Tumores de células pequeñas, redondas y azules: diagnóstico diferencial cuando el tiempo apremia
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1 Tumores de células pequeñas, redondas y azules: diagnóstico diferencial cuando el tiempo apremia Sílvia Bagué Servei de Patologia Hospital de Sant Pau Barcelona
2 Soft tissue sarcomas Heterogeneous group of rare malignancies Both rarity and heterogeneity affects diagnostic accuracy Most of tissue tumors are classified according to the type of normal mesenchymal cell or tissue that they most closely recapitulate ( differentiation )
3 Approach to diagnosis Clinical data & radiology H-E (morphology) Immunohistochemistry Molecular and cytogenetics
4 Clinical & radiological data: essential!! 1. Age, symptoms, site, size, previous history (cancer, RT ) 2. Associated syndromes or genetic disorders(li Fraumeni, Ollier, AFP, NF-1, RB1 )
5 Role of core biopsy (H&E) Is the lesion benign or malignant? if malignant, is it a sarcoma (mesenchymal)? and what type of sarcoma is it? (histologic type & grading)
6 Cellular morphology & stroma Spindle Pleomorphic Lipomatous Epithelioid Round cell Myxoid
7 Small round & blue cell tumors
8 Small round & blue cell tumors Rhabdomyosarcoma Ewing sarcoma Ewing-like sarcomas Desmoplastic SRCT PD Syn S Myoepithelial tumors Mesenchymal Ch Neuroblastoma Lymphoma Small cell carcinoma Mainly in children & adolescents High-grade by definition Often translocated-sarcomas
9 Incidence Rates per Million Population, Children (0-14), Great Britain Bone and Soft Tissue Sarcomas: [50%] [15%]
10
11 Neuroblastoma Clinical history Newborn, 7 m. Abdominal mass
12 Clinical history Boy, 12 y-o. Intraabdominal masses DSRCT
13 Mesenchymal chondrosarcoma Young adults (15-35 yrs) <10% chondrosarc Bone: maxilla, ribs, pelvis, vertebra 20-30%: soft tissue Biphasic pattern
14 Immunohistochemistry Diferential diagnosis between mesenchymal/non-mesenchymal tumor (carcinoma, melanoma, lymphoma) Standard method for establishing the line of differentiation (vascular, neural, smooth muscle, skeletal muscle, myofibroblastic) Facilitates the differential diagnosis and classification of a spindle and / or round cell neoplasms Detection of underlying molecular alterations Do not provide information about benign or malignant LMS h-caldesmon
15 Immunohistochemistry of SRCT CD99 Desmin Myogenin CK20 LMWK TdT SYN EMA a-rms 15% 95% >90% Ewing sarc 95% 20% 20% 5% PD Syn Sarc 95% 50% 90% DSRCT WT1+ 10% 80% % - 5% 95% Mesenchymal Ch 80% Neuroblastoma % - TCLL 90% <1% 90% - -
16 M1 small cell carcinoma (lung) - Age & clinica data! - > 45 yrs; IMAGING! - CD99 (-) Ker AE1/AE3 TTF1
17 Merkel cell carcinoma (skin) - Age & clinica data! - Elderly; superficial - CD99 (-) CAM 5.2 Ker 20
18 Ewing Sarcoma -3rd most common sarcoma in children % extraskeletal
19 Ewing Sarcoma
20 Immunohistochemical findings CD99 FLI-1 FLI-1 Membranous ~ 100% cases low specificity! Nuclear 71-84% cases Vimentin, synaptophysin, HNK1, CAV1, NSE: focally LMW cytokeratins in up to 30% of ES! Folpe et al. AJSP 2005; 29;
21 Lymphoblastic lymphoma Clinical history 2 year-old, female. Proximal left humerus CD99 TdT
22 Clinical history 17 y-o, male Thigh mass + inguinal lymph node
23 Clinical history 17 y-o, male Thigh mass + inguinal lymph node FNA rhabdoid cells rhabdomyosarcoma??
24 Rhabdomyosarcoma (skeletal muscle differentiation) Desmin Myogenin
25 DSRCT: IHC & Genetics Malignant small round cell tumor associated with prominent stromal desmoplasia and polyphenotypic differentiation with a consistent translocation t(11;22)(p13;q12) and EWSR1-WT1 gene fusion. WT1 CAM 5.2 Vim Desmin
26 Molecular and cytogenetics
27 Ewing s sarcoma: Genetics 95% t(11;22)(q24;q12) EWSR1-FLI1 fusion gene < 5% t(21;22)(q22;q12) EWSR1-ERG fusion gene Sarcomas thouhgt to be Ewing but EWSR1 negative: Ewing-like sarcomas t(20;22)(q13;q12) t (4;19)(q35;q13) EWSR1-NFATC2 CIC-DUX4 BCOR-CCNB3
28 Clinical history 46 y-o female. Right thigh mass + pulmonary mets Small round cell tumor with hemangiopericytoid pattern FISH: SS18 gene rearrangement
29 Clinical history 17 y-o, male Thigh mass + inguinal lymph node FNA Genetics bp PAX FKHR + - Desm PGK + - PAX FKHR + - Myogenin 50% a-rms: t(2;13)(q35;q14) PAX3-FOXO1 25% a-rms: t(1;13)(p36;q14) PAX7-FOXO1 25% fusion-neg cases biologically similar to e-rms PGK FOXO1 rearrangement by FISH
30 Classification of Rhabdomyosarcoma Superior prognosis - Botryoid rhabdomyosarcoma - Spindle cell rhabdomyosarcoma Intermediate prognosis - Embryonal rhabdomyosarcoma Poor prognosis - Alveolar rhabdomyosarcoma - Anaplastic rhabdomyosarcoma Required for patient management and tumor prognostication!
31 Desmoplastic small round cell tumor Clinical history Boy, 12 y-o. Intraabdominal masses
32 DSRCT: IHC & Genetics Malignant small round cell tumor associated with prominent stromal desmoplasia and polyphenotypic differentiation with a consistent translocation t(11;22)(p13;q12) and EWSR1-WT1 gene fusion. FISH: EWSR1 rearrangement
33 Soft tissue tumors: Molecular pathology STT other than Ewing carrying EWS translocation Ewing sarcoma t(11;22)(q24;q12) EWSR1-FLI1 DSRCT t(11;22)(p13;q12) EWSR1-WT1 AFH CCS t(2;22)(q33;q12) t(12;22)(q13;q12) t(12;22)(q13;q12) t(2;22)(q33;q12) EWSR1-CREB1 EWSR1-ATF1 EWSR1-ATF1 EWSR1-CREB1 EMC t(9;22)(q22;q12) EWSR1-NR4A3 Myoepithelioma t(19;22)(q13;q12) EWSR1-POU5F1 Mixoid liposarc t(12;16)(q13;p11) t(12;22)(q13;q12) FUS-DDIT3 EWSR1-DDIT3
34 Clinical data & imaging CNB / FNA Specimen work up FNA ME sample CNB H&E Frozen (biobanking) IHC Molecular pathology Final diagnosis
35 In summary: Accurate diagnosis provides appropriate clinical decision making Histotype: predictor of outcome Conventional morphology still powerful tool.although overlapping histologic features create diagnostic challenges Integration with immunohistochemistry is a diagnostic standard Molecular genetics helpful in increasing situations - only in context with morphology! - same genetic alterations in unrelated entities
36 Muchas gracias por su atención
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