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1
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Biancotti R, Dal Pozzo CA, Parente P, Businello G, Angerilli V, Realdon S, Savarino EV, Farinati F, Milanetto AC, Pasquali C, Vettor R, Grillo F, Pennelli G, Luchini C, Mastracci L, Vanoli A, Milione M, Galuppini F, Fassan M. Histopathological Landscape of Precursor Lesions of Gastro-Entero-Pancreatic Neuroendocrine Neoplasms. Dig Dis 2022; 41:34-48. [PMID: 35816999 DOI: 10.1159/000525421] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Accepted: 05/12/2022] [Indexed: 02/02/2023]
Abstract
BACKGROUND Despite the important advances in research on neuroendocrine neoplasms of the gastro-entero-pancreatic tract, their precursor lesions are much less well known. SUMMARY This review analyzes the preneoplastic neuroendocrine lesions of the gastro-entero-pancreatic tract, by adopting a coherent anatomical benchmark. In particular, the settings in which neuroendocrine precursor lesions represent well-recognized pathophysiological and morphological entities (with eventual molecular correlates) have been distinguished from the ones in which the nature of preneoplastic changes is still obscure. KEY MESSAGES The aim of the paper was to summarize what is known about precursor lesions of gastro-entero-pancreatic neuroendocrine tumors, with the goal of providing a useful tool for future research aimed at obtaining a fuller understanding of the underlying biology and early development of these diseases.
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Affiliation(s)
- Rachele Biancotti
- Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy
| | | | - Paola Parente
- Pathology Unit, Fondazione IRCCS Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
| | - Gianluca Businello
- Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy
| | - Valentina Angerilli
- Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy
| | | | - Edoardo Vincenzo Savarino
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Fabio Farinati
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Anna Caterina Milanetto
- Division of Surgery, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Claudio Pasquali
- Division of Surgery, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Roberto Vettor
- Endocrine-Metabolic Laboratory, Department of Medicine (DIMED), University of Padua, Padua, Italy
- Center for the Study and the Integrated Management of Obesity, Padua University Hospital, Padua, Italy
| | - Federica Grillo
- Anatomic Pathology Unit, Department of Surgical Sciences and Integrated Diagnostics (DICS), University of Genova, Genova, Italy
- Ospedale Policlinico San Martino, IRCCS for Oncology and Neuroscience, Genova, Italy
| | - Gianmaria Pennelli
- Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy
| | - Claudio Luchini
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy
| | - Luca Mastracci
- Anatomic Pathology Unit, Department of Surgical Sciences and Integrated Diagnostics (DICS), University of Genova, Genova, Italy
- Ospedale Policlinico San Martino, IRCCS for Oncology and Neuroscience, Genova, Italy
| | - Alessandro Vanoli
- Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia and Fondazione IRCCS San Matteo Hospital, Pavia, Italy
| | - Massimo Milione
- 1st Pathology Division, Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Francesca Galuppini
- Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy
| | - Matteo Fassan
- Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy
- Veneto Institute of Oncology (IOV-IRCCS), Padua, Italy
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2
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Fu ZY, Kmeid M, Aldyab M, Lagana SM, Lee H. Composite intestinal adenoma-microcarcinoid: An update and literature review. World J Gastrointest Endosc 2021; 13:593-606. [PMID: 35070021 PMCID: PMC8716980 DOI: 10.4253/wjge.v13.i12.593] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 10/19/2021] [Accepted: 11/28/2021] [Indexed: 02/06/2023] Open
Abstract
Composite intestinal adenoma-microcarcinoid (CIAM) is a rare intestinal lesion consisting of conventional adenoma and small, well differentiated carcinoid [microcarcinoid (MC)] at its base. The incidence of CIAM is 3.8% in surgically resected colorectal polyps. While its pathogenesis is unknown, studies support the role of Wnt/β-catenin pathway in the tumorigenesis of CIAM. CIAMs have been primarily reported in the colon wherein they present as polyps with well-defined margins, similar to conventional adenomatous polyps. MC is usually found in adenomatous polyps with high-risk features such as large size, villous architecture, or high grade dysplasia. Histologically, the MC component is often multifocal and spans 3.9 to 5.8 millimeters in size. MC is usually confined within the mucosa but occasional CIAM cases with MC extending to the submucosa have been reported. MC of CIAM demonstrates bland cytology and inconspicuous proliferative activity. The lesional cells are positive for synaptophysin and 60% to 100% of cases show nuclear β-catenin positivity. MC poses a diagnostic challenge with its morphologic and immunohistochemical resemblance to both benign and malignant lesions, including squamous morules/metaplasia, adenocarcinoma, squamous cell carcinoma, sporadic neuroendocrine tumor and goblet cell adenocarcinoma. CIAM is an indolent lesion with a favorable outcome. Complete removal by polypectomy is considered curative. Awareness and recognition of this rare entity will help arrive at correct diagnosis and improve patient care. Currently, CIAM is not recognized as a subtype of mixed neuroendocrine-non-neuroendocrine neoplasm by WHO.
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Affiliation(s)
- Zhi-Yan Fu
- Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY 12208, United States
| | - Michel Kmeid
- Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY 12208, United States
| | - Mahmoud Aldyab
- Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY 12208, United States
| | - Stephen M Lagana
- Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY 10032, United States
| | - Hwajeong Lee
- Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY 12208, United States
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Huang AC, Montiel-Esparza R, Scott G, Martin B, Bruzoni M, Kadapakkam M, Namjoshi SS. A Novel Case of Carcinoid Tumor in a Pediatric Patient With Short Bowel Syndrome Secondary to Gastroschisis. JPGN REPORTS 2020; 1:e023. [PMID: 37206611 PMCID: PMC10191495 DOI: 10.1097/pg9.0000000000000023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Accepted: 09/13/2020] [Indexed: 05/21/2023]
Affiliation(s)
- Alice C. Huang
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Lucile Packard Children’s Hospital, Palo Alto, California
| | - Raul Montiel-Esparza
- Department of Pediatric Hematology and Oncology, Lucile Packard Children’s Hospital, Palo Alto, California
| | - Gregory Scott
- Department of Pathology, Lucile Packard Children’s Hospital, Palo Alto, California
| | - Brock Martin
- Department of Pathology, Lucile Packard Children’s Hospital, Palo Alto, California
| | - Matias Bruzoni
- Department of Pediatric Surgery, Lucile Packard Children’s Hospital, Palo Alto, California
| | - Meena Kadapakkam
- Department of Pediatric Hematology and Oncology, Lucile Packard Children’s Hospital, Palo Alto, California
| | - Shweta S. Namjoshi
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Lucile Packard Children’s Hospital, Palo Alto, California
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Etienne D, Ofosu A, Ona MA, Reddy M. Microcarcinoid and Ulcerative Colitis: Case Report and Literature Review. Cureus 2020; 12:e8803. [PMID: 32724749 PMCID: PMC7381878 DOI: 10.7759/cureus.8803] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Gastrointestinal microcarcinoid tumors are rare, and the concomitant diagnosis of microcarcinoid tumor and inflammatory bowel disease is even rarer. A 54-year-old African American male with an eight-year history of ulcerative colitis (UC) presented with a three-day history of abdominal pain and bloody diarrhea. Rectal biopsy on colonoscopy was notable for small nests of neuroendocrine cell proliferation in the mucosa consistent with a diagnosis of microcarcinoid tumor. Whether the incidence is coincidental or represents an epiphenomenon of chronic inflammation remains to be determined.
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Affiliation(s)
- Denzil Etienne
- Gastroenterology and Hepatology, The Brooklyn Hospital Center, Academic Affiliate of the Icahn School of Medicine at Mount Sinai, Clinical Affiliate of the Mount Sinai Hospital, Brooklyn, USA
| | - Andrew Ofosu
- Gastroenterology, The Brooklyn Hospital Center, Affiliate of the Mount Sinai Hospital, Brooklyn, USA
| | - Mel A Ona
- Gastroenterology and Hepatology, Pali Momi Medical Center, Honolulu, USA
| | - Madhavi Reddy
- Gastroenterology and Hepatology, The Brooklyn Hospital Center, Affiliate of the Icahn School of Medicine at Mount Sinai, Brooklyn, USA
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Colorectal microcarcinoids in association with long-term exposure to urinary content: a case report and review of the literature. Case Rep Pathol 2015; 2015:806310. [PMID: 25922778 PMCID: PMC4398929 DOI: 10.1155/2015/806310] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2015] [Accepted: 03/16/2015] [Indexed: 12/20/2022] Open
Abstract
Long-term exposure of colonic mucosa to urinary content and its association with increased risk of infection, mechanical and biochemical irritation, and malignancy have been described in the literature. Existing case reports and studies depict the low but distinct risk of malignancy in gastrointestinal segments which come in contact with urinary content as a result of surgical correction of urinary tract abnormalities. However, these reports are largely limited to colonic adenocarcinoma and urothelial cell carcinoma. Late urointestinal carcinoma in patients with ileal incorporation into the urinary tract has also been reported. To the best of our knowledge, however, there is only one case report documenting neuroendocrine (NE) cell hyperplasia in colonic mucosa after long-term cystoplasty. Our case is the first to describe microcarcinoids and diffuse NE hyperplasia occurring in a patient with congenital anorectal anomalies, resulting in long-term exposure of colonic mucosa to fecal stream and urinary content. This case, in conjunction with the reported cases in the literature, raises the distinct possibility of an association between exposure of colonic mucosa to urine and long-term development of malignancy, including NE neoplasms.
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Khor TS, Fujita H, Nagata K, Shimizu M, Lauwers GY. Biopsy interpretation of colonic biopsies when inflammatory bowel disease is excluded. J Gastroenterol 2012; 47:226-48. [PMID: 22322659 DOI: 10.1007/s00535-012-0539-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2012] [Accepted: 01/18/2012] [Indexed: 02/04/2023]
Abstract
The interpretation of colonic biopsies related to inflammatory conditions can be challenging because the colorectal mucosa has a limited repertoire of morphologic responses to various injurious agents. Only few processes have specific diagnostic features, and many of the various histological patterns reflect severity and duration of the disease. Importantly the correlation with endoscopic and clinical information is often cardinal to arrive at a specific diagnosis in many cases.
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Affiliation(s)
- Tze S Khor
- Gastrointestinal Pathology Service, Department of Pathology, Massachusetts General Hospital, Warren 219, Boston, MA, USA.
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Borralho P, Vieira A, Loureiro R, Pereira PM, de Freitas J. Microcarcinoids associated with diversion colitis in a patient with Crohn's disease. J Crohns Colitis 2008; 2:246-9. [PMID: 21172219 DOI: 10.1016/j.crohns.2008.05.006] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2008] [Accepted: 05/06/2008] [Indexed: 02/08/2023]
Abstract
Diversion colitis is an iatrogenic disorder related to surgical diversion of the faecal stream from the colorectal mucosa, first described by Morson in 1972. Inflammation of the defunctioned mucosa seems to be related to deprivation of luminal nutrients, in particular short chain fatty acids. Histologic abnormalities include damage of the epithelium and reparative changes with crypt distortion and branching, a mixed acute and chronic inflammatory infiltrate with crypt abscesses and lymphoid hyperplasia, Paneth cell metaplasia and thickening of the muscularis mucosae. We report a case of diversion colitis in a 51-year-old female with Crohn's disease with multiple submucosal microcarcinoids in the rectal stump 17 years after diversion and discuss the hypothesis that hyperplastic and neoplastic lesions of neuroendocrine cells can result from proliferative response to chronic inflammation and repair, as well as epithelial neoplasms.
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Affiliation(s)
- Paula Borralho
- Department of Anatomical Pathology, Garcia de Orta Hospital, Almada, Portugal
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Abstract
Composite adenoma-carcinoid tumors are rare colorectal lesions consisting of intermingled adenomatous and carcinoid components. Unlike other mixed endocrine-glandular colorectal neoplasms, which are generally malignant, their glandular component is histologically benign and their natural history is favorable. We present 4 cases of colonic adenomas containing microcarcinoids, a hitherto undescribed lesion that is either a precursor of composite adenoma-carcinoids or a related but independent entity. The cases, identified among our surgical and consultation files, were endoscopically routine sessile polyps removed from 4 otherwise normal individuals, 3 from the cecum and 1 from the distal colon. The microcarcinoids were 0.5 to 1.5 mm in size and situated within the basal lamina propria, where they interposed between the crypts and muscularis mucosae without disturbing the overall polyp architecture. Histologically, they consisted of collections of low-grade epithelial cells arranged in nests, cords, tubules, and irregular clusters and characterized by eosinophilic, granular, or clear cytoplasm and by round central nuclei with stippled or dusty chromatin. Endocrine differentiation of the microcarcinoids was confirmed by the expression of 3 or more of the following: Grimelius argyrophil, chromogranin, synaptophysin, neuron-specific enolase and somatostatin. No mitotic figures or MIB-1 or p53 positivity were observed. The glandular component of the polyps was unremarkable in 3 cases, but 1 polyp, in addition to a microcarcinoid, showed a diffuse pattern of mixed adenomatous-endocrine differentiation. The patients' clinical course was benign on the basis of 2 years' median follow-up (range, 6 mo to 10 y). Two patients with incomplete polypectomies underwent hemicolectomy revealing no residual endocrine neoplasia. Awareness of microcarcinoids in colonic adenomas should help avert potential diagnostic pitfalls posed by their pleomorphism, basal location, and infiltrative patterns, and may help clarify their natural history and possible relationship to composite glandular-carcinoid tumors.
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Affiliation(s)
- Melissa Pulitzer
- Department of Pathology, Division of Gastrointestinal Pathology, The Mount Sinai School of Medicine, New York, NY 10029, USA
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Abstract
This review focuses on precursor lesions of gastrointestinal and pancreatic neuroendocrine tumors (GEP-NETs). There are three conditions that are associated with hyperplastic changes in endocrine cells preceding GEP-NETs: autoimmune chronic atrophic gastritis or multiple endocrine neoplasia type 1 (MEN1) with gastric enterochromaffin-like (ECL) cell hyperplasia; MEN1 with gastrin and somatostatin cell hyperplasia in the duodenum and glucagon cell hyperplasia in the islets of the pancreas; and inflammatory bowel disease with endocrine cell hyperplasia in the colon. In gastric ECL cell hyperplasia, it is assumed that hypergastrinemia promotes the growth of the ECL cells of the corpus mucosa and leads to hyperplasia and neoplasia. In the duodenum and the pancreas, the MEN1-associated germline mutation of the menin gene obviously causes hyperplasia of the gastrin and somatostatin cells (duodenum) and the glucagon cells (pancreas), resulting in multifocal development of tumors. These tumors show allelic deletion of the MEN1 gene, whereas the precursor lesions retain their heterozygosity. The endocrine cell hyperplasia in the colon described in inflammatory bowel disease has neither a genetic nor a definite hormonal background.
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Affiliation(s)
- Günter Klöppel
- Department of Pathology, University of Kiel, Michaelisstr. 11, 24105, Kiel, Germany.
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