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

William R. Sukov, John C. Cheville, Austin W. Carlson, Brandon M. Shearer, Eli J. Piatigorsky, Karen L. Grogg, Thomas J. Sebo, Jason P. Sinnwell, Rhett P. Ketterling

Research output: Contribution to journalArticle

67 Scopus citations

Abstract

Inflammatory myofibroblastic tumor of the urinary bladder is an unusual spindle cell neoplasm that displays cytologic atypia, infiltrative growth and mitotic activity mimicking malignant tumors, such as leiomyosarcoma, rhabdomyosarcoma and sarcomatoid carcinoma. The objective of this study was to determine if anaplastic lymphoma kinase (ALK-1) protein expression detected by immunohistochemistry and ALK rearrangements detected by fluorescence in situ hybridization (FISH) were useful in distinguishing inflammatory myofibroblastic tumor from malignant spindle cell tumors of the urinary bladder. In inflammatory myofibroblastic tumor, ALK-1 expression was identified in 13 of 21 cases (62%) and ALK rearrangements in 14 of 21 cases (67%). All cases of inflammatory myofibroblastic tumor demonstrating ALK-1 expression, carried ALK rearrangements. One case negative for ALK-1 expression exhibited ALK rearrangement. ALK rearrangements were more common in women (P=0.0032). Leiomyosarcoma, sarcomatoid carcinoma, embryonal rhabdomyosarcoma and reactive myofibroblastic proliferations were negative for ALK-1 protein and ALK rearrangements. Immunohistochemistry using markers of muscle, epithelial, neural, and follicular dendritic cell differentiation showed overlap between inflammatory myofibroblastic tumor with and without ALK gene rearrangements, and between inflammatory myofibroblastic tumor and spindle cell malignancies. However, coexpression of cytokeratin and muscle-specific antigens was unique to inflammatory myofibroblastic tumor, observed in approximately half the tumors. This study indicates that detection of ALK protein and ALK gene rearrangements are useful in distinguishing inflammatory myofibroblastic tumor from spindle cell malignancies in the urinary bladder. Additionally, our findings suggest that ALK rearrangement is the primary mechanism for ALK activation and that inflammatory myofibroblastic tumor likely represents a heterogeneous group of spindle cell proliferations with the majority associated with ALK translocations, and the remaining associated with other etiologies.

Original languageEnglish (US)
Pages (from-to)592-603
Number of pages12
JournalModern Pathology
Volume20
Issue number5
DOIs
StatePublished - May 30 2007

Keywords

  • ALK
  • Fluorescence in situ hybridization
  • Inflammatory myofibroblastic tumor
  • Spindle cell lesion
  • Urinary bladder

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Sukov, W. R., Cheville, J. C., Carlson, A. W., Shearer, B. M., Piatigorsky, E. J., Grogg, K. L., Sebo, T. J., Sinnwell, J. P., & Ketterling, R. P. (2007). Utility of ALK-1 protein expression and ALK rearrangements in distinguishing inflammatory myofibroblastic tumor from malignant spindle cell lesions of the urinary bladder. Modern Pathology, 20(5), 592-603. https://doi.org/10.1038/modpathol.3800776