Small, Blue, Round Cell Tumors (Sbrcts) Pose a Unique

Home , Rhabdomyosarcoma, Synaptophysin

SMALL, BLUE, ROUND CELL TUMORS SMALL, BLUE, ROUND CELL TUMORS S mall, blue, round cell tumors (SBRCTs) pose a unique challenge to the surgical pathologist, given the considerable histologic overlap of these tumors. The disparity in treatment modalities, and hence, clinical outcome in the different subsets of SBRCTs makes the correct diagnosis crucial. Fortunately, there are IHC studies that can be performed to distinguish among the different SBRCTs. Also, because several SBRCTs are characterized not by a particular cell type, but rather a unique chromosomal translocation, fluorescence in situ hybridization (FISH) plays an increasingly important role in the identification of these tumors. H&E Immunohistochemical approaches In the past, markers such as CD99 have been employed, but this is nonspecific and no longer plays a role in this clinical setting. More recently described IHC markers H&E Synaptophysin have proven much more useful in the diagnosis of SBRCTs. Myogenin (and MyoD1), H&E stained section of neuroblastoma, with corresponding section immunostained with antibodies to synaptophysin. transcriptional regulatory proteins involved in skeletal muscle differentiation with an early expression pattern, have become indispensible in the diagnosis of rhabdomyosarcoma, owing to their high sensitivity and specificity. Absence or decreased nuclear expression of INI-1 protein confirms deletion or mutation of the hSNF5/INI1 Some common IHC markers must be applied with caution, owing to their ‘infidelity’ in this context. For example, desmin, long gene on chromosome 22, and solidifies the diagnosis of atypical teratoid/rhabdoid considered a marker of rhabdomyosarcoma, is also expressed in a subset of desmoplastic small round cell tumors (DSRCT). Both tumors of the brain. CRX is a retinal photoreceptor cell-specific transcription factor that lymphoblastic lymphoma and PNET/Ewing sarcoma express FLI-1 in ~90% of cases and synaptophysin can be expressed in both Desmin can identify retinoblastoma, and NKX2.2 is a highly specific transcription factor marker neuroblastoma as well as rhabdomyosarcoma. All this underscores the importance of a carefully considered panel of IHC studies to for PNET/Ewing sarcoma. assist in the diagnosis of SBRCTs. IHC can assist in identifying the presence of chromosomal translocations in SBRCTs. The t(11; 22)(q24;q12) translocation resulting in fusion of the EWS and FLI-1 genes in PNET/Ewing leads to overexpression of FLI-1 protein. IHC detection of FLI-1 may be a valuable technique for identification of PNET/Ewing sarcoma in cases in which molecular genetic evaluation is not feasible. Desmoplastic small round cell tumors (DSRCTs) show a different translocation involving chromosomes 11 and 22: t(11;22)(p13;q12). This results in a unique chimeric protein transcript corresponding to the resulting fusion gene product. Antibodies to the WT-1gene product (to the carboxy terminus) can detect the unique fusion product resulting from this translocation and can thus be used to identify desmoplastic small round cell tumors by IHC.

Vimentin Rhabdomyosarcoma showing uniform expression of desmin in the cytoplasm and myogenin in the nuclei of the tumor cells.

H&E

Cytokeratin H&E FLI-1 Abdominal mass from 13-year- PNET/Ewing sarcoma with expression of the FLI-1 gene product, a consequence of the t(11;22) translocation old male, showing typical characteristic of this tumor. SBRCT features. The tumor shows positive immunostaining with antibodies to cytokeratin, vimentin, and desmin, a pattern unique to desmoplastic small round cell tumor. Desmin Myogenin