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Kaiser KM, Raabe J, ToVinh M, Hack G, Ahmad S, Müller N, Cassella J, Walravens SI, Alfaro P, Arias Garcia L, Kaczmarek DJ, Marwitz T, Goeser F, Nischalke HD, Lutz P, Sommer N, Vilz T, Toma M, Steiner S, Hommerding O, Oldenburg J, Hölzel M, Kadzik S, Maas A, Eckrich J, Zumfelde P, Shakeri F, Nesic S, Buness A, De Caro E, Becker M, Beyer MD, Ulas T, Aschenbrenner AC, Steinheuer LM, Thurley K, Kroh S, Uecker R, Hauser AE, Gohr FN, Schmidt FI, Wang D, Held K, Baranov O, Geldmacher C, Strassburg CP, Hüneburg R, Krämer B, Nattermann J. IL-17A-producing NKp44(-) group 3 innate lymphoid cells accumulate in Familial Adenomatous Polyposis duodenal tissue. Nat Commun 2025; 16:3873. [PMID: 40280932 PMCID: PMC12032359 DOI: 10.1038/s41467-025-58907-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Accepted: 04/07/2025] [Indexed: 04/29/2025] Open
Abstract
Familial adenomatous polyposis (FAP) is an inherited gastrointestinal syndrome associated with duodenal adenoma formation. Even among carriers of the same genetic variant, duodenal phenotypes vary, indicating that additional factors, such as the local immune system, play a role. We observe an increase in duodenal IL-17A(+)NKp44(-) innate lymphoid type 3 cell (ILC3) in FAP, localized near the epithelium and enriched in adenomas and carcinomas. Elevated IL1B, IL23A, and DLL4 transcript levels correlate with IL-17A(+)NKp44(-)ILC3 accumulation, and in vitro studies with duodenal organoids confirmed this relationship. Bulk RNA sequencing reveals upregulated Reactive oxygen species (ROS)-inducing enzymes DUOX2 and DUOXA2 in FAP adenomas. IL-17A-stimulated FAP organoids show increased DUOX2/DUOXA2 expression, Duox2 protein, and ROS production, leading to DNA damage, suggesting a mechanism by which these immune cells promote tumorigenesis. These findings suggest IL-17A(+)NKp44(-)ILC3s may contribute to a local environment that makes the epithelium more submissive for oncogenic transformation in FAP.
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Affiliation(s)
- Kim M Kaiser
- Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany
| | - Jan Raabe
- Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany
| | - Michael ToVinh
- Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany
| | - Gudrun Hack
- Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany
| | - Sarah Ahmad
- Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany
| | - Niko Müller
- Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany
| | - Julia Cassella
- Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany
| | - Sofia I Walravens
- Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany
| | - Paula Alfaro
- Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany
| | | | - Dominik J Kaczmarek
- Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany
- National Center for Hereditary Tumor Syndromes, University Hospital Bonn, Bonn, Germany
| | - Tim Marwitz
- Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany
- National Center for Hereditary Tumor Syndromes, University Hospital Bonn, Bonn, Germany
| | - Felix Goeser
- Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany
| | | | - Philipp Lutz
- Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany
| | - Nils Sommer
- Department of Surgery, University Hospital Bonn, Bonn, Germany
| | - Tim Vilz
- National Center for Hereditary Tumor Syndromes, University Hospital Bonn, Bonn, Germany
- Department of Surgery, University Hospital Bonn, Bonn, Germany
| | - Marieta Toma
- Department of Pathology, University Hospital Bonn, Bonn, Germany
| | - Susanne Steiner
- Department of Pathology, University Hospital Bonn, Bonn, Germany
| | - Oliver Hommerding
- National Center for Hereditary Tumor Syndromes, University Hospital Bonn, Bonn, Germany
- Department of Pathology, University Hospital Bonn, Bonn, Germany
| | - Johannes Oldenburg
- Institute of Experimental Haematology and Transfusion Medicine, University Hospital Bonn, Bonn, Germany
| | - Michael Hölzel
- Institute of Experimental Oncology, University Hospital Bonn, Bonn, Germany
| | - Sebastian Kadzik
- Institute of Experimental Oncology, University Hospital Bonn, Bonn, Germany
| | - Alexander Maas
- Department of Otorhinolaryngology, University Hospital Bonn, Bonn, Germany
| | - Jonas Eckrich
- Department for Otorhinolaryngology, Head and Neck Surgery, University Medical Center Mainz, Mainz, Germany
| | | | - Farhad Shakeri
- Institute for Medical Biometry, Informatics and Epidemiology, Medical Faculty, University of Bonn, Venusberg-Campus 1, 53127, Bonn, Germany
| | - Svetozar Nesic
- Institute for Medical Biometry, Informatics and Epidemiology, Medical Faculty, University of Bonn, Venusberg-Campus 1, 53127, Bonn, Germany
| | - Andreas Buness
- Institute for Genomic Statistics and Bioinformatics, Medical Faculty, University of Bonn, Venusberg-Campus 1, 53127, Bonn, Germany
| | - Emilia De Caro
- Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany
- Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany
| | - Matthias Becker
- Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany
| | - Marc D Beyer
- Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany
- Immunogenomics & Neurodegeneration, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany
- PRECISE Platform for Single Cell Genomics and Epigenomics, DZNE, University of Bonn, and West German Genome Center, Bonn, Germany
| | - Thomas Ulas
- Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany
- Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany
- PRECISE Platform for Single Cell Genomics and Epigenomics, DZNE, University of Bonn, and West German Genome Center, Bonn, Germany
| | - Anna C Aschenbrenner
- Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany
| | - Lisa M Steinheuer
- Institute of Experimental Oncology, University Hospital Bonn, Bonn, Germany
| | - Kevin Thurley
- Institute of Experimental Oncology, University Hospital Bonn, Bonn, Germany
- Systems Biology of Inflammation, German Rheumatism Research Center (DRFZ), Leibniz Association, Berlin, Germany
| | - Sandy Kroh
- Systems Biology of Inflammation, German Rheumatism Research Center (DRFZ), Leibniz Association, Berlin, Germany
- Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117, Berlin, Germany
| | - Ralf Uecker
- Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117, Berlin, Germany
- Immune Dynamics, Deutsches Rheuma-Forschungszentrum (DRFZ), a Leibniz Institute, 10117, Berlin, Germany
| | - Anja E Hauser
- Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117, Berlin, Germany
- Immune Dynamics, Deutsches Rheuma-Forschungszentrum (DRFZ), a Leibniz Institute, 10117, Berlin, Germany
| | - Florian N Gohr
- Institute of Innate Immunity, Medical Faculty, University of Bonn, Bonn, Germany
| | - Florian I Schmidt
- Institute of Innate Immunity, Medical Faculty, University of Bonn, Bonn, Germany
| | - Danni Wang
- Division of Infectious Diseases and Tropical Medicine, University Hospital, LMU Munich, 81377, Munich, Germany
| | - Kathrin Held
- Division of Infectious Diseases and Tropical Medicine, University Hospital, LMU Munich, 81377, Munich, Germany
- German Center for Infection Research (DZIF), Bonn, Germany
| | - Olga Baranov
- Division of Infectious Diseases and Tropical Medicine, University Hospital, LMU Munich, 81377, Munich, Germany
| | - Christof Geldmacher
- Division of Infectious Diseases and Tropical Medicine, University Hospital, LMU Munich, 81377, Munich, Germany
- German Center for Infection Research (DZIF), Bonn, Germany
| | - Christian P Strassburg
- Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany
- National Center for Hereditary Tumor Syndromes, University Hospital Bonn, Bonn, Germany
| | - Robert Hüneburg
- Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany
- National Center for Hereditary Tumor Syndromes, University Hospital Bonn, Bonn, Germany
| | - Benjamin Krämer
- Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany.
| | - Jacob Nattermann
- Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany.
- National Center for Hereditary Tumor Syndromes, University Hospital Bonn, Bonn, Germany.
- German Center for Infection Research (DZIF), Bonn, Germany.
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Argumánez V, Lorenzo-Zúñiga V, Bustamante-Balén M, García García S, Terol Cháfer I, Oltra S, Pons-Beltrán V. Genetic characteristics and extracolonic phenotypic manifestations in patients with familiar adenomatous polyposis. GASTROENTEROLOGIA Y HEPATOLOGIA 2025; 48:502266. [PMID: 39395692 DOI: 10.1016/j.gastrohep.2024.502266] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Revised: 09/25/2024] [Accepted: 10/04/2024] [Indexed: 10/14/2024]
Abstract
INTRODUCTION Familial adenomatous polyposis (FAP) is a hereditary disease caused by mutations in the APC gene, which is also associated with extracolonic manifestations. The objective was to characterize the extracolonic manifestations in a cohort of patients with classic FAP and the possible genotype-phenotype association. MATERIALS AND METHODS The study design was observational and descriptive. Demographic, clinical, and genetic variables were collected based on the type of mutation (frameshift, nonsense, splicing, rearrangement, and others). RESULTS We included 45 patients with FAP (mean age 47years, range 21-78; 51% female), belonging to 21 families, with a median of 2 (range 0-6) manifestations per patient. Eighty percent (n=36) had upper digestive tract involvement, with duodenal adenomas (73%), fundic gland polyposis (56%), and ampullary adenoma (36%) being the most frequent findings. The most common extraintestinal manifestations were desmoid tumors (16%) and papillary thyroid carcinoma (13%). Thirty eight percent of the patients presented an aggressive phenotype (SpigelmanIII-IV, high-grade dysplasia, invasive neoplasia, desmoid tumor, and papillary thyroid carcinoma). The most common genetic mutations were frameshift (56%), nonsense (26%), and splicing (16%), primarily located in exon15 (50%). No significant correlation was found between the type of genetic mutation and the severity or location of phenotypic manifestations. CONCLUSIONS One-third of patients with FAP present an aggressive phenotype, without a demonstrated correlation between the type of genetic alteration and the phenotypic manifestations.
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Affiliation(s)
- Víctor Argumánez
- Unidad de Endoscopia, Hospital Universitari i Politècnic La Fe/IIS La Fe, Valencia, España.
| | - Vicente Lorenzo-Zúñiga
- Unidad de Endoscopia, Hospital Universitari i Politècnic La Fe/IIS La Fe, Valencia, España
| | - Marco Bustamante-Balén
- Unidad de Endoscopia, Hospital Universitari i Politècnic La Fe/IIS La Fe, Valencia, España
| | - Sonia García García
- Unidad de Endoscopia, Hospital Universitari i Politècnic La Fe/IIS La Fe, Valencia, España
| | - Isabel Terol Cháfer
- Unidad de Endoscopia, Hospital Universitari i Politècnic La Fe/IIS La Fe, Valencia, España
| | - Silvestre Oltra
- Unidad de Genética, Hospital Universitari i Politècnic La Fe, Valencia, España
| | - Vicente Pons-Beltrán
- Unidad de Endoscopia, Hospital Universitari i Politècnic La Fe/IIS La Fe, Valencia, España
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Gila F, Khoddam S, Jamali Z, Ghasemian M, Shakeri S, Dehghan Z, Fallahi J. Personalized medicine in colorectal cancer: a comprehensive study of precision diagnosis and treatment. Per Med 2025; 22:59-81. [PMID: 39924822 DOI: 10.1080/17410541.2025.2459050] [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: 07/30/2024] [Accepted: 01/23/2025] [Indexed: 02/11/2025]
Abstract
Colorectal cancer is a common and fatal disease that affects many people globally. CRC is classified as the third most prevalent cancer among males and the second most frequent cancer among females worldwide. The purpose of this article is to examine how personalized medicine might be used to treat colorectal cancer. The classification of colorectal cancer based on molecular profiling, including the detection of significant gene mutations, genomic instability, and gene dysregulation, is the main topic of this discussion. Advanced technologies and biomarkers are among the detection methods that are explored, demonstrating their potential for early diagnosis and precise prognosis. In addition, the essay explores the world of treatment possibilities by providing light on FDA-approved personalized medicine solutions that provide individualized and precise interventions based on patient characteristics. This article assesses targeted treatments like cetuximab and nivolumab, looks at the therapeutic usefulness of biomarkers like microsatellite instability (MSI) and circulating tumor DNA (ctDNA), and investigates new approaches to combat resistance. Through this, our review provides a thorough overview of personalized medicine in the context of colorectal cancer, ultimately highlighting its potential to revolutionize the field and improve patient care.
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Affiliation(s)
- Fatemeh Gila
- Department of Medical Genetics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Somayeh Khoddam
- Department of Medical Genetics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Zahra Jamali
- Department of Medical Genetics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohmmad Ghasemian
- Department of Medical Genetics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Shayan Shakeri
- Department of Medical Genetics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Zeinab Dehghan
- Department of Comparative Biomedical Sciences, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
- Autoimmune Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Jafar Fallahi
- Department of Molecular Medicine, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
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Abdelmaksoud-Dammak R, Ammous-Boukhris N, Guidara S, Kamoun H, Gdoura H, Barkia B, Boudabbous M, Tahri N, Ameur HB, Boujelbene S, Gargouri RM. Gardner syndrome in a Tunisian family: Identification of a rare APC mutation through targeted NGS. Gene 2025; 935:149065. [PMID: 39486663 DOI: 10.1016/j.gene.2024.149065] [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: 07/18/2024] [Revised: 09/30/2024] [Accepted: 10/29/2024] [Indexed: 11/04/2024]
Abstract
Gardner syndrome (GS) is a subtype of familial adenomatous polyposis (FAP) characterized by colorectal polyps, multiple osteomas, soft tissue tumors, and specific oral manifestations, such as jaw osteomas. GS is caused by mutations in the APC gene, resulting in a nonfunctional protein. This study reports a comprehensive clinical evaluation and genetic analysis of a Tunisian family affected by GS. Targeted exome sequencing and Sanger sequencing techniques were employed to identify and validate mutations in the APC gene. Clinical observations of the patient revealed multiple sebaceous cysts, frontal and maxillary osteomas, and several gastrointestinal polyps. Genetic analysis revealed a pathogenic variant (c.4652-4655del) in the APC gene, leading to a truncated protein. Additionally, genetic testing of the patient's child indicated that the child does not carry the APC pathogenic variant. In conclusion, our study highlights the importance of genetic testing in raising awareness of GS among clinicians to ensure early diagnosis and effective management, thereby reducing the risk of development and progression of colorectal cancer.
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Affiliation(s)
- Rania Abdelmaksoud-Dammak
- Center of Biotechnology of Sfax, Laboratory of Eukaryotes Molecular Biotechnology. University of Sfax, Tunisia
| | - Nihel Ammous-Boukhris
- Center of Biotechnology of Sfax, Laboratory of Eukaryotes Molecular Biotechnology. University of Sfax, Tunisia
| | - Souhir Guidara
- Department of Human Genetics, Hedi Chaker Hospital, University of Sfax, Tunisia
| | - Hassen Kamoun
- Department of Human Genetics, Hedi Chaker Hospital, University of Sfax, Tunisia
| | - Hela Gdoura
- Department of Gastroenterology, Hedi Chaker Hospital, University of Sfax, Tunisia
| | - Baha Barkia
- Department of Gastroenterology, Hedi Chaker Hospital, University of Sfax, Tunisia
| | - Mouna Boudabbous
- Department of Gastroenterology, Hedi Chaker Hospital, University of Sfax, Tunisia
| | - Nabil Tahri
- Department of Gastroenterology, Hedi Chaker Hospital, University of Sfax, Tunisia
| | - Hazem Ben Ameur
- Department of Surgery, Habib Bourguiba Hospital, University of Sfax, Tunisia
| | - Salah Boujelbene
- Department of Surgery, Habib Bourguiba Hospital, University of Sfax, Tunisia
| | - Raja Mokdad Gargouri
- Center of Biotechnology of Sfax, Laboratory of Eukaryotes Molecular Biotechnology. University of Sfax, Tunisia.
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Karthik V, Jabbar PK, Alam A, Nair A. Precocious puberty: the unlikely herald of Familial adenomatous polyposis in a young girl. BMJ Case Rep 2025; 18:e263412. [PMID: 39755553 DOI: 10.1136/bcr-2024-263412] [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: 01/06/2025] Open
Abstract
We describe the case of a girl in her middle childhood who presented with signs of heterosexual precocious puberty in the form of axillary and pubic hair growth, acne and clitoromegaly. Investigations showed elevated androgens and autonomous cortisol excess, suggesting an adrenal source. CT imaging confirmed a left adrenal mass and multiple colonic polyps. The family history of colonic polyps in her father, along with the presence of congenital hypertrophy of the retinal pigment epithelium and colonic polyps on colonoscopy, led to a diagnosis of familial adenomatous polyposis (FAP), subsequently confirmed by genetic testing. The patient underwent a successful adrenalectomy, with histopathology confirming an adrenocortical adenoma. Postsurgery, her hormonal levels normalised and symptoms improved. This case presents a unique combination of heterosexual precocious puberty caused by a cortisol and androgen co-secreting adrenal tumour in a girl with FAP, highlighting the complex interplay between endocrine disorders and genetic syndromes.
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Affiliation(s)
- Vijayakumar Karthik
- Endocrinology, Government Medical College Thiruvananthapuram, Thiruvananthapuram, India
- Endocrinology, SP Medifort Hospital, Thiruvananthapuram, Kerala, India
| | | | - Ahmad Alam
- Rajiv Gandhi Centre for Diabetes and Endocrinology, Jawaharlal Nehru Medical College and Hospital, Aligarh, India
| | - Abilash Nair
- Endocrinology, Government Medical College Thiruvananthapuram, Thiruvananthapuram, Kerala, India
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Jeyaraman K, Concolino P, Falhammar H. Adrenocortical tumors and hereditary syndromes. Expert Rev Endocrinol Metab 2025; 20:1-19. [PMID: 39570085 DOI: 10.1080/17446651.2024.2431748] [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: 06/10/2024] [Accepted: 11/15/2024] [Indexed: 11/22/2024]
Abstract
INTRODUCTION Adrenocortical tumors (ACTs) are frequently encountered in clinical practice. They vary in clinical and biological characteristics from nonfunctional to life threatening hormone excess, from benign to highly aggressive malignant tumors. Most ACTs appear to be benign and nonfunctioning. It has been controversial how these apparently benign and nonfunctioning tumors should be monitored. Over the past few decades, significant advances have been made in understanding the regulation of growth and tumorigenesis in adrenocortical cells. Defining the molecular pathomechanisms in inherited tumor syndromes led to the expansion of research to sporadic ACTs. Distinct molecular signatures have been identified in sporadic ACTs and a potential genomic classification of ACT has been proposed. AREAS COVERED In this review, we discuss the various adrenocortical pathologies associated with hereditary syndromes with special focus on their molecular pathomechanisms, the understanding of which is important in the era of precision medicine. EXPERT OPINION Identifying the molecular pathomechanisms of the adrenocortical tumorigenesis in inherited syndromes has led to the understanding of the alterations in different signaling pathways that help explain the wide variations in the biology and behavior of ACTs.
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Affiliation(s)
| | - Paola Concolino
- Dipartimento di Scienze di Laboratorio ed Ematologiche, UOC Chimica, Biochimica e Biologia Molecolare Clinica, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy
| | - Henrik Falhammar
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
- Department of Endocrinology, Karolinska University Hospital, Stockholm, Sweden
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Rausa E, Duroni V, Ferrari D, Signoroni S, Ciniselli CM, Lauricella S, Brignola C, Ricci MT, Gronchi A, Verderio P, Vitellaro M. Risk factors and protective measures for desmoid tumours in familial adenomatous polyposis: retrospective cohort study. BJS Open 2024; 9:zrae148. [PMID: 39787025 PMCID: PMC11683362 DOI: 10.1093/bjsopen/zrae148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Accepted: 10/17/2024] [Indexed: 01/12/2025] Open
Abstract
BACKGROUND Familial adenomatous polyposis is a cancer-predisposing syndrome caused by germline pathogenic variants of the adenomatous polyposis coli gene, leading to numerous colorectal polyps and a high risk of colorectal cancer. Desmoid tumours have become significant in the management of familial adenomatous polyposis after a colectomy, yet the exact incidence remains undetermined due to a lack of dedicated surveillance. METHODS This retrospective study accessed data from the prospectively maintained Hereditary Digestive Tumours Registry from 2000 to 2023. Desmoid-free survival was analysed using Cox regression and Kaplan-Meier curves. RESULTS A total of 202 patients with familial adenomatous polyposis who underwent colorectal surgery were enrolled. Of the patients, 21 (10.4%) developed intra-abdominal desmoid tumours after surgery. Desmoid tumours were associated with surgical procedure, histology of cancer at the time of surgery, and family history of intra-abdominal desmoid tumours. The overall desmoid-free survival probability at a median follow-up of 84 months was 90%. Histology of cancer at the time of surgery (HR 0.25 (95% c.i. 0.10 to 0.59)), family history of intra-abdominal desmoid tumours (HR 2.92 (95% c.i. 1.22 to 6.97)), an open approach compared with a laparoscopic approach (HR 2.43 (95% c.i. 1.03 to 5.73)), and a proctocolectomy compared with a rectal-sparing total colectomy (HR 3.01 (95% c.i. 1.28 to 7.10)) emerged as significant prognostic factors affecting desmoid-free survival. CONCLUSION A minimally invasive rectal-sparing total colectomy appears protective against the development of desmoid tumours. Early surgery does not seem to increase desmoid tumour risk. A dedicated surveillance regimen for desmoid tumours in patients with familial adenomatous polyposis is needed to improve outcomes and quality of life.
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Affiliation(s)
- Emanuele Rausa
- Unit of Hereditary Digestive Tract Tumours, Fondazione IRCCS Istituto Nazionale dei Tumouri, Milan, Italy
- Colorectal Surgery Division, Fondazione IRCCS Istituto Nazionale dei Tumouri, Milan, Italy
| | - Valeria Duroni
- Unit of Bioinformatics and Biostatistics, Fondazione IRCCS Istituto Nazionale dei Tumouri, Milan, Italy
| | - Davide Ferrari
- Unit of Hereditary Digestive Tract Tumours, Fondazione IRCCS Istituto Nazionale dei Tumouri, Milan, Italy
- Colorectal Surgery Division, Fondazione IRCCS Istituto Nazionale dei Tumouri, Milan, Italy
- General Surgery Residency Programme, Università degli Studi di Milano, Milan, Italy
| | - Stefano Signoroni
- Unit of Hereditary Digestive Tract Tumours, Fondazione IRCCS Istituto Nazionale dei Tumouri, Milan, Italy
| | - Chiara M Ciniselli
- Unit of Bioinformatics and Biostatistics, Fondazione IRCCS Istituto Nazionale dei Tumouri, Milan, Italy
| | - Sara Lauricella
- Unit of Hereditary Digestive Tract Tumours, Fondazione IRCCS Istituto Nazionale dei Tumouri, Milan, Italy
- Colorectal Surgery Division, Fondazione IRCCS Istituto Nazionale dei Tumouri, Milan, Italy
| | - Clorinda Brignola
- Unit of Hereditary Digestive Tract Tumours, Fondazione IRCCS Istituto Nazionale dei Tumouri, Milan, Italy
| | - Maria T Ricci
- Unit of Hereditary Digestive Tract Tumours, Fondazione IRCCS Istituto Nazionale dei Tumouri, Milan, Italy
| | - Alessandro Gronchi
- Sarcoma Surgery Unit, Department of Surgery, Fondazione IRCCS Istituto Nazionale Dei Tumouri, Milan, Italy
| | - Paolo Verderio
- Unit of Bioinformatics and Biostatistics, Fondazione IRCCS Istituto Nazionale dei Tumouri, Milan, Italy
| | - Marco Vitellaro
- Unit of Hereditary Digestive Tract Tumours, Fondazione IRCCS Istituto Nazionale dei Tumouri, Milan, Italy
- Colorectal Surgery Division, Fondazione IRCCS Istituto Nazionale dei Tumouri, Milan, Italy
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Shah S, Lopez-Font F, Malek D, Fan J, Cruz NFSD, Negron C, Williams BK, Berrocal AM. Ovoid foveal hyperreflective lesions as a sign of familial adenomatous polyposis: A case series and review. Am J Ophthalmol Case Rep 2024; 36:102217. [PMID: 39553912 PMCID: PMC11566323 DOI: 10.1016/j.ajoc.2024.102217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Revised: 10/13/2024] [Accepted: 10/30/2024] [Indexed: 11/19/2024] Open
Abstract
Purpose To report 2 cases of presumed retinal hamartoma (RH) in pediatric patients with genetically-confirmed familial adenomatous polyposis (FAP), both evaluated by optical coherence tomography (OCT) and one evaluated with optical coherence tomography angiography (OCTA). Observations A six-year-old girl presented with occasional blurry vision in the left eye. OCT showed a foveal hyperreflective lesion with disruption of photoreceptors and retinal pigment epithelium (RPE). A nine-year-old female with a past medical history of FAP presented with progressively decreasing vision and floaters in the right eye for the past 6 months. OCT showed a well-demarcated hyperreflective ovoid lesion in the fovea. OCTA revealed no flow signal within the lesion, as well as a second smaller hyperreflective lesion temporal to the fovea. Both patients were diagnosed with presumed retinal hamartoma in the setting of FAP. Conclusions and Importance Presumed RH can occur in genetically-confirmed, pediatric FAP. On OCTA imaging, these lesions show no intrinsic vascularity. Evaluation with OCT and knowledge of foveal changes in these patients can help identify underlying systemic disease.
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Affiliation(s)
- Serena Shah
- Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, 900 NW 17 Street, Miami, FL 33136, USA
| | - Francisco Lopez-Font
- Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, 900 NW 17 Street, Miami, FL 33136, USA
| | - Davina Malek
- Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, 900 NW 17 Street, Miami, FL 33136, USA
| | - Jason Fan
- Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, 900 NW 17 Street, Miami, FL 33136, USA
| | - Natasha Ferreira Santos da Cruz
- Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, 900 NW 17 Street, Miami, FL 33136, USA
| | - Catherin Negron
- Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, 900 NW 17 Street, Miami, FL 33136, USA
| | - Basil K. Williams
- Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, 900 NW 17 Street, Miami, FL 33136, USA
| | - Audina M. Berrocal
- Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, 900 NW 17 Street, Miami, FL 33136, USA
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9
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Tahaseen SM, Kirti R, Kumar R, Pandey S, Rao R, Kumar A, Arya R, Maji T, Biswas R. Gastrointestinal pathology in patients presenting with iron deficiency anaemia: A single-centre cross-sectional study. J Family Med Prim Care 2024; 13:5341-5348. [PMID: 39722951 PMCID: PMC11668466 DOI: 10.4103/jfmpc.jfmpc_1150_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Revised: 08/13/2024] [Accepted: 08/20/2024] [Indexed: 12/28/2024] Open
Abstract
Background About a third of the world's population is estimated to suffer from anaemia, and iron deficiency is expected to account for about half of all anaemia cases. This study was designed to get an estimate of the proportion of patients with iron deficiency anaemia (IDA) who have a significant gastrointestinal (GI) pathology, in particular a GI malignancy, and to identify any risk factors or predictors for the same. Methods This cross-sectional study was conducted at a hospital in Eastern India. The study population comprised males above the age of 18 and postmenopausal females with IDA, excluding those haemodynamically unstable or with chronic diseases. Data collection included a detailed history, sociodemographic details, dietary habits, GI symptoms, and severity of anaemia. Faecal occult blood tests (OBTs) were conducted, and patients were referred for upper and lower GI endoscopy with biopsies. Results Out of the 257 patients, 50.97% (n = 131) had a significant GI pathology, and 25.68% (n = 66) had a GI malignancy. Male gender (AOR: 5.203, 95% CI: 1.725-15.698) and a positive stool OBT (AOR: 6.516, 95% CI: 2.255-18.828) were found to be independent risk factors for any GI pathology. Age 40 years or above (AOR: 11.376, 95% CI: 1.199-107.946), loss of appetite (AOR: 15.548, 95% CI: 1.416-170.735), pain abdomen (AOR: 5.566, 95% CI: 1.149-26.953), dysphagia (AOR: 7.945, 95% CI: 1.036-60.915), family history of malignancy (AOR: 46.726, 95% CI: 4.076-535.645), and positive OBT (AOR: 22.430, 95% CI: 3.933-127.915) were found to be independent risk factors of GI malignancy. Conclusions This study shows that a large proportion of adult males and postmenopausal females presenting with IDA in India have significant GI pathology. Furthermore, a significant proportion of them have GI malignancies. Thus, bidirectional endoscopy should be considered for these patients. Male patients, age >40, those with history of loss of appetite or weight, pain abdomen or dysphagia, positive family history, and positive OBT should be prioritised for the investigation.
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Affiliation(s)
- Shaik Mohammad Tahaseen
- Department of General Medicine, All India Institute of Medical Sciences, Patna, Bihar, India
| | - Ravi Kirti
- Department of General Medicine, All India Institute of Medical Sciences, Patna, Bihar, India
| | - Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna, Bihar, India
| | - Sanjay Pandey
- Department of Community and Family Medicine, All India Institute of Medical Sciences, Patna, Bihar, India
| | - Rajath Rao
- Department of Community Medicine, Kasturba Medical College, Mangalore, Karnataka, India
| | - Anjani Kumar
- Department of General Medicine, All India Institute of Medical Sciences, Patna, Bihar, India
| | - Rahul Arya
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna, Bihar, India
| | - Tanmoy Maji
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna, Bihar, India
| | - Ratnadeep Biswas
- Department of General Medicine, All India Institute of Medical Sciences, Patna, Bihar, India
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10
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Kojima T, Kurachi K, Iwaizumi M, Tatsuta K, Sugiyama K, Akai T, Sakata M, Morita Y, Kikuchi H, Hiramatsu Y, Takeuchi H. Adenomatous Polyposis Coli Gene Mutations, Risk Factors, and Long-term Outcomes Associated With Desmoid Tumors in Patients With Familial Adenomatous Polyposis After Colectomy in Japan. J Clin Gastroenterol 2024:00004836-990000000-00359. [PMID: 39729982 DOI: 10.1097/mcg.0000000000002071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Accepted: 08/06/2024] [Indexed: 12/29/2024]
Abstract
GOALS To clarify the characteristics of desmoid tumors in Japanese patients with familial adenomatous polyposis after colectomy. BACKGROUND Few comprehensive reports have been published on desmoid tumors in Asian patients with familial adenomatous polyposis. STUDY This retrospective study included the data of 81 patients with familial adenomatous polyposis who underwent surgery between 1978 and 2021. The adenomatous polyposis coli gene mutation sites, risk factors, and long-term outcomes associated with desmoid tumors in Japanese patients with familial adenomatous polyposis after colectomy were analyzed. RESULTS No association was observed between the gene mutation sites and desmoid tumor development in 40 patients who underwent genetic analyses. The rate of desmoid tumor development was 30.3% in 66 patients. Multivariate analysis revealed that age below 32 years at colectomy (hazard ratio = 5.491, 95% confidence interval 1.820-16.50, P < 0.001) and familial adenomatous polyposis-related malignancies other than colorectal cancer (hazard ratio = 5.574, 95% confidence interval 2.075-14.98, P < 0.001) were independent risk factors for desmoid tumor development following colectomy. The 10-year disease-specific survival and overall survival rates for desmoid tumors were 92.9% and 76.9%, respectively. The median surveillance duration was 90 months. CONCLUSIONS Adenomatous polyposis coli gene mutation sites alone were not considered a factor for delaying or avoiding colectomy to prevent desmoid tumors in Japanese patients with familial adenomatous polyposis. The timing of colectomy and careful surveillance should be considered for managing patients at a high risk of developing desmoid tumors. Desmoid tumors in patients with familial adenomatous polyposis did not significantly impact prognosis, and pharmacological treatments are important for disease control.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Yoshihiro Hiramatsu
- Department of Surgery
- Department of Perioperative Functioning Care and Support, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
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11
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Brahmbhatt S, Agarwal A, Shetty D, Desai A, Bhatt AA. "Genetic tumor syndromes of the head and neck: Update in the genomic era". Neuroradiol J 2024:19714009241269462. [PMID: 39110991 PMCID: PMC11571379 DOI: 10.1177/19714009241269462] [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: 11/20/2024] Open
Abstract
Genetic tumor syndromes are due to inherited genetic mutations, which have recently come to the attention of clinicians due to the widespread adoption of DNA sequencing, ultimately leading to imaging for surveillance. As a result, radiologists must be familiar with the clinical, genetic, and radiologic features of these syndromes. This article reviews genetic tumor syndromes of the head and neck according to the recently updated WHO's 5th edition.
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Affiliation(s)
| | - Amit Agarwal
- Department of Radiology, Mayo Clinic, Jacksonville, FL, USA
| | - Dhruv Shetty
- Department of Radiology, Mayo Clinic, Jacksonville, FL, USA
| | - Amit Desai
- Department of Radiology, Mayo Clinic, Jacksonville, FL, USA
| | - Alok A. Bhatt
- Department of Radiology, Mayo Clinic, Jacksonville, FL, USA
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12
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Rashi S, Seeni Mohamed AM, Ramakrishnan KK, Subramonian SG, Udaya Bhanu V. Exploring Familial Adenomatous Polyposis Through Radiology: A Case Series and Literature Review. Cureus 2024; 16:e64855. [PMID: 39156381 PMCID: PMC11330316 DOI: 10.7759/cureus.64855] [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] [Received: 05/14/2024] [Accepted: 07/18/2024] [Indexed: 08/20/2024] Open
Abstract
Familial adenomatous polyposis (FAP) is a dominantly inherited, autosomal form of hereditary condition caused by a germline mutation in the adenomatous polyposis coli (APC) gene. The early development of adenomatous polyps in the colon and rectum predisposes to rampant proliferation, which usually leads to colorectal cancer. Hence, this condition demands intensive surveillance and aggressive intervention. This case report epitomizes the convergence of advanced imaging with genetic diagnosis and, in essence, points toward a complete multidisciplinary approach as critical for proper management of FAP. The detailed evaluation of two siblings presenting with similar gut symptoms from this article focused on the individualization that this condition needs when managed, although underpinning the critical role coordinated care plays in changing disease outcomes.
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Affiliation(s)
- Seetha Rashi
- Department of Radiology, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, IND
| | - Abdul Majith Seeni Mohamed
- Department of Radiology, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, IND
| | - Karthik Krishna Ramakrishnan
- Department of Radiology, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, IND
| | - Sakthi Ganesh Subramonian
- Department of Radiology, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, IND
| | - Vadupu Udaya Bhanu
- Department of Radiology, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, IND
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13
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Zaffaroni G, Mannucci A, Koskenvuo L, de Lacy B, Maffioli A, Bisseling T, Half E, Cavestro GM, Valle L, Ryan N, Aretz S, Brown K, Buttitta F, Carneiro F, Claber O, Blanco-Colino R, Collard M, Crosbie E, Cunha M, Doulias T, Fleming C, Heinrich H, Hüneburg R, Metras J, Nagtegaal I, Negoi I, Nielsen M, Pellino G, Ricciardiello L, Sagir A, Sánchez-Guillén L, Seppälä TT, Siersema P, Striebeck B, Sampson JR, Latchford A, Parc Y, Burn J, Möslein G. Updated European guidelines for clinical management of familial adenomatous polyposis (FAP), MUTYH-associated polyposis (MAP), gastric adenocarcinoma, proximal polyposis of the stomach (GAPPS) and other rare adenomatous polyposis syndromes: a joint EHTG-ESCP revision. Br J Surg 2024; 111:znae070. [PMID: 38722804 PMCID: PMC11081080 DOI: 10.1093/bjs/znae070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Revised: 02/12/2024] [Accepted: 02/25/2024] [Indexed: 05/12/2024]
Abstract
BACKGROUND Hereditary adenomatous polyposis syndromes, including familial adenomatous polyposis and other rare adenomatous polyposis syndromes, increase the lifetime risk of colorectal and other cancers. METHODS A team of 38 experts convened to update the 2008 European recommendations for the clinical management of patients with adenomatous polyposis syndromes. Additionally, other rare monogenic adenomatous polyposis syndromes were reviewed and added. Eighty-nine clinically relevant questions were answered after a systematic review of the existing literature with grading of the evidence according to Grading of Recommendations, Assessment, Development, and Evaluation methodology. Two levels of consensus were identified: consensus threshold (≥67% of voting guideline committee members voting either 'Strongly agree' or 'Agree' during the Delphi rounds) and high threshold (consensus ≥ 80%). RESULTS One hundred and forty statements reached a high level of consensus concerning the management of hereditary adenomatous polyposis syndromes. CONCLUSION These updated guidelines provide current, comprehensive, and evidence-based practical recommendations for the management of surveillance and treatment of familial adenomatous polyposis patients, encompassing additionally MUTYH-associated polyposis, gastric adenocarcinoma and proximal polyposis of the stomach and other recently identified polyposis syndromes based on pathogenic variants in other genes than APC or MUTYH. Due to the rarity of these diseases, patients should be managed at specialized centres.
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Affiliation(s)
- Gloria Zaffaroni
- Center for Hereditary Tumors, Bethesda Hospital, Duisburg, Germany
- Faculty of Medicine and Surgery, University of Milan, Milan, Italy
| | - Alessandro Mannucci
- Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Laura Koskenvuo
- Department of Gastroenterological Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Borja de Lacy
- Department of Gastrointestinal Surgery, Hospital Clinic of Barcelona, Barcelona, Spain
| | - Anna Maffioli
- Faculty of Medicine and Surgery, University of Milan, Milan, Italy
- Department of General Surgery, Sacco Hospital, ASST Fatebenefratelli Sacco, Milan, Italy
| | - Tanya Bisseling
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Elizabeth Half
- Cancer Prevention and Hereditary GI Cancer Unit, Rambam Health Care Campus, Haifa, Israel
| | - Giulia Martina Cavestro
- Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Laura Valle
- Hereditary Cancer Program, Catalan Institute of Oncology, Oncobell Program, IDIBELL, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain
| | - Neil Ryan
- The College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK
| | - Stefan Aretz
- Institute of Human, Genetics, Medical Faculty, University of Bonn and National Center for Hereditary Tumour Syndromes, University Hospital Bonn, Bonn, Germany
| | - Karen Brown
- Leicester Cancer Research Centre, University of Leicester, Leicester, UK
| | - Francesco Buttitta
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
- IRCCS University Hospital of Bologna, Policlinico di Sant’Orsola, Bologna, Italy
| | - Fatima Carneiro
- Faculty of Medicine of Porto University, Centro Hospitalar Universitário de São João, Ipatimup, Porto, Portugal
| | - Oonagh Claber
- Department of Clinical Genetics, Northern Genetics Service, Newcastle upon Tyne, UK
| | - Ruth Blanco-Colino
- Department of Gastrointestinal Surgery, Vall d’Hebron University Hospital, Barcelona, Spain
- Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Maxime Collard
- Department of Digestive Surgery, Hôpital Saint-Antoine, Sorbonne University, APHP, Paris, France
| | - Emma Crosbie
- Division of Cancer Sciences, University of Manchester, Manchester, UK
| | - Miguel Cunha
- Department of Surgery, Algarve Universitary Hospital Center, Colorectal SurgeryGroup, Portimao, Portugal
| | - Triantafyllos Doulias
- Department of Colorectal Surgery, Colchester Hospital, East Suffolk and North Essex NHS Foundation Trust, Colchester, UK
- Colorectal Surgery Department, Kettering Hospital, University Hospitals of Northamptonshire, Kettering, Northamptonshire, UK
- Department of Genetics and Genome Biology, Honorary Lecturer in the Leicester Cancer Research Centre, Leicester, UK
| | - Christina Fleming
- Department of Colorectal Surgery, University Hospital Limerick, Limerick, Ireland
| | - Henriette Heinrich
- Department for Gastroenterology and Hepatology, Clarunis Universitäres Bauchzentrum, Universitätsspital Basel, Basel, Switzerland
| | - Robert Hüneburg
- Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany
- National Center for Hereditary Tumour Syndromes, University Hospital Bonn, Bonn, Germany
| | - Julie Metras
- Department of Digestive Surgery, Hôpital Saint-Antoine, Sorbonne University, APHP, Paris, France
| | - Iris Nagtegaal
- Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Ionut Negoi
- Department of General Surgery, Carol Davila University of Medicine and Pharmacy Bucharest, Emergency Hospital of Bucharest, Bucharest, Romania
| | - Maartje Nielsen
- Clinical Genetics Department, Leiden University Medical Center, Leiden, The Netherlands
| | - Gianluca Pellino
- Department of Gastrointestinal Surgery, Vall d’Hebron University Hospital, Barcelona, Spain
- Universitat Autònoma de Barcelona, Barcelona, Spain
- Department of Advanced Medical and Surgical Sciences, Università degli Studi della Campania ‘Luigi Vanvitelli’, Naples, Italy
| | - Luigi Ricciardiello
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
- IRCCS University Hospital of Bologna, Policlinico di Sant’Orsola, Bologna, Italy
| | | | - Luis Sánchez-Guillén
- Department of Gastrointestinal Surgery, Elche General University Hospital, Elche, Alicante, Spain
- Miguel Hernández University, Elche, Spain
| | - Toni T Seppälä
- Department of Gastroenterological Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
- Applied Tumour Genomics Research Program, University of Helsinki, Helsinki, Finland
- Faculty of Medicine and Health Technology, University of Tampere and TAYS Cancer Centre, Tampere, Finland
- iCAN Precision Medicine Flagship, University of Helsinki, Helsinki, Finland
| | - Peter Siersema
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands
| | | | - Julian R Sampson
- Institute of Medical Genetics, Division of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, UK
| | - Andrew Latchford
- Polyposis Registry, St Mark’s Hospital, Harrow, UK
- Department of Surgery and Cancer, Imperial College, London, UK
| | - Yann Parc
- Department of Digestive Surgery, Hôpital Saint-Antoine, Sorbonne University, APHP, Paris, France
| | - John Burn
- Newcastle University Translational and Clinical Research Institute, Centre for Life, Newcastle upon Tyne, UK
| | - Gabriela Möslein
- Center for Hereditary Tumors, Bethesda Hospital, Duisburg, Germany
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14
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Strakova-Peterikova A, Slisarenko M, Skopal J, Pivovarcikova K, Pitra T, Farcas M, Michal M, Michal M, Michalova K. Familial syndromes associated with testicular and paratesticular neoplasms: a comprehensive review. Virchows Arch 2024; 484:723-731. [PMID: 38619599 DOI: 10.1007/s00428-024-03803-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: 01/16/2024] [Revised: 04/02/2024] [Accepted: 04/05/2024] [Indexed: 04/16/2024]
Abstract
A syndromic association between a subset of testicular/paratesticular neoplasms is well established. Such examples include Carney complex and large cell calcifying Sertoli cell tumor, Peutz-Jeghers syndrome and intratubular large cell hyalinizing Sertoli cell neoplasia, and VHL syndrome and clear cell papillary cystadenoma of the epididymis.However, recent studies proposed potential novel links between some testicular and paratesticular neoplasms with certain tumor syndromes. While more studies are still needed to solidify these associations, recent research suggests that a subset of Leydig cell tumors may arise in patients with hereditary leiomyomatosis and renal cell carcinoma syndrome or that some seminomas may occur in Lynch syndrome patients. Additionally, an association between testicular sex cord stromal tumors and paratesticular sarcomas with Familial adenomatous polyposis syndrome and DICER1 syndrome, respectively, has been proposed as well. This review provides a comprehensive overview of the intricate relationship between familial syndromes and associated testicular and paratesticular tumors, shedding light on their clinicopathological and molecular characteristics.
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Affiliation(s)
- Andrea Strakova-Peterikova
- Department of Pathology, Faculty of Medicine in Plzeň, Charles University, Czech Republic, Bioptical Laboratory, Ltd, Plzeň, Czech Republic
| | - Maryna Slisarenko
- Department of Pathology, Faculty of Medicine in Plzeň, Charles University, Czech Republic, Bioptical Laboratory, Ltd, Plzeň, Czech Republic
- Medical Laboratory CSD, Ltd, Kiev, Ukraine
| | - Josef Skopal
- Department of Pathology, Faculty of Medicine in Plzeň, Charles University, Czech Republic, Bioptical Laboratory, Ltd, Plzeň, Czech Republic
| | - Kristyna Pivovarcikova
- Department of Pathology, Faculty of Medicine in Plzeň, Charles University, Czech Republic, Bioptical Laboratory, Ltd, Plzeň, Czech Republic
| | - Tomas Pitra
- Department of Urology, Faculty of Medicine in Plzeň, Charles University, Plzeň, Czech Republic
| | - Mihaela Farcas
- Department of Pathology, Faculty of Medicine in Plzeň, Charles University, Czech Republic, Bioptical Laboratory, Ltd, Plzeň, Czech Republic
- Onco Team Diagnostic, Bucharest, Romania
| | - Michael Michal
- Department of Pathology, Faculty of Medicine in Plzeň, Charles University, Czech Republic, Bioptical Laboratory, Ltd, Plzeň, Czech Republic
| | - Michal Michal
- Department of Pathology, Faculty of Medicine in Plzeň, Charles University, Czech Republic, Bioptical Laboratory, Ltd, Plzeň, Czech Republic
| | - Kvetoslava Michalova
- Department of Pathology, Faculty of Medicine in Plzeň, Charles University, Czech Republic, Bioptical Laboratory, Ltd, Plzeň, Czech Republic.
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Poylin VY, Shaffer VO, Felder SI, Goldstein LE, Goldberg JE, Kalady MF, Lightner AL, Feingold DL, Paquette IM. The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Inherited Adenomatous Polyposis Syndromes. Dis Colon Rectum 2024; 67:213-227. [PMID: 37682806 DOI: 10.1097/dcr.0000000000003072] [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: 09/10/2023]
Affiliation(s)
- Vitaliy Y Poylin
- Division of Gastrointestinal and Oncologic Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Virginia O Shaffer
- Department of Surgery, Emory University College of Medicine, Atlanta, Georgia
| | - Seth I Felder
- Department of Surgery, Moffit Cancer Center, Tampa, Florida
| | - Lindsey E Goldstein
- Division of General Surgery, North Florida/South Georgia Veteran's Health System, Gainesville, Florida
| | - Joel E Goldberg
- Division of General and Gastrointestinal Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Matthew F Kalady
- Division of Colon and Rectal Surgery, Ohio State University, Columbus, Ohio
| | - Amy L Lightner
- Department of Colorectal Surgery, Scripps Clinic, San Diego, California
| | - Daniel L Feingold
- Division of Colorectal Surgery, Rutgers University, New Brunswick, New Jersey
| | - Ian M Paquette
- Division of Colon and Rectal Surgery, University of Cincinnati, Cincinnati, Ohio
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16
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Ramírez Stieben LA, Pozzi D. Papillary thyroid carcinoma with desmoid fibromatosis: a case report and review of literature. REVISTA DE LA FACULTAD DE CIENCIAS MÉDICAS 2023; 80:289-300. [PMID: 37773341 PMCID: PMC10594980 DOI: 10.31053/1853.0605.v80.n3.40408] [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: 02/28/2023] [Accepted: 04/14/2023] [Indexed: 10/01/2023] Open
Abstract
Desmoid-type fibromatosis (DF) is a rare monoclonal, fibroblastic proliferation characterized by an unpredictable and variable clinical course. We present the case of a 56-year-old woman who underwent total thyroidectomy for papillary thyroid carcinoma in 2012 and who developed a cervical mass at the left laterocervical level during follow-up, raising the diagnosis of tumor recurrence. Computed tomography of the neck showed solid formations with heterogeneous contrast uptake in the right lateral region of the neck. At the level of the thoracic operculum, a second 26-mm formation was observed that medially contacted the left lateral wall of the trachea. Lateral lymphadenectomy was performed, which was incomplete. Histology showed findings consistent with desmoid-type fibromatosis. DF are slowly proliferating, non-metastatic tumors with a highly invasive capacity that are usually present in familial adenomatous polyposis (FAP)-Gardner syndrome. Our case had a history of massive colonic polyposis and first-degree relatives of colorectal cancer.
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Kyriakidis F, Kogias D, Venou TM, Karlafti E, Paramythiotis D. Updated Perspectives on the Diagnosis and Management of Familial Adenomatous Polyposis. Appl Clin Genet 2023; 16:139-153. [PMID: 37600856 PMCID: PMC10439286 DOI: 10.2147/tacg.s372241] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Accepted: 07/31/2023] [Indexed: 08/22/2023] Open
Abstract
Familial adenomatous polyposis (FAP) is an autosomal dominant cancer predisposition syndrome marked by extensive colorectal polyposis and a high risk of colorectal cancer (CRC). Having access to screening and enrollment programs can improve survival for patients with FAP by enabling them to undergo surgery before the development of colorectal cancer. Provided that there are a variety of surgical options available to treat colorectal polyps in patients with adenomatous polyposis, the appropriate surgical option for each patient should be considered. The gold-standard treatment to reduce this risk is prophylactic colectomy, typically by the age of 40. However, colectomy is linked to morbidity and constitutes an ineffective way at preventing extra-colonic disease manifestations, such as desmoid disease, thyroid malignancy, duodenal polyposis, and cancer. Moreover, extensive studies have been conducted into the use of chemopreventive agents to prevent disease progression and delay the necessity for a colectomy as well as the onset of extracolonic disease. The ideal chemoprevention agent should demonstrate a biologically plausible mechanism of action and provide safety, easy tolerance over an extended period of time and a lasting and clinically meaningful effect. Although many pharmaceutical and non-pharmaceutical products have been tested through the years, there has not yet been a chemoprevention agent that meets these criteria. Thus, it is necessary to develop new FAP agents that target novel pathways, such as the mTOR pathway. The aim of this article is to review the prior literature on FAP in order to concentrate the current and future perspectives of diagnosis and treatment. In conclusion, we will provide an update on the diagnostic and therapeutic options, surgical or pharmaceutical, while focusing on the potential treatment strategies that could further reduce the risk of CRC.
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Affiliation(s)
- Filippos Kyriakidis
- Second Chemotherapy Department, Theagenio Cancer Hospital of Thessaloniki, Thessaloniki, Greece
| | - Dionysios Kogias
- First Department of Internal Medicine, University General Hospital of Alexandroupolis, Alexandroupolis, Greece
| | - Theodora Maria Venou
- Second Chemotherapy Department, Theagenio Cancer Hospital of Thessaloniki, Thessaloniki, Greece
| | - Eleni Karlafti
- Emergency Department, AHEPA General University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
- First Propaedeutic Department of Internal Medicine, University General Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Daniel Paramythiotis
- First Propaedeutic Surgery Department, AHEPA University General Hospital of Thessaloniki, Aristotle University of Thessaloniki, Thessaloniki, Greece
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18
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Kyriakidis F, Kogias D, Venou TM, Karlafti E, Paramythiotis D. Updated Perspectives on the Diagnosis and Management of Familial Adenomatous Polyposis. Appl Clin Genet 2023; Volume 16:139-153. [DOI: https:/doi.org/10.2147/tacg.s372241] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/16/2025] Open
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Lehman B, Matthäi E, Gercke N, Denzer UW, Figiel J, Hess T, Slater EP, Bartsch DK. Characteristics of familial pancreatic cancer families with additional colorectal carcinoma. Fam Cancer 2023; 22:323-330. [PMID: 36717525 PMCID: PMC10276072 DOI: 10.1007/s10689-023-00328-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Accepted: 01/23/2023] [Indexed: 02/01/2023]
Abstract
Familial pancreatic cancer (FPC) is a rare hereditary tumor entity with broad phenotypic heterogeneity, including colorectal carcinoma (CRC) in some families. The underlying factors for this co-occurrence are still not well evaluated. FPC families in the National Case Collection of Familial Pancreatic Cancer with an additional occurrence of CRC were analyzed regarding the phenotype, genotype and recommendation for a clinical screening program. The total cohort of 272 FPC families included 30 (11%) families with at least one CRC case. The proportion of affected family members with PDAC was 16.1% (73/451) compared to 9.3% of family members with CRC (42/451, p < 0.01). Females were affected with PDAC in 49% (36/73) and CRC in 38% (16/42). The median age of PDAC was 63 compared to 66 years in CRC, whereas 8 (26.6%) of families had an early onset of PDAC and 2 (6.7%) of CRC. Seventeen families had 2 or more affected generations with PDAC and 6 families with CRC. Eleven (9.6%) of affected patients had both PDAC and CRC. Potentially causative germline mutations (2 ATM, 1 CDKN2a, 1 MLH1, 1 PALB2) were detected in 5 of 18 (27.7%) analyzed cases. These findings provide a step forward to include the phenotypic and genotypic characteristics of FPC-CRC families for the genetic counseling and management of these families. Nevertheless, results need to be verified in a larger patient cohort beforehand.
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Affiliation(s)
- Bettina Lehman
- Departments of Visceral, Thoracic and Vascular Surgery, Philipps University Marburg, Baldingerstrasse, 35043, Marburg, Germany.
| | - Elvira Matthäi
- Departments of Visceral, Thoracic and Vascular Surgery, Philipps University Marburg, Baldingerstrasse, 35043, Marburg, Germany
| | - Norman Gercke
- Departments of Visceral, Thoracic and Vascular Surgery, Philipps University Marburg, Baldingerstrasse, 35043, Marburg, Germany
| | - Ulrike W Denzer
- Gastroenterology and Endocrinology, University Hospital Marburg, Marburg, Germany
| | - Jens Figiel
- Gastroenterology and Endocrinology, University Hospital Marburg, Marburg, Germany
| | - Timo Hess
- Centre for Human Genetics, University Hospital Marburg, Marburg, Germany
| | - Emily P Slater
- Departments of Visceral, Thoracic and Vascular Surgery, Philipps University Marburg, Baldingerstrasse, 35043, Marburg, Germany
| | - Detlef K Bartsch
- Departments of Visceral, Thoracic and Vascular Surgery, Philipps University Marburg, Baldingerstrasse, 35043, Marburg, Germany
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20
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Cohen B, Cadesky A, Jaggi S. Dermatologic manifestations of thyroid disease: a literature review. Front Endocrinol (Lausanne) 2023; 14:1167890. [PMID: 37251685 PMCID: PMC10214500 DOI: 10.3389/fendo.2023.1167890] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Accepted: 04/07/2023] [Indexed: 05/31/2023] Open
Abstract
Introduction Thyroid hormone is considered one of the key regulatory hormones for skin homeostasis. Multiple organs are affected by the release of peripheral thyroid hormones (T4 and T3) further regulating various functions at a cellular level. Specifically, skin is considered an important target organ in which the thyroid hormone has a significant impact. Multiple skin diseases are associated with thyroid hormone dysregulation. However, other striking dermatologic manifestations are seen in nails and hair as well. Hypothyroidism, hyperthyroidism, and thyroid cancer can have an array of cutaneous manifestations, and we present the recent updates in this field. Methods A PubMed search was performed for updates in any new skin disease findings and treatments between 2010 and 2022. Research published in the past decade and previously known foundational skin findings associated with thyroid disease were presented in this review. Conclusion Cutaneous manifestations of thyroid disease is one of the first notable signs of thyroid hormone dysregulation. This article reviews the recent updates on the thyroid and skin interplay, and it further discusses overt visible findings and various available treatment modalities.
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21
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Vibert R, Le Gall J, Buecher B, Mouret-Fourme E, Bataillon G, Becette V, Trabelsi-Grati O, Moncoutier V, Dehainault C, Carriere J, Schwartz M, Suybeng V, Bieche I, Colas C, Vincent-Salomon A, Stoppa-Lyonnet D, Golmard L. APC germline pathogenic variants and epithelial ovarian cancer: causal or coincidental findings? J Med Genet 2023; 60:460-463. [PMID: 36270768 DOI: 10.1136/jmg-2022-108467] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Accepted: 10/08/2022] [Indexed: 04/22/2023]
Abstract
APC germline pathogenic variants result in predisposition to familial adenomatous polyposis and extraintestinal tumours such as desmoid fibromatosis, medulloblastomas and thyroid cancers. They have also been recently involved in ovarian microcystic stromal tumours. APC inactivation has been described at the tumour level in epithelial ovarian cancers (EOCs). Here, we report the identification of APC germline pathogenic variants in two patients diagnosed with premenopausal EOC in early 30s, with no other pathogenic variant detected in the known ovarian cancer predisposing genes. Subsequent tumour analysis showed neither a second hit of APC inactivation nor β-catenin activation. Both tumours did not have a homologous recombination (HR) deficiency, pointing towards the implication of other genes than those involved in HR. APC may contribute to the carcinogenesis of EOC in a multifactorial context. Further studies are required to clarify the role of APC in predisposition to EOC.
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Affiliation(s)
- Roseline Vibert
- Department of Genetics, Institut Curie, Paris, France
- PSL Research University, Paris, France
| | - Jessica Le Gall
- Department of Genetics, Institut Curie, Paris, France
- Université de Paris, Paris, Île-de-France, France
| | - Bruno Buecher
- Department of Genetics, Institut Curie, Paris, France
- PSL Research University, Paris, France
| | | | - Guillaume Bataillon
- PSL Research University, Paris, France
- Department of Pathology, Institut Curie, Paris, France
| | - Véronique Becette
- PSL Research University, Paris, France
- Department of Pathology, Institut Curie, Paris, France
| | - Olfa Trabelsi-Grati
- Department of Genetics, Institut Curie, Paris, France
- PSL Research University, Paris, France
| | - Virginie Moncoutier
- Department of Genetics, Institut Curie, Paris, France
- PSL Research University, Paris, France
| | - Catherine Dehainault
- Department of Genetics, Institut Curie, Paris, France
- PSL Research University, Paris, France
| | - Jennifer Carriere
- Department of Genetics, Institut Curie, Paris, France
- PSL Research University, Paris, France
| | - Mathias Schwartz
- Department of Genetics, Institut Curie, Paris, France
- PSL Research University, Paris, France
| | - Voreak Suybeng
- Department of Genetics, Institut Curie, Paris, France
- PSL Research University, Paris, France
| | - Ivan Bieche
- Department of Genetics, Institut Curie, Paris, France
- Université de Paris, Paris, Île-de-France, France
| | - Chrystelle Colas
- Department of Genetics, Institut Curie, Paris, France
- PSL Research University, Paris, France
| | - Anne Vincent-Salomon
- PSL Research University, Paris, France
- Department of Pathology, Institut Curie, Paris, France
| | - Dominique Stoppa-Lyonnet
- Department of Genetics, Institut Curie, Paris, France
- Université de Paris, Paris, Île-de-France, France
- INSERM U830, Institut Curie, Paris, France
| | - Lisa Golmard
- Department of Genetics, Institut Curie, Paris, France
- PSL Research University, Paris, France
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22
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Garutti M, Foffano L, Mazzeo R, Michelotti A, Da Ros L, Viel A, Miolo G, Zambelli A, Puglisi F. Hereditary Cancer Syndromes: A Comprehensive Review with a Visual Tool. Genes (Basel) 2023; 14:1025. [PMID: 37239385 PMCID: PMC10218093 DOI: 10.3390/genes14051025] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2023] [Revised: 04/23/2023] [Accepted: 04/26/2023] [Indexed: 05/28/2023] Open
Abstract
Hereditary cancer syndromes account for nearly 10% of cancers even though they are often underdiagnosed. Finding a pathogenic gene variant could have dramatic implications in terms of pharmacologic treatments, tailored preventive programs, and familiar cascade testing. However, diagnosing a hereditary cancer syndrome could be challenging because of a lack of validated testing criteria or because of their suboptimal performance. In addition, many clinicians are not sufficiently well trained to identify and select patients that could benefit from a genetic test. Herein, we searched the available literature to comprehensively review and categorize hereditary cancer syndromes affecting adults with the aim of helping clinicians in their daily clinical practice through a visual tool.
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Affiliation(s)
- Mattia Garutti
- CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy
| | - Lorenzo Foffano
- CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy
- Department of Medicine, University of Udine, 33100 Udine, Italy
| | - Roberta Mazzeo
- CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy
- Department of Medicine, University of Udine, 33100 Udine, Italy
| | - Anna Michelotti
- CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy
- Department of Medicine, University of Udine, 33100 Udine, Italy
| | - Lucia Da Ros
- CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy
| | - Alessandra Viel
- Unit of Oncogenetics and Genomics CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy
| | - Gianmaria Miolo
- CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy
| | - Alberto Zambelli
- Medical Oncology and Hematology Unit, IRCCS—Humanitas Research Hospital, Rozzano, 20089 Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20072 Milan, Italy
| | - Fabio Puglisi
- CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy
- Department of Medicine, University of Udine, 33100 Udine, Italy
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23
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Osteoma of the Jaw as First Clinical Sign of Gardner's Syndrome: The Experience of Two Italian Centers and Review. J Clin Med 2023; 12:jcm12041496. [PMID: 36836031 PMCID: PMC9963778 DOI: 10.3390/jcm12041496] [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] [Received: 01/31/2023] [Revised: 02/10/2023] [Accepted: 02/12/2023] [Indexed: 02/16/2023] Open
Abstract
Gardner's syndrome (GS) is a combination of polyposis, osteomas, fibromas, and sebaceous cysts. The aim of the study is to highlight whether maxillofacial osteoma could represent an early detection symptom of GS. Patients with suspected osteoma of the jaw underwent genetic and radiographical examinations. The database gathered 19 patients with oral osteoma that was histologically diagnosed; the whole sample was positive for APC gene mutation. Other cranial and peripheral locations were reported. Osteoma of the jaw is a crucial predictive factor of GS, and dentists and oral and maxillofacial surgeons must be aware of the importance of a timely diagnosis.
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24
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El Halabi J, LaGuardia L, Walsh RM, Kwon CHD, Menon KVN, Liska D, Burke CA. Hepatocellular carcinoma and solid pseudopapillary neoplasm of the pancreas complicating familial adenomatous polyposis: two cases and review of the literature. Fam Cancer 2023; 22:77-82. [PMID: 35896845 DOI: 10.1007/s10689-022-00305-0] [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: 04/07/2022] [Accepted: 06/28/2022] [Indexed: 01/12/2023]
Abstract
Familial adenomatous polyposis (FAP) is characterized by colorectal polyposis and extracolonic tumors. Adenocarcinoma of the pancreas and hepatocellular carcinoma are rare in FAP. In this case series, we describe a mother and daughter with FAP who developed a hepatocellular carcinoma and solid pseudopapillary neoplasm of the pancreas, respectively.
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Affiliation(s)
- Jessica El Halabi
- Department of Internal Medicine, Cleveland Clinic, Cleveland, OH, USA
| | - Lisa LaGuardia
- Department of Colorectal Surgery, Cleveland Clinic, Cleveland, OH, USA.,Sanford R. Weiss MD Center for Hereditary Colorectal Neoplasia, Cleveland Clinic, Cleveland, OH, USA
| | - R Matthew Walsh
- Department of General Surgery, Cleveland Clinic, Cleveland, OH, USA.,Sanford R. Weiss MD Center for Hereditary Colorectal Neoplasia, Cleveland Clinic, Cleveland, OH, USA
| | | | - K V Narayanan Menon
- Department of Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic, Mail Code A30, 9500 Euclid Avenue, Cleveland, OH, 44195, USA
| | - David Liska
- Department of Colorectal Surgery, Cleveland Clinic, Cleveland, OH, USA.,Sanford R. Weiss MD Center for Hereditary Colorectal Neoplasia, Cleveland Clinic, Cleveland, OH, USA
| | - Carol A Burke
- Department of Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic, Mail Code A30, 9500 Euclid Avenue, Cleveland, OH, 44195, USA. .,Sanford R. Weiss MD Center for Hereditary Colorectal Neoplasia, Cleveland Clinic, Cleveland, OH, USA.
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25
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Cronkhite-Canada syndrome: A case report and review of the literature. Ann Med Surg (Lond) 2022; 81:104090. [PMID: 36147170 PMCID: PMC9486408 DOI: 10.1016/j.amsu.2022.104090] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Revised: 06/23/2022] [Accepted: 06/24/2022] [Indexed: 11/23/2022] Open
Abstract
Cronkhite -Canada Syndrome (CCS) is a rare non-hereditary disease characterized by multiple polyps in the alimentary tract and ectoderm changes, and there is no clearly diagnostic criteria and treatment methods. A 55-year-old Chinese woman was admitted to our hospital with diarrhea. She was diagnosed with Cronkhite-Canada Syndrome (CCS). The clinical symptoms of the patient included diarrhea, nausea, retching, anorexia, weight loss, and we found that she had alopecia, onychatrophy, rampant caries and skin pigmentation from the physical examination. Gastrointestinal endoscopy revealed multiple polyps in the gastric antrum, stomach body, ileocecal part and colon, and from the microscopically the polype hyperplsique was observed. The patient was treated by eradicating Helicobacter pylori and regulating the intestinal flora disbalance and his diarrhea improved within a short period of time. We suggested that she should take glucocorticoids orally, but the patient refused. Follow-up at 1 year showed that the symptoms of the patient had recurred sometimes, and she had taken Chinese herbal medicine orally a few times. At present, the symptoms of diarrhea are relieved, the weight of the patient has increased, and the hair and nails of the patient have grown again. From this case, we learned CCS can be likely ignored and not be diagnosed promptly because the low morbidity of CCS.
The clinical manifestations of Cronkhite-Canada syndrome are diversified, including diarrhea, hyperpigmentation, hair loss, and nail malnutrition. Misdiagnosis and missed diagnosis can be caused by ignoring skin symptoms. The patient was not treated with glucocorticoids, and symptoms resolved after 1 year. According to the statistics of the article, there is no statistical difference in the remission rate between the use of glucocorticoid and no use.
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26
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Nussbaumer G, Benesch M. Hepatoblastoma in molecularly defined, congenital diseases. Am J Med Genet A 2022; 188:2527-2535. [PMID: 35478319 PMCID: PMC9545988 DOI: 10.1002/ajmg.a.62767] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Revised: 03/21/2022] [Accepted: 04/09/2022] [Indexed: 01/24/2023]
Abstract
Beckwith-Wiedemann spectrum, Simpson-Golabi-Behmel syndrome, familial adenomatous polyposis and trisomy 18 are the most common congenital conditions associated with an increased incidence of hepatoblastoma (HB). In patients with these genetic disorders, screening protocols for HB are proposed that include periodic abdominal ultrasound and measurement of alpha-fetoprotein levels. Surveillance in these children may contribute to the early detection of HB and possibly improve their chances of overall survival. Therefore, physicians must be aware of the high HB incidence in children with certain predisposing genetic diseases.
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Affiliation(s)
- Gunther Nussbaumer
- Division of Pediatric Hematology/Oncology, Department of Pediatrics and Adolescent MedicineMedical University of GrazGrazAustria
| | - Martin Benesch
- Division of Pediatric Hematology/Oncology, Department of Pediatrics and Adolescent MedicineMedical University of GrazGrazAustria
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27
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Novel Endoscopic Polypectomy Surveillance Technique for Fundic Gland Polyps in Familial Adenomatous Polyposis Can Improve Early Detection of Dysplasia and Gastric Cancer. Am J Gastroenterol 2022; 117:1246-1254. [PMID: 35584332 DOI: 10.14309/ajg.0000000000001833] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Accepted: 05/16/2022] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Fundic gland polyps (FGPs) are commonly found in patients with familial adenomatous polyposis (FAP) and are considered benign. Biopsies are not routinely performed, and conventional forceps may be time-consuming and/or yield nonrepresentative histology. The purpose of this study was to evaluate the role of a novel endoscopic polypectomy surveillance (EPS), a large volume cold-snare polypectomy technique of random FGPs, in the incidence of dysplasia and gastric cancer (GC) in FAP. METHODS This is a retrospective longitudinal cohort of patients with FAP referred to a tertiary care center for duodenal adenoma surveillance and who underwent EPS of FGPs between 2001 and 2019. Demographic, endoscopic, and clinicopathologic information was reviewed. RESULTS Thirty-five patients with FAP were identified at initial endoscopy by the mean age of 43.4 years (±12.8). One hundred thirteen surveillance endoscopies were performed in total using EPS. Dysplasia of FGPs was present on initial esophagogastroduodenoscopy in 7 patients (20%), and 13 additional patients (46.4%) progressed to low-grade dysplasia. Three patients (15%) who subsequently had progression to GC were found to have signet ring cell cancer within the foci of FGPs through EPS. One patient presented as metastatic GC. Progression from nondysplastic FGP to low-grade dysplasia occurred over 63 months (±46.3) with further progression to GC over 34 months (±8.5). Endoscopic risk factors for cancer were polyps >10 mm in size ( P < 0.001) and carpeting of polyps ( P < 0.001). The 5-year cumulative incidence of developing dysplasia was 35.7%. DISCUSSION We identified that the incidence of dysplasia and GC is higher than previously reported in patients with FAP. Our study used a novel EPS technique and was able to identify GC within the foci of FGPs. Upper endoscopic guidelines should include a more rigorous sampling method for FGPs, such as EPS, to optimize early detection of dysplasia and GC.
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28
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Horie C, Zhu C, Yamaguchi K, Nakagawa S, Isobe Y, Takane K, Ikenoue T, Ohta Y, Tanaka Y, Aikou S, Tsurita G, Ahiko Y, Shida D, Furukawa Y. Motile sperm domain containing 1 is upregulated by the Wnt/β‑catenin signaling pathway in colorectal cancer. Oncol Lett 2022; 24:282. [DOI: 10.3892/ol.2022.13402] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Accepted: 05/17/2022] [Indexed: 11/05/2022] Open
Affiliation(s)
- Chiaki Horie
- Division of Clinical Genome Research, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo 108‑8639, Japan
| | - Chi Zhu
- Division of Clinical Genome Research, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo 108‑8639, Japan
| | - Kiyoshi Yamaguchi
- Division of Clinical Genome Research, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo 108‑8639, Japan
| | - Saya Nakagawa
- Division of Clinical Genome Research, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo 108‑8639, Japan
| | - Yumiko Isobe
- Division of Clinical Genome Research, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo 108‑8639, Japan
| | - Kiyoko Takane
- Division of Clinical Genome Research, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo 108‑8639, Japan
| | - Tsuneo Ikenoue
- Division of Clinical Genome Research, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo 108‑8639, Japan
| | - Yasunori Ohta
- Department of Pathology, Research Hospital, Institute of Medical Science, The University of Tokyo, Tokyo 108‑8639, Japan
| | - Yukihisa Tanaka
- Department of Pathology, Research Hospital, Institute of Medical Science, The University of Tokyo, Tokyo 108‑8639, Japan
| | - Susumu Aikou
- Department of Surgery, Research Hospital, Institute of Medical Science, The University of Tokyo, Tokyo 108‑8639, Japan
| | - Giichiro Tsurita
- Department of Surgery, Research Hospital, Institute of Medical Science, The University of Tokyo, Tokyo 108‑8639, Japan
| | - Yuka Ahiko
- Department of Surgery, Research Hospital, Institute of Medical Science, The University of Tokyo, Tokyo 108‑8639, Japan
| | - Dai Shida
- Department of Surgery, Research Hospital, Institute of Medical Science, The University of Tokyo, Tokyo 108‑8639, Japan
| | - Yoichi Furukawa
- Department of Surgery, Research Hospital, Institute of Medical Science, The University of Tokyo, Tokyo 108‑8639, Japan
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29
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Klatte DCF, Wallace MB, Löhr M, Bruno MJ, van Leerdam ME. Hereditary pancreatic cancer. Best Pract Res Clin Gastroenterol 2022; 58-59:101783. [PMID: 35988957 DOI: 10.1016/j.bpg.2021.101783] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Revised: 12/09/2021] [Accepted: 12/15/2021] [Indexed: 01/31/2023]
Abstract
Pancreatic cancer is one of the deadliest malignancies. Therefore, there is an urgent need to detect pancreatic cancer in an earlier stage to improve outcomes. A variety of hereditary cancer syndromes have been associated with an increased risk of developing pancreatic cancer, and these individuals may benefit from surveillance programs. Surveillance programs have shown potential to improve outcomes, but have important risks such as overtreatment. In this review we will discuss the definitions and epidemiology of hereditary pancreatic cancer, recommendations for genetic testing and participation in surveillance. Important aspects are differences in surveillance strategies, target lesions, and potential benefits and harms of surveillance. Lastly we will highlight future directions for research and improvement of care for individuals at high-risk of pancreatic cancer.
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Affiliation(s)
- Derk C F Klatte
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands; Department of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, United States.
| | - Michael B Wallace
- Department of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, United States; Division of Gastroenterology and Hepatology, Sheikh Shakhbout Medical City, Abu Dhabi, United Arab Emirates.
| | - Matthias Löhr
- Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
| | - Marco J Bruno
- Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, the Netherlands.
| | - Monique E van Leerdam
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands; Department of Gastrointestinal Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
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30
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Rajabi S, Alix-Panabières C, Alaei AS, Abooshahab R, Shakib H, Ashrafi MR. Looking at Thyroid Cancer from the Tumor-Suppressor Genes Point of View. Cancers (Basel) 2022; 14:2461. [PMID: 35626065 PMCID: PMC9139614 DOI: 10.3390/cancers14102461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Revised: 05/15/2022] [Accepted: 05/16/2022] [Indexed: 11/17/2022] Open
Abstract
Thyroid cancer is the most frequent endocrine malignancy and accounts for approximately 1% of all diagnosed cancers. A variety of mechanisms are involved in the transformation of a normal tissue into a malignant one. Loss of tumor-suppressor gene (TSG) function is one of these mechanisms. The normal functions of TSGs include cell proliferation and differentiation control, genomic integrity maintenance, DNA damage repair, and signaling pathway regulation. TSGs are generally classified into three subclasses: (i) gatekeepers that encode proteins involved in cell cycle and apoptosis control; (ii) caretakers that produce proteins implicated in the genomic stability maintenance; and (iii) landscapers that, when mutated, create a suitable environment for malignant cell growth. Several possible mechanisms have been implicated in TSG inactivation. Reviewing the various TSG alteration types detected in thyroid cancers may help researchers to better understand the TSG defects implicated in the development/progression of this cancer type and to find potential targets for prognostic, predictive, diagnostic, and therapeutic purposes. Hence, the main purposes of this review article are to describe the various TSG inactivation mechanisms and alterations in human thyroid cancer, and the current therapeutic options for targeting TSGs in thyroid cancer.
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Affiliation(s)
- Sadegh Rajabi
- Traditional Medicine and Materia Medica Research Center, Shahid Beheshti University of Medical Sciences, Tehran 19839-63113, Iran;
- Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran 19839-63113, Iran
| | - Catherine Alix-Panabières
- Laboratory of Rare Human Circulating Cells (LCCRH), University Medical Centre of Montpellier, CEDEX 5, 34093 Montpellier, France
- Centre for Ecological and Evolutionary Cancer Research (CREEC), Unité Mixte de Recherches, Institut de Recherche pour le Développement (IRD) 224–Centre National de Recherche Scientifique (CNRS) 5290–University of Montpellier, 34000 Montpellier, France
| | - Arshia Sharbatdar Alaei
- Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran 19839-63113, Iran;
| | | | - Heewa Shakib
- Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran 19857-17443, Iran;
| | - Mohammad Reza Ashrafi
- Department of Biochemistry, Afzalipoor Faculty of Medicine, Kerman University of Medical Sciences, Kerman 76169-13555, Iran;
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31
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Ali A, Ahmad A, Taj S, Qaudeer SA, Ahmed SE. Familial Adenomatous Polyposis (FAP) Presenting as Iron Deficiency Anemia in a 33-Year-Old Female: A Case Report. Cureus 2022; 14:e24603. [PMID: 35651449 PMCID: PMC9138202 DOI: 10.7759/cureus.24603] [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] [Accepted: 04/29/2022] [Indexed: 11/05/2022] Open
Abstract
Iron deficiency anemia is a common clinical concern in women of reproductive age. It presents as microcytic anemia and can be due to a limited number of causes including bleeding, malabsorption, intravascular hemolysis, or a mechanical heart valve. Familial adenomatous polyposis (FAP) is an inherited autosomal dominant disorder due to mutation in the adenomatous polyposis coli (APC) gene that can cause iron deficiency anemia due to GI malignancy, most notably colon cancer. Variation of mutations within the APC gene can cause different forms of FAP, such as Gardner syndrome. This syndrome presents with epidermoid cysts typically in unconventional locations such as the face, scalp, and extremities, as seen in our patient. We report a presentation of FAP in a 33-year-old Caucasian female who initially presented with iron deficiency anemia, hematochezia, and weight loss. Colonoscopy revealed hundreds of polyps within the colon, with two that were biopsied and reported as tubulovillous adenoma. The patient underwent a robotically assisted laparoscopic total proctocolectomy with ileal pouch-anal anastomosis, as well as a diverting loop ileostomy, and was given pain medication. She was referred to genetic counseling for her daughters and herself, which revealed a pathogenic variance in the APC gene.
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Affiliation(s)
- Afrah Ali
- Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, USA
| | - Areesha Ahmad
- Oncology, Lake Erie College of Osteopathic Medicine, Bradenton, USA
| | - Shah Taj
- Oncology, Lake Erie College of Osteopathic Medicine, Bradenton, USA
| | - Shahid A Qaudeer
- Oncology, Lake Erie College of Osteopathic Medicine, Bradenton, USA
| | - Syed E Ahmed
- Hematology/Oncology, Florida Cancer Specialists & Research Institute, Sebring, USA
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Germline mutations of the adenomatous polyposis coli (APC) gene in Algerian familial adenomatous polyposis cohort: first report. Mol Biol Rep 2022; 49:3823-3837. [PMID: 35142982 DOI: 10.1007/s11033-022-07228-0] [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: 11/17/2021] [Accepted: 02/03/2022] [Indexed: 10/19/2022]
Abstract
BACKGROUND Familial adenomatous polyposis (known also as classical or severe FAP) is a rare autosomal dominant colorectal cancer predisposition syndrome, characterized by the presence of hundreds to thousands of adenomatous polyps in the colon and rectum from an early age. In the absence of prophylactic surgery, colorectal cancer (CRC) is the inevitable consequence of FAP. The vast majority of FAP is caused by germline mutations in the adenomatous polyposis coli (APC) tumor suppressor gene (5q21). To date, most of the germline mutations in classical FAP result in truncation of the APC protein and 60% are mainly located within exon 15. MATERIAL AND METHODS In this first nationwide study, we investigated the clinical and genetic features of 52 unrelated Algerian FAP families. We screened by PCR-direct sequencing the entire exon 15 of APC gene in 50 families and two families have been analyzed by NGS using a cancer panel of 30 hereditary cancer genes. RESULTS Among 52 FAP index cases, 36 had 100 or more than 100 polyps, 37 had strong family history of FAP, 5 developed desmoids tumors, 15 had extra colonic manifestations and 21 had colorectal cancer. We detected 13 distinct germline mutations in 17 FAP families. Interestingly, 4 novel APC germline pathogenic variants never described before have been identified in our study. CONCLUSIONS The accumulating knowledge about the prevalence and nature of APC variants in Algerian population will contribute in the near future to the implementation of genetic testing and counseling for FAP patients.
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Anneberg M, Svane HML, Fryzek J, Nicholson G, White JB, Edris B, Smith LM, Hooda N, Petersen MM, Baad-Hansen T, Keller JØ, Jørgensen PH, Pedersen AB. The epidemiology of desmoid tumors in Denmark. Cancer Epidemiol 2022; 77:102114. [PMID: 35121405 DOI: 10.1016/j.canep.2022.102114] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Revised: 01/14/2022] [Accepted: 01/17/2022] [Indexed: 12/15/2022]
Abstract
INTRODUCTION/AIM The epidemiology, demographic, clinical, treatment, and healthcare resource utilization (HRU) characteristics of desmoid tumor (DT) patients treated at two sarcoma centers in Denmark is described. METHODS Using Danish health registers, we studied DT patients treated at two sarcoma centers between 2009 and 2018. For each patient, ten persons from the general population were randomly matched on birth year, sex, and region of residence. RESULTS Of the 179 DT patients identified, 76% were female and the median patient age was 38 years at diagnosis (interquartile range: 31-50). An average annual incidence of DTs over the study period was 3.2 per 1000,000 individuals with the observed annual incidence of DTs ranging from 2.2 (2011) to 4.3 (2017) per 1000,000 individuals. No notable linear time trend in incidence was observed. Anatomical DT sites included extra-abdominal (49%), abdominal wall (40%), and intra-abdominal or retroperitoneal areas (8%). In total, 56% of patients were initially treated surgically. However, while 75% of patients diagnosed with DT between 2009 and 2014 were initially treated surgically, this was true for only 32% of patients diagnosed with DT between 2015 and 2018. A total of 56% of DT patients used chemotherapeutic agents, tyrosine kinase inhibitors, NSAIDs, opioids, antidepressants, or steroids at some point during the three years before their DT diagnoses. In contrast, 70% of surgically treated and 63% of non-surgically treated patients used one of these drugs in the subsequent three years, including NSAIDs (45% surgical vs. 33% non-surgical), opioids (39% surgical vs. 27% non-surgical), and steroids (22% surgical vs. 18% non-surgical). The average number of inpatient and outpatient visits, days of hospitalization, and additional surgical procedures were higher among DT patients than the comparison cohort. CONCLUSION DTs are rare but have a large impact on patients' health, HRU, and medication utilization.
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Affiliation(s)
- Marie Anneberg
- Department of Clinical Epidemiology, Aarhus University Hospital and Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Helene M L Svane
- Department of Clinical Epidemiology, Aarhus University Hospital and Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Jon Fryzek
- Department of Clinical Epidemiology, Aarhus University Hospital and Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; EpidStrategies, Johns Hopkins Campus , 9601 Medical Center Dr., Rockville, MD 20850, USA
| | - Gina Nicholson
- EpidStrategies, Johns Hopkins Campus , 9601 Medical Center Dr., Rockville, MD 20850, USA
| | - Jessica B White
- SpringWorks Therapeutics, Inc., 100 Washington Blvd., Stamford, CT 06902, USA
| | - Badreddin Edris
- SpringWorks Therapeutics, Inc., 100 Washington Blvd., Stamford, CT 06902, USA
| | - L Mary Smith
- SpringWorks Therapeutics, Inc., 100 Washington Blvd., Stamford, CT 06902, USA
| | - Naushin Hooda
- EpidStrategies, Johns Hopkins Campus , 9601 Medical Center Dr., Rockville, MD 20850, USA
| | - Michael M Petersen
- Musculoskeletal Tumor Section, Department of Orthopedic Surgery, Rigshospitalet, Copenhagen University Hospital, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
| | | | - Johnny Ø Keller
- Department of Orthopedic Surgery, Aarhus University Hospital, Denmark
| | - Peter H Jørgensen
- Department of Orthopedic Surgery, Aarhus University Hospital, Denmark
| | - Alma B Pedersen
- Department of Clinical Epidemiology, Aarhus University Hospital and Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
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Qin T, Liao J, Qin H, Meng L, Wang W, Huang Z, Liu J, Mo X. Advantages of total proctocolectomy with straight ileoanal anastomosis plus pedicled omental transposition for familial adenomatous polyposis: a preliminary study. World J Surg Oncol 2022; 20:20. [PMID: 35065641 PMCID: PMC8783503 DOI: 10.1186/s12957-022-02488-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Accepted: 12/30/2021] [Indexed: 11/28/2022] Open
Abstract
PURPOSE To achieve excellent postoperative bowel function in familial adenomatous polyposis (FAP) patients, it is important to reconstruct the digestive tract. The aim of this study is to preliminarily discuss the advantages of total proctocolectomy with straight ileoanal anastomosis (TPC-SIAA) plus pedicled omental transposition for FAP. METHODS A retrospective study was carried out in two hospitals analysing data for FAP patients who underwent surgical treatments between 2015 and 2021. Perioperative outcomes and early and mid-term anal functions were analysed. RESULTS After excluding 4 patients who underwent total proctocolectomy with permanent ileostomy, 10 patients were enrolled in the study. Among the 10 patients, 3 received TPC-SIAA plus pedicled omental transposition, 3 received total proctocolectomy with ileal pouch-anal anastomosis (TPC-IPAA), and 4 received total colectomy with ileal pouch-rectal anastomosis (TC-IPRA). Except for one case conversion to laparotomy, laparoscopic surgery was performed for the other cases. The incidence of early postoperative complications was apparently higher with pouch anastomosis (57.1%) than straight anastomosis (0%). Frequencies of bowel movement and low anterior resection syndrome (LARS) score were higher for TPC-SIAA than the other two surgical procedures in the early term; over time, however, the frequencies of bowel movement and LARS score both showed a decreasing trend. In addition, combined with anorectal pressure detection and magnetic resonance imaging defecography at the 3rd month after TPC-SIAA plus pedicled omental transposition, defecation coordination was good. The dynamics and receptivity of the new rectum tended to be as expected. CONCLUSION Although the three surgical procedures are safe and feasible surgical options for FAP, TPC-SIAA plus pedicled omental transposition is more consistent with intestinal physiology, with good intestinal compliance, and anal function tended to be as expected over time. Nevertheless, more extensive studies are needed to confirm these benefits.
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Affiliation(s)
- Tianci Qin
- Department of General Surgery, Guiping People's Hospital, No.7, People's West Road, Guiping, Guigang, 537200, Guangxi Autonomous Region, China
| | - Jiankun Liao
- Department of Gastrointestinal Surgery, Division of Colorectal and Anal, Guangxi Medical University Cancer Hospital, No.71, Hedi Road, Qingxiu District, Nanning, 530021, Guangxi Autonomous Region, China
- Guangxi Clinical Research Center for Colorectal Cancer, Division of Colorectal and Anal, Guangxi Medical University Cancer Hospital, No.71, Hedi Road, Qingxiu District, Nanning, 530021, Guangxi Autonomous Region, The People's Republic of China
| | - Haiquan Qin
- Department of Gastrointestinal Surgery, Division of Colorectal and Anal, Guangxi Medical University Cancer Hospital, No.71, Hedi Road, Qingxiu District, Nanning, 530021, Guangxi Autonomous Region, China
- Guangxi Clinical Research Center for Colorectal Cancer, Division of Colorectal and Anal, Guangxi Medical University Cancer Hospital, No.71, Hedi Road, Qingxiu District, Nanning, 530021, Guangxi Autonomous Region, The People's Republic of China
| | - Linghou Meng
- Department of Gastrointestinal Surgery, Division of Colorectal and Anal, Guangxi Medical University Cancer Hospital, No.71, Hedi Road, Qingxiu District, Nanning, 530021, Guangxi Autonomous Region, China
- Guangxi Clinical Research Center for Colorectal Cancer, Division of Colorectal and Anal, Guangxi Medical University Cancer Hospital, No.71, Hedi Road, Qingxiu District, Nanning, 530021, Guangxi Autonomous Region, The People's Republic of China
| | - Wentao Wang
- Department of Gastrointestinal Surgery, Division of Colorectal and Anal, Guangxi Medical University Cancer Hospital, No.71, Hedi Road, Qingxiu District, Nanning, 530021, Guangxi Autonomous Region, China
- Guangxi Clinical Research Center for Colorectal Cancer, Division of Colorectal and Anal, Guangxi Medical University Cancer Hospital, No.71, Hedi Road, Qingxiu District, Nanning, 530021, Guangxi Autonomous Region, The People's Republic of China
| | - Zigao Huang
- Department of Gastrointestinal Surgery, Division of Colorectal and Anal, Guangxi Medical University Cancer Hospital, No.71, Hedi Road, Qingxiu District, Nanning, 530021, Guangxi Autonomous Region, China
- Guangxi Clinical Research Center for Colorectal Cancer, Division of Colorectal and Anal, Guangxi Medical University Cancer Hospital, No.71, Hedi Road, Qingxiu District, Nanning, 530021, Guangxi Autonomous Region, The People's Republic of China
| | - Jungang Liu
- Department of Gastrointestinal Surgery, Division of Colorectal and Anal, Guangxi Medical University Cancer Hospital, No.71, Hedi Road, Qingxiu District, Nanning, 530021, Guangxi Autonomous Region, China
- Guangxi Clinical Research Center for Colorectal Cancer, Division of Colorectal and Anal, Guangxi Medical University Cancer Hospital, No.71, Hedi Road, Qingxiu District, Nanning, 530021, Guangxi Autonomous Region, The People's Republic of China
| | - Xianwei Mo
- Department of Gastrointestinal Surgery, Division of Colorectal and Anal, Guangxi Medical University Cancer Hospital, No.71, Hedi Road, Qingxiu District, Nanning, 530021, Guangxi Autonomous Region, China.
- Guangxi Clinical Research Center for Colorectal Cancer, Division of Colorectal and Anal, Guangxi Medical University Cancer Hospital, No.71, Hedi Road, Qingxiu District, Nanning, 530021, Guangxi Autonomous Region, The People's Republic of China.
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Erickson LA, Chen B. Desmoid Tumor and Multiple Colon Adenomas. Mayo Clin Proc 2022; 97:193-195. [PMID: 34996557 DOI: 10.1016/j.mayocp.2021.11.025] [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] [Received: 11/18/2021] [Accepted: 11/18/2021] [Indexed: 10/19/2022]
Affiliation(s)
- Lori A Erickson
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN
| | - Beiyun Chen
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN
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Mitra S, Paramaguru R, Das P, Katti SV. Preneoplastic Lesions and Polyps of the Gastrointestinal Tract. SURGICAL PATHOLOGY OF THE GASTROINTESTINAL SYSTEM 2022:593-698. [DOI: 10.1007/978-981-16-6395-6_16] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Bhesania S, Chelikam N, Mobin N, Ilyas S, Nimkar N. Incidental Finding of Attenuated Familial Adenomatous Polyposis. Cureus 2021; 13:e18237. [PMID: 34722036 PMCID: PMC8544803 DOI: 10.7759/cureus.18237] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2021] [Accepted: 09/24/2021] [Indexed: 11/05/2022] Open
Abstract
Attenuated familial adenomatous polyposis (AFAP) or attenuated adenomatous polyposis coli (AAPC) is defined as the milder polyposis phenotype of classic familial adenomatous polyposis (FAP). FAP syndromes are caused by germline mutations in the adenomatous polyposis coli (APC) gene. AFAP is an inherited autosomal dominant with predominant mutations at the far proximal (5′) end of the APC gene. Unlike FAP, AFAP is characterized by the occurrence of fewer than 100 adenomas that are found mostly in the proximal part of the colon with a delayed progression to colorectal cancer (CRC). The lower risk of development of colorectal cancer and extra-intestinal neoplasms is likely attributable to under-diagnosis. However, 2-5% of all CRCs happen because of inherited syndromes which include both hereditary polyposis syndromes and hereditary nonpolyposis colorectal cancer syndrome (HNPCC) or otherwise known as Lynch syndrome (LS). Here, we present a case of a 64-year-old Polish-speaking female in whom an incidental finding of polyposis turned out to be a malignancy. Our patient had a positive family history of colon cancer. The delay in performing an annual colonoscopy with endoscopic polypectomy per AFAP surveillance guidelines was supposedly delayed due to lack of insurance and language barrier. There were no metastases and she was negative for the APC gene mutation. Pathology was significant for moderately differentiated adenocarcinoma with intact mismatch repair protein (MMRP) (expression of MLH1, PMS2, MSH2, and MSH6) genes immune-histochemical staining. The patient underwent a subtotal colectomy with ileostomy without any complications. This study aimed to emphasize that communication with the patient in their primary language is essential to gather all the data which can lead to an accurate diagnosis and to provide adequate care. Physicians are required to have a professional interpreter to acquire the appropriate medical history and be more vigilant in following up with the patient in order to provide comprehensive care.
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Affiliation(s)
- Siddharth Bhesania
- Internal Medicine, Overlook Medical Center, Summit, USA.,Internal Medicine, NewYork-Presbyterian Brooklyn Methodist Hospital, Brooklyn, USA
| | - Nikhila Chelikam
- Clinical Research, Icahn School of Medicine at Mount Sinai, New York City, USA
| | - Navim Mobin
- Gastroenterology, NewYork-Presbyterian Brooklyn Methodist Hospital, Brooklyn, USA
| | - Sahar Ilyas
- Internal Medicine, NewYork-Presbyterian Brooklyn Methodist Hospital, Brooklyn, USA
| | - Neil Nimkar
- Hematology and Medical Oncology, Overlook Medical Center, Summit, USA.,Hematology and Medical Oncology, NewYork-Presbyterian Brooklyn Methodist Hospital, Brooklyn, USA
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Antohi C, Haba D, Caba L, Ciofu ML, Drug VL, Bărboi OB, Dobrovăț BI, Pânzaru MC, Gorduza NC, Lupu VV, Dimofte D, Gug C, Gorduza EV. Novel Mutation in APC Gene Associated with Multiple Osteomas in a Family and Review of Genotype-Phenotype Correlations of Extracolonic Manifestations in Gardner Syndrome. Diagnostics (Basel) 2021; 11:1560. [PMID: 34573902 PMCID: PMC8466590 DOI: 10.3390/diagnostics11091560] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Revised: 08/25/2021] [Accepted: 08/25/2021] [Indexed: 12/24/2022] Open
Abstract
Gardner syndrome is a neoplasic disease that associates intestinal polyposis and colorectal adenocarcinoma with osteomas and soft tissue tumors determined by germline mutations in the APC gene. The early diagnosis and identification of high-risk individuals are important because patients have a 100% risk of colon cancer. We present the case of a family with Gardner syndrome. Cephalometric, panoramic X-rays and CBCT of the proband and her brother showed multiple osteomas affecting the skull bones, mandible and paranasal sinuses. The detailed family history showed an autosomal dominant transmission with the presence of the disease in the mother and maternal grandfather of the proband. Both had the typical signs of disease and died in the fourth decade of life. Based on these aspects the clinical diagnosis was Gardner syndrome. By gene sequencing, a novel pathogenic variant c.4609dup (p.Thr1537Asnfs*7) in heterozygous status was identified in the APC gene in both siblings. We reviewed literature data concerning the correlation between the localization of mutations in the APC gene and the extracolonic manifestations of familial adenomatous polyposis as well as their importance in early diagnosis and adequate oncological survey of patients and families based on abnormal genomic variants.
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Affiliation(s)
- Cristina Antohi
- Odontology-Periodontology-Fixed Prosthetics Department, “Grigore T. Popa” University of Medicine and Pharmacy, 16 University Street, 700115 Iasi, Romania;
| | - Danisia Haba
- Oral and Maxillofacial Surgery Department, “Grigore T. Popa” University of Medicine and Pharmacy, 16 University Street, 700115 Iaşi, Romania; (D.H.); (B.I.D.)
| | - Lavinia Caba
- Medicine of Mother and Child Department, “Grigore T. Popa” University of Medicine and Pharmacy, 16 University Street, 700115 Iasi, Romania; (M.-C.P.); (V.V.L.); (E.V.G.)
| | - Mihai Liviu Ciofu
- Oral and Maxillofacial Surgery Department, “Grigore T. Popa” University of Medicine and Pharmacy, 16 University Street, 700115 Iaşi, Romania; (D.H.); (B.I.D.)
| | - Vasile-Liviu Drug
- Medical I Department, “Grigore T. Popa” University of Medicine and Pharmacy, 16 University Street, 700115 Iasi, Romania; (V.-L.D.); (O.-B.B.)
| | - Oana-Bogdana Bărboi
- Medical I Department, “Grigore T. Popa” University of Medicine and Pharmacy, 16 University Street, 700115 Iasi, Romania; (V.-L.D.); (O.-B.B.)
| | - Bogdan Ionuț Dobrovăț
- Oral and Maxillofacial Surgery Department, “Grigore T. Popa” University of Medicine and Pharmacy, 16 University Street, 700115 Iaşi, Romania; (D.H.); (B.I.D.)
| | - Monica-Cristina Pânzaru
- Medicine of Mother and Child Department, “Grigore T. Popa” University of Medicine and Pharmacy, 16 University Street, 700115 Iasi, Romania; (M.-C.P.); (V.V.L.); (E.V.G.)
| | | | - Vasile Valeriu Lupu
- Medicine of Mother and Child Department, “Grigore T. Popa” University of Medicine and Pharmacy, 16 University Street, 700115 Iasi, Romania; (M.-C.P.); (V.V.L.); (E.V.G.)
| | | | - Cristina Gug
- Microscopic Morphology Department, “Victor Babes” University of Medicine and Pharmacy, 300041 Timișoara, Romania;
| | - Eusebiu Vlad Gorduza
- Medicine of Mother and Child Department, “Grigore T. Popa” University of Medicine and Pharmacy, 16 University Street, 700115 Iasi, Romania; (M.-C.P.); (V.V.L.); (E.V.G.)
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Sasaki K, Nozawa H, Kawai K, Murono K, Emoto S, Kishikawa J, Ishii H, Yokoyama Y, Abe S, Nagai Y, Anzai H, Sonoda H, Taira T, Ishihara S. Risk of extracolonic malignancies and metachronous rectal cancer after colectomy and ileorectal anastomosis in familial adenomatous polyposis. Asian J Surg 2021; 45:396-400. [PMID: 34330586 DOI: 10.1016/j.asjsur.2021.06.034] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Revised: 05/12/2021] [Accepted: 06/30/2021] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Analysis of long-term clinical outcomes of patients with familial adenomatous polyposis is critical in reducing or preventing the incidence of extracolonic malignancies after initial surgery. The aim of the present study was to clarify the long-term outcomes, and establish a surveillance strategy for surgically treated familial adenomatous polyposis patients. METHODS Between January 1967 and March 2020, retrospective data were collected from 37 patients with familial adenomatous polyposis treated or monitored in our department. Occurrence of metachronous cancers, including rectal cancers and extracolonic malignancies, and other diseases was analyzed. RESULTS The median follow-up duration after the first surgery was 13.8 years. Initially, 16 patients underwent total proctocolectomy with ileal pouch-anal anastomosis, 18 underwent total colectomy with ileorectal anastomosis, and three underwent other procedures. A secondary proctectomy was performed for 9 of the 18 patients who underwent ileorectal anastomosis. Rectal cancer was diagnosed in 6 patients who underwent ileorectal anastomosis. In addition, 5 gastric cancer, 2 duodenal cancer, 1 gallbladder cancer, and 1 thyroid cancer cases were diagnosed. The age at which the extracolonic malignancies were diagnosed was >50 years. 4 patients died due to metachronous rectal cancer, gastric cancer, or gallbladder cancer. CONCLUSION Careful consideration should be paid before choosing ileorectal anastomosis as the treatment procedure for familial adenomatous polyposis patients because completion proctectomy was eventually necessary for half of the patients. Long-term surveillance, with more frequent gastric surveillance for patients over 50 years, is important for the prevention and treatment of extracolonic malignancies in familial adenomatous polyposis patients.
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Affiliation(s)
- Kazuhito Sasaki
- Department of Surgical Oncology, Faculty of Medicine, the University of Tokyo, Japan.
| | - Hiroaki Nozawa
- Department of Surgical Oncology, Faculty of Medicine, the University of Tokyo, Japan
| | - Kazushige Kawai
- Department of Surgical Oncology, Faculty of Medicine, the University of Tokyo, Japan
| | - Koji Murono
- Department of Surgical Oncology, Faculty of Medicine, the University of Tokyo, Japan
| | - Shigenobu Emoto
- Department of Surgical Oncology, Faculty of Medicine, the University of Tokyo, Japan
| | - Junko Kishikawa
- Department of Surgical Oncology, Faculty of Medicine, the University of Tokyo, Japan
| | - Hiroaki Ishii
- Department of Surgical Oncology, Faculty of Medicine, the University of Tokyo, Japan
| | - Yuichiro Yokoyama
- Department of Surgical Oncology, Faculty of Medicine, the University of Tokyo, Japan
| | - Shinya Abe
- Department of Surgical Oncology, Faculty of Medicine, the University of Tokyo, Japan
| | - Yuzo Nagai
- Department of Surgical Oncology, Faculty of Medicine, the University of Tokyo, Japan
| | - Hiroyuki Anzai
- Department of Surgical Oncology, Faculty of Medicine, the University of Tokyo, Japan
| | - Hirofumi Sonoda
- Department of Surgical Oncology, Faculty of Medicine, the University of Tokyo, Japan
| | - Tetsuro Taira
- Department of Surgical Oncology, Faculty of Medicine, the University of Tokyo, Japan
| | - Soichiro Ishihara
- Department of Surgical Oncology, Faculty of Medicine, the University of Tokyo, Japan
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Faisal MS, Burke CA, Achkar JP, Click B, O'Malley M, LaGuardia L, Milicia S, Leach B, Liska D, Church J, Kalady M, Mankaney G. Malignancy risk in individuals with familial adenomatous polyposis receiving biologics and immunomodulators. Fam Cancer 2021; 21:189-195. [PMID: 33822277 DOI: 10.1007/s10689-021-00250-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Accepted: 03/29/2021] [Indexed: 12/19/2022]
Abstract
Clinicians may be hesitant to prescribe biologics or immunomodulators to individuals with familial adenomatous polyposis (FAP) and comorbid inflammatory disease (CID) because of increased cancer risk. Our aim was to compare the risk of malignancy in FAP individuals with inflammatory bowel (IBD) and/or rheumatic disease that received biologics/immunomodulators to those who did not. Individuals with FAP and CID were included in the study. We compared the incidence of cancer between individuals exposed to biologics/immunomodulators compared to unexposed from the date of diagnosis of comorbid disease till last follow up or death. Hazard ratio (HR) for cancer was computed using Cox regression model and compared by exposure status to biologic/immunomodulators. 25 individuals with FAP and a comorbid inflammatory disease were identified including 9 (36%) with IBD and 16 (64%) with rheumatic disease. 14 (56%) were exposed to a biologic and or immunomodulator. Median duration of biologic/immunomodulator exposure was 48 (2-180) months. 3 (21.4%) in the exposed group compared to 1 (9.1%) in the unexposed group developed cancer with a HR for exposure of 1.92 (CI 0.2-18.5, p = 0.57). Median duration of follow up after the diagnosis of inflammatory disease was 10 (5.5-17.0) years in the exposed and 6 (3.0-15.0) years in the unexposed group. In the exposed group, 1 patient developed gastric and 2 developed colon cancer. One unexposed patient developed medullary thyroid cancer. There is a possible trend of more cancers in the group that received biologics/immunomodulators-but given the small number of patients and p-value, there may be no difference at all. This preliminary finding warrants study in a larger cohort.
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Affiliation(s)
- Muhammad Salman Faisal
- Department of Internal Medicine, Cleveland Clinic Foundation, Lerner Research Institute, 2111 East 96th Street, Cleveland, OH, 44195, USA.
| | - Carol A Burke
- Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic Foundation, Cleveland, USA
- Department of Colorectal Surgery, Cleveland Clinic Foundation, Cleveland, USA
- Sanford R. Weiss M.D. Center for Inherited Colorectal Neoplasia, Cleveland Clinic Foundation, Cleveland, USA
| | - Jean-Paul Achkar
- Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic Foundation, Cleveland, USA
| | - Benjamin Click
- Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic Foundation, Cleveland, USA
| | - Margaret O'Malley
- Department of Colorectal Surgery, Cleveland Clinic Foundation, Cleveland, USA
- Sanford R. Weiss M.D. Center for Inherited Colorectal Neoplasia, Cleveland Clinic Foundation, Cleveland, USA
| | - Lisa LaGuardia
- Department of Colorectal Surgery, Cleveland Clinic Foundation, Cleveland, USA
- Sanford R. Weiss M.D. Center for Inherited Colorectal Neoplasia, Cleveland Clinic Foundation, Cleveland, USA
| | - Susan Milicia
- Department of Colorectal Surgery, Cleveland Clinic Foundation, Cleveland, USA
- Sanford R. Weiss M.D. Center for Inherited Colorectal Neoplasia, Cleveland Clinic Foundation, Cleveland, USA
| | - Brandie Leach
- Department of Colorectal Surgery, Cleveland Clinic Foundation, Cleveland, USA
- Sanford R. Weiss M.D. Center for Inherited Colorectal Neoplasia, Cleveland Clinic Foundation, Cleveland, USA
| | - David Liska
- Department of Colorectal Surgery, Cleveland Clinic Foundation, Cleveland, USA
- Sanford R. Weiss M.D. Center for Inherited Colorectal Neoplasia, Cleveland Clinic Foundation, Cleveland, USA
| | - James Church
- Department of Colorectal Surgery, Cleveland Clinic Foundation, Cleveland, USA
- Sanford R. Weiss M.D. Center for Inherited Colorectal Neoplasia, Cleveland Clinic Foundation, Cleveland, USA
| | - Matthew Kalady
- Department of Colorectal Surgery, Cleveland Clinic Foundation, Cleveland, USA
- Sanford R. Weiss M.D. Center for Inherited Colorectal Neoplasia, Cleveland Clinic Foundation, Cleveland, USA
| | - Gautam Mankaney
- Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic Foundation, Cleveland, USA
- Sanford R. Weiss M.D. Center for Inherited Colorectal Neoplasia, Cleveland Clinic Foundation, Cleveland, USA
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Massimino M, Signoroni S, Boschetti L, Chiapparini L, Erbetta A, Biassoni V, Schiavello E, Ferrari A, Spreafico F, Terenziani M, Chiaravalli S, Puma N, Bergamaschi L, Ricci MT, Cattaneo L, Gattuso G, Buttarelli FR, Gianno F, Miele E, Poggi G, Vitellaro M. Medulloblastoma and familial adenomatous polyposis: Good prognosis and good quality of life in the long-term? Pediatr Blood Cancer 2021; 68:e28912. [PMID: 33459525 DOI: 10.1002/pbc.28912] [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: 09/03/2020] [Revised: 12/23/2020] [Accepted: 01/05/2021] [Indexed: 11/09/2022]
Abstract
INTRODUCTION Mutations of the APC (adenomatous polyposis coli) gene correlate mainly with familial adenomatous polyposis (FAP), but can occasionally be pathogenic for medulloblastoma (MBL) wingless-related integration site (WNT) subtype, the course of which has only recently been described. METHODS We retrieved all patients with documented germline APC mutations and a diagnosis of MBL to examine their outcome, late effects of treatment, and further oncological events. RESULTS Between 2007 and 2016, we treated six patients, all with a pathogenic APC variant mutation and all with MBL, classic histotype. None had metastatic disease. All patients were in complete remission a median 65 months after treatment with craniospinal irradiation at 23.4 Gy, plus a boost on the posterior fossa/tumor bed up to 54 Gy, followed by cisplatin/carboplatin, lomustine, and vincristine for a maximum of eight courses. Five of six diagnostic revised MRI were suggestive of the WNT molecular subgroup typical aspects. Methylation profile score (in two cases) and copy number variation analysis (chromosome 6 deletion in two cases) performed on four of six retrieved samples confirmed WNT molecular subgroup. Four out of six patients had a positive family history of FAP, while gastrointestinal symptoms prompted its identification in the other two cases. Four patients developed other tumors (desmoid, MELTUMP, melanoma, pancreatoblastoma, thyroid Tir3) from 5 to 7 years after MBL. DISCUSSION Our data confirm a good prognosis for patients with MBL associated with FAP. Patients' secondary tumors may or may not be related to their syndrome or treatment, but warrant adequate attention when planning shared guidelines for these patients.
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Affiliation(s)
- Maura Massimino
- Pediatric Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Stefano Signoroni
- Hereditary Digestive Tract Tumors Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Luna Boschetti
- Pediatric Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Luisa Chiapparini
- Neuroradiology Department, IRCCS Fondazione Istituto Neurologico Carlo Besta, Milan, Italy
| | - Alessandra Erbetta
- Neuroradiology Department, IRCCS Fondazione Istituto Neurologico Carlo Besta, Milan, Italy
| | - Veronica Biassoni
- Pediatric Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | | | - Andrea Ferrari
- Pediatric Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Filippo Spreafico
- Pediatric Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Monica Terenziani
- Pediatric Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | | | - Nadia Puma
- Pediatric Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Luca Bergamaschi
- Pediatric Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Maria Teresa Ricci
- Hereditary Digestive Tract Tumors Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Laura Cattaneo
- Department of Pathology and Laboratory Medicine, First Pathology Division, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy
| | - Giovanna Gattuso
- Pediatric Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | | | - Francesca Gianno
- Radiologic, Oncologic and Anatomo-Pathological Sciences Department, Sapienza University, Rome, Italy
| | - Evelina Miele
- Department of Paediatric Haematology/Oncology Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Geraldina Poggi
- Neuro-Oncological and Neuropsychological Rehabilitation Unit, Scientific Institute, IRCCS Eugenio Medea, Lecco, Italy
| | - Marco Vitellaro
- Hereditary Digestive Tract Tumors Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.,Colorectal Surgery Unit, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy
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A unique case of two somatic APC mutations in an early onset cribriform-morular variant of papillary thyroid carcinoma and overview of the literature. Fam Cancer 2021; 19:15-21. [PMID: 31598872 PMCID: PMC7026211 DOI: 10.1007/s10689-019-00146-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
We report a case of a 22-year-old female patient who was diagnosed with a cribriform-morular variant of papillary thyroid carcinoma (CMV-PTC). While at early ages this thyroid cancer variant is highly suggestive for familial adenomatous polyposis (FAP), there was no family history of FAP. In the tumor biallelic, inactivating APC variants were identified. The patient tested negative for germline variants based on analysis of genomic DNA from peripheral blood leukocytes. Somatic mosaicism was excluded by subsequent deep sequencing of leukocyte and normal thyroid DNA using next generation sequencing (NGS). This report presents a rare sporadic case of CMV-PTC, and to the best of our knowledge the first featuring two somatic APC mutations underlying the disease, with an overview of CMV-PTC cases with detected APC and CTNNB1 pathogenic variants from the literature.
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Naoi D, Koinuma K, Sasanuma H, Sakuma Y, Horie H, Lefor AK, Sugano K, Ushiama M, Yoshida T, Sata N. Solid-pseudopapillary neoplasm of the pancreas in a patient with familial adenomatous polyposis: a case report. Surg Case Rep 2021; 7:35. [PMID: 33511474 PMCID: PMC7843828 DOI: 10.1186/s40792-021-01121-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Accepted: 01/21/2021] [Indexed: 11/10/2022] Open
Abstract
Background Familial adenomatous polyposis (FAP) is characterized by the presence of hundreds to thousands of colonic polyps, and extracolonic manifestations are likely to occur. Pancreatic tumors are rare extracolonic manifestations in patients with FAP, among which solid-pseudopapillary neoplasm (SPN) are extremely rare. We report here a patient with an SPN of the pancreas found during the follow-up of FAP. Case presentation A 20-year-old woman was diagnosed with FAP 3 years previously by colonoscopy which revealed less than 100 colonic polyps within the entire colon. She complained of left upper abdominal pain and a 10-cm solid and cystic pancreatic tumor was found by computed tomography scan. Solid and cystic components within the tumor were seen on abdominal magnetic resonance imaging. Simultaneous laparoscopic resection of the distal pancreas and subtotal colectomy was performed. Histopathological findings confirmed the pancreatic tumor as an SPN without malignancy. Abnormal staining of beta-catenin was observed by immunohistochemical study. Multiple polyps in the colorectum were not malignant. Molecular biological analysis from peripheral blood samples revealed a decrease in the copy number of the promoter 1A and 1B region of the APC gene, which resulted in decreased expression of the APC gene. Conclusions A rare association of SPN with FAP is reported. The genetic background with relation to beta-catenin abnormalities is interesting to consider tumor development. So far, there are few reports of SPN in a patient with FAP. Both lesions were treated simultaneously by laparoscopic resection.
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Affiliation(s)
- Daishi Naoi
- Division of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University School of Medicine, Yakushiji 3311-1, Shimotsuke, Tochigi, 329-0498, Japan.
| | - Koji Koinuma
- Division of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University School of Medicine, Yakushiji 3311-1, Shimotsuke, Tochigi, 329-0498, Japan
| | - Hideki Sasanuma
- Division of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University School of Medicine, Yakushiji 3311-1, Shimotsuke, Tochigi, 329-0498, Japan
| | - Yasunaru Sakuma
- Division of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University School of Medicine, Yakushiji 3311-1, Shimotsuke, Tochigi, 329-0498, Japan
| | - Hisanaga Horie
- Division of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University School of Medicine, Yakushiji 3311-1, Shimotsuke, Tochigi, 329-0498, Japan
| | - Alan Kawarai Lefor
- Division of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University School of Medicine, Yakushiji 3311-1, Shimotsuke, Tochigi, 329-0498, Japan
| | - Kokichi Sugano
- Genome Center, Genetic Counseling Clinic, Tochigi Cancer Center Research Institute, Tochigi, Japan
| | - Mineko Ushiama
- Department of Genetic Medicine and Services, National Cancer Center Hospital, Tokyo, Japan
| | - Teruhiko Yoshida
- Department of Genetic Medicine and Services, National Cancer Center Hospital, Tokyo, Japan
| | - Naohiro Sata
- Division of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University School of Medicine, Yakushiji 3311-1, Shimotsuke, Tochigi, 329-0498, Japan
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Shaker Ardakani Z, Heidari MM, Khatami M, Bitaraf Sani M. Association of Pathogenic Missense and Nonsense Mutations in Mitochondrial COII Gene with Familial Adenomatous Polyposis (FAP). INTERNATIONAL JOURNAL OF MOLECULAR AND CELLULAR MEDICINE 2021; 9:255-265. [PMID: 33688483 PMCID: PMC7936074 DOI: 10.22088/ijmcm.bums.9.4.255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Accepted: 11/14/2020] [Indexed: 10/31/2022]
Abstract
Nuclear genetic mutations have been extensively investigated in solid tumors. However, the role of the mitochondrial genome remains uncertain. Since the metabolism of solid tumors is associated with aerobic glycolysis and high lactate production, tumors may have mitochondrial dysfunctions. Familial adenomatous polyposis (FAP) is a rare form of colorectal cancer and an autosomal dominant inherited condition that is characterized by the progress of numerous adenomatous polyps in the rectum and colon. The present study aimed at understanding the nature and effect of mitochondrial cytochrome c oxidase subunit 2 (COII) gene mutations in FAP tumorigenesis. Fifty-six (26 familial and 30 sporadic) FAP patients and 60 normal controls were enrolled in this study. COII point mutations were evaluated by PCR and direct sequencing methods, and a total of 7 mtDNA mutations were detected (3 missense, 1 nonsense, and 3 synonymous variations). Novel non-synonymous COII gene mutations were mostly in heteroplasmic state. These mutations change amino acid residues in the N-terminal and C-terminal regions of COXII. Bioinformatics analysis and three-dimensional structural modeling predicted that these missense and nonsense mutations have functional importance, and mainly affected on cytochrome c oxidase (complex IV). Also, FAP patients carried a meaningfully higher prevalence of mutations in the COII gene in comparison with healthy controls (P <0.001). Analysis of cancer-associated mtDNA mutation could be an invaluable tool for molecular assessment of FAP so that these findings can be helpful for the development of potential new biomarkers in the diagnosis of cancer for future clinical assessments.
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Affiliation(s)
| | | | - Mehri Khatami
- Department of Biology, Faculty of Science, Yazd University, Yazd, Iran
| | - Morteza Bitaraf Sani
- Animal Science Research Department, Yazd Agricultural and Natural Resources Research and Education Center, Agricultural Research, Education & Extension Organization (AREEO), Yazd, Iran
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Desmoid Tumors Characteristics, Clinical Management, Active Surveillance, and Description of Our FAP Case Series. J Clin Med 2020; 9:jcm9124012. [PMID: 33322514 PMCID: PMC7764110 DOI: 10.3390/jcm9124012] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Revised: 11/24/2020] [Accepted: 12/08/2020] [Indexed: 01/03/2023] Open
Abstract
(1) Background: desmoid tumors (DTs) are common in patients with familial adenomatous polyposis (FAP). An active surveillance approach has been recently proposed as a valuable alternative to immediate treatment in some patients. However, no clear indication exists on which patients are suitable for active surveillance, how to establish the cut-off for an active treatment, and which imaging technique or predictive factors should be used during the surveillance period. (2) Results: we retrospectively analyzed 13 FAP patients with DTs. A surveillance protocol consisting of scheduled follow-up evaluations depending on tumor location and tissue thickening, abdominal computed tomography (CT) scan/Magnetic resonance imaging (MRI) allowed prompt intervention in 3/11 aggressive intra-abdominal DTs, while sparing further interventions in the remaining cases, despite worrisome features detected in three patients. Moreover, we identified a possible predictive marker of tumor aggressiveness, i.e., the "average monthly growth rate" (AMGR), which could distinguish patients with very aggressive/life-threatening tumor behavior (AMGR > 0.5) who need immediate active treatment, from those with stable DTs (AMGR < 0.1) in whom follow-up assessments could be delayed. (3) Conclusion: surveillance protocols may be a useful approach for DTs. Further studies on larger series are needed to confirm the usefulness of periodic CT scan/MRI and the value of AMGR as a prognostic tool to guide treatment strategies.
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46
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Zhou J, Liang C, Qing D, Wang Y, Tan Y, Shi X. A novel large deletion in the APC gene associated with Gardner syndrome in a Chinese family. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2020; 113:179-182. [PMID: 33213169 DOI: 10.17235/reed.2020.6974/2020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
INTRODUCTION Gardner syndrome is a hereditary disease characterized by familial adenomatous polyposis (FAP), accompanied by soft tissue tumors. MATERIAL AND METHODS a Chinese FAP family was enrolled and followed-up for three years. RESULTS a novel large germline fragment deletion (EX10_16DEL) of the adenomatous polyposis coli (APC) gene was identified by multiplex ligation-dependent probe amplification (MLPA). An unexpected abdominal tumor grew two years after a subtotal colectomy of the proband. The immunohistochemistry study of the abdominal tumor showed SMA(focal+), calponin(+), β-catenin(nucleus+) and CD34(focal+), CD117(-), which was consistent with a desmoid tumor. CONCLUSION when a FAP related desmoid tumor appears, the possibility of Gardner syndrome should be considered. This is the first largest deletion of the APC gene in the Chinese population associated with Gardner syndrome.
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Affiliation(s)
- Junfeng Zhou
- Gastroenterology, The Second Xiangya Hospital. Central South University
| | - Chengbo Liang
- Medical Genetics, The Second Xiangya Hospital. Central South University
| | - Duxin Qing
- Medical Genetics, The Second Xiangya Hospital. Central South University
| | - Yongjun Wang
- Medical Genetics, The Second Xiangya Hospital. Central South University
| | - Yuyong Tan
- Medical Genetics, The Second Xiangya Hospital. Central South University
| | - Xiaoliu Shi
- Gastroenterology, second Xiangya Hospital. Central South University,
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47
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Matsuoka K, Bakiri L, Wolff LI, Linder M, Mikels-Vigdal A, Patiño-García A, Lecanda F, Hartmann C, Sibilia M, Wagner EF. Wnt signaling and Loxl2 promote aggressive osteosarcoma. Cell Res 2020; 30:885-901. [PMID: 32686768 PMCID: PMC7608146 DOI: 10.1038/s41422-020-0370-1] [Citation(s) in RCA: 79] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Accepted: 06/22/2020] [Indexed: 12/18/2022] Open
Abstract
Osteosarcoma (OS) is the most frequent primary malignant bone tumor in urgent need of better therapies. Using genetically modified mouse models (GEMMs), we demonstrate that Wnt signaling promotes c-Fos-induced OS formation via the actions of the collagen-modifying enzyme Loxl2. c-Fos/AP-1 directly regulates the expression of the Wnt ligands Wnt7b and Wnt9a in OS cells through promoter binding, and Wnt7b and Wnt9a in turn promote Loxl2 expression in murine and human OS cells through the transcription factors Zeb1 and Zeb2. Concordantly, inhibition of Wnt ligand secretion by inactivating the Wnt-less (Wls) gene in osteoblasts in c-Fos GEMMs either early or in a therapeutic setting reduces Loxl2 expression and progression of OS. Wls-deficient osteosarcomas proliferate less, are less mineralized and are enriched in fibroblastic cells surrounded by collagen fibers. Importantly, Loxl2 inhibition using either the pan-Lox inhibitor BAPN or a specific inducible shRNA reduces OS cell proliferation in vitro and decreases tumor growth and lung colonization in murine and human orthotopic OS transplantation models. Finally, OS development is delayed in c-Fos GEMMs treated with BAPN or with specific Loxl2 blocking antibodies. Congruently, a strong correlation between c-FOS, LOXL2 and WNT7B/WNT9A expression is observed in human OS samples, and c-FOS/LOXL2 co-expression correlates with OS aggressiveness and decreased patient survival. Therefore, therapeutic targeting of Wnt and/or Loxl2 should be considered to potentiate the inadequate current treatments for pediatric, recurrent, and metastatic OS.
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Affiliation(s)
- Kazuhiko Matsuoka
- Laboratory Genes and Disease, Department of Dermatology, Medical University of Vienna (MUV), Vienna, 1090, Austria
- Genes, Development and Disease Group, Spanish National Cancer Research Centre (CNIO), Madrid, 28029, Spain
| | - Latifa Bakiri
- Laboratory Genes and Disease, Department of Laboratory Medicine, Medical University of Vienna (MUV), Vienna, 1090, Austria
- Genes, Development and Disease Group, Spanish National Cancer Research Centre (CNIO), Madrid, 28029, Spain
| | - Lena I Wolff
- Department of Bone and Skeletal Research, Medical Faculty, Institute of Musculoskeletal Medicine, University of Münster, Münster, 48149, Germany
| | - Markus Linder
- Department of Medicine I, Comprehensive Cancer Center, Institute of Cancer Research, Medical University of Vienna (MUV), Vienna, 1090, Austria
| | | | - Ana Patiño-García
- Navarra Institute for Health Research(IdISNA) and Program in Solid Tumors, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, 31008, Spain
- Department of Pediatrics, University Clinic of Navarra, Pamplona, 31008, Spain
| | - Fernando Lecanda
- Navarra Institute for Health Research(IdISNA) and Program in Solid Tumors, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, 31008, Spain
- Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Pamplona, 31008, Spain
| | - Christine Hartmann
- Department of Bone and Skeletal Research, Medical Faculty, Institute of Musculoskeletal Medicine, University of Münster, Münster, 48149, Germany
| | - Maria Sibilia
- Department of Medicine I, Comprehensive Cancer Center, Institute of Cancer Research, Medical University of Vienna (MUV), Vienna, 1090, Austria
| | - Erwin F Wagner
- Laboratory Genes and Disease, Department of Dermatology, Medical University of Vienna (MUV), Vienna, 1090, Austria.
- Laboratory Genes and Disease, Department of Laboratory Medicine, Medical University of Vienna (MUV), Vienna, 1090, Austria.
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48
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Alkofahi AA, Kabashneh S, Alqam A. Familial Adenomatous Polyposis Complicated by Acute Myelogenous Leukemia. Cureus 2020; 12:e8703. [PMID: 32699699 PMCID: PMC7370583 DOI: 10.7759/cureus.8703] [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: 11/10/2022] Open
Abstract
Familial adenomatous polyposis (FAP) is an autosomal dominant disorder characterized by the appearance of multiple colorectal adenomatous polyps and propensity for evolving into adenocarcinoma, typically in early adulthood. We present a case of a 38-year-old man with a one-year history of bloody stool, found to have innumerable polyps throughout the colon and therefore diagnosed with FAP. Completed blood count with differential revealed blasts, a finding confirmed via a peripheral blood smear; a follow-up bone marrow biopsy also showed blasts and he was diagnosed with acute myeloid leukemia (AML). To our knowledge, FAP and AML occurring in the same patient were reported only once in the literature. In our patient and the previously reported case, it is assumed that FAP occurred first and AML developed later; no family history of FAP was noted in either patient. This case raises the question of whether a sporadic FAP is more likely to lead to AML compared to the classic FAP.
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Affiliation(s)
| | - Sohaip Kabashneh
- Internal Medicine, Wayne State University/Detroit Medical Center, Detroit, USA
| | - Ahmad Alqam
- Internal Medicine, King Hussein Cancer Center, Amman, JOR
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49
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Anderson E, Landes C, McCann E. Desmoid tumour: rare presentation following neonatal lumbar puncture. Arch Dis Child Fetal Neonatal Ed 2020; 105:298. [PMID: 32029529 DOI: 10.1136/archdischild-2018-316210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2019] [Revised: 01/14/2020] [Accepted: 01/18/2020] [Indexed: 11/03/2022]
Affiliation(s)
- Emily Anderson
- Liverpool Centre for Genomic Medicine, Liverpool Womens NHS Foundation Trust, Liverpool, UK
| | - Caren Landes
- Alder Hey Children's NHS Foundation Trust, Liverpool, UK
| | - Emma McCann
- Liverpool Centre for Genomic Medicine, Liverpool Womens NHS Foundation Trust, Liverpool, UK
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50
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Zhang S, William C. Educational Case: Histologic and Molecular Features of Diffuse Gliomas. Acad Pathol 2020; 7:2374289520914021. [PMID: 32284966 PMCID: PMC7133074 DOI: 10.1177/2374289520914021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2019] [Revised: 01/13/2020] [Accepted: 02/22/2020] [Indexed: 11/23/2022] Open
Abstract
The following fictional cases are intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, seehttp://journals.sagepub.com/doi/10.1177/2374289517715040.1
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Affiliation(s)
- Sarah Zhang
- NYU Langone Medical Center, New York, NY, USA
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