

To learn what to expect after your procedure, read the resource Caring for Yourself After a Sentinel Lymph Node Biopsy.

to come back to the beginning

synlab: lymph nodes

What is the lymphatic system?
The human lymphatic system is a huge network of tiny vessels that combine into larger ones and go to the lymph nodes.Lymphatic capillaries penetrate all human tissues, as well as blood vessels. Connecting with each other, the capillaries form the smallest network. Through it, fluid, protein substances, metabolic products, microbes, as well as foreign substances and toxins are removed from the tissues.
The lymph that fills the lymphatic system contains cells that protect the body from invading microbes and foreign substances. Combining, the capillaries form vessels of various diameters. The largest lymphatic duct flows into the bloodstream.

What are lymph nodes and why are they needed?
Lymph nodes are round or oval formations ranging in size from 1 millimeter to 2 centimeters. The lymph node is a barrier to the spread of both infection and cancer cells. It forms lymphocytes – protective cells that are actively involved in the destruction of foreign substances and cells.
There are several groups of lymph nodes. These groups are located in such a way as to become an obstacle to infection and cancer.So, the lymph nodes are located in the elbow bend, armpit, in the knee bend, and also in the groin area. The lymph nodes in the neck provide protection against infections and tumors in the head and organs located in the neck.
A huge number of lymph nodes are found in the abdominal and chest cavity. Lymphocapillaries penetrate organs as well as superficial tissues. The lymph nodes along the blood vessels perform the same functions.

An increase in lymph nodes indicates a problem in the area that the node “serves”.Most often, an increase in the lymph node is associated with an infection, less often it is a consequence of a tumor lesion.
With purulent processes, as a rule, acute lymphadenitis occurs – inflammation of the lymph node. An inflammatory process occurs due to the ingress of microbes from wounds located in the “service area” of the lymph node. The main manifestation is an increase in the lymph node, the appearance of pain when it is felt. If a purulent process occurs over the lymph node, the skin may turn red.If at this moment the resulting cavity is not opened, the lymph node membrane ruptures and pus penetrates into the surrounding tissues. There is a severe complication of lymphadenitis – phlegmon.

IMPORTANT! Ultrasound has limited capabilities, and its data without additional research cannot be the basis for a diagnosis.

How is the examination of the lymph nodes done. Lymph node ultrasound does not require special training and is extremely simple.The sensor of the apparatus is lubricated with a gel-like substance and tightly pressed against the part of the body that is not covered by clothing. An image is projected on the monitor of the ultrasound system, which is formed by sound waves sent into the body and reflected back. An exception is the procedure for ultrasound of the lymph nodes in the groin. Since the changes in the lymph nodes in this area are predominantly of a venereal nature, it is necessary to undergo an examination by a venereologist before conducting.

Ultrasound examination of lymph nodes – health articles

Table of Contents

A large number of people regularly face the problem of swollen lymph nodes and their inflammation.
of people.To identify the cause of this condition, ultrasound diagnostics allows. It is safe, painless
and at the same time informative. Ultrasound of lymph nodes makes it possible to assess their condition, determine factors
the occurrence of pathology and the solution of other problems.

In most cases, the diagnosis allows a timely diagnosis and appropriate treatment,
preserving the health of the patient.
Also, the examination can be carried out with the aim of correcting therapy and increasing
its effectiveness.

How is an ultrasound of the lymph nodes performed?

The procedure does not cause any significant discomfort to the patient and takes only 15–20 minutes.
Survey
easily
tolerated even by young children and elderly people (including in a weakened state).

First, the patient frees the area of ​​projection of the examined lymph nodes from clothing. Then on the skin the doctor
applies a special gel to ensure better sensor contact.After that, the specialist proceeds directly
to the diagnosis.

The machine emits ultrasonic waves that penetrate the skin and are reflected off the internal tissues. Appliance
catches signals and transmits the image to the monitor screen. This allows the doctor to examine the tissue
and reveal even hidden pathological changes.

Indications for referral to ultrasound

Examinations are carried out at:

• Soreness of the lymph nodes on palpation
• lymph node motility
• the appearance of seals in the assembly

Also, diagnostics are prescribed for local redness of the skin and local temperature rise.

What does an ultrasound scan of the lymph nodes of the neck and other parts of the body show?

Ultrasound of the lymph nodes of the neck and other parts of the body helps the doctor understand their condition, determine the size,
shape
and other features. Also, within the framework of diagnostics, the causes of inflammation and other pathological
processes, their nature and dynamics. The doctor can determine changes in the flow of blood and lymph.

Preparation for ultrasound

Features of preparation largely depend on which zones are being examined.

To ensure a high-quality, simple and comfortable diagnosis, it is necessary to wear for the procedure
free,
comfortable clothing that will not restrict movement and will free up the desired area for research.

Interpretation of results

As a result of the examination, the doctor can detect the following pathologies:

• Lymphadenitis
• Lymphadenopathy
• Oncological process

If the lymph nodes become inflamed under the knees, this indicates infections and other pathologies of the lower extremities.Lesions in the pelvic region may indicate infections of the genitourinary system and lower extremities.

In each case, the diagnosis is made exclusively by a doctor. In this case, the interpretation of the results is carried out
a specialist who has the necessary knowledge and skills for this. Shouldn’t try to put
diagnosis yourself.

Important! In some cases, in addition to ultrasound of the lymph nodes, other examinations are also carried out.Only
based on the joint result, an accurate diagnosis is made and adequate therapy is prescribed.

Ultrasound of lymph nodes in children

The modern technique has no contraindications for the patient’s age. The survey can even be carried out
newborns. Moreover, the procedure is easily tolerated. Kids are able to endure all the manipulations.

Important! When carrying out diagnostics, the doctor takes into account the fact that lymph nodes always remain in childhood
Little
enlarged.Moreover, this condition is the norm, not a pathology. This is because
the child’s immune system is being formed. Lymph nodes during this period are structured by structure, contours
and shape. Formations up to a centimeter in diameter are not dangerous.

This takes into account the fact that an increase in lymph nodes can occur against the background:

• Teething
• development of caries
• insect and animal allergies
• reactions to new food

Advantages of contacting MEDSI

• Experienced technicians. Diagnosis is carried out by a physician with the necessary knowledge and skills. it
  allows to increase the information content of the survey and its accuracy
• Expert grade equipment. A modern device is used for diagnostics. This makes it easier for workers
  processes
  and makes the study comfortable for the patient. Image quality assures the validity of method
• Possibilities for examining children and adults. Ultrasound of the lymph nodes is performed at the clinic
  patients
  regardless of age
• Possibilities for the therapy of identified pathologies. Doctors are ready to start treatment shortly after
  diagnosis time
• There are no queues. You can take the examination at a convenient time and without a long wait
• Capabilities for multiple surveys. If necessary, the patient can undergo an ultrasound scan at the same time
  mammary glands and lymph nodes, diagnostics of other organs and tissues.This saves time
  and provide ideal conditions for making an accurate diagnosis

To sign up for an ultrasound of the lymph nodes, just call +7
(342) 215-06-30. Our
specialist
will answer all questions. You can also use the SmartMed application for recording.

Lymph node biopsy in the neck – how it is performed, to whom it is indicated, transcript of the results

Lymph node biopsy in the neck: about the method, contraindications

About lymph

The lymphatic system consists of lymph nodes and blood vessels that feed them.It is multifunctional, but its main function is to protect the body from all sorts of pathogens.

For this, there are immune cells in the lymph nodes – T-lymphocytes and B-lymphocytes.

The passage of blood through small capillaries creates a plasma filtration effect. Partly the blood enters the surrounding tissues, partly it goes back into the bloodstream. Another one is in the vessels. The result is the formation of lymph. It is a clear, watery liquid that contains immune cells.

Lymphatic vessels, uniting, enter the thoracic lymphatic ducts, right and left, the same, in turn, flow into the veins. It turns out the return of fluid to the bloodstream.

Lymph nodes, as part of the body’s immune system, are located in different parts of the body. Their task is to be filters, a kind of barriers for infectious carriers and pathogenic cells.

Localization of lymph nodes in the neck

Lymph nodes are found throughout the body.Now we are interested in the neck, where there are such groups of lymph nodes:

• Chin;
• Submandibular;
• Prelaryngeal
• Jugular;
• Parotid;
• Behind-the-ear;
• Occipital;
• Back cervical;
• Supraclavicular.

The physical examination assumes their feeling. An enlarged lymph node means some pathological processes occurring in it.It can be an inflammatory, purulent process, the onset of infection, as well as oncology.

About method

A lymph node biopsy is the collection of a biopsy sample for further study. The procedure is very informative, the accuracy of the diagnosis is over 90 percent.

A biopsy is done if cancer, tuberculosis or other diseases are suspected. The thing is that in a normal state the lymph nodes, which are small round lumps that cannot be felt.But with the same inflammation, the lymph nodes become denser, increasing in size.

Readings

There are many indications for the procedure:

• Knot over 1 cm;
• Soreness;
• Inflammatory process for no apparent reason;
• Suspected malignant tumor;
• The lymph node does not change, although the treatment has been carried out for a long time;
• Sarcoidosis or lymphogranulomatosis, etc.d.

This procedure gives an understanding:

• What is the specificity of the course of the disease;
• What is the level of infection;
• If a patient with cancer has metastases.

Contraindications

Since the procedure involves surgical intervention, it is important to take into account the limitations and contraindications for its implementation:

• Poor blood clotting;
• Suppuration in the problem area and adjacent areas;
• Scoliosis;
• Increased body temperature;
• Problems of skin diseases.

Oncology and enlargement of cervical lymph nodes

Some cancers (lymphomas) arise and develop in the lymph nodes. They are classified as:

• Hodgkin’s lymphomas;
• Non-Hodgkin’s lymphomas.

But more often metastases penetrate into the lymph nodes.

This is due to the ability of cancerous tumors to metastasize. Benign tumors do not have this ability.

Breaking away from the focus, the mutated cells migrate, enter the blood and lymph vessels and create secondary foci. The lymph nodes adjacent to the primary focus become the most vulnerable.

Metastasis to the cervical lymph nodes

Cervical lymph nodes are at greater risk of metastasis. It is there that metastases of squamous cell carcinoma of the upper respiratory tract, cancer of the thyroid gland, skin and salivary glands penetrate.

Sometimes the primary focus is localized in another part of the body:

• Breast oncology – up to 4.5% of cases;
• Oncology of the lungs – up to 32% of cases;
• Oncology of the esophagus – up to 30% of cases;
• Renal oncology – up to 8% of cases;
• Testicular cancer – up to 4.5%.

Minor indicators of metastasis were diagnosed in oncology of the cervix, uterus, prostate, central nervous system, liver, bladder, ovaries.

How to detect metastases in the lymph nodes

The problem is not simple, because in the presence of a small number of mutated cells in the lymph nodes, there are usually no symptoms. If there is any suspicion, the doctor needs to make an accurate diagnosis.

And this is where a lymph node biopsy comes to the rescue.It is carried out in different ways:

• Biopsy with the introduction of a needle into a suspect node. It is carried out under local anesthesia. The procedure takes up to 30 minutes.
• Biopsy, open. This is a surgical procedure performed under local or general anesthesia, with the removal of part or all of the lymph node.
• Sentinel lymph node biopsy. A radiopharmaceutical or fluorescent dye is injected into the neoplasm. Penetrating into the lymphatic vessels, it shows the problem node, the so-called sentinel.

After the biopsy procedure, all materials are sent to the laboratory for study.

Study of the selected tissue in the laboratory

In the laboratory, under a microscope, research is carried out, cytological and histological. Having found mutated cells, the preliminary diagnosis is confirmed.

It is important for the doctor to understand which organ became the source of infection. Only in this way can he prescribe the optimal treatment tactics.

Consequences

Basically, patients easily tolerate the procedure, there are no consequences or complications. But you still have to deal with symptoms that arise as a consequence of the procedure. It can be:

• Feeling weak;
• Temperature rise;
• Painful sensations of pain in the head and neck area;
• Dizziness;
• Pinched or damaged nerve

Unpleasant consequences can be caused by insufficient qualifications of the doctor – damage to the vessel, penetration of bacteria.

If you find yourself with the above symptoms, you should consult a doctor. In the Onco.Rehab oncology clinic you can get the addresses of our reliable partners, where a lymph node biopsy is performed according to international standards.

Ultrasound of lymph nodes – MC “Kraina Zdorov’ya”

Ultrasound of lymph nodes is an informative and safe study that determines the state of the lymph nodes, serves as a differential method for diagnosing infectious, autoimmune diseases, and also identifies various neoplasms.

Lymph nodes are organs of the immune system that play the role of a protective filter in the human body.

Retains harmful substances circulating in the blood (viruses, bacteria, toxins, tumor cells, etc.).

Almost any pathological process leads to changes in the structure of the lymph nodes. They grow, thicken, acquire unnatural shapes and mobility

The most frequently performed ultrasound of the following lymph nodes:

• On the neck;
• In the submandibular area;
• In the groin area;
• In the area of ​​the armpits;
• In the supraclavicular zone;
• In the subclavian area;

Ultrasound is prescribed in order to:

• to study the size, shape, contours, density, vascular pattern of lymph nodes
• to determine the presence and localization of the inflammatory process;
• to monitor the treatment process.

Readings:

• pain in the area of ​​the lymph nodes
• sharp headache
• persistent chills for several days
• compaction and enlargement of the lymph nodes in size;
• infectious and viral diseases;
• Suspected connective tissue damage;
• lymph node edema and persistent fever,
• Suspicion of neoplastic diseases of the internal organs or the lymphatic system.

If you find a lump in the area of ​​the lymph nodes, or even more so you feel discomfort and pain when pressing these seals, you should definitely consult a doctor.

After the examination, the doctor will provide recommendations for an ultrasound scan, if required. Indeed, for any deviations from the normal state of health, only a doctor can prevent a complication.

90,000 ultrasound of lymph nodes – clinic CMT

Ultrasound of the lymph nodes reveals changes of an inflammatory or neoplastic nature that are observed in various diseases.

• As a rule, a study of the cervical, axillary, inguinal, and submandibular lymph nodes is performed.

• All of them are located at a shallow depth, so the technique allows you to get fairly complete information about their condition.

• In some cases, it is required to use additional types of research to establish an accurate diagnosis.

Such a need often arises when cancer is suspected, which is confirmed after a biopsy of the lymph nodes.

Indications for research.

• There are clear indications for performing ultrasound diagnostics of a certain group of lymph nodes.

• For example, ultrasound of the axillary lymph nodes is prescribed in cases where there is a suspicion of an oncological process in the tissues of the breast or in other organs of the chest.

• Another indication for the study of this group of lymph nodes is the suspicion of HIV, when, against the background of the patient’s relative health, an increase in the inguinal or cervical lymph nodes is observed.

Ultrasound in other areas is performed in the following cases:

• Submandibular lymph nodes – in the presence of visible deformities of the bones of the facial part of the skull, with suspicion of leukemia, with pathological formations in the oral cavity.

• Ultrasound of the lymph nodes in the groin is prescribed for suspected STIs, cancer and metastases, diseases of the pelvic organs in women and men.

• Ultrasound of the supraclavicular lymph nodes is indicated for inflammatory processes in the mediastinum, as well as if the patient has signs of malignant tumors.

How to perform ultrasound of the lymph nodes.

• The study is carried out without special training, its duration is from 10 minutes to half an hour.

• The patient lies down on the couch and removes clothing and other items from the scanned area.

• A sensor is pressed to the problem area, after which the doctor sees a clear picture on the monitor.

• By moving the sensor and switching between different modes of operation of the device, the specialist collects all the necessary data, which is then indicated in the conclusion.

You can perform ultrasound of lymph nodes in the armpit, neck or other parts of the body in our center. To do this, you must make an appointment by phone or fill out the form on the website, having previously selected the appropriate time. The study is carried out by an experienced doctor using modern equipment.

In order to get a high-quality picture of the study, read the memo on preparation for an ultrasound scan – download in PDFMost often, inflammation of the lymph nodes is the result of organ malfunction or the presence of an infection. Inflammation of the lymph nodes behind the ear is most often indicative of problems in the upper body. We will talk in more detail about the inflammatory processes of the latter in today’s article.

The main causes of inflammation of the lymph nodes

Below we have given the diseases in which the lymph nodes maximally increase in size and are most exposed to inflammatory processes:

• Faringitis is a disease in which there is significant inflammation of the mucous membrane of the throat
• Otitis – a disease that is characteristic of different types of inflammation in the internal and external passages of the ear
• Diseases of the mouth, such as caries (usually the cervical, posterior and submissive lymph nodes are inflamed), desin inflammation and flux
• Nevit – a disease, a characteristic feature of which is hearing impairment
• Excessive production of lymphocytes may also be the cause of an increase in lymph nodes
• Sinitis, sinusitis, sinusitis, tonsillitis and hippopotamus are the cause of the inflammatory processes that affect the size of the lymph node
• Infectious diseases, such as: dermatitis, herpes,
• Development of fungal infections and bacteria.

For more serious causes of inflammation of lymphoid tumors, the following diseases are related:

• syphilis;
• gonopey;
• Tubes;
• ctr and staphylok;
• blue stick and pathogenic folds;
• red wolf, gout, rheumatism, arthritis and even chronic alcoholism;
• Significant incidence of lymphoid malignancies in the ears and neck may be the cause of a viral disease, such as AIDS;
• Cancer diseases can rarely be the reason for changes in the size of the lymph nodes;

Treatment methods

The choice of treatment method directly depends on the stage and causes of inflammation!

It should be understood that inflammation of the lymph nodes behind the ear is the body’s response to a pathology or infection, so treatment should start with its identification.Therefore, the therapeutic method consists of two stages:

• The first is to determine the cause of the inflammation;
• Second – direct treatment and exclusion of the possibility of relapse.

Basic medicines used to treat the inflammatory process in the lymphatic system:

• Antibiotics – to eliminate bacterial infection
• Antivirals – for fighting viruses
• Antifungal drugs – for the treatment of fungal pathologies
• Antihistamines – to eliminate allergic reactions
• Medicines for unpleasant symptoms (from headache to cough) – used when there are specific signs that worsen the patient’s standard of living
• Immunity stimulants and vitamins – required in the treatment of any inflammation of the lymph nodes

It is important to note that only a specialist can prescribe treatment, based on the characteristics of your body, data obtained from analyzes and other types of diagnostics.Therefore, you should not resort to folk remedies, because you cannot establish with 100% certainty the cause of inflammation of the lymph nodes behind the ears, and therefore, choose the right treatment.

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