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Role of submucosal glands in the development and progression of carcinoma in Barrett's oesophagus
Melanie Johncilla 1,
Robert D Odze 2,
Agoston T Agoston 2
Affiliations expand
Abstract
Oesophagealsubmucosal glands secrete mucins and other chemicals that are believed to serve as protectants of the mucosal surface from luminal noxious agents, either ingested or refluxed. Changes in the type, distribution or number of submucosal glands may contribute to, or be associated with, the development of Barrett’s oesophagus and progression to cancer. The aim of this study was to investigate the anatomical, morphological and immunohistochemical characteristics of submucosal glands in Barrett’s oesophagus-associated neoplasia in 64 oesophageal resections for Barrett’s oesophagus-associated adenocarcinoma and 32 squamous cell carcinomas (as a control group). Gland density was not significantly different between the oesophageal adenocarcinoma (0.91/cm) and squamous cell carcinoma (0.81/cm) groups (p=0.7). In the oesophageal adenocarcinoma group, glands underlying Barrett’s oesophagus-associated neoplastic epithelium showed a significant decrease in the percentage of mucinous acini and a significant increase in the percentage of atrophic acini compared to glands underlying epithelium without dysplasia or carcinoma (74% vs 83%, p=0.03; and 24% vs 14%, p=0.01). There was also an increase in the percentage of glands with moderate to severe inflammation underlying neoplastic epithelium compared to glands underlying epithelium without dysplasia or carcinoma (53% vs 33%, p=0.001). None of these differences was seen in the squamous cell carcinoma group. The immunohistochemical characteristics of the different histological subtypes were also distinct. Atrophic and oncocyticacini were diffusely and strongly positive for CK7, SOX2, SOX9 and CK5/6 (a progenitor cell phenotype) while mucinous acini showed weak or moderate staining for those markers. Our results suggest that submucosal glands play a role in the progression of neoplasia, possibly by offering less protection to the mucosal surface of the oesophageal epithelium from chemical injury.
Esophagitis unrelated to reflux disease: current status and emerging diagnostic challenges
Melanie E Johncilla 1,
Amitabh Srivastava 2
Affiliations expand
Abstract
There has been much progress in our understanding of esophageal inflammatory disorders in the past few years. This is particularly true about esophageal eosinophilia and PPI responsiveness, lymphocytic esophagitis and motility disorders, and short-term risk of neoplasia in esophageal leukoplakia. The current review will summarize esophageal injury patterns that primarily occur due to non-reflux causes, with a focus on usual pitfalls in biopsy diagnosis and recent advances in our knowledge of the more common forms of esophagitis.
Keywords: Eosinophilic esophagitis; Esophagus; Histopathology; Inflammation; Leukoplakia; Lymphocytic esophagitis
Mutational landscape of goblet cell carcinoids and adenocarcinoma ex goblet cell carcinoids of the appendix is distinct from typical carcinoids and colorectal adenocarcinomas
Melanie Johncilla 1,
Matthew Stachler 1,
Joseph Misdraji 2,
Mikhail Lisovsky 3, Read More
Affiliations expand
Abstract
There is limited data on the spectrum of molecular alterations in goblet cell carcinoids and adenocarcinoma ex goblet cell carcinoids of the appendix. We used next generation sequencing to determine mutations of potential pathogenetic and therapeutic significance in this rare group of tumors. Adequate DNA was successfully extracted in 34/46 cases and the final group included 18 goblet cell carcinoids and 16 adenocarcinoma ex goblet cell carcinoids. IlluminaTruSeq™ was used for sequencing exons of a custom 282 gene panel using an IlluminaHiSeq 2000. All cases had a minimum coverage depth of at least 50 reads. After filtering through the Exome Sequencing Project, the number of mutations per case ranged from 0-9 (mean:3). The mutational burden in adenocarcinoma ex goblet cell carcinoids was significantly higher than goblet cell carcinoids (mean 5 vs. 3; p < 0.05) but the spectrum of alterations overlapped between the two groups. The most frequent mutations included ARID1A (4/34), ARID2 (4/34), CDH1 (4/34), RHPN2 (4/34), and MLL2 (3/34). Some mutations typically seen in conventional colorectal adenocarcinomas were also identified but with much lower frequency (APC :4/34; KRAS :2/34). MLL2 and KRAS mutations were only seen in adenocarcinoma ex goblet cell carcinoids and TP53 mutations were limited to poorly differentiated adenocarcinoma ex goblet cell carcinoids (2/34). Copy number changes could be evaluated in 15/34 cases and showed low copy number gains in CDKN1B (6/15) and NFKBIA (6/15), among others. The overlapping molecular alterations suggest that goblet cell carcinoids and adenocarcinoma ex goblet cell carcinoids are best considered two grades of differentiation of the same tumor rather than two distinct histological types. Mutations in TP53, CDH1 and MLL2 mutations were predominantly present in the adenocarcinoma ex goblet cell carcinoid group consistent with transformation to a higher grade lesion. The unique mutational profile also offers an explanation for the poor chemosensitivity in these tumors and highlights the need for developing new targeted therapies.
Soft tissue tumors of the sinonasal tract
Melanie Johncilla 1,
Vickie Y Jo 2
Affiliations expand
Abstract
Primary soft tissue tumors arising in the sinonasal tract are rare. While many mesenchymal neoplasms have been reported in the nasal cavity, sinuses, and nasopharynx, few are distinctive to this anatomic region. Some tumor types are relatively more common in this area, such as schwannoma and rhabdomyosarcoma. Nasopharyngeal angiofibroma and sinonasalhemangiopericytoma are unique entities of the sinonasal tract, as well as the recently characterized biphenotypicsinonasal sarcoma. This review discusses the clinical, morphologic, and immunohistochemical features and currently known molecular data of the more frequently encountered soft tissue tumors of the sinonasal tract.