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Tian ZS, Ma XP, Ruan HX, Yang Y, Zhao YL. Rare large sigmoid hamartomatous polyp in an elderly patient with atypical Peutz-Jeghers syndrome: A case report. World J Gastrointest Surg 2025; 17:102174. [PMID: 40162387 PMCID: PMC11948137 DOI: 10.4240/wjgs.v17.i3.102174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Revised: 12/17/2024] [Accepted: 01/09/2025] [Indexed: 02/24/2025] Open
Abstract
BACKGROUND Peutz-Jeghers (PJ) syndrome (PJS) is a rare autosomal dominant genetic disease characterized by the association of intestinal polyposis, mucosal skin pigmentation, and cancer susceptibility. PJS patients have a significantly increased risk of malignant tumors in the gastrointestinal tract and extra-gastrointestinal tract, including various epithelial malignant tumors (colorectal cancer, gastric cancer, pancreatic cancer, breast cancer, and ovarian cancer, etc.). PJS is commonly seen in children and adolescents with multiple small intestinal polyps, often causing intussusception. CASE SUMMARY A 62-year-old male presented with intermittent left lower abdominal pain after drinking or consuming cold beverages that was accompanied by occasional hematochezia. Abdominal contrast-enhanced computed tomography indicated an isolated sigmoid colon grape-like lesion. Subsequently, the patient underwent laparoscopic surgery, and the pathological diagnosis was PJ hamartomatous polyp. PJS was not considered at the initial visit, as the patient was older, and the facial pigmentation was not obvious. However, significant pigmentation was observed in the perineum during digital rectal examination. Interestingly, we observed that the patient exhibited nodular shadows in the adrenal glands computed tomography images that may be related to pigmentation. Therefore, we performed the determination of adrenal cortical hormones, but the results were not abnormal. Combined with skin and mucosal pigmentation and laboratory examinations, the patient was diagnosed with PJS. After laparoscopic sigmoid colon resection, the patient's symptoms improved, and no discomfort symptoms were reported in the later follow-up. CONCLUSION The age of onset and lesion location of this case are different from those of typical or isolated PJS patients.
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Affiliation(s)
- Zhe-Sen Tian
- Department of Radiotherapy, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
| | - Xiao-Peng Ma
- Department of Anus and Intestine Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
| | - Hong-Xun Ruan
- Department of Anus and Intestine Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
| | - Yang Yang
- Department of Anus and Intestine Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang 050051, Hebei Province, China
| | - Ya-Lei Zhao
- Department of Anus and Intestine Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
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2
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Kosanam A, Labak C, Herring E, Kasliwal MK. Thoracic facet overgrowth causing radiculopathy - A rare spinal manifestation of Proteus syndrome. Clin Neurol Neurosurg 2025; 249:108730. [PMID: 39787894 DOI: 10.1016/j.clineuro.2025.108730] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Revised: 12/30/2024] [Accepted: 01/05/2025] [Indexed: 01/12/2025]
Affiliation(s)
- Anish Kosanam
- Case Western Reserve University School of Medicine, Cleveland OH, United States
| | - Colllin Labak
- Depart of Neurosurgery, University Hospitals Cleveland Medical Center, Cleveland OH, United States
| | - Eric Herring
- Depart of Neurosurgery, University Hospitals Cleveland Medical Center, Cleveland OH, United States
| | - Manish K Kasliwal
- Case Western Reserve University School of Medicine, Cleveland OH, United States; Depart of Neurosurgery, University Hospitals Cleveland Medical Center, Cleveland OH, United States.
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3
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Kuhlen M, Weins AB, Stadler N, Angelova-Toshkina D, Frühwald MC. Non-malignant features of cancer predisposition syndromes manifesting in childhood and adolescence: a guide for the general pediatrician. World J Pediatr 2025; 21:131-148. [PMID: 39641826 PMCID: PMC11885337 DOI: 10.1007/s12519-024-00853-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Accepted: 10/17/2024] [Indexed: 12/07/2024]
Abstract
PURPOSE Cancer predisposition syndromes are genetic disorders that significantly raise the risk of developing malignancies. Although the malignant manifestations of cancer predisposition syndromes are well-studied, recognizing their non-malignant features is crucial for early diagnosis, especially in children and adolescents. METHODS A comprehensive literature search was conducted using the PubMed database, focusing on non-malignant manifestations of cancer predisposition syndromes in children and adolescents. Key sources included the Clinical Cancer Research pediatric oncology series and ORPHANET. Studies that described clinical signs and symptoms affecting specific organ systems were included. RESULTS Non-malignant dermatological features often serve as early indicators of cancer predisposition syndromes, including café-au-lait spots in Neurofibromatosis Type 1 and facial angiofibromas in Tuberous Sclerosis Complex. Neurological and developmental anomalies such as cerebellar ataxia in ataxia-telangiectasia and intellectual disabilities in neurofibromatosis type 1 and tuberous sclerosis complex are significant indicators. Growth and metabolic anomalies are also notable, including overgrowth in Beckwith-Wiedemann syndrome and growth hormone deficiency in neurofibromatosis Type 1. In addition, facial anomalies, ocular manifestations, hearing issues, and thyroid anomalies are prevalent across various cancer predisposition syndromes. For instance, hearing loss may be significant in neurofibromatosis Type 2, while thyroid nodules are common in PTEN hamartoma tumor syndrome and DICER1 syndrome. Cardiovascular, abdominal, musculoskeletal, pulmonary, genitourinary manifestations, and prenatal deviations further complicate the clinical picture. CONCLUSIONS Recognizing non-malignant features of cancer predisposition syndromes is essential for early diagnosis and management. This organ-specific overview furthers awareness among healthcare providers, facilitating timely genetic counseling, surveillance programs, and preventive measures, ultimately improving patient outcomes.
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Affiliation(s)
- Michaela Kuhlen
- Pediatrics and Adolescent Medicine, Faculty of Medicine, University of Augsburg, 86156, Augsburg, Germany.
| | - Andreas B Weins
- Pediatrics and Adolescent Medicine, Faculty of Medicine, University of Augsburg, 86156, Augsburg, Germany
- Augsburger Zentrum für Seltene Erkrankungen, Faculty of Medicine, University of Augsburg, 86156, Augsburg, Germany
| | - Nicole Stadler
- Pediatrics and Adolescent Medicine, Faculty of Medicine, University of Augsburg, 86156, Augsburg, Germany
| | - Daniela Angelova-Toshkina
- Pediatrics and Adolescent Medicine, Faculty of Medicine, University of Augsburg, 86156, Augsburg, Germany
| | - Michael C Frühwald
- Pediatrics and Adolescent Medicine, Faculty of Medicine, University of Augsburg, 86156, Augsburg, Germany
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Jelsig AM, Karstensen JG, Overeem Hansen TV. Progress report: Peutz-Jeghers syndrome. Fam Cancer 2024; 23:409-417. [PMID: 38493229 DOI: 10.1007/s10689-024-00362-7] [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: 10/25/2023] [Accepted: 02/04/2024] [Indexed: 03/18/2024]
Abstract
Peutz-Jeghers syndrome is a rare, autosomal dominant polyposis syndrome. Presenting with a remarkable phenotype including development of characteristic gastrointestinal polyps, mucocutaneous pigmentations, and an increased risk of cancer, the syndrome has been subject to many studies concerning the natural course of disease. In most patients, pathogenic germline variants are detected in the STK11 gene including cases of mosaicism and structural variants. Yet, studies assessing the effect of surveillance, understanding of cancer development, as well as clinical studies evaluating chemoprevention are lacking. In addition, the impact of Peutz-Jeghers syndrome on mental health, education, and family planning are insufficiently addressed. In this progress report, we describe current knowledge, clinical phenotype, surveillance strategies, and future areas of research.
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Affiliation(s)
- Anne Marie Jelsig
- Department of Clinical Genetics, University Hospital of Copenhagen - Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark.
| | - John Gásdal Karstensen
- The Danish Polyposis Register, Gastro Unit and Department of Clinical Medicine, Amager and Hvidovre, Copenhagen University Hospital and University of Copenhagen-, Copenhagen, Denmark
| | - Thomas V Overeem Hansen
- Department of Clinical Genetics and Department of Clinical Medicine, University Hospital of Copenhagen, Rigshospitalet and Copenhagen University, Copenhagen, Denmark
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La Vecchia M, Sala G, Sculco M, Aspesi A, Dianzani I. Genetics, diet, microbiota, and metabolome: partners in crime for colon carcinogenesis. Clin Exp Med 2024; 24:248. [PMID: 39470880 PMCID: PMC11522171 DOI: 10.1007/s10238-024-01505-x] [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: 08/14/2024] [Accepted: 10/15/2024] [Indexed: 11/01/2024]
Abstract
Colorectal cancer (CRC) ranks among the most prevalent malignant tumors worldwide, with a multifactorial etiology encompassing genetic, environmental, and life-style factors, as well as the intestinal microbiota and its metabolome. These risk factors often work together in specific groups of patients, influencing how CRC develops and progresses. Importantly, alterations in the gut microbiota act as a critical nexus in this interplay, significantly affecting susceptibility to CRC. This review highlights recent insights into unmodifiable and modifiable risk factors for CRC and how they might interact with the gut microbiota and its metabolome. Understanding the mechanisms of these interactions will help us develop targeted, precision-medicine strategies that can adjust the composition of the gut microbiota to meet individual health needs, preventing or treating CRC more effectively.
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Affiliation(s)
- Marta La Vecchia
- Department of Health Sciences, Università del Piemonte Orientale, 28100, Novara, Italy
| | - Gloria Sala
- Department of Health Sciences, Università del Piemonte Orientale, 28100, Novara, Italy
| | - Marika Sculco
- Department of Health Sciences, Università del Piemonte Orientale, 28100, Novara, Italy
| | - Anna Aspesi
- Department of Health Sciences, Università del Piemonte Orientale, 28100, Novara, Italy
| | - Irma Dianzani
- Department of Health Sciences, Università del Piemonte Orientale, 28100, Novara, Italy.
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Wehbe H, Gutta A, Gromski MA. Updates on the Prevention and Management of Post-Polypectomy Bleeding in the Colon. Gastrointest Endosc Clin N Am 2024; 34:363-381. [PMID: 38395489 DOI: 10.1016/j.giec.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] [Subscribe] [Scholar Register] [Indexed: 02/25/2024]
Abstract
Post-polypectomy bleeding (PPB) remains a significant procedure-related complication, with multiple risk factors determining the risk including patient demographics, polyp characteristics, endoscopist expertise, and techniques of polypectomy. Immediate PPB is usually treated promptly, but management of delayed PPB can be challenging. Cold snare polypectomy is the optimal technique for small sessile polyps with hot snare polypectomy for pedunculated and large sessile polyps. Topical hemostatic powders and gels are being investigated for the prevention and management of PPB. Further studies are needed to compare these topical agents with conventional therapy.
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Affiliation(s)
- Hisham Wehbe
- Department of Internal Medicine, Indiana University School of Medicine, 550 University Boulevard, UH 3533, Indianapolis, IN 46202, USA
| | - Aditya Gutta
- Department of Medicine, Division of Gastroenterology and Hepatology, Indiana University School of Medicine, 550 North University Boulevard, Suite 4100 Indianapolis, IN 46202, USA
| | - Mark A Gromski
- Department of Medicine, Division of Gastroenterology and Hepatology, Indiana University School of Medicine, 550 North University Boulevard, Suite 4100 Indianapolis, IN 46202, USA.
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Matsuyama S, Fukuda A, Matsumoto A, Eguchi H, Ueo T, Ohana M, Seno H. Sporadic gastric juvenile polyposis with a novel SMAD4 nonsense mutation in a mosaic pattern. Clin J Gastroenterol 2024; 17:23-28. [PMID: 37950802 DOI: 10.1007/s12328-023-01884-w] [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: 09/01/2023] [Accepted: 10/19/2023] [Indexed: 11/13/2023]
Abstract
A 50-year-old female was diagnosed with gastric hyperplastic polyps 7 years before and was followed up at another hospital. She was referred to our hospital because of the growth of gastric polyps and progression of anemia. She had no family history of polyposis. The polyps were observed only in the stomach, increased in size and number, and the erythematous edema got worse. Endoscopic mucosal resection (EMR) of the gastric polyp was performed. Pathologically, the gastric polyp was hamartomatous polyp, and the intervening mucosa between polyps showed no atypical structure without inflammation. Given that gastric juvenile polyposis (GJP) was clinically suspected, a genetic test using peripheral blood was performed. Target resequencing and Sanger sequencing analysis revealed a nonsense mutation in the SMAD4 gene at codon 169. The mutation was detected at a low frequency of 11%, and considered a mosaic mutation. Therefore, she was diagnosed with a sporadic GJP, and total gastrectomy was performed. Immunostaining of SMAD4 for the resected specimen showed a mixture of stained and unstained area in the epithelium of the polyp, indicating partial loss of SMAD4 expression. To our knowledge, this is the first reported case of GJP with a nonsense SMAD4 mutation at codon 169 in a mosaic pattern.
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Affiliation(s)
- Sho Matsuyama
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, 54 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan.
- Department of Gastroenterology, Tenri Hospital, 200 Mishima-Cho, Tenri, Nara, 632-8552, Japan.
| | - Akihisa Fukuda
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, 54 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan
| | - Atsushi Matsumoto
- Department of Gastroenterology, Tenri Hospital, 200 Mishima-Cho, Tenri, Nara, 632-8552, Japan
| | - Hidetaka Eguchi
- Diagnostics and Therapeutics of Intractable Diseases, Intractable Disease Research Center, Juntendo University Graduate School of Medicine, Tokyo, 113-8431, Japan
| | - Taro Ueo
- Department of Gastroenterology, Tenri Hospital, 200 Mishima-Cho, Tenri, Nara, 632-8552, Japan
| | - Masaya Ohana
- Department of Gastroenterology, Tenri Hospital, 200 Mishima-Cho, Tenri, Nara, 632-8552, Japan
| | - Hiroshi Seno
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, 54 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan
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Jelsig AM, Rønlund K, Gede LB, Frederiksen JH, Karstensen JG, Birkedal U, van Overeem Hansen T. Identification of a novel pathogenic deep intronic variant in PTEN resulting in pseudoexon inclusion in a patient with juvenile polyps. J Hum Genet 2023; 68:721-724. [PMID: 37336910 DOI: 10.1038/s10038-023-01174-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Revised: 05/16/2023] [Accepted: 06/12/2023] [Indexed: 06/21/2023]
Abstract
Colorectal, hamartomatous juvenile polyps occur as part of different hereditary syndromes, including Juvenile polyposis syndrome and PTEN-hamartoma tumour syndrome. However, based on clinical manifestations alone, it is difficult to differentiate between the syndromes, and genetic analysis with an NGS-panel is often used to aid diagnostics. We report a 59-year-old male with colorectal juvenile polyps, who had been referred to genetic testing but had normal genetic analysis. He did not fulfil the clinical criteria of PTEN- hamartoma tumour syndrome, but the clinical criteria of Juvenile polyposis syndrome. With Whole Genome Sequencing we detected a novel intronic variant of unknown significance in PTEN (NC_000010.11:g.89687361 A > G(chr10, hg19), NM_000314.8:c.209 + 2047 A > G). RNA analysis classified the variant as likely pathogenic as it results in a pseudoexon inclusion introducing a frameshift and a premature stop codon. The patient was then diagnosed with PTEN-hamartoma Tumour syndrome. To our knowledge this is the first report of a variant resulting in pseudoexon inclusion in PTEN.
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Affiliation(s)
- Anne Marie Jelsig
- Department of Clinical Genetics, University Hospital of Copenhagen, Rigshospitalet, Copenhagen, Denmark.
| | - Karina Rønlund
- Department of Clinical Genetics, University Hospital of Southern Denmark, Vejle Hospital, Vejle, Denmark
| | - Lene Bjerring Gede
- Department of Clinical Genetics, University Hospital of Copenhagen, Rigshospitalet, Copenhagen, Denmark
| | - Jane Hübertz Frederiksen
- Department of Clinical Genetics, University Hospital of Copenhagen, Rigshospitalet, Copenhagen, Denmark
| | - John Gásdal Karstensen
- Danish Polyposis Registry, Gastrounit, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Ulf Birkedal
- Department of Clinical Genetics, University Hospital of Copenhagen, Rigshospitalet, Copenhagen, Denmark
| | - Thomas van Overeem Hansen
- Department of Clinical Genetics, University Hospital of Copenhagen, Rigshospitalet, Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Caroleo AM, Rotulo S, Agolini E, Macchiaiolo M, Boccuto L, Antonelli M, Colafati GS, Cacchione A, Megaro G, Carai A, De Ioris MA, Lodi M, Tornesello A, Simone V, Torroni F, Cinalli G, Mastronuzzi A. SHH medulloblastoma and very early onset of bowel polyps in a child with PTEN hamartoma tumor syndrome. Front Mol Neurosci 2023; 16:1228389. [PMID: 37692099 PMCID: PMC10483120 DOI: 10.3389/fnmol.2023.1228389] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Accepted: 08/07/2023] [Indexed: 09/12/2023] Open
Abstract
Phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PHTS) is a cancer predisposition syndrome characterized by an increased risk of developing benign and malignant tumors, caused by germline pathogenic variants of the PTEN tumour suppressor gene. PTEN gene variants often present in childhood with macrocephaly, developmental delay, and/or autism spectrum disorder while tumors and intestinal polyps are commonly detected in adults. PHTS is rarely associated with childhood brain tumors with only two reported cases of medulloblastoma (MB). We report the exceptional case of an infant carrying a germline and somatic pathogenic variant of PTEN and a germline and somatic pathogenic variant of CHEK2 who developed a MB SHH in addition to intestinal polyposis.
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Affiliation(s)
- Anna Maria Caroleo
- Department of Onco-Hematology, Cell Therapy, Gene Therapy and Hemopoietic Transplant, Bambino Gesù Children’s Hospital (IRCCS), Rome, Italy
| | - Silvia Rotulo
- Department of Pediatrics, Sapienza University of Rome, Rome, Italy
| | - Emanuele Agolini
- Laboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy
| | - Marina Macchiaiolo
- Rare Diseases and Medical Genetics Unit, IRCCS Bambino Gesù Children’s Hospital, Rome, Italy
| | - Luigi Boccuto
- School of Nursing, College of Behavioral, Social and Health Sciences Healthcare Genetics Interdisciplinary Doctoral Program, Clemson University, Clemson, SC, United States
| | - Manila Antonelli
- Faculty of Medicine and Dentistry, Department of Radiological, Oncological, and Pathological Anatomy Sciences, Sapienza University of Rome, Rome, Italy
| | | | - Antonella Cacchione
- Department of Onco-Hematology, Cell Therapy, Gene Therapy and Hemopoietic Transplant, Bambino Gesù Children’s Hospital (IRCCS), Rome, Italy
| | - Giacomina Megaro
- Department of Onco-Hematology, Cell Therapy, Gene Therapy and Hemopoietic Transplant, Bambino Gesù Children’s Hospital (IRCCS), Rome, Italy
| | - Andrea Carai
- Neurosurgery Unit, Department of Neurosciences, Bambino Gesù Children’s Hospital (IRCCS), Rome, Italy
| | - Maria Antonietta De Ioris
- Department of Onco-Hematology, Cell Therapy, Gene Therapy and Hemopoietic Transplant, Bambino Gesù Children’s Hospital (IRCCS), Rome, Italy
| | - Mariachiara Lodi
- Department of Onco-Hematology, Cell Therapy, Gene Therapy and Hemopoietic Transplant, Bambino Gesù Children’s Hospital (IRCCS), Rome, Italy
| | | | - Valeria Simone
- Pediatric Oncology Unit, Ospedale Vito Fazzi, Lecce, Italy
| | - Filippo Torroni
- Digestive Endoscopy and Surgery Unit, Bambino Gesù Children Hospital, IRCCS, Rome, Italy
| | - Giuseppe Cinalli
- Pediatric Neurosurgery Unit, Department of Neuroscience, Santobono-Pausilipon Children’s Hospital, Naples, Italy
| | - Angela Mastronuzzi
- Department of Onco-Hematology, Cell Therapy, Gene Therapy and Hemopoietic Transplant, Bambino Gesù Children’s Hospital (IRCCS), Rome, Italy
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Edmondson E, Mihalopulos G, Kwok PE, Dellert A, Olsen L, Zhang ZJ. A Case of Solitary Peutz-Jeghers Syndrome Leading to Chronic Small Bowel Obstruction Due to Intussusception From a Large Hamartomatous Polyp. Cureus 2023; 15:e37679. [PMID: 37206505 PMCID: PMC10189826 DOI: 10.7759/cureus.37679] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/16/2023] [Indexed: 05/21/2023] Open
Abstract
We report a case of a 33-year-old male who presented to the emergency department with a three-day history of severe diffuse abdominal pain associated with anorexia, nausea, and vomiting. Computed tomography (CT) imaging of the abdomen and pelvis revealed a long segment of intussusception in the proximal jejunum and a round lesion along the intussusception with punctate hyperdensities. The patient underwent a diagnostic laparoscopy converted to open small bowel resection and end-to-end anastomosis that demonstrated a pedunculated jejunal mass. The mass was removed, and the pathology revealed a hamartomatous polyp with features of Peutz-Jeghers syndrome (PJS). The patient did not have a family history, previous endoscopic findings, or physical exam findings such as mucocutaneous pigmentation that could be attributed to PJS. Definitive diagnosis of solitary PJS-type hamartomatous polyps depends on histopathological findings. Genetic analysis for mutations of the PJS susceptible gene, STK11/LB1 located at 19p13.3, as well as loss of heterozygosity at that locus, have been used for the diagnosis of PJS. In patients with large pedunculated hamartomatous polyps, chronic intussusception can occur. If pathology reveals features of Peutz-Jeghers, but the patient lacks the characteristic mucocutaneous pigmentation, family history of PJS, or additional polyps within the GI tract, then solitary PJS may be suspected.
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Affiliation(s)
| | | | - Pei E Kwok
- General Surgery, Waterbury Hospital, Waterbury, USA
| | - Audrey Dellert
- Surgery, University of Connecticut School of Medicine, Farmington, USA
| | - Luke Olsen
- Pathology and Laboratory Medicine, Waterbury Hospital, Waterbury, USA
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Gorji L, Albrecht P. Hamartomatous polyps: Diagnosis, surveillance, and management. World J Gastroenterol 2023; 29:1304-1314. [PMID: 36925460 PMCID: PMC10011967 DOI: 10.3748/wjg.v29.i8.1304] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 12/08/2022] [Accepted: 02/16/2023] [Indexed: 02/28/2023] Open
Abstract
Hereditary polyposis syndrome can be divided into three categories: Ade-nomatous, serrated, and hamartomatous polyps. Hamartomatous polyps, malformations of normal tissue presenting in a disorganized manner, are characterized by an autosomal dominant inheritance pattern. These syndromes exhibit hamartomatous gastrointestinal polyps in conjunction to extra-intestinal manifestations, which require conscientious and diligent monitoring. Peutz-Jeghers syndrome, Cowden syndrome, and juvenile polyposis syndrome are the most common displays of hamartomatous polyposis syndrome (HPS). Diagnosis can be pursued with molecular testing and endoscopic sampling. Early identification of these autosomal dominant pathologies allows to optimize malignancy sur-veillance, which helps reduce morbidity and mortality in both the affected patient population as well as at-risk family members. Endoscopic surveillance is an important pillar of prognosis and monitoring, with many patients eventually requiring surgical intervention. In this review, we discuss the diagnosis, surveillance, and management of HPS.
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Affiliation(s)
- Leva Gorji
- Department of Surgery, Kettering Health Dayton, Dayton, OH 45405, United States
| | - Peter Albrecht
- Department of Surgery, Kettering Health Dayton, Dayton, OH 45405, United States
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12
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Mahmoud A, Soliman IM, Kania BE, Ghrewati M, Baddoura W. Rare Isolated Duodenal Hamartomatous Polyp in an Elderly Patient. AMERICAN JOURNAL OF CASE REPORTS 2023; 24:e938929. [PMID: 36798003 PMCID: PMC9942536 DOI: 10.12659/ajcr.938929] [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] [Indexed: 01/22/2023]
Abstract
BACKGROUND Hamartomatous polyps represent rare sporadic lesions, characterized by fibrous stroma, vascular infiltration, and dilation of mucous glands. The lesions present in a bimodal fashion in adults as well as children from 1 to 7 years old, and are often diagnosed during endoscopic procedures. Specifically, solitary Peutz-Jeghers represents a type of hamartoma that has similar histologic features to typical Peutz-Jeghers syndrome. Hamartomatous polyps represent disorganized tissue growth and can bear relationships with genetic syndromes classified as hamartomatous polyposis syndromes. A number of these syndromes, such as Peutz-Jeghers and Cowden syndrome, can demonstrate an increased risk of malignancy. A variety of symptoms, or no symptoms at all, can accompany these polyps, such as abdominal discomfort, bowel obstruction, gastrointestinal bleeding, or intussusception in severe cases. Histologically, these polyps appear similar to Peutz-Jeghers syndrome growths; however, they lack extraintestinal manifestations. Given fairly low risk of development into malignancy, patients have a good prognosis if presenting with a solitary hamartomatous polyp. There is limited data regarding screening guidelines for this patient population. CASE REPORT Here, we present a rare case of a 73-year-old woman who had a history of anemia and status post endoscopic evaluation and was diagnosed with a benign hamartomatous polyp (juvenile-like), histologically consistent with tubulovillous adenoma. CONCLUSIONS Differentiating sporadic polyps from syndromic polyps is important, as sporadic polyps have a benign course, while those associated with a syndrome have an increased lifetime malignancy risk.
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Affiliation(s)
- Anas Mahmoud
- Department of Internal Medicine, St. Joseph’s University Medical Center, Paterson, NJ, USA
| | - Isaac M. Soliman
- Department of Internal Medicine, St. Joseph’s University Medical Center, Paterson, NJ, USA,Corresponding Author: Isaac M. Soliman, e-mail:
| | - Brooke E. Kania
- Department of Internal Medicine, St. Joseph’s University Medical Center, Paterson, NJ, USA
| | - Moutaz Ghrewati
- Department of Hematology-Oncology, St. Joseph’s University Medical Center, Paterson, NJ, USA
| | - Walid Baddoura
- Department of Gastroenterology, St. Joseph’s University Medical Center, Paterson, NJ, USA
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Dardenne A, Sirmai L, Metras J, Enea D, Svrcek M, Benusiglio PR. Prédispositions génétiques au cancer gastrique et leur association au type histologique. Bull Cancer 2022; 110:512-520. [PMID: 35963792 DOI: 10.1016/j.bulcan.2022.06.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Revised: 06/24/2022] [Accepted: 06/29/2022] [Indexed: 11/27/2022]
Abstract
About 5% of gastric cancers are associated with hereditary cancer syndromes. Histology is paramount in this context, as major susceptibility genes are associated with specific subtypes. Germline pathogenic variants in CDH1 and CTNNA1 cause Hereditary Diffuse Gastric Cancer (HDGC). Major advances have been made in the past ten years regarding HDGC. Penetrance estimates for diffuse cancer are now lower than previously thought, at 30-40%. Surveillance upper gastrointestinal endoscopy is now an acceptable alternative to prophylactic total gastrectomy. Indeed, its sensitivity in detecting advanced disease is satisfactory assuming it is performed by an expert and according to a specific protocol. The risk of intestinal-type gastric cancer is increased in patients with Lynch syndrome, although it is much lower than the risk of colorectal and endometrial cancer. Intestinal-type gastric cancers are also observed in excess in patients with hereditary polyposis, the main one being APC-associated familial adenomatous polyposis. The main and most clinically relevant manifestations in patients with polyposes remain colorectal and duodenal polyps and carcinomas, well ahead of gastric cancer. Finally, recent data point towards increased gastric cancer risk in hereditary breast and ovarian cancer.
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Cotton JL, Dang K, Hu L, Sun Y, Singh A, Rajurkar MS, Li Q, Wu X, Mao J. PTEN and LKB1 are differentially required in Gli1-expressing mesenchymal cells to suppress gastrointestinal polyposis. Cell Rep 2022; 40:111125. [PMID: 35858546 DOI: 10.1016/j.celrep.2022.111125] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Revised: 04/28/2022] [Accepted: 06/29/2022] [Indexed: 11/29/2022] Open
Abstract
PTEN and LKB1 are intimately associated with gastrointestinal tumorigenesis. Mutations of PTEN or LKB1 lead to Cowden syndrome and Peutz-Jeghers syndrome characterized by development of gastrointestinal polyps. However, the cells of origin of these polyps and underlying mechanism remain unclear. Here, we reveal that PTEN or LKB1 deficiency in Gli1+ gut mesenchymal cells, but not intestinal epithelium, drives polyp formation histologically resembling polyposis in human patients. Mechanistically, although PTEN and LKB1 converge to regulate mTOR/AKT signaling in various tumor contexts, we find that mTOR is essential for PTEN-deletion-induced polyp formation but is largely dispensable for polyposis induced by mesenchymal LKB1 deficiency. Altogether, our studies identify Gli1-expressing mesenchymal cells as a common cell of origin for polyposis associated with PTEN and LKB1 and reveal their engagement of different downstream pathways in gut mesenchyme to suppress gastrointestinal tumorigenesis.
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Affiliation(s)
- Jennifer L Cotton
- Department of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA
| | - Kyvan Dang
- Department of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA
| | - Lu Hu
- Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA
| | - Yang Sun
- Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA
| | - Alka Singh
- Department of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA
| | - Mihir S Rajurkar
- Department of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA
| | - Qi Li
- Department of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA
| | - Xu Wu
- Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
| | - Junhao Mao
- Department of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
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15
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Liu S, Zhang RF, You Y, You W, Ruan GC, Liu YP, Zhang SY, Li Y, Feng YL, Yan XM, Zhou WX, Li JN, Li J, Qian JM. The genomic landscape of Cronkhite-Canada syndrome: Possible clues for pathogenesis. J Dig Dis 2022; 23:288-294. [PMID: 35678525 DOI: 10.1111/1751-2980.13101] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Revised: 05/26/2022] [Accepted: 06/06/2022] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Cronkhite-Canada syndrome (CCS) is a rare hamartomatous polyposis syndrome with a proposed association with chronic autoimmune inflammation. To date, genetic background of patients with CCS remains less investigated. In this study we aimed to explore the genomic landscape of CCS. METHODS Whole exome sequencing was performed on peripheral blood samples extracted from 18 patients with CCS. Potential function-impacting germline variants were filtered by R software. Through systematic data analysis, a number of genetic variants were identified. Enrichment analysis was performed using the R package ClusterProfiler. RESULTS Overall, 3960 low-frequency (<0.05 or not reported in the Exome Aggregation Consortium East Asian, 1000 Genomes, or ESP6500 database) potentially function-impacting germline variants were identified, with 18 genes (FDFT1, LOC400863, MUC3A, MUC4, ZNF806, GXYLT1, MUC6, PABPC3, PSPH, ZFPM1, CIC, LOC283710, ARSD, GOLGA6L2, LOC388282, SLC25A5, TMEM247, WDR89) involved over half the patients. Functional enrichment of these genes revealed several biological processes in relation to innate immune responses and glycosylation. Only one likely pathogenic germline variant of an hamartomatous polyposis syndrome-associated gene, PTCH1, was detected in one patient. CONCLUSIONS CCS has genomic alteration patterns completely distinct from those of traditional hamartomatous polyposis syndrome. The germline mutation landscape indicates potential roles of innate immune responses and glycosylation in the pathogenesis of CCS.
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Affiliation(s)
- Shuang Liu
- Department of Allergy, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Beijing, China
| | - Run Feng Zhang
- Department of Gastroenterology, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Beijing, China
| | - Yan You
- Department of Gastroenterology, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Beijing, China
| | - Wen You
- Department of Gastroenterology, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Beijing, China
| | - Ge Chong Ruan
- Department of Gastroenterology, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Beijing, China
| | - Ya Ping Liu
- McKusick-Zhang Center for Genetic Medicine, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China
| | - Sheng Yu Zhang
- Department of Gastroenterology, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Beijing, China
| | - Yue Li
- Department of Gastroenterology, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Beijing, China
| | - Yun Lu Feng
- Department of Gastroenterology, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Beijing, China
| | - Xue Min Yan
- Department of Gastroenterology, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Beijing, China
| | - Wei Xun Zhou
- Department of Pathology, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Beijing, China
| | - Jing Nan Li
- Department of Gastroenterology, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Beijing, China
| | - Ji Li
- Department of Gastroenterology, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Beijing, China
| | - Jia Ming Qian
- Department of Gastroenterology, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Beijing, China
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16
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García-García V, López-Colombo A, Gutiérrez-Quiroz C, Téllez-Cervantes J. Peutz-Jeghers syndrome: Evidence-based decision-making, regarding a case. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2022; 87:263-265. [DOI: 10.1016/j.rgmxen.2022.03.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Accepted: 04/28/2021] [Indexed: 11/28/2022] Open
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17
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González IA, Stewart DR, Schultz KAP, Field AP, Hill DA, Dehner LP. DICER1 tumor predisposition syndrome: an evolving story initiated with the pleuropulmonary blastoma. Mod Pathol 2022; 35:4-22. [PMID: 34599283 PMCID: PMC8695383 DOI: 10.1038/s41379-021-00905-8] [Citation(s) in RCA: 77] [Impact Index Per Article: 25.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Revised: 08/09/2021] [Accepted: 08/09/2021] [Indexed: 02/06/2023]
Abstract
DICER1 syndrome (OMIM 606241, 601200) is a rare autosomal dominant familial tumor predisposition disorder with a heterozygous DICER1 germline mutation. The most common tumor seen clinically is the pleuropulmonary blastoma (PPB), a lung neoplasm of early childhood which is classified on its morphologic features into four types (IR, I, II and III) with tumor progression over time within the first 4-5 years of life from the prognostically favorable cystic type I to the unfavorable solid type III. Following the initial report of PPB, its association with other cystic neoplasms was demonstrated in family studies. The detection of the germline mutation in DICER1 provided the opportunity to identify and continue to recognize a number seemingly unrelated extrapulmonary neoplasms: Sertoli-Leydig cell tumor, gynandroblastoma, embryonal rhabdomyosarcomas of the cervix and other sites, multinodular goiter, differentiated and poorly differentiated thyroid carcinoma, cervical-thyroid teratoma, cystic nephroma-anaplastic sarcoma of kidney, nasal chondromesenchymal hamartoma, intestinal juvenile-like hamartomatous polyp, ciliary body medulloepithelioma, pituitary blastoma, pineoblastoma, primary central nervous system sarcoma, embryonal tumor with multilayered rosettes-like cerebellar tumor, PPB-like peritoneal sarcoma, DICER1-associated presacral malignant teratoid neoplasm and other non-neoplastic associations. Each of these neoplasms is characterized by a second somatic mutation in DICER1. In this review, we have summarized the salient clinicopathologic aspects of these tumors whose histopathologic features have several overlapping morphologic attributes particularly the primitive mesenchyme often with rhabdomyoblastic and chondroid differentiation and an uncommitted spindle cell pattern. Several of these tumors have an initial cystic stage from which there is progression to a high grade, complex patterned neoplasm. These pathologic findings in the appropriate clinical setting should serve to alert the pathologist to the possibility of a DICER1-associated neoplasm and initiate appropriate testing on the neoplasm and to alert the clinician about the concern for a DICER1 mutation.
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Affiliation(s)
- Iván A. González
- grid.239552.a0000 0001 0680 8770Department of Pathology and Laboratory Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA USA
| | - Douglas R. Stewart
- grid.48336.3a0000 0004 1936 8075Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD USA
| | - Kris Ann P. Schultz
- International Pleuropulmonary Blastoma/DICER1 Registry, Children’s Minnesota, Minneapolis, MN USA ,Cancer and Blood Disorders, Children’s Minnesota, Minneapolis, MN USA
| | | | - D. Ashley Hill
- International Pleuropulmonary Blastoma/DICER1 Registry, Children’s Minnesota, Minneapolis, MN USA ,ResourcePath LLC, Sterling, VA USA ,grid.253615.60000 0004 1936 9510Division of Pathology, Children’s National Medical Center, George Washington University School of Medicine and Health Sciences, Washington, DC USA
| | - Louis P. Dehner
- International Pleuropulmonary Blastoma/DICER1 Registry, Children’s Minnesota, Minneapolis, MN USA ,grid.411019.cThe Lauren V. Ackerman Laboratory of Surgical Pathology, Barnes-Jewish and St. Louis Children’s Hospitals, Washington University Medical Center, St. Louis, MO USA
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18
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Duarte M, Milikowski C. Gastrointestinal polyposis with associated cutaneous manifestations. Pathology 2021; 54:157-166. [PMID: 34763900 DOI: 10.1016/j.pathol.2021.08.009] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2021] [Accepted: 08/23/2021] [Indexed: 02/06/2023]
Abstract
Cutaneous findings are commonly associated with underlying gastrointestinal disorders and, in many instances, may be the first manifestation. Many such syndromes have incomplete penetrance and variable expressivity, making them difficult to recognise. Skin manifestations may be an easily recognised feature of the underlying disorder. Most of these syndromes are hereditary but not all are associated with malignancies; either benign or premalignant extraintestinal lesions can be the initial manifestation. Some involve a single organ system, while others involve multiple organs of the gastrointestinal tract. In this review, we have focused on Lynch syndrome (hereditary nonpolyposis colon cancer and Muir-Torre syndrome), familial adenomatous polyposis, the hamartomatous polyposis syndromes that include Peutz-Jeghers syndrome and the PTEN hamartoma syndromes, which include Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome and, lastly, Cronkhite-Canada syndrome, which is not heritable. Some of these are associated with colorectal cancer, of which 15% are heritable. The majority are inherited in an autosomal dominant fashion. These syndromes are uncommon. However, because of the strong association with the cutaneous findings, early detection and screening may be possible and are key to decreasing the morbidity and mortality associated with them, for both the patient and family members. The clinical findings, epidemiological findings, underlying genetic alterations and pathological findings are reviewed.
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Affiliation(s)
- Melissa Duarte
- Department of Pathology, Jackson Memorial Hospital/University of Miami Miller School of Medicine, Miami, FL, USA
| | - Clara Milikowski
- Department of Pathology, Jackson Memorial Hospital/University of Miami Miller School of Medicine, Miami, FL, USA.
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19
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Ercoskun P, Yuce Kahraman C, Ozkan G, Tatar A. Genetic Characterization of Hereditary Cancer Syndromes Based on Targeted Next-Generation Sequencing. Mol Syndromol 2021; 13:123-131. [DOI: 10.1159/000518927] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Accepted: 08/06/2021] [Indexed: 11/19/2022] Open
Abstract
A hereditary cancer syndrome is a genetic predisposition to cancer caused by a germline mutation in cancer-related genes. Identifying the disease-causing variant is important for both the patient and relatives at risk in cancer families because this could be a guide in treatment and secondary cancer prevention. In this study, hereditary cancer panel harboring cancer-related genes was performed on MiSeq Illumina NGS system from peripheral blood samples. Sequencing files were fed into a cloud-based data analysis pipeline. Reportable variants were classified according to the American College of Medical Genetics and Genomics guidelines. Three hundred five individuals were included in the study. Different pathogenic/likely pathogenic variants were detected in 75 individuals. The majority of these variants were in the <i>MUTYH</i>, <i>BRCA2</i>, and <i>CHEK2</i> genes. Nine novel pathogenic/likely pathogenic variants were identified in <i>BRCA1</i>, <i>BRCA2</i>, <i>GALNT12</i>, <i>ATM</i>, <i>MLH1</i>, <i>MSH2</i>, <i>APC</i>, and <i>KIT</i> genes. We obtained interesting and novel variants which could be related to hereditary cancer, and this study confirmed that NGS is an indispensable method for the risk assessment in cancer families.
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20
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Huang Z, Gong H, Guo L, Xie Y, Wei B, Tang C, Hu B. Successful endoscopic submucosal dissection of a large juvenile polyp in the stomach of an infant. Endoscopy 2021; 53:E376-E377. [PMID: 33271617 DOI: 10.1055/a-1300-0865] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Zhiyin Huang
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Hui Gong
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Linjie Guo
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Yongmei Xie
- Department of Gastroenterology, West China Women's and Children's Hospital, Sichuan University, Chengdu, China
| | - Bing Wei
- Department of Pathology, West China Hospital, Sichuan University, Chengdu, China
| | - Chengwei Tang
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Bing Hu
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
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21
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Liu S, Ma Y, You W, Li J, Li JN, Qian JM. Hamartomatous polyposis syndrome associated malignancies: Risk, pathogenesis and endoscopic surveillance. J Dig Dis 2021; 22:444-451. [PMID: 34145757 DOI: 10.1111/1751-2980.13029] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 05/20/2021] [Accepted: 06/16/2021] [Indexed: 12/11/2022]
Abstract
Hamartomatous polyposis syndromes (HPS) are a heterogeneous spectrum of diseases that are characterized by diffuse hamartomatous polyps lining the gastrointestinal (GI) tract together with extra-GI manifestations. Classical HPS includes juvenile polyposis syndrome, Peutz-Jeghers syndrome, PTEN hamartoma tumor syndrome and hereditary mixed polyposis syndrome. Patients with HPS have a higher risk of GI and extra-GI malignancies than the general population, although the underlying mechanisms remain unclear and are obviously different from the carcinogenesis of classical adenocarcinoma and colitis-associated malignancy. In this review we aimed to clarify the risks, possible mechanism and endoscopic surveillance of HPS-associated GI malignancies.
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Affiliation(s)
- Shuang Liu
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Ye Ma
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Wen You
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Ji Li
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Jing Nan Li
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Jia Ming Qian
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
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22
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Chang W, Renaut P, Pretorius C. SMAD4 juvenile polyposis syndrome and hereditary haemorrhagic telangiectasia presenting in a middle-aged man as a large fungating gastric mass, polyposis in both upper and lower GI tract and iron deficiency anaemia, with no known family history. BMJ Case Rep 2020; 13:13/12/e236855. [PMID: 33370972 PMCID: PMC7757541 DOI: 10.1136/bcr-2020-236855] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Juvenile polyposis syndrome (JPS) and hereditary haemorrhagic telangiectasia (HHT) are rare autosomal dominant diseases, where symptoms manifest at childhood. A 32-year-old man with no family history of JPS or HHT with SMAD4 gene mutation who developed signs and symptoms only at the age of 32, when he was an adult. In this article, we highlight the steps taken to diagnose this rare pathology, explain its pathophysiology and management.
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Affiliation(s)
- Wendy Chang
- General Surgery, Mackay Base Hospital, Mackay, Queensland, Australia
| | - Patricia Renaut
- Pathology, Queensland Pathology, Herston, Queensland, Australia
| | - Casper Pretorius
- General Surgery, Mackay Base Hospital, Mackay, Queensland, Australia,James Cook University School of Medicine, Douglas, Queensland, Australia
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23
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Aizezi Y, Yasen A, Zhu H, Lei Y. Treatment of intussusception caused by rare hamartomatous polyps of small intestine. ANZ J Surg 2020; 91:1026-1028. [PMID: 32926580 DOI: 10.1111/ans.16318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Revised: 08/02/2020] [Accepted: 09/04/2020] [Indexed: 11/28/2022]
Affiliation(s)
- Yilixiati Aizezi
- Department of General Surgery, Xinjiang Urumqi Friendship hospital, Urumqi, China
| | - Aimaiti Yasen
- Department of Hepatobiliary and Hydatid Disease, First Clinical College of Xinjiang Medical University, Urumqi, China
| | - Haodong Zhu
- Department of General Surgery, Xinjiang Urumqi Friendship hospital, Urumqi, China
| | - Yong Lei
- Department of General Surgery, Xinjiang Urumqi Friendship hospital, Urumqi, China
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24
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Abstract
Hamartomatous polyposis syndromes (HPS) are rare autosomal-dominant inherited disorders associated with gastrointestinal (GI) tract and other cancers. HPS include Peutz-Jeghers syndrome (PJS), juvenile polyposis syndrome (JPS), and phosphatase and tensin homolog hamartomatous tumor syndromes (PHTS). Diagnosis, management, and outcome prediction of HPS pose a clinical challenge. To characterize genotype, phenotype, histology and outcomes of individuals with HPS.
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25
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DeSouza B, Georgiou D. Advances in Hereditary Colorectal Cancer: Opportunities and Challenges for Clinical Translation. CURRENT GENETIC MEDICINE REPORTS 2020. [DOI: 10.1007/s40142-020-00183-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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26
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Rodríguez Lagos F, Sorlí Guerola J, Romero Martínez I, Codoñer Franch P. Register and clinical follow-up of patients with Peutz-Jeghers syndrome in Valencia. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2020. [DOI: 10.1016/j.rgmxen.2019.02.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
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27
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Rodríguez Lagos FA, Sorlí Guerola JV, Romero Martínez IM, Codoñer Franch P. Register and clinical follow-up of patients with Peutz-Jeghers syndrome in Valencia. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2019; 85:123-139. [PMID: 31257110 DOI: 10.1016/j.rgmx.2019.02.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/10/2018] [Revised: 02/07/2019] [Accepted: 02/25/2019] [Indexed: 12/17/2022]
Abstract
INTRODUCTION AND OBJECTIVES Peutz-Jeghers syndrome is a rare autosomal dominant inherited disease caused by a germline mutation of the STK11/LKB1 gene, located on chromosome 19p13.3. It is characterized by mucocutaneous hyperpigmentation, hamartomatous polyposis, and predisposition to cancer. The aim of the present study was to identify and register patients with Peutz-Jeghers syndrome, describe the disease, and estimate its prevalence in Valencia (Spain). MATERIALS AND METHODS A print-out of the clinical histories from 10 hospitals was obtained utilizing the ICD-9 code 759.6 from the Minimum Basic Data Set of Hospital Admissions of the Spanish Ministry of Health and Consumer Affairs. RESULTS From a total of 405 clinical histories found, 15 (9 males and 6 females) fit the diagnostic criteria of Peutz-Jeghers syndrome. Mean age at diagnosis was 13.8 years and mean age at death was 54.2 years. Four males died, all from cancer. The estimated disease prevalence was 0.4/100,000 inhabitants. All the patients presented with anemia and polyps in the small bowel (80% in the duodenum, 66.7% in the ileum, and 40% in the jejunum), 93.3% underwent urgent surgical intervention and presented with intestinal invagination, and 40% of the patients developed cancer at a mean age of 48.5 years. CONCLUSION The present study is the first register of patients with Peutz-Jeghers syndrome in Valencia, Spain. The ICD-9 code is nonspecific for rare diseases. The duodenum was the most frequent location for polyps and the majority of cases presented with intestinal invagination, bowel obstruction, and urgent surgical intervention. A large percentage of patients presented with cancer. It would be of interest to review and evaluate the existing surveillance protocols in the Valencian Community.
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Affiliation(s)
- F A Rodríguez Lagos
- Departamento de Análisis Clínicos, Hospital Universitario Dr. Peset de Valencia, Universidad de Valencia, Valencia, España.
| | - J V Sorlí Guerola
- Departamento de Medicina Preventiva y Salud Pública, Universidad de Valencia, Unidad Mixta de Investigación en Enfermedades Raras FISABIO-UV, Valencia, España; CIBER obn, ISCIII, Madrid, España
| | - I M Romero Martínez
- Servicio de Urgencias Hospitalarias, Hospital Universitario y Politécnico la Fe, Valencia, España
| | - P Codoñer Franch
- Hospital Universitario Dr. Peset de Valencia, Departamento de Pediatría. Departamento de Pediatría, Obstetricia y Ginecología, Universidad de Valencia, Valencia, España
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28
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Peutz-Jegher Syndrome With Endoscopic Polypectomy for Subacute Biliary Obstruction. J Pediatr Gastroenterol Nutr 2019; 68:e34. [PMID: 29095352 DOI: 10.1097/mpg.0000000000001808] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
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29
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Boulier K, Erwin DJ, Nagamani S, Eble TN. A case report of hamartomatous polyposis in an individual with Neurofibromatosis type 1. Clin Case Rep 2019; 7:202-205. [PMID: 30656042 PMCID: PMC6333055 DOI: 10.1002/ccr3.1908] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2018] [Revised: 10/01/2018] [Accepted: 10/05/2018] [Indexed: 11/11/2022] Open
Abstract
Even in well-described genetic syndromes, such as neurofibromatosis type 1, expansion of the phenotype should be considered as a possible explanation for atypical presentations. However, it is critical to complete the evaluation for a potential dual diagnosis, as there could be significant prognostic and management implications.
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Affiliation(s)
- Kristin Boulier
- Baylor College of MedicineHoustonTexas
- Present address:
Stanford UniversityStanfordCalifornia
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30
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Li S, Duan L, Wang FD, Lu L, Jin ZY. Carney complex: Two case reports and review of literature. World J Clin Cases 2018; 6:800-806. [PMID: 30510946 PMCID: PMC6264998 DOI: 10.12998/wjcc.v6.i14.800] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Revised: 10/16/2018] [Accepted: 10/23/2018] [Indexed: 02/05/2023] Open
Abstract
Carney complex (CNC) is an extremely rare genetic syndrome of pigmented skin lesions, endocrine hyperfunction and myxoma. Given its diverse clinical manifestations, CNC is often misdiagnosed. Recognition of some special clinical manifestations and imaging features may help with the diagnosis. Early diagnosis of CNC would alert ongoing surveillance of tumors and complications; the prognosis of CNC may thus be improved by early treatment. Herein, we report two cases of CNC with bone lesions.
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Affiliation(s)
- Shuang Li
- Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
- Department of Radiology, Peking Union Medical College Hospital, Beijing 100730, China
| | - Lian Duan
- Department of Endocrinology, Peking Union Medical College Hospital, Beijing 100730, China
| | - Feng-Dan Wang
- Department of Radiology, Peking Union Medical College Hospital, Beijing 100730, China
| | - Lin Lu
- Department of Endocrinology, Peking Union Medical College Hospital, Beijing 100730, China
| | - Zheng-Yu Jin
- Department of Radiology, Peking Union Medical College Hospital, Beijing 100730, China
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31
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Ford MM. Hamartomatous polyposis syndromes: Diagnosis and management. SEMINARS IN COLON AND RECTAL SURGERY 2018. [DOI: 10.1053/j.scrs.2018.06.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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32
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Gourier G, Audebert-Bellanger S, Vourc’h P, Fraitag S, L’Hérondelle K, Labouche A, Misery L, Abasq-Thomas C. Multiple capillary malformations of progressive onset: Capillary malformation–arteriovenous malformation syndrome (CM-AVM). Ann Dermatol Venereol 2018; 145:486-491. [DOI: 10.1016/j.annder.2018.04.010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2017] [Revised: 12/20/2017] [Accepted: 04/19/2018] [Indexed: 01/14/2023]
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33
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Achatz MI, Porter CC, Brugières L, Druker H, Frebourg T, Foulkes WD, Kratz CP, Kuiper RP, Hansford JR, Hernandez HS, Nathanson KL, Kohlmann WK, Doros L, Onel K, Schneider KW, Scollon SR, Tabori U, Tomlinson GE, Evans DGR, Plon SE. Cancer Screening Recommendations and Clinical Management of Inherited Gastrointestinal Cancer Syndromes in Childhood. Clin Cancer Res 2018; 23:e107-e114. [PMID: 28674119 DOI: 10.1158/1078-0432.ccr-17-0790] [Citation(s) in RCA: 71] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2017] [Revised: 05/08/2017] [Accepted: 05/12/2017] [Indexed: 11/16/2022]
Abstract
Hereditary gastrointestinal cancer predisposition syndromes have been well characterized, but management strategies and surveillance remain a major challenge, especially in childhood. In October 2016, the American Association for Cancer Research organized the AACR Childhood Cancer Predisposition Workshop in which international experts in care of children with a hereditary risk of cancer met to define surveillance strategies and management of children with cancer predisposition syndromes. In this article, we review the current literature in polyposis syndromes that can be diagnosed in childhood and may be associated with an increased incidence of gastrointestinal neoplasms and other cancer types. These disorders include adenomatous polyposis syndromes (APC and MUTYH), juvenile polyposis coli (BMPR1A and SMAD4), Peutz-Jeghers Syndrome (STK11/LKB1), and PTEN hamartoma tumor syndrome (PHTS; PTEN), which can present with a more limited juvenile polyposis phenotype. Herein, the panel of experts provides recommendations for clinical diagnosis, approach to genetic testing, and focus on cancer surveillance recommendations when appropriate during the pediatric period. We also review current controversies on genetic evaluation of patients with hepatoblastoma and indications for surveillance for this tumor. Childhood cancer risks and surveillance associated with disorders involving the mismatch repair genes, including Lynch syndrome and constitutional mismatch repair deficiency (CMMRD), are discussed elsewhere in this series. Clin Cancer Res; 23(13); e107-e14. ©2017 AACRSee all articles in the online-only CCR Pediatric Oncology Series.
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Affiliation(s)
- Maria Isabel Achatz
- Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland.
| | | | - Laurence Brugières
- Child and Adolescent Cancer Department, Gustave Roussy Cancer Campus, Villejuif, France
| | - Harriet Druker
- Division of Hematology/Oncology, Department of Genetic Counselling, The Hospital for Sick Children, Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada
| | - Thierry Frebourg
- Department of Genetics, Rouen University Hospital, Rouen, France
| | - William D Foulkes
- Department of Medicine, Oncology and Human Genetics, McGill University, Montreal, Canada
| | - Christian P Kratz
- Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany
| | - Roland P Kuiper
- Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
| | - Jordan R Hansford
- Children's Cancer Centre, Royal Children's Hospital; Murdoch Children's Research Institute; University of Melbourne, Melbourne, Australia
| | | | | | - Wendy K Kohlmann
- Population Health Sciences Department, Huntsman Cancer Institute, Salt Lake City, Utah
| | - Leslie Doros
- Cancer Genetics Clinic, Children's National Medical Center, Washington, DC
| | - Kenan Onel
- Department of Pediatrics, Hofstra-Northwell School of Medicine and Cohen Children's Medical Center, Manhasset, New York
| | - Kami Wolfe Schneider
- Division of Hematology, Oncology, Bone Marrow Transplant, Children's Hospital Colorado, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Sarah R Scollon
- Department of Pediatrics, Division of Hematology/Oncology, Baylor College of Medicine, Houston, Texas
| | - Uri Tabori
- Division of Hematology/Oncology, The Hospital for Sick Children, Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada
| | - Gail E Tomlinson
- Department of Pediatric Hematology-Oncology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas
| | - D Gareth R Evans
- Department of Genomic Medicine, University of Manchester, St. Mary's Hospital, Manchester, United Kingdom
| | - Sharon E Plon
- Department of Pediatrics, Division of Hematology/Oncology, Baylor College of Medicine, Houston, Texas
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34
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Guerra L, Castori M, Didona B, Castiglia D, Zambruno G. Hereditary palmoplantar keratodermas. Part II: syndromic palmoplantar keratodermas - Diagnostic algorithm and principles of therapy. J Eur Acad Dermatol Venereol 2018; 32:899-925. [DOI: 10.1111/jdv.14834] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2017] [Accepted: 01/05/2018] [Indexed: 12/19/2022]
Affiliation(s)
- L. Guerra
- Laboratory of Molecular and Cell Biology; Istituto Dermopatico dell'Immacolata-IRCCS; Rome Italy
| | - M. Castori
- Division of Medical Genetics; Casa Sollievo della Sofferenza-IRCCS; San Giovanni Rotondo Italy
| | - B. Didona
- Rare Skin Disease Center; Istituto Dermopatico dell'Immacolata-IRCCS; Rome Italy
| | - D. Castiglia
- Laboratory of Molecular and Cell Biology; Istituto Dermopatico dell'Immacolata-IRCCS; Rome Italy
| | - G. Zambruno
- Genetic and Rare Diseases Research Area and Dermatology Unit; Bambino Gesù Children's Hospital-IRCCS; Rome Italy
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35
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Matsuzaki Y, Sakuma T, Yamamoto T, Saya H. Establishment of pten knockout medaka with transcription activator-like effector nucleases (TALENs) as a model of PTEN deficiency disease. PLoS One 2017; 12:e0186878. [PMID: 29053747 PMCID: PMC5650176 DOI: 10.1371/journal.pone.0186878] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2017] [Accepted: 09/21/2017] [Indexed: 12/16/2022] Open
Abstract
Phosphatase and tensin homolog (PTEN) is a lipid and protein phosphatase that antagonizes signaling by the phosphatidylinositol 3-kinase (PI3K)–AKT signaling pathway. The PTEN gene is a major tumor suppressor, with mutations of this gene occurring frequently in tumors of humans and mice. We have now developed mutant medaka deficient in PTEN with the use of transcription activator–like effector nuclease (TALEN) technology. Medaka possesses two pten genes, ptena and ptenb, similar to zebrafish. We established 16 ptena mutant lines and two ptenb mutant lines. Homozygous single pten mutants were found to be viable and fertile. In contrast, pten double-knockout (dko) embryos manifested severe abnormalities in vasculogenesis, eye size, and tail development at 72 hours post fertilization(hpf) and died before hatching. Immunoblot analysis revealed that the ratio of phosphorylated to total forms of AKT (pAKT/AKT) in pten dko embryos was four times that in wild-type embryos, indicative of up-regulation of signaling by the PI3K-AKT pathway. Treatment of pten dko embryos with the PI3K inhibitor LY294002 reduced the pAKT/AKT ratio by about one-half and partially rescued the defect in vasculogenesis. Additional inhibitors of the PI3K-AKT pathway, including rapamycin and N-α-tosyl-L-phenylalanyl chloromethyl ketone, also partially restored vasculogenesis in the dko embryos. Our model system thus allows pten dko embryos to be readily distinguished from wild-type embryos at an early stage of development and is suitable for the screening of drugs able to compensate for PTEN deficiency.
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Affiliation(s)
- Yuriko Matsuzaki
- Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, Tokyo, Japan
| | - Tetsushi Sakuma
- Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, Hiroshima, Japan
| | - Takashi Yamamoto
- Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, Hiroshima, Japan
| | - Hideyuki Saya
- Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, Tokyo, Japan
- * E-mail:
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36
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Carrera S, Sancho A, Azkona E, Azkuna J, Lopez-Vivanco G. Hereditary pancreatic cancer: related syndromes and clinical perspective. Hered Cancer Clin Pract 2017; 15:9. [PMID: 28670351 PMCID: PMC5490219 DOI: 10.1186/s13053-017-0069-6] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2017] [Accepted: 06/21/2017] [Indexed: 02/07/2023] Open
Abstract
Pancreatic cancer is a very aggressive disease with a poor prognosis. The majority of them are attributed to sporadic causes, especially to many modifiable risk factors such as tobacco or alcohol abuse. The principal histologic subtype of pancreatic cancer is ductal adenocarcinoma. Pancreatic neuroendocrine tumors, which constitute a more indolent entity, represent second type of pancreatic cancer in terms of incidence. Individuals with a family history of pancreatic cancer carry an increased risk of developing the disease, which may be related to an underlying hereditary component. Unfortunately, in the majority of these families the suspected germline genetic cause responsible of the disease will not be identified, but approximately in a 20% of the cases a hereditary cancer predisposition syndrome with increased risk of pancreatic cancer development can be recognized. This review will be focused on the leading hereditary cancer syndromes related to pancreatic ductal adenocarcinoma and pancreatic neuroendocrine tumors. Additionally, we will try to explain clinical aspects related to the identification of germline mutations in pancreatic cancer patients and their potential implications in oncologic treatment decisions.
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Affiliation(s)
- Sergio Carrera
- Hereditary Cancer Genetic Counseling Unit- Medical Oncology Department, Cruces University Hospital, Plaza de Cruces s/n. 48903, Baracaldo, Bizkaia Spain
| | - Aintzane Sancho
- Medical Oncology Department, Cruces University Hospital, Baracaldo, Spain
| | - Eider Azkona
- Medical Oncology Department, Cruces University Hospital, Baracaldo, Spain
| | - Josune Azkuna
- Medical Oncology Department, Cruces University Hospital, Baracaldo, Spain
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37
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Abstract
BACKGROUND Collagen is the most abundant protein in the body and the main structural component of the skin. OBJECTIVE To provide a review of the histopathology of collagen alterations and to propose a classification with the most important types of collagen anomalies in dermatopathology. The authors describe some of the main morphological clues of collagen anomalies for specific diagnosis of some cutaneous inflammatory and neoplastic conditions. METHODS The authors review histopathologic collagen anomalies, concerning both morphology and disposition in some inflammatory and neoplastic cutaneous conditions, and they review previous terminology and proposed a classification of the most important types of collagen anomalies that can be seen in dermatopathological practice. RESULTS Collagen anomalies in skin can be classified into lamellar fibrosis, sclerosis, and "balls" and "rings" of collagen. Lamellar fibrosis presents as long and thin collagen bundles forming a delicate network, which can be disposed in a parallel pattern, onion-bulb-like pattern, and storiform pattern. Sclerosis is characterized by large, thick, and eosinophilic bundles of collagen, which may present as a homogenous-diffuse pattern or as individual thick bundles of collagen with few or abundant number of fibroblasts between them. Finally, the authors propose the terms "balls" and "rings" of collagen. The term "balls" of collagen stands for thick, homogenous, eosinophilic, globular collagen bundles, with no distinguishable individual composing fibers, which include the floating sign and the free-floating sign. The term "rings" of collagen is characterized by sclerotic collagen arranged in a homogenous rimming pattern around vessels without independent fibers in its composition. CONCLUSIONS Collagen anomalies may be important clues to establish specific clues for specific diagnoses in dermatopathology.
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38
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Ikemoto Y, Takayama Y, Fujii K, Masuda M, Kato C, Hatsuse H, Fujitani K, Nagao K, Kameyama K, Ikehara H, Toyoda M, Umezawa A, Miyashita T. Somatic mosaicism containing double mutations in PTCH1 revealed by generation of induced pluripotent stem cells from nevoid basal cell carcinoma syndrome. J Med Genet 2017; 54:579-584. [PMID: 28363938 DOI: 10.1136/jmedgenet-2016-104490] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2016] [Revised: 01/26/2017] [Accepted: 01/30/2017] [Indexed: 12/16/2022]
Abstract
BACKGROUND Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterised by developmental defects and tumorigenesis, such as medulloblastomas and basal cell carcinomas, caused by mutations of the patched-1 (PTCH1) gene. In this article, we seek to demonstrate a mosaicism containing double mutations in PTCH1 in an individual with NBCCS. METHODS AND RESULTS A de novo germline mutation of PTCH1 (c.272delG) was detected in a 31-year-old woman with NBCCS. Gene analysis of two out of four induced pluripotent stem cell (iPSC) clones established from the patient unexpectedly revealed an additional mutation, c.274delT. Deep sequencing confirmed a low-prevalence somatic mutation (5.5%-15.6% depending on the tissue) identical to the one found in iPSC clones. CONCLUSIONS This is the first case of mosaicism unequivocally demonstrated in NBCCS. Furthermore, the mosaicism is unique in that the patient carries one normal and two mutant alleles. Because these mutations are located in close proximity, reversion error is likely to be involved in this event rather than a spontaneous mutation. In addition, this study indicates that gene analysis of iPSC clones can contribute to the detection of mosaicism containing a minor population carrying a second mutation.
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Affiliation(s)
- Yu Ikemoto
- Department of Molecular Genetics, Kitasato University Graduate School of Medical Sciences, Sagamihara, Japan.,Center for Regenerative Medicine, National Research Institute for Child Health and Development, Tokyo, Japan
| | - Yoshinaga Takayama
- Department of Molecular Genetics, Kitasato University Graduate School of Medical Sciences, Sagamihara, Japan.,Department of Molecular Genetics, Kitasato University School of Medicine, Sagamihara, Japan
| | - Katsunori Fujii
- Department of Pediatrics, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Mokuri Masuda
- Department of Molecular Genetics, Kitasato University Graduate School of Medical Sciences, Sagamihara, Japan
| | - Chise Kato
- Department of Molecular Genetics, Kitasato University Graduate School of Medical Sciences, Sagamihara, Japan
| | - Hiromi Hatsuse
- Department of Molecular Genetics, Kitasato University School of Medicine, Sagamihara, Japan
| | - Kazuko Fujitani
- Gene Analysis Center, Kitasato University School of Medicine, Sagamihara, Japan
| | - Kazuaki Nagao
- Department of Molecular Genetics, Kitasato University Graduate School of Medical Sciences, Sagamihara, Japan.,Department of Molecular Genetics, Kitasato University School of Medicine, Sagamihara, Japan
| | - Kohzoh Kameyama
- Department of Molecular Genetics, Kitasato University Graduate School of Medical Sciences, Sagamihara, Japan.,Department of Molecular Genetics, Kitasato University School of Medicine, Sagamihara, Japan
| | - Hajime Ikehara
- Center for Regenerative Medicine, National Research Institute for Child Health and Development, Tokyo, Japan.,Department of Pediatrics, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Masashi Toyoda
- Research Team for Geriatric Medicine (Vascular Medicine), Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan
| | - Akihiro Umezawa
- Center for Regenerative Medicine, National Research Institute for Child Health and Development, Tokyo, Japan
| | - Toshiyuki Miyashita
- Department of Molecular Genetics, Kitasato University Graduate School of Medical Sciences, Sagamihara, Japan.,Department of Molecular Genetics, Kitasato University School of Medicine, Sagamihara, Japan
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39
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Scollon S, Anglin AK, Thomas M, Turner JT, Wolfe Schneider K. A Comprehensive Review of Pediatric Tumors and Associated Cancer Predisposition Syndromes. J Genet Couns 2017; 26:387-434. [PMID: 28357779 DOI: 10.1007/s10897-017-0077-8] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2016] [Accepted: 01/30/2017] [Indexed: 12/11/2022]
Abstract
An understanding of the role of inherited cancer predisposition syndromes in pediatric tumor diagnoses continues to develop as more information is learned through the application of genomic technology. Identifying patients and their relatives at an increased risk for developing cancer is an important step in the care of this patient population. The purpose of this review is to highlight various tumor types that arise in the pediatric population and the cancer predisposition syndromes associated with those tumors. The review serves as a guide for recognizing genes and conditions to consider when a pediatric cancer referral presents to the genetics clinic.
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Affiliation(s)
- Sarah Scollon
- Department of Pediatrics, Baylor College of Medicine, Texas Children's Cancer Center, Texas Children's Hospital, 1102 Bates St, FC 1200, Houston, TX, 77030, USA.
| | | | | | - Joyce T Turner
- Department of Genetics and Metabolism, Children's National Medical Center, Washington, DC, USA
| | - Kami Wolfe Schneider
- Department of Pediatrics, University of Colorado, Center for Cancer and Blood Disorders, Children's Hospital Colorado, Aurora, CO, USA
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40
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Elder JE, Hardikar W. Ocular Manifestations of Gastrointestinal Disease. THE EYE IN PEDIATRIC SYSTEMIC DISEASE 2017:263-293. [DOI: 10.1007/978-3-319-18389-3_10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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41
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Jung B, Staudacher JJ, Beauchamp D. Transforming Growth Factor β Superfamily Signaling in Development of Colorectal Cancer. Gastroenterology 2017; 152:36-52. [PMID: 27773809 PMCID: PMC5550896 DOI: 10.1053/j.gastro.2016.10.015] [Citation(s) in RCA: 182] [Impact Index Per Article: 22.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2016] [Revised: 09/29/2016] [Accepted: 10/11/2016] [Indexed: 02/07/2023]
Abstract
Transforming growth factor (TGF)-β cytokines signal via a complex network of pathways to regulate proliferation, differentiation, adhesion, migration, and other functions in many cell types. A high percentage of colorectal tumors contain mutations that disrupt TGF-β family member signaling. We review how TGF-β family member signaling is altered during development of colorectal cancer, models of study, interaction of pathways, and potential therapeutic strategies.
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Affiliation(s)
- Barbara Jung
- University of Illinois at Chicago, Chicago, Illinois.
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42
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Abstract
Hamartomatous polyps of the gastrointestinal tract can occur sporadically, however, for several hereditary syndromes, their presence is one of the major clinical features. Peutz-Jeghers syndrome, juvenile polyposis syndrome, and the PTEN hamartoma syndromes are autosomal dominant inherited disorders that predispose to formation of such polyps, especially in the colon and rectum. These can lead to increased colorectal cancer risk and should be followed and managed appropriately. In this article, the three major hereditary hamartomatous syndromes are described, including presentation, colorectal surveillance, and management.
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Affiliation(s)
- Molly M Cone
- Division of Colon and Rectal Surgery, Department of General Surgery, Vanderbilt University Medical Center, Nashville, Tennessee
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43
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Sun JG, Qi J, Yang B, Gao Y, Huang JJ, Zhao C. The clinical characteristics and treatment of intestinal hamartomas. Lasers Med Sci 2016; 31:1761-1766. [PMID: 27539463 DOI: 10.1007/s10103-016-2046-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2016] [Accepted: 08/05/2016] [Indexed: 10/21/2022]
Abstract
The study aims to investigate the intestinal (small and large intestine) clinical features and treatment of hamartoma. Nowadays, with the rapid development of new technologies, digestive system endoscopy has been proven to be an effective device for treatment, rather than just a diagnostic tool. Such development plays a revolutionary role in diagnosis and treatment for digestive diseases. And endoscopic treatment was used in this study (LED light source, wavelength 580 ∼ 595 nm, power 200 W). A retrospective analysis of 20 cases of intestinal hamartomas performed from January 2012 to January 2016 to summarize its clinical characteristics and follow-up study on the therapeutic effect of the patients. There were 8 cases for endoscopic operation, and 12 cases for surgical operation. Comparison of tumor size between endoscopic and surgical estimated by using Wilcoxon rank sum test for tumor length (Z = -3.134, p = 0.001), and for tumor diameter (Z = -2.920, p = 0.002). The results of this study showed that intestinal hamartomas and gender have no significant relationship. The incidence of the disease is concentrated under 60 years, the incidence of the small intestine is significantly higher than that of the large intestine, and the rate of misdiagnosis is high. Endoscopic and surgical treatment are the main treatment, the prognosis is good, and after the radical resection, the recurrence was less.
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Affiliation(s)
- Jian-Gang Sun
- Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Erqi area Jianshe East Road No.1, Henan, China
| | - Jingwen Qi
- Pathology, The First Affiliated Hospital of Zhengzhou University, Erqi area Jianshe East Road No.1, Henan, China
| | - Bo Yang
- Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Erqi area Jianshe East Road No.1, Henan, China.
| | - Yongshun Gao
- Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Erqi area Jianshe East Road No.1, Henan, China
| | - Jing-Jing Huang
- Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Erqi area Jianshe East Road No.1, Henan, China
| | - Chengbin Zhao
- Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Erqi area Jianshe East Road No.1, Henan, China
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44
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Salido-Vallejo R, Garnacho-Saucedo G, Vélez A. Elucidation of the mTOR Pathway and Therapeutic Applications in Dermatology. ACTAS DERMO-SIFILIOGRAFICAS 2016. [DOI: 10.1016/j.adengl.2016.03.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
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45
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Gonzalez RS, Riddle ND. Syndrome-Associated Tumors by Organ System. J Pediatr Genet 2016; 5:105-15. [PMID: 27617151 PMCID: PMC4918701 DOI: 10.1055/s-0036-1580597] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2015] [Accepted: 08/26/2015] [Indexed: 12/20/2022]
Abstract
Certain tumors suggest the possibility of a patient harboring a genetic syndrome, particularly in children. Syndrome-associated tumors of the gastrointestinal tract, genitourinary tract, gynecologic tract, heart, lungs, brain, eye, endocrine organs, and hematopoietic system will be briefly discussed.
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Affiliation(s)
- Raul S. Gonzalez
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York, United States
| | - Nicole D. Riddle
- Department of Pathology, Cunningham Pathology LLC, Birmingham, Alabama, United States
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46
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Vyas M, Yang X, Zhang X. Gastric Hamartomatous Polyps-Review and Update. CLINICAL MEDICINE INSIGHTS. GASTROENTEROLOGY 2016; 9:3-10. [PMID: 27081323 PMCID: PMC4825775 DOI: 10.4137/cgast.s38452] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/26/2016] [Revised: 03/10/2016] [Accepted: 03/20/2016] [Indexed: 02/05/2023]
Abstract
Gastric polyps are frequently encountered on endoscopic examinations. While many of these represent true epithelial lesions, some of the polyps may result from underlying stromal or lymphoid proliferations or even heterotopic tissue. Histologic examination is essential for accurate typing of the polyps to predict malignant potential and underlying possible genetic abnormalities. The focus of this review is on gastric hamartomatous polyps, which are relatively rare and diagnostically challenging. Though most of the gastric hamartomatous polyps are benign, certain types are associated with increased malignant potential. These include certain polyps associated with specific genetic familial polyposis syndromes and gastric inverted hamartomatous polyps. Identification of these polyps can result in the prevention or early diagnosis of gastric carcinoma and also help in the identification of family members with polyposis syndromes. The aim of this review is to categorize gastric hamartomatous polyps and aid in the identification of high-risk categories.
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Affiliation(s)
- Monika Vyas
- Department of Pathology, Yale University School of Medicine, New Haven, CT, USA
| | - Xiu Yang
- Department of Pathology, University of Louisville School of Medicine, Louisville, KY, USA
| | - Xuchen Zhang
- Department of Pathology, Yale University School of Medicine, New Haven, CT, USA
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47
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Rahvar M, Kerstetter J. Cutaneous manifestation of gastrointestinal disease. J Gastrointest Oncol 2016; 7:S44-54. [PMID: 27034812 PMCID: PMC4783618 DOI: 10.3978/j.issn.2078-6891.2015.059] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2015] [Accepted: 03/10/2015] [Indexed: 12/29/2022] Open
Abstract
The gastrointestinal (GI) and cutaneous systems are closely linked in origin. Skin manifestations are frequently seen as a part of different GI syndromes. Gastroenterologists play an important role in recognizing the symptoms, patient workup and arriving at appropriate diagnoses, often in consultation with dermatologists. This review discusses the diseases with both cutaneous and intestinal involvement. Hereditary polyposis GI cancers, hereditary nonpolyposis colorectal cancers (CRCs), hamartomatous disorders, and inflammatory bowel disease (IBD) are reviewed with emphasis on the genetic basis, diagnostic, histologic findings, screening modalities, and therapeutic options.
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Affiliation(s)
- Maral Rahvar
- Department of Pathology and Laboratory Medicine, Loma Linda University Medical Center, Loma Linda, CA, USA
| | - Justin Kerstetter
- Department of Pathology and Laboratory Medicine, Loma Linda University Medical Center, Loma Linda, CA, USA
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48
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Abstract
The skin is often the herald of an underlying systemic illness, and gastrointestinal malignancies can present in numerous ways in the skin. Paraneoplastic phenomenon, such as acanthosis nigricans and tripe palm, may be the first indicator of a gastrointestinal malignancy. In addition, gastrointestinal cancers can metastasize to the skin, as described in the well-known Sister Mary Joseph's nodule. Inflammatory systemic conditions such as dermatomyositis and multicentric reticulohistiocytosis can be associated with underlying malignancy. Finally, in numerous genetic syndromes with underlying malignancies, such as Muir-Torre, recognition of the skin signs leads to early diagnosis and screening.
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Salido-Vallejo R, Garnacho-Saucedo G, Vélez A. Elucidation of the mTOR Pathway and Therapeutic Applications in Dermatology. ACTAS DERMO-SIFILIOGRAFICAS 2016; 107:379-90. [PMID: 26848107 DOI: 10.1016/j.ad.2015.12.006] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2015] [Revised: 12/09/2015] [Accepted: 12/10/2015] [Indexed: 12/26/2022] Open
Abstract
The member of the phosphatidylinositol 3-kinase family, mammalian target of rapamycin, is involved in modulating inflammatory response and regulating cellular processes associated with growth, differentiation, and angiogenesis. Recent years have seen major advances in our understanding of the mammalian target of rapamycin signaling pathway and the implication of this pathway in multiple genetic and inflammatory diseases and tumors. The development of the mammalian target of rapamycin inhibitors has given rise to new treatment approaches that have led to substantially improved outcomes in many diseases. In this article, we review the role of the mammalian target of rapamycin signaling pathway in the different skin diseases with which it has been associated, examine the therapeutic applications of drugs targeting this pathway, and provide an overview of current trends and future directions in research.
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Affiliation(s)
- R Salido-Vallejo
- Servicio de Dermatología, Hospital Universitario Reina Sofía, Córdoba, España.
| | - G Garnacho-Saucedo
- Servicio de Dermatología, Hospital Universitario Reina Sofía, Córdoba, España
| | - A Vélez
- Servicio de Dermatología, Hospital Universitario Reina Sofía, Córdoba, España
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Hamartomatous polyposis in tuberous sclerosis complex: Case report and review of the literature. Pathol Res Pract 2015; 211:1025-9. [PMID: 26493680 DOI: 10.1016/j.prp.2015.09.016] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2015] [Accepted: 09/17/2015] [Indexed: 01/29/2023]
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