Background Microsatellite instability (MSI) has been observed in 8-39 % of sporadic gastric cancers. However, despite numerous reports indicating a significant relationship between intestinal-type histology and MSI, detailed correlation between histological subtypes and MSI remains obscure. The purpose of the present study is to clarify the relationship between histological subtype and microsatellite status in gastric carcinomas. Methods Microsatellite status was examined for 464 consecutive gastric carcinomas from 420 patients as well as histological subtypes and other clinicopathological findings.Results MSI was observed in 82 carcinomas (17.7 %), and the greatest proportions were observed in solid-type, poorly differentiated adenocarcinoma (43.0 %) and papillary adenocarcinoma (32.5 %), both being significantly higher than those of other subtypes. The proportion increased with advancing age (0 % at 51-64 years, 8.5 % at 65-74 years, 18.4 % at 75-84 years, 35.3 % at 85-96 years). Compared with microsatellite-stable carcinomas, microsatellite-unstable carcinomas were significantly related with older age, female gender, antral location, and predominant papillary adenocarcinoma and solid-type, poorly differentiated adenocarcinoma. Poorly differentiated type carcinoma was significantly less frequent than differentiated type in microsatellite-unstable cancer at the early stage, whereas no significant difference existed at the advanced stage. Conclusions These results suggest that there are specific histological subtypes with highly frequent MSI and that gastric carcinoma with MSI originates from differentiatedtype carcinomas, indicating histological diversity during tumor growth.

Our ex vivo study suggests that DTI might be a useful tool for the diagnosis of myometrial invasion of uterine endometrial cancer ex vivo.

Aim: Elastic fiber deposition is a cause of irreversibility of liver fibrosis. However, to date, its relevance to clinical features has not yet been clarified. This study aimed to clarify the correlation between non-invasive markers of fibrosis and fiber quantity, including elastic fiber, obtained from computational analysis.Methods: This retrospective study included 270 patients evaluated by non-invasive liver fibrosis assessment prior to liver biopsy. Of these patients, 95 underwent magnetic resonance elastography (MRE) and 244 were assessed with Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA + -M2BP). Using whole-slide imaging of Elastica van Gieson-stained liver biopsy sections, the quantity of collagen, elastin, and total fiber (elastin + collagen) was determined.Results: The total fiber quantity showed significant linear correlation with fibrosis stage F0-F4. Collagen fiber quantity increased from stage F0 to F4, whereas elastic fiber quantity increased significantly only from stage F2 to F3. Spearman's rank correlation test revealed that non-invasive liver fibrosis assessment significantly correlates with each fiber quantity, including correlation between total fiber quantity and the Fibrosis-4 (FIB-4) index (r = 0.361, P < 0.001), WFA + -M2BP values (r = 0.404, P < 0.001), and liver stiffness value by MRE (r = 0.615, P < 0.001). Receiver operating characteristic (ROC) curve analyses revealed that the area under ROC for predicting higher elastic fiber (>3.6%) is 0.731 by FIB-4 index, 0.716 by WFA + -M2BP, and 0.822 by liver stiffness by MRE.Conclusion: Liver fibrosis correlates with fiber quantity through non-invasive assessment regardless of fiber type, including elastic fiber. Moreover, MRE is useful for predicting high amounts of elastic fiber.Correspondence: Professor Namiki Izumi, Department of Gastroenterology and Hepatology Musashino Red Cross Hospital 1-26-1 Kyonan-cho, Musashino-shi,

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Gastric neoplasms classified as high-grade dysplasia (HGD) by Western pathologists are frequently diagnosed as tubular adenocarcinoma in Japan. Here, we evaluated the prevalence of submucosal and lymphovascular invasion in a series of 125 endoscopically resected gastric neoplasms. On the basis of Western criteria, the lesions were classified as poorly cohesive carcinomas (n=4) (excluded from further analysis), low-grade dysplasia (n=4), pure HGD (n=78), HGD with tubular adenocarcinoma (n=4), and pure tubular adenocarcinoma (n=35). Submucosal invasion was found in 3.8% of the 78 HGDs, 75.0% of the 4 HGDs combined with adenocarcinoma, and 11.4% of the 35 adenocarcinomas. Venous invasion was detected in 1.3% of the 78 HGDs, 75% of the 4 HGDs combined with adenocarcinoma, and none of the 35 tubular adenocarcinomas. Lymphatic invasion was absent in HGD but noted in 25% of the HGDs combined with adenocarcinoma, and 2.9% of the tubular adenocarcinomas. Thus, we demonstrated that lesions characterized as HGD on the basis of Western criteria can be associated with submucosal and lymphovascular invasion. Endoscopic therapy has made it less crucial to differentiate between HGD and intramucosal adenocarcinoma in biopsy samples of small tubular neoplasms. However, it is important to recognize that the criteria for dysplasia currently used in the West may understate the degree of malignant potential. To limit any diagnostic discrepancy between biopsy, endoscopic resection, and surgical specimens, it is suggested that the features of HGD and adenocarcinoma be reevaluated, which may result in some lesions being classified as mucosal adenocarcinoma.

Objectives The diagnostic utility of En1 in the histopathologic differentiation of eccrine porocarcinoma (EPC) from invasive squamous cell carcinoma (SCC) was investigated. Methods Expression of En1 and CK19 in 16 cases of EPC was immunohistochemically examined and compared with that in 32 cases of SCC. Results In all 16 EPCs, En1 was expressed in 3% to 100% of tumor cells. In 20 of the 32 SCCs, En1 was expressed in 3% to 90% of tumor cells. A total of 13 of the 16 EPCs and five of the 32 SCCs were judged as En1 positive, with a cutoff value of 25%. In addition, 11 of the 16 EPCs and four of the 32 SCCs were CK19 positive. The frequencies of En1- and CK19-positive cases were significantly higher in EPCs than in SCCs. In a logistic regression analysis for predicting EPC, En1 and CK19 were independent markers. When expression patterns of En1 and CK19 were combined, none of the 32 SCCs was both positive. In contrast, 15 of the 16 EPCs were positive for either En1 or CK19. Conclusions A combination of En1 and CK19 expression can improve the accuracy of histologic diagnosis of EPC.

Patients with cancer of unknown primary (CUP) are generally treated with chemotherapy. Bone marrow involvement suggests an advanced stage, and CUP with disseminated carcinomatosis of the bone marrow (DCBM) appears to have a dismal prognosis. However, our case of CUP with DCBM was successfully treated with a sequence of endocrine therapy over a long period. A woman presenting with low back pain was found to have multiple bone metastasis without an identifiable primary tumor on imaging studies. Blood tests revealed anemia and thrombocytopenia. A bone marrow biopsy was performed and showed relatively uniform small cells, strongly positive for estrogen receptor and progesterone receptor expression. We considered chemotherapy to be risky due to bicytopenia and an aromatase inhibitor, letrozole, was initiated. The patient's symptoms and laboratory findings gradually improved and bone lesions almost disappeared on FDG-PET/CT after 1 year of treatment. After 2 years on letrozole, hemoglobin levels and platelet counts had been gradually decreasing. Although she had no symptoms and no significant changes were observed on a CT scan, disease progression was highly likely. Thus, second-line treatment with fulvestrant and palbociclib was commenced, and hemoglobin levels and platelet counts were restored to within the normal ranges. She currently continues to receive fulvestrant and palbociclib over a year later. CUP complicated with DCBM might be metastatic occult breast cancer, and endocrine therapy can be a valuable treatment option if tumors express hormone receptors.

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