April 2008

Fig.4

Fig.5

Diagnosis: Cowden syndrome

Histopathology (facial papule): Lobular proliferation of squamoid cells with peripheral palisading of nuclei (Figs. 4,5). The features resemble the outer root sheath of the hair follicle and are consistent with the diagnosis of a facial trichilemmoma.

Discussion: Cowden syndrome is a multiple hamartoma syndrome characterized by the proliferation of characteristic benign and malignant neoplasia. In 1996, the International Cowden Syndrome Consortium determined the pathognomonic criteria to include the presence of facial trichilemmomas, acral keratoses or other papillomatous lesions, and oral mucosal papillomatosis. Major criteria include a history of breast cancer (seen in between one-third and one-half of all patients), thyroid carcinoma (noted in 5%), macrocephaly (defined as a head circumference greater than the 97th percentile), concomitant Lhermitte-Duclos disease (a.k.a. cerebellar dysplastic gangliocytoma), and endometrical carcinoma. Minor criteria include other thyroid abnormalities (such as goiter), mental retardation, hamartomatous intestinal polyps, fibrocystic disease of the breast, lipomas, fibromas, and genitourinary tumors or malformations.

The syndrome is inherited in an autosomal dominant manner, and is caused by mutations in the PTEN tumor suppressor gene. Over 100 different germline mutations in the gene have been identified, and these mutations can cause various phenotypes including not only Cowden syndrome, but also Bannayan-Riley-Ruvalcaba, Proteus, and Proteus-like syndromes.

The management of Cowden syndrome focuses on screening for malignancy. Clinical breast exams are recommended annually beginning at age 25, with yearly mammograms starting at age 30. Annual physical examination of the thyroid is recommended starting at age 18, with a baseline ultrasound obtained at that time. Endometrial biopsies are recommended beginning at age 35, with annual ultrasounds continuing with the commencement of menopause. Annual urinalysis with cytology is recommended to rule out renal cell carcinoma, and renal ultrasounds are obtained for any family history of renal cancer.

Various modalities have been used for the treatment of facial tricholemmomas, all with varying results, including topical Efudex, oral isotretinoin, curettage, laser ablation, and surgical excision.

References:
1. Bolognia JL, Jorizzo JL, Rapini RP. (2003). Dermatology. London: Mosby.
2. Mallory SB. (2006). An Illustrated Dictionary of Dermatologic Syndromes. (2ndEdition). London and New York: Taylor and Francis.
3. Mallory SB. Cowden Syndrome (Multiple Hamartoma Syndrome). Dermatol Clin. 1995 Jan; 13(1): 27-31.

Presented By: Drs. M. Laurin Council and Debra Scarlett.

Acknowledgements: : Histopathological photos provided by Nathan Walk, M.D.