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86 Cards in this Set
- Front
- Back
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what stimulates the differentiation of hematopoetic stem cells?
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stem cell factor (SCF aka cKIT ligand)
IL-6 FLT3 ligand |
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what stimulates the differentiation myeloid progenitor cells into CFU-GM?
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GM-CSF
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what stimulates the differentiation of myeloid progenitor cells to CFU-b/Mg and BFU-E?
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Thrombopoietin, IL-11
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what mediates the differentiation of CFU-GM?
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G-CSF --> CFU-G (myeloblast --> neutrophil)
M-CSF --> CFU-M (monoblast --> monocyte) |
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what generalized changes in bone marrow are seen in disease states?
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Increased fat: aplastic anemia
Decreased fat: hematopoietic tumors, dzs w/ compensatory hyperplasia, and leukemias Local marrow fibrosis: metastatic cancers and granulomatous dzs |
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Drugs implicated in agranulocytosis?
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aminopyrine
chloramphenicol sulfonamides chlorpromazine thiouracil phenylbutazone |
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which drugs cause neutropenia thru a toxic effect on granulocytic precursors in marrow?
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chlorpromazine and thenothiazines
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what is the most common sign of agranulocytosis?
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ulcerating necrotizing lesions of the gingiva and oral cavity
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which growth factor induces neutrophilia?
what are causes of its release? |
G-CSF
acute bact infxn (esp pyogenic bact); sterile inflammation (eg tissue necrosis) |
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causes of eosinophilia?
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allergy (hay fever, asthma)
skin diseases parasitic infxns drug rxns some malignancies (hodgkin & non-hodgkin lymphomas) collagen vascular dzs and vasculitides atheroembolic dz |
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causes of basophilia?
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(Rare) myeloproliferative dzs (eg CML)
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causes of monocytosis?
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chronic infxn, bact endocarditis, rickettsiosis, malaria
collagen vascular dzs (eg SLE) inflamm bowel dzs (eg UC) |
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causes of lymphocytosis?
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comes w/ monocytosis in chronic immunological stimulation disorders (tb, brucellosis)
viral infxns B. pertussis infxn |
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morphologic neutrophil chgs in sepsis or severe inflammatory disorders?
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toxic granules (abnormally coarse, dark granules)
Dohle bodies (blue cytoplasmic patches of dilated ER) cytoplasmic vacuoles |
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activation of humoral immune response results in what type of LN rxn?
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follicular hyperplasia
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activation of T cell mediated immune response results in what type of LN rxn?
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Paracortical hyperplasia
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How to differentiate between follicular hyperplasia and follicular lymphoma?
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Hyperplasia:
-maintains LN architecture -has marked variation in shape/size of nodules -has frequent mitotic figures, phagocytic macrophages, and recognizable light and dark zones |
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MCCs of paracortical lymphoid hyperplasia?
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immunologic rxns induced by drugs (esp phenytoin)
acute viral infxn (esp EBV) |
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t(9,22) is associated with what disease(s)?
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ALL, AML, CML
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which WBC neoplasms cause symptoms through the secretion of circulating factors?
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plasma cell tumors (secretion of antibodies or fragments)
Hodgkin lymphoma (fever d/t release of inflammatory cytokines) |
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clinical features of ALLs?
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- abrupt, stormy onset
- sxs related to BMS (fatigue, fever, bleeding) - mass effect (bone pain, organomegaly, lymphadenopathy, testicular enlargement) - CNS (HA, vomiting, nerve palsies) |
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what factors are associated with poorer prognosis in ALL?
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- age < 2 or > 10
- blast counts > 100,000 - t(9,22) |
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what factors are associated with better prognosis in ALL?
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- age 2-10
- low WBC - hyperploidy - trisomy 4,7,10 - t(12,21) |
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which drug is used in t(9,22)+ ALLs and inhibits BCR-ABL kinase?
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Imatinib (Gleevec)
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difference between CLL and SLL?
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degree of peripheral blood lymphocytosis
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Neoplastic cells are positive for CD19, CD20, CD23, and CD5;
deletions in 13q, 11q, 17p, trisomy 12q? |
CLL/SLL
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poor prognosis in CLL/SLL is associated with what progression of disease?
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prolymphocytic transformation (worsening cytopenias, inc splenomegaly, inc # prolymphocytes)
Richter syndrome - transformation to diffuse large B-cell lymphoma (rapidly enlarging mass in LN or spleen) |
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LN findings in follicular lymphoma?
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centrocytes - small, cleaved cells
centroblasts - larger cells w/ open chromatin, several nucleoli, modest amts of cytoplasm |
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what are the results of t(14,18) mutation?
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BCL2 and Ig heavy chain loci switch, BCL2 is overexpressed, promotes survival of follicular lymphoma cells by blocking bax channel
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mature B-cell tumors that express CD19, CD20 and sometimes translocation of BCL6; typically present at extranodal sites (GI, skin, bone, brain); aggressive, rapidly proliferating; may respond to therapy?
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Diffuse large B-cell lymphoma
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what are special subsets of diffuse large B-cell lymphoma?
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- may occur in setting of severe T-cell immunodeficiency; cells are usually infected with EBV
- may present as malignant pleural or ascitic effusion; mostly in advanced HIV or elderly; always infected with KSHV/HHV-8 |
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what causes lytic bone lesions in multiple myeloma?
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inc osteoclast activating factor (OAF, IL-6)
MIP1a induces expression of RANKL which activates osteoclasts Modulators of Wnt pathway inhibit osteoblasts |
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B-cell neoplasm that infiltrates many organs, has M spike (IgM), but no hypercalcemia, and no lytic bone lesions present?
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Lymphoplasmacytic lymphoma
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hyperviscosity syndrome, associated with lymphoplasmacytic lymphoma, causes what complications?
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vascular dilations and retinal hemorrhages --> visual problems
neuro sxs (HA, confusion) abnml globulins cause bleeding and cryoglobulinemia (precipitate at low temp and cause Raynaud phenomenon) |
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lymphoid neoplasm of older males consisting of small, cleaved lymphocytes, but no proliferation centers, no large centroblasts; t(11,14), high levels of cyclin D, CD5+, CD23-?
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Mantle cell lymphoma
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neoplasm of CD4+ T-cells in adults infected with HTLV-1, esp. in Japan, W Africa, Caribbean; presents w/ skin lesions, hypercalcemia, enlarged LN, liver, and spleen; cloverleaf nuclei?
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Adult T-cell Leukemia/Lymphoma (ATLL)
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tumor of CD4+ T-cells that causes generalized pruritic erythematous rash (w/o hypercalcemia); abnml cells have cerebriform nuclei?
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Mycosis fungoides/Sezary syndrome
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difference btwn MF and Sezary syndrome?
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skin lesions of sezary syndrome rarely become tumors
sezary cells (cerebriform nuclei) are found in peripheral blood in sezary syndrome, only found in epidermis/dermis in MF |
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rare neoplasm of CD8 T-cells, lymphocytes have abundant cytoplasm with coarse azurophilic granules?
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Large granular lymphocytic leukemia
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neoplasm presenting as descructive midline mass involving nasopharynx, skin, or testes; highly associated with EBV?
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extranodal NK/T-cell lymphoma
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how is HD different from NHL?
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- presents with fever
- spread is to contiguous (adjacent) nodal groups - characterization based on inflammatory response instead of malignant cell - no leukemic state - extranodal spread uncommon |
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HL variant that has L&H "popcorn" cells and are negative for CD15 and CD30, but positive for B-cell markers CD20 and BCL6?
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lymphocyte predominance type
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most common type of HL; has lacunar variant Reed-Sternberg cells that are positive for PAX5, CD15 and CD30; nuclear deposition of collagen in bands?
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Nodular sclerosis type
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type of HL with infiltrate of T-cells, eosinophils, plasma cells, benign macrophages with Reed-Sternberg cells; RS cells often infected with EBV?
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Mixed-cellularity type
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stereotyped progression of spread of HL?
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nodal dz --> splenic dz --> hepatic dz --> marrow and other tissues
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many myeloblasts on PBS, auer rods, peroxidase+ azurophilic cytoplasmic granules - Dx?
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AML
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auer rods are especially pronounced in what neoplasia (specific translocation)?
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t(15,17) - acute promyelocytic leukemia
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difference between acute leukemias and chronic leukemias?
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mostly blasts (acute), more mature cells (chronic)
children or elderly (acute), midlife (chronic) short and drastic (acute), longer, less devastating (chronic) |
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karyotypic abnormalities associated with AML?
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de novo: t(8;21), inv(16), t(15;17)
following MDS or exposure to DNA-damaging agents: del or monosomies of 5 & 7 after tx w/ topoisomerase II inhibitors: MLL chromosome (11q23) |
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disorder associated with t(8;14)?
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burkitt lymphoma (c-myc activation)
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disorder associated with t(14;18)?
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follicular lymphomas (bcl-2 activation)
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disorder associated with t(15;17)?
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M3 type AML
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disorder associated with t(11;14)?
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Mantle cell lymphoma
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most common presentation of AML?
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sxs related to anemia, neutropenia, TCpenia (fatigue, fever, spontaneous mucosal and cutaneous bleeding)
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what factors contribute to bleeding diathesis in AML?
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thrombocytopenia
procoagulants and fibrinolytic factors released by leukemic cells (esp in t[15;17]) |
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primary and t-MDS are associated with what karyotypic abnormalities?
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monosomy 5 and 7
del 5q, 7q, 20q trisomy 8 |
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most common finding in MDS?
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dysplastic differentiation affecting all three myeloid lineages (erythroid, granulocytic and megakaryocytic)
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morphological changes seen in MDS?
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erythroid: ringed sideroblasts, megaloblastoid maturation, nuclear budding abnormalities
granulocytic; neutrophils with dec or abnml/toxic granules, pseudo-Pelger-Huet cells Megakaryocytic: pawn ball meg.cytes |
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what are pseudo-Pelger-Huet cells?
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neutrophils with only two lobes (seen in MDS)
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what are the chronic myeloproliferative disorders?
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- CML
- polycythemia vera - essential thrombocytosis - myelofibrosis w/ myleoid metaplasia |
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what features are common to all MPDs?
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- neoplastic stem cells home in to secondary hematopoietic organs, esp spleen, leading to splenomegaly
- terminal spent phase: marrow fibrosis and peripheral cytopenias - progression to acute leukemia |
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what is the biomechanical change that occurs in CML?
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BCR gene (22) fuses with ABL gene (9) and synthesizes a constitutively active tyr-kinase, stimulating proliferation and survival of marrow progenitors
does not interfere with differentiation --> increase in mature cells in blood, esp granulocytes and plts |
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what lab finding helps differentiate between CML and other leukemoid reactions?
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absence of leukocyte alk phos in CML
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cell counts in CML - RBCs, WBCs, Plts?
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dec RBCs
inc WBCs inc Plts |
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pharm tx of CML?
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Imatinib (anti-bcr-abl antibody)
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mutation implicated in polycythemia vera?
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activating point mutations in tyr-kinase JAK2
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difference between polycythemia vera and secondary absoulte polycythemia?
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PCV = low EPO
secondary polycythemias = high EPO |
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symptoms of PCV?
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plethora and cyanosis (d/t stagnation and deox of blood in peripheral vessels),
HA, dizziness, HTN, GI sxs, DVT, MI, stroke |
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why do some pts w/ PCV have HCT within normal range?
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chronic bleeding leads to iron deficiency which suppresses erythropoiesis
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extended survival with PCV leads to what?
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"spent phase" clinically resembling myelofibrosis
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pathogenesis of essential thrombocytosis?
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same JAK2 point mutation as in PCV - receptor tyr-kinase activation makes progenitors thrombopoeitin-independent
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major manifestations of ET?
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thrombosis and hemorrhage
DVT, portal and hepatic vein thrombosis, MI, erythromelalgia |
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what is erythromelalgia?
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throbbing and burning of hands and feet caused by occlusion of small arterioles by plt aggregates
seen in ET and PCV |
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pathogenesis of primary myelofibrosis?
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inappropriate release of PDGF and TGF-beta from neoplastic megakaryocytes (fibrogenic factors)
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in what disease are large platelets and dacryocytes found?
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myelofibrosis
(dacryocytes = teardrop shaped RBCs damaged during birthing process in fibrotic marrow) |
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cause of splenomegaly in primary myelofibrosis?
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circulating hematopoeitic stem cells home to secondary hematopoietic organs esp spleen, liver, LNs
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secondary disorder that can complicate the picture of MPDs?
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hyperuricemia and gout (from high cell turnover rate)
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infant develops cutaneous seborrheic-like eruption on chest, back, and scalp; also has hepatosplenomegaly, lymphadenopathy, pulmonary lesions. Dx?
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Letterer-Siwe disease
(Multifocal multisystem Langerhans cell histiocytosis) |
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pathogenesis of primary myelofibrosis?
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inappropriate release of PDGF and TGF-beta from neoplastic megakaryocytes (fibrogenic factors)
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in what disease are large platelets and dacryocytes found?
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myelofibrosis
(dacryocytes = teardrop shaped RBCs damaged during birthing process in fibrotic marrow) |
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What is the Hand-Schuller-Christian triad?
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calvarial bone defects, diabetes insipidus, and exophthalmos
(multifocal unisystem Langerhans cell histiocytosis that involves the posterior pituitary stalk) |
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causes of congestive splenomegaly?
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venous obstruction d/t intrahepatic disorders (esp. cirrhosis) that slow portal venous drainage or extrahepatic disorders that impinge upon portal or plenic veins (pylephlebitis, portal vein thrombosis)
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MCC of splenic infarctions?
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emboli arising from the heart
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MCC of thymic hypoplasia?
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DiGeorge syndrome
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MCC of thymic hyperplasia?
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myasthenia gravis
(also seen in other AI dz: Graves, SLE, scleroderma, RA) |
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difference between invasive thymoma and thymic carcinoma?
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invasive thymoma is cytologically benign but locally invasive
thymic carcinoma is invasive, somtimes accompanied by metastases, usually squamous cell carcinoma |
