Cowden Syndrome with a Novel GermlinePTENMutation and an Unusual Clinical Course

Abstract

Here, we report a case of Cowden syndrome with an unusual clinical course of late-onset oral papillomatosis and a novel germline PTEN mutation. Cowden syndrome is the most common phosphatase and tensin homolog hamartomatous tumor syndrome. It is characterized by multiple hamartomas in the gastrointestinal tract and mucocutaneous lesions such as trichilemmomas, oral papillomatosis, facial papules, and acral keratoses. Patients with Cowden syndrome have a higher risk of malignancies, especially breast, colon, and thyroid cancers. A 53-year-old female presented with cobblestone-like papillomatous papules on the lower gums that developed 1 year earlier. She had no other mucocutaneous lesions besides oral papillomatosis. Gastrointestinal endoscopy and colonoscopy revealed multiple hamartomas in the stomach and colon. The patient had a history of breast cancer and multinodular goiter diagnosed 4 and 5 years ago, respectively. She was diagnosed with Cowden syndrome and a novel PTEN mutation was confirmed by direct sequencing.

Mucocutaneous manifestations of Cowden's syndrome

“…[6810] The present case report fulfilled the pathognomonic (oral papillomatous lesions and facial cutaneous papules), major (breast cancer) and minor (hamartomatous intestinal polyps, goiter, and fibromas) criteria given by the International Cowden Consortium. CS with various clinical manifestations presents difficulty in diagnosis, and based on its clinical manifestations differential diagnosis includes Bannayan–Riley–Ruvalcaba syndrome, Proteus syndrome, tuberous sclerosis, fragile X syndrome, Heck's disease, Darier's disease, epidermolysis bullosa, Goltz syndrome, and juvenile polyposis syndrome.…”

“…But in 85% of the cases, mutation in the phosphate and tensin homolog (PTEN) tumor suppressor gene also termed as mutated in multiple advanced cancers (MMAC1) on chromosome 10q22-23 was observed. [567] The PTEN protein product is believed to promote cell death and lead to overproliferation of cells, due to the mutation that causes loss of protein function that may result in hamartomatous growths. [5]…”

“…Systemic features include thyroid abnormalities (75% such as benign multinodular goiter, lymphocytic thyroiditis, and adenomas); GI lesions (50% such as multiple intestinal polyps), macrocephaly, genitourinary abnormalities, and malignancies particularly adenocarcinoma of breast (25% to 50%); thyroid cancer (3% to 10%); endometrial cancer (5%–10%); and renal cell carcinoma. [6789] A recent study reported that 6% of CS patients are associated with melanoma. [9] In the present case the patient had multiple intestinal polyps, thyroid abnormalities, and also gave a history of carcinoma of breast, for which she underwent treatment.…”

“…So the International Cowden Syndrome Consortium has proposed operational criteria for the diagnosis of CS in 1996 and it was revised in 2008 by the National Comprehensive Cancer Network given below[6810] [Table 1]. …”

An Overview of Autosomal Dominant Tumour Syndromes with Prominent Features in the Oral and Maxillofacial Region

“…These flesh-coloured firm papules are 1-7 mm in diameter and their multiplicity can produce a cobblestone-like appearance [8,9].…”