Question: A 29-year-old woman of Middle Eastern descent presented to our outpatient clinic with a history of progressive abdominal pain spanning >6 months, located mostly in the lower left quadrant. Furthermore, the patient reported chronic constipation, paradoxical diarrhea, and malnutrition with a weight loss of >12 kg in 1 year. The clinical examination revealed a generally cachectic young woman with a disproportionally distended abdomen with ubiquitous tenderness with the punctum maximum in the lower left quadrant. The patient reported chronic use of analgesics, mostly opioids, and cannabis. A colonoscopy showed left-sided ulcerative colitis with histologic proof crypt abscesses and submucosal lipomatosis. Magnetic resonance imaging demonstrated pronounced left-sided large bowel distension and massively increased visceral soft tissue surrounding the whole colon, most prominently the sigmoid (Figure A). In infancy, the patient had undergone a metatarsal amputation of both feet owing to severe deformities. In her adolescence, she had a tumorous connective tissue growth removed, having caused immobilization of the left hip joint. In addition, large soft tissue tumors were apparent in the clinical and radiological examination in pleural, intercostal, and paravertebral locations, accompanied by severe scoliosis. The patient had normal cognitive development and no intellectual disability was apparent. Psychiatric evaluation revealed an anxiety disorder. According to patient history, 1 seizure had taken place at an early age. There were no other known family members who exhibited similar symptoms. What is the diagnosis? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. The patient suffers either from Proteus or CLOVES syndrome. Proteus syndrome is an extremely rare condition of progressive asymmetric overgrowth of body parts, epidermal or connective tissue nevi, lipomas, and cranial deformities owing to sporadic somatic mosaicism. Proteus syndrome is associated with mosaic mutation in the AKT1 gene encoding the serine-threonine kinase V-Akt murine thymoma viral oncogene homolog 1.1Cohen M.M. Proteus syndrome review: molecular, clinical, and pathologic features.Clin Genet. 2014; 85: 111-119Crossref PubMed Scopus (89) Google Scholar CLOVES syndrome acronymically stands for congenital lipomatous overgrowth, vascular malformations, epidermal nevi and scoliosis, spinal or skeletal abnormalities. CLOVES syndrome seems to be caused by a mosaic activating mutation in PIK3CA, the gene encoding for the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha. Similar to Proteus syndrome, CLOVES syndrome causes overgrowth and malformations. However, its manifestations are more proportional, less deforming, and usually present already prenatally.2Martinez-Lopez A. Blasco-Morente G. Perez-Lopez I. Herrera-Garcia J.D. et al.CLOVES syndrome: review of a PIK3CA-related overgrowth spectrum (PROS).Clin Genet. 2017; 91: 14-21Crossref PubMed Scopus (69) Google Scholar Importantly, gastrointestinal manifestation is rather atypical for both conditions. Owing to limited information regarding birth and early childhood, a clinical differentiation between CLOVES and Proteus syndromes could not be established in this patient. A previous genetic consultation and sequence analysis of the coding exons of the PTEN gene from whole blood had been normal, making a diagnosis of the group of PTEN hamartoma tumor syndromes (including Proteus-like syndrome) with germline pathogenic PTEN variants, unlikely.3Pilarski R. PTEN hamartoma tumor syndrome: a clinical overview.Cancers. 2019; 11: E844Crossref PubMed Scopus (73) Google Scholar Sequencing of the genes PIK3CA and AKT1 was not desired by the patient. The mass surrounding the colon caused painful obstruction of the gastrointestinal passage. After careful consideration, we recommended an open resection of the colon and the intra-abdominal mass. We performed a laparotomy. Exploration revealed dilation of the entire colon with a diameter of ≤15 cm and hypertrophy of the colonic wall; the rectum was not affected. During dissection of the colon, multiple venous collaterals in the retroperitoneum were apparent, consistent with a diagnosis of Proteus or CLOVES syndrome (vascular malformations are seen in both syndromes). Owing to the dilation and enormous soft tissue mass surrounding the colon, we performed a subtotal colectomy with complete mesocolic excision, formation of a rectal stump, and end-ileostomy. The resected colon measured >120 cm in length and had a weight of >10 kg (Figure B). Histopathological examination showed diffuse tumorous submucosal and subserosal lipomatosis and singular inflammatory fibroid polyps (Figure C). The findings were basically consistent with Proteus syndrome. After a prolonged hospitalization and parenteral feeding, the patient was discharged from the hospital with a normal passage through the ileostomy and a significant improvement in abdominal and gastrointestinal symptoms.
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Apr 19, 2024
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