Search Results (28)

Pediatric gastrointestinal polyps are frequently associated with an underlying hereditary syndrome associated with multisystem manifestations and increased risk of early-onset cancer. Thus, the identification of polyps in a child should prompt evaluation with genetic testing to (1) characterize the syndrome to determine next clinical steps including surveillance recommendations, and (2) conduct cascade testing to identify affected family members. Given the considerations for pediatric genetic testing, including autonomy and psychosocial stressors associated with the early detection of a cancer risk syndrome, it is important to conduct targeted testing. Herein, we propose a stepwise approach to genetic testing in the pediatric patient with gastrointestinal polyps. Full article

Background: Pancreatic cancer is a highly lethal malignancy, with a 5-year survival rate of approximately 8%. Roughly 10% of cases occur in individuals with familial pancreatic cancer or identified high-risk germline mutations, including STK11, CDKN2A, BRCA1/2, MLH1, and MSH2. Aim: We aimed to evaluate the risk of pancreatic cancer associated with inherited genetic mutations and to characterize these genetic syndromes. Methods: A systematic search of the PubMed database up to 2024 identified 1500 articles, of which 90 met the criteria for inclusion in this review. Results: High-risk individuals were defined as those with at least a 10-fold increased risk, moderate risk as 5–10-fold and low risk as under 5-fold. High-risk individuals included those with Peutz–Jeghers syndrome (132–140-fold risk), hereditary pancreatitis (50–87-fold risk), Familial Atypical Multiple Mole Melanoma syndrome (up to 48-fold risk), hereditary breast and ovarian cancer with BRCA2 mutation (up to 22-fold risk), and familial pancreatic cancer with at least three affected relatives (up to 32-fold risk). Moderate-risk patients had BRCA1, MLH1, MSH2, MSH6, p53, and ATM mutations, as well as familial pancreatic cancer with 1–2 affected kindred. Low-risk patients had familial adenomatous polyposis. Conclusions: Identifying high-risk individuals is crucial for effective genetic counseling, testing, and potential screening programs to facilitate early diagnosis and improve outcomes. Future research should prioritize large prospective cohorts, screening programs, and the integration of emerging technologies, such as AI-assisted imaging. Full article

Papillary thyroid cancer (PTC) is the most common endocrine malignancy with especially high incidence in Middle Eastern populations. While classical hereditary syndromes explain a minority of cases, the broader germline landscape of non-syndromic PTC remains unclear. Whole-exome sequencing was performed on 245 unselected Saudi PTC patients to identify germline pathogenic or likely pathogenic variants (PVs/LPVs) in cancer predisposition genes. Clinical and molecular characteristics, and family history were integrated to assess phenotypic correlations. Eleven patients (4.5%) harbored germline PVs/LPVs in cancer susceptibility genes including STK11, TP53, BRCA1, BRCA2, FANCA, SLX4, RAD50, MSH6, POLD1 and NF1. Four patients (36.4%) carried PVs/LPVs in canonical FA pathway genes; this increased to five patients (45.5%) when RAD50 was included. Two unrelated patients harbored the same STK11 variant (p.R304Q) without classical Peutz–Jeghers syndrome features. A TP53 hotspot mutation (p.R175H) was identified in a patient with a personal history of gastric cancer, a malignancy associated with Li–Fraumeni syndrome. Notably, the BRCA1 PV detected matches a known Saudi founder mutation in hereditary breast cancer, now observed in PTC. Most germline positive cases lacked syndromic manifestations, underscoring limitations of phenotype or family history-driven genetic testing strategies. These findings suggest that a small subset of non-syndromic PTC cases may carry germline PVs/LPVs in cancer predisposition genes, highlighting the need for broader genetic screening frameworks. Unbiased whole-exome analysis in unselected cohorts can uncover under-recognized genetic risk and guide screening strategies to address the unique hereditary landscape of thyroid cancer in underrepresented populations. Full article

Urinary bladder hamartoma is an exceptionally rare benign lesion composed of disorganized yet mature tissue elements native to the bladder, including urothelium, fibrous stroma, smooth muscle, and occasionally adipose tissue. Unlike malignant tumors, it lacks cytological atypia, mitotic activity, or necrosis. Patients most often present with lower urinary tract symptoms (LUTS) or hematuria, though some cases are incidental findings. Associations with syndromic conditions such as Peutz–Jeghers, Beckwith–Wiedemann, Goldenhar, and Loeys–Dietz have been reported. Transurethral resection is the preferred treatment and has generally been curative. We report the first case in Germany—and the 16th worldwide—of urinary bladder hamartoma, occurring in a young adult male with bothersome LUTS. Because of its proximity to both ureteral orifices, only partial transurethral resection was performed, which provided durable symptom relief at 14 months of follow-up. This case highlights partial TUR as a pragmatic, organ-preserving alternative when complete resection is anatomically unsafe, while emphasizing that TURBT remains the standard of care. We provide a detailed discussion of the histopathological features, differential diagnosis, treatment considerations, and an updated narrative review of all reported cases. Full article

Video Capsule Endoscopycapsule endoscopy (VCE) has emerged as a minimally invasive diagnostic tool for detecting and monitoring small bowel involvement in polyposis syndromes. VCE is included in the surveillance guidelines of Peutz-Jeghers syndrome. In the remaining familial polyposis syndromes, VCE may facilitate the early detection of polyps, when indicated, particularly in areas beyond the reach of conventional endoscopy, thereby aiding timely detection. Colon capsule endoscopy has been studied in symptomatic, screening and polyp surveillance populations and the second-generation colon capsule has demonstrated excellent detection rates for advanced neoplasia, however its role in colonic polyposis requires further research. The role of the panenteric capsule has not been explored in polyposis syndromes as a panintestinal examination. Despite its advantages, VCE has notable limitations; it may miss small, flat, or hidden lesions and lacks the capability for tissue sampling or therapeutic intervention. In the future, advances in imaging technology, extended battery life, and the integration of artificial intelligence (AI) are expected to further enhance the utility of VCE. Our review aims to focus on the applications of VCE in polyposis syndromes and future perspectives. Full article

Cutaneous manifestations can serve as early and sometimes the first clinical indicators in various hereditary cancer predisposition syndromes. This review provides a comprehensive overview of the dermatological signs associated with these syndromes, aiming to facilitate their recognition in clinical practice. Hereditary Breast and Ovarian Cancer syndrome is notably linked to an increased risk of melanoma. BAP1 tumor predisposition syndrome is characterized by BAP1-inactivated melanocytic tumors. Muir–Torre syndrome, a variant of Lynch syndrome, presents with distinctive cutaneous neoplasms such as sebaceous carcinomas, sebaceous adenomas, and keratoacanthomas. PTEN hamartoma tumor syndrome commonly features hamartomatous growths, trichilemmomas, acral keratoses, oral papillomas, and genital lentiginosis. Gorlin syndrome is marked by basal cell carcinomas and palmoplantar pits, while Peutz–Jeghers syndrome is identified by mucocutaneous pigmentation. In familial adenomatous polyposis, the cutaneous findings include epidermoid cysts, fibromas, desmoid tumors, and lipomas. Additionally, we examined monogenic disorders associated with cancer risk and skin involvement, such as xeroderma pigmentosum, neurofibromatosis type 1, familial atypical multiple-mole melanoma syndrome, and Fanconi anemia. The early recognition of these dermatologic features is essential for a timely diagnosis and the implementation of appropriate surveillance strategies in individuals with hereditary cancer syndromes. Full article

Background: Pancreatic cancer (PC) is among the deadliest types of cancer globally. While early detection helps avert adverse outcomes, screening is only recommended for individuals at high risk, specifically those with familial and/or genetic predispositions. The objectives of this study are to systematically review primary studies on the cost-effectiveness of PC screening and to identify the critical factors that influence cost-effectiveness. Methods: This systematic review was performed using PRISMA guidelines. Economic evaluation studies on PC screening were identified from searches on the SCOPUS and PubMed databases. The quality of reporting of the selected articles was assessed according to CHEERS 2022. Using predefined inclusion and exclusion criteria, two reviewers conducted the title–abstract review, full-text review, and data extraction to select relevant articles. The authors’ consensus was used to settle disagreements. The primary outcome was the incremental cost-effectiveness ratio, measured by cost per quality-adjusted life year and cost per life year saved. Results: Nine studies were selected for the final review. Most studies demonstrated that one-time screening for PC among high-risk individuals was cost-effective compared with no screening, while others found annual screening to also be cost-effective. High-risk was generally defined as having a >5% lifetime risk of PC and included individuals with either familial pancreatic cancer (FPC) or genetic susceptibility syndromes such as Peutz–Jeghers Syndrome, hereditary pancreatitis, hereditary non-polypoid colorectal cancer syndrome, familial adenomatous polyposis, and BRCA2 mutations. Individuals with new-onset diabetes (NOD) were also considered high-risk. Screening using mainly endoscopic ultrasound was cost-effective among FPC individuals and those with genetic syndromes. Risk-based screening was also cost-effective among patients with NOD. Conclusion: Screening for PC is cost-effective among selected high-risk individuals. However, cost-effectiveness depends on epidemiological factors, cost, the diagnostic performance of screening tools, and the overall design of studies. Full article

Background: Hereditary colorectal cancer syndromes, including familial adenomatous polyposis (FAP), Lynch syndrome (LS), and Peutz–Jeghers syndrome (PJS), are associated with an increased risk of small bowel cancer (SBC). Due to the low incidence and non-specific presentation of SBC, effective surveillance strategies are essential for early detection and management. This review aims to evaluate and compare current endoscopic techniques for small bowel surveillance in these patients. Methods: A comprehensive review was conducted using peer-reviewed studies sourced from PubMed. Various endoscopic modalities, including capsule endoscopy (CE), device-assisted enteroscopy (DAE), and intraoperative enteroscopy (IOE), were assessed for their diagnostic yield, safety, and clinical utility. Surveillance recommendations of the different syndromes were also examined. Results: CE offers high sensitivity but lacks histological sampling capability. DAE, including double-balloon enteroscopy (DBE) and single-balloon enteroscopy (SBE), enables direct visualization, biopsy, and therapeutic interventions, albeit with greater procedural complexity. In FAP, duodenal surveillance follows the Spigelman classification to stratify cancer risk, while jejunal and ileal polyps remain less studied. LS patients have an increased SBC risk, warranting tailored endoscopic approaches. In PJS, surveillance aims to mitigate intussusception risks and allow early malignancy detection. Conclusions: Optimized surveillance strategies in hereditary colorectal cancer syndromes require a multimodal approach, integrating advanced endoscopic techniques with genetic risk stratification. Centralized care in tertiary centers improves outcomes by ensuring standardized surveillance protocols and enhancing early cancer detection. Artificial intelligence (AI) applied to CE and DAE is shaping promising prospects for the future surveillance of small bowel polyps by enhancing diagnostic accuracy and reducing the duration of the diagnostic process. Further research should investigate AI-assisted imaging and molecular biomarkers to optimize screening strategies. Full article

A retrospective study in patients who underwent video capsule endoscopy (VCE) between 2006 and 2016 was conducted in the Clinic for gastroenterology and Hepatology, University Clinical Center of Serbia. A total of 245 patients underwent VCE. In 198 patients the indication was obscure gastrointestinal bleeding (OGIB), with 92 patients having overt and the other 106 occult bleeding. The remaining 47 patients underwent VCE due to suspected small bowel (SB) disease (i.e., Von Hippel–Lindau syndrome, familial adenomatous polyposis, Peutz Jeghers syndrome, Crohn’s disease, prolonged diarrhea, abdominal pain, congenital lymphangiectasia, protein-losing enteropathy, tumors, refractory celiac disease, etc.). VCE identified a source of bleeding in 38.9% of patients (in the obscure overt group in 48.9% of patients, and in the obscure occult group in 30.2% of patients). The most common findings were angiodysplasias, tumors, Meckel’s diverticulum and Crohn’s disease. In the smaller group of patients with an indication other than OGIB, 38.3% of patients had positive VCE findings. The most common indication is OGIB, and the best candidates are patients with overt bleeding; patients with IBD should be evaluated in this setting. Full article

Multiple gastric polyps are observed in various polyposis syndromes and conditions associated with polypoid lesion development in the stomach. Polyposis syndromes often occur concurrently with specific malignant tumors and can manifest at any point in an individual’s lifespan, thus explaining the diversity in surveillance methods. Furthermore, genetic counseling and surveillance are essential not only for the patients themselves but also for their blood relatives. Therefore, the accurate diagnosis and appropriate surveillance of multiple gastric polyps are crucial for improving patient outcomes. This review aims to provide essential information on such lesions along with representative endoscopic images of familial adenomatous polyposis, Peutz-Jeghers syndrome, Cowden syndrome, Cronkhite-Canada syndrome, juvenile polyposis syndrome, gastric adenocarcinoma and proximal polyposis of the stomach, neuroendocrine tumors in autoimmune gastritis, proton pump inhibitor-related gastric mucosal changes, and multiple submucosal heterotopic glands. We wish for this review to serve as a valuable resource for endoscopists seeking to deepen their comprehension of gastric polyposis. Full article

Ovarian sex cord–stromal tumors (SCSTs) account for 8% of all primary ovarian neo-plasms. Accurate diagnosis is crucial since each subtype has a specific prognostic and treatment. Apart from fibrosarcomas, stromal tumors are benign while sex cord tumors may recur, sometimes with a significant time to relapse. Although the diagnosis based on morphology is straightforward, in some cases the distinction between stromal tumors and sex cord tumors may be tricky. Indeed, the immunophenotype is usually nonspecific between stromal tumors and sex cord tumors. Therefore, molecular pathology plays an important role in the diagnosis of such entities, with pathognomonic or recurrent alterations, such as FOXL2 variants in adult granulosa cell tumors. In addition, these neoplasms may be associated with genetic syndromes, such as Peutz–Jeghers syndrome for sex cord tumors with annular tubules, and DICER1 syndrome for Sertoli–Leydig cell tumors (SLCTs), for which the pathologist may be in the front line of syndromic suspicion. Molecular pathology of SCST is also relevant for patient prognosis and management. For instance, the DICER1 variant is associated with moderately to poorly differentiated SLCTS and a poorer prognosis. The present review summarizes the histomolecular criteria useful for the diagnosis of SCST, using recent molecular data from the literature. Full article

The management of pediatric Peutz–Jeghers Syndrome (PJS) focuses on the prevention of intussusception complicating small intestinal (SI) polyposis. This hinges on the accurate appraisal of the polyp burden to tailor therapeutic interventions. Video Capsule Endoscopy (VCE) is an established tool to study SI polyps in children, but an in-depth characterization of polyp burden in this population is lacking. Methods: We performed a retrospective longitudinal cross-sectional analysis of VCE studies in pediatric PJS patients at our institution (CMKC) from 2010 to 2020. Demographic, clinical, and VCE findings reported by three reviewers in tandem were accrued. Polyp burden variables were modeled as functions of patient and study characteristics using linear mixed models adjusted for clustering. Results: The cohort included 15 patients. The total small bowel polyp count and largest polyp size clustered under 30 polyps and <20 mm in size. Luminal occlusion correlated closely with the estimated polyp size. Polyp distribution favored proximal (77%) over distal (66%) small bowel involvement. The adjusted largest polyp size was greater in males. Double Balloon Enteroscopy was associated with a decreased polyp burden. Conclusions: The polyp burden in pediatric PJS patients favors the proximal third of the small intestine, with relatively small numbers and a polyp size amenable to resection through enteroscopy. Male gender and older age were related to an increased polyp burden. Full article

Colorectal cancer is one of the most common tumors, and genetic predisposition is one of the key risk factors in the development of this malignancy. Lynch syndrome and familial adenomatous polyposis are the best-known genetic diseases associated with hereditary colorectal cancer. However, some other genetic disorders confer an increased risk of colorectal cancer, such as Li–Fraumeni syndrome (TP53 gene), MUTYH-associated polyposis (MUTYH gene), Peutz–Jeghers syndrome (STK11 gene), Cowden syndrome (PTEN gene), and juvenile polyposis syndrome (BMPR1A and SMAD4 genes). Moreover, the recent advances in molecular techniques, in particular Next-Generation Sequencing, have led to the identification of many new genes involved in the predisposition to colorectal cancers, such as RPS20, POLE, POLD1, AXIN2, NTHL1, MSH3, RNF43 and GREM1. In this review, we summarized the past and more recent findings in the field of cancer predisposition genes, with insights into the role of the encoded proteins and into the associated genetic disorders. Furthermore, we discussed the possible clinical utility of genetic testing in terms of prevention protocols and therapeutic approaches. Full article

(1) Background: Gastric carcinoma is an exceptionally rare tumor in childhood. Little is known about the etiology, epidemiology, and clinical features of pediatric gastric carcinomas. This analysis aimed to fill this gap by increasing knowledge about the occurrence of gastric carcinoma in childhood. (2) Material and methods: Data from gastric carcinoma cases diagnosed between 2000 and 2017/2018 were retrieved from the Surveillance, Epidemiology, and End Results Program (SEER) and the German Center for Cancer Registry Data. Data from patients <20 years of age were analyzed for patient- and tumor-related characteristics. In addition, clinical data from patients with gastric carcinoma registered in the German Registry for Rare Pediatric Tumors (STEP) were analyzed for diagnostics, therapy, and outcome. (3) Results: Ninety-one cases of gastric carcinoma, mainly in adolescents, were identified in the epidemiologic cancer registries. Among patients with recorded staging data, advanced tumor stages were common (66.7%). Within the follow-up period covered, 63.7% of patients with clinical follow-up data died. Eight pediatric patients with gastric carcinoma were enrolled in the STEP registry, among whom two were patients with hereditary CDH1 mutations and another was a patient with Peutz–Jeghers syndrome. Three patients were found to have distinctly decreased immunoglobulin concentrations. All four patients in whom complete resection was achieved remained in remission. Three of the other four patients died despite multimodal therapy. (4) Conclusions: A combination of Helicobacter pylori infection and tumor predisposition and/or immunodeficiency appears to promote the development of gastric carcinoma in childhood. While patients with localized disease stages have a good chance of achieving durable remission through complete resection, patients with stage IV carcinomas face a dismal prognosis, highlighting the need to develop new strategies such as mutation-guided treatments. Full article

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. Full article