Inflammatory Myofibroblastic Tumor of the Bladder With FN1-ALK Gene Fusion: Different Response to ALK Inhibition

摘要

Inflammatory myofibroblastic tumors are rare tumors with an ALK (anaplastic lymphoma kinase) gene rearrangement in up to 65% of all cases. In our patient, the tumor was not primary resectable due to its extension. Under neoadjuvant treatment with the first generation ALK inhibitor crizotinib no tumor response was seen, but the following therapy with the next generation ALK inhibitor lorlatinib led to a rapid and deep response, enabling a complete tumor resection by partial cystectomy. Our case indicates that ALK positive inflammatory myofibroblastic tumors which do not respond to ALK inhibition with crizotinib can be successfully treated with newer agents. Inflammatory myofibroblastic tumors are rare tumors with an ALK (anaplastic lymphoma kinase) gene rearrangement in up to 65% of all cases. In our patient, the tumor was not primary resectable due to its extension. Under neoadjuvant treatment with the first generation ALK inhibitor crizotinib no tumor response was seen, but the following therapy with the next generation ALK inhibitor lorlatinib led to a rapid and deep response, enabling a complete tumor resection by partial cystectomy. Our case indicates that ALK positive inflammatory myofibroblastic tumors which do not respond to ALK inhibition with crizotinib can be successfully treated with newer agents. Inflammatory myofibroblastic tumors (IMTs) are rare tumors, occurring mainly in the abdominal cavity, retroperitoneum, pelvis, lung, head and neck, and less frequently in the gastrointestinal tract, pancreas, bladder and uterus.1Fu G Xu C Yao N Gu J Jiang H Han X Inflammatory myofibroblastic tumor: a demographic, clinical and therapeutic study of 92 cases.Math Biosci Eng. 2019; 16: 6794-6804https://doi.org/10.3934/mbe.2019339Crossref PubMed Scopus (7) Google Scholar,2Coffin CM Hornick JL Fletcher CDM Inflammatory myofibroblastic tumor: comparison of clinicopathologic, histologic, and immunohistochemical features including ALK expression in atypical and aggressive cases.Am J Surg Pathol. 2007; 31: 509-520https://doi.org/10.1097/01.pas.0000213393.57322.c7Crossref PubMed Scopus (624) Google Scholar Children and young adults are affected most often, but IMTs may occur along the entire range of age, with a slight predominance for women.1Fu G Xu C Yao N Gu J Jiang H Han X Inflammatory myofibroblastic tumor: a demographic, clinical and therapeutic study of 92 cases.Math Biosci Eng. 2019; 16: 6794-6804https://doi.org/10.3934/mbe.2019339Crossref PubMed Scopus (7) Google Scholar, 2Coffin CM Hornick JL Fletcher CDM Inflammatory myofibroblastic tumor: comparison of clinicopathologic, histologic, and immunohistochemical features including ALK expression in atypical and aggressive cases.Am J Surg Pathol. 2007; 31: 509-520https://doi.org/10.1097/01.pas.0000213393.57322.c7Crossref PubMed Scopus (624) Google Scholar, 3Cook JR Dehner LP Collins MH et al.Anaplastic lymphoma kinase (ALK) expression in the inflammatory myofibroblastic tumor: a comparative immunohistochemical study.Am J Surg Pathol. 2001; 25: 1364-1371https://doi.org/10.1097/00000478-200111000-00003Crossref PubMed Scopus (438) Google Scholar, 4Teoh JYC Chan NH Cheung HY Hou SSM Ng CF Inflammatory myofibroblastic tumors of the urinary bladder: a systematic review.Urology. 2014; 84: 503-508https://doi.org/10.1016/j.urology.2014.05.039Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar, 5Sukov WR Cheville JC Carlson AW et al.Utility of ALK-1 protein expression and ALK rearrangements in distinguishing inflammatory myofibroblastic tumor from malignant spindle cell lesions of the urinary bladder.Mod Pathol. 2007; 20: 592-603https://doi.org/10.1038/modpathol.3800776Crossref PubMed Scopus (74) Google Scholar Histologically, IMTs consist of a loosely fascicular proliferation of spindle cells with myobroblastic phenotype, variable cellularity, stromal edema and myxoid change as well as varying inflammatory infiltrate of plasma cells, lymphocytes, and eosinophilic granulocy