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The Spectrum of Findings in Cowden Syndrome
Image of the Month The Spectrum of Findings in Cowden Syndrome PETER P. STANICH,* DAWN L. FRANCIS,‡ and SETH SWEETSER‡ *Department of Internal Medicine and ‡Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota
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21-year-old man presented with intermittent, small-volume hematochezia. Physical examination revealed macrocephaly with small facial papules around the nose (Figure A) and oral mucosal papillomas of the gingiva and tongue, giving it a cobblestone-like appearance (Figures B and C). Abdominal examination and laboratory testing were normal. Endoscopy was performed to evaluate the gastrointestinal bleeding. Upper endoscopy revealed whitish, flat elevations in the esophagus (Figure D), with biopsies showing glycogenic acanthosis. There were multiple gastric polyps (Figure E) and a few small polyps in the duodenum. The gastric and duodenal polyps were hyperplastic on microscopic examination. Colonoscopy showed numerous polyps ranging in size from 2 to 6 mm (Figure F) and of different histologic types: hamartomatous polyps of ganglioneuromatous origin (Figure G; arrow on ganglion cell) along with both hyperplastic and adenomatous polyps. A clinical diagnosis of Cowden syndrome (CS) was made on the basis of macrocephaly, mucocutaneous, and gastrointestinal hamartomas. Genetic testing confirmed the diagnosis.
CS is a rare, autosomal-dominant disorder caused by germline mutations in the phosphatase and tensin homolog on chromosome 10 tumor-suppressor gene that manifests with hamartomatous growths involving all 3 embryonic origins. There is considerable heterogeneity in the clinical presentation; however, mucocutaneous lesions are characteristic with multiple facial trichilemmomas (Figure A) and cobblestoning of the oral mucosa owing to papillomatosis (Figure B) being pathognomonic. Glycogenic acanthosis of the esophAcknowledgments The authors thank Schuyler O. Sanderson, MD, Division of Anatomic Pathology, Mayo Clinic, Rochester, MN, for providing the histopathology image. Conflicts of interest The authors disclose no conflicts. © 2011 by the AGA Institute 1542-3565/$36.00 doi:10.1016/j.cgh.2010.07.003 CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2011;9:e2– e3
January 2011
agus occurring in conjunction with colon polyps also is considered diagnostic for CS.1 Polyps of many different histologic types (hamartomatous, hyperplastic, inflammatory, lipomatous, fibromatous, and adenomatous) are found throughout the gastrointestinal tract in up to 85% of CS patients.2 Identifying the characteristic lesions of CS is important to allow for appropriate screening given the increased risk of breast, thyroid, and endometrial malignancies. The risk of gastrointestinal cancers in these patients is not well characterized. It has been suggested that the gastrointestinal adenomas in patients with CS are coincidental, rather than related to the disease.3 However, there is a case report of a CS patient developing metachronous colon carcinomas arising from hamar-
IMAGE OF THE MONTH
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tomatous polyps.4 Given the uncertainty of gastrointestinal cancer risk in CS, there are no specific recommendations for gastrointestinal system screening. References 1. Kay PS, Soetikno RM, Mindelzun R, et al. Diffuse esophageal glycogenic acanthosis: an endoscopic marker of Cowden’s disease. Am J Gastroenterol 1997;92:1038 –1040. 2. Marra G, Armelao F, Vecchio FM, et al. Cowden’s disease with extensive gastrointestinal polyposis. J Clin Gastroenterol 1994;18:42–47. 3. Pilarski R. Cowden syndrome: a critical review of the clinical literature. J Genet Counsel 2009;18:13–27. 4. Bosserhoff AK, Grussendorf-Conen El, Rubben A, et al. Multiple colon carcinomas in a patient with Cowden syndrome. Int J Mol Med 2006;18:643– 647.
A
21-year-old man presented with intermittent, small-volume hematochezia. Physical examination revealed macrocephaly with small facial papules around the nose (Figure A) and oral mucosal papillomas of the gingiva and tongue, giving it a cobblestone-like appearance (Figures B and C). Abdominal examination and laboratory testing were normal. Endoscopy was performed to evaluate the gastrointestinal bleeding. Upper endoscopy revealed whitish, flat elevations in the esophagus (Figure D), with biopsies showing glycogenic acanthosis. There were multiple gastric polyps (Figure E) and a few small polyps in the duodenum. The gastric and duodenal polyps were hyperplastic on microscopic examination. Colonoscopy showed numerous polyps ranging in size from 2 to 6 mm (Figure F) and of different histologic types: hamartomatous polyps of ganglioneuromatous origin (Figure G; arrow on ganglion cell) along with both hyperplastic and adenomatous polyps. A clinical diagnosis of Cowden syndrome (CS) was made on the basis of macrocephaly, mucocutaneous, and gastrointestinal hamartomas. Genetic testing confirmed the diagnosis.
CS is a rare, autosomal-dominant disorder caused by germline mutations in the phosphatase and tensin homolog on chromosome 10 tumor-suppressor gene that manifests with hamartomatous growths involving all 3 embryonic origins. There is considerable heterogeneity in the clinical presentation; however, mucocutaneous lesions are characteristic with multiple facial trichilemmomas (Figure A) and cobblestoning of the oral mucosa owing to papillomatosis (Figure B) being pathognomonic. Glycogenic acanthosis of the esophAcknowledgments The authors thank Schuyler O. Sanderson, MD, Division of Anatomic Pathology, Mayo Clinic, Rochester, MN, for providing the histopathology image. Conflicts of interest The authors disclose no conflicts. © 2011 by the AGA Institute 1542-3565/$36.00 doi:10.1016/j.cgh.2010.07.003 CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2011;9:e2– e3
January 2011
agus occurring in conjunction with colon polyps also is considered diagnostic for CS.1 Polyps of many different histologic types (hamartomatous, hyperplastic, inflammatory, lipomatous, fibromatous, and adenomatous) are found throughout the gastrointestinal tract in up to 85% of CS patients.2 Identifying the characteristic lesions of CS is important to allow for appropriate screening given the increased risk of breast, thyroid, and endometrial malignancies. The risk of gastrointestinal cancers in these patients is not well characterized. It has been suggested that the gastrointestinal adenomas in patients with CS are coincidental, rather than related to the disease.3 However, there is a case report of a CS patient developing metachronous colon carcinomas arising from hamar-
IMAGE OF THE MONTH
e3
tomatous polyps.4 Given the uncertainty of gastrointestinal cancer risk in CS, there are no specific recommendations for gastrointestinal system screening. References 1. Kay PS, Soetikno RM, Mindelzun R, et al. Diffuse esophageal glycogenic acanthosis: an endoscopic marker of Cowden’s disease. Am J Gastroenterol 1997;92:1038 –1040. 2. Marra G, Armelao F, Vecchio FM, et al. Cowden’s disease with extensive gastrointestinal polyposis. J Clin Gastroenterol 1994;18:42–47. 3. Pilarski R. Cowden syndrome: a critical review of the clinical literature. J Genet Counsel 2009;18:13–27. 4. Bosserhoff AK, Grussendorf-Conen El, Rubben A, et al. Multiple colon carcinomas in a patient with Cowden syndrome. Int J Mol Med 2006;18:643– 647.