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. Bioppysy sp ecimens of unex plained enlar ged l ym ph node will be mandatory. General causes of lymphadenopathy CAUSES: 1- Reactive hyperplasia: Infection by bacteria or viruses. Immune stimulation, as in rheumatoid arthritis. Draining degradation products from cancer. Particulate material. 2- Neop las tic conditi ons: Secondary of deposits of carcinomas. PiPrimary l ymph oid idt tumors. Reactive Lymphadenitis Reactive Lymphadenitis is often associated with in fec tions an d nonm icro bia l in flamma tory s timu li . Reactive lymphadenitis is further subdivided to: Acute Chronic non-specific & chronic specific lymphadenitis. In most instances, the histologic appearance of tthehe nodesnodes iiss eentirelyntirely nnonon-specspecific.ific. Acute Non-specific Lyypmphadenitis This form of lyypmphadenitis 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. MhlMorphology: Macroscopically, inflamed nodes in acute non-specific lyypmphadenitis are swollen, ,gy grey-red,,gg 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. Reactive lymph node. Benea ththth the capsu lithle is the paracorti tilcal zone with lymphoid follicles having a pale germinal center in which the immune responses are often generated. Beneath this are sinusoids exten ding t o th e cent er of th e nod e. Acute Non-specific Lyypmphadenitis 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 Lyypmphadenitis This condition can assume one of three patterns, depending on the causative agent: Follicular Hyperplasia . Paracortical Hyperplasia. Sinus Hi sti ocyt osi s. Follicular Hyperplasia. This pattern is associated with infections or iflinflamma tory processes thtthat ac tittivate BllB cells. Morphology; follicular hyperplasia with reactive germinal centers. Causes Rheumatoid arthritis, Toxoplasmosis, the early stages of HIV infection. This is a more ppgypgronounced reactive change in a lymph node, with a larger follicle and germinal centre containing macrophages. In general, lymph nodes in a benign reactive process are more likely to enlarge quickly and be tender. Paracortical Hyperplasia This pattern is characterized by reactive changes w ithin the T--cecell regi ons ofthf the l ymp h 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 dis tens ion an d prom inence o f the lymp ha tic sinusoids, owing to a marked hypertrophy of lini ng end oth eli al cell s and an in filtra te o f 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-Histiocyyptic neoplasms repppresent proliferative lesions of histiocytes Lymphoid Neoplasms The lymphoid neoplasms encompass a group of entities that varyyy 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 inv olv ed ly mph nodes or other tiss u es. C-Plasma cell tumours (the plasma cell dyscrasia), usuallyyp 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. Infiltration of liver by lymphoma 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-andTd T-cell tumors tha t are der ive d from spec ific 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 c lin ica l progress ion bu t may be cure d by chemotherapy, (e.g., diffuse large B-cell lymphoma) Follicular Lymphoma: Tumor cells recapitulate the growth pattern of normal germinal center B cells; More than 80% of cases are associated with c hromosoma l trans loca tion tha t 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, Aggggressive clinical behavior. Highly associated with genetic rearrangements or mutations. ONE-THIRD arise from follicular lymphomas . OilhdOccur in lymph nodes or o ther organs as stomach, small intestine, bones. Hodgkin Lymphoma: Unusual tumor mostly comprised of reactive lymphocytes, macrophages, and stromal cells;;g, 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 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 a du lts (ages 55-74) Hdki’Hodgkin’s L ymph oma 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 morppgyyphologically by the presence of distinctive neoplastic giant cells called Reed-Sternberg (RS) cells, which are admixed with reactive, nonmalignant inflammatory cells. Typical Reed-Sternberg cell Particularly characteristic are cells with two mirror-image nuclei or nuclear lobes, eachtiilh containing a large (inclusion-like) acidophilic nucleolus surrounded by a distinctive clear zone; together they impart an owl-eye appearance. The nuclear membrane is distinct. Lacunar cells HL 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. Nodular sclerosis HL Mixed cellularity HL.