Mesenchymal Neoplasms of the Female Genital Tract
Case 9 -
Desmoplastic Small Round Cell Tumor
Teri Longacre, Esther Oliva and Robert Soslow
The desmoplastic small round cell tumor (DSRCT) was described in 1989 by
Gerald and Rosai  and by
Ordonez's group ; much of the subsequent work was performed by Gerald, Rosai, Ladanyi and colleagues
and Ordonez's group . This remarkable tumor was described as disproportionately affecting
adolescent males, with a predominant intra-abdominal location, a nested pattern of growth with striking
desmoplasia, rhabdoid features, and coexpression of epithelial-related, neural and muscle markers. The
tumor was also noted to be highly aggressive. Subsequent reports in young women, including those with
make this a relevant topic for us to discuss. The differential diagnosis with
tumors occurring in young individuals and with tumors composed of small round cells is extensive.
DSRCT is a highly aggressive neoplasm that predominates in young men, the vast majority (>95%) of
whom present with disease in the peritoneal cavity . The male:female is 9:2 and the mean age of
presentation is 22 years (range 6-49 years). Presenting symptoms have included abdominal pain,
constipation, weight loss, abdominal distension and jaundice . Uncommon sites of involvement
include, but are not limited to, paratesticular tissues, pleura, ovary, posterior cranium, bones and
soft tissue of the hand and sinonasal tissues. Sites of metastasis have included liver, spleen, lung and
lymph nodes . Three-year survivals of 55% have been reported in patients who were treated with
surgery, chemotherapy and radiotherapy, although this figure drops to 27% when the three treatment
modalities were not administered .
Grossly, tumors are large and lobulated, usually solid and grey-white on sectioning. Typically, DSRCT
is composed of nests of uniform, small cells with scant cytoplasm set in a fibrous background. The
nuclei are generally hyperchromatic without apparent nucleoli, although large, atypical nuclei with
prominent nucleoli can be observed. Nearly every DSRCT contains such characteristic features at least
focally; unfortunately, atypical patterns are seen in many examples. Some examples exhibit eccentric
nuclei and ample eosinophilic cytoplasm with rounded paranuclear accentuations of filaments, reminiscent
of rhabdoid cells. Variations on the nested and desmoplastic pattern include examples showing tumor cell
nests with central necrosis, solid sheets of tumor cells, gland-like or papillary structures, trabeculae,
cords of single cells, rosettes, and spindle cells.
Immunohistochemistry and Genotype
Most DSRCTs express keratins (86%), EMA (93%), vimentin (97%), desmin (90%), NSE (81%)
 and WT1
Scant, weak or negative results have been reported with common muscle actin (2%),
myogenin (0%), chromogranin (2%) and CD99 (O13; 20%)
. Paranuclear coloration is frequently seen with
desmin in rhabdoid examples. Only antibodies that recognize the carboxy-terminal portion of the WT1
protein are useful for diagnosis as that is the only portion of WT1 that remains after a chimeric protein
Cytogenetic studies reveal a specific translocation between chromosomes 11 and 22 [t(11;22)(p13;q12)]
in up to 95% of tumors, and molecular genetic analysis demonstrates a fusion of the EWS and Wilms tumor suppressor genes (WT1)
The most commonly identified EWS/WT1
chimeric transcript is composed of an in-frame fusion of the first 7 exons of EWS, encoding the potential transcription modulating domain, and exons 8-10 of
WT1, encoding the last 3 zinc-fingers of the DNA-binding domain.
RT-PCR and FISH are routinely used in some centers for confirmation of the translocation.
Differential Diagnosis (Table 1)
The list of entities in the differential diagnosis is long and complex. On a positive note, the
immunophenotype and genotype of DSRCT and many other entities on the list are quite specific. Unlike
other tumors in the differential, DSRCT co-expresses keratins, desmin and WT1, lacks LCA, myogenin, and
almost always harbors t(11;22).
De-differentiated and undifferentiated carcinoma vs DSRCT
"Dedifferentiated" endometrial carcinoma is a recently described entity that includes a well or
moderately differentiated endometrioid adenocarcinoma juxtaposed with an undifferentiated carcinoma
. The typical patient is middle aged or older, in contrast to the typical DSRCT patient. The
undifferentiated component, which could possibly be confused with DSRCT, is made of small rounded cells
and characteristically shows only focal or weak keratin expression, unlike DSRCT. These tumors would not
be expected to express desmin, but only anecdotal information is available regarding this.
Hypercalcemic small cell carcinoma vs DSRCT
Small cell carcinoma of hypercalcemic type is a rare ovarian tumor that affects young women
predominantly. The prototypic example is composed of small, round mitotically active cells with scant
cytoplasm, arranged in sheets and forming pseudofollicular spaces. Nearly two-thirds of patients are
found to be hypercalcemic and most have high stage disease at presentation
Both the histologic
appearance of a small round cell tumor and the affected patients' ages resemble DSRCT. The large cell
variant of DSRCT can also demonstrate a rhabdoid appearance, potentially leading to confusion with
DSRCT. Despite these superficial similarities, the tumors are immunohistochemically distinct.
Hypercalcemic small cell carcinoma usually demonstrates at least focal evidence of epithelial
differentiation (with keratins and/or EMA) along with expression of p53, CD10, calretinin and WT1
They are negative for desmin, inhibin, chromogranin and TTF-1 and sometimes show reactivity for
. CD99 expression has also been reported. This tumor should not be confused with the
small cell carcinoma of undifferentiated, anaplastic, oat-cell or pulmonary type, a neuroendocrine
neoplasm that arises primarily in the ovaries of older individuals, almost always in concert with a
surface epithelial carcinoma such as serous carcinoma.
Lymphoma and leukemia vs DSRCT
With the exception of the very uncommon Burkitt lymphoma, the ovary is only rarely the primary site
for lymphoma. Examples of lymphomas that may secondarily involve ovary
include diffuse large
B-cell, follicular and extranodal marginal zone (MALT) types. T-cell lymphomas, such as anaplastic large
cell lymphoma and precursor T-lymphoblastic lymphoma are uncommon . All of the B-cell lymphomas
would be expected to express LCA, in contrast to DSRCT, although this may be lacking in anaplastic large
cell lymphoma (CD30-positive) and precursor T-lymphoblastic lymphoma (TDT-positive). Leukemias
(chloroma, granulocytic sarcoma or extramedullary myeloid tumor) infrequently involve the ovary in a
clinically significant way, although they are commonly found at autopsy in patients who died of leukemia
. They express CD43, myeloperoxidase and muramidase.
Granulosa cell tumor vs DSRCT
Both adult and juvenile granulosa cell tumors  can resemble DSRCT, although they are infrequently
disseminated at presentation. Adult granulosa cell tumors (AGCTs) only uncommonly present in
adolescence, in contrast to DSRCTs. These tumors can show nested growth of small cells with scant
cytoplasm, but microfollicles, pseudopapillary patterns and prominent nuclear grooves are all much more
common in AGCTs. Juvenile granulosa cell tumor (JGCT), particularly when high stage at presentation and
mitotically active, can also mimic DSRCT, but the cells of JGCTs generally contain more cytoplasm.
Follicle-like spaces are also a common feature of JGCTs. Like DSRCT, these tumors frequently express
WT1, and JGCT, in particular, can express EMA at low levels. Diffuse expression of EMA, desmin and
keratin is not expected. Granulosa cell tumors also express inhibin, calretinin and, frequently, CD99.
I am not aware of reports of DSRCTs with hormonal manifestations, which are commonly encountered in
granulosa cell tumors.
Dysgerminoma vs DSRCT
In most instances, the morphologic appearance of dysgerminoma is sufficiently unique and reproducible
to enable differentiation between it and DSRCT. Instead of growing in nests, dysgerminoma grows in
sheets separated by lymphocyte-bearing fibrous trabeculae. The cells contain prominent clear or pink
cytoplasm and a large nucleus with a distinctive and large nucleolus. Dysgerminoma only very rarely
expresses keratins diffusely and does not express desmin. Expression of PLAP, CD117 and OCT 3/4 is
Rhabdomyosarcoma vs DSRCT
Primary ovarian rhabdomyosarcomas are extraordinary . A more common, but still very rare
occurrence is rhabdomyosarcoma metastatic to the ovary
Rhabdomyosarcomatous components of more
frequently occurring gynecologic tumors may predominate, giving the impression of rhabdomyosarcoma. Such
tumors include adenosarcoma and carcinosarcoma, and rarely, Sertoli-Leydig cell tumors and immature
teratomas, among others. Like DSRCT, rhabdomyosarcomas almost always show some desmin staining; unlike
DSRCT, rhabdomyosarcomas are essentially always at least focally myogenin and Myo-D1 positive.
Neuroectodermal tumors vs DSRCT
Both primary and metastatic neuroectodermal tumors have been described to involve ovary
Primary tumors that might resemble DSRCT include neuroblastoma, medulloblastoma, primitive
neuroectodermal tumor of central type
and primitive neuroectodermal of peripheral type
. Neuroblastoma, in particular, can metastasize to the ovary
. None of these
tumors demonstrates the characteristic immunophenotype of DSRCT. Strikingly, some peripheral-type PNETs
demonstrate architectural growth patterns that mimic DSRCT. These are immunophenotypically and
genotypically distinct from DSRCT, however.
Tumors with rhabdoid features
Many tumors, including carcinomas (particularly the large cell variant of small cell hypercalcemic
carcinoma), sarcomas, melanomas and even lymphomas, can demonstrate rhabdoid features. Two specific
rhabdoid entities are renal/extrarenal rhabdoid tumor and epithelioid sarcoma of the proximal type.
In theory, it is possible that a renal or extrarenal rhabdoid tumor could be mistaken for DSRCT, but I
have not heard of such a case. Extrarenal rhabdoid tumors, related to CNS tumors bearing the same name,
occur in young and middle-aged patients. Like DSRCT, they bear a specific (but different) genotype.
Familial examples of central nervous system cases show mutation of INI-1
(with consequent loss of heterozygosity) on chromosome 22q and sporadic extrarenal rhabdoid tumors
demonstrate homozygous INI-1 deletions . Most express EMA and
vimentin. They would be expected to lack expression of INI-1 using the BAF47 monoclonal antibody .
Another theoretical consideration, though not a practical one, is the proximal type of epithelioid
sarcoma , a tumor that occurs in the buttocks and vulva of young to middle-aged patients. Most
express keratins, EMA and vimentin and many express desmin and CD34. Some authors have suggested that,
although they have been described as epithelioid sarcoma variants, they are instead extrarenal rhabdoid
tumor variants. One example we studied showed homozygous deletion of INI-1,
identical to extrarenal rhabdoid tumor. Loss of INI-1/BAF47 expression has also been reported
Although such tumors have a rhabdoid appearance, they can also be mistaken for squamous carcinomas,
both because of the tumor's location and because of the tumor cells' abundant eosinophilic cytoplasm.
The absence of intercytoplasmic bridges and epithelial involvement along with expression of CD34 and lack
of BAF47 all favor extrarenal rhabdoid tumor/proximal epithelioid sarcoma over squamous carcinoma.
Other miscellaneous tumors (epithelioid smooth muscle tumors, endometrioid stromal sarcoma, mesothelioma and melanoma)
It is also theoretically possible that epithelioid smooth muscle tumors, endometrioid stromal sarcoma,
mesothelioma and melanomas could resemble DSRCT. The keratin, desmin and WT1 positive immunophenotype of
DSRCT contrasts with endometrioid stromal sarcoma, mesothelioma and melanoma, although mesothelioma can
on occasion express desmin. In contrast to mesothelioma, DSRCT frequently expresses Ber-EP4, Leu-M1 and
lacks CK5/6. Using immunohistochemistry alone to distinguish epithelioid smooth muscle tumors might be
problematic, however. Close clinical correlation, morphologic study and gene rearrangement studies could
A managerial approach
As discussed, DSRCT can be separated from its histologic mimics because of characteristic and rather
specific genotypic and immunophenotypic features. Any diagnostically difficult lesion with some features
of DSRCT should therefore be studied for t(11;22)(p13;q12) or the EWS/WT1 chimeric transcript. It is
probably not necessary to study the genotype of lesions demonstrating classic morphology and
immunophenotype, but the threshold should be low when there are any doubts about the diagnosis. DSRCT is
usually, unfortunately a lethal disease, and one that triggers a diagnosis-specific treatment regimen.
Table 1. DSRCT Differential Diagnosis
| ||Desmin ||EMA ||WT1 ||t(11;22)(p13;q12)|
|DSRCT ||+ ||+ ||+ ||+|
|Small cell hyperCA++ ||- ||+ ||+ ||-|
|Lymphoma/leukemia ||- ||- ||R ||-|
|Granulosa1 ||-/+ ||- ||+/- ||-|
|Dysgerminoma ||- ||- ||? ||-|
|Rhabdomyosarcoma2 ||+ ||R ||R ||-|
|Neuroectodermal3 ||- ||R ||R ||-|
|Endometrioid stromal ||-/+ ||- ||+ ||-|
|Mesothelioma4 ||R ||+ ||+ ||-|
Abbreviations: DSRCT—desmoplastic small round cell tumor; hyperCA++--hypercalcemic; + —positive; -
—negative; -/+ —usually negative; +/- —usually positive; R—rare
1 Also expresses inhibin. JGCT can express EMA focally.
2 Also expresses myogenin and Myo D1
3 PNETs of peripheral type also express CD99 strongly and diffusely
4 Also express CK5/6, but not Ber-EP4 or Leu-M1
- Gerald WL, Rosai J. Case 2. Desmoplastic small cell tumor with divergent differentiation. Pediatr Pathol. 1989;9(2):177-83.
- Ordonez NG, Zirkin R, Bloom RE. Malignant small-cell epithelial tumor of the peritoneum coexpressing mesenchymal-type intermediate filaments. Am J Surg Pathol. 1989 May;13(5):413-21.
- Gerald WL, Miller HK, Battifora H, Miettinen M, Silva EG, Rosai J. 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. 1991 Jun;15(6):499-513.
- Ladanyi M, Gerald W. Fusion of the EWS and WT1 genes in the desmoplastic small round cell tumor. Cancer Res. 1994 Jun 1;54(11):2837-40.
- Gerald WL, Rosai J, Ladanyi M. Characterization of the genomic breakpoint and chimeric transcripts in the EWS-WT1 gene fusion of desmoplastic small round cell tumor. oc Natl Acad Sci U S A. 1995 Feb 14;92(4):1028-32.
- Antonescu CR, Gerald WL, Magid MS, Ladanyi M. Molecular variants of the EWS-WT1 gene fusion in desmoplastic small round cell tumor. Diagn Mol Pathol. 1998 Feb;7(1):24-8.
- Gerald WL, Ladanyi M, de Alava E, Cuatrecasas M, Kushner BH, LaQuaglia MP, Rosai J. 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. 1998 Sep;16(9):3028-36.
- Ordonez NG, el-Naggar AK, Ro JY, Silva EG, Mackay B. Intra-abdominal desmoplastic small cell tumor: a light microscopic, immunocytochemical, ultrastructural, and flow cytometric study. Hum Pathol. 1993 Aug;24(8):850-65.
- Young RH, Eichhorn JH, Dickersin GR, Scully RE. Ovarian involvement by the intra-abdominal desmoplastic small round cell tumor with divergent differentiation: a report of three cases. Hum Pathol. 1992 Apr;23(4):454-64.
- Ordonez NG, Sahin AA. CA 125 production in desmoplastic small round cell tumor: report of a case with elevated serum levels and prominent signet ring morphology. Hum Pathol. 1998 Mar;29(3):294-9.
- Slomovitz BM, Girotra M, Aledo A, Saqi A, Soslow RA, Spigland NA, Caputo TA. Desmoplastic small round cell tumor with primary ovarian involvement: case report and review. Gynecol Oncol. 2000 Oct;79(1):124-8.
- Lal DR, Su WT, Wolden SL, Loh KC, Modak S, La Quaglia MP. Results of multimodal treatment for desmoplastic small round cell tumors. J Pediatr Surg. 2005 Jan;40(1):251-5.
- Charles AK, Moore IE, Berry PJ. Immunohistochemical detection of the Wilms' tumour gene WT1 in desmoplastic small round cell tumour. Histopathology. 1997 Apr;30(4):312-4.
- Barnoud R, Sabourin JC, Pasquier D, Ranchere D, Bailly C, Terrier-Lacombe MJ, Pasquier B. Immunohistochemical expression of WT1 by desmoplastic small round cell tumor: a comparative study with other small round cell tumors Am J Surg Pathol. 2000 Jun;24(6):830-6.
- Lae ME, Roche PC, Jin L, Lloyd RV, Nascimento AG. Desmoplastic small round cell tumor: a clinicopathologic, immunohistochemical, and molecular study of 32 tumors Am J Surg Pathol. 2002 Jul;26(7):823-35.
- Sawyer JR, Tryka AF, Lewis JM. A novel reciprocal chromosome translocation t(11;22)(p13;q12) in an intraabdominal desmoplastic small round-cell tumor. Am J Surg Pathol. 1992 Apr;16(4):411-6.
- Shen WP, Towne B, Zadeh TM. Genetic abnormalities in an intraabdominal desmoplastic small cell tumor. Cancer Genet Cytogenet. 1992 Dec;64(2):189-91.
- Biegel JA, Conard K, Brooks JJ. Translocation (11;22)(p13;q12): primary change in intra-abdominal desmoplastic small round cell tumor. Genes Chromosomes Cancer. 1993 Jun;7(2):119-21.
- Rodriguez E, Sreekantaiah C, Gerald W, Reuter VE, Motzer RJ, Chaganti RS. A recurring translocation, t(11;22)(p13;q11.2), characterizes intra-abdominal desmoplastic small round-cell tumors. Cancer Genet Cytogenet. 1993 Aug;69(1):17-21.
- Silva EG, Deavers MT, Bodurka DC, Malpica A Association of low-grade endometrioid carcinoma of the uterus and ovary with undifferentiated carcinoma: a new type of dedifferentiated carcinoma? Int J Gynecol Pathol. 2006 Jan;25(1):52-8
- Scully RE. Small cell carcinoma of hypercalcemic type. Int J Gynecol Pathol. 1993;12:148-52.
- Young RH, Oliva E, Scully RE. Small cell carcinoma of the ovary, hypercalcemic type: a clinicopathological analysis of 150 cases. Am J Surg Pathol. 1994;18:1102-16.
- McCluggage WG, Oliva E, Connolly LE, McBride HA, Young RH. An immunohistochemical analysis of ovarian small cell carcinoma of hypercalcemic type. Int J Gynecol Pathol. 2004 Oct;23(4):330-6.
- Osborne BM, Robboy SJ. Lymphomas or leukemia presenting as ovarian tumors. An analysis of 42 cases. Cancer. 1983 Nov 15;52(10):1933-43.
- Monterroso V, Jaffe ES, Merino MJ, Medeiros LJ. Malignant lymphomas involving the ovary. A clinicopathologic analysis of 39 cases. Am J Surg Pathol. 1993 Feb;17(2):154-70.
- Vang R, Medeiros LJ, Warnke RA, Higgins JP, Deavers MT. Ovarian non-Hodgkin's lymphoma: a clinicopathologic study of eight primary cases. Mod Pathol. 2001 Nov;14(11):1093-9.
- Barcos M, Lane W, Gomez GA, Han T, Freeman A, Preisler H, Henderson E. An autopsy study of 1206 acute and chronic leukemias (1958 to 1982). Cancer. 1987 Aug 15;60(4):827-37.
- Young RH, Dickersin GR, Scully RE. Juvenile granulosa cell tumor of the ovary. A clinicopathological analysis of 125 cases. Am J Surg Pathol. 1984 Aug;8(8):575-96.
- Ferguson SE, Gerald W, Barakat RR, et al. Clinicopathologic features of rhabdomyosarcoma of gynecologic origin in adults, in press, Am J Surg Pathol
- Young RH, Scully RE. Alveolar rhabdomyosarcoma metastatic to the ovary: a report of two cases and a discussion of the differential diagnosis of small cell malignant tumors of the ovary. Cancer. 1989;64:899-904.
- Young RH, Kozakewich HP, Scully RE. Metastatic ovarian tumors in children: a report of 14 cases and review of the literature. Int J Gynecol Pathol. 1993 Jan;12(1):8-19.
- Aguirre P, Scully RE. Malignant neuroectodermal tumor of the ovary, a distinctive form of monodermal teratoma: report of five cases. Am J Surg Pathol. 1982;6:283-92.
- Kleinman GM, Young RH, Scully RE. Primary neuroectodermal tumors of the ovary. A report of 25 cases. Am J Surg Pathol. 1993 Aug;17(8):764-78.
- Kawauchi S, Fukuda T, Miyamoto S, Yoshioka J, Shirahama S, Saito T, Tsukamoto N. Peripheral primitive neuroectodermal tumor of the ovary confirmed by CD99 immunostaining, karyotypic analysis, and RT-PCR for EWS/FLI-1 chimeric mRNA. Am J Surg Pathol. 1998 Nov;22(11):1417-22.
- Biegel JA, Zhou JY, Rorke LB, Stenstrom C, Wainwright LM, Fogelgren B. Germ-line and acquired mutations of INI1 in atypical teratoid and rhabdoid tumors. Cancer Res. 1999 Jan 1;59(1):74-9.
- Haberler C, Laggner U, Slavc I, Czech T, Ambros IM, Ambros PF, Budka H, Hainfellner JA. Immunohistochemical analysis of INI1 protein in malignant pediatric CNS tumors: Lack of INI1 in atypical teratoid/rhabdoid tumors and in a fraction of primitive neuroectodermal tumors without rhabdoid phenotype. Am J Surg Pathol. 2006 Nov;30(11):1462-8.
- Guillou L, Wadden C, Coindre JM, Krausz T, Fletcher CD. "Proximal-type" epithelioid sarcoma, a distinctive aggressive neoplasm showing rhabdoid features. Clinicopathologic, immunohistochemical, and ultrastructural study of a series. Am J Surg Pathol. 1997 Feb;21(2):130-46.
- Sigauke E, Rakheja D, Maddox DL, Hladik CL, White CL, Timmons CF, Raisanen J. Absence of expression of SMARCB1/INI1 in malignant rhabdoid tumors of the central nervous system, kidneys and soft tissue: an immunohistochemical study with implications for diagnosis. Mod Pathol. 2006 19, 717-725