Desmoplastic small round cell tumor in childhood: The St. Jude Children's Research Hospital experience

Department of Surgery, St. Jude Children's Research Hospital, Memphis, Tennessee, United States
Pediatric Blood & Cancer (Impact Factor: 2.39). 09/2007; 49(3):274-9. DOI: 10.1002/pbc.20893
Source: PubMed


Desmoplastic small round cell tumor (DSRCT) is a rare, primarily intra-abdominal tumor that has a poor outcome with current therapies.
We retrospectively reviewed patient characteristics, presenting symptoms, tumor pathology, treatment, and outcome of 11 pediatric patients with DSRCT at our institution.
The cohort included 1 female and 10 male patients. Median age at diagnosis was 14 years (range 5-21 years). In eight (73%) patients, the primary tumor was abdominal or pelvic, and in one patient each, it was submental, mediastinal, and paratesticular. Nine (82%) patients had metastatic disease. All tumors showed polyphenotypic differentiation by immunohistochemistry. The EWS-WT1 transcript was detected in six of seven tumors tested. One tumor showed rhabdomyoblastic differentiation after therapy. All patients received chemotherapy; eight underwent surgical resection, seven received primary site radiation, and four received myeloablative chemotherapy with stem-cell support. Three (27%) patients are alive 23 months, 8 years, and 10 years from diagnosis. Two died of treatment-related toxicity, six died of disease. None of the patients in whom surgery and initial chemotherapy failed to induce complete remission survived.
DSRCT is an aggressive malignancy that does not respond well to contemporary treatments, and patients who do not enter complete remission after initial chemotherapy and surgery appear to have a particularly dismal outcome. Patients with localized extra-abdominal disease have a better prognosis, most likely due to increased feasibility of resection. Better understanding of molecular and genetic mechanisms of tumorigenesis and treatment-related changes may contribute to development of more effective therapy for DSRCT.

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    • "The prognosis of this tumor remains poor, with an overall progression free survival of less than 40% at 26 months [2] [3] [30]. Non-intraosseous extra-abdominal DSRCTs have been reported to have a better prognosis, likely attributed to the ease of obtaining a complete surgical resection [30].The two previously documented cases of intraosseous DSRCTs had an aggressive clinical course with metastasis and death at 18 and 36 months after diagnosis, respectively. [18] [19] In summary, primary intraosseous DSRCTs are exceedingly rare with only three reported cases to date. "
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    ABSTRACT: Desmoplastic small round cell tumor (DSRCT) is a rare, aggressive malignancy typically occurring intra-abdominally in young adolescent males. Rare extra-abdominal primaries have been reported in the mediastinum, head and neck area, central nervous system, paratesticular region, visceral organs, and soft tissue. We report a primary intraosseous DSRCT of the calvarium in a 6-year-old male who presented with right ear pain and swelling. Imaging showed an aggressive-appearing permeative mixed lytic and sclerotic lesion of the right sphenoid and temporal bones with extensive periosteal reaction, clinically concerning for osteosarcoma. An open biopsy was performed, and the tumor was composed of primitive round cells with perinuclear cytoplasmic clearing, arranged in diffuse sheets and ill-defined nests and surrounded by a prominent desmoplastic stroma. Immunohistochemically the tumor cells were reactive for desmin (dot-like), CD99 (membranous) and cytokeratin AE1/3 (focal). EWSR1-WT1 chimeric fusion transcript was detected by reverse transcriptase-polymerase chain reaction. Sequencing of the fusion transcript revealed a rare in-frame junction of EWSR1 exon 10 to WT1 exon 8. This is the third documented case of an intraosseous DSRCT with molecular confirmation, but it is the first reported case to arise in the calvarium. While the diagnosis of DSRCT is usually straightforward in the classic clinical setting of an intra-abdominal mass, awareness that this entity may present as a bone primary is necessary to prevent misclassification as osteosarcoma or other malignancy.
    03/2015; 92(1). DOI:10.1016/j.ehpc.2014.11.011
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    • "There are at least two reports of hybrid tumours with features of both DSRCT and Ewing sarcoma, one with an EWSR1-FLI1 fusion gene [8] and one with an EWSR1-ERG fusion gene [6]. Rapid growth and metastasis to liver, lungs, pleura, bone, spleen and lymph nodes [9,3] is common. The reported prognosis is poor, with a median survival of 17 months only [9-15]. "
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    ABSTRACT: Desmoplastic small round cell tumour is a rare malignant tumour with a male to female ratio of 4:1. It manifests mostly at serosal sites. Here we present a case of a 28-year-old male patient, who presented with a fast growing paratesticular mass. On biopsy nests and cords of small round cells, without a clear morphological lineage of differentiation were seen. Occasionally desmoplatic small round cell tumour shows different lines of differentiation. An unequivocal histological diagnosis might be difficult in such cases. Here we demonstrate by a combination of methods the characteristic immunohistochemical profile and - albeit unusual - molecular background and discuss the eventual link with Ewing sarcoma. Immunohistochemical studies showed a membranous staining of Keratine AE1/3 and a dot-like staining of Desmine, confirming its diagnosis. Using COBRA-FISH following a metaphase approach we demonstrated a balanced translocation, t(11;22)(p13;q12) and in RT-PCR formation of the EWSR1-WT1 fusion product, a specific translocation of desmoplastic round cell tumour. The fusion involves exon 9 of EWSR1 to exon 8 of WT1, an unusual fusion product, though earlier described in a case of a desmoplastic small round cell tumour of the hand. The EWSR1-WT1 chimera seems to function as an oncogenic transcription factor. Here the zinc finger domain of the WT1 acts with affinity with certain promoter domains influencing the expression of various downstream proteins such as: PDGFA, PAX2, insulin-like growth factor 1 receptor, epidermal growth factor receptor, IL2 receptor beta, BAIAP3, MLF1, TALLA-1, LRRC15 and ENT. We discuss their potential oncogenic roles and potential therapeutic consequences.
    01/2012; 2(1):3. DOI:10.1186/2045-3329-2-3
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    • "DSCRT are frequently characterized by a recurrent specific translocation t(11;22) (p13;q12), resulting in a fusion gene between Ewing's sarcoma gene and Wilm's tumor gene.5 Nevertheless, according to several reports,19,22 no specific gene translocation was found in our patient. "
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    ABSTRACT: The desmoplastic small round cell tumor (DSRCT) is an uncommon and highly aggressive cancer. The role of (18)F-FDG PET in management of DSRCT is little reported. We report a case of metastasized abdominal DSRCT detected in a 43-year old patient whose diagnostic and therapeutic approaches were influenced by (18)F-FDG PET-CT. The patient is still alive ten years after diagnosis. (18)F-FDG PET-CT seems to be a useful method for assessing therapeutic efficiency and detecting early recurrences even in rare malignancies such as DSRCT.
    Rare tumors 05/2009; 1(1):e19. DOI:10.4081/rt.2009.e19
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