Morphology Review - ISH Slides - 제 2 차 혈액학 종합학술대회 발표 2000 년 5 월 25 일 -5 월 26 일 COEX 한림의대 조 현 찬

Clonal Bone Marrow Disorders Metastatic Cancers Lymphoma

FAB Classification n Standard morphologic classification system n Features considered ä Morphology : Cell size, Amount of cytoplasm Nuclear size and shape, Cytoplasmic membrane Cytoplasmic basophilia, Cytoplasmic vacuolations, Other features ä Cytochemistry ä Immunophenotype ä cytogenetic & molecular genetic features ä Other features

M3 M5 M7 M6M1 M2 M0 M4

WHO Classification of Hematologic Malignancies n Myeloid Neoplasm n Lymphoid Neoplasm n Mast Cell Disorders n Histiocytic Neoplasm Diagnistic criteria ä Morphology ä Immunophenotype ä Genetic features ä Clinical syndromes

n AMLs with recurrent cytogenetic translocations AML with t(8;21), AML1/ETO Acute promyelocytic leukemia with t(15;17) AML with abnormal BM eosinophils with inv(16) AML with 11q23 (MLL) abnormalities n AML with multilineage dysplasia n AML & MDS, therapy-related n AML not otherwise categorized AML minimally differentiated AML without maturation AML with maturation Acute myelomonocytic leukemia Acute monocytic leukemia Acute erythroid leukemia Acute megakaryocytic leukemia Acute basophilic leukemia Acute panmyelosis with myelofibrosis AML, WHO Classification

(# 01) 69-year-old male Bone marrow film Poorly or minimally differentiated AML (AML-M0)

(#02) 5-year-old male, BM Acute myeloid leukemia (AML-M5a)

(#03) 67-year-old woman presented with pancytopenia Acute megakaryoblastic leukemia

(#13) 9-year-old male with pancytopenia, BM Metastatic rhabdomyosarcoma

n Morphology : The tumor cells vary in size; many have irregular cytoplasmic pseudopods. Occasional cells have cytoplasmic vacuoles. n Immunophenotype : CD41 (GpIIb/IIIa) (+) Tentative diagnosis : acute megakaryocytic leukemia was established. n Ultrastructural exam : Rhabdomyosarcoma

(#05) Newborn with Down syndrome Transient abnormal myelopoiesis(TAM) in Down syndrome

n PB ; WBC 88 x 10 9 /L, Hb 14.2 g/dl and platelets 12 x 10 9 /l. Blast 50-60% n No phenotyping or chromosome studies. n WBC count gradually returned to normal over 10 weeks. There has been no recurrence and the child is well at nine years of age. n The blasts may express megakaryocytic and/or erythroid markers; promegakaryocytes and micromegakaryocytes may be numerous. n The CBC findings are not helpful in distinguishing the transient disorder from those processes which persist.

Refractory anemia (RA) RA with ring sideroblasts (RARS) RA with excess of blasts (RAEB) RAEB in transformation (RAEB/T) CMML Other Subtypes MDS with myelofibrosis Hypoplastic MDS Pure sideroblastic anemia MDS, FAB Classification

MDS, WHO Classification n Refractory anemia with ringed sideroblasts without ringed sideroblasts n Refractory cytopenia(MDS) with multilineage dysplasia n Refractory anemia with excess blasts n 5q- syndrome n MDS, unclassifiable

(#04) 37-year-old female house painter with a history of bruising RAEB-T associated with an isolated 5q-

Congenital dyserythropoietic anemia, type III (#07) 27-year-old male, Hb 9.7 g/dl, BM

Chronic Myeloproliferative Disorders n Chronic myeloid leukemia Atypical CML Juvenile CML Chronic neutrophilic leukemia n Polycythemia vera n Myeloid metaplasia with myelofibrosis n Essential thrombocythemia

MPD, WHO Classification n Chronic myelogenous leukemia, Ph(+) (t(9;22) (q34;q11), BCR/ABL) n Chronic neutrophilic leukemia n Chronic eosinophilic leukemia/hypereosinophilic syndrome n Chronic idiopathic myelofibrosis n Polycythemia vera n Essential thrombocythemia n Myeloproliferative disease, unclassifiable Myelodysplastic/myeloproliferative disorders (MD/MPD) CMML, aCML, JMML

(#08) Ph(+) chronic myeloid leukemia

(#09) 45-year-old male PB film with Ph(+) CML Mixed lineage (B-lymphoid and myeloid) blast crisis of CML

Lymphoid neoplasm, WHO Classification  B-Cell neoplasm ä Precursor B-cell : ALL ä Mature(peripheral) B-cell : CLL, HCL, PCM, MCL, Burkitt’s Lymphoma  T-cell and NK-cell neoplasm ä Precursor T-cell ä Mature(peripheral) T-cell  Hodgkin’s lymphoma

(#10) 47-year-old male with an abdominal mass, PB Richter's transformation of B-cell CLL

(#11) 47-year-old male with easy bruisability and lethargy, BM Plasma cell leukemia

70/F, Sternal pain for 6 years (SNUH) CBC : k Total protein/Albumin : 6.2/3.3, PEP : no M-spike Plasma cell myeloma with heavy granules

Plasma cell leukemia, PBMultiple myeloma, BM

(#12) 66-year-old male, PB Mantle-cell lymphoma in leukemic phase

n Morphology : medium size lymphoid population having a nucleus with dense but not clumped chromatin, occasional nuclear clefts and a small nucleolus. n Immunophenotype : clonal B-cell population with strong expression of SIg and membrane CD22(+), CD5(+), CD23(-) n Cytogenetic analysis : t(11:14)(q13;q32) n Spleen histology : diffuse involvement by medium size lymphocytes with a cleaved nucleus

Hairy cell leukemia Middle-aged patients over 50 Weakness and lethargy Splenomegaly (80% ) Hairy cells : Fine & irregular pseudopods, immature nuclear features BM : often unsuccessful

(#14) 52-year-old male, PB Large-cell lymphoma evolving into leukemia

n Morphology : Large (> 3 times of RBC), reticular chromatin, deeply basophilic cytoplasm and 1-3 nucleoli. n Immunophenotype : Clonal B-cell population kappa+, lambda-, CD19+, FMC7+, and negative with CD5, CD23 & CD2.

(#15) 28-year-old male, BM ALL-L3, Burkitt’s lymphoma/Burkitt cell leukemia

(#16) 38-year-old black Caribbean Peripheral blood Adult T-cell leukemia lymphoma (ATLL).

n Morphology : small to medium size lymphocytes with a highly irregular nucleus with inconspicuous nucleolus and multiple indentation n Immunophenotype : mature T-cell (TdT+, CD1a-, CD2+, CD3+, CD5+, CD7-) with a CD4+, CD8-, CD25+ phenotype. n Antibodies to the human T-cell leukemia/lymphoma virus (HTLV-1) n Molecular analysis : a clonal integration of the proviral HTLV-1 in the cell's DNA

(#17) 2-year-old boy with mediastinal mass Increased hematogones 50-55% lymphoid cells with a very high N/C ratio; condensed chromatin, indistinct nucleoli, Some cleft nuclei n CBC : Within normal limits n Cell markers : non-B, non-T phenotype n Mediastinal mass : plasma cell granuloma. n Uneventful recovery from surgery. No follow-up BM study