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1
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Corradi C, Gentiluomo M, Adsay V, Sainz J, Camisa PR, Wlodarczyk B, Crippa S, Tavano F, Capurso G, Campa D. Multi-omic markers of intraductal papillary mucinous neoplasms progression into pancreatic cancer. Semin Cancer Biol 2025; 109:25-43. [PMID: 39733817 DOI: 10.1016/j.semcancer.2024.12.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Revised: 12/19/2024] [Accepted: 12/23/2024] [Indexed: 12/31/2024]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the most lethal and common form of pancreatic cancer, it has no specific symptoms, and most of the patients are diagnosed when the disease is already at an advanced stage. Chemotherapy typically has only a modest effect, making surgery the most effective treatment option. However, only a small percentage of patients are amenable to surgery. One viable strategy to reduce PDAC death burden associated with the disease is to focus on precursor lesions and identify markers able to predict who will evolve into PDAC. While most PDACs are believed to be preceded by pancreatic intraepithelial neoplasms (PanINs), 5-10 % arise from Intraductal papillary mucinous neoplasms (IPMNs), which are mass-forming cystic lesions that are very common in the general population. IPMNs offer an invaluable model of pancreatic carcinogenesis for researchers to analyse, as well as a target population for PDAC early detection by clinicians. The evolution of IPMN into cancer is a complex and multistep process, therefore the identification of individual markers will not be the solution. In recent years, multiple omics technologies have been instrumental to identify possible biomarkers of IPMN progression and carcinogenesis. The only foreseeable strategy will be to integrate multi-omics data, alongside clinical and morphological features, into a progression score or signature using either standard epidemiologic tools or artificial intelligence. The aim of this manuscript is to review the current knowledge on genetic biomarkers and to briefly mention also additional omics, such as metabolomics, the exposome, the miRNome and epigenomics of IPMNs.
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Affiliation(s)
| | | | - Volkan Adsay
- Department of Pathology, Koç University School of Medicine and Koç University Research Center for Translational Medicine, Istanbul, Turkey
| | - Juan Sainz
- Department of Biochemistry and Molecular Biology, University of Granada, Granada, Spain
| | - Paolo Riccardo Camisa
- Division of Pancreatic Surgery and Transplantation, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy
| | - Barbara Wlodarczyk
- Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland
| | - Stefano Crippa
- Division of Pancreatic Surgery and Transplantation, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy
| | - Francesca Tavano
- Division of Gastroenterology and Research Laboratory, Fondazione IRCCS "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo, Italy
| | - Gabriele Capurso
- Vita-Salute San Raffaele University, Milan, Italy; Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Daniele Campa
- Department of Biology, University of Pisa, Pisa, Italy.
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2
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Kelly P, Lauwers GY. Polyps and tumour‐like lesions of the stomach. MORSON AND DAWSON'S GASTROINTESTINAL PATHOLOGY 2024:195-226. [DOI: 10.1002/9781119423195.ch12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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3
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Mohamed Elfeky OW, Panjwani S, Cave D, Wild D, Raines D. Device-assisted enteroscopy in the surveillance of intestinal hamartomas in Peutz-Jeghers syndrome. Endosc Int Open 2024; 12:E128-E134. [PMID: 38292586 PMCID: PMC10827474 DOI: 10.1055/a-2197-8554] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Accepted: 10/24/2023] [Indexed: 02/01/2024] Open
Abstract
Background and study aims Peutz-Jeghers syndrome (PJS) is an autosomal-dominant genetic disorder characterized by the formation of hamartomatous polyps in the gastrointestinal tract. These polyps result in significant morbidity due to adverse events (AEs) including intestinal obstruction, bleeding, and malignancy. The aim of this study was to describe the role of device-assisted enteroscopy (DAE) in monitoring and prophylactic polypectomy within the small bowel. Patients and methods Electronic medical records were surveyed to identify all DAE procedures performed in patients with PJS at three US referral centers between January 1, 2007 and January 1, 2020. Individual charts were reviewed to collect and analyze specific data points. Primary end points included AEs associated with DAE-related polypectomy and the rate of laparotomy in PJS patients prior to, and following, index DAE. Secondary data points included patient characteristics, procedural details, and size/location/distribution of small bowel hamartomas. Results Twenty-three patients met our inclusion criteria. Of these, 18 (75%) had previously undergone small bowel surgery prior to index DAE. Between 2007 and 2020, 46 DAEs were performed in these patients with an average of one exam every 2.5 years. A total of 131 polypectomies were performed with an AE rate of 1.5%. None of our cohort required emergent surgery related to AEs of small bowel hamartomas over 336 years of aggregated follow-up. Conclusions Endoscopic management of small bowel polyps in patients with PJS using DAE is an effective strategy for prophylactic removal of hamartomas. DAE surveillance and endoscopic polypectomy is safe and may decrease the need for repeated laparotomy in patients with PJS.
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Affiliation(s)
| | - Suraj Panjwani
- Gastroenterology, University of Massachusetts Chan Medical School Department of Medicine, Worcester, United States
| | - David Cave
- Gastroenterology, University of Massachusetts Chan Medical School Department of Medicine, Worcester, United States
| | - Daniel Wild
- Gastroenterology, Duke University Medical Center, Durham, United States
| | - Daniel Raines
- Gastroenterology, LSU Health New Orleans, New Orleans, United States
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4
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Möslein G. [Management of the Peutz-Jeghers Syndrome]. Zentralbl Chir 2023; 148:492-501. [PMID: 37669766 DOI: 10.1055/a-2109-3140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/07/2023]
Abstract
The current evidence to guide management of Peutz-Jeghers Syndrome (PJS) is sparse. Here we summarise the European guidelines that were published in 2021 by the EHTG (European Hereditary Tumour Group), extended with new evidence on some aspects of clinical management that have been generated since then. EHTG with this revised guideline has updated and extended their own previous expert opinion guideline from 2010. For this purpose, all published literature was systematically screened and the level of evidence determined by using the GRADE methodology (Grading of Recommendations Assessment. Development and Evaluation). This was followed by a Delphi process and the consensus for a statement was achieved if the voting committee reached ≥ 80% approval.The only other more recently published guidelines encountered only addressed the clinical management of gastrointestinal and pancreatic manifestations of PJS. These recommendations were reviewed and adopted, since no further relevant literature was identified in the systematic literature search. However, additional questions were identified and formulated into recommendations after following the described process. It may be stated that 10 years after the predecessor guideline, new evidence has been sparse. As with all rare diseases, a call for more collaborative studies must here be made in order to improve patient management by addressing open clinical questions and generating collaborative evidence with increased case numbers, both nationally and internationally. With the limited published evidence, these European guidelines are the most current reference for management of PJS patients.
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Affiliation(s)
- Gabriela Möslein
- Zentrum für Hereditäre Tumore, Ev. BETHESDA Krankenhaus zu Duisburg, Duisburg, Deutschland
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5
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Zhou A, Tang B, Xie Y, Li S, Xiao X, Wu L, Tu D, Wang S, Feng Y, Feng X, Lai Y, Ning S, Yang S. Changes of gut microbiota and short chain fatty acids in patients with Peutz-Jeghers syndrome. BMC Microbiol 2023; 23:373. [PMID: 38036954 PMCID: PMC10688050 DOI: 10.1186/s12866-023-03132-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Accepted: 11/21/2023] [Indexed: 12/02/2023] Open
Abstract
Peutz-Jeghers Syndromeis a rare autosomal dominant genetic disease characterized by gastrointestinal hamartomatous polyps and skin and mucous membrane pigmentation. The pathogenesis of PJS remains unclear; however, it may be associated with mutations in the STK11 gene, and there is currently no effective treatment available. The gut microbiota plays an important role in maintaining intestinal homeostasis in the human body, and an increasing number of studies have reported a relationship between gut microbiota and human health and disease. However, relatively few studies have been conducted on the gut microbiota characteristics of patients with PJS. In this study, we analyzed the characteristics of the gut microbiota of 79 patients with PJS using 16 S sequencing and measured the levels of short-chain fatty acids in the intestines. The results showed dysbiosis in the gut microbiota of patients with PJS, and decreased synthesis of short-chain fatty acids. Bacteroides was positively correlated with maximum polyp length, while Agathobacter was negatively correlated with age of onset. In addition, acetic acid, propionic acid, and butyric acid were positively correlated with the age of onset but negatively correlated with the number of polyps. Furthermore, the butyric acid level was negatively correlated with the frequency of endoscopic surgeries. In contrast, we compared the gut microbiota of STK11-positive and STK11-negative patients with PJS for the first time, but 16 S sequencing analysis revealed no significant differences. Finally, we established a random forest prediction model based on the gut microbiota characteristics of patients to provide a basis for the targeted diagnosis and treatment of PJS in the future.
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Affiliation(s)
- An Zhou
- Department of Gastroenterology, Second Affiliated Hospital, Army Medical University, Chongqing, 400037, China
| | - Bo Tang
- Department of Gastroenterology, Second Affiliated Hospital, Army Medical University, Chongqing, 400037, China
| | - Yuhong Xie
- Department of Gastroenterology, Air Force Medical Center, Beijing, 100142, China
| | - Shengpeng Li
- Department of Gastroenterology, Second Affiliated Hospital, Army Medical University, Chongqing, 400037, China
| | - Xu Xiao
- Department of Gastroenterology, Second Affiliated Hospital, Army Medical University, Chongqing, 400037, China
| | - Lingyi Wu
- Department of Gastroenterology, Second Affiliated Hospital, Army Medical University, Chongqing, 400037, China
| | - Dianji Tu
- Department of Gastroenterology, Second Affiliated Hospital, Army Medical University, Chongqing, 400037, China
| | - Sumin Wang
- Department of Gastroenterology, Second Affiliated Hospital, Army Medical University, Chongqing, 400037, China
| | - Yunxuan Feng
- Department of Gastroenterology, Second Affiliated Hospital, Army Medical University, Chongqing, 400037, China
| | - Xiaojie Feng
- Department of Gastroenterology, Second Affiliated Hospital, Army Medical University, Chongqing, 400037, China
| | - Yi Lai
- Department of Gastroenterology, Second Affiliated Hospital, Army Medical University, Chongqing, 400037, China
| | - Shoubin Ning
- Department of Gastroenterology, Air Force Medical Center, Beijing, 100142, China.
| | - Shiming Yang
- Department of Gastroenterology, Second Affiliated Hospital, Army Medical University, Chongqing, 400037, China.
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6
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Liu BL, Ward SC, Polydorides AD. Clinicopathologic comparison between sporadic and syndromic Peutz-Jeghers polyps. Hum Pathol 2023; 141:69-77. [PMID: 37776958 DOI: 10.1016/j.humpath.2023.09.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Revised: 09/19/2023] [Accepted: 09/23/2023] [Indexed: 10/02/2023]
Abstract
Peutz-Jeghers polyps (PJPs) are hamartomatous polyps that may define patients with Peutz-Jeghers syndrome (PJS), a rare inherited polyposis syndrome with high cancer risk. However, the clinical significance of 1-2 sporadic PJPs (without other PJS stigmata) regarding malignant potential and identification of new PJS probands is still unclear. We identified 112 patients with 524 histologically confirmed PJPs and categorized them based on polyp number into syndromic (n = 38) if ≥3 PJPs or diagnosed PJS, solitary (1 PJP, n = 61), and intermediate (2 PJPs, n = 13). Clinicopathologic features, including presence of dysplasia in the polyp and development of neoplasia in the patient, were compared on a per-patient and per-polyp basis. Whereas patients with solitary and intermediate PJPs were not different from each other, patients with syndromic PJPs were, in multivariate analysis, younger (P = .001) and more likely to develop neoplasia (P = .02) over a 62.6-months median follow-up than patients with sporadic PJPs. On an individual polyp basis, syndromic PJPs were more likely, in multivariate analysis, to occur in the small intestine (P < .001), but less likely to harbor metaplasia (P = .03) or dysplasia (P = .001), than sporadic PJPs. Dysplasia and metaplasia were more likely in larger PJPs, by multivariate analysis (P = .007 and P < .001, respectively). These data suggest that strict criteria for PJS (including ≥3 PJPs), as currently used, stratify patients into distinct groups with significant differences in clinicopathologic parameters, particularly regarding risk of neoplasia. However, sporadic PJPs exhibit characteristics such as dysplasia and are thus important to recognize and diagnose but perhaps as heralding only a forme fruste PJS.
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Affiliation(s)
- Bella Lingjia Liu
- Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
| | - Stephen C Ward
- Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
| | - Alexandros D Polydorides
- Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
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7
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Hamada Y, Katsurahara M, Umeda Y, Ikenoyama Y, Shigefuku A, Fujiwara Y, Beppu T, Tsuboi J, Yamada R, Nakamura M, Tanaka K, Horiki N, Nakagawa H. Endoscopic resection for a solitary Peutz‐Jeghers type polyp in the duodenum: A case report with literature review. DEN OPEN 2023; 3:e226. [PMID: 36998347 PMCID: PMC10043356 DOI: 10.1002/deo2.226] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Revised: 02/22/2023] [Accepted: 03/08/2023] [Indexed: 03/30/2023]
Abstract
A 68‐year‐old female patient was referred to our hospital with a 30‐mm polyp in the second portion of the duodenum found via esophagogastroduodenoscopy. The polyp had an irregular, lobular surface and a thick stalk. In addition, white dots were detected on the surface. Magnifying endoscopy with narrow‐band imaging showed a white material deep in the loop‐shaped microvessels on the white dots. Endoscopic ultrasonography showed a hypoechoic elevated lesion from the mucosal layer, and a feeding vessel traversing the stalk to supply the head of the polyp. Endoscopic biopsy did not provide a definitive diagnosis. Endoscopic resection was conducted for a definitive diagnosis and treatment. The resected specimen showed a branching bundle of smooth muscle fibers covered by hyperplastic mucosa, consistent with a hamartomatous polyp. The patient had no mucocutaneous pigmentation or familial history of the hamartomatous polyp. The polyp was finally diagnosed as a solitary Peutz‐Jeghers‐type polyp. No recurrence has been observed for seven years postoperatively.
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Affiliation(s)
- Yasuhiko Hamada
- Department of Gastroenterology and HepatologyMie University HospitalTsuMieJapan
| | - Masaki Katsurahara
- Department of Gastroenterology and HepatologyMie University HospitalTsuMieJapan
| | - Yuhei Umeda
- Department of Gastroenterology and HepatologyMie University HospitalTsuMieJapan
| | - Yohei Ikenoyama
- Department of Gastroenterology and HepatologyMie University HospitalTsuMieJapan
| | - Akina Shigefuku
- Department of Gastroenterology and HepatologyMie University HospitalTsuMieJapan
| | - Yasuko Fujiwara
- Department of Gastroenterology and HepatologyMie University HospitalTsuMieJapan
| | - Tuyoshi Beppu
- Department of Gastroenterology and HepatologyMie University HospitalTsuMieJapan
| | - Junya Tsuboi
- Department of Gastroenterology and HepatologyMie University HospitalTsuMieJapan
| | - Reiko Yamada
- Department of Gastroenterology and HepatologyMie University HospitalTsuMieJapan
| | - Misaki Nakamura
- Department of Gastroenterology and HepatologyMie University HospitalTsuMieJapan
| | - Kyosuke Tanaka
- Department of Gastroenterology and HepatologyMie University HospitalTsuMieJapan
| | - Noriyuki Horiki
- Department of Gastroenterology and HepatologyMie University HospitalTsuMieJapan
| | - Hayato Nakagawa
- Department of Gastroenterology and HepatologyMie University HospitalTsuMieJapan
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8
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Long JM, Ebrahimzadeh J, Stanich PP, Katona BW. Endoscopic Surveillance in Patients with the Highest Risk of Gastric Cancer: Challenges and Solutions. Cancer Manag Res 2022; 14:2953-2969. [PMID: 36238953 PMCID: PMC9553156 DOI: 10.2147/cmar.s277898] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2022] [Accepted: 09/22/2022] [Indexed: 11/23/2022] Open
Abstract
Gastric cancer is one of the most significant causes of cancer-related morbidity and mortality worldwide. Recognized modifiable risk factors include Helicobacter pylori infection, geographic location, select dietary factors, tobacco use and alcohol consumption. In addition, multiple hereditary cancer predisposition syndromes are associated with significantly elevated gastric cancer risk. Endoscopic surveillance in hereditary gastric cancer predisposition syndromes has the potential to identify gastric cancer at earlier and more treatable stages, as well as to prevent development of gastric cancer through identification of precancerous lesions. However, much uncertainty remains regarding use of endoscopic surveillance in hereditary gastric cancer predisposition syndromes, including whether or not it should be routinely performed, the surveillance interval and age of initiation, cost-effectiveness, and whether surveillance ultimately improves survival from gastric cancer for these high-risk individuals. In this review, we outline the hereditary gastric cancer predisposition syndromes associated with the highest gastric cancer risks. Additionally, we cover current evidence and guidelines addressing hereditary gastric cancer risk and surveillance in these syndromes, along with current challenges and limitations that emphasize a need for continued research in this field.
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Affiliation(s)
- Jessica M Long
- Division of Hematology and Oncology, Penn Medicine, Philadelphia, PA, USA
| | | | - Peter P Stanich
- Division of Gastroenterology, Hepatology & Nutrition, The Ohio State University, Wexner Medical Center, Columbus, OH, USA
| | - Bryson W Katona
- Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA,Correspondence: Bryson W Katona, Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Blvd, 751 South Pavilion, Philadelphia, PA, 19104, USA, Tel +1-215-349-8222, Fax +1-215-349-5915, Email
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9
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Mafficini A, Brosens LAA, Piredda ML, Conti C, Mattiolo P, Turri G, Mastrosimini MG, Cingarlini S, Crinò SF, Fassan M, Piccoli P, Simbolo M, Nottegar A, Lawlor RT, Guglielmi A, Scarpa A, Pedrazzani C, Luchini C. Juvenile polyposis diagnosed with an integrated histological, immunohistochemical and molecular approach identifying new SMAD4 pathogenic variants. Fam Cancer 2022; 21:441-451. [PMID: 35075588 PMCID: PMC9636285 DOI: 10.1007/s10689-022-00289-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Accepted: 01/12/2022] [Indexed: 01/07/2023]
Abstract
Juvenile polyposis (JP) is a rare familial syndrome characterized by the development of numerous hamartomatous polyps of the gastrointestinal tract and by an increased risk of developing gastrointestinal cancers. It follows a pattern of autosomal dominant inheritance and is associated with germline variants of SMAD4 or BMPR1A genes. Differential diagnosis may be difficult based on histology alone, due to morphological similarities to other familial syndromes. Here we report a case of familial JP diagnosed in a 50-years woman with a familial history positive for gastrointestinal cancers and other tumor types. The patient presented with severe iron deficiency anemia and showed numerous polyps in the stomach and jejunum according to endoscopy and imaging. She underwent an intra-gastric laparoscopic removal of the major gastric polyp, followed by jejunal exploration and resection of a segment with multiple neoformations. Histological examination revealed the presence of hamartomatous polyposis. Gastric and intestinal samples were analyzed with next-generation sequencing. Molecular analysis showed that the patient harbored a germline splicing site variant of SMAD4, c.1139 + 3A > G, which was complemented by different somatic variants of the same gene in the different polyps. Immunohistochemistry for SMAD4 confirmed loss of protein expression in the polyps, with regular expression in normal cells. cDNA sequencing further confirmed the findings. We thus definitively diagnosed the woman as having JP thanks to an integrated approach based on histology, immunohistochemistry and molecular analysis. The identified variants, all previously reported as variants of unknown significance, were classified as pathogenic as they complemented each other leading to SMAD4 loss.
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Affiliation(s)
- Andrea Mafficini
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, 37134, Verona, Italy
- ARC-Net Research Center, University of Verona, Verona, Italy
| | - Lodewijk A A Brosens
- Department of Pathology, Utrecht, and Department of Pathology, University Medical Center Utrecht, Utrecht University, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Maria L Piredda
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, 37134, Verona, Italy
| | - Cristian Conti
- Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, Unit of General and Hepatobiliary Surgery, University and Hospital Trust of Verona, 37134, Verona, Italy
| | - Paola Mattiolo
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, 37134, Verona, Italy
| | - Giulia Turri
- Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, Unit of General and Hepatobiliary Surgery, University and Hospital Trust of Verona, 37134, Verona, Italy
| | - Maria G Mastrosimini
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, 37134, Verona, Italy
| | - Sara Cingarlini
- Department of Medicine, Section of Oncology, University and Hospital Trust of Verona, Verona, Italy
| | - Stefano F Crinò
- Digestive Endoscopy Unit, The Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Matteo Fassan
- Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, and Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy
| | - Paola Piccoli
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, 37134, Verona, Italy
| | - Michele Simbolo
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, 37134, Verona, Italy
| | - Alessia Nottegar
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, 37134, Verona, Italy
| | - Rita T Lawlor
- ARC-Net Research Center, University of Verona, Verona, Italy
| | - Alfredo Guglielmi
- Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, Unit of General and Hepatobiliary Surgery, University and Hospital Trust of Verona, 37134, Verona, Italy
| | - Aldo Scarpa
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, 37134, Verona, Italy
- ARC-Net Research Center, University of Verona, Verona, Italy
| | - Corrado Pedrazzani
- Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, Unit of General and Hepatobiliary Surgery, University and Hospital Trust of Verona, 37134, Verona, Italy.
| | - Claudio Luchini
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, 37134, Verona, Italy.
- ARC-Net Research Center, University of Verona, Verona, Italy.
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10
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Rahma C, Najoua BK, Mohamed Z, Manel M, Rim D, Mahdi BD, Tahya SB, Riadh M. Peutz-Jeghers syndrome revealed by recurrent small bowel intussusceptions in children: A case report. Clin Case Rep 2022; 10:e6354. [PMID: 36177085 PMCID: PMC9475123 DOI: 10.1002/ccr3.6354] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Accepted: 08/29/2022] [Indexed: 11/08/2022] Open
Abstract
Peutz-Jeghers syndrome is a rare but potentially life-threating syndrome. We report here the case of a young girl who presented recurrent small bowel intussusceptions. Laparotomy exploration showed many jejunal polyps leading to jejunojejunal intussusceptions. These were removed via mini enterotomies and pathological examination concluded to Peutz-Jeghers polyps.
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Affiliation(s)
- Chtourou Rahma
- Department of Pediatric Surgery, Hedi Chaker HospitalUniversity of SfaxSfaxTunisia
| | - Ben Kraiem Najoua
- Department of Pediatric Surgery, Hedi Chaker HospitalUniversity of SfaxSfaxTunisia
| | - Zouari Mohamed
- Department of Pediatric Surgery, Hedi Chaker HospitalUniversity of SfaxSfaxTunisia
| | - Mellouli Manel
- Department of Pathology and Research Laboratory LR18SP10, Habib Bourguiba University Hospital, Faculty of Medicine of SfaxUniversity of SfaxSfaxTunisia
| | - Dghaies Rim
- Department of Pediatric Surgery, Hedi Chaker HospitalUniversity of SfaxSfaxTunisia
| | - Ben Dhaou Mahdi
- Department of Pediatric Surgery, Hedi Chaker HospitalUniversity of SfaxSfaxTunisia
| | - Sellami Boudawara Tahya
- Department of Pathology and Research Laboratory LR18SP10, Habib Bourguiba University Hospital, Faculty of Medicine of SfaxUniversity of SfaxSfaxTunisia
| | - Mhiri Riadh
- Department of Pediatric Surgery, Hedi Chaker HospitalUniversity of SfaxSfaxTunisia
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11
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Boland CR, Idos GE, Durno C, Giardiello FM, Anderson JC, Burke CA, Dominitz JA, Gross S, Gupta S, Jacobson BC, Patel SG, Shaukat A, Syngal S, Robertson DJ. Diagnosis and Management of Cancer Risk in the Gastrointestinal Hamartomatous Polyposis Syndromes: Recommendations From the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology 2022; 162:2063-2085. [PMID: 35487791 DOI: 10.1053/j.gastro.2022.02.021] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The gastrointestinal hamartomatous polyposis syndromes are rare, autosomal dominant disorders associated with an increased risk of benign and malignant intestinal and extraintestinal tumors. They include Peutz-Jeghers syndrome, juvenile polyposis syndrome, the PTEN hamartoma tumor syndrome (including Cowden's syndrome and Bannayan-Riley-Ruvalcaba syndrome), and hereditary mixed polyposis syndrome. Diagnoses are based on clinical criteria and, in some cases, confirmed by demonstrating the presence of a germline pathogenic variant. The best understood hamartomatous polyposis syndrome is Peutz-Jeghers syndrome, caused by germline pathogenic variants in the STK11 gene. The management is focused on prevention of bleeding and mechanical obstruction of the small bowel by polyps and surveillance of organs at increased risk for cancer. Juvenile polyposis syndrome is caused by a germline pathogenic variant in either the SMAD4 or BMPR1A genes, with differing clinical courses. Patients with SMAD4 pathogenic variants may have massive gastric polyposis, which can result in gastrointestinal bleeding and/or protein-losing gastropathy. Patients with SMAD4 mutations usually have the simultaneous occurrence of hereditary hemorrhagic telangiectasia (juvenile polyposis syndrome-hereditary hemorrhagic telangiectasia overlap syndrome) that can result in epistaxis, gastrointestinal bleeding from mucocutaneous telangiectasias, and arteriovenous malformations. Germline pathogenic variants in the PTEN gene cause overlapping clinical phenotypes (known as the PTEN hamartoma tumor syndromes), including Cowden's syndrome and related disorders that are associated with an increased risk of gastrointestinal and colonic polyposis, colon cancer, and other extraintestinal manifestations and cancers. Due to the relative rarity of the hamartomatous polyposis syndromes, recommendations for management are based on few studies. This U.S Multi-Society Task Force on Colorectal Cancer consensus statement summarizes the clinical features, assesses the current literature, and provides guidance for diagnosis, assessment, and management of patients with the hamartomatous polyposis syndromes, with a focus on endoscopic management.
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Affiliation(s)
- C Richard Boland
- Division of Gastroenterology, University of California-San Diego School of Medicine, San Diego, California
| | - Gregory E Idos
- Divisions of Gastroenterology and Clinical Cancer Genomics, Center for Precision Medicine, City of Hope National Medical Center, Duarte, California
| | - Carol Durno
- The Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada; Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
| | - Francis M Giardiello
- Division of Gastroenterology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Joseph C Anderson
- Veterans Affairs Medical Center, White River Junction, Vermont; Geisel School of Medicine at Dartmouth, Hanover, New Hampshire; University of Connecticut, Farmington, Connecticut
| | - Carol A Burke
- Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic, Cleveland, Ohio
| | - Jason A Dominitz
- Veterans Affairs Puget Sound Health Care System, Seattle, Washington; University of Washington School of Medicine, Seattle, Washington
| | - Seth Gross
- Division of Gastroenterology and Hepatology, New York University Langone Health, New York, New York
| | - Samir Gupta
- Veterans Affairs Medical Center, San Diego, California; University of California San Diego, La Jolla, California; Veterans Affairs San Diego Healthcare System, San Diego, California
| | - Brian C Jacobson
- Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts
| | - Swati G Patel
- University of Colorado School of Medicine, Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, Colorado
| | - Aasma Shaukat
- Minneapolis Veterans Affairs Health Care System, Minneapolis, Minnesota; University of Minnesota, Minneapolis, Minnesota
| | - Sapna Syngal
- Brigham and Women's Hospital, Boston Massachusetts; Dana-Farber Cancer Institute, Boston Massachusetts; Harvard Medical School, Boston Massachusetts
| | - Douglas J Robertson
- Veterans Affairs Medical Center, White River Junction, Vermont; Geisel School of Medicine at Dartmouth, Hanover, New Hampshire
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12
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Boland CR, Idos GE, Durno C, Giardiello FM, Anderson JC, Burke CA, Dominitz JA, Gross S, Gupta S, Jacobson BC, Patel SG, Shaukat A, Syngal S, Robertson DJ. Diagnosis and management of cancer risk in the gastrointestinal hamartomatous polyposis syndromes: recommendations from the U.S. Multi-Society Task Force on Colorectal Cancer. Gastrointest Endosc 2022; 95:1025-1047. [PMID: 35487765 DOI: 10.1016/j.gie.2022.02.044] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
The gastrointestinal hamartomatous polyposis syndromes are rare, autosomal dominant disorders associated with an increased risk of benign and malignant intestinal and extraintestinal tumors. They include Peutz-Jeghers syndrome, juvenile polyposis syndrome, the PTEN hamartoma tumor syndrome (including Cowden's syndrome and Bannayan-Riley-Ruvalcaba syndrome), and hereditary mixed polyposis syndrome. Diagnoses are based on clinical criteria and, in some cases, confirmed by demonstrating the presence of a germline pathogenic variant. The best understood hamartomatous polyposis syndrome is Peutz-Jeghers syndrome, caused by germline pathogenic variants in the STK11 gene. The management is focused on prevention of bleeding and mechanical obstruction of the small bowel by polyps and surveillance of organs at increased risk for cancer. Juvenile polyposis syndrome is caused by a germline pathogenic variant in either the SMAD4 or BMPR1A genes, with differing clinical courses. Patients with SMAD4 pathogenic variants may have massive gastric polyposis, which can result in gastrointestinal bleeding and/or protein-losing gastropathy. Patients with SMAD4 mutations usually have the simultaneous occurrence of hereditary hemorrhagic telangiectasia (juvenile polyposis syndrome-hereditary hemorrhagic telangiectasia overlap syndrome) that can result in epistaxis, gastrointestinal bleeding from mucocutaneous telangiectasias, and arteriovenous malformations. Germline pathogenic variants in the PTEN gene cause overlapping clinical phenotypes (known as the PTEN hamartoma tumor syndromes), including Cowden's syndrome and related disorders that are associated with an increased risk of gastrointestinal and colonic polyposis, colon cancer, and other extraintestinal manifestations and cancers. Due to the relative rarity of the hamartomatous polyposis syndromes, recommendations for management are based on few studies. This U.S. Multi-Society Task Force on Colorectal Cancer consensus statement summarizes the clinical features, assesses the current literature, and provides guidance for diagnosis, assessment, and management of patients with the hamartomatous polyposis syndromes, with a focus on endoscopic management.
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Affiliation(s)
- C Richard Boland
- Division of Gastroenterology, University of California-San Diego School of Medicine, San Diego, California.
| | - Gregory E Idos
- Divisions of Gastroenterology and Clinical Cancer Genomics, Center for Precision Medicine, City of Hope National Medical Center, Duarte, California
| | - Carol Durno
- The Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada; Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
| | - Francis M Giardiello
- Division of Gastroenterology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Joseph C Anderson
- Veterans Affairs Medical Center, White River Junction, Vermont; Geisel School of Medicine at Dartmouth, Hanover, New Hampshire; University of Connecticut, Farmington, Connecticut
| | - Carol A Burke
- Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic, Cleveland, Ohio
| | - Jason A Dominitz
- Veterans Affairs Puget Sound Health Care System, Seattle, Washington; University of Washington School of Medicine, Seattle, Washington
| | - Seth Gross
- Division of Gastroenterology and Hepatology, New York University Langone Health, New York, New York
| | - Samir Gupta
- Veterans Affairs Medical Center, San Diego, California; University of California San Diego, La Jolla, California; Veterans Affairs San Diego Healthcare System, San Diego, California
| | - Brian C Jacobson
- Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts
| | - Swati G Patel
- University of Colorado School of Medicine, Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, Colorado
| | - Aasma Shaukat
- Minneapolis Veterans Affairs Health Care System, Minneapolis, Minnesota; University of Minnesota, Minneapolis, Minnesota
| | - Sapna Syngal
- Brigham and Women's Hospital, Boston Massachusetts; Dana-Farber Cancer Institute, Boston Massachusetts; Harvard Medical School, Boston Massachusetts
| | - Douglas J Robertson
- Veterans Affairs Medical Center, White River Junction, Vermont; Geisel School of Medicine at Dartmouth, Hanover, New Hampshire
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Diagnosis and Management of Cancer Risk in the Gastrointestinal Hamartomatous Polyposis Syndromes: Recommendations From the US Multi-Society Task Force on Colorectal Cancer. Am J Gastroenterol 2022; 117:846-864. [PMID: 35471415 DOI: 10.14309/ajg.0000000000001755] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Accepted: 03/24/2022] [Indexed: 12/11/2022]
Abstract
The gastrointestinal hamartomatous polyposis syndromes are rare, autosomal dominant disorders associated with an increased risk of benign and malignant intestinal and extraintestinal tumors. They include Peutz-Jeghers syndrome, juvenile polyposis syndrome, the PTEN hamartoma tumor syndrome (including Cowden's syndrome and Bannayan-Riley-Ruvalcaba syndrome), and hereditary mixed polyposis syndrome. Diagnoses are based on clinical criteria and, in some cases, confirmed by demonstrating the presence of a germline pathogenic variant. The best understood hamartomatous polyposis syndrome is Peutz-Jeghers syndrome, caused by germline pathogenic variants in the STK11 gene. The management is focused on prevention of bleeding and mechanical obstruction of the small bowel by polyps and surveillance of organs at increased risk for cancer. Juvenile polyposis syndrome is caused by a germline pathogenic variant in either the SMAD4 or BMPR1A genes, with differing clinical courses. Patients with SMAD4 pathogenic variants may have massive gastric polyposis, which can result in gastrointestinal bleeding and/or protein-losing gastropathy. Patients with SMAD4 mutations usually have the simultaneous occurrence of hereditary hemorrhagic telangiectasia (juvenile polyposis syndrome-hereditary hemorrhagic telangiectasia overlap syndrome) that can result in epistaxis, gastrointestinal bleeding from mucocutaneous telangiectasias, and arteriovenous malformations. Germline pathogenic variants in the PTEN gene cause overlapping clinical phenotypes (known as the PTEN hamartoma tumor syndromes), including Cowden's syndrome and related disorders that are associated with an increased risk of gastrointestinal and colonic polyposis, colon cancer, and other extraintestinal manifestations and cancers. Due to the relative rarity of the hamartomatous polyposis syndromes, recommendations for management are based on few studies. This US Multi-Society Task Force on Colorectal Cancer consensus statement summarizes the clinical features, assesses the current literature, and provides guidance for diagnosis, assessment, and management of patients with the hamartomatous polyposis syndromes, with a focus on endoscopic management.
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Liu Z, Jiang L, Li C, Li C, Yang J, Yu J, Mao R, Rao Y. LKB1 Is Physiologically Required for Sleep from Drosophila melanogaster to the Mus musculus. Genetics 2022; 221:6586797. [PMID: 35579349 DOI: 10.1093/genetics/iyac082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Accepted: 05/10/2022] [Indexed: 11/14/2022] Open
Abstract
Liver Kinase B1 (LKB1) is known as a master kinase for 14 kinases related to the adenosine monophosphate (AMP)-activated protein kinase (AMPK). Two of them salt inducible kinase 3 (SIK3) and AMPKα have previously been implicated in sleep regulation. We generated loss-of-function (LOF) mutants for Lkb1 in both Drosophila and mice. Sleep, but not circadian rhythms, was reduced in Lkb1-mutant flies and in flies with neuronal deletion of Lkb1. Genetic interactions between Lkb1 and Threonine to Alanine mutation at residue 184 of AMPK in Drosophila sleep or those between Lkb1 and Threonine to Glutamic Acid mutation at residue 196 of SIK3 in Drosophila viability have been observed. Sleep was reduced in mice after virally mediated reduction of Lkb1 in the brain. Electroencephalography (EEG) analysis showed that non-rapid eye movement (NREM) sleep and sleep need were both reduced in Lkb1-mutant mice. These results indicate that LKB1 plays a physiological role in sleep regulation conserved from flies to mice.
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Affiliation(s)
- Ziyi Liu
- Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program, School of Life Sciences, PKU-IDG/McGovern Institute for Brain Research, School of Chemistry and Molecular Engineering, School of Pharmaceutical Sciences, Peking University, Beijing 100871, China
- Chinese Institute for Brain Research, Beijing, China
- Capital Medical University, Beijing, China
- Changping Laboratory, Beijing, China
| | - Lifen Jiang
- Shenzhen Bay Laboratory, Institute of Molecular Physiology, Shenzhen, Guangdong, China
| | - Chaoyi Li
- Shenzhen Bay Laboratory, Institute of Molecular Physiology, Shenzhen, Guangdong, China
| | - Chengang Li
- Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program, School of Life Sciences, PKU-IDG/McGovern Institute for Brain Research, School of Chemistry and Molecular Engineering, School of Pharmaceutical Sciences, Peking University, Beijing 100871, China
- Chinese Institute for Brain Research, Beijing, China
- Capital Medical University, Beijing, China
- Changping Laboratory, Beijing, China
| | - Jingqun Yang
- Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program, School of Life Sciences, PKU-IDG/McGovern Institute for Brain Research, School of Chemistry and Molecular Engineering, School of Pharmaceutical Sciences, Peking University, Beijing 100871, China
- Chinese Institute for Brain Research, Beijing, China
- Capital Medical University, Beijing, China
- Changping Laboratory, Beijing, China
| | - Jianjun Yu
- Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program, School of Life Sciences, PKU-IDG/McGovern Institute for Brain Research, School of Chemistry and Molecular Engineering, School of Pharmaceutical Sciences, Peking University, Beijing 100871, China
- Chinese Institute for Brain Research, Beijing, China
- Capital Medical University, Beijing, China
- Changping Laboratory, Beijing, China
| | - Renbo Mao
- Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program, School of Life Sciences, PKU-IDG/McGovern Institute for Brain Research, School of Chemistry and Molecular Engineering, School of Pharmaceutical Sciences, Peking University, Beijing 100871, China
- Chinese Institute for Brain Research, Beijing, China
- Capital Medical University, Beijing, China
- Changping Laboratory, Beijing, China
| | - Yi Rao
- Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program, School of Life Sciences, PKU-IDG/McGovern Institute for Brain Research, School of Chemistry and Molecular Engineering, School of Pharmaceutical Sciences, Peking University, Beijing 100871, China
- Chinese Institute for Brain Research, Beijing, China
- Capital Medical University, Beijing, China
- Changping Laboratory, Beijing, China
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Maity P, Das N, Chatterjee U, Basak D. Sex-Cord Tumor with Annular Tubules with Unusual Morphology in an Infant with Peutz-Jeghers Syndrome. Fetal Pediatr Pathol 2022; 41:306-311. [PMID: 32609034 DOI: 10.1080/15513815.2020.1786200] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Background Peutz-Jeghers syndrome (PJS) is characterized by hamartomatous gastrointestinal polyposis, mucocutaneous pigmentation and cancer predisposition. The clinical features of PJS manifest in first two decades of life; however, neonatal presentation is uncommon. Case report: We present a five day old girl with PJS that presented with obstructive hamartomatous polyps in the sigmoid colon. At colostomy closure at six months, an incidental ovarian sex-cord tumor with annular tubules (SCTAT) was detected. It showed predominantly a solid pattern with limited tubule formation and was composed of lipid-rich cells. She had no hormonal symptoms. Conclusion: SCTAT can occur as young as six months of age in PJS, and may show histologic overlap with lipid-rich Sertoli cell tumors.
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Affiliation(s)
- Priyanka Maity
- Department of Pathology, Institute of Post Graduate Medical Education & Research, Kolkata, India
| | - Nandini Das
- Department of Pathology, Medical College and Hospital Kolkata, India
| | - Uttara Chatterjee
- Department of Pathology, Institute of Post Graduate Medical Education & Research, Kolkata, India
| | - Dhananjay Basak
- Department of Pediatric Surgery, Park Clinic, Kolkata, India
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Nonmalignant Features Associated with Inherited Colorectal Cancer Syndromes-Clues for Diagnosis. Cancers (Basel) 2022; 14:cancers14030628. [PMID: 35158896 PMCID: PMC8833640 DOI: 10.3390/cancers14030628] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 01/22/2022] [Accepted: 01/23/2022] [Indexed: 12/13/2022] Open
Abstract
Simple Summary Familiarity with nonmalignant features and comorbidities of cancer predisposition syndromes may raise awareness and assist clinicians in the diagnosis and interpretation of molecular test results. Genetic predisposition to colorectal cancer (CRC) should be suspected mainly in young patients, in patients with significant family histories, multiple polyps, mismatch repair-deficient tumors, and in association with malignant or nonmalignant comorbidities. The aim of this review is to describe the main nonmalignant comorbidities associated with selected CRC predisposition syndromes that may serve as valuable diagnostic clues for clinicians and genetic professionals. Abstract Genetic diagnosis of affected individuals and predictive testing of their at-risk relatives, combined with intensive cancer surveillance, has an enormous cancer-preventive potential in these families. A lack of awareness may be part of the reason why the underlying germline cause remains unexplained in a large proportion of patients with CRC. Various extracolonic features, mainly dermatologic, ophthalmic, dental, endocrine, vascular, and reproductive manifestations occur in many of the cancer predisposition syndromes associated with CRC and polyposis. Some are mediated via the WNT, TGF-β, or mTOR pathways. However the pathogenesis of most features is still obscure. Here we review the extracolonic features of the main syndromes, the existing information regarding their prevalence, and the pathways involved in their pathogenesis. This knowledge could be useful for care managers from different professional disciplines, and used to raise awareness, enable diagnosis, and assist in the process of genetic testing and interpretation.
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Zvizdic Z, Milisic E, Ibisevic N, Pasic IS, Vranic S. Appendiceal carcinoid in a pediatric patient with Peutz-Jeghers syndrome: A case report and comprehensive literature review. Medicine (Baltimore) 2021; 100:e27389. [PMID: 34596162 PMCID: PMC8483869 DOI: 10.1097/md.0000000000027389] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Accepted: 09/15/2021] [Indexed: 01/05/2023] Open
Abstract
RATIONALE Peutz-Jeghers syndrome (PJS), a rare autosomal dominant disorder, is characterized by mucocutaneous pigmentations, hamartomatous polyps in the gastrointestinal tract, and a high risk of developing various malignancies. To the best of our knowledge, only 1 case of appendiceal carcinoid associated with PJS has been previously reported in the pediatric population. PATIENT CONCERNS We report a 7-year-old girl who was admitted for severe, intermittent abdominal pain and cramps, nausea, and vomiting. Multiple brown melanotic macules on the lips, buccal mucosa, and the tongue were noted. DIAGNOSIS A plain abdominal X-ray in a standing position revealed dilated intestinal loops with multiple air-fluid levels. A computed tomography scan of the abdomen showing a "coffee bean" appearance of the jejunal loop with a transition point to the duodenal loop. Axial-contrast-enhanced computed tomography scan of the abdomen showing dilated jejunum loops, filled with fluid with the swirled appearance of mesentery typical for volvulus. The diagnosis of PJS was based on clinical findings along with the histopathologic confirmation of the hamartomatous polyps. INTERVENTIONS An emergency laparotomy was performed, revealing a jejunojejunal intussusception starting 40 cm from the duodenojejunal flexure. Jejunotomy revealed that a lead-point intussusception was a necrotic hamartomatous polyp. After resecting the involved jejunal necrotic segment, including the polyp, end-to-end jejuno-jejunal anastomosis was performed. Further exploration revealed the presence of a jejunal mass 80 cm from the duodenojejunal flexure identified as another hamartomatous pedunculated polyp. The polyp was resected, and the enterotomy was then closed transversely. The grossly normal appendix was also removed. OUTCOMES Clinical findings along with the histopathologically confirmed hamartomatous polyps were consistent with PJS. An appendiceal carcinoid (well-differentiated neuroendocrine tumor, European Neuroendocrine Tumor Society stage pT2) was incidentally detected during histological examination of the appendix. The patient and parents were counseled accordingly, focusing on active surveillance and control of symptoms. Two additional hamartomatous polyps (gastric and jejunal) were detected endoscopically and resected in the fourth postoperative week. A regular, 1-year follow-up and surveillance revealed no complications or recurrences. LESSONS Unusual neoplasms can occasionally be encountered in well-defined syndromes such as PJS. Therefore, active follow-up and surveillance are mandatory for all patients with PJS.
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Affiliation(s)
- Zlatan Zvizdic
- Clinic of Pediatric Surgery, University Clinical Center Sarajevo, Sarajevo, Bosnia and Herzegovina
| | - Emir Milisic
- Clinic of Pediatric Surgery, University Clinical Center Sarajevo, Sarajevo, Bosnia and Herzegovina
| | - Nermina Ibisevic
- Department of Pathology, University Clinical Center Sarajevo, Sarajevo, Bosnia and Herzegovina
| | - Irmina Sefic Pasic
- Department of Radiology, University Clinical Center Sarajevo, Sarajevo, Bosnia and Herzegovina
| | - Semir Vranic
- College of Medicine, QU Health, Qatar University, Doha, Qatar
- Biomedical and Pharmaceutical Research Unit, QU Health, Qatar University, Doha, Qatar
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Kim K, Clauditz TS, Lee JH, Lauwers GY. Polyps of the Stomach. GASTROINTESTINAL PATHOLOGY 2021:99-123. [DOI: 10.1002/9781119073048.ch5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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19
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Al Harbi R, McNeish IA, El-Bahrawy M. Ovarian sex cord-stromal tumors: an update on clinical features, molecular changes, and management. Int J Gynecol Cancer 2021; 31:161-168. [PMID: 33414107 DOI: 10.1136/ijgc-2020-002018] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Revised: 11/24/2020] [Accepted: 11/30/2020] [Indexed: 12/17/2022] Open
Abstract
Sex cord stromal-tumors are rare tumors of the ovary that include numerous tumor subtypes of variable histological features and biological behavior. Surgery is the main therapeutic modality for the management of these tumors, while chemotherapy and hormonal therapy may be used in some patients with progressive and recurrent tumors. Several studies investigated molecular changes in the different tumor types. Understanding molecular changes underlying the development and progression of sex cord-stromal tumors provides valuable information for diagnostic and prognostic biomarkers and potential therapeutic targets for these tumors. In this review, we provide an update on the clinical presentation, molecular changes, and management of sex cord-stromal tumors.
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Affiliation(s)
- Rehab Al Harbi
- Department of Metabolism, Digestion, and Reproduction, Imperial College London, London, UK
| | - Iain A McNeish
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Mona El-Bahrawy
- Department of Metabolism, Digestion, and Reproduction, Imperial College London, London, UK
- Department of Pathology, Faculty of Medicine, University of Alexandria, Alexandria, Egypt
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Wagner A, Aretz S, Auranen A, Bruno MJ, Cavestro GM, Crosbie EJ, Goverde A, Jelsig AM, Latchford AR, van Leerdam ME, Lepisto AH, Puzzono M, Winship I, Zuber V, Möslein G. The Management of Peutz-Jeghers Syndrome: European Hereditary Tumour Group (EHTG) Guideline. J Clin Med 2021; 10:jcm10030473. [PMID: 33513864 PMCID: PMC7865862 DOI: 10.3390/jcm10030473] [Citation(s) in RCA: 65] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2020] [Revised: 01/21/2021] [Accepted: 01/23/2021] [Indexed: 02/06/2023] Open
Abstract
The scientific data to guide the management of Peutz–Jeghers syndrome (PJS) are sparse. The available evidence has been reviewed and discussed by diverse medical specialists in the field of PJS to update the previous guideline from 2010 and formulate a revised practical guideline for colleagues managing PJS patients. Methods: Literature searches were performed using MEDLINE, Embase, and Cochrane. Evidence levels and recommendation strengths were assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). A Delphi process was followed, with consensus being reached when ≥80% of the voting guideline committee members agreed. Recommendations and statements: The only recent guidelines available were for gastrointestinal and pancreatic management. These were reviewed and endorsed after confirming that no more recent relevant papers had been published. Literature searches were performed for additional questions and yielded a variable number of relevant papers depending on the subject addressed. Additional recommendations and statements were formulated. Conclusions: A decade on, the evidence base for recommendations remains poor, and collaborative studies are required to provide better data about this rare condition. Within these restrictions, multisystem, clinical management recommendations for PJS have been formulated.
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Affiliation(s)
- Anja Wagner
- Department of Clinical Genetics, Erasmus MC Cancer Institute, University Medical Center Rotterdam, 3000CA Rotterdam, The Netherlands;
- Correspondence: ; Tel.: +31-10-7036913
| | - Stefan Aretz
- Institute of Human Genetics, Medical Faculty, University of Bonn, 53127 Bonn, Germany;
- National Center for Hereditary Tumor Syndromes, University Hospital Bonn, 53127 Bonn, Germany
| | - Annika Auranen
- Department of Obstetrics and Gynecology and Tays Cancer Center, Tampere University Hospital, 33520 Tampere, Finland;
| | - Marco J. Bruno
- Department of Gastroenterology & Hepatology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, 3000CA Rotterdam, The Netherlands;
| | - Giulia M. Cavestro
- Division of Experimental Oncology, Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; (G.M.C.); (M.P.)
| | - Emma J. Crosbie
- Department of Gynecology, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9WL, UK;
- Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, St Mary’s Hospital, Manchester M13 9WL, UK
| | - Anne Goverde
- Department of Clinical Genetics, Erasmus MC Cancer Institute, University Medical Center Rotterdam, 3000CA Rotterdam, The Netherlands;
| | - Anne Marie Jelsig
- Department of Clinical Genetics, University Hospital of Copenhagen, 2100 Copenhagen, Denmark;
| | - Andrew R. Latchford
- Department of Surgery and Cancer, Imperial College London, London SW7 2AZ, UK;
- Polyposis Registry, St. Marks Hospital, London HA1 3UJ, UK
| | - Monique E. van Leerdam
- Department of Gastro-intestinal Oncology, Netherlands Cancer Institute, 1006BE Amsterdam, The Netherlands;
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, 2300RC Leiden, The Netherlands
| | - Anna H. Lepisto
- Department of Surgery, University Hospital of Helsinki, 00029 Helsinki, Finland;
| | - Marta Puzzono
- Division of Experimental Oncology, Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; (G.M.C.); (M.P.)
| | - Ingrid Winship
- Department of Genomic Medicine, The Royal Melbourne Hospital, University of Melbourne, Melbourne 3052, Australia;
| | - Veronica Zuber
- Breast Surgery Unit, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy;
| | - Gabriela Möslein
- Center for Hereditary Tumors, Ev. BETHESDA Khs. Duisburg, Academic Hospital University of Düsseldorf, 47053 Duisburg, Germany;
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21
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Molecular Features and Clinical Management of Hereditary Gynecological Cancers. Int J Mol Sci 2020; 21:ijms21249504. [PMID: 33327492 PMCID: PMC7765001 DOI: 10.3390/ijms21249504] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Revised: 12/08/2020] [Accepted: 12/11/2020] [Indexed: 12/18/2022] Open
Abstract
Hereditary gynecological cancers are caused by several inherited genes. Tumors that arise in the female reproductive system, such as ovaries and the uterus, overlap with hereditary cancers. Several hereditary cancer-related genes are important because they might lead to therapeutic targets. Treatment of hereditary cancers should be updated in line with the advent of various new methods of evaluation. Next-generation sequencing has led to rapid, economical genetic analyses that have prompted a concomitant and significant paradigm shift with respect to hereditary cancers. Molecular tumor profiling is an epochal method for determining therapeutic targets. Clinical treatment strategies are now being designed based on biomarkers based on tumor profiling. Furthermore, the National Comprehensive Cancer Network (NCCN) guidelines significantly changed the genetic testing process in 2020 to initially consider multi-gene panel (MGP) evaluation. Here, we reviewed the molecular features and clinical management of hereditary gynecological malignancies, such as hereditary breast and ovarian cancer (HBOC), and Lynch, Li–Fraumeni, Cowden, and Peutz–Jeghers syndromes. We also reviewed cancer-susceptible genes revealed by MGP tests.
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Lipsa A, Kowtal P, Sarin R. Novel germline STK11 variants and breast cancer phenotype identified in an Indian cohort of Peutz-Jeghers syndrome. Hum Mol Genet 2020; 28:1885-1893. [PMID: 30689838 DOI: 10.1093/hmg/ddz027] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2018] [Revised: 12/17/2018] [Accepted: 01/22/2019] [Indexed: 12/26/2022] Open
Abstract
Peutz-Jeghers syndrome (PJS) caused by germline STK11 variants is a rare autosomal dominant cancer predisposition syndrome characterized by multiple gastrointestinal (GI) hamartomatous polyps, mucocutaneous pigmentation and a high inherited risk of developing GI, breast and other cancers. Despite GI and breast being the two most common PJS-associated cancer sites, the immunohistochemical (IHC) and molecular features of these tumors in carriers of STK11 variant is not known. Detailed phenotyping including tumor IHC and its correlation with comprehensive STK11 genotyping by full gene sequencing followed by large genomic rearrangement analysis was performed in an Indian PJS cohort. A total of 4 distinct STK11 pathogenic or likely pathogenic variants were identified in 10 PJS cases from 7 of the 19 families tested-in 4/5 classical PJS families and 3/14 suspected PJS families. The pathogenic STK11 variant identified was novel in 3/7 families. In addition, four distinct, likely benign variants identified in seven families were also novel. All of the four breast cancer cases in families with STK11 pathogenic variant were estrogen receptor (ER)-positive and Her2-negative. Several novel STK11 variants identified in this Indian PJS cohort highlight the need to study PJS in different populations across the world. This is the first report showing ER positivity in breast cancer in carriers of STK11 variants and needs confirmation in a larger pooled cohort of PJS associated breast cancers. This could help establish the role of chemoprevention or prophylactic oophorectomy in female carriers of STK11 pathogenic variants.
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Affiliation(s)
- Anuja Lipsa
- Sarin Lab, Advanced Centre for Treatment Research and Education in Cancer-Tata Memorial Centre, Kharghar, Navi Mumbai, Maharashtra, India.,Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai, Maharashtra, India
| | - Pradnya Kowtal
- Sarin Lab, Advanced Centre for Treatment Research and Education in Cancer-Tata Memorial Centre, Kharghar, Navi Mumbai, Maharashtra, India.,Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai, Maharashtra, India
| | - Rajiv Sarin
- Sarin Lab, Advanced Centre for Treatment Research and Education in Cancer-Tata Memorial Centre, Kharghar, Navi Mumbai, Maharashtra, India.,Cancer Genetics Clinic, Tata Memorial Hospital, Tata Memorial Centre, Parel, Mumbai, Maharashtra, India.,Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai, Maharashtra, India
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23
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Benson AB, Venook AP, Al-Hawary MM, Arain MA, Chen YJ, Ciombor KK, Cohen SA, Cooper HS, Deming DA, Garrido-Laguna I, Grem JL, Hoffe SE, Hubbard J, Hunt S, Kamel A, Kirilcuk N, Krishnamurthi S, Messersmith WA, Meyerhardt J, Miller ED, Mulcahy MF, Nurkin S, Overman MJ, Parikh A, Patel H, Pedersen KS, Saltz LB, Schneider C, Shibata D, Skibber JM, Sofocleous CT, Stoffel EM, Stotsky-Himelfarb E, Willett CG, Johnson-Chilla A, Gregory KM, Gurski LA. Small Bowel Adenocarcinoma, Version 1.2020, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2019; 17:1109-1133. [PMID: 31487687 PMCID: PMC10191182 DOI: 10.6004/jnccn.2019.0043] [Citation(s) in RCA: 104] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Small bowel adenocarcinoma (SBA) is a rare malignancy of the gastrointestinal tract that has increased in incidence across recent years. Often diagnosed at an advanced stage, outcomes for SBA are worse on average than for other related malignancies, including colorectal cancer. Due to the rarity of this disease, few studies have been done to direct optimal treatment, although recent data have shown that SBA responds to treatment differently than colorectal cancer, necessitating a separate approach to treatment. The NCCN Guidelines for Small Bowel Adenocarcinoma were created to establish an evidence-based standard of care for patients with SBA. These guidelines provide recommendations on the workup of suspected SBA, primary treatment options, adjuvant treatment, surveillance, and systemic therapy for metastatic disease. Additionally, principles of imaging and endoscopy, pathologic review, surgery, radiation therapy, and survivorship are described.
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Affiliation(s)
- Al B Benson
- Robert H. Lurie Comprehensive Cancer Center of Northwestern University
| | - Alan P Venook
- UCSF Helen Diller Family Comprehensive Cancer Center
| | | | | | | | | | - Stacey A Cohen
- Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance
| | | | | | | | | | | | | | - Steven Hunt
- Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
| | | | | | - Smitha Krishnamurthi
- Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute
| | | | | | - Eric D Miller
- The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute
| | - Mary F Mulcahy
- Robert H. Lurie Comprehensive Cancer Center of Northwestern University
| | | | | | | | | | - Katrina S Pedersen
- Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
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24
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Lo W, Morris MC, Ahmad SA, Patel SH. Screening patients at high risk for pancreatic cancer—Is it time for a paradigm shift? J Surg Oncol 2019; 120:851-857. [DOI: 10.1002/jso.25616] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2019] [Accepted: 06/16/2019] [Indexed: 12/19/2022]
Affiliation(s)
- Winifred Lo
- Department of SurgeryUniversity of Cincinnati College of MedicineCincinnati Ohio
| | - Mackenzie C. Morris
- Department of SurgeryUniversity of Cincinnati College of MedicineCincinnati Ohio
| | - Syed A. Ahmad
- Department of SurgeryUniversity of Cincinnati College of MedicineCincinnati Ohio
| | - Sameer H. Patel
- Department of SurgeryUniversity of Cincinnati College of MedicineCincinnati Ohio
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25
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Wendt C, Margolin S. Identifying breast cancer susceptibility genes - a review of the genetic background in familial breast cancer. Acta Oncol 2019; 58:135-146. [PMID: 30606073 DOI: 10.1080/0284186x.2018.1529428] [Citation(s) in RCA: 84] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Heritage is the most important risk factor for breast cancer. About 15-20% of breast cancer is familial, referring to affected women who have one or more first- or second-degree relatives with the disease. The heritable component in these families is substantial, especially in families with aggregation of breast cancer with low age at onset. Identifying breast cancer susceptibility genes: Since the discovery of the highly penetrant autosomal dominant susceptibility genes BRCA1 and BRCA2 in the 1990s, several more breast cancer genes that confer a moderate to high risk of breast cancer have been identified. Furthermore, during the last decade, advances in genomic technologies have led to large scale genotyping in genome-wide association studies that have identified a considerable amount of common low penetrance loci. In total, the high risk genes, BRCA1, BRCA2, TP53, STK11, CD1 and PTEN account for approximately 20% of the familial risk. Moderate risk variants account for up to 5% of the inherited familial risk. The more than 180 identified low-risk loci explain 18% of the familial risk. Altogether more than half of the genetic background in familial breast cancer remains unclear. Other genes and low risk loci that explain a part the remaining fraction will probably be identified. Clinical aspects and future perspectives: Definitive clinical recommendations can be drawn only for carriers of germline variants in a limited number of high and moderate risk genes for which an association with breast cancer has been established. Future progress in evaluating previously identified breast cancer candidate variants and low risk loci as well as exploring new ones can play an important role in improving individual risk prediction in familial breast cancer.
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Affiliation(s)
- Camilla Wendt
- Department of Oncology, Södersjukhuset, Stockholm, Sweden
- Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden
| | - Sara Margolin
- Department of Oncology, Södersjukhuset, Stockholm, Sweden
- Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden
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26
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Duan N, Zhang YH, Wang WM, Wang X. Mystery behind labial and oral melanotic macules: Clinical, dermoscopic and pathological aspects of Laugier-Hunziker syndrome. World J Clin Cases 2018; 6:322-334. [PMID: 30283795 PMCID: PMC6163135 DOI: 10.12998/wjcc.v6.i10.322] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2018] [Revised: 06/28/2018] [Accepted: 07/23/2018] [Indexed: 02/05/2023] Open
Abstract
Labial and oral melanotic macules are commonly encountered in a broad range of conditions ranging from physiologic pigmentation to a sign of an underlying life-threatening disease. Although Laugier-Hunziker syndrome (LHS) shares some features of labial and oral pigmentation with a variety of conditions, it is a benign and acquired condition, frequently associated with longitudinal melanonychia. Herein, the demographic, clinical, dermoscopic, and pathological aspects of LHS were reviewed comprehensively. The important differential diagnoses of mucocutaneous and nail pigmentation are provided. An accurate diagnosis is crucial to design a reasonable medical strategy, including management options, malignant transformation surveillance, and psychological support. It is important that clinicians conduct long-term follow-up and surveillance due to the potential risks of malignant transformation and local severe complications in some conditions.
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Affiliation(s)
- Ning Duan
- Department of Oral Medicine, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing 210008, Jiangsu Province, China
| | - Yang-Heng Zhang
- Department of Periodontology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing 210008, Jiangsu Province, China
| | - Wen-Mei Wang
- Department of Oral Medicine, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing 210008, Jiangsu Province, China
| | - Xiang Wang
- Department of Oral Medicine, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing 210008, Jiangsu Province, China
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27
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Sanchez-Mete L, Stigliano V. Update on small bowel surveillance in hereditary colorectal cancer syndromes. TUMORI JOURNAL 2018; 105:12-21. [PMID: 30117372 DOI: 10.1177/0300891618792461] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Despite its rarity in the general population, small bowel adenocarcinoma risk is increased in individuals with hereditary colorectal cancer syndromes (HCCS). In the last decade, the advent of capsule endoscopy and device-assisted balloon enteroscopy procedures in patients with HCCS have allowed to investigate the whole small bowel, increasing the diagnostic yield of small bowel tumor. Nonetheless, there is a significant variability in the international guideline recommendations. The aim of this review is to provide an update on surveillance of small bowel in HCCS and to identify the key points for the clinical management of these patients.
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Affiliation(s)
- Lupe Sanchez-Mete
- Division of Gastroenterology and Digestive Endoscopy, Regina Elena National Cancer Institute, Rome, Italy
| | - Vittoria Stigliano
- Division of Gastroenterology and Digestive Endoscopy, Regina Elena National Cancer Institute, Rome, Italy
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28
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Yoshikawa T, Abe T, Amano H, Hanada K, Minami T, Kobayashi T, Yonehara S, Nakahara M, Ohdan H, Noriyuki T. Metachronous triple cancer associated with Peutz-Jeghers syndrome treated with curative surgery: a case report. Surg Case Rep 2018; 4:84. [PMID: 30069736 PMCID: PMC6070452 DOI: 10.1186/s40792-018-0492-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2018] [Accepted: 07/23/2018] [Indexed: 12/17/2022] Open
Abstract
Background Peutz–Jeghers syndrome (PJS) is an autosomal dominant disorder characterized by mucocutaneous pigmentation and hamartomatous gastrointestinal polyposis. It is well known that individuals with PJS are at an increased risk of cancer in a variety of organs. Case presentation Here, we present a patient with PJS who achieved long-term survival by undergoing repeat curative surgery for metachronous triple cancer. Her medical history included hilar cholangiocarcinoma and cervical carcinoma; curative surgery was performed for both conditions. On annual follow-up, the level of carcinoembryonic antigen was elevated at 6.9 ng/ml. Enhanced computed tomography revealed a cystic tumor consisting of mural nodules at the pancreatic head; the maximal diameter was 15 mm. Magnetic resonance imaging clearly demonstrated the tumor with low intensity on T1-weighted images and high intensity on T2-weighted images. Endoscopic ultrasound sonography showed a high echoic tumor at the pancreatic head, which was confirmed as adenocarcinoma by fine-needle aspiration biopsy. The preoperative diagnosis was intraductal papillary mucinous carcinoma (IPMC; T1N0M0, stage IA). Subtotal stomach-preserving pancreaticoduodenectomy was performed and the final diagnosis was IPMC, stage 0 (TisN0M0). Conclusions Aggressive surgery for metachronous triple cancer resulted in good long-term prognosis. Continuous and systematic follow-up would allow the detection of malignancy at an early stage and make treatment with curative surgery possible.
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Affiliation(s)
- Toru Yoshikawa
- Department of Surgery, Onomichi General Hospital, 1-10-23, Onomichi, Hiroshima, 722-8508, Japan
| | - Tomoyuki Abe
- Department of Surgery, Onomichi General Hospital, 1-10-23, Onomichi, Hiroshima, 722-8508, Japan.
| | - Hironobu Amano
- Department of Surgery, Onomichi General Hospital, 1-10-23, Onomichi, Hiroshima, 722-8508, Japan.,Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Keiji Hanada
- Department of Gastroenterology, Onomichi General Hospital, Onomichi, Hiroshima, Japan
| | - Tomoyuki Minami
- Department of Gastroenterology, Onomichi General Hospital, Onomichi, Hiroshima, Japan
| | - Tsuyoshi Kobayashi
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Shuji Yonehara
- Department of Pathology, Onomichi General Hospital, Onomichi, Hiroshima, Japan
| | - Masahiro Nakahara
- Department of Surgery, Onomichi General Hospital, 1-10-23, Onomichi, Hiroshima, 722-8508, Japan
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Toshio Noriyuki
- Department of Surgery, Onomichi General Hospital, 1-10-23, Onomichi, Hiroshima, 722-8508, Japan.,Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
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29
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Jogo T, Oki E, Fujiwara M, Kurashige J, Nakanishi R, Sugiyama M, Nakashima Y, Saeki H, Tsuruta S, Nishimura M, Oda Y, Maehara Y. Non-familial juvenile polyposis of the stomach with gastric cancers: a case report. Surg Case Rep 2018; 4:79. [PMID: 30043121 PMCID: PMC6057863 DOI: 10.1186/s40792-018-0488-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2018] [Accepted: 07/16/2018] [Indexed: 01/02/2023] Open
Abstract
Background Juvenile polyposis is an autosomal dominant inherited disease characterized by the development of numerous hamartomatous and nonneoplastic polyps of the gastrointestinal tract. Juvenile polyposis has also recently been reported as a predisposition for gastrointestinal cancer. Case presentation A 63-year-old man underwent esophagogastroduodenoscopy because of anemia and hypoalbuminemia during a follow-up for gastric polyposis, which showed multiple reddish polyps and two elevated lesions in the stomach. The elevated lesions were diagnosed as well-differentiated adenocarcinomas by biopsy. He had no specific physical findings or family history. Computed tomography showed gastric wall thickening without lymphadenopathy or distant metastasis. Colonoscopy showed an adenoma in the transverse colon. He underwent laparoscopy-assisted total gastrectomy with Roux-en-Y esophagojejunostomy. The resected specimen revealed numerous variously sized non-pedunculated polyps throughout the stomach, diagnosed histopathologically as hamartomatous polyps. The two elevated lesions were diagnosed as a well-differentiated adenocarcinoma restricted to the mucosa and a well-to-poorly differentiated adenocarcinoma invading the submucosa with prominent lymphatic permeation, respectively. Genetic analysis failed to identify any germline mutations in the genes usually associated with juvenile polyposis, including SMAD4 and BMPR1A. However, based on the few characteristic physical findings and histopathological features, the final diagnosis was juvenile polyposis restricted to the stomach. Conclusions This patient represented a rare case of non-familial juvenile polyposis of the stomach with gastric cancers. Juvenile polyposis has malignant potential, and patients should therefore be carefully followed up. Surgical treatment, particularly total gastrectomy, is recommended as a standard treatment in patients with juvenile polyposis of the stomach with gastric cancer.
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Affiliation(s)
- Tomoko Jogo
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.,Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Eiji Oki
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
| | - Minako Fujiwara
- Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Junji Kurashige
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Ryota Nakanishi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Masahiko Sugiyama
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Yuichiro Nakashima
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Hiroshi Saeki
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Shinichi Tsuruta
- Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Masataka Nishimura
- Nishimura Internal Medicine and Gastroenterology Hospital, Fukuoka, Japan
| | - Yoshinao Oda
- Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yoshihiko Maehara
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
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30
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Welinsky S, Lucas AL. Familial Pancreatic Cancer and the Future of Directed Screening. Gut Liver 2018; 11:761-770. [PMID: 28609837 PMCID: PMC5669591 DOI: 10.5009/gnl16414] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2016] [Revised: 11/01/2016] [Accepted: 11/01/2016] [Indexed: 12/11/2022] Open
Abstract
Pancreatic cancer (PC) is the third most common cause of cancer-related death in the United States and the 12th most common worldwide. Mortality is high, largely due to late stage of presentation and suboptimal treatment regimens. Approximately 10% of PC cases have a familial basis. The major genetic defect has yet to be identified but may be inherited by an autosomal dominant pattern with reduced penetrance. Several known hereditary syndromes or genes are associated with an increased risk of developing PC and account for approximately 2% of PCs. These syndromes include the hereditary breast-ovarian cancer syndrome, Peutz-Jeghers syndrome, familial atypical multiple mole melanoma, Lynch syndrome, familial polyposis, ataxia-telangiectasia, and hereditary pancreatitis. Appropriate screening using methods such as biomarkers or imaging, with endoscopic ultrasound and magnetic resonance imaging, may assist in the early detection of neoplastic lesions in the high-risk population. If these lesions are detected and treated before the development of invasive carcinoma, PC disease morbidity and mortality may be improved. This review will focus on familial PC and other hereditary syndromes implicated in the increased risk of PC; it will also highlight current screening methods and the future of new screening modalities.
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Affiliation(s)
- Sara Welinsky
- Samuel F. Bronfman Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Aimee L Lucas
- Samuel F. Bronfman Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.,Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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31
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Abstract
Colorectal adenomatous polyposis syndromes encompass a diverse group of disorders with varying modes of inheritance and penetrance. Children may present with overt disease or within screening programs for families at high risk. We provide an overview of the array of pediatric polyposis syndromes, current screening recommendations, and surgical indications and technical considerations. Optimal disease management for these pediatric patients is still evolving and has implications for screening, surveillance, pediatric surgical management, and transition of care gastroenterologic neoplasia physicians and surgeons.
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Affiliation(s)
- Aodhnait S Fahy
- Division of Pediatric Surgery, Department of Surgery, Mayo Clinic, Rochester, Minnesota
| | - Christopher R Moir
- Division of Pediatric Surgery, Department of Surgery, Mayo Clinic, Rochester, Minnesota
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32
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33
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Fostira F, Mollaki V, Lypas G, Alexandrakis G, Christianakis E, Tzouvala M, Zacharopoulou E, Kalfakakou D, Konstantopoulou I, Yannoukakos D. Genetic analysis and clinical description of Greek patients with Peutz-Jeghers syndrome: Creation of a National Registry. Cancer Genet 2017; 220:19-23. [PMID: 29310834 DOI: 10.1016/j.cancergen.2017.11.004] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2017] [Revised: 10/09/2017] [Accepted: 11/07/2017] [Indexed: 01/09/2023]
Abstract
Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant disorder caused by germline mutations in the STK11 tumor suppressor gene. PJS patients face a cumulative cancer risk as high as 93% for all sites combined. The present study reports the spectrum of STK11 mutations in eight families with clinical diagnosis of PJS, summarizes the clinical characteristics of sixteen mutation carriers and launches a National Registry for PJS in Greece. STK11 loss-of-function (LoF) mutations were detected in 87.5% of index patients. Carriers presented with their first manifestation at a median age of 24.9 years, while early-onset breast cancer was the most frequent malignancy observed, highlighting the need for breast surveillance. Out of the deleterious STK11 mutations identified, two were novel: c.375_376delGT and c.676_679dupAACG, with 57.2% of these potentially occurring de novo. Using all available clinical and genetic data, the National Registry for Greek PJS was established in an attempt to better characterize the syndrome and raise awareness among patients and clinicians (available at https://www.peutzjeghersgreece.org). This is the first comprehensive genetic analysis and clinical characterization of Greek PJS patients, where a high incidence of breast cancer was observed and the first attempt to centralize all data in a National Registry.
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Affiliation(s)
- Florentia Fostira
- Molecular Diagnostics Laboratory, INRaSTES, National Center for Scientific Research "Demokritos", Athens, Greece.
| | - Vasiliki Mollaki
- Molecular Diagnostics Laboratory, INRaSTES, National Center for Scientific Research "Demokritos", Athens, Greece
| | - George Lypas
- 1st Oncology Clinic, Hygeia Hospital, Athens, Greece
| | | | | | - Maria Tzouvala
- Department of Gastroenterology, General Hospital Nikaias, Piraeus, Greece
| | | | - Despoina Kalfakakou
- Molecular Diagnostics Laboratory, INRaSTES, National Center for Scientific Research "Demokritos", Athens, Greece
| | - Irene Konstantopoulou
- Molecular Diagnostics Laboratory, INRaSTES, National Center for Scientific Research "Demokritos", Athens, Greece
| | - Drakoulis Yannoukakos
- Molecular Diagnostics Laboratory, INRaSTES, National Center for Scientific Research "Demokritos", Athens, Greece
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34
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Chen HY, Jin XW, Li BR, Zhu M, Li J, Mao GP, Zhang YF, Ning SB. Cancer risk in patients with Peutz-Jeghers syndrome: A retrospective cohort study of 336 cases. Tumour Biol 2017; 39:1010428317705131. [PMID: 28653895 DOI: 10.1177/1010428317705131] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Peutz-Jeghers syndrome is a rare autosomal dominant inherited disorder characterized by mucocutaneous pigmentation and hamartomatous gastrointestinal polyposis. A growing body of evidence has shown that Peutz-Jeghers syndrome could cause an increased risk of various cancers, yet the range of cancer risk estimates was wide among different studies. In this retrospective cohort study, 336 patients with Peutz-Jeghers syndrome in China were enrolled. The clinical characteristics, cancer spectrum, relative cancer risks, and cumulative cancer risks were analyzed. In total, 52 patients were diagnosed of cancer in the follow-up period, at a median age of 41 years (range: 21-67). The relative risk for cancer in Peutz-Jeghers syndrome patients was 63.858 (confidence interval: 47.514-85.823), and the cumulative cancer risk at the age of 60 years was 55%. Colorectal cancer was the most common cancer for Peutz-Jeghers syndrome patients (relative risk: 237.918, confidence interval: 154.417-366.572) and the cumulative cancer risk at the age of 60 years was 28%. There was a statistically significant difference in the cumulative cancer risk between patients with family history and those without family history, as well as between patients living in rural area and those living in urban areas ( p < 0.05), while no significant effects of gender and intussusception history on the cumulative cancer risk was found ( p > 0.05). Hopefully, our study may contribute to the management of this rare disorder and establishment of related surveillance projects, especially in China.
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Affiliation(s)
- Hong-Yu Chen
- 1 Department of Gastroenterology, Clinical College of Air Force General Hospital, Anhui Medical University, Beijing, China
| | - Xiao-Wei Jin
- 1 Department of Gastroenterology, Clinical College of Air Force General Hospital, Anhui Medical University, Beijing, China
| | - Bai-Rong Li
- 1 Department of Gastroenterology, Clinical College of Air Force General Hospital, Anhui Medical University, Beijing, China
| | - Ming Zhu
- 1 Department of Gastroenterology, Clinical College of Air Force General Hospital, Anhui Medical University, Beijing, China
| | - Jing Li
- 1 Department of Gastroenterology, Clinical College of Air Force General Hospital, Anhui Medical University, Beijing, China
| | - Gao-Ping Mao
- 1 Department of Gastroenterology, Clinical College of Air Force General Hospital, Anhui Medical University, Beijing, China
| | - Ya-Fei Zhang
- 1 Department of Gastroenterology, Clinical College of Air Force General Hospital, Anhui Medical University, Beijing, China.,2 Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Shou-Bin Ning
- 1 Department of Gastroenterology, Clinical College of Air Force General Hospital, Anhui Medical University, Beijing, China
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Korsse SE, van Leerdam ME, Dekker E. Gastrointestinal diseases and their oro-dental manifestations: Part 4: Peutz-Jeghers syndrome. Br Dent J 2017; 222:214-217. [DOI: 10.1038/sj.bdj.2017.127] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/22/2016] [Indexed: 01/06/2023]
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Kennedy RA, Thavaraj S, Diaz-Cano S. An Overview of Autosomal Dominant Tumour Syndromes with Prominent Features in the Oral and Maxillofacial Region. Head Neck Pathol 2017; 11:364-376. [PMID: 28110467 PMCID: PMC5550396 DOI: 10.1007/s12105-017-0778-1] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2016] [Accepted: 01/07/2017] [Indexed: 12/16/2022]
Abstract
Several autosomal dominant inherited tumour syndromes demonstrate prominent features in the oral and maxillofacial region. Although multiple organ systems are frequently involved, the target organs more frequently affected are the skin (nevoid basal cell carcinoma syndrome, Brooke-Spiegler syndrome, Birt-Hogg-Dube syndrome and Muir-Torre syndrome), gastrointestinal tract (Peutz-Jegher syndrome and Gardner syndrome) or endocrine system (multiple endocrine neoplasia type 2b and hyperparathyroidism-jaw tumour syndrome). In some syndromes, the disease is multisystem with skin index lesions presenting in the head and neck (Cowden syndrome and tuberous sclerosis complex). The pertinent features of these syndromes are reviewed with a systems-based approach, emphasising their clinical impact and diagnosis.
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Affiliation(s)
- Robert A. Kennedy
- Head and Neck Pathology, King’s College London Dental Institute, Guy’s & St, NHS Foundation Trust, London, SE1 9RT UK ,Head and Neck Pathology, Guy’s Hospital, Floor 4, Tower Wing, Great Maze Pond, London, SE1 9RT UK
| | - Selvam Thavaraj
- Head and Neck Pathology, King’s College London Dental Institute, Guy’s & St, NHS Foundation Trust, London, SE1 9RT UK
| | - Salvador Diaz-Cano
- Department of Histopathology, King’s College Hospital, London, SE5 9R UK
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Moreira L, Castells A. Surveillance of patients with hereditary gastrointestinal cancer syndromes. Best Pract Res Clin Gastroenterol 2016; 30:923-935. [PMID: 27938787 DOI: 10.1016/j.bpg.2016.10.004] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2016] [Revised: 10/10/2016] [Accepted: 10/13/2016] [Indexed: 02/06/2023]
Abstract
Gastrointestinal cancers are among the most frequent tumors. Although most cases are sporadic, up to 5-6% develops in the context of gastrointestinal hereditary syndromes. These entities have specific characteristics and often a germline mutation identified, thus allowing performing genetic counseling. This review summarizes the most common gastrointestinal hereditary syndromes, focusing on the surveillance recommendations.
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Affiliation(s)
- Leticia Moreira
- Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd), IDIBAPS, University of Barcelona, Villarroel 170, 08036 Barcelona, Catalonia, Spain.
| | - Antoni Castells
- Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd), IDIBAPS, University of Barcelona, Villarroel 170, 08036 Barcelona, Catalonia, Spain.
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Chen C, Zhang X, Wang D, Wang F, Pan J, Wang Z, Liu C, Wu L, Lu H, Li N, Wei J, Shi H, Wan H, Zhu M, Chen S, Zhou Y, Zhou X, Yang L, Liu J. Genetic Screening and Analysis of LKB1 Gene in Chinese Patients with Peutz-Jeghers Syndrome. Med Sci Monit 2016; 22:3628-3640. [PMID: 27721366 PMCID: PMC5070620 DOI: 10.12659/msm.897498] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Peutz-Jeghers syndrome (PJS) is an autosomal dominant genetic disease. It severely decreases patient quality of life and leads elevated cancer risk. Germline mutation of LKB1 is the leading cause of familial PJS. MATERIAL AND METHODS To characterize the germline mutation of LKB1 gene in Chinese familial and sporadic PJS patients, 14 PJS families, 5 sporadic PJS patients, and 250 healthy adults were collected and genomic DNAs of peripheral blood were extracted. Mutation screenings of LKB1 were performed using MLPA (multiplex ligation-dependent probe amplification), PCR, direct sequencing, and PCR-DHPLC (denaturing high-performance liquid chromatography). RESULTS A total of 12 kinds of germline mutations were found in 9 familial PJS patients, most of which were point mutations (7/12); 4 large deletions of LKB1 were also observed. Of the 12 mutations, 7 were pathogenic (2 were de novo), 4 were just polymorphisms, and 1 was indefinitely pathogenic. No pathogenic mutation in exons of the LKB1 gene was detected in the 5 sporadic PJS patients. The mutation detection rate for the LKB1 gene was 85.7% in our Chinese familial PJS and 63.2% in all Chinese PJS patients. Eight familial PJS patients were identified with pathogenic germline mutations in 14 unrelated families (57.1%). Further methylation detection and analysis showed promoter methylation in carcinomatous polyps. CONCLUSIONS LKB1 gene germline mutation with pathogenic effect is a common cause of familial PJS in Chinese patients; however, it is not the only molecular pathogen of PJS. Methylation in the LKB1 gene promoter region may cause carcinomatous change in intestinal polyps.
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Affiliation(s)
- Chunyan Chen
- Department of Gastroenterology and Hepatology, Jinling Hospital, Nanjing, Jiangsu, China (mainland)
| | - Xiaomei Zhang
- Laboratory of Genetics and Molecular Biology, Jiangsu Province Cancer Hospital and Jiangsu Institute of Cancer Research, Nanjing, Jiangsu, China (mainland)
| | - Deqiang Wang
- The Cancer Therapy Center, Affiliated Hospital of Jiangsu University, Nanjing, Jiangsu, China (mainland)
| | - Fangyu Wang
- Department of Gastroenterology and Hepatology, Jinling Hospital, Nanjing, Jiangsu, China (mainland)
| | - Jian Pan
- Department of Gastroenterology, Nanjing Children's Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu, China (mainland)
| | - Zhenkai Wang
- Department of Gastroenterology and Hepatology, Jinling Hospital, Nanjing, Jiangsu, China (mainland)
| | - Chang Liu
- Department of Gastroenterology and Hepatology, Jinling Hospital, Nanjing, Jiangsu, China (mainland)
| | - Lin Wu
- Department of Gastroenterology and Hepatology, Jinling Hospital, Nanjing, Jiangsu, China (mainland)
| | - Heng Lu
- Department of Gastroenterology and Hepatology, Jinling Hospital, Nanjing, Jiangsu, China (mainland)
| | - Nan Li
- Department of Gastroenterology and Hepatology, Jinling Hospital, Nanjing, Jiangsu, China (mainland)
| | - Juan Wei
- Department of Gastroenterology and Hepatology, Jinling Hospital, Nanjing, Jiangsu, China (mainland)
| | - Hui Shi
- Department of Gastroenterology and Hepatology, Jinling Hospital, Nanjing, Jiangsu, China (mainland)
| | - Haijun Wan
- Department of Gastroenterology and Hepatology, Jinling Hospital, Nanjing, Jiangsu, China (mainland)
| | - Ming Zhu
- Laboratory of Genetics and Molecular Biology, Jiangsu Province Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, Jiangsu, China (mainland)
| | - Senqing Chen
- Laboratory of Genetics and Molecular Biology, Jiangsu Province Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, Jiangsu, China (mainland)
| | - Yun Zhou
- Department of Medicine, Jiangsu Cancer Hospital, Nanjing, Jiangsu, China (mainland)
| | - Xin Zhou
- Department of General Surgery, Jiangsu Cancer Hospital, Nanjing, Jiangsu, China (mainland)
| | - Liu Yang
- Department of General Surgery, Jiangsu Cancer Hospital, Nanjing, Jiangsu, China (mainland)
| | - Jiong Liu
- Department of Gastroenterology and Hepatology, Jinling Hospital, Nanjing, Jiangsu, China (mainland)
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Santosh T, Patro M, Nayak J, Behera B. A classical case of Peutz–Jeghers syndrome with brief review of literature. HUMAN PATHOLOGY: CASE REPORTS 2016. [DOI: 10.1016/j.ehpc.2015.06.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022] Open
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Ravishankar S, Mangray S, Kurkchubasche A, Yakirevich E, Young RH. Unusual Sertoli Cell Tumor Associated With Sex Cord Tumor With Annular Tubules in Peutz-Jeghers Syndrome. Int J Surg Pathol 2015; 24:269-73. [DOI: 10.1177/1066896915620663] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
We report the case of an 11-year-old girl with Peutz-Jeghers syndrome and a unilateral ovarian tumor most consistent with Sertoli cell tumor associated with sex cord tumor with annular tubules. The ovary was replaced by a lobular, solid, yellow tumor. Microscopic examination showed 2 components that focally merged. The first was composed of uniform, cytologically bland cells arranged mostly in diffuse sheets and focally in tubules. The second showed typical sex cord tumor with annular tubules with extensive calcification. The predominant component of the tumor clearly fell in the sex cord category and most closely resembled Sertoli cell tumor. This case adds to the limited information on ovarian sex cord tumors, other than typical sex cord tumor with annular tubules, arising in association with Peutz-Jeghers syndrome, a topic reviewed herein.
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Affiliation(s)
- Sanjita Ravishankar
- Rhode Island Hospital and Hasbro Children’s Hospital, Providence, RI, USA
- Alpert Medical School of Brown University, Providence, RI, USA
| | - Shamlal Mangray
- Rhode Island Hospital and Hasbro Children’s Hospital, Providence, RI, USA
- Alpert Medical School of Brown University, Providence, RI, USA
| | - Arlet Kurkchubasche
- Rhode Island Hospital and Hasbro Children’s Hospital, Providence, RI, USA
- Alpert Medical School of Brown University, Providence, RI, USA
| | - Evgeny Yakirevich
- Rhode Island Hospital and Hasbro Children’s Hospital, Providence, RI, USA
- Alpert Medical School of Brown University, Providence, RI, USA
| | - Robert H. Young
- Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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Abstract
Aims and background Guidelines for surveillance in patients with familial adenomatous polyposis (FAP) recommend mutation carriers to undergo periodic colorectal examination starting in the early teens. Performing colonoscopy in children may lead to complications. Wireless capsule endoscopy (WCE) has been introduced recently to evaluate both the upper and lower gastrointestinal tract, and seems suitable as a first screening examination for adolescents. The aim of this study was to evaluate the pros and cons of WCE. Methods This was a retrospective review of a single institution database of adolescent patients with FAP identified through the Hereditary Colorectal Tumor Registry between 2007 and 2013. The main outcomes were identification of upper and lower gastrointestinal tract polyps, tolerance of the examination, and number and size of polyps. Results Of 46 adolescent patients with FAP, 14 (30.4%) patients carrying adenomatous polyposis coli gene ( APC) mutation, 6 male and 8 female, age (median, range) 12 (10-17) years, body mass index 19 (13-24), underwent WCE as first screening examination. The examination was completed in 13 patients (93.3%). Wireless capsule endoscopy identified the duodenal papilla in 4 patients and colonic and rectal polyps in all 13 patients. In 7 patients, fewer than 25 polyps were identified. No complications were recorded related to the use of the video capsule. Conclusions Wireless capsule endoscopy is feasible and well-tolerated as a first screening examination in adolescent patients. It cannot be used as alternative to the colonoscopy, but could improve compliance with colonoscopy, and increase early adherence to a surveillance program.
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Wendt C, Lindblom A, Arver B, von Wachenfeldt A, Margolin S. Tumour spectrum in non-BRCA hereditary breast cancer families in Sweden. Hered Cancer Clin Pract 2015; 13:15. [PMID: 26082817 PMCID: PMC4469256 DOI: 10.1186/s13053-015-0036-z] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2015] [Accepted: 06/09/2015] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Approximately 30 % of all breast cancer is at least partly attributed to hereditary factors. Familial breast cancer is often inherited in the context of cancer syndromes. The most commonly mutated genes are BRCA1 and BRCA2 in hereditary breast and ovarian cancer syndrome. The genetic background in families with hereditary breast cancer without predisposing germ line mutations in BRCA1 and BRCA2 (non-BRCA families) is still to a large extent unclear even though progress has been made. The aim of this study was to compare cancer proportions in familial non-BRCA hereditary breast cancer compared to the general population in search of putative new breast cancer syndromes. METHODS Pedigrees from 334 non-BRCA hereditary breast cancer families in the county of Stockholm, Sweden, were investigated and the distribution of cancer diagnoses other than breast cancer was compared with the distribution of cancer diagnoses in the general Swedish population in two reference years, 1970 and 2010. A cancer diagnosis was regarded as overrepresented in the non-BRCA families if the confidence interval was above both population reference values. RESULTS We found that endometrial cancer was overrepresented in the non-BRCA families with a 6.36 % proportion (CI 4.67-8.2) compared to the proportion in the general population in the reference years 1970 (3.07 %) and 2010 (2.64 %). Moreover tumours of the ovary, liver, pancreas and prostate were overrepresented. CONCLUSION In conclusion, we found an overrepresentation of endometrial cancer in our cohort of hereditary non-BRCA families. Our result supports previous inconsistent reports of a putative breast and endometrial cancer syndrome. An association has been suggested in studies of families with several cases of breast cancer in close relatives or bilateral breast cancer. To clarify this issue we suggest further studies on a breast and endometrial cancer syndrome in cohorts with a strong pattern of hereditary breast cancer. Identifying new breast cancer syndromes is of importance to improve genetic counselling for women at risk and a first step towards detection of new susceptibility genes.
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Affiliation(s)
- Camilla Wendt
- Department of Oncology-Pathology, Karolinska Institutet Solna, S-17177 Stockholm, Sweden ; Department of Oncology, Karolinska University Hospital Solna, S-17177 Stockholm, Sweden
| | - Annika Lindblom
- Department of Clinical Genetics, Karolinska University Hospital Solna, S-17177 Stockholm, Sweden ; Department of Molecular Medicine and Surgery, Karolinska Institutet Solna, S-17177 Stockholm, Sweden
| | - Brita Arver
- Department of Oncology-Pathology, Karolinska Institutet Solna, S-17177 Stockholm, Sweden ; Department of Oncology, Karolinska University Hospital Solna, S-17177 Stockholm, Sweden
| | - Anna von Wachenfeldt
- Department of Oncology-Pathology, Karolinska Institutet Solna, S-17177 Stockholm, Sweden ; Department of Oncology, Karolinska University Hospital Solna, S-17177 Stockholm, Sweden
| | - Sara Margolin
- Department of Oncology-Pathology, Karolinska Institutet Solna, S-17177 Stockholm, Sweden ; Department of Oncology, Karolinska University Hospital Solna, S-17177 Stockholm, Sweden
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Ge Y, Jia G, Lin T. Gütegeschaltete Nd:YAG-Laserbehandlung labialer Lentigines bei Peutz-Jeghers-Syndrom. J Dtsch Dermatol Ges 2015. [DOI: 10.1111/ddg.12627_suppl] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Affiliation(s)
- Yiping Ge
- Department of Cosmetic Laser Surgery, Institute of Dermatology, Chinese Academy of Medical Sciences; China
| | - Gaorong Jia
- Department of Cosmetic Laser Surgery, Institute of Dermatology, Chinese Academy of Medical Sciences; China
| | - Tong Lin
- Department of Cosmetic Laser Surgery, Institute of Dermatology, Chinese Academy of Medical Sciences; China
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Ge Y, Jia G, Lin T. Q-switched Nd:YAG laser treatment for labial lentigines associated with Peutz-Jeghers syndrome. J Dtsch Dermatol Ges 2015; 13:551-5. [PMID: 26018367 DOI: 10.1111/ddg.12627] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/20/2014] [Indexed: 01/26/2023]
Abstract
BACKGROUND AND OBJECTIVE Labial lentigines associated with Peutz-Jeghers syndrome are cosmetically disfiguring and distressful. Although multiple treatment modalities including Q-switched ruby laser and Q-switched alexandrite laser have been proposed, experience with Q-switched Nd:YAG laser has been lacking. This study aimed to retrospectively evaluate the efficacy and safety of Q-switched Nd:YAG laser (532 nm) for labial lentigines in Peutz-Jeghers syndrome. PATIENTS AND METHODS Demographic and clinical data of 11 patients diagnosed with Peutz-Jeghers syndrome were analyzed. A quartile grading system was used. All patients were treated with a Q-switched Nd:YAG laser system with the following parameters: wavelength 532 nm; spot size 3 mm; pulse duration 5-20 ns; fluence 1.8-2.2 J/cm(2) . RESULTS After two to six (mean 3.6) treatment sessions, an average grade of 3.73 was achieved. Eight patients (72.7 %) showed an excellent response with more than 75 % lesion clearance. Three patients (27.3 %) showed a good response. Repeated treatments led to improved clearance of labial lentigines. Age, gender, and Fitzpatrick skin type were not statistically associated with efficacy grades after the first treatment session. Neither recurrence in treated areas nor significant complications were observed. CONCLUSIONS Q-switched Nd:YAG laser provides an effective and safe treatment option for labial lentigines associated with Peutz-Jeghers syndrome.
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Affiliation(s)
- Yiping Ge
- Department of Cosmetic Laser Surgery, Institute of Dermatology, Chinese Academy of Medical Sciences, China
| | - Gaorong Jia
- Department of Cosmetic Laser Surgery, Institute of Dermatology, Chinese Academy of Medical Sciences, China
| | - Tong Lin
- Department of Cosmetic Laser Surgery, Institute of Dermatology, Chinese Academy of Medical Sciences, China
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[Hereditary predisposition to cancers of the digestive tract, breast, gynecological and gonadal: focus on the Peutz-Jeghers]. Bull Cancer 2015; 101:813-22. [PMID: 25036236 DOI: 10.1684/bdc.2014.1942] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant disease due to mutations in the tumor suppressor gene STK11. PJS is characterized by periorificial hyperpigmented macules (lentiginosis) and hamartomatous polyposis. Polyps can be located anywhere in the gastrointestinal tract, but are preferably observed in the small bowel (70-90%), the colon (50%) and the stomach (25%). They tend to be cancerous in a particular sequence hamartoma-dysplasia-cancer. The diagnosis is often made in the first or second decade following the appearance of lentigines or upon the occurrence of complications due to polyps (obstruction, intussusception, occult bleeding responsible for anemia). Furthermore PJS is associated with a significant increase in cancer risk (relative risk of 89% over the life according to the most recent series). Digestive cancers are the more frequent with cumulative incidences of 55% for gastro-intestinal cancer (39% for colorectal cancer, 13% for small bowel cancer and between 11 and 36% for pancreatic cancer, respectively). There is also an increased risk of non digestive cancers. In particular the risk of breast cancer is similar to that of patients carrying deleterious BRCA1 or BRCA2 mutations (cumulative incidence of 45%). Gynecological and gonadal tumors are frequent as well and can be more (adenoma malignum) or less aggressive (ovarian sex cord tumors with annular tubules and testicular tumors with calcified Sertoli cells). Finally the frequency of lung cancer is moderately increased. Recommendations for screening and management based on retrospective series in the literature have led to various strategies. The aim of this paper is to summarize the clinical and molecular diagnostic criteria of PJS as well as recommendations on screening strategies, management and monitoring.
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Gupta R, Liu AY, Glazer PM, Wajapeyee N. LKB1 preserves genome integrity by stimulating BRCA1 expression. Nucleic Acids Res 2014; 43:259-71. [PMID: 25488815 PMCID: PMC4288185 DOI: 10.1093/nar/gku1294] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Serine/threonine kinase 11 (STK11, also known as LKB1) functions as a tumor suppressor in many human cancers. However, paradoxically loss of LKB1 in mouse embryonic fibroblast results in resistance to oncogene-induced transformation. Therefore, it is unclear why loss of LKB1 leads to increased predisposition to develop a wide variety of cancers. Here, we show that LKB1 protects cells from genotoxic stress. Cells lacking LKB1 display increased sensitivity to irradiation, accumulates more DNA double-strand breaks, display defective homology-directed DNA repair (HDR) and exhibit increased mutation rate, compared with that of LKB1-expressing cells. Conversely, the ectopic expression of LKB1 in cells lacking LKB1 protects them against genotoxic stress-induced DNA damage and prevents the accumulation of mutations. We find that LKB1 post-transcriptionally stimulates HDR gene BRCA1 expression by inhibiting the cytoplasmic localization of the RNA-binding protein, HU antigen R, in an AMP kinase-dependent manner and stabilizes BRCA1 mRNA. Cells lacking BRCA1 similar to the cell lacking LKB1 display increased genomic instability and ectopic expression of BRCA1 rescues LKB1 loss-induced sensitivity to genotoxic stress. Collectively, our results demonstrate that LKB1 is a crucial regulator of genome integrity and reveal a novel mechanism for LKB1-mediated tumor suppression with direct therapeutic implications for cancer prevention.
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Affiliation(s)
- Romi Gupta
- Department of Pathology, Yale University School of Medicine, New Haven, CT 06510, USA
| | - Alex Y Liu
- Department of Pathology, Yale University School of Medicine, New Haven, CT 06510, USA
| | - Peter M Glazer
- Department of Therapeutic Radiology and Genetics, Yale University School of Medicine, New Haven, CT 06510, USA
| | - Narendra Wajapeyee
- Department of Pathology, Yale University School of Medicine, New Haven, CT 06510, USA
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Hofmann S, Barth TFE, Kornmann M, Henne-Bruns D. Appendix carcinoid associated with the Peutz-Jeghers syndrome. Int J Surg Case Rep 2014; 5:964-7. [PMID: 25460448 PMCID: PMC4276270 DOI: 10.1016/j.ijscr.2014.06.024] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2013] [Revised: 05/09/2013] [Accepted: 06/25/2014] [Indexed: 12/28/2022] Open
Abstract
INTRODUCTION The Peutz-Jeghers syndrome (PJS) is a rare hereditary, autosomal-dominant disorder. It is characterized by a gastrointestinal polyposis and mucocutaneous melanic spots. It has also been reported as a precondition for malignancies with a life-time-hazard for cancer up to 93%, caused by a germline mutation in the STK11 gene. PRESENTATION OF CASE A 21-year-old man presented with nausea and abdominal pain. He had a known history of PJS since the age of 13 when he was treated for intussusception due to a hamartomatous polyp. Preoperative diagnostics revealed a second intussusception and an extensive intestinal polyposis. Intraoperative findings confirmed the suspected diagnoses and desvagination was performed. Nearly 50 polyps were removed from the small intestinum over several longitudinal sections. As the appendix appeared thickened an appendectomy was performed simultaneously. Histology showed hamartomatous polyps and the incidental finding of a pT1 carcinoid of the appendix. The patient recovered well and needed no further treatment for his carcinoid tumor. DISCUSSION The mechanism of carcinogenesis in PJS still remains debatable, although the genetic disorder underlying the syndrome is known. A predisposition for carcinoid tumors also stays questionable. To our knowledge there is no description of an association between carcinoid tumors of the appendix and PJS to date. CONCLUSION Life-expectancy in patients with PJS is reduced. Causes are the development of malignancies and complications from the polyps such as intussusception. Since there is no treatment possible main focus must be aimed at early recognition of malignancies and the prevention of complications.
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Affiliation(s)
- Sabine Hofmann
- Department of General and Visceral Surgery, University of Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany.
| | - Thomas F E Barth
- Institute of Pathology University of Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany
| | - Marko Kornmann
- Department of General and Visceral Surgery, University of Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany
| | - Doris Henne-Bruns
- Department of General and Visceral Surgery, University of Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany
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Abstract
IMPORTANCE The differential diagnosis for oral lentigines includes several syndromes with important associated systemic findings. McCune-Albright syndrome (MAS), a mosaic condition associated with café au lait pigmentation, is not typically considered a mucosal lentiginosis syndrome. The clinical phenotype of MAS is variable because of mosaicism, but oral pigmentation developing in mid-childhood to early adulthood should be recognized as a clinical feature of MAS. OBSERVATIONS We present 4 patients with MAS who developed oral mucosal pigmentation during childhood or early adulthood. All patients had other characteristic findings of MAS including hyperfunctioning endocrinopathies, polyostotic fibrous dysplasia, and café au lait pigmentation. CONCLUSIONS AND RELEVANCE Oral pigmentation is an underrecognized finding in MAS and presents later in development compared with the other mucosal lentiginosis syndromes. The diagnosis of MAS is most commonly a clinical diagnosis because mutational analysis is challenging in mosaic conditions. Expanding the cutaneous phenotype to include oral pigmentation further characterizes the clinical findings in this mosaic condition, broadens the differential diagnosis of syndromes with oral pigmentation, and in some cases may aid in earlier diagnosis of MAS.
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Affiliation(s)
- Dominique C Pichard
- Department of Dermatology, Georgetown University Hospital/Washington Hospital Center, Washington, DC
| | - Alison M Boyce
- Division of Endocrinology and Diabetes, Children's National Medical Center, Washington, DC3Bone Health Program, Division of Orthopaedics and Sports Medicine, Children's National Medical Center, Washington, DC
| | - Michael T Collins
- Skeletal Clinical Studies Unit, Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland
| | - Edward W Cowen
- Center for Cancer Research, Dermatology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
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50
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Abstract
Peutz-Jeghers syndrome (PJS), caused by germ-line mutations in LKB1, is characterized by the development of hamartomatous polyps in the gastrointestinal (GI) tract. McCune Albright syndrome (MAS), caused by somatic activating mutations in GNAS, presents with cutaneous, skeletal, and endocrine manifestations. Recently, hamartomatous GI polyps with histological features similar to those in PJS were observed in MAS patients, suggesting a role for GNAS in the pathogenesis of PJS. This study reports the first somatic GNAS mutation analysis in GI tumours of PJS patients. No mutations were observed, suggesting that GNAS is not involved in the pathogenesis of GI tumours in PJS.
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