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OBJECTIVE This study aimed to investigate the clinical features and potential pathogenesis of a rare nonhereditary polyposis syndrome, Cronkhite-Canada syndrome (CCS). METHODS Medical records of eight patients with CCS who were admitted to our hospital from January 2005 to November 2019 were reviewed. Transcriptome profiling was performed in one patient to investigate its difference between gastric polyp tissue and normal mucosa. Differentially expressed genes (DEGs) were determined for functional analysis. The expression of inhibin beta A (INHBA) was further assessed by using immunohistochemistry. RESULTS All patients presented with gastrointestinal polyposis, accompanied by diarrhea, skin hyperpigmentation, hair loss and nail dystrophy. Hyperplastic polyps were observed in seven patients, tubular adenoma in two, inflammatory polyps in one and hamartomatous polyps in one, respectively. All patients underwent comprehensive treatment and five achieved clinical remission. A total of 2107 DEGs, including 1265 upregulated and 842 downregulated, were found in the gastric polyp. Gene ontology analysis showed that upregulated genes were significantly enriched in the positive regulation of cell proliferation, epithelium development and angiogenesis. A protein-protein interaction analysis suggested that INHBA was at the center of the interaction network and might play an important role in CCS. Immunohistochemistry confirmed that INHBA expression was upregulated in CCS gastric polyps. CONCLUSIONS CCS is a rare disease and its diagnosis mainly depends on typical clinical manifestations, endoscopic findings and histological features. INHBA upregulation may contribute to its pathogenesis.

A 59-year-old man with refractory Cronkhite-Canada syndrome (CCS) had poor clinical response to high-dose intravenous steroids, azathioprine, total parenteral nutrition and best supportive care. He remained highly symptomatic with abdominal pain, diarrhoea, recurrent sepsis and profound weight loss. Infliximab induction was given as rescue therapy, with marked clinical improvement observed within 3 weeks. This allowed steroid taper. Within 12 months of infliximab therapy, he achieved complete clinical remission and returned to his baseline weight and a full oral diet. Sequential endoscopies observed significant regression of previous marked gastrointestinal polyposis, including histological remission on colonic biopsies at 3.5 and 5 years of treatment. He currently remains in remission following 6 years of combination therapy with 5 mg/kg 8 weekly infliximab and azathioprine, and there is ongoing discussion with regard to the benefits and risks of therapy de-escalation. This case demonstrates the effectiveness of infliximab in inducing and maintaining remission in refractory CCS.

Hamartomatous polyposis syndromes (HPS) are a heterogeneous spectrum of diseases that are characterized by diffuse hamartomatous polyps lining the gastrointestinal (GI) tract together with extra-GI manifestations. Classical HPS includes juvenile polyposis syndrome, Peutz-Jeghers syndrome, PTEN hamartoma tumor syndrome and hereditary mixed polyposis syndrome. Patients with HPS have a higher risk of GI and extra-GI malignancies than the general population, although the underlying mechanisms remain unclear and are obviously different from the carcinogenesis of classical adenocarcinoma and colitis-associated malignancy. In this review we aimed to clarify the risks, possible mechanism and endoscopic surveillance of HPS-associated GI malignancies.

Background: Cronkhite-Canada syndrome (CCS), chronic enteropathy associated with SLCO2A1 gene (CEAS), and intestinal Behçet’s disease (BD) are classified as intractable intestinal disorders in Japan. However, the national prevalence of these diseases remains unknown. We performed a nationwide survey to estimate the patient numbers and prevalence rates of these diseases throughout Japan in 2017. Methods: We conducted a mail-based survey targeting hospitals across Japan to estimate the annual numbers of patients with CCS, CEAS, and intestinal BD in 2017. Using a stratified random sampling method, we selected 2,979 hospital departments and asked them to report the number of patients who met specific diagnostic criteria. The total number of patients for each disease was estimated by multiplying the reported numbers by the reciprocal of the sampling rate and response rate. The corresponding prevalence rates per 1,000,000 population were calculated based on the mid-year population of Japan in 2017. Results: The overall survey response rate was 68.1% (2,029 departments). The estimated numbers of patients with CCS, CEAS, and intestinal BD were 473 (95% confidence interval [CI], 357–589), 388 (95% CI, 289–486), and 3,139 (95% CI, 2,749–3,529), respectively; the prevalence rates per 1,000,000 population were 3.7 (male: 4.0; female: 3.5), 3.1 (male: 3.0; female: 3.1), and 24.8 (male: 24.5; female: 25.0), respectively. The male-to-female ratios were 1.10, 0.94, and 0.93 for patients with CCS, CEAS, and intestinal BD, respectively. Conclusions: Estimates of the national prevalence of CCS, CEAS, and intestinal BD in Japan were generated and found to be higher than those previously reported.

Background: Cronkhite-Canada syndrome (CCS) is a rare non-inherited disease characterized by extensive gastrointestinal polyposis and ectodermal dysplasia. Its etiology still remains indefinite to us. Currently, the diagnosis is mainly based on typical clinical manifestations and endoscopic features. However, there is a lack of these information from Chinese CCS patients. Our study was to investigate the clinical and endoscopic characteristics of Chinese CCS patients. Methods: This retrospective study was conducted in 103 Chinese CCS patients (102 cases from literature and 1 case from our department). Their clinical and endoscopic data were collected, and statistical analyses were performed. Results: 1) In Chinese population, people aged 50-70 years (62.62%) had a high incidence of CCS, and the ratio of male-to-female was 2.68:1. 2) The diverse range of gastrointestinal (GI) manifestations were observed in all the patients, and the most common symptoms were weight loss (98.80%) and loss of appetite (93.94%). Almost all the patients had at least one symptom of ectodermal dysplasias. 3) All CCS patients presented multiple polyps in the GI tract except esophagus. The size of polyps varied from 0.5 cm (88.64%) to 0.6-1.0 cm (81.82%) . The polyps were various in shapes, the most of them were nodular polyps (58.14%) ,what’s more,the sessile polyps were the most common(90.24%). Congestion, edema and erosion were very common on the surface of polyps (96.83%) and the surrounding mucosa (85.71%) . 4) The common pathological features of polyps were hyperplastic polyps (49.25%) and tubular adenomatous polyps (44.78%). There is only 5.97% cancer reported. Conclusions: middle-aged and elderly people are the high-risk group; various gastrointestinal symptoms are observed in Chinese patients; the typical endoscopic finding is multiple small sessile polyps; these gastrointestinal polyps has a chance of malignant potential. Long-term endoscopic surveillance and follow-up are recommended for the CCS patients in China.

A 47-year-old man presented with dysgeusia, anorexia, and diarrhea. An endoscopic evaluation showed widespread gastrointestinal nodular inflammation and polyps. The pathological findings were consistent with Cronkhite-Canada Syndrome (CCS). Prednisolone therapy resulted in clinical improvement. However, CCS relapse complicated with gastric obstruction was observed during drug tapering. Although his symptoms disappeared after the reintroduction of steroids, he developed membranous nephritis. Additional cyclosporine A (CyA) treatment dramatically improved his proteinuria and residual gastrointestinal polyposis. The clinical symptoms resolved with steroid treatment, while CyA was effective for both CCS lesions and membranous nephropathy. CyA might therefore be a potential treatment option for CCS associated with membranous nephropathy.

Das Cronkhite-Canada-Syndrom (CCS) ist eine seltene, nicht erbliche Erkrankung, die durch multiple Polypen des Gastrointestinaltrakts, Alopezie, Hyperpigmentierungen der Haut sowie Gewichtsverlust und Diarrhoen gekennzeichnet ist. Wir berichten uber den Fall eines 80-jahrigen Patienten mit CCS, der sich mit seit drei Monaten bestehendem Gewichtsverlust, Diarrhoen und dystrophen Veranderungen der Fingernagel stationar vorstellte. Im ambulanten Bereich waren bereits eine Osophagogastroduodenoskopie und Koloskopie durchgefuhrt worden. Hier hatten sich ein Polypenbefall der Magenschleimhaut und eine unklare generalisierte Kolitis gezeigt. Die Einweisung erfolgte aufgrund zunehmender klinischer Verschlechterung sowie eines weiteren Gewichtsverlusts. In der endoskopischen Diagnostik stellte sich eine ungewohnliche kontinuierliche Ileopankolitis sowie eine polypoid veranderte Schleimhaut des Magens dar. Histomorphologisch ergab sich das Bild hyperplastischer Polypen mit ausgepragtem umgebendem Stromaodem. Zusammen mit den ektodermalen Veranderungen wurde die Diagnose eines CCS gestellt und eine Therapie mit Steroiden, parenteraler Ernahrung und Protonenpumpeninhibitoren begonnen. Im weiteren Aufenthalt erfolgte die Erstdiagnose einer mittelgradig eingeschrankten linksventrikularen Pumpfunktion. Der Patient musste aufgrund einer verlangerten QTc-Zeit passager intensivmedizinisch uberwacht werden. Im Follow-up drei Monate spater zeigte der Patient ein gutes klinisches und endoskopisches Ansprechen auf die medikamentose Therapie mit Sistieren der Diarrhoen, Gewichtszunahme von 8 kg und Nachwachsen der Fingernagel sowie der Kopfbehaarung. Die linksventrikulare Pumpfunktion blieb jedoch auch unter Therapie weiterhin eingeschrankt.

Serrated polyposis syndrome (SPS) can transform to malignant lesions through the sessile serrated pathway and traditional serrated pathway. These pathways may cause rapid neoplastic progression compared to the adenoma-carcinoma sequence, which may cause interval colorectal cancer. The authors experienced a case of SPS with a synchronous colon adenocarcinoma that was treated with an endoscopic mucosal resection. In pathology reviews, other parts of the adenocarcinoma showed sessile serrated adenoma. Therefore, patients with SPS have a potential for malignant transformation, highlighting the need for strict colonoscopy surveillance starting at the time of SPS diagnosis.

Post-polypectomy syndrome is a rare complication of polypectomy with electrocautery and is characterized by a transmural burn of the colon wall. Patients typically present within 12 hours after the procedure with symptoms mimicking colonic perforation. We present the case of a 45-year-old female who developed abdominal pain seven hours after colonoscopy during which polypectomy was performed using electrocoagulation. CT imaging of the abdomen revealed circumferential thickening of the wall of the colon without evidence of free air. The patient was treated conservatively as and had resolution of his pain over the following days. Recognition of the diagnosis and understanding of the treatment are important to avoid unnecessary exploratory laparotomy or hospitalization.

BackgroundJuvenile polyposis syndrome (JPS) is a rare disorder characterized by the presence of multiple juvenile polyps in the gastrointestinal tract, and germline mutations in SMAD4 or BMPR1A. Due to its rarity and complex clinical manifestation, misdiagnosis often occurs in clinical practice.Case presentationA 42-year-old man with multiple pedunculated colorectal polyps and concomitant rectal adenocarcinoma was admitted to our hospital. His mother had died of colon cancer. He was diagnosed with familial adenomatous polyposis (FAP) and underwent total proctocolectomy and ileal pouch anal anastomosis. Two polyps were selected for pathological examination. One polyp had cystically dilated glands with slight dysplasia. The other polyp displayed severe dysplasia and was diagnosed as adenoma. Three years later, his 21-year-old son underwent a colonoscopy that revealed more than 50 pedunculated colorectal juvenile polyps. Both patients harbored a germline pathogenic mutation inBMPR1A. Endoscopic resection of all polyps was attempted but failed. Finally, the son received endoscopic resection of polyps in the rectum and sigmoid colon, and laparoscopic subtotal colectomy. Ten polyps were selected for pathological examination. All were revealed to be typical juvenile polyps, with cystically dilated glands filled with mucus. Thus, the diagnosis of JPS was confirmed in the son. A review of the literatures revealed that patients with JPS can sometimes have adenomatous change. Most polyps in patients with JPS are benign hamartomatous polyps with no dysplasia. A review of 767 colorectal JPS polyps demonstrated that 8.5% of the polyps contained mild to moderate dysplasia, and only 0.3% had severe dysplasia or cancer. It is difficult to differentiate juvenile polyps with dysplasia from adenoma, which could explain why juvenile polyps have been reported to have adenomatous changes in patients with JPS. Therefore, patients with JPS, especially those with concomitant dysplasia and adenocarcinoma, might be easily diagnosed as FAP in clinical practice.ConclusionsJuvenile polyp with dysplasia is often diagnosed as adenoma, which might lead to the misdiagnosis of JPS as FAP. The differential diagnosis of JPS versus FAP, should be based on comprehensive evaluation of clinical presentation, endoscopic appearance and genetic investigations; not on the presence or absence of adenoma.

International audience; Purpose: Juvenile polyposis syndrome (JPS) is a rare, autosomal-dominantly inherited cancer predisposition caused in approximately 50% of cases by pathogenic germline variants in SMAD4 and BMPR1A. We aimed to gather detailed clinical and molecular genetic information on JPS disease expression to provide a basis for management guidelines and establish open access variant databases.Methods: We performed a retrospective, questionnaire-based European multicenter survey on and established a cohort of SMAD4/BMPR1A pathogenic variant carriers from the medical literature.Results: We analyzed questionnaire-based data on 221 JPS patients (126 kindreds) from ten European centers and retrieved literature-based information on 473 patients. Compared with BMPR1A carriers, SMAD4 carriers displayed anemia twice as often (58% vs. 26%), and exclusively showed overlap symptoms with hemorrhagic telangiectasia (32%) and an increased prevalence (39% vs. 13%) of gastric juvenile polyps. Cancer, reported in 15% of JPS patients (median age 41 years), mainly occurred in the colorectum (overall: 62%, SMAD4: 58%, BMPR1A: 88%) and the stomach (overall: 21%; SMAD4: 27%, BMPR1A: 0%).Conclusion: This comprehensive retrospective study on genotype-phenotype correlations in 694 JPS patients corroborates previous observations on JPS in general and SMAD4 carriers in particular, facilitates recommendations for clinical management, and provides the basis for open access variant SMAD4 and BMPR1A databases.

Background: Juvenile polyps (JPs) are the most common gastrointestinal polyps diagnosed in children. There is paucity of evidence differentiating polyp burden groups and the presence and significance of neoplastic changes. Methods: A retrospective chart review of patients, ages birth through 18 years with nonsyndromic JPs was performed from 2003 to 2017. Abstracted data included basic demographics, age, clinical presentation, colonoscopy findings, and pathology report. Slides of polyps with neoplasia were reviewed by a pathologist. Results: A total of 213 subjects underwent 326 procedures and 435 polypectomies. Subjects with positive family history, positive gene mutations, or numerous (>10) polyps were excluded. Groups were defined by polyp number (1, 2–4, 5–10). Polyp recurrence on repeat colonoscopy was significantly related to polyp burden (1 polyp: 1.5%/2–4 polyps 19.2%/5–10 polyps 82.6%: P

Patient: Female, 49-year-old Final Diagnosis: Juvenile polyposis syndrome Symptoms: Anemia Medication:— Clinical Procedure: Surgery Specialty: Gastroenterology and Hepatology • Genetics Objective: Rare disease Background: Juvenile polyposis syndrome is an uncommon, autosomal-dominant hereditary disease that is distinguished by multiple polyps in the stomach or intestinal tract. It is associated with a high risk of malignancy. Pathogenic variants in SMAD4 or BMPR1A account for 40% of all cases. Case Report: A 49-year-old woman underwent esophagogastroduodenoscopy because of exacerbation of anemia. She had numerous erythematous polyps in most parts of her stomach. Based on biopsy findings, juvenile polyposis syndrome (JPS) was suspected morphologically, but there was no evidence of malignancy. Colonoscopy showed stemmed hyperplastic polyps and an adenoma; video capsule endoscopy revealed no lesions in the small intestine. After preoperative surveillance, laparoscopic total gastrectomy with D1 lymph node dissection was performed to prevent malignant transformation. The pathological diagnosis was juvenile polyp-like polyposis with adenocarcinoma. In addition, a germline pathogenic variant in the SMAD4 gene was detected with genetic testing. Conclusions: JPS can be diagnosed with endoscopy and genetic testing. Further, appropriate surgical management may prevent cancer-related death in patients with this condition.

Cronkhite-Canada syndrome (CCS) is a rare polyposis disorder accompanied by alopecia and onychodystrophy. A 63-year-old man with a history of CCS and repeated embolism developed progressive thrombocytopenia and mild anemia. Laboratory testing, a bone marrow examination, and magnetic resonance imaging of the spine resulted in a diagnosis of concurrent aplastic anemia (AA). Paroxysmal nocturnal hemoglobinuria (PNH)-type cells were detected in a peripheral blood specimen. In addition, human leukocyte antigen (HLA) included DRB1*15:01 and DRB1*15:02. Mesalazine was discontinued in consideration of possible drug-induced pancytopenia. Immunosuppressive therapy ameliorated both the gastrointestinal symptoms of CCS and pancytopenia. A common autoimmune abnormality might underlie both CCS and AA.

Mutations of the SMAD4 gene can result in a distinct syndrome with combined clinical features of both juvenile polyposis syndrome (JPS) and hereditary hemorrhagic telangiectasia (HHT). Even though it is known that patients with the overlap syndrome are at increased risk for colorectal malignancies and bleeding, the outcomes of this patient population have not been extensively studied. Retrospective study aiming to describe the phenotype and clinical outcomes of patients with genetically confirmed JP–HHT combined syndrome in a single large tertiary center in North America. A total of 22 patients were identified, the majority females (59%) with a median age diagnosis at 24 years. Polyps were more commonly seen in the lower gastrointestinal (GI) tract, and tubular adenomas were seen in 50%. Epistaxis and pulmonary arteriovenous malformations (AVM) were the most common manifestations of HHT, with a median Curacao score of 3 [1–4]. Hospitalization for gastrointestinal bleeding and cerebrovascular events occurred at a rate of 28% and 4%, respectively. Two patients had GI malignancies, one rectal and one small bowel adenocarcinoma. Overall mortality was 14%. Patients with the combined JP–HHT syndrome remain at risk for life-threatening vascular complications and gastrointestinal malignancies; close follow-up is necessary to minimize morbidity and mortality in this patient population.

Introduction Hamartomatous polyposis syndromes (HPS) are rare autosomal-dominant inherited disorders associated with gastrointestinal (GI) tract and other cancers. HPS include Peutz-Jeghers syndrome (PJS), juvenile polyposis syndrome (JPS), and phosphatase and tensin homolog hamartomatous tumor syndromes (PHTS). Diagnosis, management, and outcome prediction of HPS pose a clinical challenge. To characterize genotype, phenotype, histology and outcomes of individuals with HPS. Methods A retrospective cohort study (2004-2017) of consecutive patients that were clinically diagnosed with HPS that visited a specialized GI oncology clinic. Demographic, clinicopathological, and genetic data were obtained from medical records. Results Fifty-two individuals from 34 families were included. Common clinical manifestations were GI bleeding (40% JPS, 23% PJS, and 25% PHTS) and bowel obstruction (46.15% PJS and 11.4% JPS). Twenty patients (38.4%) underwent surgery, 5 of whom required multiple procedures. Higher polyp burden was associated with the need for surgery (P = 0.007). Polyp histology varied widely with 69.2% of patients exhibiting histology different from the syndrome hallmark. GI cancer history was positive in 65%, 40%, and 50% of JPS, PJS, and PHTS families, respectively. Five (9.6%) patients developed cancers (one patient each had small bowel-1, colon-1, and thyroid-1, one patient had both small bowel adenocarcinoma and breast cancer, and one had both breast cancer and liposarcoma). Twenty (38.4%) patients tested positive for STK11, PTEN, SMAD4, BMPR1A, or AKT1 mutations: Sanger sequencing and multi-gene next generation sequencing panels detected mutations in 40.9% and 100% of tested cases, respectively. Discussion HPS patients present versatile phenotypes with overlapping clinical and histological characteristics. Polyp burden is associated with the need for surgery. Next-generation sequencing increases mutation detection.

Juvenile polyposis syndrome is a rare autosomal-dominant disorder characterized by multiple hamartomatous polyps in the gastrointestinal tract. It is associated with an increased risk of gastrointestinal cancer. We report the case of a 49-year-old woman presenting with proximal muscle weakness, weight loss, severe anemia, and melena. One year before, the diagnosis of a "fundic gland polyposis" was presumed after endoscopic evaluation for iron deficiency anemia had shown numerous polyps limited to the gastric mucosa. On admission, the diagnosis of dermatomyositis was made based on laboratory results with a marked elevated creatine kinase as well as the presence of characteristic clinical findings and muscle histology. Upper endoscopy revealed multiple pedunculated, edematous polyps in the stomach without apparent cancerous lesions intraluminally. Infiltration of the muscular layer was not detectable on endoscopic ultrasound. Histopathological examination of the polyps showed smooth outer surfaces and multiple dilated cystic glands, consistent with hamartomatous juvenile-type polyps. Magnetic resonance imaging revealed a peritoneal mass close to the greater curvature of the stomach, which was identified as a poorly differentiated adenocarcinoma by laparoscopic sampling. Immunohistochemical analysis of resected polyps was remarkable for a loss of SMAD4 expression, a finding that is very commonly observed in patients with gastric juvenile polyposis syndrome. Despite initial treatment response to glucocorticoids and chemotherapy, the patient died 5 months later due to progressive illness. Patients with gastric juvenile polyposis and SMAD4 mutations are at a high risk of developing gastric cancer; hence, early gastrectomy should be considered.Das juvenile Polyposis-Syndrom ist eine seltene autosomal-dominant erbliche Erkrankung, die durch multiple hamartomatöse Polypen im Gastrointestinaltrakt gekennzeichnet ist. Das Krankheitsbild ist mit einem erhöhten Risiko für die Entstehung gastrointestinaler Malignome assoziiert. Wir berichten über eine 49-jährige Patientin, die sich mit proximal betonter Muskelschwäche, Gewichtsverlust, Anämie und Meläna in unserer Klinik vorstellte. Ein Jahr zuvor hatte sich bei der endoskopischen Abklärung einer Eisenmangelanämie ein auf die Magenschleimhaut beschränkter Polypenbefall gezeigt, der als „Drüsenkörperzystenpolyposis“ interpretiert wurde. Bei deutlich erhöhter Kreatinkinase sowie passender Symptomatik und Histologie wurde die Diagnose einer Dermatomyositis gestellt. In der Gastroskopie zeigten sich multiple gestielte ödematöse Polypen ohne Hinweise auf eine eindeutig maligne intraluminale Raumforderung und ohne endosonographischem Anhalt auf wandinfiltrierendes Wachstum. Histologisch waren die untersuchten Polypen mit ihrer glatten Oberfläche und multiplen dilatierten Drüsenstrukturen vereinbar mit hamartomatösen juvenilen Polypen. Kernspintomografisch stellte sich in Nachbarschaft zur großen Magenkurvatur eine peritoneale Raumforderung dar, die nach laparoskopischer Probenentnahme als Adenokarzinom identifiziert wurde. Die immunhistochemische Untersuchung resezierter Polypen ergab eine fehlende SMAD4-Expression, was eine sehr häufige Veränderung bei Patienten mit juvenilem Polyposis-Syndrom des Magens darstellt. Nach initialem Therapieansprechen auf Glukokortikoide und Chemotherapie verstarb die Patientin fünf Monate später an ihrer progredienten Erkrankung. Patienten mit gastraler juveniler Polyposis und SMAD4-Mutation haben ein hohes Malignomrisiko, weshalb eine frühe Gastrektomie erwogen werden sollte.

Background Cronkhite-Canada syndrome is a rare disease of unknown etiology and the optimal treatment for this syndrome is unknown. Case presentation We present the case of a man who at the age of 66.0 years was diagnosed with Cronkhite-Canada syndrome (CCS). In addition to watery diarrhea, alopecia, and a complete loss of toenails and fingernails, the patient had been suffering from dysgeusia and rapid weight loss of more than 10.0 kg within a few months. The patient had recently incurred a distal radius fracture. During the initial endoscopy an extensive polyposis of the stomach and jejunum was found. The diagnosis of CCS was made and after initiation of a steroid therapy his diarrhea improved immediately. A discontinuation of the steroid therapy was not possible and mesalazine (1000 mg t.i.d.) was added to prednisolone (10.0 mg/d). This therapy led to a remission within 6.0 months with weight gain and normalization of serum albumin levels. The prednisolone dose was reduced to 7.5 mg/d. During the following year, the steroids could be further reduced and nails had regrown again. Within three years, all polyps had disappeared and the steroid therapy was finished while the dosage of mesalazine was reduced in a stepwise fashion. Four years later, the mesalazine was stopped and more than 14.0 years after the initial diagnosis the patient is still in complete remission without any treatment. Conclusion The optimal treatment for CCS is unknown. In our case, the initial combination therapy of corticosteroids plus mesalazine followed by a mesalazine monotherapy has led to a remarkable long-lasting remission with complete resolution of all intestinal polyps.

A 52-year-old man with recurrent epistaxis and palpebral conjunctival telangiectasia visited our hospital for a follow-up checkup for gastrointestinal polyposis. At 48 years of age, he underwent Y-graft replacement for an abdominal aortic aneurysm. Arteriovenous malformation was detected in his lungs, and a genetic test revealed an SMAD4 mutation. Eventually, he was diagnosed with juvenile polyposis-hereditary hemorrhagic telangiectasia (JP-HHT) syndrome. In addition, fatty degeneration of the left ventricle and a coronary aneurysm were detected. This is the first report suggesting the possibility of an association between these manifestations and JP-HHT due to SMAD4 mutations. Examining cardiovascular disorders in JP-HHT patients is imperative.

Molecular and Cellular Pediatrics 8, 7 (2021). doi:10.1186/s40348-021-00117-9, Published by Springer Open, Berlin

Juvenile polyposis syndrome (JPS) and hereditary haemorrhagic telangiectasia (HHT) are rare autosomal dominant diseases, where symptoms manifest at childhood. A 32-year-old man with no family history of JPS or HHT with SMAD4 gene mutation who developed signs and symptoms only at the age of 32, when he was an adult. In this article, we highlight the steps taken to diagnose this rare pathology, explain its pathophysiology and management.

Rationale: Juvenile polyposis syndrome (JPS) is a rare genetic gastrointestinal disorder with hidden and variable clinical features. Early detection is crucial for good prognosis. Patient concerns: A 20-year-old female went to hospital for fever, and was unexpectedly diagnosed as JPS during treatment. She reported no clinical signs or family history of JPS. Diagnosis: Blood routine examination on hospital admission suggested a moderate anemia. Bone marrow cytology and leukemia fusion gene test were performed to rule out leukemia. Other examinations including ultrasound and computed tomography were also conducted for differential diagnosis. Further electronic colonoscopy identified more than 20 pedicle polyps located at her ileocecum and rectum. Mutation analysis detected a novel de novo pathogenic variant, c.910C>T (p.Gln304Ter) within bone morphogenetic protein receptor type 1A gene, establishing the diagnosis of JPS. Interventions: The patient was treated with endoscopic interventions. We also provided a genetic counseling for this family. Outcomes: The patient's polyps were removed, some of which already had adenomatous changes. The patient received surveillance of hereditary colorectal cancer according to guidelines. Lessons: Variable features and lack of family history probably lead to a great underestimation of potential JPS population. It is recommended to perform genetic testing by a multigene panel in individuals who have suspected symptoms of polyposis.

Multiple lymphomatous polyposis (MLP) is a rare condition, described in the literature as a presentation of extranodal mantle cell lymphoma. We report a rare case of follicular lymphoma presenting as MLP in a young woman with a short history of haematochezia who underwent colonoscopy. Immunohistochemistry on colonic biopsies confirmed follicular lymphoma. Microscopic examination found an extensive and dense lymphoid infiltrate, which demonstrated a follicular growth pattern. The neoplastic cells were positive with BCL2, BCL6, CD10 and CD20, and were negative with CD3, CD5, Cyclin D1 and SOX11. CT staging showed disseminated lymphadenopathy and the patient was commenced on chemotherapy. Endoscopic evaluation and histopathological analysis are vital for the accurate diagnosis of MLP. Our case demonstrates that follicular lymphoma should be considered as a differential, as not all cases of diffuse colonic MLP are related to mantle cell lymphoma. This distinction must be made to provide the best clinical management for the patient.

ispartof: GASTROINTESTINAL ENDOSCOPY vol:92 issue:5 pages:1141-1142 ispartof: location:United States status: published

Background Juvenile polyposis syndrome (JPS) is a rare autosomal dominant hereditary disorder characterized by the development of multiple distinct juvenile polyps in the gastrointestinal tract with an increased risk of colorectal cancer. Germline mutations in two genes, SMAD4 and BMPR1A, have been identified to cause JPS. Case presentation Here, we report a germline heterozygous missense variant (c.299G > A) in exon 3 BMPR1A gene in a family with juvenile polyposis. This variant was absent from the population database, and concluded as de novo compared with the parental sequencing. Further sequencing of the proband’s children confirmed the segregation of this variant with the disease, while the variant was also predicted to have damaging effect based on online prediction tools. Therefore, this variant was classified as likely pathogenic according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Conclusions Germline genetic testing revealed a de novo germline missense variant in BMPR1A gene in a family with juvenile polyposis. Identification of the pathogenic variant facilitates the cancer risk management of at-risk family members, and endoscopic surveillance is recommended for mutation carriers.

A 41-year-old woman with irritable bowel syndrome symptoms presented for colonoscopy after her mother was diagnosed with multiple juvenile colon polyps positive for Bone morphogenic protein receptor type-1A ( BMPR1A ) mutation and subsequently colon cancer at age 64. Colonoscopy revealed multiple

Juvenile polyposis syndrome (JPS) and hereditary hemorrhagic telangiectasia (HHT) are both relatively rare hereditary disorders. Some patients with the SMAD4 gene mutation develop both JPS and HHT, a condition termed JPS-HHT. We herein report a case of childhood-onset JPS-HHT. At nine years old, the patient underwent colonoscopy under suspicion of Crohn’s disease, which revealed multiple polyps. A genetic analysis for familial adenomatous polyposis and Peutz-Jeghers syndrome found no mutations. After several years, extraintestinal manifestations, such as repeated epistaxis and several telangiectasias in the upper palate and stomach, were identified, which led to the performance of gene mutation analysis for SMAD4. As a result, a missense mutation in exon 8, codon 361 from arginine to cysteine (c.1081 C>T) was found. Based on this finding, the patient underwent cerebral magnetic resonance angiography, pulmonary perfusion scintigraphy and thoracoabdominal contrast computed tomography. The examination revealed that she had pulmonary arteriovenous fistulas and arteriovenous malformations in both the liver and right mammary gland. Thus, continuous surveillance for vascular lesions and gastrointestinal cancer is scheduled. Making a precise diagnosis of JPS-HHT can lead to the detection of asymptomatic complications and enable appropriate future disease management.

Background: Osseous metaplasia is considered as a response to insults such as chronic inflammation or mucin extravasation in colorectal polyps.Case report: we report two cases of osseous metaplasia in juvenile (retention) polyps as incidental histopathological findings in a case of rectal juvenile polyposis and a patient with solitary rectal juvenile polyp.Conclusion: Osseous metaplasia can occur in colorectal juvenile polyps and is considered a probable response to mucin extravasation and/or chronic inflammation. The clinical and prognostic significance of osseous metaplasia in these polyps is unknown.

Cronkhite–Canada syndrome is rarely encountered in clinical practice. Notably, most patients with Cronkhite–Canada syndrome exhibit hypoalbuminemia. Because the cause of Cronkhite–Canada syndrome is unknown, no specific treatment method has been established. Here, we describe a 59-year-old woman with Cronkhite–Canada syndrome in whom clinical manifestations were considerably relieved after treatment with prednisone.

Cap-polyposis is a rare benign condition characterized by inflammatory colorectal polyps covered by a "cap" of fibrinopurulent exudate. Mucous diarrhea and rectal bleeding are frequent symtoms. It can be difficult to diagnose and it is necessary to make a differential diagnosis from other entities. Its pathogenesis is unknown and it has a variable clinical course. The optimal treatment has not been established.

Background Development of multiple rib fractures leading to bilateral flail chest in Cronkhite–Canada Syndrome (CCS) has not been reported. Case presentation A 59-year-old man presented with complaints of fatigue, chest pain, respiratory distress and orthopnea requiring ventilatory support to maintain oxygenation. CCS with bilateral anterior and posterior flail chest due to multiple rib fractures (2nd-10th on the right side and 2nd-11th on the left side). He underwent open reduction and anterior and posterior internal fixation using a titanium alloy fixator and a nickel-titanium memory alloy embracing fixator for chest wall reconstruction. He recovered gradually from the ventilator and showed improvement in his symptoms. He gained about 20 kg of weight in the follow up period (6 months after discharge from the hospital). Conclusion CCS is a rare, complex disease that increases the risk of developing multiple rib fractures, which can be successfully treated with open reduction and internal fixation.

Heritable factors account for approximately 35% of colorectal cancer (CRC) risk, and almost 30% of the population in the UK have a family history of CRC. The quantification of an individual’s lifetime risk of gastrointestinal cancer may incorporate clinical and molecular data, and depends on accurate phenotypic assessment and genetic diagnosis. In turn this may facilitate targeted risk-reducing interventions, including endoscopic surveillance, preventative surgery and chemoprophylaxis, which provide opportunities for cancer prevention. This guideline is an update from the 2010 British Society of Gastroenterology/Association of Coloproctology of Great Britain and Ireland (BSG/ACPGBI) guidelines for colorectal screening and surveillance in moderate and high-risk groups; however, this guideline is concerned specifically with people who have increased lifetime risk of CRC due to hereditary factors, including those with Lynch syndrome, polyposis or a family history of CRC. On this occasion we invited the UK Cancer Genetics Group (UKCGG), a subgroup within the British Society of Genetic Medicine (BSGM), as a partner to BSG and ACPGBI in the multidisciplinary guideline development process. We also invited external review through the Delphi process by members of the public as well as the steering committees of the European Hereditary Tumour Group (EHTG) and the European Society of Gastrointestinal Endoscopy (ESGE). A systematic review of 10 189 publications was undertaken to develop 67 evidence and expert opinion-based recommendations for the management of hereditary CRC risk. Ten research recommendations are also prioritised to inform clinical management of people at hereditary CRC risk.

Polyps of the gastrointestinal tract are very common lesions and most frequently sporadic in nature. Some polyp subtypes are associated with rare hereditary polyposis syndromes, including juvenile polyposis syndrome, Peutz-Jeghers syndrome, and Cowden syndrome. However, many sporadic benign lesions of the gastrointestinal tract can mimic some of these syndromic hamartomatous polyps. The role of the surgical pathologist is to raise the possibility of a hereditary condition in case of suggestive polyp histology and to look for clinical information to support the suspected diagnosis. In this review, the clinical presentation and the pathology associated with these rare hamartomatous polyposis syndromes are discussed in an attempt to provide pathologists clues in suggesting one such syndrome on the basis of histologic findings and clinical context. Identification of affected individuals is important because of the increased gastrointestinal and other malignancies. Recently, new adenomatous polyposis syndromes have been discovered, expanding the genetic causes of patient diagnosed with multiple colonic adenomas. By being aware of the clinical phenotype and the tumor spectrum associated with gastrointestinal polyposis syndromes, surgical pathologists can play a critical role in recommending genetic counseling when suspicious of such a diagnosis. This may lead to the identification of a genetic cause and appropriate surveillance of affected family members to screen for associated malignancies.

Background The presence of peripheral circulating tumor cells indicates the possible existence of a tumor in vivo; however, low numbers of circulating tumor cells (CTCs) can be detected in peripheral blood of healthy individuals as well as patients with benign tumors. It is not known whether peripheral CTC counts differ between patients with benign colorectal disease and those with colorectal cancer. Methods Comparative analysis of preoperative peripheral circulating tumor cells counts was completed in patients with benign colorectal disease (colorectal polyps) and non-metastatic cancer of the colon and rectum. Results The results of this analysis showed that patients with colorectal cancer had higher CTC counts than patients with colorectal polyps (3.47 ± 0.32/3.2 ml vs 1.49 ± 0.2/3.2 ml, P

The risk of malignant tumors developing in association with juvenile polyposis syndrome (JPS) was evaluated to explore the optimal treatment for this rare disease. We reviewed the data on JPS cases reported in Japan between January, 1971 and March, 2016. A total of 171 cases were evaluable. Of these 171 patients, 83 (48.5%) were female and the median age at diagnosis was 28 years (range 1–80 years). The polyps were located in the stomach alone (n = 62; 36.3%), in the stomach and intestine (n = 47; 27.4%), or in the colorectum alone (n = 62; 36.3%). The sites of malignant tumors were the stomach (n = 31), colorectum (n = 29), small intestine (n = 2), breast (n = 1), and thyroid (n = 1). The lifetime risk (at 70 years) of any malignant tumor was 86.2%. The lifetime risk of gastric cancer was 73.0% and that of colorectal cancer was 51.1%. The risk of these cancers developing was dependent on the type of polyp distribution. Long-term surveillance of the stomach and colorectum based on the phenotype of JPS seems a reasonable approach to monitor these patients for the development of malignant tumors.