Neoplastic hematopathology Flashcards

Question

Lymphoproliferative disorders arising in primary immunodeficiency

Answer 1

* Primary immunodeficiencies * ataxia telangiectasia * Wiskott Alrdich * CVID * X linked LP disorder (Duncan) * Nijmegen chromosomal breakage syndrome * Most common LPDs * DLBCL, LG, and T cell neoplasm

Answer 2

* BL * DLBCL (especially CNS) * PEL * plasmablastic lymphoma * HL

Answer 3

* Usually \<1 year after transplant * EBV implicated in most (especially in 1st year) * Heralded by elevated EBV viral load * Late (\>5 years out) PTLD is most aggressive and EBV- * Risk factors * allograft * renal and BMT have lowest risk * heart-lung and liver-bowel have higher risk * children * EBV- at time of transplant * PTLD clone usually of recipient origin * often involves the allograft itself

Answer 4

* 3 clinicopathologic types of Burkitt lymphoma are recognized * **African** (endemic): jaw mass in child, EBV+ * **Western** (sporadic): nodal, abdominal, less associated with EBV; kids and adults * **Burkittlike lymphoma**: nodes, IC hosts * morphology * tissue * diffuse proliferation; medium sized nuclei with 2-5 nucleoli * many tingible body macrophages, high rate of mits/apoptosis * Wright stained blood * deep blue cytoplasm with lipid containing vacuoles * Immunophenotype * **positive**: CD19, CD20, CD22, CD10, bcl-6, sIg, C-myc * **negative**: CD5, CD23, Tdt, CD34, bcl-2 * **Ki67 \>99%** * vs DLBCL, NOS * BL positive for c-myc, negative for bcl-2, and Ki67 \>99% * BL unlikely if CD10 negative, bcl-6 negative, or bcl-2 positive * BL unlikely if either BCL2 or BCL6 rearrangements are present * vs B-LBL/B-ALL * BL is Tdt negative, CD20 positive, and sIg positive * **Molecular** * rearrangement of C-MYC on chromosome 8 * t(8;14) * Igkappa t(2;8) * Iglambda t(8;22)

Answer 5

* B-ALL/LBL, NOS * B-ALL/LBL with recurrent cytogenetic abnormalities * T-ALL/LBL

Answer 6

* LBL: lesions involving tissue and sparing blood and marrow * ALL: marked involvement of marrow (\>25%) and blood (\>20%) regardless of tissue involvement * ALL: B lineage in 80% * LBL: T lineage in 80%

Answer 7

* B-ALL is most common malignancy in children; peaks at **3 years** of age * T-LBL presents as **anterior mediastinal mass**; **hypercalcemia** is common * **Morphology** * undifferentiated blasts * cytochemically negative for MPO and SBB; **PAS+** in blocklike/coarse granular pattern

Answer 8

* Immunophenotype * positive: **CD19, CD10, PAX5, CD34, CD99, HLA-DR, nuclear TdT** * Usually **negative for CD20 and sIg** * absence of CD10 suggests MLL anomaly * 30-50% express at least 1 myeloid antigen (CD13 or CD33) * Prognosis * Good * lower initial white count * 2-10 years old * female * complete remission (day 14 marrow) following induction chemo * Hematogones vs ALL * hematogones disperse, both in CD34 stained marrow sections and in flow plots * blasts cluster * by flow cytometry, hematogones display a range of expression of CD10, CD20, Cd34, Tdt, sIg * blasts express a relativly uniform strength * Molecular and cytogenetic * 6q * 9p * 12p * "recurrent genetic abnormalities" absent

Answer 9

* Most common structural abnormality is t(9;22)(q34;q11) * unfavorable * minor breakpoint (m-bcr) rearrangement, chimeric protein of 190kD most common * t(v;11q23), usually t(4;11) * MLL * infants * unfavorable * overexpress FLT3 * t(12;21) * TEL-AML1 (ETV6-RUNX1) * 25% of children * good * Hyperdiploid * \>50 * 25% of children * good * Hypodiploid * \<46 * \<5% of children * unfavorable * t(1;19) * E2A-PBX1 (TCF3-PBX1) * 5% of children * unfavorable * t(5;14) * IL3-IGH * \<1% of children and adults * usual prognosis * eosinophilia

Answer 10

* Immunophenotype * positive: **CD99, CD7, CD2, CD5, CD3 (cytoplasmic), and TdT** (nuclear) * **CD34** variable; **HLA-DR is usually negative** * **CD4 and CD8** often both positive or both negative * some express myeloid antigens (**CD13 or CD33**) * T-LBL vs thymoma * Thymoma is **EMA** positive * By flow, similar to distinction of hematogones and B-ALL * Thymoma: dispersal plots of CD4 vs CD8 and CD45 vs CD3 * T-LBL: tight clustering in plots of CD4 vs CD8 and CD45 vs CD3

Answer 11

* median 70 years * blacks \> whites * males \>females * forms * symptomatic * smouldering * renal manifestations * hypercalcemia and/or hyperuricemia induced tubular injury * AL amyloidosis most commonly found with lambda light chains * Light chain deposition disease most commonly with kappa light chains * myeloma cast nephropathy

Answer 12

* isotype (heavy chain) is most commonly IgG * IgA (22%) * none - light chain only (18%) * IgD (1-2%) * biclonal (1-2%) * IgE (1-2%) * idiotype (light chain) is most commonly kappa * nonsecretory myeloma is found in 5% of cases

Answer 13

* positive: CD38, CD138, CD56, cytoplasmic lambda or kappa, and PCA1 * negative: CD45, CD19, CD20, CD21, CD22, sIg * some are cyclin D1+ (bcl-1), correlating with t(11;14) * 10-30% express myelomonocytic markers (CD117, CD33, CD13, CD11b, CD15) * 10-50% express CALLA (CD10) * occasionally EMA and CD30+

Answer 14

* most common abnormality is in IgH (14q32) * 14q32 rearrangement found in \>70% of myeloma and 50% of MGUS * t(11;14) produces CCND1/IgH fusion

Answer 15

* adverse: * higher levels of **beta2 microglobulin** * high **plasma cell labeling index** * high **stage** * chromosomal abnormalities by **FISH**

Answer 16

* **\>20%** or **\>2 x 10⁹/L** plasma cells in the peripheral blood * 1/2 of cases present de novo * present abruptly and follows an **aggressive** course * high incidence of **monosomy 13** * plasma cells often **CD56 negative**

Answer 17

* solitary osseous plasmactyoma arises most often in vertebrae, ribs, and pelvis * 1/2 have detectable M protein * Most develop MM within 10 years * Solitary extraosseous arises most commonly in the nasal cavity, oropharynx, or larynx * most do not have a detectable M protein * most do not develop MM

Answer 18

* present in 3% of adults over the age of 50 years and 5% of adults over the age of 70 years * 60% of patients with an M protein are classified as MGUS * 1% progression per year to MM or another PCN * after 20 years, 1 in 3 develops overt myeloma

Answer 19

* 5% of lymphoid neoplasms * incidence highest in Asia * enteropathy associated T cell lymphoma strongly associated with Welsh and Irish ancestry * Most common T cell neoplasms, in decreasing order: PTCL NOS, AITCL, ALCL, ATCL

Answer 20

* Any T cell neoplasm that does not fit any other clinicopathologic entity * Most common T cell lymphoma * Morphology * diffuse proliferation of polymorphic small and large lymphoid cells * neoplastic lymphs may have cloverleaf nuclei * admixed eos, plasma cells, and/or histiocytes * postcapillary venules may be prominent * Immunophenotype * CD4+ * CD8- * Loss of one or several pan T cell markers * CD25-

Answer 21

* Caused by HTLV-1 * endemic in southwest Japan, Oceania, and the Caribbean * rare in North America * Lifetime risk of ATCL in HTLV-1 positive people is **5%** (greater for **men** than women) * **Clinical presentation** * LAD and HSM * visceral involvement (CNS, lungs, GI tract) * rash * hyperCa * lytic bone lesions * **Morphology** * nuclear irregularity with cloverleaf or flower forms * **Immunophenotype** * positive: CD2, CD3, CD5, CD4, and CD25 * negative: CD7 usually and CD8

Answer 22

* **EBV** associated neoplasm affecting **older** adults * **Clinical presentation** * abrupt onset * constitutional symptoms: fever, night sweats, weight loss * generalized LAD * pruritic rash * pleural effusion * Coombs+ autoimmune hemolytic anemia * cold agglutinins * anti-smooth muscle antibody * RF * polyclonal hypergammaglobulinemia * **Morphology** * diffuse nodal effacement with prominence of postcapillary venules * immunoblasts, lymphs, plasma cells, eos, aggregates of cells with clear cytoplasm * deposition of **PAS+** extracellular material, and a mixed lymphoid infiltrate * absence of apparent follicles; **CD21** displays **hyperplastic** follicular dendritic cells * Immunophenotype * **positive**: CD4, most pan T markers (CD2, CD3, CD5, CD7) and TFH markers (CD10, bcl-6, CXCL-13) * **negative**: CD8, loss of one or several pan T cell markers (CD2, CD3, CD5, CD7) * **EBV** is present in B cells

Answer 23

* children and young adults * 50% of childhood high grade lymphomas * morphology * diffuse proliferation with many large lymphs, some of which are anaplastic * anaplastic cells cluster near **blood vessels** * **small cell variant** is composed of large, but not anaplastic lymphoid cells; may be mistaken for PTCL * prognosis depends on expression of Alk; **Alk+ has best prognosis** * WHO classification has separate categories for Alk+ and Alk- ALCL * Alk- ALCL has worse prognosis than Alk+ but better than PTCL NOS * Immunophenotype * **positive**: **CD30** (membranous and golgi), **clusterin, EMA, CD45** * **often positive for myeloid** antigens (CD13, CD33) * often positive for **T cell antigens** (CD4) * Alk expression correlates with **t(2;5)** * with usual t(2;5) NPM-ALK, Alk is expressed in cytoplasm and nucleus * variant translocations result in various patterns of Alk expression * **negative for B cell antigens, CD15, and EBV** * Molecular and cytogenetics * **t(2;5) in \>95%** * ALK (anaplastic lymphoma kinase) gene on 2p23 and NPM (nucleophosmin) on 5q * clonal **TCR** rearrangement in 90%

Answer 24

* **\> 6 month increase** **(\>2 x 10⁹**) in LGL * may be T cells or NK cells * Tc cytotoxic LGL leukemia * **neutropenia** * **splenomegaly** * polyclonal **hypergamma**globulinemia * older **men** * associated with **rheumatoid arthritis** * usually indolent; **more aggressive if CD56+ blast-like cells** present * **Immunophenotype** * positive: CD2, CD3, CD8, CD16, CD57, granzyme M, granzyme B * negative: CD4, often negative/dim for CD7 and or CD5 * **TCR rearranged**

Answer 25

* neutropenia, anemia, fever, jaundice, HSM * EBV negative (in contrast to aggressive NK cell leukemia) * Immunophenotype * **positive**: CD2, CD16, CD56 * **variable**: CD7, CD8, CD57 * **negative**: surface CD3 (cytoplasmic epsilon chain of CD3 is positive) and CD4 * TCR germline

Answer 26

* aggressive **EBV** associated neoplasm * **Asians** * mean age **40**

Answer 27

* extranodal, usually nasal, **EBV** associated neoplasm * **angioinvasive** growth pattern * more common in **Asians, Native Americans**

Answer 28

* **high grade** T cell lymphoma in patients with longstanding **celiac sprue** * often preceded by refractory sprue with mucosal ulceration (**ulcerative jejunoileitis**) * **jejunum and/or ileum** * like sprue, Welsh and Irish ancestry common * most have the **HLADQA1\*0501, DQB1\*0201** genotype * **CD3+, CD30+, and usually CD4-/CD8-**

Answer 29

* **gamma-delta type** * young males * B symptoms * HSM * cytopenias * **CD8+** cytotoxic T cells that express gamma delta TCR and isochrome **7q** * **alpha-beta type** * female * wider age distribution

Answer 30

* CTCL is a CD4+ T cell neoplasm with epidermotropic growth pattern * small to large lymphoid cells with cerebriform nuclei * MF is CTCL which involves lymph nodes * Sezary syndrome is CTCL involving peripheral blood

Answer 31

* **morphology** * nodular or vaguely nodular * RS cells rare to absent * **L&H cells** with large vesicular convoluted (popcorn) nucleus * **progressive tranformation of germinal centers** thought to be precursor lesion * **NLPHL vs TCRBCL** * Meshwork of follicular dendritic cells, highlighted by **CD21 or CD23 IHC** * predominance of **CD20+ B cells** * wreath of **CD3+/CD57+ T cells** * **NLPHL vs CHL** * neoplastic cell in NLPHL * L&H cells express **CD45, CD20, surface Ig, bcl-6, and EMA, OCT2, BOB1 (latter two stains incorrectly described in Compendium)** * L&H cells negative for **EBV**

Answer 32

* Immunophenotype * positive: CD15, Cd30 * often positive for **fascin**, IRF4/**MUM1**, **PAX5 (weak)**, **EBV**, antigens (LMP-1, EBER1/2) * negative: CD45, CD20, bcl-6, **ALK**, EMA * 10-20% are CD20+ * background lymphs predominantly T cells * Incidence: bimodal (15-25 years and after age 50) * Clinical presentation: * localized LAD * cervical lymph nodes most often, followed by mediastinum * spread via contiguous lymphatic sites; noncontiguous spread in LD * B symptoms * Bone marrow * LD and HIV-associated have highest involvement * 10% overall * atypical mononuclear CD30+ cells

Answer 33

* Mediastinum * Micro * nodular with bands of sclerosis * RS cells, Hodgkin cells, and lacunar cells * lacunar appearance due to formalin fixation artifact * **syncytial** NS an aggressive form of CHL that presents at high stage with bulky mediastrinal disease, composed of sheets of RS cells and RS variants; may have necrosis * **25% EBV positive** * background is mixed

Answer 34

* **peripheral nodes** * **25-45** years * **HIV** associated * **developing nations** * diffuse proliferation of **lymphs, eos, histiocytes, and plasma cells** with varying numbers of classic **RS** cells and mononuclear **Hodgkin** cells * **75% EBV** positive

Answer 35

* similar NLPHL but has typical immunophenotype of CHL * peripheral nodes * 35-55 yo * Micro * R-S cells * Hodgkin cells * popcorn cells * 50% EBV positive

Answer 36

* retroperitoneum * \<1% of CHL * 30-40 years * HIV associated * Developing nations * RS cells and variants \> 15/HPF * Pleomorphic cells * mixed background * **50%** EBV positive * relatively aggressive

Answer 37

* promonocyts in diagnosis of acute monocytic or myelomonocytic leukemia * promyelocytes in APL * erythroblasts in pure erythroleukemia

Answer 38

Usually splenomegaly is not present in MDS

Answer 39

* chemotherapy (alkylating agents) * associated with 5q or 7q * radiation * benzenes * Fanconi anemia

Answer 40

* Marrow is usually hypercellular; sometimes abnormal localization of immature precursors * blasts \< 20% * dyspoiesis present in at least one cell line * **erythroid** * PB: anemia, basophilic stippling, poikilocytosis, and macrocytosis * Marrow: megaloblastoid change and/or nuclear lobation, internuclear bridging, multinuclearity, karyorrhexis, **ringed sideroblasts** (at least 5 siderosomes surrounding at least 1/3 nucleus), cytoplasmic **PAS+,** cytoplasmic vacuoles * Functional: increased susceptibility to c**omplement mediated lysis**, increased **HbF,** abnormal expression of red cell antigens, **acquired enzyme defects** (e.g., pyruvate kinase deficiency), **acquired thalassemia** * **Granulocytic (myeloid)** * PB: neutropenia, abnormal cytoplasmic granulation, or abnormal nuclear segmentation (including **pseudo Pelger-Huet** anomaly) * Marrow: megaloblastoid maturation, abnormal cytoplasmic granulation * Functional: increased susceptibility to bacterial infection * **Megakaryocytic dyspoiesis:** * PB: thrombocytopenia, variable size, variable granulation * Marrow: micromegs, multinucleated megs, hypolobated megs * Functional: abnormal platelet aggregometry * Heathly marrow contains dyspoietic cells (\<5% of any cell line) * Dyspoiesis must be **\>10%** in a cell line to diagnose dysplasia

Answer 41

* B12 and folate deficiency * alcohol * HIV * lead * arsenic * copper deficiency/zinc intoxication (prominent erythroid vacuolization and iron laden plasma cells are clues) * medications * INH * chloramphenicol * chemo

Answer 42

* 30-40% of low grade (RA, RARS) have cytogentetic abnormalities * 70-80% of high grade have abnormalities * most common is complex karyotype (2 or more clonal abnormalities) * 2nd most common is isolated 7 or 7q- * 3rd most common is isolated 5q- * disproportionately affects elderly women * anemia, normal to elevated platelets, micromegs in bone marrow * indolent clinical course

Answer 43

* primary features * persistent absolute monocytosis (\>1 x 10⁹/L) * marrow dysplasia * \<20% blasts (blasts + promonocytes) * absence of Philadelphia chromosome * HSM * anemia * thrombocytopenia * abnormal monocyte morphology * 2 types * CMML-1: blasts and promonocytes \< 5% in PB and \<10% in marrow * CMML-2: 5-19% in PB , 10-19% in marrow * Molecular and cytogenetic * JAK2 mutation in some * if eosinophilia is present, rearrangement of PDGFRA and PDGFRB should be excuded

Answer 44

* **neutrophilia** * **spectrum** of neutrophils, metamyelocytes, myelocytes, and promyelocytes * marrow dysplasia * \<20% blasts * **absence of Philadelphia chromosome** * most have cytogenetic anomalies, especially **+8 or del(20q)** * some have **JAK2** mutations

Answer 45

* monocytosis and/or granulocytosis * HSM * B symptoms * may have anemia, thrombocytopenia, increased HbF * may have monosomy 7 * in vitro spontaneous formation of granulocyte macrophage colonies that are hypersensitive to GM-CSF is confirmatory * nearly 10% of patients have NF-1

Answer 46

* t(9;22) * ABL locus at 9 and BCR at 22 * chimeric Bcr-Abl protein with enhanced tyrosine kinase activity * major breakpoint cluster **p210** fusion protein * uncommonly occurs at mu-BCR breakpoint with **p230** fusion protein * associated with **thrombocytosis** and **more** **mature leukemic neutrophils** * uncommonly m-BCR breakpoint with **p190** fusion protein associated with * **CML with marked monocytosis** * **Ph+ ALL**

Answer 47

* Indices * leukocytosis with neutrophilia, monocytosis, basophilia, eosinophilia * thrombocytosis common * **neutrophils immature**, and myelocyte proportion is high * marrow * hypercellular with **high M:E** ratio and small hypolobated **dwarf megs** * mild reticulin **fibrosis** and thickening of paratrabecular generative cuffs * **splenomegaly** * low leukocyte alkaline phosphatase **(LAP)** score * elevated **B12**

Answer 48

Marked by at least one of the following: 1. progressive **basophilia** (\>20%) 2. progressive **thrombocytopenia** (\<100 x 10⁹/L) or **thrombocytosis** (\<1000 x 10⁹/L) 3. **clonal cytogenetic progression** (+8, i17q, +19, 2nd Ph chromosome) 4. **increasing blasts**: \> 10% (but less than 20%)

Answer 49

* **\>20%** blasts in blood or marrow, a tissue infiltrate of blasts (**chloroma**), or a prominent focal accumulation of blasts in the **marrow** biopsy (filling an intertrabecular space) * **70% AML, 30% ALL** * often additional **cytogenetic abnormalities**

Answer 50

* Most powerful prognostic factor is response to **TKI therapy** as measured by **RT-PCR** * imatinib resistance present in 5% of cases * resistance often result of mutations within BCR-ABL gene; **tyrosine kinase domain** and the **P loop**

Answer 51

* presentation * HTN * thrombosis * pruritis * plethora * erythromelalgia * headache * splenomegaly * Phases * Proliferative (chronic) * erythrocytosis, sometimes with neutrophilia, basophilia, and/or thrombocytosis * marrow hypercellular, usually with megakaryocytic hyperplasia; iron decreased * Spent phase (postpolycythemic myelofibrosis with myeloid metaplasia) * peripheral myelophthisic pattern, marrow reticulin fibrosis, and extramedullary hematopoiesis * Cause of death: thrombosis is #1, acute leukemia is #2 * JAK2 mutation * \>90% of PV and over 50% of ET and PMF * involved in stimulating the STAT pathway * most common mutation is G to T at nt 1849 resulting in val to phe at codon 617 * 2nd activating mutation within JAK2 exon 12 in some cases * mutations in MPL is present in some PMF and ET, but are not seen in PV

Answer 52

* bimodal ages: **30 and 60** * **longest survival** of the MPNs with the lowest transformation to acute leukemia * presents as isolated thrombocytosis * marrow: * **large, hyperlobated megs** that are **paratrabecular** and display **emperipolesis** * **iron** usually present (helpful to exclude iron deficiency)

Answer 53

* Cellular phase (prefibrotic) * anemia, mild leukocytosis, thrombocytosis * marrow hypercellular * megs abnormal (aberrantly lobulated with clumped, inky chromatin) in clusters adjacent to sinuses and trabeculae * Fibrotic phase * leukoerythroblastic pattern in PB * marrow is inaspirable * reticulin fibrosis, intrasinusoidal hematopoiesis * abnormal clustered megs

Answer 54

* Male:female = **9:1** * ages **25-45** * PB eosinophilia **(\>1.5 x 10⁹/L)** with tissue infiltration and damage * **heart** * **GI** * **lung** * **CNS** * eos may be hypogranular, but granules highlighted by **cyanide resistant MPO stain** * must exclude allergic reaction, parasitic infection, collagen vascular disease, mastocytosis, other hematolymphoid neoplasms (PDGFRalpha, PDGFRbeta, and FGFR1 rearrangement) * must have **evidence of clonality**, such as increased blasts or clonal cytogenetic abnormality; without this the diagnosis is **hypereosinophilic syndrome**

Answer 55

* Most common type of acute leukemia in adults and infants \< 1 year of age * median age 65 years * Presentation * leukocytosis or pancytopenia or soft tissue mass (chloroma) * blasts usually present in PB * Diagnosis * blasts \>20% * blasts \<20% if there is pure erythroleukemia, myeloid sarcoma, or defining genetic abnormalities * blast count may include promyelocytes in APML or promonocytes in acute monocytic leukemia * Immunophenotype * positive: CD13, CD33, HLA-DR, CD34, and CD45 (dim) * some express CD7 or CD19 * Classfied: * AML with recurrent genetic abnormalities * AML arising secondary to therapy * AML with myelodysplasia related changes * AML, NOS

Answer 56

* **young adults** * very **chemosensitive** * involves **AML1 (RUBX1)** and **ETO (RUNX1T1)** genes * AML1 encodes alpha chain of core binding factor (**CBFalpha**) * blasts have **azurophilic** granularity, sometimes with large granules (**pseudo Chidiak Higashi**) and **Auer rods** * favorable prognosis * Immunophenotype: * positive: CD34, CD13, CD33, CD56, HLA-DR, CD19 * high rate of activating **KIT mutations** in relapsed cases

Answer 57

* **M4-like** * **increased/abnormal eosinophils** * involves **MYH1 (myosin)** and **CBFBeta genes** * **blasts** with **myelomonocytic** differentiation and **abnormal eosinophils** * eos with large granules with **alpha napththyl acetate esterase** * usually **no eosinophilia** in PB * Immunophenotype: * positive: **CD13, CD33, CD14, CD64, CD11b, HLA-DR, lysozyme, and CD2** * younger adults * chemosensitive * favorable prognosis

Answer 58

Acute promyelocytic leukemia * promyelocytes * cytoplasm varies from intensely granulated to agranular (microgranular variant) * microgranular variant has occasional Auer rods and is strongly **MPO positive** * often have **DIC** * respond to tranretinoic acid (ATRA) * Immunophenotype: * positive: **CD33, CD13, CD15 (DIM)** * negative: **HLA-DR and CD34** * t(15;17) results in RARalpha next to PML * variant translocations: **t(11;17) and t(5;17)** * insensitive to ATRA * middle age * favorable prognosis

Answer 59

* common in children * MLL anomalies * monoblastic differentiation (M5-like) * immunophenotype: * positive: CD4, CD14, CD64, CD11b, lysozyme * negative: usually CD34 * intermediate prognosis

Answer 60

* multilineage dysplasia * RS * increased platelets * erythroid hyperplasia * Topo II: 11q23 (MLL) or 21q22 (RUNX1) * Therapy + 5 years * poor prognosis

Answer 61

* any morphology, especially M4 with basophilia * DEK/NUP214 * children and adults * poor prognosis * immunophenotype: * positive: CD34, HLA-DR, CD13, CD33 * Tdt +/-

Answer 62

* megakaryocytic (M7-like) * RBM15/MKL1 * infants * intermediate prognosis * immunophenotype: * positive: CD13, CD33, CD41, CD61 * negative: CD34, HLA-DR

Answer 63

* M0, M1, or M7-like * thrombocytosis * giant agranular platelets * RPN1/EVI1 * adults * poor prognosis

Answer 64

* **Agranular** cytoplasm * **\<3%** blasts stain with SBB, MPO, and NSE * myeloid differentiation demonstrable only by immunophenotyping (or ultrastructural cytochemical reactions) * Immunophenotype * positive: CD13, CD33, CD117, CD34, HLA-DR * negative: CD14, CD15, CD11b * **Tdt+** in up to 30% of cases * **Poor** prognosis

Answer 65

* 3-10% of blasts show maturation (stain with MPO, CAE, or SBB) * rare Auer rods and/or granulation * usually express CD34, CD13, CD33, HLA-DR, CD117 * poor prognosis

Answer 66

* maturation in greater than 10% of blasts * monocytic differentiation in \<20% of nonerythroid cells * cytoplasmic granulation and Auer rods frequent * rule out t(8;21) * immunophenotype: * positive: HLA-DR, CD13, CD33, CD117, CD15 * may or not be CD34 positive * Variable prognosis

Answer 67

* at least 20% of nonerythroids have monocytic differentiation * at least 20% of nonerythroids have neutrophilic differentiation * immunophenotype * positive: **CD13, CD33, CD4, CD14, CD64, CD11b** * smaller population may be CD34+ * variable prognosis

Answer 68

* **monocytic differentiation in over 80% of nonerythroid cells** (including monoblasts, promonocytes, and monocytes) * acute monoblastic leukemia * **\>80% of monocytic cells are monoblasts** * acute monocytic leukemia * \<80% monoblasts * Immunophenotype * postiive: **HLA-DR, CD4, CD14, CD64, CD11b, lysozyme** * variable expression of CD13, CD33, CD117 * variable but usually negative CD34 * younger people * often have soft tissue infiltration (**gingival, CNS**) * poor prognosis

Answer 69

* 2 subtypes * **erythroleukemia** * **\>50%** of all nucleated cells are **erythroids** and **\>20%** of nonerythroids are **myeloblasts** * **pure erythroid leukemia** (true erythroleukemia, acute erythremic myelosis) * **\>80% of all nucleated cells** are erythroid precursors; **without excess myeloblasts** * peripheral **anemia**, not erythrocytosis, with numerous circulating nucleated **RBCs** * marrow erythroids dysplastic and megaloblastoid * erythroid cytoplasm may have **vacuoles and PAS positivity** (like ALL blasts) * **Immunophenotype** * Myeloblasts variably positive for CD34, HLA-DR, CD13, CD33, CD117 * Erythroids: HLA-DR, CD34, glycophorin (CD235a), and CD71 (may be aberrantly dim) * cases wtih \>50% erythroids but \<20% myeloblasts may be classified as **MDS** (RAEB) * **poor prognosis**

Answer 70

* **\>50% of blasts megakaryocytic**, either by platelet peroxidase (**PPO**) technique (electron microscopy with staining for peroxidase), or by immunophenotyping (**CD41 or CD61**) * associated with * **mediastinal germ cell tumors (Isochromosome 12p)** * often AML and transient myeloproliferative disorders in **Down** syndrome are often megakaryoblastic * **poor prognosis**

Answer 71

* 1/2 ALL and 1/2 AML * **DS associated ALL** * generally similar to non-DS ALL * **DS associated AML** * increased chemosensitivity, particular to **MTX** * relatively favorable prognosis * peaks between **1-5 years of age** * blasts express **CD11b and CD13; negative for CD34** * **Transient myeloproliferative disorder** (TMD)/**transient abnormal myelopoiesis** (TAM) * 10% of neonates with DS * **1st week** of life usually * may be trisomy 21 mosaic or confined to the clone itself * marked **leukocytosis and HSM** * difficult to distinguish from **congenital acute leukemia** * in most cases, complete resolution without therapy * still at **high risk for AML** during childhood * **TMD blasts negative for CD11b and CD13, positive for CD34** * somatic mutations in the **GATA1 gene** in blasts of both **TMD** and **DS associated AML**

Answer 72

* arbitrarily defined as an **acute leukemia presenting before 4 weeks of age** * must be distinguished from a **leukemoid reaction and TMD** (need FISH/cytogenetics) * most commonly myeloblastic (AML) * vast majority are **monocytic/monoblastic** * commonly with **leukemia cuti**s, often described as "blueberry muffin" babies * 10% have abnormalities of 11q23 (**MLL**) gene

Answer 73

* **systemic mastocytosis** * skin * spleen * bone marrow * GI tract * elevated * **serum tryptase** * **urine N-methylhistamine (NMH)** * **urine prostaglandin D2** * **histamine** (hypereosinophilic states can also increase histamine) * Morphology * in marrow, **spindled or round** cell infiltrates, often with **fibrosis** and **eosinophils** * **Immunophenotype** * positive: **LCA, CD11c, CD33, CD43, CD117, FceRI** * unlike benign mast cells, malignant mast cells express **CD25 and CD2 with decreased CD117** * CD25 expression correlates with **CKIT** mutation * **molecular** * **CKIT** mutation, most commonly **D816V**

Neoplastic hematopathology Flashcards

(173 cards)