Section 10 -

Tables Cheryl M. Coffin, M.D. David M. Parham, M.D.

Table 1. Key Pathologic Features of Pediatric Round Cell (SRC) Tumors Diagnosis Histopathology Immunophenotype Ewing sarcoma/PNET SRCs in sheets with round nuclei, fine chromatin, scanty cytoplasm. Variable rosettes, prominent nucleoli, spindle cells, necrosis. Vimentin, CD99, synaptophysin, Fli-1, NSE, cytokeratin. DSRCT SRCs in nests with prominent stromal desmoplasia, central necrosis, variable cystic degeneration and epithelial differentiation. Polyphenotypic: cytokeratins, epithelial membrane antigen, vimentin, desmin, NSE, WT-1 (C-terminus). Clear cell sarcoma Uniform nested or fascicular pattern, polygonal or spindle cells, vesicular nucleus, prominent nucleolus, scattered giant cells, thin fibrous septa. HMB45, S100 protein, and other melanoma antigens. Variable NSE, synaptophysin, CD57, cytokeratin, actin. Extraskeletal myxoid chondrosarcoma Multinodular architecture with fibrous septa, abundant myxoid matrix, and cords or clusters of SRCs with even chromatin, inconspicuous nucleoli. Variants: epithelioid, rhabdoid, and spindle cells. Vimentin. Variable and focal S100 protein, cytokeratin, epithelial membrane antigen. Alveolar rhabdomyosarcoma Alveolar or solid architecture. SRCs with variable rhabdomyoblastic differentiation, giant rhabdomyoblastic cells, clear cells. Myogenin, Myo-D1, desmin, muscle-specific actin. Variable cytokeratin, CD99, CD20, NSE, S100 protein, smooth muscle actin. Malignant rhabdoid tumor Polygonal or SRCs in sheets or trabeculae with large, vesicular nuclei, prominent central nucleoli, abundant eccentric cytoplasm, frequent mitoses. Globoid, hyaline, eosinophilic cytoplasmic inclusion. Polyphenotypic: vimentin cytokeratin, epithelial membrane antigen. Variable CD99, synaptophysin, NSE, S100 protein, muscle-specific actin. Neuroblastoma SRCs in sheets or nests with variable mitoses, karyorrhexis, neuropil, rosettes, fibrovascular septa, and schwannian stroma. NSE, synaptophysin, chromogranin, neurofilament, PGP9.5. Lymphoblastic lymphoma SRCs in discohesive sheets, scant cytoplasm, nuclear convolutions, fine chromatin TdT, CD43, CD79a, CD10, CD99, Fli-1. May be negative for CD45, CD3, CD20, vimentin. May be positive for cytokeratin. Table 2. Cytogenetic and Molecular Genetic Abnormalities in Non-Hematolymphoid Round Cell Tumors Tumor Alteration Genes Involved Frequency EWS/PNET t(11;22)(q24;q12) EWS-FLI-1 85% t(21;22)(q22:q12) EWS-ERG 10% t(7;22)(p22;q11.2) EWS-ETV1 Rare t(17;22)(q12;q12) EWS-E1AF Rare t(2;22)(q33;q12) EWS-FEV Rare t(X;22)(q27;q11) EWS-? Rare Desmoplastic small round cell tumor t(11;22)(p13;q12) EWS-WT1 >99% Myxoid chondrosarcoma t(9;22)(q22;q12) EWS-CHN 75% t(9;17)(q22;q11) TAF2N-CHN 25% Clear cell sarcoma (melanoma of soft parts) t(12;22)(q13;q12) EWS-ATF1 ? Alveolar rhabdomyosarcoma t(2;13)(q35;q14) PAX3-FKHR 75% t(1;13)(p36;q14) PAX7-FKHR 10% Malignant rhabdoid tumor Deletion of 22q HSNF5 ? Myxoid liposarcoma, round cell type t(12;22)(q13;q12) EWS/CHOP >90% Neuroblastoma N-myc amplification N-myc ? Table 3. Pathologic Features of Pediatric Spindle Cell Sarcomas Diagnosis Histopathology Immunophenotype Embryonal rhabdomyosarcoma Primitive spindled, stellate, round, and polygonal cells in variably myxoid background. Variable rhabdomyoblasts, strap cells, multinucleated cells, and myotube forms. Myogenin, Myo-D1, muscle-specific actin, desmin. Variable smooth muscle actin, cytokeratin, NSE, S100 protein, neurofilaments, CD20, immunoglobulins. Synovial sarcoma Biphasic spindle and epithelial or monophasic, patterns. Epithelial component glandular, papillary, squamoid, clusters, or nests. Indistinct cell borders. Hemangiopericytomatous vessels. Wiry collagen. Variable mast cells, rhabdoid cells, myxoid change, SRCs. Vimentin, Cytokeratins, including 7 and 19, epithelial membrane antigen, bcl-2. Variable S100 protein, CD99, calponin, actin. Dermato-fibrosarcoma protuberans Spindle cells in short interfacing fascicles with a storiform pattern. Honeycomb infiltrative pattern. CD34, vimentin Infantile fibrosarcoma Fascicles of spindle cells, herringbone pattern, zonal necrosis, hemangiopericytomatous vessels. Variable round cell, polygonal cell, and myxoid foci. Vimentin Inflammatory myofibroblastic tumor Fibroblasts, myofibroblasts, and primitive ganglion-like mesenchymal cells with lymphoplasmacytic and eosinophilic inflammation. Myxoid, cellular, and collagenized patterns. Vimentin. Variable smooth muscle actin, muscle specific actin, desmin, ALK-1 Malignant peripheral nerve sheath tumor Spindle cells in sheets or fascicles, variable cellularity, mitoses, pleomorphism, necrosis. Divergent differentiation with mesenchymal and epithelial features. Variable S100 protein, Leu-7, neurofilaments, GFAP. Table 4. Cytogenetic and Molecular Genetic abnormalities in Spindle Cell Tumors Tumor Cytogenetic Abnormality Molecular Abnormality Desmoid tumor Trisomies 8 and 20 APC mutation Schwannoma Deletion 5q Deletion 22q NF2 inactivation Dermatofibrosarcoma protuberans and giant cell fibroblastoma Ring chromosomes 17 and 22 t(17;22)(q21;q13) COL1A1-PDGFB fusion Infantile fibrosarcoma t(12;15)(p13;q25) Trisomies 8, 11, 17, 20 ETV6-NTRK3 fusion Inflammatory myofibroblastic tumor 2p23 rearrangement TPM3-ALK TPM4-ALK Clathrin-ALK Other-ALK Gastrointestinal stromal tumor Monosomies 14 and 22 Deletion of 1p Kit mutation Synovial sarcoma t(X;18)(p11;q11) SYT-SSX1 fusion SYT-SSX2 fusion SYT-SSX4 fusion Leiomyosarcoma Deletion of 1p - Malignant peripheral nerve sheath tumor Complex -