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2 March 2016 - Case of the Week #380

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Case of the Week #380

Clinical history:
A 42 year old woman presented with a clinical diagnosis of Cowden syndrome. She had clinical stigmata of the disease, and long term constipation. She underwent colonoscopy with biopsy, and subsequently had a panproctocolectomy.

Gross images:

Micro images:

What is your diagnosis?

Diffuse ganglioneuromatosis polyposis in patient with Cowden syndrome

Ganglioneuromas are fully differentiated, benign hamartomatous polyps characterized by an overgrowth of nerve ganglion cells, nerve fibers and supporting stroma. Involvement of the gastrointestinal tract in the absence of a systemic syndrome is rare but has been reported (Dig Dis Sci 2005;50:506, Gastrointestinal Pathology: An Atlas and Text, 2007). Systemic syndromes associated with intestinal ganglioneuromas include endocrine neoplasia type IIB (MEN IIB), neurofibromatosis type 1 (NF1), juvenile polyposis, polyposis coli, tuberous sclerosis and Cowden disease (J Med Case Rep 2012;6:304, J Clin Gastroenterol 1996;22:66, Dis Colon Rectum 2001;44:591). Cowden syndrome is a multisystem disorder with autosomal dominant inheritance caused by a mutation in the PTEN gene. It is characterized by hamartomatous tissue overgrowth and an increased risk of breast, colon, thyroid and endometrial cancer. Cutaneous manifestations include facial trichilemmomas, multiple acral keratoses and storiform collagenomas (Hum Pathol 2012;43:601).

Ganglioneuromas are classified as polypoid ganglioneuroma, ganglioneuromatous polyposis (GP), or diffuse ganglioneuromatosis, depending on the extent of the lesions. In GP, there are typically greater than 20 sessile or pedunculated mucosal or submucosal lesions. Clinical symptoms, if any, include abdominal pain, obstruction, constipation, appendicitis and diarrhea (Turk J Gastroenterol 2012;23:780). There are no distinguishing features on colonoscopy - intestinal ganglioneuromatosis is a microscopic diagnosis.

Gross examination of the colon reveals multiple sessile or pedunculated polyps.

Histopathologic examination shows a hamartomatous collection of ganglion cells, nerve fibers and supporting stroma. The lesional cells are spindled and express S100 protein and glial fibrillary acidic protein (GFAP). Ganglion cells are large and round, and contain prominent nucleoli. They show positive staining with neuron specific enolase (Turk J Gastroenterol 2012;23:780).

Treatment of ganglioneuromas depends on the clinical history; polypectomy is curative for polypoid subgroups, but colectomy may be necessary for polyposis or diffuse forms. Because of the link between polypoid ganglioneuroma and other systemic diseases, patients should be carefully screened for both associated syndromes and malignancies in the colon and other locations, including the thyroid, breast and uterus (J Med Case Rep 2012;6:304).

Discussion by Dr. Jennifer R. Kaley, University of Arkansas for Medical Sciences (USA).