Desmoplastic Small Round Cell Tumor

Not clinically relevant

DSRCT is characterized by a recurrent chromosomal translocation t(11;22)(p13;q12), resulting in fusion of the EWSR1 gene on 22q12.2 and the Wilms tumor gene, WT1, on 11p13. The most common chimeric transcript is composed of an in-frame fusion of the first seven exons of EWSR1, encoding the potential transcription-modulating domain, and exons 8–10 of WT1, encoding the last three zinc fingers of the DNA-binding domain. Rare variants including additional exons of EWSR1 can also occur. Detection of the EWSR1-WT1 gene fusion can be especially useful in cases with unusual clinical or histological features. Studies of the EWSR1-WT1 aberrant transcription factor have revealed deregulation of several target genes and activation of neural gene expression and partial neural differentiation via ASCL1.

The typical gross appearance consists of multiple tumor nodules studding the peritoneal surface. Often there is a dominant tumor mass accompanied by satellite smaller nodules. The cut surface is firm and greyish-white, with foci of hemorrhage and necrosis.

DSRCT is characterized by sharply outlined nests of small neoplastic round (more rarely epithelioid or even spindled) cells, usually surrounded by a prominent desmoplastic stroma. The nests can vary considerably in size, ranging from minute clusters to large irregular confluent sheets. Central necrosis is common and cystic degeneration can also be seen. Some tumors focally exhibit epithelial features, with glands or a rosette pattern. The tumor cells are typically uniform, with small hyperchromatic nuclei, scant cytoplasm, and indistinct cytoplasmic borders. In a subset of cases, tumor cells can show cytoplasmic eosinophilic rhabdoid inclusions. Some tumors have larger cells with greater pleomorphism. The chromatin is typically dispersed, with inconspicuous nucleoli. Mitoses are frequent and individual cell necrosis is common. The desmoplastic stroma is composed of fibroblasts or myofibroblasts embedded in a loose extracellular matrix or collagen. Prominent stromal vascularity is also present, ranging from complex capillary tufts to larger vessels with eccentric thickened walls.

Immunohistochemically, DSRCT shows a distinctive and complex pattern of multiphenotypic differentiation, expressing proteins associated with epithelial, muscular, and neural differentiation. Most cases are immunoreactive for cytokeratins, EMA, and desmin. A distinctive dot-like cytoplasmic localization is seen with desmin and occasionally with other intermediate filaments. Myogenin and MYOD1 are consistently negative. Nuclear expression of WT1 (using antibodies to the C-terminus but not the N-terminus) is usually seen.

Ultrastructurally, most tumor cells have a primitive/undifferentiated appearance, with minimal cytoplasm and scant organelles. A notable feature is the presence of paranuclear aggregates and whorls of intermediate filaments. Rare dense core granules can be also seen occasionally. Few cells are connected by cell junction complexes, including well-formed desmosomes.

Cytological specimens are cellular and show cells with a high N:C ratio, having granular chromatin, nuclear molding, and variable nuclear membranes. Pseudorosettes are common.

The overall survival remains poor, despite multimodality therapy. The 5-year overall survival rate is about 10–15% at most.

The presence of EWSR1 and WT1 gene rearrangements or alternatively of the EWSR1-WT1 chimeric transcript may represent a useful diagnostic tool.

Essential: nests of small round cells in a desmoplastic stroma; immunopositivity for cytokeratin, desmin (dot-like pattern), and WT1 (antibody to C-terminus).

Desirable (but often not required): molecular studies to demonstrate EWSR1 gene rearrangement or EWSR1-WT1 fusion transcript.