A 90-year-old woman presented with a 2-month history of gross hematuria associated with worsening of diabetes mellitus. The patient visited a local general physician and underwent an abdominal ultrasound in December 2015. However, no abnormal findings were found at that time. Approximately one week later, the patient was referred to Okayama Medical Center (Okayama, Japan) for the assessment of hematuria. Urine cytology showed increased chromatin and irregularly shaped epithelial cells in clusters, suggesting the possibility of malignancy. Cystoscopy revealed a 15-mm, non-papillary, broad-based tumor on the posterior wall of the bladder (Fig. 1). Complete blood cell count and other laboratory test results were within the normal ranges, except for blood sugar levels (209 mg/dl; normal range, 73-140 mg/dl) and hemoglobin A1c levels (9.2%; normal range, 4.9-6.0%).

A transurethral resection of the bladder tumor (TURBT) from the posterior wall was performed, and a histopathological diagnosis of invasive adenocarcinoma was established, as the main locus of the tumor was submucosal to intramuscular. The urothelium did not show any atypia. In addition, the adenocarcinoma appeared to grow from the muscular layer to the surface (Fig. 2). Therefore, it was necessary to determine whether this adenocarcinoma was primary or metastatic. Immunostaining for cytokeratin (CK)7 and S100p was positive. However, immunohistochemistry was negative for CK20, estrogen receptor, trans-acting T-cell-specific transcription factor GATA-3 and nuclear β-catenin. This staining pattern suggested that the lesion was unlikely to have a gynecological or a colorectal origin (Fig. 3). Contrast-enhanced computed tomography scan revealed a tumor with poor contrast effect in the pancreatic tail, which infiltrated the splenic vessels and metastasized to the left adrenal gland (Fig. 4). Based on these findings, a diagnosis of invasive ductal carcinoma of the pancreas, cT4N0M1, was established according to the Union for International Cancer Control (UICC) staging system (8), with metastasis to the urinary bladder and left adrenal gland. This carcinoma had not been revealed by ultrasound examination previously performed at the general clinic; it is possible that the doctor did not examine the pancreas region, as the chief complaint of the patient was hematuria. The patient declined aggressive treatment due to old age and chose to receive the best supportive care. The patient died 6 months after the diagnosis.

For analysis of the resected sample, the tissue was fixed with 10% neutral buffered formalin at room temperature overnight and paraffin embedded. Immunohistochemistry was performed using 5-µm-thick sections on an automated immunohistochemistry system (Ventana BenchMark GX; Roche Diagnostics, Inc.) and the iVIEWDAB universal detection kit (Roche Diagnostics, Inc.). The primary antibodies were diluted with Antibody Diluent with Background Reducing Components (cat. no. S3022; Dako; Agilent Technologies, Inc.) containing carrier protein for blocking, accordingly the blocking time was the same as the incubation time, and the temperature was 35˚C. The antibody clone, supplier, dilution ratio, CC1 pretreatment time, incubation time and magnification set for each primary antibody were as follows: CK7 (OV-TL 12/30; Dako; Agilent Technologies, Inc.; 1:100; 60 min; 26 min; x200), CK20 (Ks 20.8; Dako; Agilent Technologies, Inc.; 1:100; 60 min; 20 min; x200), estrogen receptor (SP1; Ventana Medical Systems, Inc.; ready-to-use; 60 min; 26 min; x200), S100P (rabbit polyclonal; Atlas Antibodies AB; 1:3,000; 30 min; 26 min; x200) and GATA-3 (L50-823; Biocare Medical LLC; 1:200; 60 min; 32 min; x200). The counterstaining was performed with hematoxylin for 5 min at room temperature. β-catenin (β-catenin-1; Dako; Agilent Technologies, Inc.) was stained for at another facility, thus, the details of the staining conditions are unknown. The specimens were observed with a light microscope.