RESUMO
BACKGROUND: Infantile Juvenile polyposis of infantile (JPI) is a rare and aggressive form of juvenile polyposis syndrome (JPS) typically diagnosed in the first year of life. It often carries a poor prognosis due to chronic gastrointestinal bleeding, protein-losing enteropathy, malnutrition and immune deficiency. CASE PRESENTATION: We report a case of a girl initially presented with pallor at 7 months of age, which progressed to gastrointestinal bleeding and protein-losing enteropathy. Endoscopic examination, which included both upper gastrointestinal endoscopy and enteroscopy, showed diffuse polyposis. Histopathology results indicated the presence of juvenile polyps with no dysplasia in all removed polyps. Genetic testing identified a 2.1 Mb deletion on chromosome 10q23.2q23.31 involving the phosphatase and tensin homolog (PTEN) and bone morphogenetic protein receptor type IA (BMPR1A) genes. Treatment with sirolimus initiated at 10 months of age led to a reduction in the need for blood and albumin infusions, improved patient growth, and quality of life. While the frequency of endoscopic evaluations decreased with sirolimus, regular endoscopic polypectomy every 5 months remained necessary. However, discontinuation of sirolimus resulted in polyp recurrence after 2 months due to pneumonia. CONCLUSION: This case highlights sirolimus treatment can alleviate many complications of JPI, it does not eliminate the need for aggressive polypectomy.
Assuntos
Polipose Intestinal , Sirolimo , Humanos , Feminino , Sirolimo/uso terapêutico , Polipose Intestinal/congênito , Polipose Intestinal/genética , Polipose Intestinal/tratamento farmacológico , Polipose Intestinal/diagnóstico , Lactente , Síndromes Neoplásicas Hereditárias/tratamento farmacológico , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/genética , Imunossupressores/uso terapêutico , PTEN Fosfo-Hidrolase/genéticaRESUMO
Juvenile polyposis syndrome (JPS) is a rare disease characterized by multiple hamartomatous polyps in the gastrointestinal tract, associated with pathogenic variants of BMPR1A and SMAD4. We present the description of SMAD4 mosaicism in a 30-year-old man who had caecum adenocarcinoma, 11 juvenile colon polyps and epistaxis since childhood. We conducted NGS polyposis and CRC panel analysis on DNA extracted from two polyps, revealing a likely pathogenic SMAD4 variant: NM_005359.5:c. 1600C>T, p.(Gln534*). This variant was then identified at a very low frequency on blood and normal colonic tissue, by targeted visualization of previously obtained NGS data. These findings support the presence of a likely pathogenic mosaic SMAD4 variant that aligns with the patient's phenotype. Given the relatively frequent occurrence of de novo SMAD4 mutations, somatic mosaicism could account for a significant proportion of sporadic JPS patients with unidentified pathogenic variants. This case underscores the diagnosis challenge of detecting mosaicism and emphasizes the importance of somatic analyses.
Assuntos
Polipose Intestinal , Mosaicismo , Síndromes Neoplásicas Hereditárias , Proteína Smad4 , Adulto , Humanos , Masculino , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/genética , Sequenciamento de Nucleotídeos em Larga Escala , Polipose Intestinal/congênito , Polipose Intestinal/diagnóstico , Polipose Intestinal/genética , Mutação , Síndromes Neoplásicas Hereditárias/diagnóstico , Síndromes Neoplásicas Hereditárias/genética , Fenótipo , Proteína Smad4/genéticaAssuntos
Telangiectasia Hemorrágica Hereditária , Humanos , Telangiectasia Hemorrágica Hereditária/complicações , Telangiectasia Hemorrágica Hereditária/diagnóstico , Polipose Intestinal/congênito , Polipose Intestinal/diagnóstico , Polipose Intestinal/complicações , Polipose Intestinal/genética , Malformações Arteriovenosas Intracranianas/complicações , Malformações Arteriovenosas Intracranianas/diagnóstico por imagem , Síndromes Neoplásicas Hereditárias/complicações , Síndromes Neoplásicas Hereditárias/genética , Síndromes Neoplásicas Hereditárias/diagnóstico por imagem , Síndromes Neoplásicas Hereditárias/diagnóstico , Adulto , Masculino , Feminino , Angiografia CerebralRESUMO
Constitutional loss of SMAD4 function results in Juvenile Polyposis-Hereditary Haemorrhagic Telangiectasia Overlap Syndrome (JP-HHT). A retrospective multi-centre case-note review identified 28 patients with a pathogenic SMAD4 variant from 13 families across all Scottish Clinical Genetics Centres. This provided a complete clinical picture of the Scottish JP-HHT cohort. Colonic polyps were identified in 87% (23/28) and gastric polyps in 67% (12/18) of screened patients. Complication rates were high: 43% (10/23) of patients with polyps required a colectomy and 42% (5/12) required a gastrectomy. Colorectal cancer occurred in 25% (7/28) of patients, at a median age of 33 years. Pulmonary arteriovenous malformations were identified in 42% (8/19) of screened patients. 88% (23/26) and 81% (17/21) of patients exhibited JP and HHT features respectively, with 70% (14/20) demonstrating features of both conditions. We have shown that individuals with a pathogenic SMAD4 variant are all at high risk of both gastrointestinal neoplasia and HHT-related vascular complications, requiring a comprehensive screening programme.
Assuntos
Polipose Intestinal , Proteína Smad4 , Telangiectasia Hemorrágica Hereditária , Humanos , Proteína Smad4/genética , Telangiectasia Hemorrágica Hereditária/genética , Telangiectasia Hemorrágica Hereditária/patologia , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Polipose Intestinal/genética , Polipose Intestinal/congênito , Polipose Intestinal/patologia , Polipose Intestinal/diagnóstico , Adolescente , Escócia , Síndromes Neoplásicas Hereditárias/genética , Síndromes Neoplásicas Hereditárias/patologia , Síndromes Neoplásicas Hereditárias/diagnóstico , Criança , Mutação , Estudos Retrospectivos , IdosoRESUMO
BACKGROUND: Cronkhite-Canada syndrome (CCS) is a rare, noninherited disease characterized by gastrointestinal polyposis with diarrhea and ectodermal abnormalities. CCS polyps are distributed through the whole digestive tract, and they are common in the stomach and colon but very uncommon in the esophagus. CASE SUMMARY: Here, we present a case of a 63-year-old man with skin hyperpigmentation accompanied by diarrhea, alopecia, and loss of his fingernails. Laboratory data indicated anemia, hypoalbuminemia, hypocalcemia, hypokalemia, and positive fecal occult blood. Endoscopy showed numerous polyps scattered throughout the digestive tract, including the esophagus. He was treated with nutritional support and glucocorticoids with remission of his symptoms. CONCLUSION: Comprehensive treatment led by hormonal therapy can result in partial or full remission of clinical symptoms. Treatment should be individualized for each patient according to their therapy response. Surveillance endoscopy is necessary for assessing mucosal disease activity and detecting malignant transformation.
Assuntos
Endoscopia Gastrointestinal , Polipose Intestinal , Masculino , Humanos , Pessoa de Meia-Idade , Endoscopia Gastrointestinal/efeitos adversos , Glucocorticoides/uso terapêutico , Esôfago/patologia , Polipose Intestinal/complicações , Polipose Intestinal/diagnóstico , Polipose Intestinal/terapia , Diarreia/etiologiaRESUMO
Cronkhite-Canada syndrome (CCS) is an acquired polyposis syndrome with gastrointestinal and extraintestinal manifestations. Given its rarity and lack of standard treatment, diagnosis and treatment are challenging. Steroid therapy and nutritional support are conventional treatments. There is no consensus on management of steroid-refractory cases. Here, we report the diagnosis and treatment course of a 54-year-old Asian male with CCS, whose initial treatment with prednisone 60 mg a day led to partial response and disease flare up during prednisone tapering. The use of infliximab and azathioprine led to promising remission of his symptoms.
Assuntos
Polipose Intestinal , Humanos , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Polipose Intestinal/tratamento farmacológico , Polipose Intestinal/diagnóstico , Polipose Intestinal/patologia , Azatioprina/uso terapêutico , NecroseRESUMO
Juvenile polyposis syndrome is an autosomal dominant syndrome characterised by hamartomatous polyps in the gastrointestinal tract and has a high risk for colon carcinoma. This case explores the presentation of multiple polyps throughout the gastrointestinal tract, located in the stomach, proximal duodenum, colon, rectum and up to the anal canal. The locations and number of these polyps themselves were not typical and the histopathological studies suggested the condition to be an inflammatory fibroid polyp, which is a rare, benign and solitary neoplasm. Prompt and accurate diagnostic modality remains the keystone in the identification and management of such condition which was a limitation in this case as the patient was lost to follow up before a definitive diagnosis was made. Keywords: case reports; children; juvenile polyposis syndrome.
Assuntos
Polipose Intestinal , Síndromes Neoplásicas Hereditárias , Pólipos , Criança , Humanos , Adolescente , Polipose Intestinal/diagnóstico , Polipose Intestinal/patologia , Síndromes Neoplásicas Hereditárias/diagnóstico , Síndromes Neoplásicas Hereditárias/patologia , RetoAssuntos
Polipose Intestinal , Síndromes Neoplásicas Hereditárias , Neoplasias Gástricas , Humanos , Estômago , Endoscopia Gastrointestinal , Síndromes Neoplásicas Hereditárias/diagnóstico , Síndromes Neoplásicas Hereditárias/genética , Polipose Intestinal/diagnóstico , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/terapiaRESUMO
Chronkhite-Canada Syndrome is characterised by diffuse gastrointestinal polyposis, dystrophic changes of the fingernails, cutaneous hyperpigmentation, alopecia, diarrhoea, weight loss, and abdominal pain. This disease is also associated with peripheral neuropathies and autoimmune disorders. Its association with other diseases may cause the polyps to turn into malignant tumours and worsen the condition. The first-line treatment is a combination of prednisone and mesalamine. NSAIDs and antibiotic administration is based on the symptoms and needs of patients. Here, we describe a 51-year-old male who presented to us with abdominal pain and significant weight loss. His physical examination showed dystrophic nails, alopecia and hyperpigmentation. Endoscopy and colonoscopy showed multiple polyps. His manifestations were consistent with Cronkhite-Canada syndrome. We prescribed oral corticosteroids, which improved his condition.
Assuntos
Hiperpigmentação , Polipose Intestinal , Doenças do Sistema Nervoso Periférico , Masculino , Humanos , Pessoa de Meia-Idade , Paquistão , Polipose Intestinal/complicações , Polipose Intestinal/diagnóstico , Polipose Intestinal/tratamento farmacológico , Alopecia/complicações , Hiperpigmentação/etiologia , Hiperpigmentação/complicações , Dor Abdominal/etiologia , Redução de PesoRESUMO
A 27-year-old female presented at 13 weeks' gestation with epigastric pain and anemia requiring blood and iron transfusions but no family history of gastrointestinal malignancy. Upper endoscopy revealed a giant circumferential polyp and associated hyperplastic-appearing polyps in the proximal stomach. Biopsies revealed hyperplasia with lamina propria eosinophils. She was supported with intermittent transfusions until labor was induced at 34 weeks' gestation. Total gastrectomy was performed at seven weeks post-partum. Final pathology revealed multiple hamartomatous polyps without malignancy. Her anemia resolved postoperatively. Genetic testing revealed mutation of the SMAD4 gene and Juvenile Polyposis Syndrome. JPS is caused by germline mutations in the SMAD4 or BMPR1A genes and is characterized by hamartomatous polyps in the gastrointestinal tract. While most polyps are benign, malignant transformation can occur. One should have low threshold to send patients for genetic screening when multiple polyps are found in a young patient, even without family history.
Assuntos
Polipose Intestinal , Humanos , Feminino , Adulto , Polipose Intestinal/complicações , Polipose Intestinal/diagnóstico , Polipose Intestinal/genética , Mutação , Mutação em Linhagem Germinativa , Pólipos Intestinais , Hemorragia Gastrointestinal/etiologia , Proteína Smad4/genéticaRESUMO
INTRODUCTION: Cronkhite-Canada syndrome (CCS) is currently considered to be a non-hereditary disease, which is relatively rare clinically. It is also known as polyposis hyperpigmentation alopecia nail dystrophy syndrome, it is a syndrome characterized by gastrointestinal polyposis and ectodermal changes, the main manifestations are gastrointestinal symptoms, skin pigmentation, alopecia, and hypothyroidism. CASE PRESENTATION: In this paper, the clinical characteristics, diagnosis and treatment of a case of CCS admitted to Huanghe Sanmenxia Hospital were analyzed. In the course of treatment, traditional Chinese medicine was used, but no hormone, and the patient's clinical symptoms were greatly relieved. CONCLUSIONS: CCS is rare, there is no specific treatment, and traditional Chinese medicine may can greatly relieve the clinical symptoms of patients. However, it's still having to be verified by a large sample, multi-center, long-term treatment follow-up studies.
Assuntos
Hiperpigmentação , Polipose Intestinal , Doenças da Unha , Humanos , Polipose Intestinal/complicações , Polipose Intestinal/diagnóstico , Alopecia/terapia , Alopecia/complicações , Hiperpigmentação/etiologia , Hiperpigmentação/terapia , Doenças da Unha/diagnóstico , Doenças da Unha/etiologiaRESUMO
Cronkhite-Canada syndrome(CCS)is a rare non-inherited disease characterized by gastrointestinal polyposis and ectodermal abnormalities. We report a rare case of CCS associated with gastric cancer and gastric outlet obstruction with a review of the literature. A 75-year-old man was admitted because of frequent vomiting and hypoproteinemia. He was diagnosed with CCS due to typical clinical and laboratory findings including alopecia, nail atrophy, hypoproteinemia, and typical gastrointestinal polyposis. Upper endoscopic examination also pointed out a large gastric cancer mainly located in the antrum and the reversible pyloric obstruction caused by the gastric tumor. Biopsy of the tumor revealed tubular adenocarcinoma. Computed tomography demonstrated the dilated duodenum caused by packing of the gastric tumor. 1.5 months after prednisolone therapy, he underwent total gastrectomy with complete resection of the dilated duodenal bulb. Histological examination revealed gastric cancer(pap>tub1)classified into Stage â ¢C. Postoperative course was uneventful and he moved to another hospital. To our knowledge, including the present case, there were 20 reported cases of CCS associated with gastric cancer from Japan(1979-2022). Also, 7 cases of CCS associated with gastric outlet obstruction was reported.
Assuntos
Obstrução da Saída Gástrica , Hipoproteinemia , Polipose Intestinal , Estenose Pilórica , Neoplasias Gástricas , Masculino , Humanos , Idoso , Neoplasias Gástricas/complicações , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/diagnóstico , Obstrução da Saída Gástrica/etiologia , Obstrução da Saída Gástrica/cirurgia , Polipose Intestinal/complicações , Polipose Intestinal/diagnóstico , Polipose Intestinal/patologiaRESUMO
Juvenile polyposis syndrome (JPS) is a rare precancerous condition that confers an increased risk of developing gastrointestinal cancers. The inheritance pattern is autosomal dominant. JPS should be clinically suspected when the other hamartomatous polyposis syndromes are excluded (i.e., Peutz- Jeghers and Cowden), in presence of numerous juvenile polyps in the colorectum or in other GI locations. Among the syndromic features, JPS can present with concomitant extra-intestinal manifestations, above all cutaneous manifestations such as telangiectasia, pigmented nevi, and skeletal stigmata. Pathogenic germline variants of either BMPR1A or SMAD4 cause the syndrome. In JPS a cumulative risk of CRC of 39-68% has been estimated. The oncological risk justifies and imposes prevention strategies that aim at the cancer risk reduction through endoscopic screening, as recommended by international scientific societies. The aim of this review is to summarize clinical and genetic features of JPS and to elucidate the steps of the clinical management from diagnosis to surveillance.
Assuntos
Neoplasias Colorretais , Neoplasias Gastrointestinais , Polipose Intestinal , Síndromes Neoplásicas Hereditárias , Síndrome de Peutz-Jeghers , Neoplasias Colorretais/genética , Humanos , Polipose Intestinal/congênito , Polipose Intestinal/diagnóstico , Polipose Intestinal/genética , Polipose Intestinal/patologia , Síndromes Neoplásicas Hereditárias/diagnóstico , Síndromes Neoplásicas Hereditárias/genética , Síndrome de Peutz-Jeghers/diagnóstico , Síndrome de Peutz-Jeghers/genética , Síndrome de Peutz-Jeghers/patologiaRESUMO
Juvenile polyposis represents an heterogeneous disease as different genetic dominant backgrounds have been evidenced leading to different clinical presentations. It is associated in some patients with a different syndrome, Hereditary Hemorragic Telangiectasia, justifying a complementary and different management. Recent international recommendations help in managing this very rare disease, and this management should probably be restricted to expert centers able to take care of the multiple manifestations and risks of these patients and families. This paper will focus on the poorly known and evaluated aspects of juvenile polyposis, excluding the colonic involvement and epidemiology that are addressed in a different article of this issue.