Summary This document provides a comprehensive overview of various hematologic malignancies, including Hodgkin lymphoma, other lymphoid and myeloid neoplasms, a
Summary This document provides a comprehensive overview of various hematologic malignancies, including Hodgkin lymphoma, other lymphoid and myeloid neoplasms, and Langerhans cell histiocytoses, detailing their pathogenesis, clinical features, and treatment. It also explores bleeding disorders, categorizing them by underlying mechanisms such as vascular fragility, platelet defects, coagulation factor deficiencies, and mixed defects like Disseminated Intravascular Coagulation (DIC). Key molecular insights, diagnostic features, staging, and prognostic indicators are highlighted across these diverse conditions. Key Points - Hodgkin lymphoma is pathologically defined by the presence of Reed-Sternberg (RS) giant cells and typically spreads in an orderly, contiguous fashion. - The histological diagnosis of Hodgkin lymphoma necessitates the definitive identification of RS cells or variants within an appropriate reactive background, often supported by immunophenotyping. - Extranodal marginal zone lymphomas, frequently associated with chronic antigenic stimulation from autoimmune disorders or infections like H. pylori , may regress with eradication of the inciting agent. - Hairy Cell Leukaemia is an uncommon but highly treatable indolent B cell neoplasm, exhibiting excellent response to purine nucleoside chemotherapy due to its characteristic BRAF mutation . - Mycosis Fungoides and Sézary Syndrome represent cutaneous T cell lymphomas where malignant CD4+ T cells primarily infiltrate the skin, leading to characteristic rashes, plaques, and tumors. - Acute Myeloid Leukaemia (AML) is marked by the accumulation of immature myeloid blasts in the bone marrow and often involves specific genetic mutations, with Acute Promyelocytic Leukaemia being notably responsive to targeted differentiation therapy. - Myelodysplastic Syndromes (MDS) are characterized by ineffective hematopoiesis, leading to peripheral cytopenias despite a frequently hypercellular marrow, and carry a risk of transformation to AML. - Chronic Myelogenous Leukaemia (CML) is pathognomonically linked to the BCR-ABL fusion gene , typically from the Philadelphia chromosome , and its treatment has been revolutionized by targeted tyrosine kinase inhibitors. - Langerhans Cell Histiocytoses are rare proliferative disorders of immature dendritic cells, often driven by the BRAF V600E mutation , presenting in varied clinical forms from localized bone lesions to aggressive multisystem disease. - Bleeding disorders arise from defects in the vessel wall, platelets, or coagulation factors, necessitating distinct diagnostic approaches and management strategies based on their etiology. - Disseminated Intravascular Coagulation (DIC) is a paradoxical condition caused by systemic coagulation activation, simultaneously leading to microthrombotic tissue ischemia and a severe bleeding diathesis due to consumptive coagulopathy. Detailed Notes Hodgkin Lymphoma Key concepts: Reed-Sternberg cells · Subtypes · Pathogenesis · Staging · Clinical features · Prognosis Hodgkin lymphoma is characterised by the presence of Reed-Sternberg (RS) giant cells — the neoplastic cell — which are typically vastly outnumbered by non-neoplastic inflammatory cells. Unlike most NHLs, it arises in a single lymph node or chain and spreads in a stepwise, contiguous fashion to anatomically adjacent nodes. Reed-Sternberg cell morphology — very large cells (15–45 µm) with an enormous multilobate nucleus, exceptionally prominent nucleoli, and abundant slightly eosinophilic cytoplasm. The classic form has two mirror-image nuclear lobes each containing a large acidophilic nucleolus surrounded by a clear zone — the "owl-eye" appearance. RS cells express CD15 and CD30 and fail to express CD45, B cell antigens, and T cell antigens. Origin of RS cells — long mysterious, but molecular studies on single microdissected RS cells showed every RS cell in a given case carries identical immunoglobulin gene rearrangements that have undergone somatic hypermutation → Hodgkin lymphoma is a neoplasm of germinal centre B cells that has lost normal B cell gene expression programmes. EBV and pathogenesis — EBV is present in RS cells in up to 70% of mixed-cellularity cases and a smaller fraction of other classical subtypes. EBV genome integration is identical in all RS cells within a case, indicating infection precedes transformation. RS cells secrete several cytokines generating the characteristic inflammatory background: IL-5 (attracts eosinophils), TGF-β (fibrogenic), and IL-13 (may stimulate RS cells via autocrine loop). In turn, responding inflammatory cells produce CD30 ligand which aids RS cell growth and survival. Subtypes Nodular Sclerosis — most common subtype; equally frequent in men and women; strong predilection for lower cervical, supraclavicular, and mediastinal lymph nodes; most patients are adolescents or young adults; overall prognosis excellent. - Characteristic RS cell variant: lacunar cell — large cell with single multilobate nucleus, multiple small nucleoli, and abundant pale cytoplasm; in formalin-fixed tissue, cytoplasm retracts leaving nucleus in an empty space (lacune) - Collagen bands divide involved lymphoid tissue into circumscribed nodules; fibrosis may be scant or abundant; cellular infiltrate contains lymphocytes, eosinophils, histiocytes, and lacunar cells Mixed Cellularity — most common subtype in patients 50 years; comprises ~25% of all cases; male predominance. Classic RS cells are plentiful within a heterogeneous inflammatory infiltrate of small lymphocytes, eosinophils, plasma cells, and macrophages. More likely to be disseminated and associated with systemic manifestations than nodular sclerosis. Lymphocyte-Rich — abundant lymphocytes; rare RS cells; best prognosis among classical subtypes. Lymphocyte Depletion — few lymphocytes; many RS cells or fibrosis; worst prognosis; often advanced stage at presentation. Lymphocyte Predominance — accounts for ~5% of Hodgkin lymphoma; set apart as a distinct entity. Characteristic RS cell variant: lymphohistiocytic (L&H) "popcorn cell" — delicate multilobed puffy nucleus. L&H variants are found within large nodules of mainly small resting B cells with variable macrophages; eosinophils, neutrophils, and plasma cells are scanty or absent. Unlike classical RS cells, L&H variants express CD20 and usually fail to express CD15 and CD30. Most patients present with isolated cervical or axillary lymphadenopathy; prognosis typically excellent. ⚠️ Histologic diagnosis of Hodgkin lymphoma rests on definitive identification of RS cells or variants in the appropriate reactive background. Immunophenotyping plays an important adjunct role — some forms closely mimic inflammatory reactive processes. Clinical Features and Staging Feature Hodgkin Lymphoma Non-Hodgkin Lymphoma :-------- :---------------- :-------------------- Node involvement Single axial group (cervical, mediastinal, para-aortic) Multiple peripheral nodes Spread Orderly, contiguous Noncontiguous Mesenteric nodes / Waldeyer ring Rarely involved Commonly involved Extranodal involvement Uncommon Common Ann Arbor Staging: Stage Distribution :------ :------------ I Single lymph node region (I) or single extralymphatic organ (IE) II Two or more lymph node regions on same side of diaphragm (II) ± limited contiguous extralymphatic organ (IIE) III Lymph node regions on both sides of diaphragm (III) ± spleen (IIIS) ± extralymphatic organ (IIIE) IV Multiple or disseminated extralymphatic organ involvement ± lymphatic involvement All stages further divided: A (no systemic symptoms) vs B (fever, night sweats, unexplained 10% weight loss). Younger patients with favourable subtypes tend to present at stage I or II without systemic symptoms. Advanced disease (stages III and IV) more likely to present with systemic complaints, fever, weight loss, pruritus, and anaemia. Treatment — even stage I disease is now treated with systemic chemotherapy due to long-term complicatio