Leukemias

Question 1

FAB M5b

Answer 1

Well differentiated monocytic majority cells are promonocytes

Question 2

FAB M5a

Answer 2

poorly differentiated monoblastic leukemia >80% of monocytes are blasts

Question 3

General Characteristics of Leukemias

Answer 3

WBC Count = variable Blasts: agranular w/ nuclear-cytoplasmic asynchrony, Monocytosis, neutropenia, absolute basophilia RBC Count: Normocytic/normochromic anemia w/ HJ bodies, pappenheimer bodies, basophilic stippling PLATELET: thrombocytopenia BONE MARROW: Hypercellular >20% blasts

Question 4

AML-M0

Answer 4

WHO: AML Minimally Differentiated ■ Characteristics – Undifferentiated blasts. Cannot ID by morphology or cytochemical staining. ■ CD markers/Cytochemical staining – CD34+, CD13+, CD33+, no reactions with cytochemical stains ■ Incidence – <5% of AML cases

Question 5

FAB: AML-M4

Answer 5

WHO: Acute myelomonocytic leukemia (AMML) ■ Characteristics – Proliferation of both myeloid AND monocytic cells – PB: ≥5 x109/L monocytic cells – BM: myeloid & monocytic cells are ≥20% ■ CD marker/Cytochemical Staining – CD13+, CD33+, CD11b+, CD14+, CD34= – MPO/SBB/SE (+), NSE(+), NSE w/ NaFl (=) ■ Other Lab Tests – Serum and urinary lysozymes (muramidase) are 3x normal

Question 6

FAB: AML-M7

Answer 6

WHO: Acute Megakaryoblastic Leukemia ■ Characteristics – ≥50% of the leukemic blasts are megakaryocytic – PB: micromegakaryocytes, megakaryocyte fragments, pancytopenia – BM: Dry tap due to fibrosis, blasts with cytoplasmic blebs ■ CD Markers/Cytochemical Staining – CD41+, CD61+, platelet peroxidase(+

Question 7

FAB: AML-M5

Answer 7

WHO: Acute Monoblastic & Monocytic Leukemia ■ Characteristics – PB: >5 x109/L monocytic cells, usually monoblasts present – BM: ≥ 80% cells are monocytic, <20% of all cells are granulocytes ■ CD Markers/Cytochemical Staining – CD14+, CD11b+, CD33+, CD13+, CD34= – MPO & SBB (=), NSE(+), NSE+NaFl (=) ■ Incidence – 10-15% of AML cases – Usually seen in children or young adults ■ Symptoms: weakness, bleeding, erythematous rash ■ Other Lab Tests – Serum and urine lysozyme (muramidase) moderately elevated

Question 8

AML-M2

Answer 8

WHO: AML w/ Maturation t(8;21)(q22;q22);RUNX1-RUNX11T1 Characteristics – PB: Fewer blasts than M1 (+/- auer Rods), promyelocytes, myelocytes, metamylocytes ■ >10% granulocytes differentiated past blast stage ■ Dysmyelopoiesis with nuclear/cytoplasmic asynchrony, hyper/hypogranulation, hyper/hyp nuclear segmentation ■ <20% monocytes and their precursors – BM: ■ 20-89% of nonerythroid cells are myeloblasts ■ CD Markers/Cytochemical Staining – CD34+, CD33+, CD13+, MPO/SBB/SE(+), NSE(=) ■ Incidence – 10% of AML cases

Question 9

Non Hodgkin Lymphoma

Answer 9

Follicular Lymphoma – Cleft Lymphs (Butt Cells) BCL-2 mutation Mantle Cell Lymphoma – multiple tissues, BCL-1 mutation MALT – Chronic inflamation, H. pylori

Question 10

HCL

Answer 10

Hairy Cell Leukemia Incidence – Uncommon B-cell neoplasm that presents in middle age (>50) – (7:1 male to female ratio) ■ Clinical Findings – Massive Splenomegaly w/o lymphadenopathy PB= Pancytopenia due to extensive BM infiltration, HAIRY CELL (LYMPHS) BM=Fibrotic dry tap, “Fried Egg Cells” CD MARKERS CD19, CD20, CD22, TRAP+

Question 11

AML with inv(16)(p13q22) or t(16;16)(p13;q22), CBF β-MYH1

Answer 11

Immature monocytic & granulocyte cells in PB, abnormal eosinophils with immature basophilic granules in cytoplasm seen in BM – CBFβ-MYH1 fusion gene protein binds to RUNX1 and represses its transcription factor function

Question 12

FAB: AML-M6

Answer 12

WHO: Acute Erythroid Leukemia Characteristics – Predominance of erythroid cells – PB: anemia, anisocytosis, poikilocytosis, many dysplastic nRBCs – BM: ≥50% erythroid cells, ≥20% myeloblasts of nonerythroid cells, bizarre morphological features (nuclear budding, multi-nucleated cells,etc) ■ Pure erythroid leukemia = ≥80% erythroid precursors in BM (very rare) ■ CD Markers/Cytochemical Staining – CD17+, PAS(+) (PAS is normally negative in normal erythroblasts)

Question 13

PLL

Answer 13

Prolymphocytic Leukemia Rare, aggressive leukemia does not respond to treatment severe splenomegaly extreme lymphocytosis (>300x10 9) prolymphocytes predominate (>55%) CD MARKERS CD5+/=. CD19+,CD20++,CD23=

Question 14

Primary Cutaneous T-Cell Lymphoma

Answer 14

Like Sezary syndrome, but w/ MYCOSIS FUNGOIDES

Question 15

FAB: ALL-L3

Answer 15

■ Incidence – Rarest: occurs in adults and children ■ Blast Characteristics – Burkitt lymphoma-like lymphoblasts – Large, homogeneous cell size – Fine homogeneous chromatin pattern – Nuclear shape is oval to round prominent nucleoli – Abundant, intensely basophilic cytoplasm with prominent vacuoles ■ Cytogenetics – Diagnostic cytogenetic abnormality: t(8;14)(q24:q32) – cMYC gene rearrangement ■ All of the ALL-L3 are B-cell ALLs

Question 16

CD Markers of CLL

Answer 16

CD5, CD19, CD22, CD23, CD10(CALLA) =

Question 17

ALL lab tests

Answer 17

WBC= variable (can be >100x10^9) - absolute neutropenia - circulating lymphoblasts RBC=N/N anemia, NO anisocytosis, poiks, nrbcs PLT=Thrombocytopenia Hypercellular BM w/ >25% blasts

Question 18

CLL

Answer 18

Chronic Lymphocytic Leukemia ■ Clonal accumulation of neoplastic, mature looking, non-functional lymphocytes – Majority of B-CLL have high amounts of BCL2 protein but no chromo5somal translocation ■ Incidence – >50 yrs (average 70 yrs) – Most common leukemia in older adults ■ Clinical Findings – Asymptomatic PB=N/N anemia, neutropenia, thrombocytopenia, CLL LYMPHS! BM= absolute lymphocytosis,

Question 19

AML with t(9;11)(p22;q23); MLLt3-MLL

Answer 19

– Monoblasts and promonocytes – more commonly seen in children – MLL protein helps regulate DNA transcription

Question 20

ALL physiology

Answer 20

Acute Lymphocytic Leukemia Multiple somatic mutations primarily in young children and >60 yrs abrupt or insidious onset nonspecific signs B cell is more common causes blood viscosity increase T cell more aggressive, lymphadenopathy and hepatosplenomegaly

Question 21

Cytochemical stains for ALL’s

Answer 21

– MPO/SBB (=), NSE (= or w+) – PAS (periodic acid-Schiff) (+) with coarse granular positivity in lymphoblasts – Tdt (Terminal deoxynucleotidyl transferase)

Question 22

T CELL precursor

Answer 22

TdT (only immature lymphs), CD2, CD3,CD4,CD5,CD7

Question 23

Burkitt Lymphoma

Answer 23

Same as FAB ALL-3 EBV DNA present + HIV infection Biopsy= starry sky appearance in BM

Question 24

APL with t(15;17)(q22;a12), PML/RAR α and variants

Answer 24

– Formerly FAB AML-M3

Question 25

Adult T Cell Leukemia

Answer 25

Caused by HTLV-1 Virus Common in Japan, Caribbean abnormal "Cloverleaf" lymphs CD Markers CD2, CD3, CD5, CD7=

Question 26

FAB: ALL-L1

Answer 26

Incidence – Most common in children – Best prognosis ■ Blast Characteristics – Small, homogeneous cell size – Fine homogeneous chromatin pattern – Nuclear shape regular (occasional clefts) with faint nucleoli – Scant slightly basophilic cytoplasm

Question 27

AML with t(8;21)(q22;q22.3), RUNX1/RUNX1T1

Answer 27

– Formerly FAB AML-M2 – Large myeloblasts with lots of cytoplasm, other stages of myeloid maturation present – Fusion gene protein blocks normal function of RUNX1 and results in blocked cellular differentiation and increased proliferaiton

Question 28

FAB: AML-M3

Answer 28

WHO: Acute Promyelocytic Leukemia, AML with t(15:17)(q22;q12), PML/RARα & variants Characteristics – PB: Abnormal promyelocytes with heavy granulation predominate, also see other maturation stages of myeloid cells. – BM: \>30% of nonerythroid cells are Promyelocytes ■ Dysmyelopoiesis with nuclear: cytoplasmic asynchrony, hypogranularity, PPH cells ■ CD Marker/Cytochemical Staining – CD13+, CD33+, MPO/SBB/SE (+), NSE(=) ■ Treatment: All-transretinoic acid (ATRA)

Question 29

B Cell ALL CD markers

Answer 29

CD19, CD22, CD10 (CALLA - in early cells)

Question 30

AML-M1

Answer 30

AML Without maturation ■ Characteristics – PB: predominantly blasts seen (often with Auer rods) ■ \<10% granulocytes mature past the blasts stage ■ Leukemic hiatus: lack of intermediate maturation stages of cells – BM: \>90% non-erythroid cells are myeloblasts, Auer rods (50% of the time), Dysmyelopoiesis ■ CD Markers/Cytochemical stains – CD 34+, CD33+, CD13+, MPO (+), SBB (+), SE(+), NSE (=) ■ Incidence – 5-10% of AML cases

Question 31

Multiple Myeloma

Answer 31

Plasma Cell Neoplasm Clinical: Lytic bone lesions, fractures, bone pain PB, N/N Anemia, Rouleaux, blue background BM: abnormally high plasma cells Increased ESR M Spike in urine Renal impairment ----\> Bence Jones protein

Question 32

Sezary Syndrome

Answer 32

CD4 T cell neoplasm erythroderma sezary cells= lymphs w/ irregular nuclear outline \>1.0x10 9 sezary cells for diagnosis CD2, CD3, CD4, CD7=

Question 33

Hodgkin Lympoma

Answer 33

Reed sternberg Cell (Owl eyes) – Large tumor cells that do not resemble a normal cell counterpart along with many reactive cells – Biopsy: shows reactive lymphs, plasma cells, histiocytes, and eosinophils accompanied by a few tumor cells

Question 34

FAB: ALL-L2

Answer 34

■ Incidence – Most common in adults ■ Blast Characteristics – Large, heterogeneous cell size ■ Can be difficult to differentiate from AML M0 and M1 – Heterogeneous chromatin pattern – Nuclear shape is irregular with clefting and indentations, plus prominent nucleoli – Variable amount and basophilia of cytoplasm