Composite intestinal adenoma-microcarcinoid clues to diagnosing an under-recognised mimic of invasive adenocarcinoma
ABSTRACT AIMS: Microcarcinoids refer to microscopic nests of monotonous cells with endocrine and squamoid features. Their peculiar morphology can appear infiltrative with a desmoplastic-like background, raising concerns for an infiltrating adenocarcinoma. To further characterise microcarcinoids, we undertook a prospective clinicopathological study. METHODS: 11 specimens originating from five men and six women (average age=58.9 years) were prospectively collected from December 2004 to December 2011. RESULTS: Microcarcinoids were most commonly identified in high-risk adenomas (size ≥10 mm (n=10), villous components (n=8) and/or high-grade dysplasia (n=4)). All polyps had mucosal prolapse and four displayed background fibrosis reminiscent of desmoplasia. The microcarcinoid component was most often multifocal (n=7) within the individual polyp and extended over an average length of 3.9 mm. The individual microcarcinoid cells were cuboidal with abundant eosinophilic cytoplasm. All cases had monotonous nuclei which lacked pleomorphism, hyperchromasia and mitotic activity. All available microcarcinoids were β-catenin and synaptophysin reactive and non-reactive for chromogranin and p53 with a negligible Ki-67 proliferation index (<2%). In addition, the microcarcinoids were variably reactive for p63 and/or CK 5/6, thereby demonstrating focal squamoid features. Two of the study cases were submitted with a concern for invasive carcinoma. Clinical information was available in 10 patients with up to 24 months of follow-up: all patients are alive and well and no subsequent malignancy has been reported. CONCLUSIONS: Awareness of this unique morphology is important to avoid overdiagnosing microcarcinoids as invasive adenocarcinoma. Moreover, this immunohistochemical panel can be helpful in discriminating microcarcinoids from its malignant mimic in challenging cases.
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ABSTRACT: The National Institute of Clinical Excellence (NICE) has recommended that neoadjuvant chemoradiotherapy (CRT) be administered to patients with advanced rectal adenocarcinoma prior to surgery (1). This induces tumour regression with c onsequent improved surgical outcome and patient survival (2, 3). Histologically, tumour regression can be roughly quantified using the Mandard Tumour Regression Grade(4) and studies have shown an association between histological regression and patient outcome (5). This article is protected by copyright. All rights reserved.Colorectal Disease 08/2013; DOI:10.1111/codi.12398 · 2.02 Impact Factor
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ABSTRACT: Low grade neuroendocrine tumors (NETs) arising in intestinal adenomas are rare. They are occasionally observed in patients with familial adenomatous polyposis (FAP), suggesting a role for the adenomatous polyposis coli (APC)/β-catenin pathway. We identified 25 composite adenoma/low grade NETs from colorectum (21) and duodenum (4) and evaluated their clinicopathologic features, survival, and nuclear β-catenin expression by immunohistochemistry. β-catenin staining was scored as % positivity x intensity (weak = 1, moderate = 2, strong = 3), for a total possible score of 300. Control groups included 1,781 adenomas without NET, 63 composite adenoma/high grade neuroendocrine carcinomas (NECs), and 32 sporadic NETs. Among 25 adenoma/low grade NETs, 4 (16%) occurred in patients with FAP. Size of the NET component ranged from 0.01-0.9 cm (mean, 0.32 cm). Most (84%) arose in “advanced” adenomas (size >1 cm, villous architecture [72%], or high grade dysplasia [56%]). In contrast, villous architecture and high grade dysplasia were present in only 14% (P < 0.001) and 7% (P < 0.001), respectively, of adenomas without NET. Overall survival with adenoma/low grade NET was significantly higher than adenoma/high grade NEC but significantly lower than sporadic NET (P < 0.001). Higher β-catenin expression was seen in adenoma/low grade NETs (mean score, 231) compared to sporadic NETs (mean score, 48; P < 0.0001) and adenoma/high grade NEC (mean score, 173; P = 0.04). In summary, composite adenoma/low grade NETs most commonly occur with advanced polyps, but the NET component itself is generally small and indolent. In contrast to sporadic NETs, the occurrence of these lesions in FAP and their high levels of nuclear β-catenin expression support a pathogenic role for the APC/β-catenin pathway.Human pathology 10/2014; 45(10). DOI:10.1016/j.humpath.2014.07.001 · 2.81 Impact Factor