Desmoplastic small round cell tumour, DSRCT,

variously desmoplastic / malignant small cell / epithelial / neuroectodermal tumour of the peritoneum / intra-abdominal with divergent differentiation / coexpressing mesenchymal type intermediate filaments / with multiphenotypic differentiation of childhood

Definition

This is a highly malignant mesenchymal tumour, most often involving the peritoneum of young men. The tumour cells are polyphenotypic, showing features of epithelial/mesothelial, muscle and neural differentiation. It has been suggested that it arises from mesothelium17 (a mesthelioblastoma), on the grounds that it is positive for cytokeratins and WT1. However, negativity for CK5/6 and thrombomodulin, combined with positivity for Ber-EP4, CD15 and MOC-31, as well as occurrence at sites remote from mesothelium, argues against this.

DSRCT forms part of the family of paediatric "small round cell" tumours.

Clinical features

This tumour is most commonly seen in adolescent boys / young adult men, but also occurs in girls6 and older adults.

Anatomical sites The abdominal cavity is by far the most common site. But DSRCT has also been reported in association with other coelomic cavities and remote from any site lined by mesothelium.

(some tumours occupied more than one site)

Macroscopic appearances

The tumour masses are solid, firm and lobulated with a grey-white cut surface. There is often extensive peritoneal involvement3.

Histopathology

The characteristic histological pattern of "small, blue cells" embedded in a dense hypocellular fibrous stroma is seen in most cases. The cells form solid sheets, nests of variable size or cords. Less often, the cells form tubules, glands and rosettes. The cells are small to medium size, round, oval or spindle. There is little cytoplasm. Nuclei are hyperchromatic with clumped chromatin. There may be necrosis within larger nests of cells and calcification.

About one third of the tumors exhibited a wide range of morphologic features3. Cytoplasm may be more abundant, clear or eosinophilic. It may be vacuolated sometimes with signet ring-like morphology3. Rhabdoid cells may occur. If desmoplasia is limited and the nests are solid, there may be a resemblance to the insular pattern of carcinoid tumour or organoid zellenballen3. Some cases resemble transitional cell carcinoma3. A case with extensive papillary areas, no necrosis and little desmoplasia has been described, with areas resembling lobular carcinoma22.

Immunohistochemistry

These tumours characteristically coexpress epithelial, mesenchymal (vimentin and desmin) and neural markers.

*: summary of published literature.

Cytogenetics

Tumours are consistently associated with translocation t(11;22)(p13;q12). This typically fuses exon 7 of the Ewing sarcoma gene (EWS) on chromosome 22 with exon 8 of the Wilms' tumour suppressor gene (WT1) on chromosome 11. The fusion product may be demonstrated by reverse transcriptase PCR16. Variants involving other exons are known1,12,18. Functional EWS-WT1 gene fusion is evident in a very high proportion of cases (29/302, 25/262). The EWS-WT1 chimeric protein may activate the insulin-like growth factor-1 gene promotor20.

Ultrastructure

Cells are surrounded by a thin basement membrane. There are  juxtanuclear aggregates of intermediate filaments, but microfilaments with densities or Z-band-like material suggestive of either smooth or skeletal muscle differentiation are absent4. Dendritic-like processes containing microtubules and dense core granules were seen in some tumors and these tumors react for neural markers4. Cell junctions are usually poorly developed4.

Differential diagnosis

• In children: paediatric "small round cell" tumours. A hybrid tumour with the light and electron microscopic appearances and the EWS/FLI1 fusion transcript of a PNET, but the polyphenotypic expression of a DSRCT, has been reported from the abdomen of a young man19:

  • Ewing's sarcoma/PNET

  • rhabdomyosarcoma

  • Wilm's tumour

  • neuroblastoma

• In adults, depending on the site:

  • small cell carcinoma

  • Merkel cell carcinoma

  • transitional cell carcinoma

  • carcinoid tumour

  • neuroendocrine carcinoma

  • esthesioneuroblastoma

  • small cell mesothelioma: occurs in older patients with a history of asbestos exposure 3

  • lymphoma

Management

Aggressive chemotherapy is required.

Prognosis

This is an aggressive tumour with an average survival of about 2 years3. It usually recurs locally but distant metastases are uncommon1.

References

1Lae, M. E., P. C. Roche, et al. (2002). "Desmoplastic small round cell tumor: a clinicopathologic, immunohistochemical, and molecular study of 32 tumors." Am J Surg Pathol 26(7): 823-35.

2Gerald, W. L., M. Ladanyi, et al. (1998). "Clinical, pathologic, and molecular spectrum of tumors associated with t(11;22)(p13;q12): desmoplastic small round-cell tumor and its variants." J Clin Oncol 16(9): 3028-36.

3Ordonez, N. G. (1998). "Desmoplastic small round cell tumor: I: a histopathologic study of 39 cases with emphasis on unusual histological patterns." Am J Surg Pathol 22(11): 1303-13.

4Ordonez, N. G. (1998). "Desmoplastic small round cell tumor: II: an ultrastructural and immunohistochemical study with emphasis on new immunohistochemical markers." Am J Surg Pathol 22(11): 1314-27.

5Goldsmith, J.D., Pawel, B., Goldblum, J.R., Pasha, T.L., Roberts, S., Nelson, P., Khurana, J.S., Barr, F.G. and Zhang, P.J. Detection and diagnostic utilization of placental alkaline phosphatase in muscular tissue and tumors with myogenic differentiation. Am J Surg Pathol 2002;26:1627-33.

6Basade, M. M., D. S. Vege, et al. (1996). "Intra-abdominal desmoplastic small round cell tumor in children: a clinicopathologic study." Pediatr Hematol Oncol 13(1): 95-9.

7Cummings, O. W., T. M. Ulbright, et al. (1997). "Desmoplastic small round cell tumors of the paratesticular region. A report of six cases." Am J Surg Pathol 21(2): 219-25.

8Furman, J., W. M. Murphy, et al. (1997). "Urogenital involvement by desmoplastic small round-cell tumor." J Urol 158(4): 1506-9.

9Choi, J. K., K. van Hoeven, et al. (1995). "Desmoplastic small round cell tumor presenting in pleural fluid and accompanied by desmin-positive mesothelial cells." Acta Cytol 39(2): 377-8.

10Parkash, V., W. L. Gerald, et al. (1995). "Desmoplastic small round cell tumor of the pleura." Am J Surg Pathol 19(6): 659-65.

11Tison, V., S. Cerasoli, et al. (1996). "Intracranial desmoplastic small-cell tumor. Report of a case." Am J Surg Pathol 20(1): 112-7.

12Adsay, V., J. Cheng, et al. (1999). "Primary desmoplastic small cell tumor of soft tissues and bone of the hand." Am J Surg Pathol 23(11): 1408-13.

13Slomovitz, B. M., M. Girotra, et al. (2000). "Desmoplastic small round cell tumor with primary ovarian involvement: case report and review." Gynecol Oncol 79(1): 124-8.

14Young, R. H., J. H. Eichhorn, et al. (1992). "Ovarian involvement by the intra-abdominal desmoplastic small round cell tumor with divergent differentiation: a report of three cases." Hum Pathol 23(4): 454-64.

15Wolf, A. N., M. Ladanyi, et al. (1999). "The expanding clinical spectrum of desmoplastic small round-cell tumor: a report of two cases with molecular confirmation." Hum Pathol 30(4): 430-5.

16Argatoff, L. H., J. X. O'Connell, et al. (1996). "Detection of the EWS/WT1 gene fusion by reverse transcriptase-polymerase chain reaction in the diagnosis of intra-abdominal desmoplastic small round cell tumor." Am J Surg Pathol 20(4): 406-12.

17Gerald, W. L., H. K. Miller, et al. (1991). "Intra-abdominal desmoplastic small round-cell tumor. Report of 19 cases of a distinctive type of high-grade polyphenotypic malignancy affecting young individuals." Am J Surg Pathol 15(6): 499-513.

18Antonescu, C. R., W. L. Gerald, et al. (1998). "Molecular variants of the EWS-WT1 gene fusion in desmoplastic small round cell tumor." Diagn Mol Pathol 7(1): 24-8.

19Katz, R. L., M. Quezado, et al. (1997). "An intra-abdominal small round cell neoplasm with features of primitive neuroectodermal and desmoplastic round cell tumor and a EWS/FLI-1 fusion transcript." Hum Pathol 28(4): 502-9.

20Karnieli, E., H. Werner, et al. (1996). "The IGF-I receptor gene promoter is a molecular target for the Ewing's sarcoma-Wilms' tumor 1 fusion protein." J Biol Chem 271(32): 19304-9.

21Hill AD et al. WT1 staining reliably differentiates desmoplastic small round cell tumor from Ewing sarcoma/primitive neuroectodermal tumor. An immunohistochemical and molecular diagnostic study. Am J Clin Pathol 2000;114:345-353.

22Dorsey, B. V., L. E. Benjamin, et al. (1996). "Intra-abdominal desmoplastic small round-cell tumor: expansion of the pathologic profile." Mod Pathol 9(6): 703-9.

23Charles, A. K., I. E. Moore, et al. (1997). "Immunohistochemical detection of the Wilms' tumour gene WT1 in desmoplastic small round cell tumour." Histopathology 30(4): 312-4.

24Bismar, T. A., O. Basturk, et al. (2004). "Desmoplastic small cell tumor in the pancreas." Am J Surg Pathol 28(6): 808-12.

25Su, M. C., Y. M. Jeng, et al. (2004). "Desmoplastic small round cell tumor of the kidney." Am J Surg Pathol 28(10): 1379-83.

This page last revised 18.11.2004.

©SMUHT/PW Bishop