Anaplastic lymphoma kinase (ALK 1) staining and molecular analysis in inflammatory myofibroblastic tumours of the bladder: a preliminary clinicopathological study of nine cases and review of the literature

Abstract

Inflammatory myofibroblastic tumours (IMFT) may arise at any anatomical site, including lung, soft tissues, retroperitoneum and bladder. Although morphologically similar, these lesions encompass a spectrum of entities with differing aetiology, ranging from reactive/regenerative proliferations to low-grade neoplasms with a risk of local recurrence, but no significant metastatic potential. Vesical IMFT usually presents as a polypoid mass with a pale firm cut surface and can be of considerable size, mimicking a malignant tumour clinically and radiologically. Its good outcome, however, warrants conservative surgical excision, emphasising the importance of identification and distinction from malignant tumours of the bladder that may require more radical surgery and/or adjuvant therapy. We conducted a preliminary retrospective, comparative immunocytochemical study of 20 bladder tumours, including nine IMFTs, five spindle cell (sarcomatoid) carcinomas, two rhabdomyosarcomas, two leiomyosarcomas and two neurofibromas. The results confirmed IMFT positivity for smooth muscle actin, desmin and cytokeratin in 78-89% cases, resulting in potential confusion with sarcomatoid carcinoma or leiomyosarcoma. In contrast, cytoplasmic anaplastic lymphoma kinase (ALK 1) staining was present in eight IMFT (89%), but was not seen in any other lesion examined. The ALK 1 staining was confirmed by fluorescence in situ hybridisation, with translocation of the ALK gene present in 15-60% tumour cells in four of six IMFT examined, but not in four cases of sarcomatoid carcinoma or three of leiomyosarcoma. In conclusion, ALK 1 staining may be of value in the distinction of vesical IMFT from morphologically similar entities, and often reflects ALK gene translocations in these lesions.

Alternative epithelial markers in sarcomatoid carcinomas of the head and neck, lung, and bladder—p63, MOC-31, and TTF-1

“…23,24 Spindle cell carcinomas are negative for ALK-1 in the few cases examined. 24,25 We found only one of 12 (1/12) cases to be very focally positive for p63 and none for TTF-1 and MOC-31.…”

Utility of ALK-1 protein expression and ALK rearrangements in distinguishing inflammatory myofibroblastic tumor from malignant spindle cell lesions of the urinary bladder

“…Similar to previous reports, in the present study, we noted ALK-1 expression in 62% (13 of 21 cases) of bladder inflammatory myofibroblastic tumor cases. 7,[13][14][15]19 ALK-1 positivity by immunohistochemistry was not detected in leiomyosarcoma or sarcomatoid carcinoma. Previous studies have also reported ALK expression in both alveolar and embryonal rhabdomyosarcoma, using a polyclonal ALK antibody.…”

“…Originally identified as a protein overexpressed in anaplastic large-cell lymphoma, ALK-1 has subsequently been shown to be overexpressed in a substantial proportion of inflammatory myofibroblastic tumors of various anatomic locations, [1][2][3][4][5][6][7][8][9]15 including the urinary bladder. 3,7,[10][11][12][13][14]16,19,25 Several studies have demonstrated a variable degree of cytoplasmic immunohistochemical staining for ALK-1. In inflammatory myofibroblastic tumor of the urinary bladder, positivity for ALK-1 by immunohistochemistry ranges from 33 to 89%, whereas ALK-1 protein expression in leiomyosarcoma and sarcomatoid urothelial carcinoma has not been reported, suggesting that ALK-1 immunohistochemical studies may be useful in the differentiation of inflammatory myofibroblastic tumor from other spindle cell lesions in the urinary bladder.…”

“…2,4,9,15,18,19 ALK, located on chromosome 2p23, encodes the ALK protein, a tyrosine kinase receptor, originally shown to be overexpressed in anaplastic large cell lymphoma. Rearrangements of ALK with various gene partners have been identified in inflammatory myofibroblastic tumor from a number of anatomic sites.…”

“…In the urinary bladder, a few series and case studies have reported cases of inflammatory myofibroblastic tumor exhibiting ALK rearrangements. 7,10,13,19,25 In addition, studies have identified a subset of inflammatory myofibroblastic tumors in locations outside of the urinary bladder, demonstrating the immunophenotype of a follicular dendritic cell tumor, harboring Epstein-Barr virus (EBV) or human herpes virus-8. 1,6,8,26,27 The objective of the present study was to determine if ALK-1 protein expression detected by immunoperoxidase methods and ALK rearrangements detected by FISH are useful in discriminating between inflammatory myofibroblastic tumor and malignant spindle cell tumors of the urinary bladder.…”