Overview on some causes of lymphadenopathy

General causes of lymphadenopathy Lymph nodes, act as defensive barriers ,so any immune response against foreign antigens is often associated with lymph node enlargement (lymphadenopathy). Lymph node enlargement may be localized or generalized. The presence of lymphadenopathy may raise the possibility of lymphoma, or metastatic carcinoma. Biopsy specimens of unexplained enlarged lymph node will be mandatory.

General causes of lymphadenopathy 1- Reactive hyperplasia: Infection by bacteria or viruses. Immune stimulation, as in rheumatoid arthritis. Draining degradation products from cancer. Particulate material. 2- Neoplastic conditions: Secondary of deposits of carcinomas. Primary lymphoid tumors.

Reactive Lymphadenitis Reactive Lymphadenitis is often associated with infections and nonmicrobial inflammatory stimuli . Reactive lymphadenitis is further subdivided to: Acute Chronic non-specific & chronic specific lymphadenitis. In most instances, the histologic appearance of the nodes is entirely non-specific.

Acute Non-specific Lymphadenitis This form of lymphadenitis may be: Localized: confined to a local group of nodes draining a focal infection, as in case of suppurative tonsillitis, or breast abscess. Generalized: in case of systemic bacterial or viral infections ,as in infectious mononucleosis disease. Morphology: Macroscopically, inflamed nodes in acute non-specific lymphadenitis are swollen, grey-red, and engorged. Histologically, there are large germinal centres containing numerous mitotic figures. When the cause is a pyogenic organism, a neutrophilic infiltrate is seen about the follicles and within the lymphoid sinuses.

Acute Non-specific Lymphadenitis With severe infections, the centres of follicles can undergo necrosis, resulting in the formation of an abscess. Clinically, the affected nodes are tender and, when abscess formation is extensive, become fluctuant. The overlying skin is frequently red, and penetration of the infection to the skin can produce draining sinuses. With control of the infection, the lymph nodes can revert to their normal appearance or, if damaged by the immune response, undergo scarring.

Chronic Non-specific Lymphadenitis This condition can assume one of three patterns, depending on the causative agent: Follicular Hyperplasia. Paracortical Hyperplasia. Sinus Histiocytosis.

Follicular Hyperplasia. This pattern is associated with infections or inflammatory processes that activate B cells. Morphology; follicular hyperplasia with reactive germinal centers. Causes Rheumatoid arthritis, Toxoplasmosis, the early stages of HIV infection.

Paracortical Hyperplasia This pattern is characterized by reactive changes within the T-cell regions of the lymph node. Causes: viral infections (such as EBV), following certain vaccinations (e.g., smallpox), in immune reactions induced by certain drugs

Sinus Histiocytosis This reactive pattern is characterized by distension and prominence of the lymphatic sinusoids, owing to a marked hypertrophy of lining endothelial cells and an infiltrate of macrophages (histiocytes). Sinus histiocytosis is often encountered in lymph nodes draining cancers and may represent an immune response to the tumour or its products.

Neoplastic Proliferations Of White Cells Tumours represent the most important of the white cell disorders. They can be divided into three broad categories based on the origin of the tumour cells: 1-Lymphoid neoplasms, which include lymphomas, lymphocytic leukaemia, and plasma cell dyscrasia. 2-Myeloid neoplasms arise from stem cells that normally give rise to the formed elements of the blood: granulocytes, red cells, and platelets. 3-Histiocytic neoplasms represent proliferative lesions of histiocytes

Lymphoid Neoplasms The lymphoid neoplasms encompass a group of entities that vary widely in their clinical presentation and behaviour. A-Lymphocytic leukaemia, tumours that primarily involve the bone marrow with spillage of neoplastic cells into the peripheral blood. B- Lymphomas, tumours that produce masses in involved lymph nodes or other tissues. C-Plasma cell tumours (the plasma cell dyscrasia), usually present within the bones as discrete masses and cause systemic symptoms related to the production of a complete or partial monoclonal immunoglobulin.

Lymphoid Neoplasms Clinical presentation: All lymphoid neoplasms have the potential to spread to lymph nodes and various tissues throughout the body, especially the liver, spleen, and bone marrow. In some cases lymphomas or plasma cell tumours spill over into the peripheral blood, creating a leukaemia-like picture. Conversely, leukaemia of lymphoid cells, originating in the bone marrow, can infiltrate lymph nodes and other tissues, creating the histologic picture of lymphoma. Because of the overlap in clinical presentations, the various lymphoid neoplasms can only be distinguished based on the appearance and molecular characteristics of the tumour cells.

Lymphoid Neoplasms Two groups of lymphomas are recognized: A -Hodgkin lymphoma and B- Non-Hodgkin lymphomas Although both arise most commonly in lymphoid tissues ,the biologic behaviour and clinical treatment of Hodgkin lymphoma are different from those of most NHLs, making the distinction of practical importance.

Non-Hodgkin lymphomas Classification World Health Organization (WHO) has formulated a widely accepted classification scheme that relies on a combination of 1-morphologic, 2-phenotypic, 3-genotypic, and 4-clinical features.

Non-Hodgkin lymphomas 1-Classification Non-Hodgkin lymphoma is further subclassified into; B- and T-cell tumors that are derived from specific stages of their normal differentiation pathways. The diagnosis and classification of these tumors relies heavily on tests that detect lineage-specific antigens (B-cell, T-cell, and NK-cell markers) ; Immunohistochemistry Flow cytometry Analysis of antigen receptor genes and their protein products is frequently used to differentiate monoclonal neoplasms from polyclonal, reactive processes

Non-Hodgkin lymphomas 2-Classification Indolent types (low grade): long natural history but not curable, (e.g., follicular lymphoma) Aggressive types (high grade): rapid clinical progression but may be cured by chemotherapy, (e.g., diffuse large B-cell lymphoma) 4

Follicular Lymphoma: Tumor cells recapitulate the growth pattern of normal germinal center B cells; More than 80% of cases are associated with chromosomal translocation that results in the over-expression of the anti-apoptotic protein BCL2.

Diffuse Large B-Cell Lymphoma: The most common type of lymphoma. Heterogeneous group of mature B cell tumors, Aggressive clinical behavior. Highly associated with genetic rearrangements or mutations. ONE-THIRD arise from follicular lymphomas . Occur in lymph nodes or other organs as stomach, small intestine, bones.

Hodgkin Lymphoma: Unusual tumor mostly comprised of reactive lymphocytes, macrophages, and stromal cells; the malignant cell, the Reed-Sternberg cell (which is derived from B cells), typically makes up a minor fraction of the tumor mass.

Hodgkin’s Lymphoma older adults (ages 55-74) Malignant disorder of lymph nodes thought to be of B cell origin spreads sequentially along lymph node chain Bimodal age distribution adolescents and young adults (ages 15-40) older adults (ages 55-74)

Hodgkin’s Lymphoma Molecular studies have shown that it is a tumor of B-cell origin. Arises almost in a single lymph node or chain of lymph nodes. Spreads characteristically in a stepwise fashion to the anatomically contiguous nodes. It is characterized morphologically by the presence of distinctive neoplastic giant cells called Reed-Sternberg (RS) cells, which are admixed with reactive, nonmalignant inflammatory cells.

Hodgkin’s Lymphoma It is often associated with somewhat distinctive clinical features, including systemic manifestations such as fever. It is treated differently than most other lymphoid neoplasms. Despite these distinguishing features,

Hodgkin’s Lymphoma Five subtypes of Hodgkin lymphoma are recognized: lymphocyte predominance nodular sclerosis, mixed cellularity, lymphocyte depletion.