Satoshi Nimura

Predictive histopathologic factors for lymph node metastasis in patients with nonpedunculated submucosal invasive colorectal carcinoma.

PURPOSERisk factors for lymph node metastasis in patients with nonpedunculated submucosal invasive colorectal carcinoma remain to be characterized. This study examines the relationship between lymph node metastasis and clinicopathologic factors in nonpedunculated submucosal invasive colorectal carcinoma.METHODSThe study cohort comprised 155 patients who had undergone surgical treatment for nonpedunculated submucosal invasive colorectal carcinoma. The clinicopathologic factors investigated included gender, age, tumor location, macroscopic type, tumor size, histologic type and grade, intramucosal growth pattern, lymphatic invasion, venous invasion, degree of focal dedifferentiation at the submucosal invasive front, status of the remaining muscularis mucosa, and the depth and width of submucosal invasion.RESULTSLymph node metastases were found in 19 patients (12.3 percent). Univariate analysis showed that lymphatic invasion, focal dedifferentiation at the submucosal invasive front, status of the remaining muscularis mucosa, and depth of submucosal invasion all had a significant influence on lymph node metastasis. Multivariate analysis showed lymphatic invasion (P = 0.014) and high-grade focal dedifferentiation at the submucosal invasive front (P = 0.049) to be independent factors predicting lymph node metastasis. No lymph node metastasis was found in tumors with a depth of submucosal invasion of <1.3 mm.CONCLUSIONSLymphatic invasion and high-grade focal dedifferentiation at the submucosal invasive front are important predictors of lymph node metastasis in patients with nonpedunculated submucosal invasive colorectal carcinoma. Depth of submucosal invasion can be used as an identifying marker for patients who do not require subsequent surgery after endoscopic resection.

Guidelines for endoscopic submucosal dissection and endoscopic mucosal resection for early gastric cancer

In response to the rapid and wide acceptance and use of endoscopic treatments for early gastric cancer, the Japan Gastroenterological Endoscopy Society (JGES), in collaboration with the Japanese Gastric Cancer Association (JGCA), has produced ‘Guidelines for ESD and EMR for Early Gastric Cancer’, as a set of basic guidelines in accordance with the principles of evidence‐based medicine. These Guidelines cover the present state of knowledge and are divided into the following seven categories: Indications, Preoperative diagnosis, Techniques, Evaluation of curability, Complications, Long‐term postoperative surveillance, and Histology. Twenty‐three statements were finally accepted as guidelines, and the majority of these were obtained from descriptive studies with lower evidence levels. A number of statements had to be created by consensus (the lowest evidence level), as evidence levels remain low for many specific areas in this field.

Pathological and immunohistological findings and genetic aberrations of intestinal enteropathy-associated T cell lymphoma in Japan

Takeshita M, Nakamura S, Kikuma K, Nakayama Y, Nimura S, Yao T, Urabe S, Ogawara S, Yonemasu H, Matsushita Y, Karube K & Iwashita A
(2011) Histopathology58, 395–407
Pathological and immunohistological findings and genetic aberrations of intestinal enteropathy‐associated T cell lymphoma in Japan

Adenosquamous Carcinoma of the Esophagus

Objectives: Adenosquamous carcinoma (ASC) of the esophagus is an uncommon form of esophageal cancer. Despite isolated case reports on this tumor type, no large clinicopathologic series appears to have been studied at a single institution. Methods: At our institution, 20 cases of ASC were diagnosed pathologically between 1970 and 2001 (20/2,056 total esophageal cancers; 1.0%). Excluding 2 patients who received preoperative radiation therapy, 18 were selected for review of their clinicopathologic features, including survival time, in comparison with those of patients with conventional squamous cell carcinomas (SCCs; n = 850) and adenocarcinomas (ACs; n = 40) of the esophagus. Results: The location and macroscopic type of the ASCs were similar to those of the SCCs. ASC tumors were significantly smaller than SCC (p = 0.004) and AC (p = 0.012) tumors, and the depth of invasion of ASCs was significantly less than that of SCCs (p = 0.028). Lymphatic permeation and blood vessel invasion were seen in 14 (77.8%) and 7 (38.9%) of the 18 patients with ASCs, respectively, and intraepithelial carcinoma contiguous to the main lesion was evident in 10 cases (56.6%). The cumulative postoperative survival rates of patients with ASC at 3, 5 and 10 years were 71.5, 63.6 and 47.7%, respectively, the outcome being significantly better than for patients with either SCC (p = 0.027) or AC (p = 0.013). Conclusion: In the esophagus, ASCs have better prognosis than conventional SCCs or ACs, probably due to their smaller size and lower stage.

High-grade dysplasia associated with fundic gland polyposis in a familial adenomatous polyposis patient, with special reference to APC mutation profiles

We report a patient with familial adenomatous polyposis who developed high-grade dysplasia against a background of fundic gland polyposis. Two large high-grade dysplasia lesions were found in the gastric body, where numerous fundic gland polyps were present. In both lesions, the dysplastic epithelium covered non-neoplastic oxyntic glands that occasionally exhibit cystic changes. A genetic analysis for APC (adenomatous polyposis coli) revealed a somatic 50-bp deletion involving codons 1502–1517 and 2-bp deletion at codon 1465 in each lesion of high-grade dysplasia. In contrast, six of the 18 fundic gland polyps were found to harbor an identical mutation: 1-bp insertion at codon 1556. Both lesions of high-grade dysplasia and the fundic gland polyps were similarly located in the fundic gland area and were caused by the inactivation of APC; however, their mutation profiles of APC were different. These results imply that fundic gland polyps and high-grade dysplasia of the stomach have distinct preferences for APC genotypes in their development.

Malignant mesothelioma of testicular tunica vaginalis

We report here a case with malignant mesothelioma of testicular tunica vaginalis. An 81‐year‐old Japanese man with left hydrocele was referred for operation. When hydrocelectomy was performed, a thick wall of tunica vaginalis without malignancy was observed. Seven months after hydrocelectomy, a hard irregular mass was noticed in the left scrotum, therefore inguinal orchiectomy was performed. Pathologically, the mass showed severe atypia and mitosis. The diagnosis of malignant mesothelioma was made. He refused any adjuvant treatment and died 1 year later from multiple metastases to the paraaortic lymph nodes and lumbar supine.

Dumbbell‐shaped leiomyosarcoma of the inferior vena cava with foci of rhabdoid changes and osteoclast‐type giant cells

An inferior vena cava (IVC) tumor was incidentally found in a 67‐year‐old Japanese man. The resected tumor was lobulated and multinodular, measuring 14.0 × 6.5 × 7.0 cm, showing a dumbbell‐shaped appearance with a central constriction. The tumor showed both intra‐ and extra‐luminal growth. The tumor was primarily composed of well‐differentiated leiomyosarcoma. Spindle tumor cells in the well‐differentiated area were positive for vimentin, muscle actin, α‐smooth muscle actin, and desmin. Foci of rhabdoid cells and osteoclast‐type multinucleated giant cells were also found. Rhabdoid cells ultrastructurally had paranuclear aggregates or whorls of intermediate filaments that were positive for vimentin, low molecular weight cytokeratin, and desmin. Osteoclast‐type multinucleated giant cells were positive for only CD68 antigen, suggesting a reactive histiocytic lineage. To the best of our knowledge, this is the first case of IVC leiomyosarcoma accompanied by both rhabdoid tumor cells and osteoclast‐type reactive multinucleated giant cells. These unusual features should be kept in mind in the diagnosis of dumbbell‐shaped retroperitoneal tumors that involve the IVC.

Detailed clinicopathological characteristics and possible lymphomagenesis of type II intestinal enteropathy-associated T-cell lymphoma in Japan

Twenty-six Japanese cases of type II enteropathy-associated T-cell lymphoma (EATL) were examined. Multiple tumors throughout the small intestine were found in 15 patients (58%) and duodenal and colonic mucosal lesions in 8 and 6 cases, respectively. Histologically, intramucosal tumor spread and a zone of neoplastic intraepithelial lymphocytes (IELs) neighboring the main transmural tumors were detected in 20 (91%) and 17 (77%) of the 22 cases examined, respectively. Inside and outside the IEL zone, some degree of enteropathy with many reactive small IELs and villous atrophy was detected in 11 cases (50%). Immunohistologically, many CD56/CD8-positive small IELs were found in the enteropathic lesions of 4 (36%) and 7 (64%) of these 11 cases. Lymphoma cells expressed tyrosine kinase receptor c-Met, serial phosphorylated (p)-mitogen-activated protein kinase/extracellular signal-regulated kinase, c-Myc, and Bcl2 in 18 (78%), 21 (91%), 11 (42%), and 19 (73%) of the total cases, respectively. By fluorescence in situ hybridization, chromosomal loci 7q31 (c-Met) and 8q24 (c-Myc) were amplified in 11 (65%) and 12 (71%) of the 17 cases analyzed. Gain of 7q31 and c-Met expression were significantly (P < .01) higher than in peripheral CD8-positive T-cell or CD56-positive natural killer-cell lymphomas. Enteropathy was seen near the IEL zone in type II EATL, and activation of the c-Met, mitogen-activated protein kinase/extracellular signal-regulated kinase-mitogen-activated protein kinase pathway, and c-Myc-Bcl2-mediated cell survival may play important roles in lymphomagenesis, converting enteropathy to type II EATL. Seven cases in the early clinical stages I and II-1 showed significantly (P < .01) better prognoses than did those in the advanced stages. Early detection of the mucosal lesions and tumors may improve patient prognosis.

Early colorectal carcinomas: CD10 expression, mucin phenotype and submucosal invasion

We analyzed 170 tumors (polypoid, 98; non‐polypoid, 72) of early colorectal carcinoma with or without submucosal invasions (Tis and T1 of TNM classification) from 161 patients to evaluate correlations between clinicopathological factors and immunohistochemical expressions of CD10, MUC2, and MUC5AC. The coexistence of adenomatous components was significantly less common in non‐polypoid carcinomas (4.2%) than in polypoid carcinomas (66.3%) (P < 0.0001). Non‐polypoid carcinomas were smaller in size and tended to infiltrate into the submucosa with higher incidence of lymphatic and venous permeations. CD10 was more frequently expressed in non‐polypoid carcinomas (70.8%) than in polypoid carcinomas (51.0%) (P= 0.01). Total carcinomas with high grade atypia showed higher incidence of CD10 expression (60.6%) than those with low grade atypia (28.9%) (P < 0.0001). Carcinomas with low grade atypia exhibited a higher incidence of MUC2 and MUC5AC expression (91.1% and 57.8%, respectively), when compared with carcinomas with high grade atypia (41.6% and 20.0%, respectively) (both, P < 0.0001). In submucosal invasive carcinomas with residual intramucosal carcinoma component (IMCC), CD10 expression in IMCC and submucosal invasive carcinoma component (SMCC) simultaneously exhibited identical positive or negative results, regardless of the polypoid or non‐polypoid growth pattern. The CD10 expression may occur in the early stage of carcinogenesis within the mucosa, and these neoplasms may retain CD10 in SMCC, possibly resulting in more advanced stages of stromal invasion and distant metastases. In conclusion, our data suggest that the CD10 expression and mucin phenotypes may be potentially useful markers for estimating biological properties of early colorectal carcinomas.

Clinicopathological characteristics of primary gastric T-cell lymphoma.

Aims:  To investigate the clinicopathological characteristics of 20 primary gastric T‐cell lymphoma (GTCL) cases without human T‐lymphotropic virus type I infection in Japan, a non‐endemic area for coeliac disease.