Tumors of Lymphoid System - 2024-2025 PDF

Libyan International Medical University Faculty Of AMS 3rd year (2024- 2025) Block :Immune block Week -III Tumors of Lymphoid System Dr. Warda Musbah 1  Intended learning outcome By the end of this lecture , you...

Libyan International Medical University Faculty Of AMS 3rd year (2024- 2025) Block :Immune block Week -III Tumors of Lymphoid System Dr. Warda Musbah 1  Intended learning outcome By the end of this lecture , you will be able to: 1. List classification of lymphoid neoplasms 2. Discuss pathogenesis & morphology of the common forms of lymphomas 3. Outline cytogenetics, molecular profiles and immunologic markers of different lymphoid neoplasms  Tumors of Lymphoid System Leukemias are malignant neoplasms of the hematopoietic stems cells arising in the bone marrow, that flood the circulating blood or other organs. Lymphoma is used for proliferations that arise as discrete tissue masses.  The WHO Classification of Lymphoid Neoplasm The current World Health Organization (WHO) classification scheme uses morphologic, immunophenotypic, genotypic, and clinical features to sort the lymphoid neoplasms into five broad categories, separated according to the cell of origin. Precursor B cell Neoplasm Peripheral B cell Neoplasm Precursor T cell Neoplasm Peripheral T cell Neoplasm Hodgkin Lymphoma 4 10/10/2024 03:25 Dr: Warda Musbah WHO Classification of lymphoid neoplasms 10/10/2024 3:25 AM WHO Classification of lymphoid neoplasms 10/10/2024 3:25 AM WHO Classification of lymphoid neoplasms 10/10/2024 3:25 AM  Common Lymphomas Small lymphocytic lymphoma/Chronic lymphocytic leukemia Follicular lymphoma Diffuse large B cell lymphoma Burkitt lymphoma Lymphoblastic lymphoma Hodgkin lymphoma  Hodgkin Lymphoma It is a group of lymphoid neoplasms arising in a single node and spreads from the nodes to spleen, then liver and finally bone marrow. Clinical importance of this predictable route of spread is highlighted by the importance of staging which determines prognosis as well guides the choice of therapy of HL There is presence of neoplastic giant cell called Reed-Sternberg cell (derived from the germinal center B cell) which induces the accumulation of reactive lymphocytes, macrophages and granulocytes  Constitutional symptoms’ (fever, night sweats, unexplained weight loss of greater than 10% body weight) are observed more with disseminated disease (Stages III and IV) and mixed cellularity or lymphocyte depletion subtypes.  Reed Sternberg Cell  Reed - Sternberg cell is a relatively large cell Particularly characteristic are cells with two mirror - image nuclei or nuclear lobes, each 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  Classical RS cells are common in mixed cellularity Variants of RS cells – Lacunar cell in Nodular Sclerosis. Popcorn cell in Lymhocyte predominance, Anaplastic RS cell in lymphocyte depleted Nodular Sclerosis, Mixed Cellularity are the common types, others are less common  Classification of Hodgkin Lymphoma (WHO) Lymphocyte Classical Hodgkin Predominance Lymphoma Lymphocyte Lymphocyte Rich Predominance Nodular Sclerosis Immunophenotype: Mixed Cellularity Lymphocyte depleted Neoplastic cells are positive for LCA, CD20 and other Immunophenotype: B lineage marker. Neoplastic cells are positive for CD30, CD15 are negative CD30,CD15,LMP and negative for LCA  Pathogenesis of HL It is now agreed that Hodgkin lymphoma is a neoplasm that arises from germinal center B cells Every RS cell possesses the same immunoglobulin gene rearrangements have undergone somatic hypermutation. EBV episomes are frequently present in RS cells. EBV-positive tumour cells express latent membrane protein or LMP-1 (a protein encoded by EBV genome that has transforming activity). LMP-1 upregulates NF-KB (transcription factor responsible for lymphocyte activation). NF-KB activation possibly rescues cells from apoptosis.  The characteristic non-neoplastic, inflammatory cell infiltrate is generated by a number of cytokines (e.g., IL-5, IL-10, and M-CSF) Hodgkin lymphoma is a cardinal example of a tumour that escapes from the host immune response by expressing proteins that inhibit T cell function Typical RS cells and variants have a characteristic immunophenotype, CD15+, CD30+ and CD45 - except NLPHL (CD15-, CD30- ). Classic Hodgkin lymphoma is highly responsive to immune checkpoint inhibitors, which antagonize the activity of PD-L1 and PD-L2 expressed on the surface of Reed-Sternberg cells 16 Nodular sclerosis HL Is the most common form (70%). Propensity to involve the lower cervical, supraclavicular, and mediastinal lymph nodes. Adolescents or young adults.( M=F) Hodgkin lymphoma, nodular sclerosis type—lymph node. A It is characterized morphologically by the lowpower view shows well- defined bands of pink, acellular following: collagen that have subdivided the tumor cells into nodules. 1)Lacunar cell Variant of the RS cell, ( has a single multilobate nucleus, multiple small nucleoli, and abundant, pale-staining cytoplasm) 2)Collagen bands that divide involved lymphoid tissue into circumscribed nodules. 3)Cellular infiltrate ; lymphocytes, eosinophils and histiocytes A distinctive “lacunar cell” with a multilobed nucleus Prognosis is excellent. containing many small nucleoli is seen lying within a clear space created by retraction of its cytoplasm.It is surrounded 10/10/2024 3:25 AM by lymphocytes. NODULAR SCLEROSIS TYPE Immunophenotyping: CD15 +ve ,CD30 +ve. EBV –ve. Prognosis: Very good. Mixed-cellularity HL. Is the most common form of Hodgkin lymphoma in patients older than 50 years of age  Comprises about 22% of cases overall. There is a male predominance. EBV +ve (70%).  Classic RS cells are plentiful  Inflammatory infiltrate containing small lymphocytes, eosinophils, plasma cells, and macrophages. More likely to be disseminated and Hodgkin lymphoma, mixed-cellularity type lymph node.A diagnostic, binucleate associated with systemic manifestations. Reed-Sternberg cell is surrounded by 10/10/2024 3:25 AM eosinophils, lymphocytes, and histiocytes.  Precursor B and T cell lymphoblastic lymphoma/leukemia Aggressive tumors composed of immature lymphocytes (lymphoblasts) Occur predominantly in children and young adults Pre B lymphoblastic tumor appear as leukemia Pre T lymphoblastic tumor occur as mediastinal mass and later spill over as leukemia  Both pre B and pre T lymphoblasic tumors usually take on the clinical appearance of an acute lymphoblastic leukemia (ALL) at some time during their course). \ T lymphoblastic lymphoma(LL) shows sheets of immature cells with scanty cytoplasm, enlarged , immature nuclei with inconspicuous nucleoli. Positive for Tdt. CD3 and CD43 are positive B cell LL shows positivity for CD20, CD79,CD19 and Tdt  Acute Lymphoblastic leukemia Lymphoblasts with condensed nuclear , small nucleoli, and scant agranular cytoplasm. Precursor B and T cell lymphoblastic lymphoma/leukemia  Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia These two disorders are morphologically, phenotypically and genotypically identical differing only in the extent of peripheral blood involvement. CLL if lymhocytosis exceeds >5000/mm3 cells/cmm. Occurs in old age, associated with hyogammaglobulinemia, autoimmune haemolytic anemia. Loss of lymph node architecture by sheets of small lymphoid cells with proliferation center  IHC: CD5, CD23 and CD43 positive. 99% of cases positive for B cell marker like CD20 and CD79a. Karyotype: trisomy12 and deletions of chromosome11 and 12 Prognosis: Median survival 4 to 6 years. Many patient live for more than 10 years  Small Lymphocytic Lymphoma Low-power view shows diffuse effacement of nodal At high power, a majority of the tumor cells have the architecture appearance of small, round lymphocytes. A prolymphocyte,”a larger cell with a centrally placed nucleolus, also is present in this field (arrow).  Diffuse Large B Cell Lymphoma(DLBCL) Includes several forms of NHL that share certain features including a B cell phenotype, diffuse growth pattern and an aggressive clinical history Commonest NHL (about 50% of NHL) Somatic hypermutation that result in overexpression of BCL6, which has several important consequences. BCL6 represses the expression of factors that normally serve to promote germinal center B-cell differentiation, growth arrest, and apoptosis, and each of these effects is believed to contribute to the development of DLBCL.  Mutations similar to those found in BCL6 are also seen in multiple other oncogenes, including MYC. Positive for B cell markers like CD19,CD20 and CD79a Any age can be affected. Present as rapidly enlarging mass. Extra nodal site presentation is well known. BM involvement is not common at the time of diagnosis Aggressive tumors that are rapidly fatal if untreated. With intensive chemotherapy remission can be achieved in 60% to 80% of cases DLBCL involving spleen  Follicular Lymphoma(FL) Relatively common tumor Morphology: Lymph nodes are effaced by nodular appearance with close back to back arrangement. Graded I to 3. IHC: BCL2 positive, B cell marker positive, Ki-67 index around 20%, BCL6 also positive. CD10 can be positive Karyotype: t(14;18) Pathogenesis: It is strongly associated with chromosomal translocations involving BCL2 The t(14;18) is seen in up to 90% of follicular lymphoma (IGH locus on chromosome 14 and the BCL2 locus on chromosome 18) Overexpression of BCL2 protein/an inhibitor of apoptosis  Clinical Features: Occurs predominatly in older persons. Causes painless generalized lymphadenopathy. Spread to bone marrow is very common Prognosis:  Natural history is prolonged (median survival, 7 - 9 years), follicular lymphoma is not curable  40% of patients, follicular lymphoma progresses to diffuse large B cell lymphoma  Follicular Lymphoma Nodular aggregates of lymphoma cells are present High magnification,small lymphoid cells with condensed throughout chromatin and irregular or cleaved nuclear outlines (centrocytes) are mixed with a population of larger cells with nucleoli(centr blasts). Follicular lymphoma - spleen  Follicular hyperplasia versus Follicular Lymphoma – BCl2 Ab. BCL2 expression in reactive and neoplastic follicles. BCL2 protein was detected by using an immunohistochemical technique that produces a brown stain. In reactive follicles (A), BCL2 is present in mantle zone cells but not follicular-center B cells, whereas follicular lymphoma cells (B) show strong BCL2 staining  Mycosis fungoides and Sézary syndrome Cutaneous T-cell lymphomas composed of neoplastic CD4 T cells that home to the skin. Most often have a characteristic CD3+, CD4+ , CD7− The patient presents with chronic erythrodermic rash manifesting as a localized plaque-like lesion (plaque phase) which later becomes nodular and ulcerated (tumour phase). In some cases, a leukaemic phase called Sézary syndrome appears, which is characterized by: (i) Generalized exfoliative erythroderma (ii) Tumour cells in the peripheral blood  Patients with erythrodermic phase of mycosis fungoides usually survive for many years; survival less (1–3 years) for patients in tumour phase of the disease, visceral disease and Sézary syndrome  Clinical Hodgkin’s differences between Lymphoma Non –Hodgkin’s Hodgkin’s and Lymphoma Non- Hodgkin’s Lymphoma More often localized to a single axial More often involvement of multiple group of nodes ( cervical , mediastinal , peripheral nodes para aortic) Orderly spread by contiguity Non contiguous spread Mesenteric nodes and Waldeyer’s ring Waldeyer’s ring and mesenteric nodes rarely involved commonly involved Extra nodal involvement uncommon Extra nodal involvement common Characterized by the presence of Reed – Reed – Sternberg cells are absent Sternberg Cells Admixed with a variable infiltrate of No reactive or inflammatory cells seen. reactive , non- malignant inflammatory cells  References Robbins pathologic basis of disease, 2020 40