Molecularly confirmed primary malignant rhabdoid tumor of the urinary bladder: implications of accurate diagnosis

Abstract

Malignant rhabdoid tumors (MRTs) are well recognized in the kidney and extrarenal sites such as soft tissues, retroperitoneum, and bladder but are classified as atypical teratoid/rhabdoid tumors in the central nervous system. The unifying features of both extracranial MRT and atypical teratoid/rhabdoid tumors are the exon deletions/mutations of the SMARCB1 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily b, member 1) gene in 22q11.23 and resulting loss of SMARCB1/INI1 (integrase interactor 1) protein expression by immunohistochemistry. We herein report a case of extrarenal rhabdoid tumor confined to the bladder in a 3-year-old child, diagnosed by histopathology and confirmed by immunohistochemical and molecular studies. This is only the fourth molecularly proven primary MRT of the bladder to be reported. The patient’s peripheral blood was negative for the deletions observed in the tumor, thereby confirming a sporadic origin for the tumor. Given the possible dismal outcome, urgency for definitive diagnosis to institute intensive multimodality therapy, histopathologic differential diagnosis with rhabdomyosarcoma and urothelial carcinoma with rhabdoid features, and lack of consensus management guidelines, oncologists, urologists, and pathologists must be aware of this entity. Evaluation for a germ line SMARCB1 alteration may greatly aid risk stratification and family planning.

Genetics of Bladder Malignant Tumors in Childhood

“…(2) Botryoid histology, common in bladder and vaginal RMS, which is a variant of E-RMS. (3) Alveolar histology (A-RMS) accounts for the remaining 10% of GURMS and is associated with the worst outcomes [ 3 ]. Beyond basic histologic classification, the pathologic diagnosis of RMS is complimented by immunohistochemistry (IHC) and cytogenetics.…”

“…Neurofibromatosis type 1 (NF1) is a common autosomal dominant syndrome affecting 1/3,500 individuals worldwide [ 1 ]. Clinical features of the disease are pigmentary anomalies, skinfold freckling and Lisch nodules [ 2 ], learning disabilities, orthopedic problems, and benign and malignant tumors [ 3 , 4 ]. NF1 patients develop neural tumors more frequently than normal population.…”

“…Soft tissue tumors are more commonly seen in pediatric patients, with rhabdomyosarcoma being the most common malignancy in this location. Other non epithelial malignant tumors of the bladder, such as malignant rhabdoid tumor (MRT) and inflammatory myofibroblastic tumor are even more rarely observed and some others, as neuroblastoma, have exceptionally been reported [ 3 - 5 ]. Urothelial carcinoma and other epithelial neoplasms of the urinary bladder are rare in children and young adults.…”

Pure malignant rhabdoid tumour of the bladder

“…11 Older patients (>3 years) appear to have a better response to high-dose alkylating therapy. 1,6,11,12 Radiation therapy has been reserved for older patients in managing extracranial rhabdoid tumours, but appears to have a positive effect. Future management in the form of targeted therapies to induce cell cycle arrest in the rhabdoid cell lines, in addition to a standard chemotherapy regimen, are being explored.…”

A Rapid Progression of Disease After Surgical Excision of a Malignant Rhabdoid Tumor of the Bladder

“…Chemotherapy regimens tend to be based on Wilms tumor protocols and often include vincristine, dactinomycin, doxorubicin, and cyclophosphamide, as well as cisplatin, etoposide, ifosfamide, and carboplatin. 7 Others have been treated according to primitive neuroectodermal tumor/medulloblastoma protocols, 10 or modification of a regimen initially developed for the third intergroup rhabdomyosarcoma study group trial. 9 …”