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

Intra-Abdominal Desmoplastic Small Round Cell Tumor: Case Report and Brief Review of the Literature

Desmoplastic small round cell tumor (DSRCT) is a rare and high malignant soft tissue tumor with very poor prognosis. It usually occurs in the abdominopelvic cavity of adolescents and young males. DSRCT is prone to occur distant metastasis, mainly in the liver and lung. The histopathological manifestation is featured with nests of small round blue cells separated by desmoplastic stroma. DSRCT can co-express epithelial, neural and mesenchymal markers. The molecular characteristic of DSRCT is the production of EWS-WT1 fusion protein via the translocation of chromosome t (11; 22) (p13; q12). Treatments of DSRCT include radical resection or cytoreductive surgery, high intensity systemic chemotherapy, local radiotherapy and hyperthermic intraperitoneal chemotherapy. Key words: Diagnosis; Therapy; Desmoplastic small round cell tumor

Desmoplastic small round cell tumor is a rare malignant neoplasm mostly occurring in the vicinity of or within the peritoneal cavity, and is uncommon in the head and neck region. Tumor location within a major salivary gland is exceptional. We report a case of a 41-year-old Chinese man with a history of diabetes mellitus and end-stage renal failure on peritoneal dialysis with a desmoplastic small round cell tumor occurring in the left submandibular gland. Fine-needle aspiration cytology showed variably cohesive clusters of small cells with hyperchromatic nuclei and fine granular chromatin. On histology the neoplasm displayed classic features of a desmoplastic small round cell tumor with angulated nests of small round blue cells in a fibromyxoid/desmoplastic stroma. Neoplastic cells were immunoreactive for cytokeratins (AE1/3), desmin (paranuclear dot-like), WT-1 (nuclear), epithelial membrane antigen, and CD56. EWS gene translocation and EWS-WT1 gene fusion were detected by fluorescence in situ hybridization and reverse transcriptase polymerase chain reaction, respectively. The case presented is the sixth case of and the oldest reported patient with a desmoplastic small round cell tumor occurring in a major salivary gland to date. Desmoplastic small round cell tumor should be considered in the differential diagnosis of a salivary gland neoplasm with a basaloid or small cell pattern on fine-needle aspiration cytology.

Objective To investigate the pathological characteristics, diagnosis, treatment decision and short-term curative effect of abdominal desmoplastic small round cell tumor. Methods The clinical data of a case of desmoplastic small round cell tumor admitted to Gansu provincial people′s Hospital in April 2018 were analyzed retrospectively.The clinical manifestations, pathological features, diagnosis and differential diagnosis, treatment and prognosis of desmoplastic small round cell tumor were summarized and analyzed. Results The patient was successfully treated with maximum tumor reduction.The operation time was 360 minutes.The estimated blood loss during operation was 200 ml, and no blood was transfused during operation.The abdominal drainage tube was removed on the 8th day after operation and the liver function recovered well.Postoperative pathology: (retroperitoneal) small round cell malignant tumor.Combined with clinical and immunohistochemical staining results: highly considered: desmoplastic small round cell tumor.The patient was discharged on the 16th day after operation.The patient was followed up for 4 months and the tumor recurred and liver metastasis.The follow-up period is now up to October 2018. Conclusion Desmoplastic small round cell tumor is a rare and highly malignant soft tissue small cell tumor with poor prognosis.Imaging examination and detection of tumor markers have no specificity and diagnose of it is difficult.Complete resection of the tumor and combined chemotherapy can improve the prognosis of the patients, but the prognosis is still not satisfactory, and more effective treatment decisions still need to be explored. Key words: Desmoplastic Small Round Cell Tumor; Chemotherapy; Histopathology

PDGF-A, PDGF-Rβ, TGFβ3 and bone morphogenic protein-4 in desmoplastic small round cell tumors with EWS-WT1 gene fusion product and their role in stromal desmoplasia: an immunohistochemical study

Desmoplastic Small Round Cell Tumors: A review with focus on clinical management and therapeutic options

A new molecular variant of desmoplastic small round cell tumor: significance of WT1 immunostaining in this entity

Patient: Female, 23Final Diagnosis: Desmoplastic small round cell tumorSymptoms: Nausea • vomiting • severe abdominal pain of two weeks • weight lossMedication: —Clinical Procedure: —Specialty: Obstetrics and GynecologyObjective:Rare diseaseBackground:Desmoplastic small round cell tumor (DSRCT) is a rare soft tissue sarcoma that usually arises in the abdomen or pelvis in young boys and adolescents. Presenting symptoms include abdominal pain and ascites. However, DSRCT is often disseminated throughout the peritoneal cavity at diagnosis, and the prognosis is poor. This report is of a case of DSRCT in a 23-year-old Jordanian woman who presented with abdominal pain.Case Report:An unmarried 23-year-old woman presented with abdominal pain. On examination, she was found to have ascites. A computed tomography (CT) scan of the abdomen and pelvis showed a complex cystic mass in the left ovary, multiple peritoneal deposits, a large amount of ascitic fluid, two hypodense lesions in the liver, and multiple enlarged lymph nodes. Diagnostic laparoscopy was performed, and multiple tumor biopsies were obtained. Histopathology showed a cellular tumor composed nests of small round cells embedded in desmoplastic stroma. Immunohistochemistry showed positive staining of the tumor cells for pan-cytokeratin, desmin, Wilms tumor 1 (WT1) antigen, epithelial membrane antigen (EMA), and CD56, which supported the diagnosis of DSRCT. After the second cycle of the P6 Protocol, which included seven courses of chemotherapy, the patient developed a severe and fatal infection.Conclusions:It is important to consider the diagnosis of DSRCT that may present atypically, particularly in patients who present with abdominal and pelvic masses. DSRCT has a rapid and aggressive course that requires early and definitive diagnosis with prompt treatment that includes systemic chemotherapy.

BACKGROUND Desmoplastic small round cell tumor (DSRCT) is a rare and highly aggressive soft tissue sarcoma, mainly occurring in male adolescents and young adults. It most commonly arises from the peritoneum and is characterized by the EWSR1-WT1 fusion gene. Patients typically present with widespread intra-abdominal disease and have a poor prognosis, with a 5-year survival rate of less than 15%. CASE REPORT A 23-year-old man presented with acute right upper quadrant abdominal pain, significant unintentional weight loss, early satiety, and constipation. Computed tomography (CT) of the abdomen and pelvis revealed multiple large hepatic masses, mesenteric lymphadenopathy, and duodenal thickening with partial luminal narrowing. CT-guided biopsy of a hepatic mass was performed but was inconclusive. Subsequent upper endoscopy with duodenal biopsy revealed a characteristic perinuclear dot-like Desmin staining pattern consistent with small round blue cell tumor, with immunohistochemistry positive for epithelial and myogenic markers. The patient was referred to a sarcoma center where he was started on systemic chemotherapy with a VAC/IE (vincristine, doxorubicin, cyclophosphamide/ifosfamide, etoposide) regimen. CONCLUSIONS This case highlights the diagnostic complexity of DSRCT, particularly in atypical liver-dominant presentations, and reinforces the importance of comprehensive tissue sampling and molecular confirmation to guide early, appropriate therapy. Continued research into targeted strategies is crucial to improve outcomes in this aggressive malignancy.

Immunophenotype of Desmoplastic Small Round Cell Tumors as Detected in Cases with EWS-WT1 Gene Fusion Product

Desmoplastic small round cell tumor (DSRCT) is a rare, aggressive sarcoma subtype that harbors a pathognomonic EWSR1::WT1 fusion protein (FP). DSRCT is usually incurable and FP-targeted agents are nonexistent. The five-year survival rate is below 20%. Tumor nests are classically surrounded by desmoplastic stroma in DSRCT, yet the interactions between the tumor cells and the stromal cells are poorly understood. Given this context, our study aims to understand the spatial heterogeneity within DSRCT and the tumor-stroma interactions. We utilized a 20-panel marker to study the cellular constituents of the tumor microenvironment (TME) in DSRCT and to characterize its multilineage expression, including epithelial and neural (NE) signatures. The markers included: DSRCT (ST6GALNAC, pan-Cytokeratin), Fibroblasts (Collagen, α-smooth muscle actin), Endothelial Cells (CD31, α-smooth muscle actin), T-cells (CD45, CD4, CD8), Macrophages (CD45, CD68, CD163, CD11c), and AR/NE markers (androgen receptor, neural-specific enolase, synaptophysin). Marker expression was explored in a nine-patient cohort using 9 x 9 mm2 tissue sections imaged by the Lunaphore COMET system. A deep learning model, Visiopharm, extracted high-quality regions and segmented cells based on nuclear staining. Spatial data were transformed into matrix format for analysis in Python, where UMAP and Leiden clustering identified distinct clusters consisting of tumoral cells, fibroblasts, and endothelial cells. Our analysis revealed two distinct fibroblast clusters—one with high α-SMA expression and the other with high collagen expression. These two clusters exhibited distinct spatial distributions and proportions across patient samples, indicating heterogeneity in stromal composition within the DSRCT microenvironment. Our previous study identified three DSRCT subtypes: AR+/NE-, AR-/NE+, and Hybrid AR+/NE+. The current spatial analysis suggests that AR+/NE- tumor nests are consistently surrounded by α-SMA-high fibroblasts, hinting at subtype-specific stromal interactions. Preliminary findings from co-culture experiments of DSRCT cells with human mesenteric fibroblasts suggest that fibroblasts enhance the proliferative capacity of DSRCT cells. These findings provide novel insights into the stromal heterogeneity of the DSRCT microenvironment and its association with tumor subtypes. Our future work will focus on quantifying spatial relationships and patterns, which includes how tumor nest characteristics are associated with fibroblast cell type or DSRCT subtype. Proximity and neighborhood analysis in python and Visiopharm analysis will be applied. Ultimately, our results might reveal novel drug targets that stop oncogenic tumor-stroma signaling. Citation Format: Jiaqian Fan, Adewale A. Adebayo, Diana Shamsutdinova, Davis Ingram, Clement Agyemang, Roberto Cardenas-Zuniga, Alexander Lazar, Danh Truong, Joseph Ludwig. Spatial heterogeneity of tumor and stromal cells in desmoplastic small round cell tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5323.

Desmoplastic small round cell tumor (DSRCT) is an aggressive small round cell neoplasm which predominantly occurs intra-abdominally in adolescents and young adults with a male predominance, and which is characterized by a recurrent t(11;22)(p13;q12) translocation leading to formation of the EWSR1-WT1 fusion gene, which generates a chimeric protein with transcriptional regulatory activity. Histologically, DSRCT has a characteristic morphology, of islands of monotonous small cells within prominent sparsely cellular fibroblastic stroma, and immunohistochemically it shows polyphenotypic multidirectional differentiation, with expression of epithelial, muscle, and neural markers. However, DSRCT can arise more rarely in other sites and exhibit a spectrum of both histologic features and immunoprofile, which may confuse diagnosis with other small round cell neoplasms. Correct diagnosis is important to ensure correct treatment and prognostication; DSRCT are almost universally fatal neoplasms with patients usually succumbing to disease within the first 2 years of diagnosis. While combination treatment strategies can confer a survival benefit, the overall prognosis remains poor. Further insight into the tumorigenic molecular changes generated by the fusion oncogene may lead to the generation of specific targeted therapies. We review DSRCT, discussing morphology and immunohistochemistry, molecular genetic findings, potential targeted treatments, and the differential diagnosis.

Background: Desmoplastic small round cell tumor (DSRCT) is a rare and highly aggressive soft tissue sarcoma, typically affecting young males and characterized by the EWSR1–WT1 fusion gene. Its diagnosis is challenging due to non-specific clinical features and overlapping histological patterns, making immunohistochemistry and molecular testing essential.  Case Presentation: We report the case of a young patient presenting with an abdominal mass. Histopathological analysis revealed a small round cell tumor with desmoplastic stroma. Immunohistochemistry was consistent with DSRCT, showing co-expression of epithelial, mesenchymal, and neural markers. Molecular confirmation of the EWSR1–WT1 fusion established the diagnosis. The patient underwent multimodal treatment including high-dose chemotherapy and cytoreductive surgery.  Discussion: This case illustrates the critical role of immunohistochemistry in diagnosing DSRCT and the importance of an aggressive multimodal approach combining chemotherapy, surgery, and, in selected cases, locoregional strategies such as HIPEC. Nevertheless, relapses remain frequent and prognosis is dismal, highlighting the urgent need for novel therapeutic strategies, including targeted agents and immunotherapy.  Conclusion: DSRCT is a rare but distinct entity requiring comprehensive pathological evaluation and aggressive multimodal management. Early recognition is crucial, although outcomes remain poor despite intensive therapy.

10016 Background: Desmoplastic small round cell tumor (DSRCT) is an aggressive tumor with poor response to multimodality therapies. Given the vascular nature of many DSRCT, we sought to determine if VEGF targeting could be effective in a preclinical model of DSRCT. Methods: RNA was extracted from frozen tumor samples (DSRCT, alveolar soft part sarcoma, alveolar rhabdomyosarcoma, synovial sarcoma, and Ewing sarcoma) and a human DSRCT cell line, JN-DSRCT. Microarray profiling utilized Affymetrix U133A/B or Affymetrix U133 Plus 2.0 chips. DSRCT xenografts were established by intramuscular injection of 20 million JN-DSRCT cells into the lower extremity of SCID/bg mice. A primary tumor developed within 8 - 12 weeks with concomitant development of abdominal metastases. Mice were treated during primary tumor growth with bevacizumab (5ug/kg IP weekly), irinotecan (2.5mg/kg IP ×10 days q3 weeks), or a combination of both. Results: Microarray data demonstrated an average of 4.5 times higher RNA expression of VEGFR-2 (KDR) in DSRCT tumor samples as compared to the other translocation-associated sarcomas (p = 3.6 E-12). VEGFR-2 was highly expressed in the JN-DSRCT line as compared to other sarcoma lines. VEGFA was also highly overexpressed in the DSRCT line and tumor samples when compared to the other translocation-associated sarcomas (2.5 times, p = 1.1E-10). Xenografts treated with bevacizumab had slowed growth over 100 days compared to control groups (volume of 0.52 mm3 vs 1.52, p = 0.002). Marked long term regressions were evident following treatment with the combination of irinotecan plus bevacizumab compared with irinotecan alone (0.12mm3 vs 0.44 at 100 days, p < 0.0001). Conclusions: VEGFR-2 and VEGFA are overexpressed in DSRCT. DSRCT xenografts were highly responsive to bevacizumab or bevacizumab plus irinotecan. Taken together, the expression data and the sustained response of DSRCT xenografts to bevacizumab suggest that VEGF-dependent angiogenesis is important for DSRCT tumor biology and represents an attractive target for therapy. These studies suggest that irinotecan and bevacizumab should be considered for inclusion in clinical trials for the treatment of DSRCT. No significant financial relationships to disclose.

Desmoplastic small round cell tumour is a rare malignancy most often seen in the abdomen or pelvis of young men. Unfortunately, this disease is usually metastatic at diagnosis and has dismal outcomes. Since 1991, when it was first described as a distinct clinical entity by Gerald WL and Rosai J some 200 cases were reported. All cases are characterized by the chromosomal translocation t (11;22) (p13; q12), which results in a formation of EWSR1-WT1 fusion gene. The diagnosis of IDSRCT is often made with core-needle tissue biopsy specimens of laparoscopy or laparotomy. Immunohistochemical analyses have shown the co-expression of epithelial, neuronal, myogenic, and mesenchymal differentiation markers. Multimodal therapy is usually indicated with chemotherapy, surgery & radiotherapy. We report a rare and unusual case of an extensive abdominopelvic desmoplastic small round cell tumour with liver & lung metastases, in an adolescent male patient from Bangladesh who presented with abdominal mass, pain & hepatomegaly. With various difficulties in diagnosis, we ultimately reached at diagnosis by open biopsy and immunohistochemistry as desmoplastic small round cell tutor. Now patient is on multidrug chemotherapy (modified p6) protocol.