Background: A case of peritoneal mesothelioma with an anaplastic lymphoma kinase (ALK) translocation was identified, and we conducted further studies to obtain diagnostic and therapeutic insights. We believe that this is the first report describing the cytology of this new tumor type. Case: A teenage woman was referred for severe pleural effusion. Enhanced computed tomography indicated an abdominal mass with ascites. Laparoscopy revealed tumor dissemination from the pelvis to the upper abdomen. Because a high-grade serous carcinoma was suspected, ascitic cytology and biopsy were performed. Cytologically, the tumor displayed characteristics of both adenocarcinoma and reactive or neoplastic mesothelial cells. After extensive pathological evaluation, the tumor was diagnosed as malignant peritoneal mesothelioma. To verify the diagnosis and aid in developing a therapeutic strategy, several companion diagnostics were tried. Surprisingly, the tumor was ALK-positive, and ALK recombination was confirmed by an ALK break-apart test. Retrospectively, cells and tissue specimens were stained with ALK intercalated antibody-enhanced polymer. Tumor cells were clearly distinguished from the nonneoplastic background. Recombination in ALK was reconfirmed by the National Cancer Center Japan, and the patient was enrolled in a clinical trial for alectinib. Conclusion: Companion diagnostics-based cytology may provide a useful means of monitoring and evaluating a molecular-targeted therapy.

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