LAUSR

To the Editor: Pancreatic undifferentiated rhabdoid carcinoma is rare, and has not been described in the World Health Organization (WHO) Classification of Tumours. Agaimy et al. reported 14 cases of pancreatic undifferentiated rhabdoid carcinoma, and classified them into two subtypes; loss of SMARCB1/INI1 and alteration of KRAS. The morphology of tumor cells is different between the two subtypes; the former is monomorphic, whereas the latter is pleomorphic. To date, no cytological feature on pancreatic undifferentiated rhabdoid carcinoma has been reported. Here, we report a case of pancreatic undifferentiated rhabdoid carcinoma with loss of SMARCB1/INI1, in which metastases were found in tongue, muscle, liver and lung. Cytological specimens were obtained from the metastatic lesion, in which monomorphic tumor cells with eccentric nuclei and prominent nucleoli were discohesively arranged and occasionally had cytoplasmic inclusion bodies. This is the first report on the cytological features of pancreatic undifferentiated rhabdoid carcinoma. Since the molecular target therapy against loss of SMARCB1/INI1 is under development, the discrimination of pancreatic undifferentiated rhabdoid carcinoma subtypes would be necessary in future. Cytological analysis is less invasive, and useful for such discrimination even when the general condition of patients is poor. The patient was a 67-year-old woman, who was introduced to our hospital to examine a mass in the pancreas. She had a history of colon cancer resection 6 years prior and the follow-up computed tomography (CT) revealed a mass in the pancreas. The contrast-enhanced CT scan in our hospital showed a hypovascular mass measuring 1.9 cm in the body of the pancreas with surrounding swollen lymph nodes and a ring-enhanced lesion measuring 1.9 cm in the liver (Fig. S1). An endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) was carried out for the pancreatic mass and a biopsy was taken for the liver mass. She was diagnosed with pancreatic cancer and received chemotherapy. In the next half year, tumors occurred in multiple organs, such as lung, bone, submucosa of the tongue, and muscle. Fine needle aspiration cytology (FNAC) was conducted for the submucosal nodule of the tongue to confirm metastasis. After that, surgical resection was performed for the metastatic tumor of the tongue. Surgical resection was also performed for the intramuscular metastatic tumor in the right thigh in order to control the hemorrhage. Her general condition gradually deteriorated and she died 2 weeks after the resection of the intramuscular tumor. The tumor cells of the pancreatic mass (EUS-FNA), liver mass (biopsy), submucosal nodule of the tongue (surgical resection) and intramuscular mass (surgical resection) were morphologically similar. Monomorphic tumor cells with enlarged nuclei and acidophilic cytoplasm spread diffusely. Tumor cells were discohesive and loosely arranged without prominent desmoplastic reaction. No glandular formation was found. Tumor cells occasionally had eosinophilic cytoplasmic inclusion bodies (Fig. 1a, b). Immunohistochemically, tumor cells were diffusely positive for pan-cytokeratin (AE1/AE3), negative for leukocyte common antigen (LCA), S-100, and desmin. Moreover, cytoplasmic inclusion bodies were positive for AE1/AE3 and vimentin (Fig. 1c). Tumor cells were negative for SMARCB1/INI1 (Fig. 1d). These characteristics were different from the past colon cancer, the histological finding of which was moderately differentiated tubular adenocarcinoma. By the clinical course and image findings, we concluded that the tumor originated in the pancreas and diagnosed it as pancreatic undifferentiated rhabdoid carcinoma. We performed mutational analysis of KRAS exons 2 (codons 12, 13, 19) and 3 (codon 61), and found no mutation. In the FNAC specimen, monomorphic tumor cells with eccentric nuclei and prominent nucleoli were discohesively arranged. Tumor cells occasionally had cytoplasmic inclusion bodies. The characteristics of tumor cells in cytological specimen were similar to those in histological specimen (Fig. 1e, f). In this report, we describe the case of pancreatic undifferentiated rhabdoid carcinoma of an elderly woman. Although pancreatic undifferentiated rhabdoid carcinoma has not been described in the WHO Classification of Tumours in pancreatic cancer due to its rarity, several cases have recently been reported. Agaimy et al. reported 14 cases of pancreatic undifferentiated rhabdoid carcinoma, and classified them into two subtypes; loss of SMARCB1/ INI1 and alteration of KRAS. Four of 14 cases belonged to the former, in which tumor cells showed monomorphic anaplastic histology. The remaining 10 cases belonged to the latter, in which tumor cells showed pleomorphic giant cell histology. In fact, monomorphic anaplastic histology was characteristic in our case, in which SMARCB1/INI1 expression was lost and KRAS wasn’t mutated. We describe the histogenesis of pancreatic undifferentiated rhabdoid carcinoma. KRAS is activated by point mutations in >90% of ordinary ductal adenocarcinoma of the pancreas. This finding suggests that in two subtypes of pancreatic undifferentiated rhabdoid carcinoma, the KRAS