Abnormalities of WBCs PDF

Abnormalities of White Blood Cells  Objectives Contrast reactive changes in granulocytes and lymph node morphology with neoplastic changes in granulocytes and lymphocytes. Review production of leukocytes, platelets and red blood cells by hematopeitic stem cells and colo...

Abnormalities of White Blood Cells  Objectives Contrast reactive changes in granulocytes and lymph node morphology with neoplastic changes in granulocytes and lymphocytes. Review production of leukocytes, platelets and red blood cells by hematopeitic stem cells and colony- forming units. Recognize the most common malignancies of lymphocyte precursors, more mature lymphocytes, and chronic leukemias. Ascertain the methods used to identify hematopeitic cells (cell surface antigens). Understand production of immunoglobulins and development of multiple myeloma.  Leukophilia/Leukopenia Increased leukocytes-inflammation, infection. Granulocytes (neutrophils) increase secondary to TNFα and IL-1, decreased margination (catecholamines and corticosteroids), decreased extravasation into tissue (corticosteroids). Lymphocytosis-viral infections, tuberculosis Decreased leukocytes-auto-immune, drug toxicity, infiltrating diseases of bone marrow, hereditary diseases, ineffective erythropoiesis. Overwhelming infection Decreased lymphocytes- viral infections (HIV).  Lymphoid Hyperplasia Acute lympadenitis-proliferation of B- cells in germinal centers. Chronic non-specific lymphadenitis- Follicular hyperplasia.  Hematologic Malignancies Mutations of genes that regulate cell differentiantion. – Conversion of stem cells to next level of differentiation. Mutations of genes that drive proliferation-MCY, RAS Mutations that prevent apoptosis. Precursor B-Cell Malignancy Acute lymphoblastic leukemia-B-cell – Most common early childhood malignancy – Commonly presents with bleeding (thrombocytopenia), infection (neutropenia), CNS, liver/spleen involvement – Chromosomal abnormalities, RUNX1, ET1/6, PAX3, etc Chronic Lymphocytic leukemia, B-cell lymphomas – Chromosomal abnormalities Acute Lymphoblastic Leukemia  Lymphomas Non-Hodgkin’s – B-cell Follicular Diffuse large B-cell lymphoma Marginal zone Mantle cell Burkitt’s Hairy cell leukemia – T-cell Large cell lymphoma Mycosis Fungoides Sezary syndrome NK cell leukemia  Lymphoma Hodgkin’s – Reed Sternberg cells Nodular sclerosis Mixed cellularity Lymphocyte-rich Lymphocyte depletion Lymphocyte predominance  Multiple Myeloma/Plasmacytoma  Acute myelogenous Leukemia AML – Chromosomal aberrations – Differentiating genes – Epigenetic modifications Myelodysplasia – Maturation defects and ineffective erythropoiesis – Chromosomal defects, epigenetic factors, transcription factors, loss of p53 Myeloproliferative Mutations of tyrosine kinase  Chronic Myelogenous Leukemia BCR-ABL translocation