Mature B-cell Neoplasms.pdf

Blood and Lymphatic system Dr. Raya D. Marji Al-Balqa Applied University Faculty of Medicine  Malignant tumors of lymphoid tissue Lymphoid characterized by abnormal proliferation of B and T cells in the lymphoid tissue. Neoplasms  Le...

Blood and Lymphatic system Dr. Raya D. Marji Al-Balqa Applied University Faculty of Medicine  Malignant tumors of lymphoid tissue Lymphoid characterized by abnormal proliferation of B and T cells in the lymphoid tissue. Neoplasms  Leukemia: Tumors that involve the bone marrow and peripheral blood. Lymphoma: Tumors that involve lymph nodes or other organs predominantly. Plasma cell myeloma is confined to the bones as discrete masses or bone marrow with no lymph node or peripheral blood involvement. Neoplastic proliferations are monoclonal, while reactive conditions are polyclonal. Lymphoid neoplasms often disrupt normal immune function. Both immunodeficiency and autoimmunity may be seen. Non-Hodgkin’s Lymphoma B-Cell Neoplasms: ❑Precursor B-cell neoplasms (ALL) ❑Mature B-cell neoplasms Small Lymphocytic Lymphoma (SLL)/Chronic Lymphocytic Leukemia (CLL) Indolent malignant proliferation of small mature B-lymphocytes. These two disorders differing only in the extent of peripheral blood involvement. CLL is the most common leukemia in adults(median age 70 y). SLL constitutes only 4% of NHLs. If the peripheral blood lymphocytes >5000 cell/microliter with or without nodal or extra-nodal involvement, the patient is diagnosed as CLL, if 50, M=F. It presents as a painless generalized lymphadenopathy. The bone marrow is involved at diagnosis in 80% of cases. Extra-nodal sites are rare. 85% of cases are associated with a t(14;18), that fuses the BCL2 anti- apoptotic gene on chromosome 18 to the IgH locus on chromosome 14. The disease is incurable but indolent course (median survival 7-9 years). In 30-40% of follicular lymphomas progress to DLBCL. ❖ Morphology Vaguely nodular pattern in cut section with bulging surface.  Microscopically: Effaced architecture by proliferations with nodular follicular appearance. The follicles have two populations of neoplastic cells: ❖ Centrocytes: Slightly larger than resting lymphocytes, have angular “cleaved” nuclei with coarse condensed chromatin and indistinct nucleoli. ❖ Centroblasts: Large cells with fine chromatin, prominent nucleoli and modest amounts of cytoplasm. In most tumors, centroblasts are a minor component of the overall cellularity. Mitoses are infrequent, and single necrotic cells (cells undergoing apoptosis) are not seen. These features help to distinguish follicular lymphoma from follicular hyperplasia, in which mitoses and apoptosis are prominent. Immunophenotyping: - B-cell markers - Germinal center B cell markers CD10 and BCL6 (a transcription factor) FL, Microscopic The follicles are numerous, irregularly shaped and present throughout giving the nodular appearance.  2 types of cells: 1. Centrocytes 2. Centroblasts Follicular Hyperplasia vs follicular lymphoma BCL2  MALT-Type Lymphoma (Extranodal Marginal Zone Lymphoma) Lymphoma is a cancer that arises within and is sustained by chronic inflammation or autoimmune disorder such as: 1. Helicobacter gastritis in stomach. 2. Sialadenitis in salivary glands. 3. Hashimoto thyroiditis in thyroid gland. Tendency to remain localized at the site of origin for prolonged time. In early stages, withdrawal of the cause of the inflammation leads to tumor regression (e.g. Eradication of H. Pylori by antibiotic treatment). Morphology: Small round to irregular cells, infiltrate the epithelium of involved tissues, often collecting in small aggregates that are called lymphoepithelial lesions. In some tumors the tumor cells exhibit plasma cell differentiation.  Mantle Cell Lymphoma Composed of cells resembling the naive B cells found in the mantle zones of normal lymphoid follicles. Occurs mainly in men, > 50 years of age. Generalized disease The bone marrow is involved in most cases, and about 20% of patients have peripheral blood involvement. Patients present with fatigue and lymphadenopathy. A specific translocation t(11;14)that results in over expression of cyclin D1. These tumors are aggressive and incurable and are associated with a median survival of 4 to 6 years.  Morphology: Effaced lymph nodes by diffuse or vaguely nodular infiltration. The tumor cells usually are slightly larger than normal lymphocytes and have an irregular nucleus(cleaved) inconspicuous nucleoli, and scant cytoplasm.  Diffuse Large B-cell Lymphoma (DLBL) The most common type of lymphoma in adults. The median age is about 60 years (but occurs at any age). Patients present with a rapidly enlarging, often symptomatic mass at one or several sites. Extranodal presentations are common (The GIT is the most common extranodal site). Involvement of the liver, spleen, and bone marrow is NOT common at diagnosis. This tumor is highly associated with rearrangements or mutations of BCL6 gene, one- third arise from follicular lymphomas and carry t(14;18) translocation (BCL-2 overexpression). Other diverse driver mutations, such as translocations involving the MYC gene. ❖ Morphology: Diffuse growth pattern. The neoplastic B cells are large (at least 3-4 times the size of resting lymphocytes) and vary in appearance from tumor to tumor: 1. resembles the centroblasts: cells with round or oval nuclei, dispersed chromatin, several distinct nucleoli, and modest amounts of cytoplasm or 2. resembles Immunoblasts: large round vesicular nucleus, one or two centrally placed prominent nucleoli, and abundant cytoplasm. Mitoses are frequent. Immunophenotyping: CD10, and CD20. ❖ Subtypes Of Diffuse Large B Cell Lymphoma 1. EBV-associated: in AIDS, iatrogenic immunosuppression (in transplant recipient) and elderly. 2. Kaposi sarcoma herpes virus also called Human Herpes virus 8 (HHV-8)is associated with a rare primary effusion lymphoma in pleura, pericardium & peritoneum. 3. Mediastinal Large B cell lymphoma occurs in young women with predilection to spread to abdominal viscera & CNS. ❖Prognosis Without treatment, are aggressive and rapidly fatal. With intensive therapy complete remissions or cure rate can be achieved. To be continued... Thank You