Kazunori Fugo

Napsin A is frequently expressed in clear cell carcinoma of the ovary and endometrium

Napsin A is a reliable marker for pulmonary adenocarcinoma and is expressed in a subset of ovarian clear cell carcinomas (O-CCCs), endometrial (EM) CCCs, and endometrioid carcinomas (EC). We investigated napsin A levels in O-CCC and EM-CCC and compared these with levels in other nonmucinous ovarian carcinomas and EM-EC, respectively. Napsin A, thyroid transcription factor (TTF)-1, paired box (PAX) 8, and cancer antigen (CA) 125 expression was evaluated in 111 ovarian and uterine carcinoma cases (22 O-CCC, 15 EM-CCC, 13 ovarian EC (O-EC), 39 high-grade serous carcinoma [HGSC], and 22 EM-EC) using immunohistochemistry. Napsin A immunoreactivity was observed in 21 (95.5%) of 22 O-CCC and 10 (66.7%) of 15 EM-CCC cases but was rare in O-EC and EM-EC (7.7% and 4.5%) and undetectable in HGSC cases. Thyroid transcription factor 1 was not expressed in O-CCC but was detected in 1 (6.7%) of 15 EM-CCC, 3 (23.1%) of 13 O-EC, 2 (5.1%) of 39 HGSC, and 1 (4.5%) of 22 EM-EC cases. All 111 cases examined were positive for PAX8, whereas 3 (20.0%) of 15 of EM-CCC and 1 (4.5%) of 22 EM-EC cases were negative for CA125. There were no napsin A/TTF-1 double-positive cases, except for 1 EM-CCC, in which cells had a focal expression pattern. All napsin A- and/or TTF-1-positive cases expressed PAX8 and CA125. In conclusion, napsin A is frequently expressed in O-CCC and EM-CCC, rarely in O-EC and EM-EC, and never in HGSC cases. These findings confirm the importance of using a panel of antibodies that includes napsin A, TTF-1, and PAX8 when evaluating metastatic carcinomas of unknown origin, particularly when gynecologic and pulmonary adenocarcinomas are included in the differential diagnosis.

Intracellular position of G2/M-phase nuclei in neoplastic and non-neoplastic pseudostratified glands suggests the occurrence of interkinetic nuclear migration

It has been established that nuclear pseudostratification of the neural epithelium in vertebral embryos is caused by interkinetic nuclear migration, a cell cycle-dependent regulation of nuclear movement, during which the G2/M-phase nuclei move apically before returning basally in the G1/S phase. Here we demonstrate the cell cycle-related nuclear location characteristic of interkinetic nuclear migration in human neoplastic and non-neoplastic pseudostratified glands. Immunohistochemical analysis with phosphohistone H3 (a G2/M-phase marker) and Ki67 was performed on fetal tissues, proliferative-phase endometrium (5 cases), and colonic adenomas (12 cases). In all cases, G2/M nuclei were significantly located apically, whereas Ki67-positive nuclei were widely distributed along the basal–apical axis. In the proliferating zone of the normal colon mucosa, elongated nuclei in the G2/M phase were occasionally found on the apical side of the cells. These results suggest that the interkinetic nuclear migration occurs in association with cell proliferation in both neoplastic and non-neoplastic glands.

Mucoepidermoid carcinoma with extensive spindled morphology and melanocytic marker expression

Mucoepidermoid carcinoma (MEC) is the most common malignant neoplasm of the salivary gland. Albeit common, histologic variants have rarely been noted in MEC. Here, we report a 49-year-old man with a sublingual gland tumor. Histologically, the tumor was composed of spindle cells arranged in interlacing fascicules or globular nests. A few bland small glands containing mucous cells were also scattered. The spindle tumor cells completely lacked immunoreactivity for cytokeratin, and exhibited immunoreactivity for vimentin, S-100, HMB-45, Melan A, and SOX10. The tumor was initially suspected to be clear cell sarcoma, malignant melanoma, or perivascular epithelioid cell tumor with a few entrapped nonneoplastic duct epitheliums. However, reverse-transcription polymerase chain reaction revealed the CRTC3-MAML2 fusion gene product diagnostic of MEC. In fact, a very minor component of the epithelial cells was reminiscent of conventional MEC, whereas major spindled tumor cells possessed markedly altered differentiation. This is the first case report of MEC with extensive spindled morphology and melanocytic marker expression.

Preserving the Mucosa to the Maximum Possible Extent for Endoscopic Submucosal Dissection of Subcircumferential Superficial Esophageal Carcinoma

Aim To show our unique strategy of endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma larger than the subcircumference. Methods From April 2011, we used a mucosal preservation method called the log bridge (LB) method for the lesion larger than the subcircumference. The patients in whom the circumference of the mucosal defect was 5/6 to <1 were classified into the LB group; those who underwent whole circumferential ESD were classified into the non-LB group. The data were collected retrospectively and were compared between the two groups. Results Eighteen patients into the LB group and 7 into the non-LB group were classified. The median number of endoscopic balloon dilation sessions after ESD in the LB group tended to be lower than that in the non-LB group. The mean period until complete epithelialization after ESD was significantly shorter in the LB group. The rates of curative resection were 100% (7/7) in the non-LB group and 61.1% (11/18) in the LB group. However, there was no local recurrence in either group for approximately two years. Conclusion In cases involving subcircumferential esophageal lesions, the LB method is useful for achieving rapid healing and might be related to a reduced degree of esophageal stricture.

Forkhead box protein A2, a pioneer factor for hepatogenesis, is involved in the expression of hepatic phenotype of alpha-fetoprotein-producing adenocarcinoma

Alpha-fetoprotein (AFP)-producing adenocarcinoma is a high-malignant variant of adenocarcinoma with a hepatic or fetal-intestinal phenotype. The number of cases of AFP-producing adenocarcinomas is increasing, but the molecular mechanism underlying the aberrant production of AFP is unclear. Here we sought to assess the role of Forkhead box A (FoxA)2, which is a pioneer transcription factor in the differentiation of hepatoblasts. FoxA2 expression was investigated in five cases of AFP-producing gastric adenocarcinomas by immunohistochemistry, and all cases showed FoxA2 expression. Chromatin immunoprecipitation revealed the DNA binding of FoxA2 on the regulatory element of AFP gene in AFP-producing adenocarcinoma cells. The inhibition of FoxA2 expression with siRNA reduced the mRNA expression of liver-specific proteins, including AFP, albumin, and transferrin. The inhibition of FoxA2 also reduced the expressions of liver-enriched nuclear factors, i.e., hepatocyte nuclear factor (HNF) 4α and HNF6, although the expressions of HNF1α and HNF1β were not affected. The same effect as FoxA2 knockdown in AFP producing adenocarcinoma cells was also observed in hepatocellular carcinoma cells. Our results suggest that FoxA2 plays a key role in the expression of hepatic phenotype of AFP-producing adenocarcinomas.

Diffusion-weighted whole‑body imaging with background body signal suppression/T2 image fusion for the diagnosis of colorectal polyp and cancer

Diffusion-weighted whole-body imaging with background body signal suppression/T2 image fusion (DWIBS/T2) is useful for the diagnosis of cancer as it presents a clear contrast between cancerous and non-cancerous tissue. The present study investigated the limitations and advantages of DWIBS/T2 with regards to the diagnosis of colorectal polyp (CP) or cancer (CRC). The current study included patients diagnosed with CP or CRC following colonoscopy, who were subjected to DWIBS/T2 between July 2012 and March 2015. Patient records were analyzed retrospectively. Patients were subjected to DWIBS/T2 when they presented with abdominal cancers or inflammation. Colonoscopy was performed as part of screening, or if patients had suspected colon cancer or inflammatory bowel disease. A total of 8 male and 7 female patients were enrolled in the present study. All patients, with the exception of one who had been diagnosed with CRC following colonoscopy, had positive results and all patients diagnosed with CP following a colonoscopy, with the exception of one, had negative results on DWIBS/T2. Thus, CRC was detected by DWIBS/T2, while CP was not (P=0.0028). The diameter of CRC lesions was significantly larger than that of CP (P<0.0001) and that of lesions positive on DWIBS/T2 was significantly larger than that of negative lesions (P=0.0004). The depth of invasion tended to be greater for lesions positive on DWIBS/T2 compared with that of negative ones. This indicated that DWIBS/T2 may be suitable for the detection of CRC but not for detection of CP. The results of DWIBS/T2 may also be affected by lesion diameter and depth of invasion.

Diagnostic accuracy of diffusion-weighted whole-body imaging with background body signal suppression/T2-weighted image fusion for the detection of abdominal solid cancer

Diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) images show significant contrast for cancer tissues against non-cancerous tissues. Fusion of a DWIBS and a T2-weighted image (DWIBS/T2) can be used to obtain functional, as well as anatomic, information. In the present study, the performance of DWIBS/T2 in the diagnosis of abdominal solid cancer was evaluated. The records of 14 patients were retrospectively analyzed [5 patients with hepatocellular carcinoma (HCC), 4 with metastatic liver cancer, 3 with pancreatic cancer, 1 with renal cellular carcinoma and 1 with malignant lymphoma of the para-aortic lymph node]. T1WI and T2WI scans did not detect pancreatic cancer in certain cases, whereas DWIs and DWIBS/T2 clearly demonstrated pancreatic cancer in all cases. In addition, metastatic liver cancer and HCC were successfully detected with abdominal US and CECT; however, US did not detect pancreatic cancer in 1 case, while CECT and DWIBS/T2 detected pancreatic cancer in all cases. In conclusion, the diagnostic performance of DWIBS/T2 was the same as that of abdominal US and CECT in detecting primary and metastatic liver cancer. DWIBS/T2 enabled the diagnosis of pancreatic cancer in cases where it was not detected with US, T1WI or T2WI.

Unenhanced areas revealed by contrast-enhanced abdominal ultrasonography with SonazoidTM potentially correspond to colorectal cancer

The present study investigated the potential utility of contrast-enhanced abdominal ultrasonography (CEUS), using Sonazoid™, in colorectal cancer (CRC). Three patients were subjected to CEUS with Sonazoid™. Surgical specimens were immunostained for CD31. Numbers of blood vessels positive for CD31 were analyzed in each of five fields at ×400 magnification and averaged to determine blood vessel density. Blood vessel density was compared between non-tumorous and tumorous areas. Prior to the administration of Sonazoid™, CRC was illustrated as irregular-shaped wall thickening. One minute after the administration of Sonazoid™, the majority of the thickened wall was enhanced, while some parts of the thickened wall remained unenhanced. Blood vessel densities of non-tumorous and tumorous areas in patient two were 25.2±2.5 and 5.2±1.1 (P<0.0001). Blood vessel densities of non-tumorous and tumorous areas in patient three were 19.0±3.1 and 2.2±0.8 (P<0.0001). Tumorous areas of CRC were not enhanced 1 min after the administration of Sonazoid™. Blood vessel density was lower in tumorous areas compared with non-tumorous areas, as evidenced by immunohistochemistry for CD31. These findings suggest that CEUS may be useful for the determination of the extent of CRC.