A 13-year-old boy presented at an outside hospital with an abdominal mass. Prior to this, he had experienced some indigestion and lack of weight gain. A computerized tomography scan was performed that showed multiple large masses involving the lesser curvature of the stomach, mesentery of the transverse colon, and pelvis. The latter tumors were impinging on the liver. Smaller nodules on the diaphragm were also detected. His chest computerized tomography scan as well as a bone scan were negative for metastatic disease. A biopsy showed a “small blue round cell tumor” with marked crush artifact. The patient received chemotherapy (vincristine, doxorubicin, and cyclophosphamide) and subsequently was referred to our institution for tumor debulking and further follow-up.

Several pieces of nodular white-tan tumor involving the mesentery of transverse colon, spleen, retroperitoneum, gallbladder fossa, periportal area, diaphragm, and lesser curvature of the stomach were submitted to the pathology laboratory (Figure 1). The tumor nodules ranged from 1.2 cm to 30 cm in greatest diameter. Fresh tissue for molecular studies was saved. Microscopically, the tumor showed intersecting fibrotic bands (Figure 2) separating islands and sheets of small round blue cells that exhibited prominent rosette formation (Figure 3). The cells were monotonous, with hyperchromatic nuclei, inconspicuous nucleoli, and indistinct cytoplasmic borders. The mitotic activity was not increased and no abnormal mitotic figures were detected. The tumor cells showed positive immunoreactivity with desmin, vimentin, Leu-7, neuron-specific enolase, and Wilms tumor gene (WT1) (Figure 4) and were negative for epithelial markers (epithelial membrane antigen, AE1:AE3, CAM 5.2), CD99, S100 protein, synaptophysin, common muscle actin, and myogenin. A reverse transcriptase–polymerase chain reaction study revealed the presence of Ewing sarcoma (EWS)/WT1 gene fusion [ie, t(11;22)(p13;icq12)].

What is your diagnosis?

Desmoplastic small round cell tumor (DSRCT) is a relatively newly described tumor that primarily occurs in children or adolescents.1 The male to female ratio is 4 to 1, and patients with this tumor usually present with widespread abdominal serosal involvement.2 Its frequent association with serosal surfaces indicates the possibility that this tumor is a primitive tumor of mesothelial origin. However, because of its rare occurrence at the nonserosal sites, there is still some doubt about its origin.2 Specific to this tumor is the fusion of EWS gene on chromosome 22 and the WT1 on chromosome 11 [ie, translocation t(11;22)(p13;icq12)].3 These tumors are highly aggressive, and despite an initial response to tumor debulking and chemotherapy, the tumors usually relapse and the majority of patients die of tumor progression.4 On gross examination, the tumors are large (up to 40 cm in some cases) and are usually accompanied by multiple peritoneal implants. Their outer surface is usually bosselated, and the cut surfaces are gray-tan, with areas of necrosis and sometimes with myxoid changes. Microscopically, tumor cells are arranged in islands and nests separated by a desmoplastic stroma. Peripheral palisading of the tumor cells is common in some of the nests. Rosette formation, although previously reported, is rare.2 The tumor cells are usually uniform, with round to oval nuclei, inconspicuous nucleoli, and indistinct cell borders. Eosinophilic cytoplasmic inclusions can sometimes be detected. The stroma is composed of fibroblasts and myofibroblasts and contains vessels that may be in the form of tufts of capillary proliferations or large vessels with eccentric walls.

Ultrastructural findings include cell junctions, paranuclear intermediate cytoplasmic filaments, and basal lamina surrounding nests of tumor. In some cases, intraluminal microvillus-like structures, polar cell processes, microtubules, lipid droplets, glycogen, and dense-core granules have been noted.4 The immunophenotypic profile of DSRCT is distinctive and shows a multidirectional phenotype. Epithelial (low-molecular-weight cytokeratins, epithelial membrane antigen), neural (Leu-7, neuron-specific enolase), and muscle (desmin) markers are usually positive in DSRCTs. Vimentin is also positive, and like desmin, it often shows an intense intracytoplasmic dotlike staining pattern that appears to correspond to the eosinophilic inclusions seen on hematoxylin-eosin stains.2 

Antibodies directed against EWS and WT1 proteins can be used to identify the chimeric EWS-WT1 protein in tumor cells. It is important to note that the chimeric EWS-WT1 protein contains only the carboyx terminus of the wild-type WT1 protein. Therefore, while both WT1 (C-19, raised against the carboxy terminus of the protein) and WT (180, raised against the amino terminus of the protein) antibodies will react with the wild-type WT1 protein, only WT1 (C19) antibody will show nuclear positivity in DSRCTs.2 Antibodies against Mic2 antigen (O13) can also be positive in DSRCTs; however, the staining pattern is usually cytoplastic, as opposed to the membranous staining observed in EWS.2 

The current case exhibits 2 unusual but previously reported features: negativity for epithelial markers and rosette formation. In one study of 109 cases of DSRCTs, the authors2 report negative staining for cytokeratins (AE1:AE3 and CAM 5.2) in 4.1% and negative staining for epithelial membrane antigen in 7.4% of the cases. In small biopsy specimens, the absence of reactivity to epithelial markers together with a positive desmin stain may lead to a possible diagnostic pitfall (ie, rhabdomyosarcoma). Although DSRCTs are positive for desmin, they lack true muscle differentiation. Therefore, other muscle markers like common muscle actin and myogenin are negative. In difficult cases, the detection of EWS/WT1 gene fusion by reverse transcriptase–polymerase chain reaction is considered diagnostic.

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Author notes

Corresponding author: Gulbeyaz Omeroglu, MD, Department of Pathology, Loyola University Medical Center, EMS Building, 2nd Floor, 2160 S First Ave, Maywood, IL 60153 ([email protected])