Primitive neuroectodermal tumor/Ewing's sarcoma of the urinary bladder: a case report and its molecular diagnosis.
ABSTRACT We report a rare case of primitive neuroectodermal tumor/Ewing's sarcoma (PNET/ES) arising from the urinary bladder. A 65-year-old man presented with hematuria and dysuria. Computed tomography revealed an enlarged invasive tumor at the base of the bladder. No additional abnormal findings were disclosed by other diagnostic imaging methods. The surgical specimens showed small round cell tumor with positive staining for MIC2 gene product (CD99). EWS-FLI1 fusion transcripts were detected by reverse transcriptase polymerase chain reaction and direct sequencing, confirming the diagnosis of PNET/ES. The patient developed swollen pelvic lymph nodes as well as multiple lung metastases at 8 months postoperatively. No effective results could be obtained even with systemic chemotherapy consisting of vincristine, ifosfamide, doxorubicin and etoposide (VIDE) based on the EUROpean Ewing tumour Working Initiative of National Groups 1999 (EURO-E.W.I.N.G. 99) multinational trial. The patient died of acute superior mesenteric artery thrombosis at 22 months postoperatively. PNET/ES could have been included in past cases of small cell carcinoma because of the difficulty in its differential diagnosis. Exact diagnosis is crucial for deciding the treatment strategy for rare bladder tumors consisting of small round cells.
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ABSTRACT: Primary primitive neuroectodermal tumours (PNETs) of the bladder are extremely rare and aggressive neoplasms, and only six examples have been reported in the literature. The case of a 21-year-old woman, who remains disease free 3 years after tumour resection, is reported here. Morphological features were found to correspond to a small round blue cell tumour without rosette formation and with extensive areas of necrosis. Strong expression of CD99, vimentin and CD117 (c-kit), and focal reactivity to cytokeratin and S-100 protein was observed in tumour cells. Ultrastructurally, sparse neurosecretory granules were observed. Diagnosis of PNET was supported by molecular genetic analysis, showing the EWS-FLI-1 fusion transcript type 2 by RT-PCR and EWS gene rearrangement by fluorescence in situ hybridisation. A normal genetically balanced genotype was shown by comparative genomic hybridisation, which, together with the expression of c-kit, a known therapeutic target for imatinib, may have prognostic and therapeutic implications.Journal of Clinical Pathology 08/2006; 59(7):775-8. · 2.44 Impact Factor
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ABSTRACT: Ewing's sarcoma is the second most frequent primary bone cancer, with approximately 225 new cases diagnosed each year in patients less than 20 years of age in North America. It is one of the pediatric small round blue cell tumors, characterized by strong membrane expression of CD99 in a chain-mail pattern and negativity for lymphoid (CD45), rhabdomyosarcoma (myogenin, desmin, actin) and neuroblastoma (neurofilament protein) markers. Pathognomonic translocations involving the ews gene on chromosome 22 and an ets-type gene, most commonly the fli1 gene on chromosome 11, are implicated in the great majority of cases. Clinical presentation is usually dominated by local bone pain and a mass. Imaging reveals a technetium pyrophosphate avid lesion that, on plain radiograph, is destructive, diaphyseal and classically causes layered periosteal calcification. Magnetic resonance best defines the extent of the lesion. Biopsy should be undertaken by an experienced orthopedic oncologist. Approximately three quarters of patients have initially localized disease. About two thirds survive disease-free. Management, preferably at a specialist center with a multi-disciplinary team, includes both local control-either surgery, radiation or a combination-and systemic chemotherapy. Chemotherapy includes cyclic combinations, incorporating vincristine, doxorubicin, cyclophosphamide, etoposide, ifosfamide and occasionally actinomycin D. Topotecan in combination with cyclophosphamide has shown preliminary activity. Patients with initially metastatic disease fare less well, with about one quarter surviving. Studies incorporating intensive therapy followed by stem cell infusion show no clear benefit. New approaches include anti-angiogenic therapy, particularly since vascular endothelial growth factor is an apparent downstream target of the ews-fli1 oncogene.The Oncologist 06/2006; 11(5):503-19. · 4.10 Impact Factor
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ABSTRACT: Peripheral primitive neuroectodermal tumor (PNET) is a highly aggressive neoplasm belonging to the Ewing family of tumors. It is characterized by the expression of MIC2 and neural markers (eg, neuron-specific enolase, synaptophysin, S-100, vimentin, Leu-7), and the presence of the EWS-FLI1 translocation. We performed a MEDLINE search for PNET in urologic malignancies. Additionally, we report on 2 cases of renal and 1 case of bladder PNET. The data obtained by reviewing patients with renal PNET were analyzed using Kaplan-Meier analysis. Renal PNET is diagnosed in young adults (median age 24 years). In contrast, the incidence of bladder PNET seems to be dependent on a defective immune mechanism. Patients often present with pain (84%), palpable tumor (60%), and hematuria (38%). The radiologic findings are uncharacteristic; therefore, the diagnosis should be based on the histologic and immunohistochemistry findings. Renal and bladder PNET are both often diagnosed at an advanced stage and, therefore, the prognosis is poor, despite aggressive multimodal treatment (surgery, polychemotherapy, radiotherapy). We identified palpable tumor masses (log-rank test, P = 0.0027) and synaptophysin expression (log-rank test, P = 0.0422) as prognostic unfavorable markers for renal PNET. Renal PNET should be considered in young patients who present with the classic triad of renal cancer, hematuria, and pain and palpable tumor. Once PNET is diagnosed, multimodal treatment (radical surgery, multidrug chemotherapy, radiotherapy) must be initiated. Despite this, the prognosis is poor if distant metastases are present. Furthermore, palpable tumor masses and synaptophysin expression are associated with a shorter cancer-specific survival.Urology 09/2006; 68(2):257-62. · 2.42 Impact Factor