Frequent GNAS and KRAS mutations in pyloric gland adenoma of the stomach and duodenum

Gastric and duodenal adenomas exhibit a significant morphological and phenotypical diversity and are classified into intestinal‐type, foveolar‐type and pyloric gland adenomas. We analysed the mutations in GNAS, KRAS, BRAF and CTNNB1 and the expressions of mismatch repair (MMR) proteins in 80 gastric and 32 duodenal adenomas with histologically distinct subtypes, as well as in 71 gastric adenocarcinomas. Activating GNAS mutations were found in 22 of the 35 pyloric gland adenomas (PGAs; 63%) but in none of the foveolar‐type or intestinal‐type adenomas or the adenocarcinomas. Fourteen PGAs (41%), two foveolar‐type adenomas (9%), five intestinal‐type adenomas (9%) and one adenocarcinoma (1%) had KRAS mutations. BRAF mutations were absent in all the adenomas and adenocarcinomas that were examined. CTNNB1 mutations were only found in two intestinal‐type adenomas (4%). Notably, 13 of the 14 KRAS‐mutated gastric and duodenal PGAs had concurrent GNAS mutations. The loss of the MMR proteins, which is indicative of microsatellite instability, was observed in one PGA (3%), 12 foveolar‐type adenomas (52%), one intestinal‐type adenoma (2%) and five adenocarcinomas (7%). These observations indicate that each histological subtype of gastric and duodenal adenomas has a distinct genetic background. In particular, the present study identified the frequent presence of activating GNAS mutations, which are often associated with KRAS mutations, as a characteristic genetic feature of PGAs of the stomach and duodenum.     

Oxyntic gland polyp/adenoma

Gastric oxyntic gland polyp/adenomas, OGA are uncommon polypoid lesions that arise from oxyntic mucosa located in the body and fundus of the stomach. A case of oxyntic gland polyp/adenoma with typical histological and immunohistochemical features is presented and controversy over nomenclature and biological behavior is discussed.     

Gastric dysplasia and adenomas: how it all MAPS out!

Gastric polyps can be truly neoplastic but most polypoid dysplastic lesions are manifestations of gastritis-associated dysplasia that happens to form a polypoid lesion rather than true adenomas arising in normal background mucosa as is typically observed in the colon. However, the term adenoma has been used over the years to describe polyps with intestinal and pyloric gland differentiation, and this terminology is entrenched in our lexicon. In this review, we briefly discuss the issue of terminology, gastritis, and the following polyp types: intestinal type adenoma, pyloric gland adenoma, foveolar adenoma, and oxyntic gland adenoma (also termed oxyntic gland neoplasm and adenocarcinoma of fundic gland type.     

Molecular pathogenesis of adenoma and differentiated adenocarcinoma of the stomach

Advances In molecular biology have revealed a consistent set of genetic aiterations that may correspond to multistep tumor development. The pathogenesis of adenoma and differentiated adenocarcinoma of the stomach are reviewed from a genetic perspective with reference to the colorectal adenoma-carcinoma sequence. The sequential accumulation of genetic alterations characteristic of the colorectal adenoma-carclnoma sequence does not occur between sdenoma and differentiated adenocarclnoma of the stomach, although adenomatous polyposis coli (Am) mutation in adenoma, and p53 mutation and loss of heterozygosity (LOH) of DCC (deleted In colorectal cancer) gene in carcinoma are prevalent genetlc alterations. Allelotype, LOH and micro-satelllte anatyses have revealed several chromosomal regions of ddetlon, as well as genetic Instability, that accumulate during the development and progression of differentiated adenocarcinomas. However, these alterations are rarely found In adenomas of the stomach. These findings suggest that the adenoma-carcinoma sequence Is relatively rare in gastric carcinogenesis, and that most differentiated adenocarcinomas of the stomach develop through a de novo pathway.     

The discrete nature and distinguishing molecular features of pancreatic intraductal tubulopapillary neoplasms and intraductal papillary mucinous neoplasms of the gastric type,pyloric gland variant

Intraductal tubulopapillary neoplasms (ITPNs) are composed of tubulopapillary glands with high‐grade dysplasia in the pancreatic duct. Intraductal papillary mucinous neoplasms of the gastric type, pyloric gland variant (IPMN‐PGs) are composed of tubular glands mimicking pyloric glands with low‐grade dysplasia and were formerly called intraductal tubular adenomas. Because of their apparent common tubular morphology, IPMN‐PGs and ITPNs could be associated. While the former might progress to the latter, this has not been fully assessed. In this study, we compared the molecular features of ITPNs and IPMN‐PGs to determine their association using formalin‐fixed, paraffin‐embedded tissues of 14 ITPNs and 15 IPMN‐PGs. Somatic mutations in PIK3CA, GNAS, KRAS, and BRAF were determined by Sanger sequencing. Expression of phosphorylated AKT was examined by immunohistochemistry. Somatic PIK3CA mutations were found in 3 of 14 ITPNs (21.4%) but in none of the IPMN‐PGs (p = 0.0996). In contrast, GNAS mutations were found in none of the ITPNs but in 9 of 15 IPMN‐PGs (60.0%; p < 0.001). KRAS mutations were detected in 1 of 14 ITPNs (7.1%) and 12 of 15 IPMN‐PGs (80.0%; p < 0.001). BRAF mutation was found in one ITPN but in none of the IPMN‐PGs. Phosphorylated AKT expression in ITPNs was significantly more evident than that in IPMN‐PGs (p = 0.0401). These results indicate that ITPNs and IPMN‐PGs are molecularly distinct, suggesting that IPMN‐PG does not progress to ITPN. Furthermore, the molecular features of IPMN‐PGs are confirmed to be identical to those of IPMNs reported elsewhere. These results validate the current World Health Organization system that classifies pancreatic intraductal neoplasms into IPMN and ITPN and confirm that IPMN‐PG is not a benign counterpart of ITPN. The term ‘intraductal tubular adenoma’ should be eliminated and replaced with IPMN‐PG. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Pathology of seven mucous cell adenomas of the bronchial glands with particular reference to ultrastructure

The pathology, including ultrastructure, of seven mucous cell adenomas of the bronchial glands is described. They occurred as polypoid intraluminal lesions in both male and female patients between the ages of 7 and 55 years (mean 26 years). Histologically they were all benign and consisted of predominantly mucus-secreting cells arranged in acini or ducts or in solid groups. A little squamous differentiation was evident in four cases, insufficient in our opinion, to justify the term mucoepidermoid tumour. By electron microscopy, many tumour cells resembled mucous cells of the bronchial glands, containing typical large mucous granules of finely granular, reticular or fibrillated material, and sometimes small electron-dense bodies. In four cases some cells showed both secretory granules and features of squamous differentiation such as numerous tonofilaments and desmosomes. Oncocytic differentiation was seen occasionally.     

涎腺基底细胞腺瘤和腺癌与腺样囊性癌的比较观察

目的 研究涎腺基底细胞腺瘤和基底细胞腺癌与腺样囊性癌的形态学特征、免疫表型和鉴别诊断。方法 对5例基底细胞腺瘤，5例基底细胞腺癌和7例腺样囊性癌进行了免疫组化和双重免疫电镜(2例)的观察。结果 基底细胞腺瘤和基底细胞腺癌在免疫表型方面非常相似；基底细胞腺瘤(癌)与腺样囊性癌之间在免疫表型和超微结构方面有一定的差别。结论 基底细胞腺瘤和基底细胞腺癌的鉴别诊断基于两者的生长方式和组织学特征。免疫组化和免疫电镜观察有助于基底细胞腺瘤(癌)与腺样囊性癌的鉴别诊断。     

Significance of GLUT1 expression in adenocarcinoma and adenoma of the ampulla of Vater

The expression of glucose transporter protein 1 (GLUT1) in malignant tumors is increased due to the higher metabolic needs of the proliferating cell populations. Aberrant GLUT1 expression is exhibited in a wide spectrum of epithelial malignancies and their precursors, which occur with low frequency and intensity; aberrant GLUT1 expression does not occur in normal epithelial cells. The expression of GLUT1 in tumors of the ampulla of Vater was evaluated on immunohistochemistry, and the relationships of GLUT1 expression to histological parameters and p53 expression were analyzed. Twenty-one (58.3%) of 36 adenocarcinomas and three (17.6%) of 17 adenomas had GLUT1 immunoreactivity. None of the regenerating or normal epithelia had any immunoreactivity. No significant relationships were found between GLUT1 expression and histological parameters or p53 expression. It was found that histological subtypes originated from different epithelium were strongly related to different macroscopic types. In the ampulla of Vater, GLUT1 expression was associated with malignant change, and might be a useful marker of malignancy.     

筛状结构为主的涎腺基底细胞腺瘤临床病理特征及免疫表型

目的探讨以筛状结构为主的涎腺基底细胞腺瘤(basal cell adenoma,BCA)的临床病理学及免疫表型特征。方法回顾性分析4例以筛状结构为主的涎腺BCA临床病史和病理学特征,采用免疫组化法检测CK、CK14、CK8/18、CK19、EMA、CD10、CD117、BCL-2、CDX-2、SMA、S-100、p63、p53、EGFR、Ki-67的表达。结果 4例以筛状结构为主的BCA均生长缓慢,分界清楚,无周围组织浸润,有被膜内浸润但未突破被膜,镜下见瘤组织中筛状结构占50%以上。免疫表型:肿瘤细胞中CK、EMA、CD10、CD117、BCL-2、CDX-2、p53、EGFR均呈(+),CK14、CK8/18、SMA、S-100均呈(),CK19和p63呈();Ki-67增殖指数<1%。结论以筛状结构为主的BCA较罕见,与腺样囊性癌(adenoid cystic carcinoma,ACC)不易区分,结合临床病理及免疫表型特征等可进行鉴别。     

Bidirectional gastric differentiation in cellular mucin phenotype (foveolar and pyloric) in serrated adenoma and hyperplastic polyp of the colorectum

This study examined whether gastric pyloric gland-type mucin is expressed in serrated adenoma (SA) and in hyperplastic polyp (HP) of the colorectum, and whether cellular position-based gastric differentiation is observed in these lesions as previously hypothesized. Immunostaining was performed for MUC6 and alpha-linked GlcNAc residue (pyloric gland-type mucin markers), human gastric mucin (HGM; foveolar-type mucin marker) and Ki-67 (proliferating cell marker) for 31 SA, 22 HP, 21 traditional tubular adenoma (TA) and 20 hyperplastic nodule (HN). MUC6 showed varying expression in SA, 22/31 (71.0%); HP, 15/22 (68.2%); TA, 2/21 (9.5%); and HN, 0/20 (0%) with significantly higher frequencies in SA and HP compared to those in TA and HN. The alpha-linked GlcNAc residue was found only in SA (3/31, 9.7%) and in HP (2/22, 9.1%). In SA and HP, HGM was typically expressed in the entire crypt length, but some reduction in expression was shown in the basal crypt portion below the proliferative zone. MUC6 and alpha-linked GlcNAc residues were expressed in the basal crypt portion below or below and including proliferative zone. These data demonstrate that SA and HP show bidirectional gastric (foveolar and pyloric gland) differentiation with respect to mucin cellular phenotype and the potential for cellular position-based differentiation, which mimics the gastric antral mucosa.     

Fine-needle aspiration cytology of basal cell adenoma of the parotid gland: characteristic cytological features and diagnostic pitfalls

We retrospectively studied the cytological features of aspiration cytology in 12 cases of basal cell adenoma (BCA) and 5 cases mistakenly diagnosed as BCA. On macroscopic findings, the 12 cases of BCA included 7 cases of solid type and 5 cases of cystic type. The characteristic cytological features of solid type BCA were three-dimensional clusters in 71%, sharp-angle small clusters in 86%, basement membrane- like material in 71%, and cell crush in 86%. In contrast, 3 of the 5 cystic type BCA cases showed inadequate cellular components or no basaloid tumor cells, and the cytological diagnosis of BCA could not be determined. In the 5 cases misdiagnosed as BCA, there were 2 cases of pleomorphic adenoma, 2 cases of benign lymphoepithelial cyst, and 1 case of basal cell adenocarcinoma. Accurate differential cytological diagnosis of BCA is relatively easy to determine the solid type BCA, but is more difficult for cystic type BCA.     

Cribriform adenocarcinoma of the minor salivary gland arising in the tonsil with metastasis to a cervical lymph node: A case report with description of fine needle aspiration cytology

Cribriform adenocarcinoma of minor salivary gland (CAMSG) is a rare tumor of the head and neck. We report a case of a 70‐year‐old female who presented with a 4–5‐month history of a left neck mass. CT scan of the neck showed a left neck mass just inferior to the angle of the mandible and left tonsillar prominence. Fine‐needle aspiration (FNA) of the neck mass showed epithelial groups with focal cribriform architecture. The cells had round to oval nuclei and fine chromatin. The background contained scattered lymphocytes. A preliminary diagnosis of low grade adenocarcinoma with cribriform features metastatic to a lymph node was made. Subsequent biopsy of the tonsil mass showed a tumor with a combination of tubular, solid, and papillary architecture containing round to ovoid nuclei with very fine chromatin, consistent with cribriform adenocarcinoma of the minor salivary gland. Cribriform adenocarcinoma of minor salivary gland has a documented tendency to metastasize to cervical lymph nodes. Since this neoplasm can cytologically and histologically resemble other neoplasms of the head and neck, including polymorphous low‐grade adenocarcinoma (PLGA), papillary thyroid carcinoma (PTC), and occasionally adenoid cystic carcinoma, being aware of and familiar with the cytologic features of CAMSG on FNA smears is important for patient management. Diagn. Cytopathol. 2017;45:468–471. © 2017 Wiley Periodicals, Inc.     

MUC5B、Villin、P53在胆囊黏膜幽门腺化生、肠上皮化生及胆囊腺癌中的表达及意义

目的：通过观察MUC5B、Villin、P53蛋白在胆囊黏膜幽门腺化生、肠上皮化生及胆囊腺癌的表达,探讨胆囊黏膜两种化生与胆囊腺癌发生的关系。方法：收集2013年1月至2015年1月兰州市第二人民医院病理科诊断的胆囊黏膜幽门腺化生40例、肠上皮化生40例及胆囊腺癌40例,采用免疫组化方法检测MUC5B、Villin、P53在胆囊黏膜幽门腺化生、肠上皮化生及胆囊腺癌的表达。结果：MUC5B在胆囊黏膜幽门腺化生、肠上皮化生、胆囊腺癌的阳性表达率分别为95.00%(38/40)、75.00%(30/40)、27.50%(11/40);Villin在三组中的阳性表达率分别为0.00%(0/40)、87.50%(35/40)、22.50%(9/40);P53在三组中的阳性表达率分别为2.50%(1/40)、7.50%(3/40)、80.00%(32/40)。各组间比较MUC5B在幽门腺及肠上皮化生的阳性表达率明显高于胆囊腺癌,差异有统计学意义(χ2=42.754,P=0.001);Villin在肠上皮化生的阳性表达率明显高于幽门腺化生及胆囊腺癌,差异有统计学意义(χ2=71.124, P=0.001);P53在胆囊腺癌中的阳性表达率明显高于幽门腺及肠上皮化生,差异有统计学意义(χ2=71.667,P=0.001)。MUC5B、Villin在幽门腺化生、肠上皮化生及胆囊腺癌的阳性表达率递减;P53在幽门腺化生、肠上皮化生及胆囊腺癌的阳性表达率递增。结论：幽门腺及肠上皮化生可能参与了胆囊腺癌的发生。