White Cell Disorders — Must-Know Notes

This document provides a comprehensive overview of white blood cell disorders, encompassing both non-neoplastic conditions like leukopenias and reactive proliferations, and a range of neoplastic conditions. It details the pathogenesis, morphology, clinical features, and prognosis of various lymphoid and myeloid malignancies, alongside plasma cell tumors. Key emphasis is placed on molecular mechanisms, classification, and diagnostic distinctions for each entity. Key Points Neutropenia, particularly when severe (agranulocytosis) with counts below 500 cells/µL, significantly elevates the risk of fatal bacterial and fungal infections. Reactive leukocytosis, an increase in circulating white cells in response to stimuli, must be carefully distinguished from true leukemias, especially in leukemoid reactions . Infectious mononucleosis, caused by Epstein-Barr virus (EBV) , is characterized by lymphocytosis of activated CD8+ T cells (atypical lymphocytes) and can lead to complications such as splenic rupture. Chronic nonspecific lymphadenitis manifests in patterns like follicular hyperplasia (B cell), paracortical hyperplasia (T cell), or sinus histiocytosis (macrophages), requiring differentiation from lymphoma. Lymphoid neoplasms are clonal proliferations often arising from germinal center or post-germinal center B cells , with classification based on morphology, immunophenotype, genotype, and clinical features. Acute Lymphoblastic Leukemia (ALL) is the most common childhood leukemia, primarily of pre-B cell origin, with a high cure rate in children, though prognosis varies with age and specific genetic abnormalities. Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL) are indolent B cell tumours characterized by increased tumour cell survival due to BCL2 and are the most common adult leukemias in the Western world, prone to immune dysregulation and transformation. Follicular Lymphoma is a prevalent adult non-Hodgkin lymphoma defined by the t(14;18) translocation leading to BCL2 overexpression and a nodular proliferation of neoplastic germinal center B cells. Multiple Myeloma, the most common plasma cell neoplasm, involves the bone marrow, causing lytic lesions throughout the skeleton and producing monoclonal immunoglobulins ( M proteins ) which lead to bone pain, hypercalcaemia, and renal dysfunction. Hodgkin Lymphoma is distinct from non-Hodgkin lymphomas due to the presence of Reed-Sternberg (RS) giant cells and its predictable contiguous spread pattern, which allows for local therapy in early stages. Detailed Notes Non-Neoplastic Disorders of White Cells Conditions covered: Leukopenia · Neutropenia · Reactive Leukocytosis · Infectious Mononucleosis · Reactive Lymphadenitis Leukopenia & Neutropenia Key concepts: Mechanisms · Morphology · Clinical features · Treatment Leukopenia results most commonly from a decrease in granulocytes. Lymphopenia is less common and is associated with congenital immunodeficiency, advanced HIV infection, and high-dose corticosteroid therapy. Neutropenia / Agranulocytosis — a reduction in granulocyte count. When severe, it is called agranulocytosis. The risk of fatal bacterial and fungal infection rises sharply once the neutrophil count falls below 500 cells/µL. Two mechanisms of neutropenia: Decreased production — caused by marrow failure (aplastic anaemia), extensive marrow replacement by tumour (e.g. leukaemia), cancer chemotherapy, or drugs that selectively impair differentiation of committed granulocytic precursors. Isolated neutropenias of this type are also caused by neoplastic proliferations of cytotoxic T cells and NK cells. Increased destruction — caused by immune-mediated injury (sometimes drug-triggered), overwhelming bacterial, fungal, or rickettsial infections (increased peripheral utilisation), or splenomegaly (sequestration and accelerated removal of neutrophils). Morphology — depends on the underlying cause. Marrow is hypercellular when there is excessive destruction or ineffective granulopoiesis (as in megaloblastic anaemia). Marrow is hypocellular when drugs suppress granulopoiesis. Most myelotoxic drugs reduce elements from all marrow lineages, not just granulocytes. Clinical features — ulcerating, necrotizing lesions of the gingiva, floor of mouth, buccal mucosa, and pharynx ( agranulocytic angina ). Lesions contain large masses of organisms because of the absence of leukocytes. Treatment — remove the offending drug, control infection, and administer G-CSF (granulocyte colony-stimulating factor) to stimulate neutrophil production by the bone marrow. Reactive Leukocytosis Key concept: Types and their distinguishing causes An increase in circulating white cells in response to microbial or non-microbial stimuli. Classified according to the white cell series affected. In some cases, reactive leukocytosis may mimic leukaemia — these leukemoid reactions must be distinguished from true malignancy. Type Common Causes ------ -------------- Neutrophilic