title: 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.
authors.affiliation: Department of Histopathology, University College Hospital, London. afreeman@doctorsorg.uk
authors.forename: Alex
authors.initials: A
authors.lastname: Freeman
authors.forename: Nicola
authors.initials: N
authors.lastname: Geddes
authors.forename: Philippa
authors.initials: P
authors.lastname: Munson
authors.forename: Jean
authors.initials: J
authors.lastname: Joseph
authors.forename: Pramila
authors.initials: P
authors.lastname: Ramani
authors.forename: Ann
authors.initials: A
authors.lastname: Sandison
authors.forename: Cyril
authors.initials: C
authors.lastname: Fisher
authors.forename: M Connie
authors.initials: MC
authors.lastname: Parkinson
mesh_terms: D000199:Actins / Q000032:analysis; D000293:Adolescent; D000328:Adult; D000077548:Anaplastic Lymphoma Kinase; D002135:Calcium-Binding Proteins / Q000032:analysis; D002148:Calmodulin-Binding Proteins / Q000032:analysis; D003893:Desmin / Q000032:analysis; D003937:Diagnosis, Differential; D005260:Female; D015321:Gene Rearrangement; D006104:Granuloma, Plasma Cell / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007633:Keratins / Q000032:analysis; D008297:Male; D008840:Microfilament Proteins; D008875:Middle Aged; D009130:Muscle, Smooth / Q000737:chemistry; D011505:Protein-Tyrosine Kinases / Q000032:analysis* / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases; D013194:Staining and Labeling; D001745:Urinary Bladder Diseases / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D001749:Urinary Bladder Neoplasms / Q000201:enzymology / Q000473:pathology; D014746:Vimentin / Q000032:analysis; D000096985:Calponins
chemical_list: D000199:Actins; D000077548:Anaplastic Lymphoma Kinase; D002135:Calcium-Binding Proteins; D002148:Calmodulin-Binding Proteins; D003893:Desmin; D007633:Keratins; D008840:Microfilament Proteins; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D014746:Vimentin; D000096985:Calponins; C000626173:ALK protein, human