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Jafari P, Drogan C, Keel E, Kupfer S, Hart J, Setia N. Screening at the scope: enhancing the role of pathologists in diagnosing gastrointestinal polyposis syndromes. Virchows Arch 2025:10.1007/s00428-025-04118-1. [PMID: 40358740 DOI: 10.1007/s00428-025-04118-1] [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: 04/15/2025] [Revised: 04/15/2025] [Accepted: 04/25/2025] [Indexed: 05/15/2025]
Abstract
Only a minority of patients at high likelihood of a gastrointestinal polyposis syndrome (GPS) are appropriately referred for workup. This proof-of-concept study evaluates a GPS screening rubric based exclusively on information in prior pathology reports and intended to facilitate pathologist engagement in GPS screening and referral. We sought to (1) identify patients who would benefit from further GPS workup, (2) assign a probable polyposis syndrome category (adenomatous, hamartomatous, serrated, or mixed), and (3) suggest a specific syndrome, such as familial adenomatous polyposis, whenever possible. We retrospectively tested the rubric against the pathology records of 108 patients (median, 6 reports/patient) with an established clinical diagnosis of GPS (adenomatous (N = 88), hamartomatous (N = 18), and mixed (N = 2) polyposis syndromes). Records were reviewed chronologically (mean, 4.4 min/patient) by a GI pathologist blinded to clinical history. Ninety-five patients (88%) had a positive GPS screen (N = 76 with an adenomatous polyposis syndrome, N = 17 with a hamartomatous polyposis syndrome, N = 2 with a mixed polyposis syndrome); all were assigned to the correct syndrome category. In a subset of cases, the histopathologic record suggested a specific syndrome (correct in 28 of 30 instances). Of 13 patients with a negative screen (failure to meet any rubric parameters), N = 6 (46.2%) had incomplete records. These findings demonstrate that when robust records are available, structured review of pathology reports is a sensitive and efficient tool for the identification of patients with a high suspicion of a GPS. While prospective studies are necessary, pathologists are indeed well positioned to play an expanded role in GPS screening.
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Affiliation(s)
- Pari Jafari
- Department of Pathology, University of Chicago Medicine, 5841 S. Maryland Avenue, MC 6101, Room S-638, IL 60637-1470, Chicago, USA.
| | - Christine Drogan
- Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago Medicine, Chicago, USA
| | - Emma Keel
- Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago Medicine, Chicago, USA
| | - Sonia Kupfer
- Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago Medicine, Chicago, USA
| | - John Hart
- Department of Pathology, University of Chicago Medicine, 5841 S. Maryland Avenue, MC 6101, Room S-638, IL 60637-1470, Chicago, USA
| | - Namrata Setia
- Department of Pathology, University of Chicago Medicine, 5841 S. Maryland Avenue, MC 6101, Room S-638, IL 60637-1470, Chicago, USA
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2
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Arshad H, Crawford CK, Fishman EK. An uncommon intersection: Familial adenomatous polyposis and solid pseudopapillary neoplasm of the pancreas: A case report and review of the literature. Radiol Case Rep 2025; 20:2432-2436. [PMID: 40129818 PMCID: PMC11930510 DOI: 10.1016/j.radcr.2025.01.096] [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: 12/02/2024] [Revised: 01/29/2025] [Accepted: 01/30/2025] [Indexed: 03/26/2025] Open
Abstract
The co-occurrence of both Familial Adenomatous Polyposis (FAP) and Solid Pseudopapillary Neoplasms (SPN) of the pancreas is extremely uncommon, with limited reports published in the literature. FAP is a rare inherited disorder caused by a mutation in the adenomatous polyposis coli (APC) gene, while SPN is generally a low-grade malignant pancreatic lesion. We present the case of a 33-year-old female with a familial history of FAP, who initially presented with breast fibromatoses and was subsequently found to have colonic polyps, consistent with FAP, along with rare events like pancreatic SPNs in the head and tail of the pancreas and large desmoid tumors. It is a unique case that has never been reported in the literature and we provide findings of computed tomography (CT) and volume rendering to correlate the radiological features with pathology for an optimized diagnosis.
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Affiliation(s)
- Hajra Arshad
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, USA
| | - Charles K. Crawford
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, USA
| | - Elliot K. Fishman
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, USA
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3
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Yeap BT, Nasir I, Koo TH, Paul AG, Zakaria MH. A Rare Case of Desmoid Fibromatosis in a Pediatric Patient: Surgical Management and Outcomes. Radiol Case Rep 2025; 20:2384-2387. [PMID: 40129797 PMCID: PMC11930522 DOI: 10.1016/j.radcr.2025.01.083] [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: 01/01/2025] [Revised: 01/18/2025] [Accepted: 01/25/2025] [Indexed: 03/26/2025] Open
Abstract
Desmoid fibromatosis (DF) is a rare, locally aggressive tumor arising from the abdominal fascia or musculoaponeurosis, commonly affecting individuals between 15 and 60 years of age. We present a case of a 13-year-old boy with a 9-month history of progressive swelling in the left posterior thigh. Magnetic resonance imaging (MRI) revealed a soft tissue tumor encasing the sciatic nerve. A biopsy confirmed the diagnosis of DF, showing spindle cells arranged in fascicles. The patient underwent wide local excision of the tumor with preservation of the sciatic nerve. Postoperative recovery was smooth, and 1-year follow-up MRI showed no recurrence. Surgical excision remains the primary treatment, especially in symptomatic patients, although recurrence is common even with negative margins. This case underscores the importance of regular follow-up for DF and a multidisciplinary approach to optimize management and surveillance.
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Affiliation(s)
- Boon Tat Yeap
- Department of Anaesthesiology and Intensive Care, Hospital Universiti Malaysia Sabah, Kota Kinabalu, Sabah, Malaysia
- Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, Kota Kinabalu, Sabah, Malaysia
| | - Ikhwan Nasir
- Department of Anaesthesiology and Intensive Care, Hospital Universiti Malaysia Sabah, Kota Kinabalu, Sabah, Malaysia
| | - Thai Hau Koo
- Department of Internal Medicine, School of Medical Sciences, Hospital Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia
| | - Aaron Gerarde Paul
- Department of Orthopaedics, Hospital Queen Elizabeth, Kota Kinabalu, Sabah, Malaysia
| | - Mohd Hazeman Zakaria
- Department of Radiology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor, Malaysia
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4
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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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Tanaka Y, Toyokawa T, Yoshii M, Miki Y, Tamura T, Lee S, Maeda K. Giant Intra-Abdominal Desmoid Tumor in a Young Man: A Case Report and Literature Review. Surg Case Rep 2025; 11:24-0019. [PMID: 40124320 PMCID: PMC11926331 DOI: 10.70352/scrj.cr.24-0019] [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: 10/16/2024] [Accepted: 02/05/2025] [Indexed: 03/25/2025] Open
Abstract
INTRODUCTION Desmoid tumors are rare soft-tissue tumors with a high recurrence rate; however, histologically, these tumors are benign. We describe a case in which a giant desmoid tumor was resected in a young man without any apparent causative factors. CASE PRESENTATION A 21-year-old man was referred to our hospital for treatment after presenting to a nearby hospital with right inguinal pain. Abdominal magnetic resonance imaging showed an intra-abdominal mass measuring 34 × 15 × 8 cm with partial signal hyperintensity on T2-weighted imaging and hypointensity on T1-weighted imaging, extending from the left abdominal cavity to the pelvic region. Although no definitive diagnosis was obtained preoperatively, surgery was performed under suspicion of gastrointestinal stromal tumor or other significant disease. A mass was identified firmly adherent to the transverse colon, gastric wall, and diaphragm, and these organs were partially resected. The excised specimen measured 38 × 21 × 8 cm and weighed 6400 g. Macroscopically, the tumor showed a smooth surface and homogeneous interior. Pathological examination revealed atypical cells with spindle-shaped nuclei and collagen fiber hyperplasia in the stroma, and immunostaining was negative for c-kit, CD34, desmin, S-100, and positive for β-catenin, leading to a confirmed diagnosis of desmoid tumor. Fifteen months after surgery, a local recurrence with a diameter of 3.0 cm was identified, and the patient remains under careful follow-up. CONCLUSIONS Intra-abdominal desmoid tumors larger than 30 cm are extremely rare. When encountering a young patient with a large intra-abdominal tumor, the possibility of desmoid tumor should be considered.
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Affiliation(s)
- Yusuke Tanaka
- Department of Gastroenterological Surgery, Tsukazaki Hospital, Himeji, Hyogo, Japan
- Department of Gastroenterological Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, Osaka, Japan
| | - Takahiro Toyokawa
- Department of Gastroenterological Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, Osaka, Japan
| | - Mami Yoshii
- Department of Gastroenterological Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, Osaka, Japan
| | - Yuichiro Miki
- Department of Gastroenterological Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, Osaka, Japan
| | - Tatsuro Tamura
- Department of Gastroenterological Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, Osaka, Japan
| | - Shigeru Lee
- Department of Gastroenterological Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, Osaka, Japan
| | - Kiyoshi Maeda
- Department of Gastroenterological Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, Osaka, Japan
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Zouaghi A, Hafsi M, Maroua O, Khouloud M, Chaouech A, Haifa B. An intra-abdominal desmoid tumour: Case report. Int J Surg Case Rep 2025; 127:110897. [PMID: 39874801 PMCID: PMC11808673 DOI: 10.1016/j.ijscr.2025.110897] [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: 10/10/2024] [Revised: 01/12/2025] [Accepted: 01/14/2025] [Indexed: 01/30/2025] Open
Abstract
INTRODUCTION AND IMPORTANCE Desmoid tumours typically arise in the abdomen and extremities. They are rare, originating from mesenchymal cells, with intra-abdominal desmoid tumours (DT) being even less common. While non-malignant and non-metastatic, they can be locally invasive, often necessitating surgical intervention for complete resection. CASE PRESENTATION We present the case of a 26-year-old woman referred to our emergency department with pelvic pain three months after cesarean delivery. Abdominal computed tomography revealed a 7 cm retro-uterine mass extending to the right colon, appendix, and cecum. Although MRI suggested an intra-mesenteric benign tumour, a definitive diagnosis was not established. Surgical excision was performed for both diagnostic and therapeutic purposes, revealing a 5.5 cm desmoid tumour infiltrating adipose and muscular tissue of the last ileal loop, with negative resection margins. Postoperative recovery was uneventful, and the patient is under CT surveillance. CLINICAL DISCUSSION Intra-abdominal DTs are exceedingly rare and can present with a spectrum of symptoms. Imaging findings may mimic other conditions, making diagnosis challenging. Surgical expertise is crucial for optimal management, with complete resection being the primary therapeutic approach. CONCLUSION In conclusion, intra-abdominal desmoid tumours are rare entities that pose diagnostic and therapeutic challenges. Surgeons experienced in handling such cases are essential for achieving favourable outcomes. Continued surveillance is necessary due to the potential for recurrence.
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Affiliation(s)
- Asma Zouaghi
- Department of Obstetrics and Gynecology, Tahar Sfar University Hospital, 5111 Mahdia, Tunisia.
| | - Montacer Hafsi
- Department of Obstetrics and Gynecology, Tahar Sfar University Hospital, 5111 Mahdia, Tunisia
| | - Othman Maroua
- Department of Obstetrics and Gynecology, Tahar Sfar University Hospital, 5111 Mahdia, Tunisia
| | - Marzouk Khouloud
- Department of Obstetrics and Gynecology, Tahar Sfar University Hospital, 5111 Mahdia, Tunisia
| | - A Chaouech
- Department of Gastro Enterological Surgery, Tahar Sfar University Hospital; 5111 Mahdia, Tunisia
| | - Bouchahda Haifa
- Department of Obstetrics and Gynecology, Tahar Sfar University Hospital, 5111 Mahdia, Tunisia
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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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8
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Aelvoet AS, Pellisé M, Miedema TN, Daca-Alvarez M, Bastiaansen BAJ, van Leerdam ME, Jover R, Balaguer F, Kaminski MF, Buttitta F, Ricciardiello L, Jespersen N, Karstensen JG, Bossuyt PMM, Latchford A, Hompes R, Dekker E. Development of Desmoid Tumors After Ileorectal Anastomosis Versus Ileal Pouch-Anal Anastomosis in Familial Adenomatous Polyposis. Clin Gastroenterol Hepatol 2024; 22:2319-2326. [PMID: 38969075 DOI: 10.1016/j.cgh.2024.06.018] [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: 01/08/2024] [Revised: 06/07/2024] [Accepted: 06/12/2024] [Indexed: 07/07/2024]
Abstract
BACKGROUND & AIMS Desmoid tumors (DT) are an important cause of morbidity and mortality in patients with familial adenomatous polyposis (FAP). DT development might be related to the type and approach of colectomy. We aimed to compare DT development after colectomy with ileorectal anastomosis (IRA) and proctocolectomy with ileal pouch-anal anastomosis (IPAA). METHODS We performed an international historical cohort study in patients with FAP who underwent IRA or IPAA between 1961 and 2020. The primary outcome was the incidence of abdominal DT (either mesenteric, retroperitoneal, or abdominal wall). Patients with a DT diagnosis before or at colectomy were excluded. Time to DT was considered censored at an eventual secondary proctectomy after IRA. We used multivariable Cox regression modelling to adjust for potential confounders. RESULTS We analyzed data from 852 patients: 514 after IRA and 338 after IPAA (median follow-up, 21 and 16 years, respectively). DTs were diagnosed in 64 IRA patients (12%) and 66 IPAA patients (20%). The cumulative DT incidence at 5 and 10 years was 7.5% and 9.3% after open IRA and 4.7% and 10.9% after laparoscopic IRA. These estimates were 13.6% and 15.4% after open IPAA and 8.4% and 10.0% after laparoscopic IPAA. The postoperative risk was significantly higher after IPAA (P < .01) in multivariable analysis, whereas approach did not significantly influence the risk. CONCLUSIONS The risk of developing an abdominal DT was found to be significantly higher after IPAA than after IRA. Postoperative DT risk should be taken into account when choosing between IRA and IPAA in FAP.
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Affiliation(s)
- Arthur S Aelvoet
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Cancer Center Amsterdam, Amsterdam, the Netherlands; Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, the Netherlands
| | - Maria Pellisé
- Department of Gastroenterology, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, University of Barcelona, Barcelona, Spain
| | - Thymen N Miedema
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Cancer Center Amsterdam, Amsterdam, the Netherlands; Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, the Netherlands
| | - Maria Daca-Alvarez
- Department of Gastroenterology, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, University of Barcelona, Barcelona, Spain
| | - Barbara A J Bastiaansen
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Cancer Center Amsterdam, Amsterdam, the Netherlands; Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, the Netherlands
| | - Monique E van Leerdam
- Department of Gastrointestinal Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands; Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands
| | - Rodrigo Jover
- Servicio de Medicina Digestiva, Hospital General Universitario de Alicante, Instituto de Investigación Biomédica ISABIAL, Universidad Miguel Hernández, Alicante, Spain
| | - Francesc Balaguer
- Department of Gastroenterology, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, University of Barcelona, Barcelona, Spain
| | - Michal F Kaminski
- Department of Oncological Gastroenterology, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland; Department of Cancer Prevention, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| | - Francesco Buttitta
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola, Bologna, Italy
| | - Luigi Ricciardiello
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola, Bologna, Italy
| | - Niels Jespersen
- Danish Polyposis Registry, Gastrounit, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark
| | - John G Karstensen
- Danish Polyposis Registry, Gastrounit, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Patrick M M Bossuyt
- Department of Epidemiology and Data Science, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
| | - Andrew Latchford
- Polyposis Registry, St Mark's Hospital, Harrow, United Kingdom; Department of Surgery and Cancer, Imperial College, London, United Kingdom
| | - Roel Hompes
- Cancer Center Amsterdam, Amsterdam, the Netherlands; Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
| | - Evelien Dekker
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Cancer Center Amsterdam, Amsterdam, the Netherlands; Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, the Netherlands.
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9
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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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10
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Ajabnoor R. Different Shades of Desmoid-Type Fibromatosis (DTF): Detection of Noval Mutations in the Clinicopathologic Analysis of 32 Cases. Diagnostics (Basel) 2024; 14:2161. [PMID: 39410565 PMCID: PMC11476057 DOI: 10.3390/diagnostics14192161] [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: 05/25/2024] [Revised: 08/30/2024] [Accepted: 09/13/2024] [Indexed: 10/20/2024] Open
Abstract
BACKGROUND Desmoid-type fibromatosis (DTF) is a locally aggressive myofibroblastic/fibroblastic neoplasm with a high risk of local recurrence. It has a variety of histologic features that might confuse diagnosis, especially when detected during core needle biopsy. The Wnt/β-catenin pathway is strongly linked to the pathogenesis of DT fibromatosis. METHOD This study examined 33 desmoid-type fibromatoses (DTFs) from 32 patients, analyzing its clinical characteristics, histologic patterns, occurrence rates, relationship with clinical outcomes, immunohistochemical and molecular findings. RESULTS The DTFs exhibit a range of 1 to 7 histologic patterns per tumor, including conventional, hypercellular, myxoid, hyalinized/hypocellular, staghorn/hemangiopericytomatous blood vessels pattern, nodular fasciitis-like, and keloid-like morphology. No substantial association was found between the existence of different histologic patterns and the clinical outcome. All thirty-three (100%) samples of DTF had a variable percentage of cells that were nuclear positive for β-catenin. An NGS analysis detected novel non-CTNNB1 mutations in two DTFs, including BCL10, MPL, and RBM10 gene mutations. CONCLUSIONS This study reveals a diverse morphology of DTFs that could result in misdiagnosis. Therefore, surgical pathologists must comprehend this thoroughly. Also, the importance of the newly identified non-CTNNB1 gene mutations is still unclear. More research and analyses are needed to completely grasp the clinical implications of these mutations.
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Affiliation(s)
- Rana Ajabnoor
- Department of Pathology, Faculty of Medicine, King Abdulaziz University and King Abdulaziz University Hospital, Jeddah 22252, Saudi Arabia
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11
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Almjersah A, Olaisheh H, Salloum R, Alshehabi Z, Almjersah E. Incidental discovery of unilateral hydronephrosis unveiling psoas major desmoid-type fibromatosis in a 24-year-old male: A case report with a 5-year follow-up. Medicine (Baltimore) 2024; 103:e39042. [PMID: 39058836 PMCID: PMC11272233 DOI: 10.1097/md.0000000000039042] [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: 05/13/2024] [Accepted: 07/02/2024] [Indexed: 07/28/2024] Open
Abstract
RATIONALE Desmoid-type fibromatosis (DTF), also known as aggressive fibromatosis, is a rare neoplasm originating from the fascial or musculoaponeurotic tissues. While benign and characterized by slow growth, it exhibits local aggressiveness and lacks specific clinical characteristics. However, in a considerable percentage of patients, it could be asymptomatic and discovered by accident during routine clinical examinations. Only a few cases of DTF arising from the psoas major muscle have been reported in the medical literature. PATIENT CONCERNS A 24-year-old male, asymptomatic and without significant personal or family medical history, was diagnosed with grade 2 hydronephrosis by abdominal ultrasonography during a routine physical examination. This diagnosis was made 15 days after undergoing uncomplicated open-heart surgery to repair an atrial septal defect. DIAGNOSIS Intravenous pyelogram revealed hydronephrosis with dilation of the pelvicalyceal system. Ureteroscopy ruled out any intrinsic lesions of the ureter. Contrast-enhanced computed tomography identified a 3.5 × 2 × 5.2 cm mass in the retroperitoneum, closely associated with the psoas muscle and enveloping the ureter adjacent to the iliac artery. Postoperative pathological analysis confirmed a definitive diagnosis of sporadic DTF. INTERVENTIONS The patient underwent exploratory abdominal surgery, during which the tumor was resected without any intraoperative complications. RESULTS After close monitoring over a 5-year follow-up period, which included periodic physical examinations, magnetic resonance imaging, and ultrasonography, no local recurrence was detected. LESSONS Achieving an accurate preoperative diagnosis presents a challenge in cases involving retroperitoneal tumors originating from the psoas major muscle and encasing the ureter. However, the insertion of a double J stent is deemed a crucial step in the surgical process, facilitating the dissection and isolation of the ureter from the tumor while preserving kidney function.
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Affiliation(s)
- Abdulrahman Almjersah
- Faculty of Medicine, Cancer Research Center, Tishreen University, Latakia, Syria
- Syrian Medical Research Group, Damascus, Syria
| | - Habib Olaisheh
- Faculty of Medicine, Cancer Research Center, Tishreen University, Latakia, Syria
- Syrian Medical Research Group, Damascus, Syria
| | - Rabab Salloum
- Department of Pathology, Cancer Research Center, Tishreen University, Latakia, Syria
| | - Zuheir Alshehabi
- Department of Pathology, Cancer Research Center, Tishreen University, Latakia, Syria
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12
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Lauricella S, Rausa E, Pellegrini I, Ricci MT, Signoroni S, Palassini E, Cavalcoli F, Pasanisi P, Colombo C, Vitellaro M. Current management of familial adenomatous polyposis. Expert Rev Anticancer Ther 2024; 24:363-377. [PMID: 38785081 DOI: 10.1080/14737140.2024.2344649] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Accepted: 04/15/2024] [Indexed: 05/25/2024]
Abstract
INTRODUCTION APC-associated polyposis is a rare hereditary disorder characterized by the development of multiple adenomas in the digestive tract. Individuals with APC-associated polyposis need to be managed by specialized multidisciplinary teams in dedicated centers. AREAS COVERED The study aimed to review the literature on Familial adenomatous polyposis (FAP) to provide an update on diagnostic and surgical management while focusing on strategies to minimize the risk of desmoid-type fibromatosis, cancer in anorectal remnant, and postoperative complications. FAP individuals require a comprehensive approach that includes diagnosis, surveillance, preventive surgery, and addressing specific extracolonic concerns such as duodenal and desmoid tumors. Management should be personalized considering all factors: genotype, phenotype, and personal needs. Total colectomy and ileo-rectal anastomosis have been shown to yield superior QoL results when compared to Restorative Procto colectomy and ileopouch-anal anastomosis with acceptable oncological risk of developing cancer in the rectal stump if patients rigorously adhere to lifelong endoscopic surveillance. Additionally, a low-inflammatory diet may prevent adenomas and cancer by modulating systemic and tissue inflammatory indices. EXPERT OPINION FAP management requires a multidisciplinary and personalized approach. Integrating genetic advances, innovative surveillance techniques, and emerging therapeutic modalities will contribute to improving outcomes and quality of life for FAP individuals.
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Affiliation(s)
- Sara Lauricella
- Hereditary Digestive Tract Tumors Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Emanuele Rausa
- Hereditary Digestive Tract Tumors Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Ilaria Pellegrini
- Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Maria Teresa Ricci
- Hereditary Digestive Tract Tumors Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Stefano Signoroni
- Hereditary Digestive Tract Tumors Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Elena Palassini
- Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Federica Cavalcoli
- Gastroenterology and Digestive Endoscopy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Patrizia Pasanisi
- Nutrition Research and Metabolomics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Chiara Colombo
- Sarcoma Surgery Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Marco Vitellaro
- Hereditary Digestive Tract Tumors Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
- Colorectal Surgery Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
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13
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Antal G, Zsigmond A, Till Á, Orsi E, Szanto I, Büki G, Kereskai L, Herbert Z, Hadzsiev K, Bene J. Case report: Initial atypical skeletal symptoms and dental anomalies as first signs of Gardner syndrome: the importance of genetic analysis in the early diagnosis. Pathol Oncol Res 2024; 30:1611768. [PMID: 38807857 PMCID: PMC11130347 DOI: 10.3389/pore.2024.1611768] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Accepted: 04/29/2024] [Indexed: 05/30/2024]
Abstract
Background: Gardner syndrome is a rare genetic cancer predisposition disorder characterized by intestinal polyposis, multiple osteomas, and soft and hard tissue tumors. Dental anomalies are present in approximately 30%-70% of patients with Gardner syndrome and can be discovered during routine dental examinations. However, sometimes the diagnosis is challenging due to the high clinical variability and incomplete clinical picture. Herein, we report a family with various dental and bone anomalies, in which the definitive diagnosis was established with the help of a comprehensive genetic analysis based on state-of-the-art next-generation sequencing technology. Case presentation: A 17-year-old female index patient presented with dental (caries, impacted, retained and anteriorly located teeth) and atypical bone anomalies not resembling Gardner syndrome. She was first referred to our Genetic Counselling Unit at the age of 11 due to an atypical bone abnormality identified by a panoramic X-ray. Tooth 3.6 was surgically removed and the histopathology report revealed a Paget's disease-like bone metabolic disorder with mixed osteoblastic and osteoclastic activity of the mandible. A small lumbar subcutaneous tumor was discovered by physical examination. Ultrasound examination of the tumor raised the possibility of a soft tissue propagation of chondromatosis. Her sister, 2 years younger at the age of 14, had some benign tumors (multiple exostoses, odontomas, epidermoid cysts) and impacted teeth. Their mother had also skeletal symptoms. Her lower teeth did not develop, the 9th-10th ribs were fused, and she complained of intermittent jaw pain. A cranial CT scan showed fibrous dysplasia on the cranial bones. Whole exome sequencing identified a heterozygous pathogenic nonsense mutation (c.4700C>G; p.Ser1567*) in the APC gene in the index patient's DNA. Targeted sequencing revealed the same variant in the DNA of the other affected family members (the sister and the mother). Conclusion: Early diagnosis of this rare, genetically determined syndrome is very important, because of the potentially high malignant transformation of intestinal polyps. Dentists should be familiar with the typical maxillofacial features of this disorder, to be able to refer patients to genetic counseling. Dental anomalies often precede the intestinal polyposis and facilitate the early diagnosis, thereby increasing the patients' chances of survival. Genetic analysis may be necessary in patients with atypical phenotypic signs.
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Affiliation(s)
- Gréta Antal
- Department of Dentistry, Oral and Maxillofacial Surgery, Clinical Center, Medical School, University of Pécs, Pécs, Hungary
| | - Anna Zsigmond
- Department of Medical Genetics, Clinical Center, Medical School, University of Pécs, Pécs, Hungary
| | - Ágnes Till
- Department of Medical Genetics, Clinical Center, Medical School, University of Pécs, Pécs, Hungary
| | - Eniko Orsi
- Department of Dentistry, Oral and Maxillofacial Surgery, Clinical Center, Medical School, University of Pécs, Pécs, Hungary
| | - Ildiko Szanto
- Department of Dentistry, Oral and Maxillofacial Surgery, Clinical Center, Medical School, University of Pécs, Pécs, Hungary
| | - Gergely Büki
- Department of Medical Genetics, Clinical Center, Medical School, University of Pécs, Pécs, Hungary
| | - László Kereskai
- Department of Pathology, Clinical Center, Medical School, University of Pécs, Pécs, Hungary
| | - Zsuzsanna Herbert
- Department of Medical Imaging, Clinical Center, Medical School, University of Pécs, Pécs, Hungary
| | - Kinga Hadzsiev
- Department of Medical Genetics, Clinical Center, Medical School, University of Pécs, Pécs, Hungary
| | - Judit Bene
- Department of Medical Genetics, Clinical Center, Medical School, University of Pécs, Pécs, Hungary
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Shimamoto Y, Takeuchi Y, Ishiguro S, Nakatsuka S, Yunokizaki H, Ezoe Y, Nakajima T, Tanaka K, Ishihara R, Takayama T, Yoshida T, Sugano K, Mutoh M, Ishikawa H. Genotype-phenotype correlation for extracolonic aggressive phenotypes in patients with familial adenomatous polyposis. Cancer Sci 2023; 114:4596-4606. [PMID: 37798255 PMCID: PMC10728006 DOI: 10.1111/cas.15945] [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: 05/04/2023] [Revised: 08/03/2023] [Accepted: 08/18/2023] [Indexed: 10/07/2023] Open
Abstract
Familial adenomatous polyposis (FAP) patients develop various life-threatening extracolonic comorbidities that appear individually or within a family. This diversity can be explained by the localization of the adenomatous polyposis coli (APC) variant, but few reports provide definitive findings about genotype-phenotype correlations. Therefore, we investigated FAP patients and the association between the severe phenotypes and APC variants. Of 247 FAP patients, 126 patients from 85 families identified to have APC germline variant sites were extracted. These sites were divided into six groups (Regions A to F), and the frequency of severe comorbidities was compared among the patient phenotypes. Of the 126 patients, the proportions of patients with desmoid tumor stage ≥III, number of FGPs ≥1000, multiple gastric neoplasms, gastric neoplasm with high-grade dysplasia, and Spigelman stage ≥III were 3%, 16%, 21%, 12%, and 41%, respectively, while the corresponding rates were 30%, 50%, 70%, 50%, and 80% in patients with Region E (codons 1398-1580) variants. These latter rates were significantly higher than those for patients with variants in other regions. Moreover, the proportion of patients with all three indicators (desmoid tumor stage ≥III, number of FGPs ≥1000, and Spigelman stage ≥III) was 20% for those with variants in Region E and 0% for those with variants in other regions. Variants in Region E indicate aggressive phenotypes, and more intensive management is required.
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Affiliation(s)
- Yusaku Shimamoto
- Department of Gastrointestinal OncologyOsaka International Cancer InstituteOsakaJapan
| | - Yoji Takeuchi
- Department of Gastrointestinal OncologyOsaka International Cancer InstituteOsakaJapan
- Department of Genetic Oncology, Division of Hereditary TumorsOsaka International Cancer InstituteOsakaJapan
- Department of Gastroenterology and HepatologyGunma University Graduate School of MedicineMaebashiJapan
| | | | - Shin‐ichi Nakatsuka
- Department of Diagnostic Pathology and CytologyOsaka International Cancer InstituteOsakaJapan
| | | | - Yasumasa Ezoe
- Medical Ethics and Medical Genetics, School of Public HealthKyoto UniversityKyotoJapan
| | - Takeshi Nakajima
- Medical Ethics and Medical Genetics, School of Public HealthKyoto UniversityKyotoJapan
| | - Kumiko Tanaka
- Department of Gastroenterology and Oncology, Institute of Biomedical SciencesTokushima University Graduate SchoolTokushimaJapan
| | - Ryu Ishihara
- Department of Gastrointestinal OncologyOsaka International Cancer InstituteOsakaJapan
| | - Tetsuji Takayama
- Department of Gastroenterology and Oncology, Institute of Biomedical SciencesTokushima University Graduate SchoolTokushimaJapan
| | - Teruhiko Yoshida
- Department of Genetic Medicine and ServicesNational Cancer Center HospitalTokyoJapan
| | - Kokichi Sugano
- Department of Genetic Medicine, Sasaki FoundationKyoundo HospitalTokyoJapan
| | - Michihiro Mutoh
- Department of Molecular‐Targeting Prevention, Graduate School of Medical ScienceKyoto Prefectural University of MedicineKyotoJapan
| | - Hideki Ishikawa
- Ishikawa Gastroenterology ClinicOsakaJapan
- Department of Molecular‐Targeting Prevention, Graduate School of Medical ScienceKyoto Prefectural University of MedicineKyotoJapan
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15
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D'Eusebio C, Merlo FD, Ossola M, Bioletto F, Ippolito M, Locatelli M, De Francesco A, Anrò M, Romagnoli R, Strignano P, Bo S, Aimasso U. Mortality and parenteral nutrition weaning in patients with chronic intestinal failure on home parenteral nutrition: A 30-year retrospective cohort study. Nutrition 2023; 107:111915. [PMID: 36566610 DOI: 10.1016/j.nut.2022.111915] [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: 08/18/2022] [Revised: 11/06/2022] [Accepted: 11/13/2022] [Indexed: 11/18/2022]
Abstract
BACKGROUND Home parenteral nutrition (HPN) is the standard treatment for patients with chronic intestinal failure (CIF). Mortality and weaning rates of these patients differ widely among cohorts; however, these outcomes were often considered independent-rather than competing-events, leading to an upward bias of the retrieved estimates. OBJECTIVES The aim of this retrospective cohort study was to evaluate, evaluating through a competing risk analysis, the rates and predictors of mortality and weaning in CIF patients from an Italian referral center. METHODS All adult patients with CIF receiving > 3 mo HPN from 1985 until 2016 were enrolled. Clinical information was collected from the database of the Intestinal Failure Unit of Torino, Italy. Patients were stratified according to the presence or not of short bowel syndrome (SBS). RESULTS The cumulative incidences of death and weaning were 27.3% and 32.3% and 39.0% and 33.7% at 5 and 10 y from HPN initiation, respectively. At multivariable competing risk analyses, mortality was predicted by age (sub-distribution hazard ratio [SHR] = 1.65 per 10-y increase; 95% CI, 1.35-2.01), type 3 SBS (SHR = 0.38; 0.15-0.94), small bowel length ≥ 100 cm (SHR = 0.42; 0.22-0.83), and reconstructive surgery (SHR = 0.11; 0.02-0.64) in SBS patients, and by age (SHR = 1.38 per 10-y increase; 1.16-1.64) and presence of stoma (SHR = 0.30; 0.12-0.78) in non-SBS patients. In the same model, weaning was predicted by type 3 SBS (SHR = 6.86; 3.10-15.16), small bowel length ≥ 100 cm (SHR = 3.54; 1.99-6.30), and reconstructive surgery (SHR = 2.86; 1.44-5.71) in SBS patients, and by age (SHR = 0.79 per 10-y increase; 0.66-0.94) and presence of stoma (SHR = 2.64; 1.38-5.07) in non-SBS patients. CONCLUSIONS Surgical procedures strongly affected mortality and weaning risk in CIF patients.
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Affiliation(s)
- Chiara D'Eusebio
- Department of Medical Science, University of Torino, 10124 Torino, Italy
| | - Fabio Dario Merlo
- Unit of Dietetic and Clinical Nutrition, Città della Salute e della Scienza Hospital, 10126 Torino, Italy.
| | - Marta Ossola
- Unit of Dietetic and Clinical Nutrition, Città della Salute e della Scienza Hospital, 10126 Torino, Italy
| | - Fabio Bioletto
- Department of Medical Science, University of Torino, 10124 Torino, Italy
| | - Mirko Ippolito
- Department of Medical Science, University of Torino, 10124 Torino, Italy
| | - Monica Locatelli
- Food Chemistry, Biotechnology and Nutrition Unit, University of Piemonte Orientale, 28100 Novara, Italy
| | - Antonella De Francesco
- Unit of Dietetic and Clinical Nutrition, Città della Salute e della Scienza Hospital, 10126 Torino, Italy
| | - Marta Anrò
- Unit of Dietetic and Clinical Nutrition, Città della Salute e della Scienza Hospital, 10126 Torino, Italy
| | - Renato Romagnoli
- General Surgery 2U, Liver Transplantation Unit, Città della Salute e della Scienza Hospital, 10126 Torino, Italy
| | - Paolo Strignano
- General Surgery 2U, Liver Transplantation Unit, Città della Salute e della Scienza Hospital, 10126 Torino, Italy
| | - Simona Bo
- Unit of Dietetic and Clinical Nutrition, Città della Salute e della Scienza Hospital, 10126 Torino, Italy.
| | - Umberto Aimasso
- Unit of Dietetic and Clinical Nutrition, Città della Salute e della Scienza Hospital, 10126 Torino, Italy
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16
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Campos FG, Martinez CAR, Bustamante-Lopez LA, Mendonça RLDS, Kanno DT. Intra-abdominal desmoid tumors in familial adenomatous polyposis: How much do clinical and surgical variables interfere with their development? Clinics (Sao Paulo) 2023; 78:100144. [PMID: 36476966 PMCID: PMC9723922 DOI: 10.1016/j.clinsp.2022.100144] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 11/03/2022] [Accepted: 11/07/2022] [Indexed: 12/07/2022] Open
Abstract
OBJECTIVE Familial Adenomatous Polyposis is a complex hereditary disease that exposes the carrier to a great risk of Colorectal Cancer (CRC). After prophylactic surgery, intra-abdominal desmoid tumors are known to be one the most important cause of death. Therefore, recognition of increased-risk patients and modification of operative strategy may be crucial. AIM The objective of this study was to estimate the desmoid tumor risk in relation to various surgical and clinical variables. METHODS Patients who had undergone polyposis since 1958 were included in the study. After exclusion criteria were met, those who had developed desmoid tumors were selected to undergo further evaluation. RESULTS The study revealed that the risk of developing desmoid tumors was associated with various factors such as sex ratio, colectomy, and reoperations. On the other hand, the type of surgery, family history, and surgical approach did not affect the risk of developing desmoid tumors. The data collected from 146 polyposis patients revealed that 16% had desmoid polyps. The sex ratio was 7:1, and the median age at colectomy was 28.6 years. Family history, multiple abdominal operations, and reoperations were some of the characteristics that were common in desmoid patients. CONCLUSION Recognition of clinical (female sex) and surgical (timing of surgery and previous reoperations) data as unfavorable variables associated with greater risk may be useful during the decision-making process.
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Affiliation(s)
- Fábio Guilherme Campos
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil
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Strong Hereditary Predispositions to Colorectal Cancer. Genes (Basel) 2022; 13:genes13122326. [PMID: 36553592 PMCID: PMC9777620 DOI: 10.3390/genes13122326] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 12/01/2022] [Accepted: 12/05/2022] [Indexed: 12/14/2022] Open
Abstract
Cancer is one of the most common causes of death worldwide. A strong predisposition to cancer is generally only observed in colorectal cancer (5% of cases) and breast cancer (2% of cases). Colorectal cancer is the most common cancer with a strong genetic predisposition, but it includes dozens of various syndromes. This group includes familial adenomatous polyposis, attenuated familial adenomatous polyposis, MUTYH-associated polyposis, NTHL1-associated polyposis, Peutz-Jeghers syndrome, juvenile polyposis syndrome, Cowden syndrome, Lynch syndrome, and Muir-Torre syndrome. The common symptom of all these diseases is a very high risk of colorectal cancer, but depending on the condition, their course is different in terms of age and range of cancer occurrence. The rate of cancer development is determined by its conditioning genes, too. Hereditary predispositions to cancer of the intestine are a group of symptoms of heterogeneous diseases, and their proper diagnosis is crucial for the appropriate management of patients and their successful treatment. Mutations of specific genes cause strong colorectal cancer predispositions. Identifying mutations of predisposing genes will support proper diagnosis and application of appropriate screening programs to avoid malignant neoplasm.
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Gitto L, Vandermeer T, Lubin DJ, Zaccarini DJ. Mesenteric desmoid fibromatosis entrapping metastatic urothelial carcinoma: a unique collision tumor or fibromatosis-like variant? SURGICAL AND EXPERIMENTAL PATHOLOGY 2022. [DOI: 10.1186/s42047-022-00114-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
AbstractA collision tumor is a neoplastic lesion comprised of two or more distinct cell populations with distinct borders. Desmoid fibromatosis (DF) is a rare musculoaponeurotic tissue tumor that grows deep in the connective tissue and shows locally aggressive behavior. Only two cases of collision tumors with desmoid fibromatosis are reported in the English literature, albeit papillary thyroid carcinoma with desmoid fibromatosis-like stroma is regarded as a variant rather than a collision tumor. We present a unique case of collision tumor with desmoid fibromatosis surrounding intra-abdominal metastasis from urothelial carcinoma. A 65-year-old white male with history of bladder and left renal pelvis high-grade papillary urothelial carcinoma status post-nephrectomy was found to have a small bowel obstruction due to a soft tissue mass. Histology of the mass showed multiple matted lymph nodes with metastatic urothelial carcinoma admixed with a proliferation of spindle cells positive for nuclear beta-catenin, consistent with desmoid fibromatosis. While the prior surgical site likely acted as a nidus for development of desmoid fibromatosis, we also hypothesize that a dysregulation of beta-catenin signaling pathways within the cancer cells might have attributed to the spindle cell proliferation in the stroma surrounding the tumor. Our case emphasized the importance of clinical suspicion of desmoid fibromatosis in patients with metastatic cancer, requiring a prompt diagnosis and treatment to decrease the risk of complications and local recurrence.
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Albino L, Guo Y, Bacani J, Mather C, Nilsson JE, Dieleman LA. Case report: Desmoid fibromatosis diagnosed in a 27-year-old male after being mistaken for a gastrointestinal stromal tumour. Front Med (Lausanne) 2022; 9:998473. [PMID: 36438058 PMCID: PMC9684322 DOI: 10.3389/fmed.2022.998473] [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: 07/20/2022] [Accepted: 10/25/2022] [Indexed: 11/04/2023] Open
Abstract
Despite being distinct lesions, gastrointestinal stromal tumours (GISTs) and desmoid fibromatosis may appear similar on imaging when they involve the stomach wall or bowel. As a result, they may be confused with one another when initially diagnosed. This report aims to present a case where a desmoid tumour was mistaken for a gastric GIST in a 27-year-old gentleman despite extensive investigation prior to exploratory laparotomy, and why differentiation through pathology, with a focus on the immunohistochemistry profile, is key for proper prognostication and appropriate management, including timely investigation for associated diseases such as Familial Adenomatous Polyposis in patients with desmoid tumours.
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Affiliation(s)
- Larissa Albino
- Department of Medicine, University of Alberta, Edmonton, AB, Canada
| | - Yimeng Guo
- Division of Gastroenterology, University of Alberta, Edmonton, AB, Canada
| | - Julinor Bacani
- Division of Anatomical Pathology, Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada
| | - Cheryl Mather
- Division of Anatomical Pathology, Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada
| | - Jan-Erick Nilsson
- Division of Gastroenterology, University of Alberta, Edmonton, AB, Canada
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Qureshi A, Andrade R, Saavedra J, Xiao P, Asarian A. Incidental discovery of desmoid-type fibromatosis encapsulating granular cell tumor in a neck mass. J Surg Case Rep 2022; 2022:rjac439. [PMID: 36226135 PMCID: PMC9541280 DOI: 10.1093/jscr/rjac439] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Accepted: 09/03/2022] [Indexed: 11/07/2022] Open
Abstract
Multiple primary cancers are defined as primary malignant tumors of different histological origins in one person. Desmoid-type fibromatosis (DF) is an extremely rare, locally aggressive, connective tissue malignancy that can be rooted anywhere in the body with the most common sites being thoracic wall and extremities. In contrast, granular cell tumors are rare neoplasms derived from Schwann cells commonly found in the oral cavity, skin and gastrointestinal tract. Moreover, diagnosing a patient with two primary cell tumors has become more common and the challenge of treatment becomes the focus in clinical situations. However, findings of a mass containing DF encapsulated by a granular cell tumor. Currently, there are no established guidelines for this rare condition. This case report serves to raise awareness of these two uncommon primary tumors emerging in an idiosyncratic nature.
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Affiliation(s)
- Abid Qureshi
- Correspondence address. Department of Surgery, The Brooklyn Hospital Center, Brooklyn, NY 11201, USA. Tel: +1 917-519-1749; E-mail:
| | - Roberto Andrade
- Department of Surgery, The Brooklyn Hospital Center, Brooklyn, NY, USA
| | - Jonathan Saavedra
- Department of Surgery, The Brooklyn Hospital Center, Brooklyn, NY, USA
| | - Philip Xiao
- Department of Pathology, The Brooklyn Hospital Center, Icahn School of Medicine at Mount Sinai, Brooklyn, NY, USA
| | - Armand Asarian
- Department of Surgery, The Brooklyn Hospital Center, Icahn School of Medicine at Mount Sinai, Brooklyn, NY, USA
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21
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Benech N, Bonvalot S, Lopez-Trabada D, Orbach D, Bouché O, Saurin JC. Author's reply: "A lesion suspected of being a desmoid tumor in the context of familial adenomatous polyposis should be biopsied". Dig Liver Dis 2022; 54:1448. [PMID: 35840485 DOI: 10.1016/j.dld.2022.06.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2022] [Accepted: 06/27/2022] [Indexed: 12/29/2022]
Affiliation(s)
- Nicolas Benech
- Service d'Hépato-Gastroentérologie, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, 69003, France.
| | | | - Daniel Lopez-Trabada
- Service d'Oncologie Médicale, Hôpital Saint-Antoine, 184, rue du Faubourg Saint-Antoine, Paris, 75012, France
| | - Daniel Orbach
- SIREDO Oncology Center (Care, Innovation and Research for Children, Adolescents and Young Adults with Cancer), Institut Curie, Paris, France
| | - Olivier Bouché
- Department of Digestive Oncology, CHU Reims, Reims, France
| | - Jean-Christophe Saurin
- Service d'Hépato-Gastroentérologie, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, 69003, France
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22
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Benech N, Bonvalot S, Dufresne A, Gangi A, Le Péchoux C, Lopez-Trabada-Ataz D, Meurgey A, Nicolas N, Orbach D, Penel N, Salas S, Saurin JC, Walter T, Lecomte T, Bouché O. Desmoid tumors located in the abdomen or associated with adenomatous polyposis: French intergroup clinical practice guidelines for diagnosis, treatment, and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, ACHBT, SFR). Dig Liver Dis 2022; 54:737-746. [PMID: 35508462 DOI: 10.1016/j.dld.2022.03.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 03/07/2022] [Accepted: 03/10/2022] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Desmoid tumor (DT) of the abdomen is a challenging and rare disease. The level of evidence available to document their treatment is relatively low, however, recent publications of prospective studies have allowed to precise their management. METHODS This document is a summary of the French intergroup guidelines realized by all French medical and surgical societies involved in the management of DT located in the abdomen or associated with adenomatous polyposis. Recommendations are graded in four categories (A, B, C and D), according to the level of evidence found in the literature until January 2021. RESULTS When the diagnosis of DT is suspected a percutaneous biopsy should be performed when possible. A molecular analysis looking for pathogenic mutations of the CTNNB1 and APC genes should be systematically performed. When a somatic pathogenic variant of the APC gene is present, an intestinal polyposis should be searched. Due to a high rate of spontaneous regression, non-complicated DT should first benefit from an active surveillance with MRI within 2 months after diagnosis to assess the dynamic of tumor growth. The treatment decision must be discussed in an expert center, favoring the less toxic treatments which can include broad spectrum tyrosine kinase inhibitor or conventional chemotherapy (methotrexate-vinblastine). Surgery, outside the context of emergency, should only be considered for favorable location in an expert center. CONCLUSION French guidelines for DT management were elaborated to help offering the best personalized therapeutic strategy in daily clinical practice as the DT therapeutic landscape is complexifying. Each individual case must be discussed within a multidisciplinary expert team.
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Affiliation(s)
- Nicolas Benech
- Service d'Hépato-Gastroentérologie, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon 69003, France.
| | | | - Armelle Dufresne
- Département d'Oncologie Médicale, Léon Bérard Cancer Center, 28, rue Laennec, Lyon 69373 CEDEX 08, France
| | - Afshin Gangi
- Interventional Radiology, University Hospitals of Strasbourg, Strasbourg University, Strasbourg 67200, France
| | - Cécile Le Péchoux
- Département d'Oncologie Radiothérapie, Gustave- Roussy Cancer Campus, 114, rue Edouard- Vaillant, Villejuif 94800, France
| | - Daniel Lopez-Trabada-Ataz
- Service d'Oncologie Médicale, Hôpital Saint-Antoine, 184, rue du Faubourg Saint-Antoine, Paris 75012, France
| | - Alexandra Meurgey
- Department of Biopathology, Léon Bérard Cancer Center, 28, rue Laennec, Lyon 69373 CEDEX 08, France
| | - Nayla Nicolas
- Department of Radiology, Institut Curie, Paris, France
| | - Daniel Orbach
- SIREDO Oncology Center (Care, Innovation and Research for Children, Adolescents and Young Adults with Cancer), Institut Curie, Paris, France
| | - Nicolas Penel
- Centre Oscar Lambret and Lille University, Lille, France
| | - Sébastien Salas
- Oncology Unit, AP-HM, Aix-Marseille University, Marseille, France
| | - Jean-Christophe Saurin
- Service d'Hépato-Gastroentérologie, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon 69003, France
| | - Thomas Walter
- Service d'Oncologie, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon 69003, France
| | - Thierry Lecomte
- Department of Hepatogastroenterology and Digestive Oncology, CHU de Tours, Tours, France
| | - Olivier Bouché
- Department of Digestive Oncology, CHU Reims, Reims, France
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McLean TD, Duchi S, Di Bella C. Molecular Pathogenesis of Sporadic Desmoid Tumours and Its Implications for Novel Therapies: A Systematised Narrative Review. Target Oncol 2022; 17:223-252. [PMID: 35446005 PMCID: PMC9217905 DOI: 10.1007/s11523-022-00876-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/15/2022] [Indexed: 12/22/2022]
Abstract
Sporadic desmoid-type fibromatosis is a rare, fibroblastic soft-tissue neoplasm with local aggressiveness but no metastatic potential. Aberrant Wnt/β-catenin signalling has been extensively linked to desmoid pathogenesis, although little is known about other molecular drivers and no established treatment approach exists. We aimed to summarise the current literature regarding the molecular pathogenesis of sporadic desmoid-type fibromatosis and to discuss the effects of both current and emerging novel therapies targeting these mechanisms. A literature search was conducted of MEDLINE® ALL and EMBASE databases for published studies (2000–August 2021) using keywords related to ‘fibromatosis aggressive’, ‘immunohistochemistry’, ‘polymerase chain reaction’ and ‘mutation’. Articles were included if they examined the role of proteins in sporadic or extra-abdominal human desmoid-type fibromatosis pathogenesis. Searching identified 1684 articles. Following duplicate removal and eligibility screening, 36 were identified. After a full-text screen, 22 were included in the final review. At least 47% of desmoid-type fibromatosis cases displayed aberrant β-catenin immunoreactivity amongst ten studies. Cyclin D1 overexpression occurred in at least 40% of cases across five studies. Six studies reported oestrogen receptor-β expression with a range of 7.4–90%. Three studies implicated matrix metalloproteinases, with one study demonstrating vascular endothelial growth factor overexpression. One study explored the positive relationship between cyclooxygenase-2 and platelet-derived growth factor receptor-β. Aberrant Wnt/β-catenin signalling is a well-established pathogenic driver that may be targeted via downstream modulation. Growth factor signalling is best appreciated through the clinical trial effects of multi-targeted tyrosine kinase inhibitors, whilst oestrogen receptor expression data may only offer a superficial insight into oestrogen signalling. Finally, the tumour microenvironment presents multiple potential novel therapeutic targets. Sporadic desmoid tumours are rare soft-tissue neoplasms that arise from connective tissues in the chest wall, head, neck and limbs. Whilst lacking metastatic potential, uncertainty surrounding their locally aggressive growth and unpredictable recurrence complicates treatment approaches. At the molecular level, alterations in the Wnt/β-catenin signalling pathway, a fundamental coordinator of cell growth and development, have been strongly linked to desmoid tumour development. Beyond this, however, little is known about other molecular drivers. In the case of progressive or life-threatening disease, complex treatment decisions are made regarding the use of surgery, radiotherapy or systemic treatment modalities. Of the targeted systemic therapies, a lack of comparative clinical studies further complicates medical treatment decision making as no definitive treatment approach exists. Therefore, this review aimed to summarise the literature regarding the molecular drivers of desmoid tumour pathogenesis and to discuss the current and emerging novel therapies targeting such mechanisms. Utilising findings from human desmoid tissue samples, we present the rationale for targeting downstream mediators of the central Wnt/β-catenin pathway and outline potential treatment targets in the tumour microenvironment. We also highlight the knowledge gained from clinical drug trials targeting desmoid growth factor signalling and present the potentially superficial insight provided by oestrogen receptor expression profiles on the role of oestrogen signalling in desmoid pathogenesis. In doing so, this work may assist in the eventual development of an evidence-based treatment approach for sporadic desmoid tumours.
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Affiliation(s)
- Thomas D McLean
- Melbourne Medical School, The University of Melbourne, Melbourne, VIC, Australia.
| | - Serena Duchi
- Department of Surgery, The University of Melbourne, Melbourne, VIC, Australia.,Biofab 3D, Aikenhead Centre for Medical Discovery, Melbourne, VIC, Australia
| | - Claudia Di Bella
- Department of Surgery, The University of Melbourne, Melbourne, VIC, Australia.,Department of Orthopaedics, St Vincent's Hospital Melbourne, VIC, Australia
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24
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Zhou MY, Bui NQ, Charville GW, Ghanouni P, Ganjoo KN. Current management and recent progress in desmoid tumors. Cancer Treat Res Commun 2022; 31:100562. [PMID: 35460976 DOI: 10.1016/j.ctarc.2022.100562] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Revised: 03/31/2022] [Accepted: 04/04/2022] [Indexed: 06/14/2023]
Abstract
Desmoid tumors are rare soft tissue tumors that can have aggressive infiltrative growth and relapse locally. Desmoid tumors can impact functionality and cause treatment-related morbidity and mortality. Here, the authors review current management strategies and avenues for further investigation. As part of the evolution of therapy away from primary surgical approaches to less invasive options, image-guided ablation has been accepted as less morbid and include cryoablation and high-intensity focused ultrasound. Systemic therapy options currently include hormonal agents, nonsteroidal anti-inflammatory drugs, tyrosine kinase inhibitors, and anthracycline-based regimens. Hormonal agents and nonsteroidal anti-inflammatory drugs have benign side effect profiles but generally limited efficacy. Anthracycline-based therapies are limited by the risk of secondary malignancies and cardiomyopathy. Tyrosine kinase inhibitors are well studied, and sorafenib is now one of the most utilized therapies, though limited by its side effect profile. Nirogacestat (PF-0308401) is an investigational small molecule gamma-secretase (GS) inhibitor that has demonstrated efficacy in phase 1 and II trials. A phase III trial investigating patients with desmoid tumors or aggressive fibromatosis is estimated to be completed December 2021 (NCT03785964). In addition to nirogacestat, the gamma-secretase inhibitor AL102 is being investigated for the treatment of patients with progressing desmoid tumors in the phase II/III RINGSIDE trial. Finally, the beta-catenin inhibitor Tegavivint (BC2059) is being investigated in a phase 1 open-label trial in patients with a proven primary or recurrent desmoid tumor that is unresectable and symptomatic or progressive.
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Affiliation(s)
- Maggie Y Zhou
- Department of Medicine, Stanford University School of Medicine, Stanford, CA
| | - Nam Q Bui
- Department of Medicine (Oncology), Stanford University School of Medicine, 875 Blake Wilbur Drive, Stanford, CA, 94305, USA
| | - Gregory W Charville
- Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA
| | - Pejman Ghanouni
- Department of Radiology, Stanford University School of Medicine, Stanford, CA
| | - Kristen N Ganjoo
- Department of Medicine (Oncology), Stanford University School of Medicine, 875 Blake Wilbur Drive, Stanford, CA, 94305, USA.
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Balaguer F, Stoffel EM, Burke CA, Dekker E, Samadder NJ, Van Cutsem E, Lynch PM, Wise PE, Hüneburg R, Lim RM, Boytim ML, Du W, Bruckheimer EM, Cohen A, Church J. Combination of Sulindac and Eflornithine Delays the Need for Lower Gastrointestinal Surgery in Patients With Familial Adenomatous Polyposis: Post Hoc Analysis of a Randomized Clinical Trial. Dis Colon Rectum 2022; 65:536-545. [PMID: 34261858 DOI: 10.1097/dcr.0000000000002095] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND Colectomy and proctocolectomy are the initial standard of care for patients with familial adenomatous polyposis. Pharmacotherapy to prevent the progression of polyposis and surgeries in the lower GI tract would be beneficial to patients with this disease. OBJECTIVE This analysis aimed to evaluate the impact of eflornithine-sulindac combination versus monotherapy in delaying time to disease progression in the lower GI tract of patients with familial adenomatous polyposis. DESIGN This is a post hoc analysis of a randomized phase 3 trial. SETTING This study was conducted in 21 hospitals in 7 countries treating patients with familial adenomatous polyposis. PATIENTS Adults with familial adenomatous polyposis were randomly assigned 1:1:1 into 3 arms. INTERVENTIONS Patients received either eflornithine (750 mg), sulindac (150 mg), or both once daily for up to 48 months. MAIN OUTCOME MEASURES Efficacy was evaluated as the time from randomization to predefined primary disease progression end points. RESULTS A total of 158 patients were included in the study. Disease progression was observed in 2 of 54 (3.7%), 9 of 53 (17.0%), and 10 of 51 (19.6%) patients with at least partial lower GI tract in the combination, sulindac, and eflornithine arms, corresponding to risk reductions of 80% (p = 0.02) and 83% (p = 0.01) between combination and sulindac or eflornithine. When endoscopic excision of adenomas ≥10 mm in size was censored, the need for major surgery was observed in 0 of 54, 7 of 53 (13.2%), and 8 of 51 (15.7%) patients in the combination, sulindac, and eflornithine arms, corresponding to risk reductions approaching 100% between combination and sulindac (p = 0.005) or combination and eflornithine (p = 0.003). LIMITATIONS This was a post hoc analysis, the sample size was small, and there were fewer than expected events. CONCLUSIONS Eflornithine-sulindac combination therapy was superior to either drug alone in delaying or preventing the need for lower GI tract surgery in patients with familial adenomatous polyposis. See Video Abstract at http://links.lww.com/DCR/B658. REGISTRATION ClinicalTrials.gov, NCT01483144; EU Clinical Trials Register, EudraCT 2012-000427-41. LA COMBINACIN DE SULINDAC Y EFLORNITINA RETRASA LA NECESIDAD DE CIRUGA DEL TUBO DIGESTIVO BAJO EN PACIENTES CON PAF ANLISIS POSTHOC DE UN ENSAYO CLNICO ALEATORIZADO ANTECEDENTES:La colectomía y la proctocolectomía son el estándar inicial de atención para los pacientes con poliposis adenomatosa familiar. La farmacoterapia para prevenir la progresión de la poliposis y las cirugías en el tracto gastrointestinal inferior sería beneficiosa para los pacientes con esta enfermedad.OBJETIVO:Este análisis tuvo como objetivo evaluar el impacto de la combinación de eflornitina-sulindac versus la monoterapia en el retraso del tiempo hasta la progresión de la enfermedad en el tracto gastrointestinal inferior de pacientes con poliposis adenomatosa familiar.DISEÑO:Este es un análisis posthoc de un ensayo de fase 3 aleatorizado.ENTORNO CLINICO:Veintiún hospitales en 7 países que tratan a pacientes con poliposis adenomatosa familiar.PACIENTES:Adultos con poliposis adenomatosa familiar fueron aleatorizados 1: 1: 1 en 3 brazos.INTERVENCIONES:Los pacientes recibieron eflornitina (750 mg), sulindac (150 mg) o ambos una vez al día durante un máximo de 48 meses.PRINCIPALES MEDIDAS DE VALORACION:La eficacia se evaluó como el tiempo desde la aleatorización hasta los criterios de valoración primarios predefinidos de progresión de la enfermedad.RESULTADOS:Los resultados se informan para la población de estudio excluyendo a los pacientes que se habían sometido a ileostomías permanentes (n = 158). Se observó progresión de la enfermedad en 2/54 (3,7%), 9/53 (17,0%) y 10/51 (19,6%) pacientes con al menos tracto gastrointestinal inferior parcial en los brazos de combinación, sulindac y eflornitina, respectivamente, correspondientes al riesgo de reducciones del 80% (p = 0,02) y del 83% (p = 0,01) entre la combinación y el sulindaco o la eflornitina, respectivamente. Cuando se censuró la escisión endoscópica de adenomas ≥10 mm de tamaño, se observó la necesidad de cirugía mayor en 0/54, 7/53 (13,2%) y 8/51 (15,7%) pacientes en la combinación, sulindac y eflornitina, respectivamente, correspondientes a reducciones de riesgo cercanas al 100% entre combinación y sulindac (p = 0,005) o combinación y eflornitina (p = 0,003).LIMITACIONES:Este fue un análisis posthoc, el tamaño de la muestra fue pequeño y hubo menos eventos de los esperados.CONCLUSIONES:La terapia de combinación de eflornitina-sulindac fue superior a cualquier fármaco solo para retrasar o prevenir la necesidad de cirugía del tracto gastrointestinal inferior en pacientes con poliposis adenomatosa familiar. Consulte Video Resumen en http://links.lww.com/DCR/B658.
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Affiliation(s)
- Francesc Balaguer
- Department of Gastroenterology, Hospital Clinic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain
| | - Elena M Stoffel
- Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan
| | - Carol Ann Burke
- Department of Gastroenterology, Hepatology & Nutrition, Cleveland Clinic, Cleveland, Ohio
| | - Evelien Dekker
- Department of Gastroenterology & Hepatology, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam, The Netherlands
| | - N Jewel Samadder
- Division of Gastroenterology & Hepatology, Mayo Clinic, Phoenix, Arizona
| | | | - Patrick M Lynch
- Department of Gastroenterology, Hepatology and Nutrition, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Paul E Wise
- Department of Surgery, Washington University School of Medicine, St. Louis, Missouri
| | - Robert Hüneburg
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
- National Center for Hereditary Tumor Syndromes, Bonn, Germany
| | - Ramona M Lim
- Division of Population Sciences, Dana-Farber Cancer Institute, Boston, Massachusetts
- Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Boston, Massachusetts
- Harvard Medical School, Boston, Massachusetts
| | | | - Wei Du
- Clinical Statistics Consulting, Blue Bell, Pennsylvania
| | | | - Alfred Cohen
- Cancer Prevention Pharmaceuticals, Inc, Tucson, Arizona
| | - James Church
- Department of Gastroenterology, Hepatology & Nutrition, Cleveland Clinic, Cleveland, Ohio
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Johns MS, Merritt WT, Rhodes L, Ford CN, Thompson M, Lee WM, Sheldon Y, Petrelli NJ, Tiesi GJ. A cost analysis of sorafenib for desmoid tumors. J Oncol Pharm Pract 2022; 29:663-668. [PMID: 35112974 DOI: 10.1177/10781552221077927] [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] [Indexed: 11/16/2022]
Abstract
INTRODUCTION A recent randomized trial demonstrated that sorafenib improved progression free survival (PFS) in patients with desmoid tumors despite many patients experiencing stable disease or spontaneous regression without treatment. Utilizing these trial data, we performed a cost analysis of sorafenib efficacy through two years of treatment. METHODS Current Medicare Part D rates for sorafenib were utilized (dose 400 mg/day, cost $309/day). Annual costs per progression and objective response were calculated. Radiologic progression and response were defined using RECIST criteria. Patients with disease progression were separately analyzed in two groups: both clinical and radiologic (CAR), and radiologic alone. RESULTS 84 previously randomized patients were analyzed (placebo: 35, sorafenib: 49). At one year, sorafenib was associated with a 43% absolute risk reduction (ARR) of CAR progression and number-needed-to-treat (NNT) of 2.3 patients/year, costing $259,406. At two years, ARR was 48% and NNT of 2.1 patients/year, costing $473,697. When evaluating only patients with RECIST defined radiologic progression, sorafenib patients experienced ARR of 13.9% with NNT 7.2 and estimated costs of $812,052 at one year. Two-year ARR was 17.5% with NNT 5.7 and estimated costs $1,285,052. Sorafenib patients experienced improved RECIST partial response rates at 1 and 2 years of 14.7% and 14.3%, with NNT 6.8 and 6.9, and costs of $766,938 and $1,556,433; respectively. CONCLUSION For the treatment of desmoid tumors, Sorafenib led to improved PFS, but at a significant cost per patient. Favorable RECIST outcomes were less likely and costlier. Patients should be informed of possible benefits of treatment versus potential financial burden.
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Affiliation(s)
- Michael S Johns
- Division of Surgical Oncology, Helen F. Graham Cancer Center and Research Institute, 5973Christiana Care, Newark, DE, USA
| | - William T Merritt
- Division of Surgical Oncology, Helen F. Graham Cancer Center and Research Institute, 5973Christiana Care, Newark, DE, USA
| | - Lori Rhodes
- Department of General Surgery, 12315Temple University Hospital, Philadelphia, PA, USA
| | - Candice N Ford
- Division of Surgical Oncology, Helen F. Graham Cancer Center and Research Institute, 5973Christiana Care, Newark, DE, USA
| | | | - William M Lee
- Division of Surgical Oncology, Helen F. Graham Cancer Center and Research Institute, 5973Christiana Care, Newark, DE, USA
| | - Yarrow Sheldon
- Division of Surgical Oncology, Helen F. Graham Cancer Center and Research Institute, 5973Christiana Care, Newark, DE, USA
| | - Nicholas J Petrelli
- Division of Surgical Oncology, Helen F. Graham Cancer Center and Research Institute, 5973Christiana Care, Newark, DE, USA
| | - Gregory J Tiesi
- Division of Surgical Oncology, Helen F. Graham Cancer Center and Research Institute, 5973Christiana Care, Newark, DE, USA
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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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Recurrent CTNNB1 mutations in craniofacial osteomas. Mod Pathol 2022; 35:489-494. [PMID: 34725446 PMCID: PMC8964415 DOI: 10.1038/s41379-021-00956-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2021] [Revised: 10/09/2021] [Accepted: 10/11/2021] [Indexed: 11/08/2022]
Abstract
Osteoma is a benign bone forming tumor predominantly arising on the surface of craniofacial bones. While the vast majority of osteomas develops sporadically, a small subset of cases is associated with Gardner syndrome, a phenotypic variant of familial adenomatous polyposis caused by mutations in the APC gene resulting in aberrant activation of WNT/β-catenin signaling. In a sequencing analysis on a cohort of sporadic, non-syndromal osteomas, we identified hotspot mutations in the CTNNB1 gene (encoding β-catenin) in 22 of 36 cases (61.1%), harbouring allelic frequencies ranging from 0.04 to 0.53, with the known S45P variant representing the most frequent alteration. Based on NanoString multiplex expression profiling performed in a subset of cases, CTNNB1-mutated osteomas segregated in a defined "WNT-cluster", substantiating functionality of CTNNB1 mutations which are associated with β-catenin stabilization. Our findings for the first time convincingly show that osteomas represent genetically-driven neoplasms and provide evidence that aberrant WNT/β-catenin signaling plays a fundamental role in their pathogenesis, in line with the well-known function of WNT/β-catenin in osteogenesis. Our study contributes to a better understanding of the molecular pathogenesis underlying osteoma development and establishes a helpful diagnostic molecular marker for morphologically challenging cases.
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Mundada A, Tote D, Zade A. Desmoid tumor of Meckel's diverticulum presenting as intestinal obstruction: A rare case report with literature review. J Cancer Res Ther 2022; 18:880-884. [DOI: 10.4103/jcrt.jcrt_582_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/10/2023]
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Mabrouk MY, Bouzayan L, Malki S, Jabi R, Bennani A, Bouziane M. Desmoid tumor of the anterolateral abdominal wall: A rare case report. Ann Med Surg (Lond) 2021; 70:102804. [PMID: 34691412 PMCID: PMC8519763 DOI: 10.1016/j.amsu.2021.102804] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Revised: 08/31/2021] [Accepted: 09/03/2021] [Indexed: 11/22/2022] Open
Abstract
INTRODUCTION AND IMPORTANCE Desmoid tumors of the abdominal wall are rare fibroblastic proliferative tissue, included in the group of soft tissue tumors, not metastasizing but locally aggressive as an infiltrating tumor and a source of recurrence. CASE PRESENTATION This case report describes a rare case of desmoid tumor of the anterolateral abdominal wall presented with a large mass of the left flank and iliac fossa. The diagnostic was suspected radiologically following an abdominopelvic computed tomography (CT) and magnetic resonance imaging (MRI). An exploratory laparotomy found a large mass infiltrating the left rectus abdominis muscle, a part of the flat left abdominal muscles, and the left iliac crest. The patient underwent a total resection of the mass involving the left rectus muscle with autoplasty by a pedicled flap of the left LATA fascia with the placement of a bifacial mesh.Histologic analysis of the operatory specimen confirmed the diagnosis of a desmoid tumor of the abdominal wall.The patient has been discharged from the hospital on the fifth day post-operatory with an uneventful recovery; she was in good health after a one-year follow-up. CLINICAL DISCUSSION Desmoid tumors of the abdomen are very rare. Although this tumor is histologically benign, it has the potential of invading vital structures and has a high rate of local recurrence.Histology staining confirms the diagnosis, surgery is the gold standard in the management of this pathology. CONCLUSION We highlight the importance of radical surgical excision to avoid desmoid tumor complications and to minimize the recurrence risk.
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Affiliation(s)
- Mohamed Yassine Mabrouk
- Department of General Surgery, Mohamed VI University Hospital, Oujda, Morocco
- Faculty of Medicine and Pharmacy, Laboratory of Anatomy, Microsurgery and Surgery Experimental and Medical Simulation (LAMCESM), Mohammed 1st University, Oujda, Morocco
| | - Laila Bouzayan
- Department of General Surgery, Mohamed VI University Hospital, Oujda, Morocco
- Faculty of Medicine and Pharmacy, Laboratory of Anatomy, Microsurgery and Surgery Experimental and Medical Simulation (LAMCESM), Mohammed 1st University, Oujda, Morocco
| | - Samia Malki
- Department of Pathology, Mohammed VI University Hospital, Oujda, Morocco
| | - Rachid Jabi
- Department of General Surgery, Mohamed VI University Hospital, Oujda, Morocco
- Faculty of Medicine and Pharmacy, Laboratory of Anatomy, Microsurgery and Surgery Experimental and Medical Simulation (LAMCESM), Mohammed 1st University, Oujda, Morocco
| | - Amal Bennani
- Department of Pathology, Mohammed VI University Hospital, Oujda, Morocco
| | - Mohammed Bouziane
- Department of General Surgery, Mohamed VI University Hospital, Oujda, Morocco
- Faculty of Medicine and Pharmacy, Laboratory of Anatomy, Microsurgery and Surgery Experimental and Medical Simulation (LAMCESM), Mohammed 1st University, Oujda, Morocco
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Kuwabara H, Katayanagi S, Koganezawa I, Nakagawa M, Katsumata K, Tsuchida A, Kawachi S. Sporadic intra-abdominal desmoid tumor with a very unusual onset: two case reports. J Med Case Rep 2021; 15:457. [PMID: 34526110 PMCID: PMC8444561 DOI: 10.1186/s13256-021-03058-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Accepted: 08/11/2021] [Indexed: 01/10/2023] Open
Abstract
Background Intra-abdominal desmoid tumors are rare soft tissue tumors that arise mainly in the mesentery and pelvis. Their etiology may include genetic mutations, estrogen-associated changes after childbirth, and mechanical factors such as a history of abdominal surgery. However, there are cases of intra-abdominal desmoid tumors that develop in the absence of such causes. Since they are rare, diagnosis is often difficult based on clinical findings. We encountered two cases of patients with sporadic intra-abdominal desmoid tumors with a very unusual onset and contrasting features. Case presentation The first patient was a 51-year-old asian man who presented with sudden onset of abdominal pain. He was referred to our department because of a giant tumor detected on abdominal ultrasonography. Imaging revealed a 19-cm tumor with internal tumoral hemorrhage; however, no definitive diagnosis was made. Tumor resection was performed for diagnostic and therapeutic purposes. The second patient was a 41-year-old asian man, and right hydronephrosis was detected on abdominal ultrasonography during a periodic medical checkup. We diagnosed invasion of the primary mesenteric tumor into the right ureter using diagnostic imaging and performed ileocecal resection with partial right ureteral resection for a definitive diagnosis and therapeutic purposes. Although the tumors of both patients had developed from the ileal mesentery, the tumors were substantially different from each other based on their imaging findings, macroscopic morphology, and progression pattern. Meanwhile, they showed similar pathological characteristics. Both consisted of bundles of collagen fibrils of spindle-shaped fibroblasts with low cell atypia. Moreover, they were diagnosed as desmoid tumors using positive immunohistochemical staining for β-catenin. Conclusions Neither patient had susceptibility factors for desmoid tumors, and to our knowledge, there have been very few reports to date of intra-abdominal desmoid tumors that were diagnosed because of acute abdominal pain caused by tumoral hemorrhage or asymptomatic obstructive uropathy. Furthermore, it is clinically interesting that the two patients showed contrasting progression patterns and imaging findings. Intra-abdominal desmoid tumors are rare and may present with various symptoms and findings similar to those observed in our patients. Diagnosis therefore requires experience and knowledge that is not bound by preconceptions.
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Affiliation(s)
- Hiroshi Kuwabara
- Department of Digestive and Transplantation Surgery, Tokyo Medical University Hachioji Medical Center, 1163 Tatemachi, Hachioji, Tokyo, 193-0998, Japan. .,Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku Ward, Tokyo, 160-0012, Japan.
| | - Sou Katayanagi
- Department of Digestive and Transplantation Surgery, Tokyo Medical University Hachioji Medical Center, 1163 Tatemachi, Hachioji, Tokyo, 193-0998, Japan
| | - Itsuki Koganezawa
- Department of Digestive and Transplantation Surgery, Tokyo Medical University Hachioji Medical Center, 1163 Tatemachi, Hachioji, Tokyo, 193-0998, Japan
| | - Masashi Nakagawa
- Department of Digestive and Transplantation Surgery, Tokyo Medical University Hachioji Medical Center, 1163 Tatemachi, Hachioji, Tokyo, 193-0998, Japan
| | - Kenji Katsumata
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku Ward, Tokyo, 160-0012, Japan
| | - Akihiko Tsuchida
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku Ward, Tokyo, 160-0012, Japan
| | - Shigeyuki Kawachi
- Department of Digestive and Transplantation Surgery, Tokyo Medical University Hachioji Medical Center, 1163 Tatemachi, Hachioji, Tokyo, 193-0998, Japan
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Patel N, Slivkova R, James S, Almond M. Surgical management of a giant abdominal wall desmoid tumour. BMJ Case Rep 2021; 14:e244361. [PMID: 34479897 PMCID: PMC8420700 DOI: 10.1136/bcr-2021-244361] [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] [Accepted: 08/29/2021] [Indexed: 11/04/2022] Open
Abstract
Desmoid tumours are clonal fibroblastic proliferations in soft tissues, characterised by infiltrative growth and local recurrence, but not metastasis. Various treatment strategies for desmoid tumours exist, varying from observation, medical and systemic therapy to radiotherapy and surgery. A 25-year-old woman with a background of familial adenomatous polyposis was referred with an enlarging abdominal desmoid tumour measuring 40×40×40 cm despite repeated radiofrequency ablation, surgical debulking and hormone therapy. The patient had a two-stage operation. The first stage involved excision of the desmoid tumour with full-thickness abdominal wall. The abdominal wall was not closed, and a topical negative pressure seal was applied. After 2 days, she underwent the second stage: reconstruction of the abdominal wall defect with a large porcine mesh which was covered with anterolateral thigh flaps. Postoperative complications included ileus and a fall which required further surgery. The patient was discharged 1 month after the first operation. Abdominal MRI scans were performed at 3 and 7 months postdischarge and showed no recurrence of diseaseBackground.
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Affiliation(s)
- Nandesh Patel
- Acute Medical Unit, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, UK
| | - Ralitsa Slivkova
- Acute Medical Unit, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, UK
| | - Sunil James
- Acute Medical Unit, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, UK
- Sarcoma Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Max Almond
- Sarcoma Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
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Approach to screening for Familial Adenomatous Polyposis (FAP) in a cohort of 226 patients with Desmoid-type Fibromatosis (DF): experience of a specialist center in the UK. Fam Cancer 2021; 21:69-74. [PMID: 33547536 DOI: 10.1007/s10689-021-00230-8] [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: 11/07/2020] [Accepted: 01/15/2021] [Indexed: 10/22/2022]
Abstract
INTRODUCTION Desmoid-type fibromatosis (DF) are locally infiltrative, non-metastasizing tumours associated with significant morbidity and mortality if located intra-abdominally, retroperitoneally or in head and neck localisation. They are mostly sporadic, due to somatic CTNNB1 mutations. Alternatively, they can be associated with germline pathogenic variants in APC causing Familial Adenomatous Polyposis (FAP). Germline APC variants and somatic CTNNB1 mutations are mutually exclusive. AIMS AND METHODS We conducted a retrospective descriptive analysis of patients with DF seen at the Royal Marsden NHS Foundation Trust Sarcoma Unit in London. We aimed to describe the methods of screening for FAP in patients with DF from a specialist unit. Patients diagnosed between 1992 and 2020 were selected from the prospectively maintained Sarcoma Unit database. RESULTS 226 patients were identified and 67% (n = 152) were female. Median age at diagnosis was 37.5 (range 2-81) years. Tumour localisation was limbs/pelvis in 30.9% (N = 70), intra-abdominal 16.8% (N = 38), abdominal wall 23.5% (N = 53), thorax 18.6% (N = 42), head and neck 3.1% (N = 7) and vertebral/paravertebral 7.1% (N = 16). Colonoscopy was requested in 65 patients (28.8% of all cases) and was completed in forty-six (20.4%). Molecular testing of CTNNB1 testing was requested in 35 cases (15.5%). APC germline test was requested in 12 cases. Four patients in our cohort had an FAP-associated DF. CONCLUSIONS CTNNB1 ± APC testing and colonoscopy are useful tools for the screening of patients with DF. CTNNB1 molecular testing should be performed in all cases of newly diagnosed DF. Negative CTNNB1 results, alongside clinical assessment, should prompt APC testing and/or colonoscopy.
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Deshpande A, Tamhane A, Deshpande YS, Pagey R, Pangarkar M. Ball in the Wall: Mesenteric Fibromatosis-a Rare Case Report. Indian J Surg Oncol 2020; 11:73-77. [PMID: 33082700 PMCID: PMC7534782 DOI: 10.1007/s13193-020-01070-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Accepted: 04/01/2020] [Indexed: 12/31/2022] Open
Abstract
Introduction Mesenteric fibromatosis-desmoid tumor of mesentery is a rare benign soft tissue tumor of mesentery. On CT, it mimics gastrointestinal stromal tumor (GIST). Case Report A 44-year-old female with small intestinal mass, preoperatively diagnosed radiologically and pathologically as GIST. Conclusion Mesenteric fibromatosis is a rare tumor often mistaken for GIST. Histopathology and immunohistochemistry is the key as management of both the tumors differs.
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Affiliation(s)
- Abhinav Deshpande
- National Cancer Institute,Nagpur, 25, Outer Hingna Ring Road, Mouza-Jamtha, Nagpur,, 441108 Maharashtra India
| | - Ankita Tamhane
- National Cancer Institute,Nagpur, 25, Outer Hingna Ring Road, Mouza-Jamtha, Nagpur,, 441108 Maharashtra India
| | | | - Radhika Pagey
- National Cancer Institute,Nagpur, 25, Outer Hingna Ring Road, Mouza-Jamtha, Nagpur,, 441108 Maharashtra India
| | - Meena Pangarkar
- National Cancer Institute,Nagpur, 25, Outer Hingna Ring Road, Mouza-Jamtha, Nagpur,, 441108 Maharashtra India
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Desmoid-Type Fibromatosis. Cancers (Basel) 2020; 12:cancers12071851. [PMID: 32660036 PMCID: PMC7408653 DOI: 10.3390/cancers12071851] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Revised: 07/06/2020] [Accepted: 07/06/2020] [Indexed: 12/12/2022] Open
Abstract
Desmoid tumors represent a rare entity of monoclonal origin characterized by locally aggressive behavior and inability to metastasize. Most cases present in a sporadic pattern and are characterized by a mutation in the CTNNB1 gene; while 5–15% show a hereditary pattern associated with APC gene mutation, both resulting in abnormal β-catenin accumulation within the cell. The most common sites of presentation are the extremities and the thoracic wall, whereas FAP associated cases present intra-abdominally or in the abdominal wall. Histopathological diagnosis is mandatory, and evaluation is guided with imaging studies ranging from ultrasound, computed tomography or magnetic resonance. Current approaches advocate for an initial active surveillance period due to the stabilization and even regression capacity of desmoid tumors. For progressive, symptomatic, or disabling cases, systemic treatment, radiotherapy or surgery may be used. This is a narrative review of this uncommon disease; we present current knowledge about molecular pathogenesis, diagnosis and treatment.
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Gamboa AC, Gronchi A, Cardona K. Soft-tissue sarcoma in adults: An update on the current state of histiotype-specific management in an era of personalized medicine. CA Cancer J Clin 2020; 70:200-229. [PMID: 32275330 DOI: 10.3322/caac.21605] [Citation(s) in RCA: 327] [Impact Index Per Article: 65.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2020] [Revised: 02/11/2020] [Accepted: 02/12/2020] [Indexed: 12/13/2022] Open
Abstract
Soft-tissue sarcomas (STS) are rare tumors that account for 1% of all adult malignancies, with over 100 different histologic subtypes occurring predominately in the trunk, extremity, and retroperitoneum. This low incidence is further complicated by their variable presentation, behavior, and long-term outcomes, which emphasize the importance of centralized care in specialized centers with a multidisciplinary team approach. In the last decade, there has been an effort to improve the quality of care for patients with STS based on anatomic site and histology, and multiple ongoing clinical trials are focusing on tailoring therapy to histologic subtype. This report summarizes the latest evidence guiding the histiotype-specific management of extremity/truncal and retroperitoneal STS with regard to surgery, radiation, and chemotherapy.
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Affiliation(s)
- Adriana C Gamboa
- Division of Surgical Oncology, Department of Surgery, Emory University, Atlanta, Georgia
| | - Alessandro Gronchi
- Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Kenneth Cardona
- Division of Surgical Oncology, Winship Cancer Institute, Emory University Hospital Midtown, Atlanta, Georgia
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Sugimachi K, Iguchi T, Ohta M, Mano Y, Hisano T, Yokoyama R, Taguchi K, Ikebe M, Morita M, Toh Y. Laparoscopic spleen-preserving distal pancreatectomy for a solid-cystic intraabdominal desmoid tumor at a gastro-pancreatic lesion: a case report. BMC Surg 2020; 20:24. [PMID: 32013941 PMCID: PMC6998096 DOI: 10.1186/s12893-020-0691-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2019] [Accepted: 01/29/2020] [Indexed: 11/12/2022] Open
Abstract
Background We report a case of an intraabdominal desmoid tumor that occurred at a gastro-pancreatic lesion with spontaneous cystic features, and present the successful laparoscopic resection of the tumor. Case presentation A 20-mm retroperitoneal cystic mass with a solid component was found adjacent to the stomach and pancreatic body in a 52-year-old woman with no history of familial adenomatous polyposis. Laparoscopic spleen-preserving distal pancreatectomy with wedge resection of the stomach was performed, and complete resection was achieved without intraoperative and postoperative complications. Histopathological examination by immunohistochemistry enabled diagnosis of a desmoid tumor that had originated from the stomach and invaded the pancreatic parenchyma with a spontaneous cystic change. We herein report an extremely rare case of an intraabdominal desmoid tumor with a spontaneous cystic change. Conclusion Regardless of its rarity, desmoid tumor should be included in the preoperative differential diagnosis of a cystic intraabdominal mass, and laparoscopic function-preserving surgery may be an optimal treatment option.
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Affiliation(s)
- Keishi Sugimachi
- Department of Hepatobiliary-Pancreatic Surgery, National Hospital Organization Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka, 811-1395, Japan.
| | - Tomohiro Iguchi
- Department of Hepatobiliary-Pancreatic Surgery, National Hospital Organization Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka, 811-1395, Japan
| | - Mitsuhiko Ohta
- Department of Gastroenterological Surgery, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan
| | - Yohei Mano
- Department of Hepatobiliary-Pancreatic Surgery, National Hospital Organization Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka, 811-1395, Japan
| | - Terumasa Hisano
- Department of Hepato-Biliary-Pancreatology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan
| | - Ryohei Yokoyama
- Department of Orthopedic Surgery, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan
| | - Kenichi Taguchi
- Department of Pathology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan
| | - Masahiko Ikebe
- Department of Gastroenterological Surgery, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan
| | - Masaru Morita
- Department of Gastroenterological Surgery, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan
| | - Yasushi Toh
- Department of Gastroenterological Surgery, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan
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[Familial adenomatous polyposis, desmoid tumors and Gardner syndrome]. Bull Cancer 2019; 107:352-358. [PMID: 31882269 DOI: 10.1016/j.bulcan.2019.10.011] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2019] [Revised: 10/17/2019] [Accepted: 10/22/2019] [Indexed: 01/10/2023]
Abstract
About 15 % of patients with familial adenomatous polyposis "PAF" develop one or more desmoid tumors in their lifetime. These are benign mesenchymal tumors with local aggressivity but with no potential for metastases. Most of the desmoids tumors result from a sporadic genetic anomaly in the β catenin gene. When related to familial adenomatous polyposis or "PAF", this mutation is not present, and the patients must be sent in genetic counselling. The PAF is a dominant autosomic illness related to a germinal mutation in the APC gene. Sometimes, these tumors can be the first manifestation of the illness. The diagnosis in a context of PAF can be easily done by imaging, but a pathological confirmation is needed. These tumors raise a therapeutic problem because of their heterogeneity and the absence of predictive biomarkers along illness evolution. The identification of prognostic biological and clinical factors would make easier the selection of patients requiring first-line treatment, as spontaneous remissions have also been observed in patients with FAP whom which an active surveillance could also be a valid therapeutic option. The particularity of desmoids tumors associated to PAF lies in their predominantly intra-abdominal location and the risk of complication. In the last ten years, surgery has largely given way to conservative treatments such as chemotherapy and more recently to tyrosine kinase inhibitors that have shown their efficacy with a significant improvement in progression-free survival of patients.
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Siozopoulou V, Marcq E, Jacobs J, Zwaenepoel K, Hermans C, Brauns J, Pauwels S, Huysentruyt C, Lammens M, Somville J, Smits E, Pauwels P. Desmoid tumors display a strong immune infiltration at the tumor margins and no PD-L1-driven immune suppression. Cancer Immunol Immunother 2019; 68:1573-1583. [DOI: 10.1007/s00262-019-02390-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2019] [Accepted: 09/01/2019] [Indexed: 12/11/2022]
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Al Ali A, Garrido I, Le Guellec S, Duazo-Cassin L, Brouchet L, Chaput B, Chantalat E, Vaysse C. Rapidly growing breast desmoid tumor with intra-thoracic involvement after reconstructive surgery for breast cancer. Breast J 2019; 25:307-309. [PMID: 30746818 DOI: 10.1111/tbj.13212] [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: 07/11/2018] [Accepted: 09/25/2018] [Indexed: 11/30/2022]
Abstract
Desmoid tumors are very rare soft tissue neoplasia that are slow growing and locally aggressive. They grow anywhere in the body and are rarely develop in the breast . Histopathologic examination confirms diagnosis. Recurrence rate is very high even after complete resection. We report the management of a rare case of rapidly growing breast desmoid with intra-thoracic involvement causing cardiac compression.
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Affiliation(s)
- Amal Al Ali
- Department of Surgical Oncology, Centre Hospitalier Universitaire de Toulouse, Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France
| | - Ignacio Garrido
- Department of Plastic and Reconstructive Surgery, Centre Hospitalier Universitaire de Toulouse, Toulouse, France
| | - Sophie Le Guellec
- Pathology Department, Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse- Oncopole, Toulouse, France
| | - Ludwig Duazo-Cassin
- Gynaecology and Obstetrics Department, Centre Hospitalier Général, Albi, France
| | - Laurent Brouchet
- Surgery Thoracic Department, Centre Hospitalier Universitaire de Toulouse, Toulouse, France
| | - Benoit Chaput
- Department of Plastic and Reconstructive Surgery, Centre Hospitalier Universitaire de Toulouse, Toulouse, France
| | - Elodie Chantalat
- Department of Surgical Oncology, Centre Hospitalier Universitaire de Toulouse, Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France
| | - Charlotte Vaysse
- Department of Surgical Oncology, Centre Hospitalier Universitaire de Toulouse, Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France
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Luo N, He X, Li G, Liao Y, Tang Q, Ye R, Zhong D. Desmoid Tumor Presenting as a Typical Cervical Dumbbell Tumor:A Case Report and Literature Review. World Neurosurg 2019; 124:151-156. [PMID: 30639503 DOI: 10.1016/j.wneu.2019.01.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2018] [Revised: 12/31/2018] [Accepted: 01/02/2019] [Indexed: 12/30/2022]
Abstract
BACKGROUND Dumbbell-shaped tumor is a type of the inner and outer cervical spinal canal tumor, and most of them are neurogenic tumors. Desmoid tumor is a rare tumor, and no case of them involving intervertebral foramen formed dumbbell-shaped in cervical spine have been reported before in English literature. Here we report a case of desmoid tumor arising in the cervical spine which is presented as typical dumbbell-shaped tumor. CASE DESCRIPTION A 47-year-old female was admitted to our department with a mass in her left neck. The tumor was initially thought to be a neurogenic cervical dumbbell tumor based on physical and radiological examination. Postoperative HE and immunohistochemical staining verified the diagnosis of a cervical dumbbell desmoid tumor, which had never been reported before. We report our experience and reviewed literature about desmoid tumor to share our experience and explore proper treatment option of such lesion. CONCLUSION Desmoid tumors in the head and neck may present as cervical dumbbell-shaped tumors. Before the treatment plan was undertaken, thorough examinations including surgical pathology were necessary.
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Affiliation(s)
- Ning Luo
- Department of Spinal Surgery, Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou, China
| | - Xia He
- Department of Pediatric Surgery, Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou, China
| | - Guangzhou Li
- Department of Spinal Surgery, Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou, China
| | - Yehui Liao
- Department of Spinal Surgery, Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou, China
| | - Qiang Tang
- Department of Spinal Surgery, Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou, China
| | - Rupei Ye
- Department of Pathology, Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou, China
| | - Dejun Zhong
- Department of Spinal Surgery, Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou, China.
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A Decision Analysis for Rectal-Sparing Familial Adenomatous Polyposis: Total Colectomy With Ileorectal Anastomosis Versus Proctocolectomy With IPAA. Dis Colon Rectum 2019; 62:27-32. [PMID: 30394986 DOI: 10.1097/dcr.0000000000001186] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND There are different approaches for the surgical management of rectal-sparing familial adenomatous polyposis with variable impacts on both quality of life and survival. OBJECTIVE The aim of this study was to quantify the trade-offs between total proctocolectomy with IPAA versus total colectomy with ileorectal anastomosis using decision analysis. DESIGN We created a disease simulation Markov model to simulate the clinical events after IPAA and ileorectal anastomosis for rectal-sparing familial adenomatous polyposis in a cohort of individuals at the age 30 years. We used available literature to obtain different transition probabilities and health-states utilities. The output parameters were quality-adjusted life-years and life-years. Deterministic and probabilistic sensitivity analyses were performed. SETTINGS A decision analysis using a Markov model was conducted at a single center. PATIENTS Patients with rectal-sparing familial adenomatous polyposis at age 30 years were included. Rectal-sparing familial adenomatous polyposis is defined as the presence of 0 to 20 polyps that can be removed endoscopically. MAIN OUTCOME MEASURES Quality-adjusted life-years were measured. RESULTS Our model showed that the mean quality-adjusted life-years for IPAA was 25.12 and for ileorectal anastomosis was 27.12 in base-case analysis. Mean life-years for IPAA were 28.81 and 28.28 for ileorectal anastomosis. A 1-way sensitivity analysis was performed for all of the parameters in the model. None of the deterministic sensitivity analyses changed the model results across the range of plausible values. Probabilistic analysis identified that, in 86.9% of scenarios, ileorectal anastomosis had improved quality-adjusted life-years compared with IPAA. LIMITATIONS The study was limited by characteristics inherent to modeling studies. CONCLUSIONS Ileorectal anastomosis was found to be preferable for patients with rectal-sparing familial adenomatous polyposis when quality of life is taken into consideration. This model was robust based on both deterministic and probabilistic sensitivity analyses. These data should be taken into consideration when counseling patients regarding a surgical approach in rectal-sparing familial adenomatous polyposis. See Video Abstract at http://links.lww.com/DCR/A715.
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Abstract
OBJECTIVE The purpose of this article is to review the etiopathogenesis, molecular cytogenetics, histopathology, clinical features, and multimodality imaging features of desmoid fibromatosis. Recent advances in the management of desmoid fibromatosis will also be discussed. CONCLUSIONS Desmoid fibromatosis is a rare soft tissue neoplasm with a high incidence of local recurrence. Imaging plays an important role in the diagnosis and management of this disease.
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Affiliation(s)
| | - Behrang Amini
- Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Paul Nikolaidis
- Northwestern University, Feinberg School of Medicine, Chicago, IL
| | - Matthew Assing
- Department of Radiology, Stanford University School of Medicine, Stanford, CA
| | - Raghunandan Vikram
- Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX
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Santti K, Ihalainen H, Rönty M, Böhling T, Karlsson C, Haglund C, Tarkkanen M, Blomqvist C. High cyclin A expression, but not Ki67, is associated with early recurrence in desmoid tumors. J Surg Oncol 2018; 118:192-198. [PMID: 29878366 DOI: 10.1002/jso.25121] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2018] [Accepted: 05/07/2018] [Indexed: 11/10/2022]
Abstract
BACKGROUND AND OBJECTIVES Desmoid tumors are soft-tissue tumors originating from myofibroblasts with a tendency to recur after surgery. High expression of proliferation markers is associated with shortened progression-free and/or overall survival in many neoplasms, including soft-tissue sarcomas. We investigated the prognostic role of cyclin A and Ki67 in desmoid tumors by immunohistochemistry. METHODS The study included 76 patients with desmoid tumor operated at Helsinki University Hospital between 1987 and 2011. A tissue micro array (TMA) was constructed and the TMA sections were immunostained with cyclin A and Ki67 antibodies. A computer-assisted image analysis was performed. RESULTS Cyclin A expression was evaluable in 74 and Ki67 in 70 patients. Cyclin A immunopositivity varied from 0% to 9.9%, with a mean of 1.9%. Cyclin A expression correlated significantly with Ki67. Cyclin A expression was associated with recurrence-free survival (HR 1.9, 95% CI = 1.1-3.2, P = .02), as were positive margin (HR 6.0, 95% CI = 1.6-22.5, P = .008) and extremity location (HR 5.3, 95% CI = 1.7-16.8, P = 0.005). Ki67 immunopositivity varied from 0.33% to 13.8%, with a mean of 4.6%, but had no significant prognostic impact (HR 1.1, P = .2). CONCLUSIONS Our study indicates that cyclin A may be a new prognostic biomarker in surgically treated desmoid tumors.
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Affiliation(s)
- Kirsi Santti
- Comprehensive Cancer Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Hanna Ihalainen
- Comprehensive Cancer Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.,Department of Plastic Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Mikko Rönty
- Department of Pathology, HUSLAB and University of Helsinki, Helsinki, Finland
| | - Tom Böhling
- Department of Pathology, HUSLAB and University of Helsinki, Helsinki, Finland
| | - Christina Karlsson
- Department of Medical Diagnostics, School of Health Sciences, Örebro University, Örebro, Sweden
| | - Caj Haglund
- Department of Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.,Reseach Program Unit, Translational Cancer Biology, University of Helsinki, Helsinki, Finland
| | - Maija Tarkkanen
- Comprehensive Cancer Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Carl Blomqvist
- Comprehensive Cancer Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.,Department of Oncology, Örebro University Hospital, Örebro, Sweden
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Tonelli F, Ficari F, Valanzano R, Brandi ML. Treatment of Desmoids and Mesenteric Fibromatosis in Familial Adenomatous Polyposis with Raloxifene. TUMORI JOURNAL 2018; 89:391-6. [PMID: 14606641 DOI: 10.1177/030089160308900408] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Background Among the great variety of extracolonic manifestations of familial adenomatous polyposis, the most serious are desmoids and fibromatosis of the abdominal cavity. These may be a danger to the patient and a concern to the clinician. Pharmacological management of this relentless problem is favored by surgical intervention. At present, however, beneficial actions of medical therapy are not separable from undesirable side effects. Methods We studied the effects of 120 mg daily of raloxifene, a non-steroidal benzothiophene, on progressive desmoid tumors and mesenteric fibromatosis by evaluation of lesion size and symptoms in 13 patients with familial adenomatous polyposis, selected on the basis of intra-abdominal localization of the lesion, on refractoriness to other medical treatments, and on estrogen receptor-α expression. Results The patients had a significant response to raloxifene therapy, with complete remission in 8 cases and partial response in 5 cases, evaluated by regression of symptoms and tumor size. Serum biochemical parameters did not show any significant changes. Side effects were never observed. Conclusions Although the number of patients included in the study is limited and in spite of some limitations, the available results support that, in the evaluation of response, daily therapy with raloxifene decreases desmoid tumor and mesenteric fibromatosis size and symptoms and does not cause side effects. These findings offer a novel option in the pharmacological treatment of desmoids, leading to medical therapy of these neoplastic lesions in familial adenomatous polyposis patients.
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Affiliation(s)
- Francesco Tonelli
- Department of Clinical Physiopathology, University of Florence, Italy
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Krishnamurthy G, Jha VC, Verma GR. Port site desmoid tumour following laparoscopic cholecystectomy: A case report. J Minim Access Surg 2018; 14:247-249. [PMID: 29319019 PMCID: PMC6001309 DOI: 10.4103/jmas.jmas_209_17] [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] [Indexed: 11/24/2022] Open
Abstract
Desmoid tumours are locally aggressive tumours occurring either spontaneously or in familial conditions. History of trauma is invariably present with surgical trauma being a common cause. Port site desmoid tumours are extremely rare conditions. Inadequate treatment results in high recurrence rate and substantial morbidity. Reconstruction, if required, by the appropriate technique is vital to avoid an incisional hernia. Adjuvant therapy may be useful in large locally advanced or recurrent tumours. We describe a young female with large port site desmoid tumour following laparoscopic cholecystectomy managed with wide local excision and mesh placement.
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Affiliation(s)
- Gautham Krishnamurthy
- Department of General Surgery, Division of Surgical Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Vijay Chetan Jha
- Department of General Surgery, Division of Surgical Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Ganga Ram Verma
- Department of General Surgery, Division of Surgical Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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Walter T, Zhenzhen Wang C, Guillaud O, Cotte E, Pasquer A, Vinet O, Poncet G, Ponchon T, Saurin JC. Management of desmoid tumours: A large national database of familial adenomatous patients shows a link to colectomy modalities and low efficacy of medical treatments. United European Gastroenterol J 2017; 5:735-741. [PMID: 28815038 PMCID: PMC5548349 DOI: 10.1177/2050640616678150] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2016] [Accepted: 10/12/2016] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Desmoid tumours represent a major complication of familial adenomatous polyposis. Our aims were to study the factors associated with the development of desmoid tumours in familial adenomatous polyposis patients, and to describe presentation and management of desmoid tumours. METHODS AND PATIENTS We reviewed all patients with familial adenomatous polyposis followed at our institution between 1965-2013, with either identified adenomatous polyposis coli gene mutation, or a personal and family history suggesting adenomatous polyposis coli-related polyposis. Response to treatment of desmoid tumours was assessed by Response Evaluation Criteria In Solid Tumor (RECIST) criteria. RESULTS A total of 180 patients with familial adenomatous polyposis were included with a median follow-up of 19 years since diagnosis. Thirty-one (17%) patients developed 58 desmoid tumours, a median (range) 4.7 (0.8-41.6) years after their diagnosis of familial adenomatous polyposis. The only factor significantly associated with occurrence of desmoid tumours was the type of surgery: 12 (12%) desmoid tumours in 104 patients treated by colectomy, versus 19 (25%) desmoid tumours in 76 patients treated by proctocolectomy, p = 0.027. The localisation of desmoid tumours was: mesenteric (n = 25), abdominal wall (n = 30) or extra-abdominal (n = 3). Nineteen patients underwent 36 surgical procedures for desmoid tumours. Recurrence occurred in 26 (72%) cases and the recurrence-free survival was 2.6 (95% confidence interval (CI), 0.2-5.9) years. Thirteen patients received 27 medical treatments over a median 14 months. Objective response was observed in four (15%) patients and the median progression-free survival was nine (95% CI, 1.1-16.9) months. CONCLUSION If confirmed, colectomy (versus proctocolectomy) should be performed in adenomatous polyposis coli-related familial adenomatous polyposis patients to avoid desmoid tumours. We show that there is a high prevalence of post-surgical recurrence and the low efficacy of available medical treatments for desmoid tumours.
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Affiliation(s)
- T Walter
- Gastroenterology Department, Edouard Herriot Hospital, Lyon, France
| | - C Zhenzhen Wang
- Gastroenterology Department, Edouard Herriot Hospital, Lyon, France
- Ruijin Hospital, Shanghai Jiaotong University, China
| | - O Guillaud
- Gastroenterology Department, Edouard Herriot Hospital, Lyon, France
| | - E Cotte
- Surgery Department, Lyon Sud Hospital, Lyon, France
| | - A Pasquer
- Surgery Department, Edouard Herriot Hospital, Lyon, France
| | - O Vinet
- Gastroenterology Department, Edouard Herriot Hospital, Lyon, France
| | - G Poncet
- Surgery Department, Edouard Herriot Hospital, Lyon, France
| | - T Ponchon
- Gastroenterology Department, Edouard Herriot Hospital, Lyon, France
| | - J-C Saurin
- Gastroenterology Department, Edouard Herriot Hospital, Lyon, France
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Skubitz KM. Biology and Treatment of Aggressive Fibromatosis or Desmoid Tumor. Mayo Clin Proc 2017; 92:947-964. [PMID: 28578783 DOI: 10.1016/j.mayocp.2017.02.012] [Citation(s) in RCA: 69] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2016] [Revised: 01/24/2017] [Accepted: 02/16/2017] [Indexed: 12/14/2022]
Abstract
Aggressive fibromatosis, also known as desmoid-type fibromatosis (DTF) or desmoid tumor, is an uncommon locally invasive tumor. Because of its low incidence and variable behavior, DTF is often first seen by physicians who are not familiar with it, and recent advances in understanding this disease have led to changes in treatment approaches. The Wnt (β-catenin) pathway appears to play a key role in DTF pathogenesis, and recent studies of DTF biology suggest a possible model of DTF pathogenesis. Histologically, DTF shows a poorly circumscribed proliferation of myofibroblast-like cells with variable collagen deposition, similar to the proliferative phase of wound healing, and DTF has been associated with trauma and pregnancy. Desmoid-type fibromatosis may be a useful model of the tumor stroma in carcinomas as well as other fibrosing diseases such as progressive pulmonary fibrosis. The clinical course of DTF can vary greatly among patients, complicating the determination of the optimal treatment approach. Treatment options include surgery, nonsteroidal anti-inflammatory drugs with or without hormonal manipulation, chemotherapy, radiation therapy, and other forms of local therapy. Many treatments have been used, but these are not without toxicities. Because of the variable nature of the disease and the potential morbidity of treatment, some cases of DTF may do better without treatment; simple observation is often the best initial treatment. This review used a PubMed search from January 1, 1980, through October 31, 2016, using the terms fibromatosis and desmoid and discusses DTF disease characteristics, pathophysiology, and treatment options as well as examines several cases illustrating key points in the biology and treatment of this heterogeneous disease.
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Affiliation(s)
- Keith M Skubitz
- Department of Medicine, University of Minnesota Medical School, Minneapolis.
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Nair KK, Chaudhuri K, Lingappa A, Shetty R, Vittobarao PG. Aggressive fibromatosis of the oral cavity in a 5 year old boy: a rare case report. Pan Afr Med J 2017; 27:47. [PMID: 28819469 PMCID: PMC5554660 DOI: 10.11604/pamj.2017.27.47.11739] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2017] [Accepted: 05/06/2017] [Indexed: 11/14/2022] Open
Abstract
Fibrous tissue proliferations express a wide spectrum of histologic and morphologic variation in both infants and adults. This ranges from hypertrophic scar formation at one end to malignant fibrosarcoma at the other end of the spectrum. Aggressive fibromatosis is an intermediate tumor which is in proximity to fibrosarcomas. These are locally invasive and often recur after excision, but do not metastasize. Histologically, they are characterized by proliferating fibroblasts with little mitotic activity. Aggressive fibromatosis in the head and neck region is not common, and very sporadically occurs in the oral cavity or jaw bones. Here we report a rare case of aggressive fibromatosis occurring in a 5 year old boy.
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Affiliation(s)
- Keerthi Krishnankutty Nair
- Department of Oral Medicine and Radiology SJM Dental College and Hospital, Chitradurga, Karnataka, India
| | - Kanad Chaudhuri
- Dental Surgeon, Lifeline Polyclinic Kalyani, Nadia, West Bengal, India
| | - Ashok Lingappa
- Department of Oral Medicine and Radiology Bapuji Dental College and Hospital MCC B Block, Davangere, Karnataka, India
| | - Ranjani Shetty
- Department of Oral Medicine and Radiology Bapuji Dental College and Hospital MCC B Block, Davangere, Karnataka, India
| | - Pramod Gujjar Vittobarao
- Department of Oral Medicine and Radiology Bapuji Dental College and Hospital MCC B Block, Davangere, Karnataka, India
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Abstract
INTRODUCTION Desmoid tumors are benign myofibroblastic neoplasms, originating from the muscle aponeurosis and classified as deep fibromatoses. The aim of this study was to evaluate the utility of multi-parametric (mp)-MRI for the diagnosis of abdominal wall desmoid tumor (awdt). MATERIAL AND METHODS This Institutional review board approved retrospective study compared 10 patients (mean age±SD; 38.2±13years; 9 females and 1 male) with awdt to 14 subjects (mean age±SD; 45.6±14.7years; 9 females and 5 males) with non-desmoid abdominal wall tumors (ndawt). All included subjects underwent mp-MRI, which included conventional, diffusion weighted and dynamic contrast-enhanced (DCE) MRI. Two blinded experienced fellowship trained radiologists (MK and SR) evaluated each lesion characteristics qualitatively and quantitatively which included margin, homogeneity, T2W/T1W signal intensity (SI), T2 dark strands, and fascial tail together with measurements of apparent diffusion coefficient (ADC) and semi-quantitative DCE analysis. Inter-observer agreement was assessed using Cohen's kappa and data were compared between groups using independent sample t-tests and Chi-square tests. RESULTS No significant differences in age or gender appeared between groups. On qualitative analysis, T2 dark strands were identified in 90% by both radiologist (K=0.82) of awdt, while fascial tail was identified in 70% by radiologist 1 and 80% by second radiologist (k=0.91) of awdt; however no other lesions showed these findings. Other subjective imaging findings did not significantly differ between groups with moderate-to-strong agreements (k=0.7-1.0). On quantitative measurements, diffusion imaging awdt lesions showed higher mean ADC value compared to other lesions, although it did not reached at the level of significance. While on DCE MRI, all awdt lesions showed type 1 (progressive) DCE curve, however no significant difference was observed between groups. CONCLUSIONS T2 dark strands and fascial tail are characteristic features of awdt, whereas other subjective/qualitative findings are not useful. Quantitative findings such as ADC measurements and DCE curve analysis may have additional value to differentiate awdt from ndawt, but will require further analysis.
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