Hematopoietic Malignancies

Question 1

Mature Lymphoid Neoplasms (3)

Answer 1

Hodgkin Lymphoma, Non-Hodgkin Lymphoma, and Plasma Cell Neoplasm

Question 2

Nodular Lymphocyte Predominant Hodgkins Lymphoma (NLPHL)

Answer 2

B-cell orgin and indolent. Minority of large lymphocytes with multilobated nuclei (“popcorn” cells); majority are reactive to lymphocytes and histiocytes.

Question 3

Classical Hodgkins Lymphoma (Pertinent cells and Markers)

Answer 3

Based on RS cells (large, many or multilobed nucleus, eosinophilic inclusion-like nucleolus, CD30+ and CD15+, large cytoplasm, and ned for common leukocyte CD45)

Question 4

Classical Hodgkins Lymphoma (Manifestations (4))

Answer 4

1. Nodular Sclerosis: most common, effects young females, usually above the diaphragm, EBV in 10-25% , broad collagen bands and lacunar cells. 2) Mixed cellularity: 20-25% higher in kids and elderly, NO collagen bands, constituional B symptoms, EBV in 75%, below or both side of diaphragm. 3) Lymphocyte rich: 5% of CHL, RS cells present but rare. 4) Lymphocyte depleted: 1% of CHL (better prog.), no lymphocytes, numerous RS cells, some of which are anaplastic and bizzare (sarcomatous), and usually EBV+.

Question 5

Types of Non-Hodgkin Lymphoma (4)

Answer 5

Burkitt lymphoma (GC B cell), follicular lymphoma (GC B cell), Mantle Cell Lymphoma (mantle cell), and SLL/CLL (pre or post GC, mature B cells)

Question 6

Burkitt Lymphoma (GC B cell)

Answer 6

Aggressive; endemic (African, and jaw), sporadic (effects abdomen), starry sky pattern (tons of reactive cells surrounding macrophage), t(8;14) c-MYC (results in overexpression of cMYC, which results in a high proliferation index), CD10. CD19, CD20, BCL6, and MYC!, EBV in 30% sporadic cases.

Question 7

Follicular Lymphoma (GC B cell)

Answer 7

40% of adult lymphoma, median age 60, indolent. Crowded follicles; node effacement, no mantle zone, polarity or starry sky. t(14;18) which causes overexpression of BCL2 and prevents apoptosis in cells that fail somatic mutation). CD10, CD19, CD20, BCL2!, and BCL6. Different from reactive follicularhyperplasia because variable follicle size, neg t(14;18) and neg BCL2.

Question 8

Mantle Cell Lymphoma (mantle cell)

Answer 8

More in elderly and males; usu asymptomatic, effaced node, centroblst-like cells, characteristic t(11;14) (overexp. of BCL1, which increase CycD), CD19, CD20, CD5!, BCL1!, CD10, and BCL6 (neg for CD23)

Question 9

SLL/CLL (pre or post GC, mature B cells)

Answer 9

CLL:blood lymphocytosis, BM involved, males and >65 years affected), most common leukemia of Western world. SLL: extramedullary site. Both: small round dense nuclei, with smudge cells, effaced nodes, 13q14 deletion in >50% of CLL. CD5, CD23!, CD19 (negative for CD10 or FMC7)

Question 10

Plasma Cell Neoplasms Types (3)

Answer 10

Multiple/ Plasma Cell Myeloma, MGUS, and Plasmacytoma

Question 11

Multiple/ Plasma Cell Myeloma

Answer 11

Usu >40 yrs, median age 68. CRAB symptoms (Hypercalcemia, renal insufficiency, anemia, and bone lesions), M spike meaning increase in immunoglobin, disturbs ionization of RBCs causes Rouleux formation on smear. Almost always need BM biopsy to diagnose; hypercellular with clockface chromatin and IgG inclusions. Lack antigenic diversity so more prone to infections.

Question 12

Monoclonal Gammapathy of Undetermined Significance (MGUS)

Answer 12

M spike is present in protein electrophoresis, but no symptoms of Plasma Cell Myeloma. Have marrow plasmocytosis, no CRAB.

Question 13

Plasmacytoma (Two types)

Answer 13

Solitary plasmacytoma of bone: local tumor of bone with multiple myeloma like cells (Diag: lesion in BONE, with PCM cells, no other lesions, no CRA, low/ no Mspike). Extraosseous plasmacytoma of bone: PCM-cell mass lesions outside of bone/ BM, usually in respiratory tract (75%); rare, median age 50 y w/ 2/3 favoring male.

Question 14

Categories of AML

Answer 14

Congenital (cytogenetic findings), therapy related AML (t-AML), and AML,NOS

Question 15

Congenital AML

Answer 15

RUNX1-RUNX1T1 t(8;21): RUNX! Encodes alpha subunit of CBF, good prognosis. CBFB-MYH11 inv(16) or t(16;16): see baso eos (immature eosinophils with baso granules), aka myelomonocytic leukemia, good prognosis, CBFB encodes beta subunit of CBF. PML-RARA t(15;17) aka PML: promyelocytes with faggot cells, RARA encodes for retinoic acid receptor alpha, can treat w/ ATRA and need to identify early because risk for DIC. MLL: bad prognosis. RBM15-MKL1 t(1;22): megaloblastic differentiation, often in infants with down syndrome; relatively good prognosis.

Question 16

t-AML

Answer 16

Alkylating agent or radiation: 2-8 year latency period; whole or partial loss of Chr. 5 and 7. Topoisomerase II Inhibitors: 1-2 year latency period, often has rearrangement of MLL gene; poor prognosis.

Question 17

AML, NOS

Answer 17

Molecular abnormalities: FLT3-ITD: poor prognosis, and trumps all. NPM1: good prognosis. CEBPA: good prognosis.

Question 18

B-ALL

Answer 18

80-85% of ALL cases, CD19, CD22, and CD79a, lack CD20 of mature B cells. Three types: BCR-ABL t(9;22) (p190): more common in adults, worst prognosis of all AML (good prog in CML b/c of Gleevac). ETV6-RUNX1 t(12,21): 25% of childhood B-ALL, very favorable prognosis. MLL 11q23: common in neonates/ infants. Poor prognosis.

Question 19

T-ALL

Answer 19

20-25% of ALL cases, CD2, CD3, CD7, CD99, and CD1a are markers. More in teenager males. May present with T-LBL w/ mediatinal mass), has better prognosis in children than adults.

Question 20

Myelodysplastic Syndrome (MDS)- Characteristics and Types

Answer 20

Ineffective hematopoeisis and increased risk of progression to AML. Diagnosis: at least one peristent cytopenia, marrow findings with ring sideroblasts,, bilobed PMN, hypolobated small megakaryocytes. Two types: Primary/ Idiopathic (>50 y, insidious onset, w/ monosomy or delq Chr 5 and 7, trisomy 8) and Secondary/ Therapy-related (chemo drugs, B12/folic acid deficiency, virus, toxin, heavy metals, also related to t-AML with Chr 5 and 7 partial or whole deletion).

Question 21

Low Grade MDS

Answer 21

Myeloblasts are less than 5% in BM. 1) RC-UD (good prog. Can specify further lineage, i.e. Refratory Neutropenia). 2) RC-MD (dysplasia in 2+ lineages w/ worst prognosis). 3) MDS with deletion 5q (associated with anemia, increased platelets, and marrow with distinctive megakaryocytes with small, round non-lobated nuclei).

Question 22

High Grade MDS

Answer 22

Myeloblasts >5% of marrow cells. 1) Refractory Anemia with Excess Blasts (RAEB-1): 5-9% of blasts in marrow, median survival of 16 mo, with 25% progressing to AML. 2) Refractory Anemia Excess Blasts 2 (RAEB-2): 10-19% of blasts in marrow, median survival of 9 months, 33% transform to AML.

Question 23

Myeloproliferative Neoplasms (Characteristics and Types)

Answer 23

Increase in one or more cell types (NO dysplasia), causes hypercellular marrow. Splenomegaly and/or hepatomegaly (sequestration and extramed. Hematopoiesis), can escalate to excessive marrow fibrosis leading to BM failure; can transform to acute leukemia or MDS). Types: CML, PV, PMF, and ET.

Question 24

Chronic Myelogenous Leukemia (CML, a type of MPN)

Answer 24

Initial Phase: chronic; neutrophilia, BM hypercellularity, small megakaryocytes, no dysplasia. Blast Phase: transform to acute leukemia (AML or ALL) (>20% blast in marrow). BCR-ABL t(9;22) phil chr (p210) Tx w/ Imatinib, and dasatinib (2nd gen) PTKIs.

Question 25

Polycythemia Vera (PV, a type of MPN)

Answer 25

Erythrocytosis; trilineage hyperplasia in marrow with clusters of large megakaryocytes. Nearly all have JAK2 mutations; most have V617F point mutation. Polycythemic Stage (increase in cell counts) and spent phase (marrow fibrosis and cell count decreases). Predilection for thromboisi (esp. mesenteric, portal, or splenic vein), treat with phlebotomy to reduce clotting.

Question 26

Primary Myelofibrosis (PMF, a type of MPN)

Answer 26

Proliferation of granulocytic/ megakaryocytic lineages, marrow fibrosis. JAK2 mutations. Pre-fibrotic stage: BM hypercellularity w/ large mega to Fibrotic Stage: reticulin fibrosis of marrow, hypercellularity, dadrocytes, and extramed. hematopoiesis in spleen). Usu not diagnosed until fibrotic stage,median survival ~5 years; AML transformation not likely.

Question 27

Essential Thrombocytopenia (ET, a type of MPN)

Answer 27

Usu asymptomatic, diagnosed from high platelet count; can have TIAs, digital ischemia w/ paraesthesia,thrombosis, NO splenomeg. Thrombocytosis, no granulocytic hyperplasia (normocellular marrow), large/bizarre mega, JAK2 mutations in 50% of patients, indolent disease, rarely progress.