© 2013 PhenoPath Laboratories, PLLC. All rights reserved.18

SMALL, BLUE, ROUND CELL TUMORS

Small, 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.

Immunohistochemical approachesIn 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

have proven much more useful in the diagnosis of SBRCTs. Myogenin (and MyoD1),

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

gene on chromosome 22, and solidifies the diagnosis of atypical teratoid/rhabdoid

tumors of the brain. CRX is a retinal photoreceptor cell-specific transcription factor that

can identify retinoblastoma, and NKX2.2 is a highly specific transcription factor marker

for PNET/Ewing sarcoma.

Abdominal mass from 13-year-old male, showing typical SBRCT features. The tumor shows positive immunostaining with antibodies to cytokeratin, vimentin, and desmin, a pattern unique to desmoplastic small round cell tumor.

Cytokeratin

Vimentin

Desmin

H&E

Myogenin

H&E

Desmin

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

© 2013 PhenoPath Laboratories, PLLC. All rights reserved. 19

SMALL, BLUE, ROUND CELL TUMORS

H&E FLI-1PNET/Ewing sarcoma with expression of the FLI-1 gene product, a consequence of the t(11;22) translocation characteristic of this tumor.

Some common IHC markers must be applied with caution, owing to their ‘infidelity’ in this context. For example, desmin, long

considered a marker of rhabdomyosarcoma, is also expressed in a subset of desmoplastic small round cell tumors (DSRCT). Both

lymphoblastic lymphoma and PNET/Ewing sarcoma express FLI-1 in ~90% of cases and synaptophysin can be expressed in both

neuroblastoma as well as rhabdomyosarcoma. All this underscores the importance of a carefully considered panel of IHC studies to

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-1 gene

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.

H&E stained section of neuroblastoma, with corresponding section immunostained with antibodies to synaptophysin.

H&E Synaptophysin