Desmoplastic Small Round Cell Tumor of the Ovary: A Case Report With Atypical Morphologic Features and Literature Review

Abstract

Desmoplastic small round cell tumor (DSRCT), an aggressive malignancy classically seen in adolescents and young adults with a strong male predominance, is exceptionally rare in the ovary. We report a 33-year-old woman with ovarian DSRCT presenting as a pelvic mass and peritoneal metastases. Histopathology revealed small round cell nests within desmoplastic stroma, exhibiting atypical architectural patterns (single-file, follicular-like cystic, microcystic, and solid). Immunohistochemistry demonstrated coexpression of epithelial (pan-keratin) and mesenchymal markers (vimentin, desmin), while molecular analysis confirmed the EWSR1::WT1 gene fusion. Despite multimodal therapy, the patient died 24 months after surgery. A review of 23 ovarian DSRCTs proposed a classification: ovarian-dominant and extraovarian-dominant subtypes. Ovarian-dominant patients showed significantly prolonged median survival (24 vs 10 months, P = .026), underscoring the prognostic relevance of anatomical classification. Ovarian DSRCT poses diagnostic challenges due to histomorphological mimicry of common malignancies. Although this subclassification may aid prognostication, multicenter validation is warranted.

Keywords

desmoplastic small round cell tumor ovary pathological morphology

Introduction

Desmoplastic small round cell tumor (DSRCT) is a rare and aggressive soft-tissue sarcoma with distinct clinicopathological features. It predominantly affects young individuals, with a median age of diagnosis at 25 years, and exhibits a striking male predominance.¹ Over 88.5% of tumors originate in the abdominal or pelvic cavities, while rare occurrences have been documented in the lungs, testis, cerebellopontine angle, mandible, heart, and other sites.² Ovarian involvement is exceptionally rare (<30 reported tumors). DSRCT exhibits insidious onset, rapid progression, and a propensity for local invasion, peritoneal dissemination, and hematogenous or lymphatic metastasis. Only 10% to 25% of patients present with localized disease at initial diagnosis.^2–3 Despite multimodal therapies, standardized protocols remain elusive, and prognosis remains dismal. This study aims to delineate the clinicopathological features of an ovarian DSRCT with atypical morphologic features to improve diagnostic precision and therapeutic insights.

Patient Presentation

A 33-year-old woman presented with a 3-month pelvic mass and 1-month hypogastric distension. Magnetic resonance imaging revealed a right adnexal lobulated mass (10.7 cm) with heterogeneous T1/T2 signals and restricted diffusion (ADC: 0.7 × 10⁻³ mm²/s), while contrast-enhanced sequences highlighted marked solid enhancement with necrotic foci. Metastases involved cervix–body junction, pelvic floor, intestinal serosa, and omentum (max 3.7 cm). Serum cancer antigen 125 (CA-125) was elevated (69.41 U/mL; normal: < 35 U/mL). Intraoperative frozen section confirmed malignant small round cell tumor, prompting total hysterectomy, bilateral salpingo-oophorectomy, and tumor debulking.

Grossly, the ovarian tumor measured 11 cm with a predominantly solid, gray-yellow cut surface and focal cystic changes. Microscopy revealed small round cells arranged in nests, single-file, follicular-like cystic, microcystic, and solid patterns, featuring hyperchromatic nuclei, scant-to-moderate biphasic cytoplasm, and ill-defined borders, with rare spindle forms (Figure 1A-E). Frequent mitotic figures and focal necrosis were observed (Figure 1F). The desmoplastic stroma contained focal myxoid change.

Immunohistochemistry revealed coexpression of vimentin, pan-keratin, desmin (Figure 1G）, GATA3, and CD99, while other epithelial (epithelial membrane antigen [EMA], keratin 7, keratin 20), neuroendocrine (synaptophysin, chromogranin A, CD56), and lineage-specific (PAX8, WT1, inhibin) markers were negative. Ki-67 index was 70%. Fluorescence in situ hybridization using an EWSR1::WT1 dual-fusion probe confirmed the diagnosis of ovarian DSRCT with metastases (Figure 1H). Despite aggressive therapy (specific regimen unavailable), the patient died 24 months postsurgery.

Discussion

DSRCT was first described by Gerald and Rosai in 1989.⁴ It predominantly affects young individuals (male-to-female ratio: 4-6:1), is highly aggressive, and carries a poor prognosis.^2–5 Although rare, its reported incidence has risen to 0.31 cases per million.⁵ DSRCT typically arises in the abdominopelvic cavity, presenting with nonspecific symptoms such as abdominal pain, ascites, constipation, or palpable masses.

The distinction between primary ovarian DSRCT and secondary involvement remains challenging due to the lack of standardized criteria. Given that DSRCT frequently presents with widespread abdominal disease, determining the precise site of origin is often clinically unfeasible. To address this diagnostic challenge, we propose a practical, anatomy-based classification system: ovarian-dominant (predominant disease burden in the ovary ± extraovarian spread) and extraovarian-dominant (predominant burden outside the ovary ± ovarian involvement).

We analyzed 23 patients with DSRCT involving the ovary, classifying 19 as ovarian-dominant and 4 as extraovarian-dominant (Tables 1 and 2). Patients with ovarian-dominant disease were significantly older than those with extraovarian-dominant disease (median age, 23 years vs 14 years; Mann-Whitney U test, P = .016) and exhibited large tumors (median size, 11.5 cm), frequent bilateral involvement (47%), advanced-stage disease (International Federation of Gynecology and Obstetrics stage III/IV: 95%), and elevated CA-125 levels (93%). The high frequency of CA-125 elevation suggests its utility as a monitoring tool. Notably, ovarian-dominant patients showed a significantly longer median overall survival compared to extraovarian-dominant patients (24 months vs 10 months, P = .026; Figure 2). This anatomical classification shows potential prognostic relevance, possibly due to a barrier effect of the ovarian tunica albuginea delaying spread. The influence of tumor biology cannot be excluded, and future multicenter studies are needed for validation.

Table 1.

Clinicopathological Findings of Ovarian-Dominant DSRCT.

Patient(reference)	Age(yrs)	Site/size (cm)	CA125(U/ml)	Grosstype	PositiveIHC	Geneticevidence	FIGOstage	Outcome(months)
1 (Young, 1992⁶)	15	Bilateral/15	N/A	S + C/S	KRT, EMA, desmin, vimentin	N/A	IIIC	AWD 7
2 (Zaloudek, 1995⁷)	22	Bilateral/10	107	S + C	KRT, EMA, desmin, NSE	N/A	IVB	DOD 18
3 (Slomovitz, 2000⁸)	11	Right/17	88.5	S + C	KRT, EMA, desmin	N/A	IVB	DOD 11
4 (Parker, 2002⁹)	23	Right/6.8	140	N/A	KRT, desmin	N/A	IVB	N/A
5 (Elhajj, 2002¹⁰)	27	Bilateral/20	N/A	Multi-N	KRT, desmin, vimentin, NSE	N/A	IVB	DOD 42
6 (Ota, 2010¹¹)	26	Bilateral/N/A	745.8	S + C	KRT, EMA, desmin	N/A	IIIC	DOD 23
7 (Ota, 2010¹¹)	19	Bilateral/10	2823	Multi-N	KRT, EMA, desmin	Supports	IIIC	DOD 11
8 (Fang, 2008¹²)	23	Bilateral/12	52	S + C	KRT, desmin, NSE,CD56, SYP, CHGA	Supports	IIIC	AWD 7
9 (D'Ippolito, 2012¹³)	29	Right/8.5	N/A	N/A	KRT, EMA, desmin, CD56, SYP, CHGA	Negative	I	NED 35
10 (Nakayama, 2014¹⁴)	6	Bilateral/N/A	N/A	S	KRT, EMA, desmin, NSE, CD56	Supports	IVB	DOD 28
11 (Nakayama, 2014¹⁴)	28	Right/10	42	S + C	KRT, desmin	Negative	III	DOD 40
12 (Nakayama, 2014¹⁴)	17	Right/15	35.9	Multi-C	KRT, desmin	Supports	IVB	NED 11
13 (Xie, 2016¹⁵)	30	Right/6.5	50.8	S + C	KRT, EMA, desmin, vimentin	N/A	IVB	AWD 15
14 (Neff, 2016¹⁶)	31	Right/20	89	N/A	N/A	Supports	III	AWD 14
15 (Altal, 2019¹⁷)	23	Left/6.5	91.03	C	KRT, EMA, desmin, CD56, SYP, CHGA	N/A	IVB	DOD 4
16 (Atef, 2019¹⁸)	22	Bilateral/N/A	Normal	N/A	KRT, desmin	N/A	III	N/A
17 (Vujić, 2020¹⁹)	19	Bilateral/20	271	mainly S	KRT, EMA, desmin, vimentin	Supports	III	NED 40
18 (Phulware, 2021²⁰)	19	Right/13	N/A	S + C	KRT, EMA, CD56, SYP, Vimentin	N/A	IIIC	DOD 3
19 (Current)	33	Right/11	69.41	S + C	KRT, desmin, vimentin	Supports	IIIC	DOD 24

Abbreviations: S, solid; C, cystic; N, nodular; DOD, dead of tumor; NED, no evidence of disease; AWD, alive with disease; N/A, information not available or test was not done; SYP, synaptophysin; CHGA, chromogranin A; KRT, pan-keratin; EMA, epithelial membrane antigen; NSE, neuron-specific enolase; FIGO, International Federation of Gynecology and Obstetrics; IHC, immunohistochemistry; DSRCT, desmoplastic small round cell tumor.

Table 2.

Clinicopathological Findings of Extraovarian-Dominant DSRCT.

Patient(reference)	Age(yrs)	Extraovarian site/size (cm)	Ovariansite/size (cm)	Grosstype	PositiveIHC	Outcome(months)
1 (Young, 1992⁶)	15	Omentum and mesentery/30	Bilateral/9	Mainly S	KRT, EMA, NSE, desmin, vimentin	DOD 4
2 (Young, 1992⁶)	14	Pelvic/7.8	Right/4.4	S	KRT, EMA, NSE, desmin, vimentin	N/A
3 (Shen, 1992²¹)	14	Pelvic/N/A	Bilateral/N/A	N/A	N/A	DOD 10
4 (Fang, 2008¹²)	13	Retroperitoneum/13	Left/10	S	KRT, desmin	DOD 21

Abbreviations: S, solid; DOD, dead of tumor; N/A, information not available or test was not done; KRT, pan-keratin; EMA, epithelial membrane antigen; NSE, neuron-specific enolase; IHC, immunohistochemistry; DSRCT, desmoplastic small round cell tumor.

Accurate diagnosis of DSRCT requires integration of histopathological, immunohistochemical, and molecular findings. Classic histology demonstrates variably sized nests of uniform small round cells with hyperchromatic nuclei and scant cytoplasm within a dense desmoplastic stroma. However, DSRCT may display uncommon morphological subtypes (eg, single-file infiltration, follicular-like cysts, or solid sheets). These subtypes are underrecognized in ovarian tumors and can mimic other malignancies, which complicates biopsy interpretation. For instance, they may resemble metastatic lobular breast carcinoma (showing characteristic linear infiltration), granulosa cell tumors (forming follicular patterns), or hypercalcemic small cell carcinoma (sharing a primitive round cell morphology).

Immunophenotypically, ovarian-dominant DSRCT consistently coexpressed epithelial and mesenchymal markers: pan-keratin (18/18), EMA (11/12), desmin (17/18), and vimentin (6/8), while neuroendocrine markers were inconsistently expressed (7/12). In our tumor, desmin exhibited a strong diffuse cytoplasmic pattern, a well-documented and diagnostically valid alternative to the classic dot-like staining.²² The negative WT1 result is expected as an N-terminus-specific antibody (clone EP122) was used; the EWSR1::WT1 fusion oncoprotein retains the C-terminal domain of WT1 but lacks the N-terminal region. While diagnostic, the EWSR1::WT1 fusion necessitates cautious interpretation of WT1 immunohistochemistry alongside molecular findings, as rare alternative fusions can cause aberrant staining (C-terminus negativity and N-terminus positivity).²³

The differential diagnosis of DSRCT requires exclusion of ovarian carcinomas, germ cell tumors, and sex cord-stromal tumors (expressing lineage-specific markers: estrogen receptor, PAX8, SALL4, inhibin, and SF1), and gynecologic small round cell neoplasms (eg, cervical small cell carcinoma, SMARCA4-deficient uterine sarcoma). Extragonadal mimics include CIC-rearranged sarcoma, Ewing sarcoma (EWSR1::FLI1 fusion), and embryonal rhabdomyosarcoma. Unlike DSRCT, these tumors lack hallmark desmoplastic stroma and multilineage coexpression (epithelial, mesenchymal, and neuroendocrine markers) but exhibit distinct molecular alterations. Malignant mesothelioma and melanoma, despite overlapping morphology (eg, small cell morphology, desmoplasia), are distinguished by absent EWSR1::WT1 fusion and divergent immunohistochemistry profiles (eg, calretinin in mesothelioma).

Recent advances in molecular pathology have revealed the “promiscuous” nature of EWSR1::WT1 gene fusions, which are now known to occur in a spectrum of neoplasms with distinct clinicopathological features.^24–25 Although this fusion was once regarded as a specific marker for conventional DSRCT, emerging evidence indicates that it can also drive indolent tumors characterized by low-grade morphological features—such as bland myoid or glomoid cytomorphology, inconspicuous desmoplastic stroma, and low mitotic activity—along with a favorable clinical prognosis.^22–24 In contrast to conventional DSRCT, these nonconventional EWSR1::WT1-fused tumors typically exhibit flat copy-number variation profiles and distinct DNA methylation patterns.²²

Our findings illustrate the morphological heterogeneity of DSRCT. Histologically, classic pattern, characterized by desmoplastic stroma with nests of small round cells, coexisted with atypical architectures, including single-file, microcystic, follicular-like, and solid growth. Importantly, these atypical areas still exhibited significant cytologic atypia and high proliferation, clearly distinguishing them from the previously reported indolent “nonconventional” EWSR1::WT1-fused tumors. The patient's aggressive course (death at 24 months) further aligns with conventional DSRCT rather than indolent subtypes. This morphological and clinical dichotomy underscores that the detection of an EWSR1::WT1 fusion represents a starting point rather than a diagnostic endpoint. Final classification must incorporate both histological phenotype and clinical behavior. Differences in underlying mechanisms—such as cell of origin, tumor microenvironment, epigenetics, or additional genetic alterations—may account for this clinicopathological diversity.²⁴

Management of DSRCT remains controversial in clinical oncology, with complete surgical resection recognized as pivotal for survival. Despite 3 decades of intensive multiagent chemotherapy (eg, vincristine-adriamycin-ifosfamide-actinomycin D), 5-year survival stagnates at 15%-30%.²⁶ A notable multimodal approach achieved 40-month disease-free survival through 2 cytoreductive surgeries, 9 Cooperative Weichteilsarkom Study regimen cycles, and adjuvant radiotherapy.¹⁹ Emerging preclinical strategies show promise: ertugliflozin with cabozantinib induced complete tumor regression in xenografts, while HER2 × CD3 bispecific T-cell engagers eliminated peritoneal metastases via T-cell redirection.^27–28 Androgen receptor pathway targeting with enzalutamide and antisense oligonucleotides suppressed tumor growth in models.²⁹ Conversely, intraperitoneal hyperthermic chemotherapy failed clinically.³⁰ Ovarian DSRCT poses particular challenges, often mimicking high-grade serous carcinoma with peritoneal spread, yielding median survival of 24 months despite aggressive multimodal therapy (Table 1).

Conclusion

DSRCT must be considered in young female patients with disseminated ovarian tumors, as misdiagnosis precipitates catastrophic therapeutic consequences. Key diagnostic features include small round cell histology, divergent immunophenotype, and EWSR1::WT1 fusion confirmation. A proposed classification stratifying ovarian-dominant versus extraovarian-dominant disease may refine prognostication and therapeutic planning, though validation through multicenter collaboration is essential.

Footnotes

Acknowledgments

We thank Mr Junyi Zhu for data analysis support.

ORCID iDs

Feng Shi

Yun Gu

Ethical and Informed Consent Statement

This article includes a case report and a literature review. Informed consent was obtained for the publication of the case report. The literature review is based on previously published studies; therefore, informed consent was not required for that component.

CRediT Authorship Contribution Statement

Feng Shi: writing—original draft and data curation; Xiaomin Feng: resources and data curation; Ning Qian: resources and methodology; Yun Gu: writing—review and editing, and methodology.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Data Availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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