Pancreatic Metastasis from Mixed Adenoneuroendocrine Carcinoma of the Uterine Cervix: A Case Report
A 44-year-old woman had undergone radical hysterectomy and subsequent radiation therapy (50.4 Gy) for cervical cancer 8 years before this presentation. The final pathological diagnosis was MANEC, comprising small cells with a high nucleus-to-cytoplasm ratio growing in a trabecular pattern (fig. ). Although the patient had been treated with oral chemotherapy using tegafur-uracil, small bilateral pulmonary nodules appeared after 3 years. Percutaneous computed tomography (CT)-guided needle biopsy and histopathological examination were performed, showing neuroendocrine carcinoma (NEC). Pathological findings were similar to those of the previous cervical carcinoma, and immunostaining for thyroid transcription factor-1 (TTF-1) yielded negative results. TTF-1 expression is specific for the lungs, thyroid and brain and is used as a reliable marker for distinguishing between primary lung carcinoma and metastases within the lungs. Given these findings, metastatic lung cancer from the earlier cervical cancer was diagnosed. Some lesions in the lungs disappeared following combined chemotherapy using nedaplatin (CDGP) plus irinotecan hydrochloride (CPT-11). For some remaining lesions in the right lung, video-assisted partial lung resection had been performed. After surgery, she was treated with additional chemotherapy (CDGP + CPT-11, paclitaxel + carboplatin, docetaxel hydrate + cyclophosphamide) and followed up with (18F)fluoro-2-deoxy-D-glucose positron emission tomography/CT (PET/CT) every 6 months. A small number of new lesions in the left lung diagnosed on CT were resected with video-assisted thoracic surgery and pathologically confirmed as metastasis from cervical NEC. One year after this lung operation, the patient was referred to our department when PET/CT showed abnormal uptake in the pancreatic body (fig. , arrow) accompanied by slight back pain. Laboratory data on admission revealed no abnormalities in inflammation tests or tumor markers such as carcinoembryonic antigen, carbohydrate antigen (CA)19-9 and CA125. CT obtained in the arterial phase of enhancement showed a 20-mm faintly attenuating homogeneous round mass located in the pancreatic body (fig. , arrow). Endoscopic ultrasonography (EUS) revealed a well-circumscribed hypoechoic mass (fig. , arrow) in the pancreatic body and upstream pancreatic duct dilatation. Magnetic resonance cholangiopancreatography (MRCP) revealed stenosis of the main pancreatic duct in the pancreatic body (fig. , arrow) and dilated upstream pancreatic ducts. Brush cytology specimens seen under endoscopic retrograde pancreatography and repeated pancreatic juice cytology specimens collected through an endoscopic nasopancreatic drainage tube were negative. EUS-guided fine needle aspiration (EUS-FNA) was therefore performed, resulting in a diagnosis of NEC. As no extrapancreatic disease was detected on imaging, middle pancreatectomy was performed. Postoperative pathological examination showed atypical cells derived from small to large neuroendocrine cells with a high nucleus-to-cytoplasm ratio growing in a trabecular to solid and nodular pattern under hematoxylin and eosin (HE) staining, as were seen in the patient's cervical and lung tumors (fig. ). Rosette formation was also observed (fig. , arrow). High mitotic activity was seen, with 20 or more mitoses per 10 high-power fields (fig. ), along with positive immunostaining for synaptophysin (fig. ) and chromogranin A (fig. ) and negative results for TTF-1. The proliferative index indicated by MIB-1 was over 30% (fig. ). These results were compatible with secondary deposition from the cervical NEC. On the basis of the morphological features and results of immunohistochemical staining, metastatic pancreatic cancer from the cervical carcinoma was finally diagnosed. She has been followed up for 7 months since the surgery without any signs of local recurrence or other metastatic lesions.