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.

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.

Cytokeratin

67/78², 97/107^4*, 4/4²³

AE1/AE3

28/32 (staining was sometimes only focal)¹, 1/1²⁴, 1/1²⁵

37/39 (using a cocktail of AE1/AE3 and Cam5.2: usually diffuse, dot-like in four cases)⁴

Cam5.2

27/31 (staining was sometimes only focal)¹, 1/1²⁴

EMA

24/25⁴, 50/54², 64/73^4*, 0/1²⁵

Ber-EP4

5/7⁴, 1/1^4*

Desmin

26/32 (staining was sometimes limited to a few cells but was always dot-like and perinuclear)¹, 39/39 (about 75% of cases showed globoid or dot-like positivity)⁴, 70/78², 107/117^4*, 1/1 (dot-like pattern)²⁴, 4/4²³, 1/1²⁵

Desmoplakin

1/1^4*

WT1

29/31 (there was weak and focal nuclear staining, with fairly constant paranuclear cytoplasmic staining)¹, 8/9⁴, 25/27², 13/13²¹, 4/4 (strong nuclear granular staining)²³, 1/1 (focal strong positivity)²⁴

Vimentin

22/27 (globoid in 8 cases)⁴, 64/66², 87/103^4*, 4/4²³, 1/1²⁵

CD15

11/15⁴, 15/24^4*

CD 34

0/5^4*

CD56

0/1²⁴

CD57

10/15⁴, 17/35^4*

CD99

7/30¹, 6/17⁴, 9/47², 4/33^4*, 0/1²⁴, 0/4 (some non-specific cytoplasmic staining in one case)²³, 0/1²⁵

CD117

0/1²⁴

NSE

27/32¹, 18/25⁴, 60/74², 88/107^4*, 1/1²⁴, 3/4²³, 1/1²⁵

MOC-31

9/10⁴

Ca-125

5/12 (in only one case was staining strong)⁴, 1/5^4*

NB84

2/6⁴, 3/6^4*

Synaptophysin

3/19⁴, 11/43^4*, 0/1²⁴, 0/1²⁵

Chromogranin

1/22⁴, 1/46², 7/64^4*, 0/1²⁴, 0/1²⁵

PGP9.5

3/13^4*

HHF35

1/31¹, 3/19⁴, 1/58², 6/69^4*

SMA

3/16⁴, 5/35^4*

CK5/6

0/6⁴

CK7

0/1²⁵

CK20

0/7⁴, 0/1²⁵

B72.3

0/11⁴, 3/16^4*

Neurofilament

0/13⁴, 6/50^4*, 1/4²³

GFAP

0/10⁴, 3/41^4*

Peripherin

0/7⁴

Ca19.9

0/10⁴

Thrombomodulin

0/14⁴

a-fetoprotein

0/12⁴, 0/15^4*

CEA

0/13⁴, 0/16^4*

Placental alkaline phosphatase

0/11⁴, 15/19 (>50% of cells staining in 6 cases, 10-50% of cells staining in 6 cases, <10% of cells staining in 3 cases. Tended to be dot-like paranuclear positivity. Positivity paralleled other markers of myogenic differentiation.)⁵, 0/12^4*

S-100

0/22⁴, 13/74^4*, 0/1²⁴, 0/1²⁵

HMB45

0/15⁴, 0/19^4*

Myoglobin

0/20⁴, 0/6^4*

Myogenin

0/10⁴, 0/8²

Myo-D1

0/10⁴, 0/1^4*

Myosin

0/10^4*

p53

5/17 (cases with >20% cells staining)²

Oestrogen receptor

0/1²⁴

Progesterone receptor

0/1²⁴

*: 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 known^1,12^,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 exposure³
- 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.

Abdominal cavity	28 cases, including liver involvement in 9 cases¹,130 cases², 1 case (76 year old woman)¹⁵	37 cases³
Pelvic cavity	15 cases¹,	37 cases³
Retroperitoneum	12 cases¹, 8 cases³
Pancreas	1 case²⁴
Kidney	1 case²⁵
Ovary	1 case¹³, 3 cases¹⁴
Paratesticular	6 cases⁷
Thoracic	4 cases²
Mediastinum	2 cases¹
Pleura	1 case⁹, 3 cases¹⁰
Liver	1 case³
Parotid gland	1 case¹⁵
Ethmoid sinuses	1 case¹
Posterior cranial fossa	1 case², 1 case¹¹
Scalp	1 case¹
Hand	1 case², 1 case (soft tissues and bone)¹², 1 case¹⁸
Scrotum	1 case³

Cytokeratin	67/78², 97/107^4*, 4/4²³
AE1/AE3	28/32 (staining was sometimes only focal)¹, 1/1²⁴, 1/1²⁵	37/39 (using a cocktail of AE1/AE3 and Cam5.2: usually diffuse, dot-like in four cases)⁴
Cam5.2	27/31 (staining was sometimes only focal)¹, 1/1²⁴
EMA	24/25⁴, 50/54², 64/73^4*, 0/1²⁵
Ber-EP4	5/7⁴, 1/1^4*
Desmin	26/32 (staining was sometimes limited to a few cells but was always dot-like and perinuclear)¹, 39/39 (about 75% of cases showed globoid or dot-like positivity)⁴, 70/78², 107/117^4*, 1/1 (dot-like pattern)²⁴, 4/4²³, 1/1²⁵
Desmoplakin	1/1^4*
WT1	29/31 (there was weak and focal nuclear staining, with fairly constant paranuclear cytoplasmic staining)¹, 8/9⁴, 25/27², 13/13²¹, 4/4 (strong nuclear granular staining)²³, 1/1 (focal strong positivity)²⁴
Vimentin	22/27 (globoid in 8 cases)⁴, 64/66², 87/103^4*, 4/4²³, 1/1²⁵
CD15	11/15⁴, 15/24^4*
CD 34	0/5^4*
CD56	0/1²⁴
CD57	10/15⁴, 17/35^4*
CD99	7/30¹, 6/17⁴, 9/47², 4/33^4*, 0/1²⁴, 0/4 (some non-specific cytoplasmic staining in one case)²³, 0/1²⁵
CD117	0/1²⁴
NSE	27/32¹, 18/25⁴, 60/74², 88/107^4*, 1/1²⁴, 3/4²³, 1/1²⁵
MOC-31	9/10⁴
Ca-125	5/12 (in only one case was staining strong)⁴, 1/5^4*
NB84	2/6⁴, 3/6^4*
Synaptophysin	3/19⁴, 11/43^4*, 0/1²⁴, 0/1²⁵
Chromogranin	1/22⁴, 1/46², 7/64^4*, 0/1²⁴, 0/1²⁵
PGP9.5	3/13^4*
HHF35	1/31¹, 3/19⁴, 1/58², 6/69^4*
SMA	3/16⁴, 5/35^4*
CK5/6	0/6⁴
CK7	0/1²⁵
CK20	0/7⁴, 0/1²⁵
B72.3	0/11⁴, 3/16^4*
Neurofilament	0/13⁴, 6/50^4*, 1/4²³
GFAP	0/10⁴, 3/41^4*
Peripherin	0/7⁴
Ca19.9	0/10⁴
Thrombomodulin	0/14⁴
a-fetoprotein	0/12⁴, 0/15^4*
CEA	0/13⁴, 0/16^4*
Placental alkaline phosphatase	0/11⁴, 15/19 (>50% of cells staining in 6 cases, 10-50% of cells staining in 6 cases, <10% of cells staining in 3 cases. Tended to be dot-like paranuclear positivity. Positivity paralleled other markers of myogenic differentiation.)⁵, 0/12^4*
S-100	0/22⁴, 13/74^4*, 0/1²⁴, 0/1²⁵
HMB45	0/15⁴, 0/19^4*
Myoglobin	0/20⁴, 0/6^4*
Myogenin	0/10⁴, 0/8²
Myo-D1	0/10⁴, 0/1^4*
Myosin	0/10^4*
p53	5/17 (cases with >20% cells staining)²
Oestrogen receptor	0/1²⁴
Progesterone receptor	0/1²⁴