Pathology of Neoplastic Lymphoproliferative Disorders (NHL) PDF

Lymphomas Non Hodgkin Lymphomas (NHLs) Dr. Mie Ali Mohamed Dr Mona younis Professors of Pathology Pathology Department, Faculty of Medicine, Mansoura University Dr. Mona Hany Emile Lecturer of Path...

Lymphomas Non Hodgkin Lymphomas (NHLs) Dr. Mie Ali Mohamed Dr Mona younis Professors of Pathology Pathology Department, Faculty of Medicine, Mansoura University Dr. Mona Hany Emile Lecturer of Pathology Pathology Department, Faculty of Medicine, Mansoura University  Objectives By the end of this lecture you will be able to: 1. Define Non Hodgkin lymphoma (NHLs) 2. Understand the Idea of WHO classification 3. Discuss and compare between the different types of non Hodgkin lymphomas // Some examples of B cell lymphoma// Some examples of T cell lymphoma Normal Hematopoiesis & cell differentiation  Characters of NHL Heterogeneous group of hematologic malignancies that are derived from clonal expansion of B cells , T cells or their precursors Neoplastic B and T cells tend to recapitulate the behavior of their normal counterparts. They interfere with the immune system by dysregulating the function of normal B and T cells. They often contain chromosomal translocations or mutations involving genes that regulate development and survival  Characters of NHL Characterized microscopically by : loss of nodal architecture, all cells are malignant & absence of RS cells Immunohistochemically, * B cells express CD20 * T cells express CD3  Characters of NHL More common than Hodgkin’s lymphoma Incidence increases with age (median age; 50y) More frequent involvement of multiple peripheral nodes Non contiguous spread Mesenteric nodes & Waldeyer ring are commonly involved Extra-nodal involvement is common May show indolent or aggressive behavior.  What is extra nodal involvement? The term extranodal disease refers to lymphomatous infiltration of anatomic sites other than the lymph nodes. Almost any organ can be affected by lymphoma, with the most common extranodal sites of involvement being the stomach, spleen, Waldeyer ring, central nervous system, lung, bone, and skin.  Some examples of NHL B cell NHL Diffuse large B cell lymphoma (DLBCL) Chronic lymphocytic leukemia/ Small lymphocytic lymphoma (CLL/SLL) Burkitt Lymphoma Follicular lymphoma Marginal zone lymphoma (MALT lymphoma) T cell NHL Peripheral T-cell lymphoma Mycosis fungoides Some examples of B cell lymphomas  Diffuse Large B-Cell Lymphoma (DLBCL) The most common form of NHL Occurs in all ages, mostly older above 60 Often arise at extra-nodal sites Aggressive course Highly associated with rearrangements or mutations of BCL6 gene.  Diffuse Large B-Cell Lymphoma Diffuse pattern of growth of large transformed lymphoid cells (usually 4-5 times the diameter of a small lymphocyte) Transformed lymphoid cells with large vesicular nuclei and prominent nucleoli & multiple mitotic figures B cells with variable expression of CD10 and surface Ig  Chronic lymphocytic leukemia/ Small lymphocytic lymphoma (CLL/SLL) 3 % of adult lymphomas, 30% of all leukemias Occurs in older adults Usually involves nodes, marrow, and spleen. Most patients have peripheral blood involvement Indolent course Diffuse effacement by small lymphocytes with round nuclei, condensed chromatin & scant cytoplasm. CD5+ B-cell expressing surface Ig.  Burkitt Lymphoma Endemic in Africa, sporadic elsewhere Often associated with infection by Epstein-Barr virus. Predominantly affects children, young adults. Often presents at extranodal sites with visceral involvement Highly aggressive tumor of B cells It is associated with translocations t(8;14) involving c-MYC proto-oncogene  Burkitt Lymphoma Formed of diffuse involvement by intermediate-sized B cells, excess mitoses & apoptosis (starry-sky appearance). Immunophenotyping expression of CD10+B cells & surface Ig.  Follicular Lymphoma 2nd most common NHL Middle age (males and females equally) It usually involves lymph nodes, marrow, and spleen. The most common form of indolent NHLs It is associated with t(14;18) with BcL-2 over expression.  Follicular Lymphoma Nodular growth pattern formed of: Small/ mixed small & large/ large  Prognosis depends on proportion of large cells Follicular Lymphoma  Marginal zone lymphoma  7% of adult lymphomas  Extranodal MALT (mucosal associated lymphoid tissue) lymphoma  Any mucosa (GIT, conjunctiva, respiratory…..)  Arise at sites of chronic immune stimulation.  Often remain localized for long periods of time.  Indolent tumors Some examples of T cell lymphomas  Peripheral T-cell lymphoma Most common adult T-cell lymphoma. Often disseminated. Spectrum of small to large lymphoid cells with irregular nuclear contours. CD3+mature T-cell phenotype. Generally aggressive  Mycosis fungoides Most common cutaneous lymphoid malignancy. Presents with localized or more generalized skin involvement. Small lymphoid cells often infiltrate the epidermis (Pautrier microabscesses) CD4+mature T cells. Generally indolent Sézary syndrome: a more aggressive variant characterized by diffuse skin erythema and peripheral blood involvement.  Plasma Cell Neoplasms B-cell proliferations contain neoplastic plasma cells that secretes monoclonal Ig or Ig fragments. The most common of these neoplasms is multiple myeloma Multiple Myeloma (plasma cell myeloma) Incidence higher in men, older adults, peak (65-70 y) Commonly associated with: o Bone pain due to Lytic bone lesions, o Hypercalcemia, o Renal failure, o Anemia, o Acquired immune abnormalities, o Increased levels of monoclonal Ig (M protein) in blood and/or light chains (Bence Jones proteins) in urine.  Multiple Myeloma (plasma cell myeloma) Presents as destructive bone lesions mostly involving the axial skeleton, (mostly the vertebral column, ribs, skull, pelvis, femur, clavicle, and scapula) & often leading to pathologic fractures. The bony disease dominates but it can spread late in its course to lymph nodes and extra-nodal sites. Radiographically, bone lesions appear as punched-out defects (1- 4 cm in diameter) Grossly, consist of soft, gelatinous, red tumor masses Microscopically, formed of sheets of plasma cells at different stages of maturation  Case 1 A child 15 years old, presented with generalized lymph node enlargement, biopsy examination showed infiltration of lymph node by a mixture of small lymphocytes, esinophils, plasma cells and giant cells with bilobed nucleus and large prominent nucleoli 1. What is the diagnosis of this case? 2. What is the name of the giant cells?/enumerate the variety of these cells? 3. Which of the above mentioned cells are neoplastic? 4. Mention the microscopic types of this disease?  Case 2 10 years old child presented with a hard woody mass arising from the maxilla histologic examination revealed diffuse infiltration by malignant lymphocytes with starry sky appearance A- What is the type of lymphoma? B-What is the immunophenotyping of the malignant lymphocytes? C- Explain the appearance of starry sky appearance? D- What is the genetic hallmark of this lymphoma?  Question A 15 years old male presented by mass in the jaw and maxilla, he has a history of EBV infection. Biopsy of the mass was diagnosed as high grade lymphoma, the most probable type is: 1. Hodgkin lymphoma 2. Diffuse large B cell lymphoma 3. Burkitt’s lymphoma 4. T cell lymphoma 5. Multiple myeloma  RECOMMENDED REFERENCES 1. Robbins & Cotran Pathologic Basis of Disease, (Robbins Pathology), 2018 ISBN: 978-0-323-35317-5, Edition: 10th 2. Pathmax: http://www.pathmax.com/ 3. Webpath: http://library.med.utah.edu/webpath/webpath.html