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Iasella MP, Ruttens D, Hompes D, Vandecaveye V, Sciot R, Deroose C, Douchy T, Decramer T, Jacobs S, Denayer E, Van Calenbergh F, Legius E, Brems H. Close Follow-Up of Patients with Neurofibromatosis Type 1 Reduces the Incidence of Malignant Peripheral Nerve Sheath Tumour. Cancers (Basel) 2025; 17:1306. [PMID: 40282482 PMCID: PMC12025940 DOI: 10.3390/cancers17081306] [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: 03/06/2025] [Revised: 04/03/2025] [Accepted: 04/04/2025] [Indexed: 04/29/2025] Open
Abstract
Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic condition with a birth incidence of one in 2000 to one in 3000 [...].
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Affiliation(s)
- Maria Pia Iasella
- Centre for Human Genetics, University Hospitals Leuven, KU Leuven, 3000 Leuven, Belgium
| | - Dries Ruttens
- Department of Paediatric Oncology, University Hospitals Leuven, 3000 Leuven, Belgium
- Department of Paediatric Oncology, Princess Máxima Centre for Pediatric Oncology, 3584 CS Utrecht, The Netherlands
| | - Daphne Hompes
- Department of Surgical Oncology, University Hospitals Leuven, 3000 Leuven, Belgium
| | | | - Raf Sciot
- Department of Pathology, University Hospitals Leuven, KU Leuven, 3000 Leuven, Belgium
| | - Christophe Deroose
- Nuclear Medicine, University Hospitals Leuven, and Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, KU Leuven, 3000 Leuven, Belgium
| | - Thomas Douchy
- Department of Surgical Oncology, University Hospitals Leuven, 3000 Leuven, Belgium
| | - Thomas Decramer
- Department of Neurosurgery, University Hospitals Leuven, 3000 Leuven, Belgium
| | - Sandra Jacobs
- Department of Paediatric Oncology, University Hospitals Leuven, 3000 Leuven, Belgium
| | - Ellen Denayer
- Centre for Human Genetics, University Hospitals Leuven, KU Leuven, 3000 Leuven, Belgium
| | | | - Eric Legius
- Centre for Human Genetics, University Hospitals Leuven, KU Leuven, 3000 Leuven, Belgium
| | - Hilde Brems
- Centre for Human Genetics, University Hospitals Leuven, KU Leuven, 3000 Leuven, Belgium
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Gupta S, Ahuja S, Kalwaniya DS. A rare unifocal gastric gastrointestinal stromal tumor in a young NF1 patient: A case report. Int J Surg Case Rep 2025; 129:111126. [PMID: 40054407 PMCID: PMC11930091 DOI: 10.1016/j.ijscr.2025.111126] [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: 01/20/2025] [Revised: 03/01/2025] [Accepted: 03/03/2025] [Indexed: 03/26/2025] Open
Abstract
INTRODUCTION AND IMPORTANCE Gastrointestinal stromal tumors (GISTs) are the most prevalent mesenchymal neoplasms of the gastrointestinal tract, predominantly associated with mutations in the KIT and PDGFRA genes. Neurofibromatosis type 1 (NF1) increases the risk of developing GISTs, particularly in younger individuals, and often presents with atypical features. CASE PRESENTATION A 16-year-old female with a known diagnosis of NF1 presented with severe anemia, hematemesis, and melena. Physical examination revealed multiple café-au-lait spots and cutaneous nodular masses. A contrast-enhanced CT scan showed a large mass arising from the stomach's greater curvature, consistent with GIST. The patient underwent a sleeve gastrectomy, and histopathological evaluation confirmed high-grade spindle cell GIST. Immunohistochemistry was positive for CD117, CD34, and DOG-1. Postoperative PET-CT showed no residual disease. CLINICAL DISCUSSION GIST in NF1 patients typically presents with a multifocal pattern, but our patient exhibited a rare unifocal GIST in the stomach. The diagnosis was complicated by atypical presentation and required multimodal imaging and histopathological confirmation. NF1-associated GISTs generally lack KIT and PDGFRA mutations, rendering targeted therapies like imatinib ineffective, emphasizing surgical management as the primary treatment. CONCLUSION This case highlights the unique clinical and pathological characteristics of NF1-associated GISTs, stressing the need for vigilant assessment in NF1 patients with gastrointestinal symptoms.
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Affiliation(s)
- Sumedha Gupta
- Department of Obstetrics and Gynaecology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India
| | - Sana Ahuja
- Department of Pathology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India.
| | - Dheer Singh Kalwaniya
- Department of Surgery, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India
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Honda M, Iwamuro M, Tanaka T, Yamasaki Y, Kawano S, Hiraoka S, Kawahara Y, Otsuka M. Frequency and Characteristics of Gastrointestinal Diseases in Patients With Neurofibromatosis. JGH Open 2025; 9:e70151. [PMID: 40247846 PMCID: PMC12003917 DOI: 10.1002/jgh3.70151] [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: 12/11/2024] [Revised: 03/03/2025] [Accepted: 03/31/2025] [Indexed: 04/19/2025]
Abstract
Background and Aim Patients with neurofibromatosis (NF) frequently experience gastrointestinal symptoms, but the specific characteristics of these lesions are not well understood. Methods To investigate the prevalence and nature of gastrointestinal diseases in this population, we analyzed the gastrointestinal lesions identified through endoscopic examinations in patients with NF. Results We included 225 patients with NF type 1 (NF1) and 15 with NF type 2 (NF2). None of the NF2 patients underwent endoscopy. Among the NF1 patients, 27 received endoscopies, and 13 (59%) had gastrointestinal lesions. These 13 patients were predominantly male (10 males and three females), with a median age of 53 years (range: 19-76 years). The identified lesions included colorectal polyps (n = 6), gastrointestinal stromal tumors ([GIST], n = 4), subepithelial lesions (n = 3), gastric fundic gland polyps (n = 3), diffuse intestinal ganglioneuromatosis (n = 2), esophageal polyps (n = 2), a Schwann cell hamartoma (n = 1), esophageal cancer (n = 1), and a gastric hyperplastic polyp (n = 1). All GISTs and one case of diffuse intestinal ganglioneuromatosis were surgically resected. Interestingly, six out of 13 patients were asymptomatic. Additionally, all patients who required surgery were 40 years of age or older. Conclusions These findings suggest that routine endoscopic examinations, along with imaging techniques like computed tomography and magnetic resonance imaging, could be beneficial for the early detection of gastrointestinal lesions in NF1 patients aged 40 and above.
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Affiliation(s)
- Manami Honda
- Department of Gastroenterology and HepatologyOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan
| | - Masaya Iwamuro
- Department of Gastroenterology and HepatologyOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan
| | - Takehiro Tanaka
- Department of PathologyOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesOkayamaJapan
| | - Yasushi Yamasaki
- Department of Gastroenterology and HepatologyOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan
| | - Seiji Kawano
- Department of Gastroenterology and HepatologyOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan
| | - Sakiko Hiraoka
- Department of Gastroenterology and HepatologyOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan
- Inflammatory Bowel Disease CenterOkayama University HospitalOkayamaJapan
| | - Yoshiro Kawahara
- Department of Practical Gastrointestinal EndoscopyOkayama University HospitalOkayamaJapan
| | - Motoyuki Otsuka
- Department of Gastroenterology and HepatologyOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan
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Tsegaye H, Tigabu A. Multiple small bowel GIST as GI manifestation of neurofibromatosis type I: A case report. Radiol Case Rep 2025; 20:1548-1551. [PMID: 39811049 PMCID: PMC11731583 DOI: 10.1016/j.radcr.2024.11.094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2024] [Accepted: 11/28/2024] [Indexed: 01/16/2025] Open
Abstract
Neurofibromatosis type 1 (NF1) is characterized by café-au-lait patches on the skin and the presence of neurofibromas. Gastrointestinal stromal tumor (GIST) is the most common GI tumour in NF1 patients. In NF1-associated GIST, KIT and PDGFRA mutations are frequently absent and imatinib is ineffective. Surgical resection is first-line treatment. A 58-year-old woman present with dyspepsia symptoms and physical examination was notable for multiple café-au-lait patches and multiple subcutaneous nodular masses of the skin of the face, trunk, and limbs. Abdomininoplevic CT shows multiple different size avidly enhancing small bowel mass. The patient underwent laparotomy and resection with jejenu-jejunal anastomosis was done with smooth post op condition. Histopathology shows Grade I GIST with score 4+ immune reactivity for CD117. It is typically difficult to make a conclusive preoperative diagnosis of GISTs. Computed tomography of the abdomen should be done in Neurofibromatosis type 1 Patients with gastrointestinal symptoms as GISTs may be the cause of these symptoms. Surgical resection may also be performed for both diagnosis and treatment. The objective of this case repot is to describe the radiological feature of multiple GIST in elder NF1 patient in resource limited setup.
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Affiliation(s)
- Habtamu Tsegaye
- Department of Radiology, School of medicine, college of medicine and health science, Bahir Dar University, Bahir Dar, Ethiopia
| | - Adamu Tigabu
- Department of Radiology, School of medicine, college of medicine and health science, Bahir Dar University, Bahir Dar, Ethiopia
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Kallionpää RA, Määttänen J, Leppävirta J, Peltonen S, Peltonen J. Pregnancy and the Risk for Cancer in Neurofibromatosis 1. Genes Chromosomes Cancer 2025; 64:e70017. [PMID: 39985314 PMCID: PMC11846020 DOI: 10.1002/gcc.70017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Revised: 12/11/2024] [Accepted: 12/13/2024] [Indexed: 02/24/2025] Open
Abstract
BACKGROUND Neurofibromatosis type 1 (NF1) is associated with a high risk for cancer. Benign cutaneous neurofibromas of women with NF1 may increase in size and number during pregnancy. However, it is not known whether pregnancy affects the risk for cancer in NF1. METHODS We retrieved the pregnancies of women in the Finnish NF1 cohort and in a 10-fold control cohort from the Finnish Medical Birth Register. Cancers occurring during or after pregnancy were obtained from the Finnish Cancer Registry and summarized using standardized incidence ratio (SIR). The cancer incidence of nonNF1 mothers of individuals with NF1 was also estimated. RESULTS Totals of 263 pregnancies in 136 women with NF1 and 3176 pregnancies in 1720 controls were observed. In the NF1 group, two cancers were identified during pregnancy and the year following the delivery (SIR 6.44, 95% CI 1.07-19.89). Among controls, the SIR was markedly lower (0.25, 95% CI 0.01-1.08). Within 1-10 years after pregnancy, the SIR of women with NF1 was 7.54 (95% CI 4.15-12.41). The SIR of women with NF1 aged 20-49 years, and without a known history of deliveries was 8.63 (95% CI 6.08-11.81). The nonNF1 mothers displayed a SIR of 0.81 (95% CI 0.66-1.00) after giving birth to a child with NF1. CONCLUSIONS The pregnancy-related cancer incidence in women with NF1 is similar to women with NF1 aged 20-49 years overall, although notably higher than in the general population. Giving birth to a child with NF1 does not affect the risk for cancer in women without NF1.
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Affiliation(s)
- Roope A. Kallionpää
- Institute of BiomedicineUniversity of TurkuTurkuFinland
- FICAN West Cancer CentreUniversity of Turku and Turku University HospitalTurkuFinland
| | - Juha Määttänen
- Institute of BiomedicineUniversity of TurkuTurkuFinland
- Department of Dermatology and VenereologyUniversity of TurkuTurkuFinland
- Department of DermatologyTurku University HospitalTurkuFinland
| | - Jussi Leppävirta
- Department of Dermatology and VenereologyUniversity of TurkuTurkuFinland
- Department of DermatologyTurku University HospitalTurkuFinland
| | - Sirkku Peltonen
- Department of Dermatology and VenereologyUniversity of TurkuTurkuFinland
- Department of DermatologyTurku University HospitalTurkuFinland
- Department of Dermatology and Venereology, Institute of Clinical Sciences, Sahlgrenska AcademyUniversity of GothenburgGothenburgSweden
- Department of Dermatology and Venereology, Region Västra GötalandSahlgrenska University HospitalGothenburgSweden
- Department of Dermatology and AllergologyUniversity of HelsinkiHelsinkiFinland
- Skin and Allergy HospitalHelsinki University HospitalHelsinkiFinland
| | - Juha Peltonen
- Institute of BiomedicineUniversity of TurkuTurkuFinland
- FICAN West Cancer CentreUniversity of Turku and Turku University HospitalTurkuFinland
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Sunder-Plassmann V, Azizi AA, Farschtschi S, Gruber R, Hutterer M, Ladurner V, Röhl C, Welponer T, Bergmeister-Berghoff AS. Neurofibromatosis type 1 adult surveillance form for Austria. Wien Klin Wochenschr 2024:10.1007/s00508-024-02443-0. [PMID: 39264447 DOI: 10.1007/s00508-024-02443-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Accepted: 08/27/2024] [Indexed: 09/13/2024]
Abstract
BACKGROUND Neurofibromatosis type 1 (NF1) is a rare autosomal dominant tumor predisposition syndrome with a birth prevalence of approximately 1 in 2000-3000 individuals. Management of both benign and malignant tumors arising in individuals with NF1 is demanding and tumors may be difficult to treat. Both standardized and individual surveillance programs are therefore highly important to prevent morbidity and mortality in patients with NF1. METHODS The guidelines for the clinical management of NF1 recently proposed by the European Reference Network for Genetic Tumor Risk Syndromes provide the cornerstone of the present surveillance form and were discussed through three rounds of voting and a final consensus meeting involving experts from five Austrian and one German clinical NF1 centers for adults and one patient organization representative. Subsequently, 31 items within 4 categories were integrated into the proposed surveillance form for Austria. All recommendations, unless otherwise specified, pertain to primarily asymptomatic patients in routine follow-up. RECOMMENDATIONS At healthcare transition from pediatric to adult surveillance or the initial visit in adulthood, we suggest a thorough clinical, laboratory and radiological examination to obtain a baseline for future diagnostics. To comply with the general screening recommendations in Austria, we suggest extending the frequency of clinical visits from annual to biennial at 50 years of age. In cases of clinical dynamics, early follow-up is recommended to facilitate early detection of potential complications. Particular emphasis should be placed on preventive patient education.
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Affiliation(s)
- Vincent Sunder-Plassmann
- Division of Oncology, Department of Medicine I, Medical University of Vienna, Waehringer Gürtel 18-20, 1090, Vienna, Austria.
- Christian Doppler Laboratory for Personalized Immunotherapy, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
| | - Amedeo A Azizi
- Division of Neonatology, Pediatric Intensive Care and Neuropediatrics, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria
- Comprehensive Center for Pediatrics, Medical University of Vienna, Vienna, Austria
- Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
| | - Said Farschtschi
- International Center for Neurofibromatoses, Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg-Eppendorf, Germany
| | - Robert Gruber
- Department of Dermatology, Venereology and Allergy, Medical University of Innsbruck, Innsbruck, Austria
| | - Markus Hutterer
- Department of Neurology with Acute Geriatrics, Saint John of God Hospital Linz, Linz, Austria
| | | | | | - Tobias Welponer
- Department of Dermatology and Allergology, University Hospital of the Paracelsus Medical University, Salzburg, Austria
| | - Anna-Sophie Bergmeister-Berghoff
- Division of Oncology, Department of Medicine I, Medical University of Vienna, Waehringer Gürtel 18-20, 1090, Vienna, Austria
- Christian Doppler Laboratory for Personalized Immunotherapy, Department of Medicine I, Medical University of Vienna, Vienna, Austria
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Fueng-Hin Liang R, Chau CYP, Lim WC. Neurofibromatosis Type 1 Presenting as Bleeding Jejunal Gastrointestinal Stromal Tumour. Case Rep Gastroenterol 2024; 18:299-305. [PMID: 38895585 PMCID: PMC11185854 DOI: 10.1159/000538688] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Accepted: 03/24/2024] [Indexed: 06/21/2024] Open
Abstract
Introduction Gastrointestinal stromal tumours (GISTs) are an important, though uncommon, cause of obscure gastrointestinal bleeding and may rarely be associated with genodermatoses such as neurofibromatosis type 1 (NF1). NF1-related GISTs have unique phenotypic features compared with sporadic GISTs and may elude diagnosis due to their predilection for the small bowel. Case Presentation We report a case of a 45-year-old Singaporean woman with café-au-lait macules and cutaneous neurofibromas who presented with occult obscure gastrointestinal bleeding and was eventually discovered to have a bleeding jejunal GIST. This finding, considered together with her cutaneous signs, eventually led to the diagnosis of NF1. Conclusion Genodermatoses and their gastrointestinal complications are likely under-reported in adult Southeast Asian populations and deserve greater awareness from gastroenterologists practising in this region.
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Affiliation(s)
- Raymond Fueng-Hin Liang
- Department of Gastroenterology and Hepatology, Tan Tock Seng Hospital, Singapore, Singapore
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
| | | | - Wee Chian Lim
- Department of Gastroenterology and Hepatology, Tan Tock Seng Hospital, Singapore, Singapore
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
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Yao MQ, Jiang YP, Yi BH, Yang Y, Sun DZ, Fan JX. Neurofibromatosis type 1 with multiple gastrointestinal stromal tumors: A case report. World J Clin Cases 2023; 11:2336-2342. [PMID: 37122520 PMCID: PMC10131015 DOI: 10.12998/wjcc.v11.i10.2336] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 02/01/2023] [Accepted: 03/14/2023] [Indexed: 03/30/2023] Open
Abstract
BACKGROUND Neurofibromatosis type 1 (NF1) is characterized by café-au-lait patches on the skin and the presence of neurofibromas. Gastrointestinal stromal tumor (GIST) is the most common non-neurological tumor in NF1 patients. In NF1-associated GIST, KIT and PDGFRA mutations are frequently absent and imatinib is ineffective. Surgical resection is first-line treatment.
CASE SUMMARY A 56-year-old woman with NF1 was hospitalized because of an incidental pelvic mass. Physical examination was notable for multiple café-au-lait patches and numerous subcutaneous soft nodular masses of the skin of the head, face, trunk, and limbs. Her abdomen was soft and nontender. No masses were palpated. Digital rectal examination was unremarkable. Abdominal computed tomography was suspicious for GIST or solitary fibrous tumor. Laparoscopy was performed, which identified eight well-demarcated masses in the jejunum. All were resected and pathologically diagnosed as GISTs. The patient was discharged on day 7 after surgery without complications. No tumor recurrence was evident at the 6-mo follow-up.
CONCLUSION Laparoscopy is effective for both diagnosis and treatment of NF1-associated GIST.
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Affiliation(s)
- Min-Quan Yao
- Department of Gastrointestinal Surgery, Tongxiang First People’s Hospital, Jiaxing 314500, Zhejiang Province, China
| | - Yu-Peng Jiang
- Department of Gastrointestinal Surgery, Tongxiang First People’s Hospital, Jiaxing 314500, Zhejiang Province, China
| | - Bing-Hong Yi
- Department of Gastrointestinal Surgery, Tongxiang First People’s Hospital, Jiaxing 314500, Zhejiang Province, China
| | - Yong Yang
- Department of Gastrointestinal Surgery, Tongxiang First People’s Hospital, Jiaxing 314500, Zhejiang Province, China
| | - Da-Zhuang Sun
- Department of Gastrointestinal Surgery, Tongxiang First People’s Hospital, Jiaxing 314500, Zhejiang Province, China
| | - Jin-Xing Fan
- Endoscopy Center, Tongxiang First People’s Hospital, Jiaxing 314500, Zhejiang Province, China
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Girma T, Nureta TH, Abebe DM. Unusual presentation of GIST associated with type 1 neurofibromatosis: A case report. Int J Surg Case Rep 2023; 105:107992. [PMID: 36940542 PMCID: PMC10036922 DOI: 10.1016/j.ijscr.2023.107992] [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: 12/16/2022] [Revised: 03/09/2023] [Accepted: 03/16/2023] [Indexed: 03/23/2023] Open
Abstract
INTRODUCTION AND IMPORTANCE Type 1 neurofibromatosis (NF1) is an autosomal dominant disorder caused by NF1 gene mutation, which is associated with several types of tumors. GIST is an intestinal stromal tumor arising from interstitial cells of Cajal in the intestine. GIST is one of the neoplasms seen in NF1 and usually affects elderly individuals with a median age around 60-65 years but rarely occur in children, adolescent and young adults. CASE PRESENTATION An 18-year-old male patient presented to our hospital with abdominal swelling of one-year duration. He also has multiple skin nodules and café au lait spots all over his body. Objectively, the abdomen is grossly distended; with a palpable non-tender mobile mass above the umbilicus measuring 20 × 15 cm. CT imaging of the abdomen and histologic examination of the skin lesion was done. The diagnosis of GIST was made and surgical resection followed by adjuvant therapy with imatinib was given. CLINICAL DISCUSSION Patients who have a gene mutation in NF 1 have a high probability (7 %) of developing GIST and mostly occur in the small intestine, whereas our finding was solitary GIST localized to the stomach. NF 1-associated GISTs are very rare and account for <5 % of all GISTs. The standard therapy for GIST is surgical resection of the tumor. Targeted therapy with tyrosine kinase inhibitors is an effective adjuvant therapy in patients harboring KIT/PDGFRA mutation. CONCLUSION The incidence of GIST is higher in NF1 patients than in the general population. The definitive diagnosis of GISTs preoperatively is usually challenging and is usually confirmed by immunohistochemistry. NF1-associated GISTs are mainly treated with surgery and have limited response to tyrosine kinase inhibitors.
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Affiliation(s)
- Tadesse Girma
- Department of Surgery, Faculty of Medicine, Institute of health, Jimma University, Ethiopia.
| | - Tilahun Habte Nureta
- Department of Surgery, Faculty of Medicine, Institute of health, Jimma University, Ethiopia
| | - Dabessa Mossisa Abebe
- Department of Surgery, Faculty of Medicine, Institute of health, Jimma University, Ethiopia
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Bharath BG, Rastogi S, Ahmed S, Barwad A. Challenges in the management of metastatic gastrointestinal stromal tumor in a patient with neurofibromatosis type 1: a case report. J Med Case Rep 2022; 16:174. [PMID: 35490251 PMCID: PMC9057061 DOI: 10.1186/s13256-022-03382-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2021] [Accepted: 03/21/2022] [Indexed: 12/02/2022] Open
Abstract
BACKGROUND Neurofibromatosis type 1 is an inherited cancer predisposition syndrome that is caused by a mutation in the NF1 gene that encodes neurofibromin. Patients with neurofibromatosis type 1 have a higher risk of gastrointestinal stromal tumor. This study reports the case of a patient with gastrointestinal stromal tumor who was later diagnosed to have neurofibromatosis type 1 and, unlike usual features, had some uncommon features such as occurrence at an early age and unusual site of origin. CASE We report the case of a 29-year-old Indian female diagnosed to have gastrointestinal stromal tumor originating from the greater curvature of the stomach. Gastrointestinal stromal tumor was wild type, negative for c-kit and platelet-derived growth factor receptor, and had an aggressive clinical course not responding to oral tyrosine kinase inhibitors. On later evaluation, we found that the patient had germline mutation in NF1. This case has some unusual features compared with gastrointestinal stromal tumor cases reported in neurofibromatosis type 1. Firstly, the age of onset for gastrointestinal stromal tumor in neurofibromatosis type 1 is earlier in our case compared with previous cases reported in literature. Secondly, the site of occurrence is in the stomach, without involving other parts of the intestine. Gastrointestinal stromal tumor in neurofibromatosis type 1 is usually multifocal, and small intestine is the common site of occurrence. When occurring in the stomach, it is usually associated with other lesions in the small intestine. Lastly, the clinical course is aggressive compared with previous case reports and series. CONCLUSION Our patient had germline NF1 mutation and cutaneous stigmata of neurofibromatosis. Our patient had unicentric gastrointestinal stromal tumor occurring at younger age and involving greater curvature of the stomach, with spindle cell type histology and high-risk features. If gastrointestinal stromal tumor occurs at young age, we should look into neurocutaneous markers.
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Affiliation(s)
- B G Bharath
- Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India
| | - Sameer Rastogi
- Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India.
| | - Shamim Ahmed
- Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Adarsh Barwad
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
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Lin Y, Wang C, Chiu Y, Lin R, Mo L. Small intestine gastrointestinal stromal tumor and malignant peripheral nerve sheath tumor in a patient with neurofibromatosis type 1: A case report. ADVANCES IN DIGESTIVE MEDICINE 2021. [DOI: 10.1002/aid2.13235] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Affiliation(s)
- Yu‐Hung Lin
- Division of Gastroenterology and Hepatology, Department of Internal Medicine Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation) Tainan Taiwan
| | - Chun‐Hsiang Wang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation) Tainan Taiwan
| | - Yin‐I Chiu
- Department of General Surgery Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation) Tainan Taiwan
| | - Ruey‐Chang Lin
- Division of Gastroenterology and Hepatology, Department of Internal Medicine Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation) Tainan Taiwan
| | - Lein‐Ray Mo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation) Tainan Taiwan
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Arslan ME, Li H, Fu Z, Jennings TA, Lee H. Plexiform fibromyxoma: Review of rare mesenchymal gastric neoplasm and its differential diagnosis. World J Gastrointest Oncol 2021; 13:409-423. [PMID: 34040702 PMCID: PMC8131905 DOI: 10.4251/wjgo.v13.i5.409] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 03/22/2021] [Accepted: 04/26/2021] [Indexed: 02/06/2023] Open
Abstract
Plexiform fibromyxoma (PF) is a very rare mesenchymal neoplasm of the stomach that was first described in 2007 and was officially recognized as a subtype of gastric mesenchymal neoplasm by World Health Organization (WHO) in 2010. Histologically, PF is characterized by a plexiform growth of bland spindle to ovoid cells embedded in a myxoid stroma that is rich in small vessels. The lesion is usually paucicellular. While mucosal and vascular invasion have been documented, no metastasis or malignant transformation has been reported. Its pathogenesis is largely unknown and defining molecular alterations are not currently available. There are other mesenchymal tumors arising in the gastrointestinal tract that need to be differentiated from PF given their differing biologic behaviors and malignant potential. Histologic mimics with spindle cells include gastrointestinal stromal tumor, smooth muscle tumor, and nerve sheath tumor. Histologic mimics with myxoid stroma include myxoma and aggressive angiomyxoma. Molecular alterations that have been described in a subset of PF may be seen in gastroblastoma and malignant epithelioid tumor with glioma-associated oncogene homologue 1 (GLI1) rearrangement. The recent increase in publications on PF reflects growing recognition of this entity with expansion of clinical and pathologic findings in these cases. Herein we provide a review of PF in comparison to other mesenchymal tumors with histologic and molecular resemblance to raise the awareness of this enigmatic neoplasm. Also, we highlight the challenges pathologists face when the sample is small, or such rare entity is encountered intraoperatively.
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Affiliation(s)
- Mustafa Erdem Arslan
- Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY 12208, United States
| | - Hua Li
- Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY 12208, United States
| | - Zhiyan Fu
- Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY 12208, United States
| | - Timothy A Jennings
- Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY 12208, United States
| | - Hwajeong Lee
- Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY 12208, United States
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Kallionpää RA, Ahramo K, Aaltonen M, Pennanen P, Peltonen J, Peltonen S. Circulating free DNA in the plasma of individuals with neurofibromatosis type 1. Am J Med Genet A 2021; 185:1098-1104. [PMID: 33484105 DOI: 10.1002/ajmg.a.62081] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Accepted: 12/26/2020] [Indexed: 02/06/2023]
Abstract
Neurofibromatosis type 1 (NF1) is an autosomal dominant syndrome whose characteristic manifestations include benign neurofibromas, yet NF1 is also associated with a high risk of cancer. Measurements of circulating free plasma DNA (cfDNA) are gaining wider applicability in cancer diagnostics, targeting of therapy, and monitoring of therapeutic response. Individuals with NF1 are likely to be followed up using this method, but the effects of NF1 and neurofibromas on cfDNA levels are not known. We studied peripheral blood samples from 19 adults with NF1 and 12 healthy controls. The cfDNA was isolated from plasma with QIAamp Circulating Nucleic Acid Kit and quantified using the Qubit 2.0 Fluorometer. The cfDNA concentration of each sample was normalized relative to the plasma protein concentration. The normalized median concentration of cfDNA in plasma was 19.3 ng/ml (range 6.6-78.6) among individuals with NF1 and 15.9 ng/ml (range 4.8-47.0) among controls (p = .369). Individuals with NF1 who also had plexiform neurofibroma (pNF) showed non-significantly elevated cfDNA concentration compared to individuals with NF1 and without known pNF (median 25.4 vs. 18.8 ng/ml, p = .122). The effect of NF1 on cfDNA seems to be relatively small and NF1 is therefore unlikely to hamper the use of cfDNA-based assays.
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Affiliation(s)
- Roope A Kallionpää
- Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku, Turku, Finland
| | - Kaisa Ahramo
- Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku, Turku, Finland
| | - Marianna Aaltonen
- Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku, Turku, Finland.,Turku University of Applied Sciences, Turku, Finland
| | - Paula Pennanen
- Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku, Turku, Finland
| | - Juha Peltonen
- Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku, Turku, Finland
| | - Sirkku Peltonen
- Department of Dermatology and Venereology, University of Turku, Turku, Finland.,Department of Dermatology, Turku University Hospital, Turku, Finland.,Department of Dermatology and Venereology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Department of Dermatology and Venereology, Region Västra Götaland Sahlgrenska University Hospital, Gothenburg, Sweden
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14
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Eulo V, Lesmana H, Doyle LA, Nichols KE, Hirbe AC. Secondary Sarcomas: Biology, Presentation, and Clinical Care. Am Soc Clin Oncol Educ Book 2020; 40:1-12. [PMID: 32213089 DOI: 10.1200/edbk_280985] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
Secondary sarcomas are a subset of sarcomas that occur in patients with prior cancer diagnoses and are associated with environmental or genetic factors. Although secondary sarcomas are rare in general, there are predisposing factors that can substantially increase this risk in certain populations. Herein, we review the environmental factors with the strongest association of sarcoma risk, including chemical exposure, certain viruses, cytotoxic and immunosuppressive agents, chronic edema, and radiation exposure. Additionally, the most common genetic disorders that carry a predisposition for sarcoma development will be discussed, including hereditary retinoblastoma (RB), Li-Fraumeni syndrome (LFS), neurofibromatosis type 1 (NF1), and DICER1 syndrome. Although treatment does not generally differ for sporadic versus secondary sarcomas, awareness of the risk factors can alter therapeutic strategies to minimize risk, aid prompt diagnosis by increasing clinical suspicion, and allow for appropriate surveillance and genetic counseling for those patients with cancer predisposition syndromes.
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Affiliation(s)
- Vanessa Eulo
- Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO
- Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO
| | - Harry Lesmana
- Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN
| | - Leona A Doyle
- Department of Pathology, Brigham and Women's Hospital, Boston, MA
| | - Kim E Nichols
- Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN
| | - Angela C Hirbe
- Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO
- Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO
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Ylä-Outinen H, Loponen N, Kallionpää RA, Peltonen S, Peltonen J. Intestinal tumors in neurofibromatosis 1 with special reference to fatal gastrointestinal stromal tumors (GIST). Mol Genet Genomic Med 2019; 7:e927. [PMID: 31397088 PMCID: PMC6732307 DOI: 10.1002/mgg3.927] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2019] [Revised: 07/23/2019] [Accepted: 07/26/2019] [Indexed: 12/18/2022] Open
Abstract
Background Type 1 neurofibromatosis (NF1) is a genetic tumor predisposing Rasopathy. NF1 patients have an increased risk for developing benign and malignant tumors, but the occurrence of intestinal tumors has not been investigated at the population level. Methods In this retrospective register‐based total population study, diagnoses of gastrointestinal tract tumors were retrieved from the Finnish Care Register for Health Care for 1,410 NF1 patients and 14,030 reference persons. We also reviewed the death certificates of 232 NF1 patients who died during years 1987–2013, and specifically searched for diagnosis of gastrointestinal stromal tumor (GIST). Results The register analysis revealed an increased overall hazard ratio (HR) of 2.6 (95% CI 1.9–3.6) for intestinal tumors in NF1 compared to general population. The highest HR of 15.6 (95% CI 6.9–35.1) was observed in the small intestine. The focused analysis of NF1 death certificates and GISTs demonstrated that the GIST was the primary cause of death in seven patients. Conclusion This study emphasizes the need for careful evaluation of NF1 patients with gastrointestinal complaints. The challenge in diagnosis is that the tumors preferably occur at the small intestine, which is difficult target for diagnostic procedures. We also show that the NF1 GISTs may lead to fatal outcome despite of benign histopathological findings at the time of the diagnosis.
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Affiliation(s)
- Heli Ylä-Outinen
- Department of Cell Biology and Anatomy, University of Turku, Turku, Finland.,Department of Pulmonary Diseases, Turku University Hospital, Turku, Finland
| | - Niina Loponen
- Department of Cell Biology and Anatomy, University of Turku, Turku, Finland
| | - Roope A Kallionpää
- Department of Cell Biology and Anatomy, University of Turku, Turku, Finland
| | - Sirkku Peltonen
- Department of Dermatology, Turku University Hospital, Turku, Finland
| | - Juha Peltonen
- Department of Cell Biology and Anatomy, University of Turku, Turku, Finland
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