Mediastinal desmoplastic small round cell tumor.

RATIONALE: Desmoplastic small round cell tumor (DSRCT) is a rare distinct tumor with a high-grade malignancy. PATIENT CONCERNS: A 51-year-old male visited a local hospital in April 2016 complaining of shortness of breath, chest tightness and pain, and exhibited significant swelling in both sides of the chest. DIAGNOSES: CT demonstrated thoracic symmetry and no abnormalities were observed in the soft tissues of the ribs and the chest wall. A general observation of CT-guided puncture biopsy revealed 2 stripes of gray and grayish-white puncture tissues of 0.5 and 1 cm in length, respectively, and 0.1 cm in diameter. These results preliminarily suggested a (mediastinum) malignant small round cell tumor. INTERVENTION: Given the progression of the disease, the chemotherapy regimen, consisting of ifosfamide and etoposide, was altered during the course and radiotherapy (total of 70 Gy of mediastinal Y field radiation) was conducted. OUTCOMES: The patient and his family declined further treatment. Through follow-up, the total survival period was determined as 17 months. LESSONS: DSRCT is a rare interstitial malignant tumor. Effective cytoreduction combined with comprehensive therapies could achieve partial remission or prolong the survival of patients.

Mechanism of action of trabectedin in desmoplastic small round cell tumor cells.

BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is a rare and highly aggressive disease, that can be described as a member of the family of small round blue cell tumors. The molecular diagnostic marker is the t(11;22)(p13;q12) translocation, which creates an aberrant transcription factor, EWS-WT1, that underlies the oncogenesis of DSRCT. Current treatments are not very effective so new active drugs are needed. Trabectedin, now used as a single agent for the treatment of soft tissue sarcoma, was reported to be active in some pre-treated DSRCT patients. Using JN-DSRCT-1, a cell line derived from DSRCT expressing the EWS-WT1 fusion protein, we investigated the ability of trabectedin to modify the function of the chimeric protein, as in other sarcomas expressing fusion proteins. After detailed characterization of the EWS-WT1 transcripts structure, we investigated the mode of action of trabectedin, looking at the expression and function of the oncogenic chimera. METHODS: We characterized JN-DSRCT-1 cells using cellular approaches (FISH, Clonogenicity assay) and molecular approaches (Sanger sequencing, ChIP, GEP). RESULTS: JN-DSRCT-1 cells were sensitive to trabectedin at nanomolar concentrations. The cell line expresses different variants of EWS-WT1, some already identified in patients. EWS-WT1 mRNA expression was affected by trabectedin and chimeric protein binding on its target gene promoters was reduced. Expression profiling indicated that trabectedin affects the expression of genes involved in cell proliferation and apoptosis. CONCLUSIONS: The JN-DSRCT-1 cell line, in vitro, is sensitive to trabectedin: after drug exposure, EWS-WT1 chimera expression decreases as well as binding on its target promoters. Probably the heterogeneity of chimera transcripts is an obstacle to precisely defining the molecular mode of action of drugs, calling for further cellular models of DSRCT, possibly growing in vivo too, to mimic the biological complexity of this disease.