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White Blood Cell Neoplasms

AB
Precursor B cell: CD19, CD10, TdT
t(12;21) – CBFα /ETV6, t(9;22), t(4;11)
lobulated nucleus, starry sky with tingible body macrophages
M0-M7
CD 34, CD33, CD15
t(8;21) and inv(16) form CBF1α and CBFβ fusion protein, blocks terminal differentiation
acute promyelocytic leukemia:
Deletions in xsomes 5,7 following myelodysplastic syndromes or exposure to DNA-damaging chemo/radiation
Translocation of MLL gene on xsome 11q23 after topoisomerase II inhibitor treatment
Myeloblasts: delicate nuclear chromatin, 2-4 nucleoli,fine, azurophilic, peroxidaze + granules, red peroxidase + Auer rods
Monoblasts: folded or lobulated nuclei, no Auer rods, peroxidase - nonspec. esterase +
Monocyte tumors in the skin and gingival, CNS spread
Good prognosis for t(8;21) or inv(16) w/ chemo
Cytotoxic CD8 T cell
Rearranged 2p23 with ALK gene
Tumor cells cluster around venules and infiltrate lymphoid sinuses
Anaplastic Large Cell Lymphoma
Translocationof c-myc and Ig loci, t(8;14), t(8;22), t(2;8)
CD19, CD20, CD10, BCL6, IgM, κ or λ light chain-- LIKE DARK ZONE
EBV in endemic African cases, 15-20% of sporadic and 25% HIV
EBV in endemic African cases, 15-20% of sporadic and 25% HIV
AGGRESSIVE:Responds well to short-term, high dose chemo
Jaw (mandible) or extranodal abdominal masses,
Trisomy 12, deletions of 11q, 13q, 12q, 17p
Naïve B-cell or post germinal center memory B-cell
CD19, CD 20, C23, CD5
Prolymphocytic transf. to diffuse lg B-cell lymphoma (Richter syndrome)
Node: Larger prolymphocytes aggregate into mitotically active proliferation centers
Indolent, median sv.4-6 y, worse pronois w/ 11q 17p
Diffuse pattern of small lymphocytes peripheral blood may be leukopenic
Diffuse Large B-Cell Lymphoma
BCL6 dysregulation on 3q27,t(14;18), cREl amplification
Single rapidly growing mass, extranodal, common at Waldeyer ring, liver, spleen
Immunodef.- associated (HIV, SCID, transplants, EBV)
Rapidly fatal if untreated; Chemo: 60-80% remission
germinal or < center B cell CD19, CD20, TdT -; vrble exprssn of CD10, BCL6, SIg,
All ages (5% childhood lymphomas), most commonly adults (60 yrs), slight male predominance
Megakaryocytes have decrease requirement for growth factors
Hematopoietic stem cell that gives rise mainly to megakaryocytes
Erythromelalgia – burning and throbbing in hands and feet caused by occlusion of small arterioles with platelet aggregates
CD19, CD20, CD10, SIg, BCL2, BCL6
t(14;18)-BCL2 and IgH - antiapoptotic
Nodes:Centrocytes – small cleaved cells (majority)
most common form of NHL in the U.S.
Centroblasts – larger, open chromatin, several nucleoli, modest cytoplasm
30-50% transform to diffuse large B-cell lymphoma with survival
Follicular Lymphoma
Indolent, Incurable, median survival 7-9 years (good prognosis, low grade)
CD19, CD20, IgG, κ or λ light chain, CD11c, CD25, CD103
hairlike projections, round, oblong or reniform nuclei, moderate pale blue cytoplasm
Pancytopenia,
Post germinal center memory B cell
Older Caucasian males, Indolent, Sensitive to chemo
Monoclonal,HLA-DR, S-100, CD1A, CCR6 and CCR7
Abundant, vacuolated cytoplasm containing Birbeck granules (tennis-racket), vesicular nuclei with linear grooves or folds
Multifocal multisystemic: rapidly fatal if untreated, intensive chemo – 50% survive 5 yrs
Secreted IgM for plasma cells
B-cells, plasma Cells, deletion on 6q; Older adults (60-70 yrs)
Lymphoplasmacytic Lymphoma
Bone Marrow:Lymphocytes, plasma cells and intermediate plasmacytoid lymphocytes, hyperplasia of mast cells
PAS positive inclusions of Ig in cystoplasm (Russell bodies) or nucleus (Dutcher bodies)
IgM causes Hyperviscosity syndrome
Weakness, fatigue, weight loss, lymphadenopathy, hepatosplenomegaly, anemia (autoimmune hemolysis by cold agglutinins at <37 C)
(Waldenstrom macroglobulinemia) – visual impairment, headaches, dizziness, deafness, bleeding, cryoglobulinemia (precipitation of macroglobulins at low T)
Plasmapheresis alleviates hyperviscosity and hemolysis, incurable, progressive Meidan survival: 4 yrs
Transformation to large-cell lymphoma
Mantle Cell Lymphoma
CD19, CD20, IgM, IgD, κ or λ light chain, CD5, Cyclin D
t(11;14) involving BCL1 (cyclin D1) and IgH
Node:Tumor cells surround reactive germinal centers
Disseminated disease, painless lymphadenopathy, bone marrow, splenic white pulp, hepatic periportal areas, gut, lymphomatoid polyposis
Naïve B cell
Small lymphocytes with round or clefted nuclei, condensed chromatin, inconspicuous nucleoli, scant cytoplasm
Myelodysplastic Syndromes: Pawn ball megakaryocytes (single nuclear lobes or multiple separate nuclei)
Survival dependent on IL-6 produced by neoplastic plasma cells and normal stromal cells in the marrow
Neoplastic plasma cells produce osteoclast factors MIP1α and RANKL (R’ for NF-κB)
Multiple Myeloma, Solitary Plasmacytoma, Monoclonal Gammopathy of Uncertain Significance (MGUS)
Most common symptomatic monoclonal gammopathy
Chemo with alkylating agents 50-70% remission with survival of 3 yrs
Gelatinous soft, red tumor masses esp. in vertebral column, ribs, skull.
Osteoprotegrin inhibits RANKL,
multiple myeloma Intracellular accumulation of degraded Ig – flame cells with red cytoplasm
(Russell bodies – cytoplasmic, Dutcher bodies – nuclear) Multiple myeloma
blue grapelike cytoplasmic droplets, inclusions of fibrils, crystalline rods and globules, multiple myeloma, Mott cells
Plasmacytosas and MGUS may progress to MM
Older adults (50-60 yrs), men, African descent
Plasma cells infiltrate marrow diffusely or in sheetlike masses.
Lytic bone lesions, pathologic fractures, renal failure (myeloma kidney), primary amyloidosis, hypercalcemia
Small Lymphocytic Lymphoma (Nodal)
Nucleated Red Cell Progenitors
CD2, CD5, CD3, αβ or γδ receptor, sometimes CD4, CD8
Diffuse involvement of lymph node:Variable sized T cells, eosinophils, macrophages, angiogenesis
Peripheral T-Cell Lymphoma, Unspecified
Mature T cells: Diffuse involvement of lymph node
Lymphadenopathy, eosinophilia, pruritus, fever, weight loss
Worse than comparable B cell neoplasms; poor prognosis but some cures reported
Multipotent myeloid stem cell that gives rise to erythrocytes, granulocytes, megakaryocytes
Peripheral blood: basophilia, polycythemia, granulocytosis, thrombocytosis
fibrosis in bone marrow specimen: often referred to as the spent phase of polycythemia vera
Lymphocyte predominance Reed Sternberg Cells
Primary Myelofibrosis: Identical to spent phase of other chronic myeloproliferative disorders
Rapid dev. of obliterative marrow fibrosis due to inappropriate release of PDGF and TGFβ from neoplastic megakaryocytes
Peripheral blood:dacryocytes (tear-drop erythrocytes), large platelets, basophilia, cytopenias, Leukoerythroblastosis-erythroid/granulocytic precursors
Ringed sideroblasts- erythroblasts with iron laden mitochondria
Pseudo-Pelger-Huet cells – PMNs w/ 2 nuclear lobes
Reed Sternberg Cell
Hodgkin Lymphoma
Giant RS cells that secrete IL-5, IL-6, IL-13, TNF, GM-CSF, attracting lymphocytes, macrophages and granulocytes which in turn support growth of the tumor cells
-During cell death cell shrinks and becomes pyknotic (mummification)
Mediastinal mass in young females. Moderately aggressive.
Nodular sclerosis most common HL (65-70%)
RS Mononuclear Variant; Single round or oblong nucleus; Large inclusion like nucleolus
R-S cells found in HL of Mixed cellularity,Lymphocyte-rich



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