Multiple Familial Trichoepitheliomas

Authors: Doctor Evangelia Bozi1, Doctor Alexander C. Katoulis Creation date: April 2004

Scientific Editor: Professor Nikolaos G. Stavrianeas

1National University of Athens, 2nd Department of Dermatology and Venereology, “Attikon” Hospital, Athens, Greece

Abstract Keywords Synonyms Definition Epidemiology Etiology Clinical description Diagnostic methods Differential diagnosis Treatment References

Abstract Trichoepithelioma is a benign hamartomatous tumor of the pilosebaceous follicle that may occur either as a nonhereditary solitary lesion or as multiple lesions that are often dominantly inherited. The gene for multiple trichoepitheliomas (MTs) has been mapped to a locus 9p21. MTs may represent a syndrome in which tumors develop from undifferentiated germinative cells of the pilosebaseous-apocrine unit. The exact prevalence is unknown. MTs appear to be rather uncommon. They most commonly appear in early childhood or at puberty. They appear as multiple, skin-colored to pink, firm, papulonodular lesions, which are located mainly on the face or, occasionally, on the scalp, the neck and the upper trunk. Trichoepitheliomas gradually increase in number and in size, producing significant cosmetic disfigurement. Malignant transformation to basal cell carcinoma (BCC) is rare and occurs late in the course of the disease. However, BCC associated with MTs is commonly reported. Diagnosis is based on history, clinical examination and it is confirmed by skin biopsy. Treatment is difficult. Surgical excision and various destructive modalities have been tried with occasionally good results. All methods carry significant risk of side-effects, most importantly scarring. Recurrences are common. Long-term vigilance and follow up for BCC development is warranted.

Keywords Hamartoma of pilosebaceous follicle, skin tumor, locus 9p21, locus 16q12-13, epitelioma adenoids cysticum, basal cell carcinoma, Brooke-Spiegler syndrome

Synonyms Trichoepithelioma may occur either as a Multiple benign cystic epithelioma nonhereditary solitary lesion or, less commonly, as multiple lesions (multiple trichoepitheliomas) Definition that are often dominantly inherited. Trichoepithelioma is a benign hamartomatous tumor of the pilosebaceous follicle that usually Epidemiology appears in childhood or early adolescence and The exact prevalence is unknown. Multiple occurs on the face or, less often, on the scalp, trichoepitheliomas (MTs) appear to be rather neck and trunk. In 1892, Brooke originally uncommon. They most commonly appear in described it as epithelioma adenoides cysticum early childhood or at puberty. Both sexes are and Fordyce as multiple benign cystic equally affected. There is no racial epithelioma. predisposition.

Bozi E, Katoulis AC. Multiple Familial Trichoepitheliomas. Orphanet Encyclopedia. April 2004. http://www.orpha.net/data/patho/GB/uk- Trichoepithelioma.pdf 1

Etiology Diagnostic methods MTs are often dominantly inherited. The gene for Diagnosis is based on history, clinical MTs has been mapped to a locus on examination and it is confirmed by skin biopsy. If chromosome 9p21 (Harada H et al, 1996). necessary, genetic studies may be used to The Brooke-Spiegler syndrome, which is detect the abnormalities in band 9p21. Horn characterized by the development of multiple cysts are the characteristic histologic feature of trichoepitheliomas, cylindromas and, trichoepithelioma. They consist of a fully occasionally, spiradenomas, is also inherited as keratinized inner shell surrounded by strands an autosomal dominant trait. The responsible and solid nests of flattened basophilic cells gene has been mapped to chromosome 16q12- resembling the cells of BCC. Adenoid structures 13 (Hu G et al, 2003). may be present and calcification of cystic It is possible that these two separate genes material and foreign body reaction to it may be influence each other to develop different tumors. seen. Occasionally, primitive hair papillae and Current data suggest that a defective tumor even hair shaft-like structures may be observed, suppressor gene may be involved. indicating a high degree of differentiation. A MTs may represent a syndrome in which tumors fibrous stroma surrounds the horny cysts. develop from undifferentiated germinative cells Histological differentiation from keratotic BCC of the pilosebaceous-apocrine unit (Clarke J, may be difficult (Odom RB et al, 2000). 2002). Mutations in genes regulating proliferation and differentiation of putative stem cells of the Differential diagnosis pilosebaceous-apocrine unit would give rise to Differential diagnosis includes BCC, other different combinations of adnexal skin tumors, as appendageal tumors, syringoma and well as to other neoplasms. Consequently, on angiofibroma. histological examination some of the lesions of MTs show features either of pilosebaceous Treatment differentiation (trichoepithelioma or basal cell Treatment is difficult and often unrewarding carcinoma BCC) or apocrine differentiation (Sindu SK, 1997). Preventive measures are (spiradenoma or spiradenocylindroma). unknown. Surgical excision and various destructive modalities, including cryotherapy, Clinical description dermabrasion, electrodessication and curettage, MTs begin to develop during childhood or have been tried with occasionally good results. puberty. They appear as multiple, skin-colored to Multiple treatments may be needed in several pink, firm, rounded, transluscent, shiny, well- occasions. All methods carry significant risk of demarcated, papulonodular lesions. They are side-effects, most importantly scarring. located mainly on the face, particularly on the Recurrences are common. Recently, satisfactory nasolabial folds, nose, upper lip, forehead and clinical results have been reported with high eyelids. Occasionally, the scalp, the neck and energy pulsed CO2 laser, with no recurrences in the upper trunk may be affected as well. The the treated area for 12 months (Rosenbach A lesions are grouped but discrete. On the face, and Alster TS, 2001). they are often symmetrical. The center may be With the time, lesions of MTs may become less slightly depressed or umbilicated. obvious; therefore a wait-and-see strategy may Trichoepitheliomas gradually increase in number be advisable (Crotty K et al, 2003). and in size, producing significant cosmetic Nevertheless, long-term vigilance and follow up disfigurement. They are usually 2-5 mm in for BCC development is warranted (Pariser RJ, diameter; however, lesions may enlarge up to 1986). 5mm on face and ears and up to 2-3 cm in other sites. References The patient is otherwise asymptomatic. Telangiectatic vessels may be observed on the surface of the larger lesions, mimicking BCC. In Clarke J, Ioffreda M, Helm KF. Multiple familial contrast to BCC, ulceration occurs very rarely. trichoepitheliomas: a follicular sebaceous- Malignant transformation to BCC is rare and apocrine genodermatosis. Am J Dermatopathol occurs late in the course of the disease. 2002; 24:402-5. Although, BCC associated with MTs is not Crotty K, Dutta B, Hogan P. Multiple uncommonly reported (Misago N et al, 2001), trichoepitheliomas in a mother and daughter. some authors believe that this does not Australas J Dermatol 2003; 44:270-2. represent a true association (Wallace ML et al, Harada H, Hashimoto KY, Ko MSH. The gene 1997). for multiple trichoepitheliomas to chromosome 9p21. J Invest Dermatol 1996; 107:41-3. Hu G, Onder M, Gill M et al. A novel missense mutation in CYLD in a family with Brooke-

Bozi E, Katoulis AC. Multiple Familial Trichoepitheliomas. Orphanet Encyclopedia. April 2004. http://www.orpha.net/data/patho/GB/uk- Trichoepithelioma.pdf 2

Spiegler syndrome. J Invest Dermatol 2003; Rosenbach A, Alster TS. Multiple 121:732-4. trichoepitheliomas sucessfully treated with a high Misago N, Narisawa Y. Basal cell carcinoma in energy, pulsed carbon dioxide laser. Dermatol association with multiple trichoepitheliomas. Surg 1997; 23:708-10. Dermatology 2001; 202:261-5. Sindu SK, Wakelin SH, Wilkinson JD. Multiple Odom RB, James WD, Berger TG (eds) familial trichoepitheliomas. Cutis 1999; 63: 239- Andrews’ Diseases of the Skin. Clinical 40. Dermatology, 9th ed. Philadelphia: WB Saunders Wallace ML, Smoller BR. Trichoepithelioma with Company, 2000, pp 858-9. an adjacent basal cell carcinoma, transormation Pariser RJ. Multiple hereditary or collision. J Am Acad Dermatol 1997; 37:343- trichoepitheliomas and basal cell carcinomas. J 5. Cutan Pathology 1986; 13:111-7.

Bozi E, Katoulis AC. Multiple Familial Trichoepitheliomas. Orphanet Encyclopedia. April 2004. http://www.orpha.net/data/patho/GB/uk- Trichoepithelioma.pdf 3