Desmoplastic Small Round Blue Cell Tumor: A Review of Treatment and Potential Therapeutic Genomic Alterations

Abstract

Desmoplastic small round blue cell tumors (DSRCTs) originate from a cell with multilineage potential. A molecular hallmark of DSRCT is the EWS-WT1 reciprocal translocation. Ewing sarcoma and DSRCT are treated similarly due to similar oncogene activation pathways, and DSRCT has been represented in very limited numbers in sarcoma studies. Despite aggressive therapy, median survival ranges from 17 to 25 months, and 5-year survival rates remain around 15%, with higher survival reported among those undergoing removal of at least 90% of tumor in the absence of extraperitoneal metastasis. Almost 100% of these tumors contain t(11;22) (p13;q12) translocation, and it is likely that EWS-WT1 functions as a transcription factor possibly through WT1 targets. While there is no standard protocol for this aggressive disease, treatment usually includes the neoadjuvant HD P6 regimen (high-dose cyclophosphamide, doxorubicin, and vincristine (HD-CAV) alternating with ifosfamide and etoposide (IE) chemotherapy combined with aggressively attempted R0 resection). We aimed to review the molecular characteristics of DSRCTs to explore therapeutic opportunities for this extremely rare and aggressive cancer type.

Metastasized Intraabdominal Desmoplastic Small Round Cell Tumor

“…In most cases, patients with desmoplastic tumors present with advanced disease. Most remain asymptomatic for extended periods of time, and the diagnosis is made when tumor burden is significant [5].…”

“…The size of those masses varies between 2 and 15 cm in diameter. Ultrasound and MRI do not seem to add any value in the characterization of lesions, although ultrasound may be useful for guiding percutaneous biopsy of more superficial lesions [5,6,9]. The PET_FDG is a useful test for the identification of occult lesions not identified in the CT and MRI, evaluation of the response to chemo and radiotherapy and early detection of recurrence [4,5,8,10].…”

“…Fine-needle aspiration specimens, although commonly employed, are not adequate during the workup of desmoplastic tumors due to issues with low cellularity of the sample, necrosis, and predominantly a desmoplastic reaction. Fine needle aspiration is challenging and requires pathological expertise in the utilization of ancillary techniques such as immunocytochemistry and cytometric immunophenotyping [5]. There is a wide range of differential diagnoses, including neoplastic and non-neoplastic diseases, such as peritoneal carcinomatosis, desmoid tumor, fibrous histiocytoma and peritoneal tuberculosis [2,8,11,12].…”

“…The diagnosis is based on histology, immunohistochemistry and cytogenetics. It is associated to specific chromosomal translocations t(11;22) (p13; q12), t(5;19), t(X; 16) and t(4; 10) [2,4,5,6]. Histologically it is characterized by the presence of small round blue and undifferentiated cells surrounded by fibrous and desmoplastic stroma.…”

“…Histologically it is characterized by the presence of small round blue and undifferentiated cells surrounded by fibrous and desmoplastic stroma. Immunohistochemical findings of these tumor cells expresses cytokeratin and EMA (> 90% of cases), desmin (90%) and neural markers in a variable percentage [5,6].…”