Leukemia and plasma cell dyscrasias Flashcards
multiple myeloma
lineage: plasma cells
immunophenotype: clonal Ab/light-chain production
genotype:
histology: lytic bone lesions, Bence Jones proteinuria, renal tubular casts, RBC rouleaux
presentation: middle-aged/elderly African-American men with hypercalcemia, renal insufficiency, anemia, and bone disease; recurrent infections
progression: moderately aggressive (median survival: 4-6 years), incurable
monoclonal gammopathy of undetermined significance
most common form of monoclonal gammopathy; histologically similar to multiple myeloma, but asymptomatic; diagnostic criteria include
plasmacytoma
localized growth of monoclonal plasma cells either in the context of multiple myeloma or isolated; when isolated, no clonal plasma cells in BM, presents as extra medullary plasmacytoma (usually URT) or solitary plasmacytoma of bone; treated with radiation
lymphoplasmactyic lymphoma
lineage: B-cells and plasma cells
immunophenotype: IgM+
genotype:
histology:
presentation: Waldenstrom’s macroglobulinema
progression:
amyloidosis
diseases characterized by deposition of amyloid; apple-green birefringence with Congo red staining; affects heart (conduction abnormalities), kidney (glomerular damage, nephrotic syndrome), liver (hepatomegaly), nerves (polyneuropathy), GI tract (malabsorption, diarrhea), and tongue (macroglossia); may be primary (associated with multiple myeloma or other plasma cell disorders), secondary (chronic inflammatory conditions), or hemodialysis-associated
Waldenstrom’s macroglobulinemia
symptom constellation associated with IgM production in lymphoplasmacytic lymphoma; visual/neurologic impairment, cryoglobulinemia, Raynaud’s phenomenon, bleeding
chronic myelogenous leukemia
lineage: HSC –> myeloblast
immunophenotype:
genotype: t(9;22) BCR-ABL fusion
histology: blood smear shows leukocytosis (> 100,000), few myeloblasts (2-3%), basophilia
presentation: middle-aged adults with hepatosplenomegaly, fatigue, weight loss, anorexia
progression: moderately aggressive; may progress to AML; treated with imatinib or HSCT
polycythemia vera
lineage: HSC –> erythroblast
immunophenotype:
genotype: JAK2 mutation (constitutively active)
histology: blood smear shows polycythemia (Hb > 18.5 in men, > 16.5 in women), possibly increased granulocytes and platelets; hyper cellular BM with trilineage growth, low EPO, normal O2 sat
presentation: splenomegaly, thrombotic events, gout, histamine rxns
progression: indolent; tx = phlebotomy; most pts die of thrombosis or hemorrhage; may progress to MDS or AML
primary myelofibrosis
rapidly-progressive BM fibrosis with atypical megakaryocytes and extramedullary hematopoiesis (spleen, liver, lymph nodes); blood smear shows teardrop RBCs, possible leukoerythroblastic rxn; pts present with splenomegaly, portal hypertension, splenic infarcts, left-sided pleural effusions; may progress to AML; most pts die of BM failure, thromboembolic events, portal hypertension, cardiac failure, or AML
essential thrombocytopenia
neoplastic proliferation of megakaryocytes; platelet count > 450,000 with atypical morphology (large, hypo granular); may have mild neutrophilic leukocytosis; treated with alkylating agents
myelodysplastic syndrome
lineage: multiple
immunophenotype:
genotype: monosomy 7
histology: dysplastic neutrophils (hypogranular, hypolobated), dysplastic platelets (large, hypogranular), ring sideroblasts
presentation: elderly adult with weakness, infections, hemorrhage, cytopenia(s); may also be asymptomatic
progression: tx with hypomethylating agents; may progress to AML; pts usually die of infection or bleeding
acute myelocytic leukemia
lineage: myeloid progenitors
immunophenotype: CD34+ CD117+ MPO+ (myeloblasts) NSE+ (monocytic blasts)
genotype: t(8;21), t(15;17), inv(16) (good prognosis); 11q23 rearrangement, complex karyotype with loss of chromosomes or parts of chromosomes (poor prognosis)
histology: blasts are large and uniform with fine chromatin, abundant cytoplasm, granules, Auer rods
presentation: adults with weakness, fatigue, petechiae, infections, anemia, thrombocytopenia; may also have organomegaly, lymphadenopathy, coagulopathy
progression: aggressive
acute lymphocytic leukemia
lineage:
immunophenotype: CD34+ TdT+ CD1a (immature T-cells)
genotype:
histology: blasts are small with variable morphology, course chromatin, and very little cytoplasm
presentation: children (most common cancer in children)
progression:
T-cell lineage markers
CD1a, CD2, CD3, CD4, CD5, CD7, CD8
B-cell lineage markers
CD19, CD20, CD22
