Definition

Trichilemmoma is a tumor that exhibits features of outer root sheath differentiation of hair. In Cowden disease, multiple trichilemmomas are associated with multiple hamartomatous neoplasms of ectodermal, mesodermal, and endodermal origin.^288–292

Epidemiology

Cowden disease is a rare autosomal dominant condition with variable expressivity. Less than 100 cases are reported to date. Male patients slightly exceed females among all the cases reported. All reported patients are white, except for one Japanese and two black patients. The age span is between 4 and 75 years, with the median age being 39 years.

Clinical Features

In Cowden disease, multiple trichilemmomas are associated with a wide variety of hamartomas and tumors of other organ systems; the most important include fibrocystic disease and carcinoma of the breast, adenoma and follicular adenocarcinoma of the thyroid, gastrointestinal polyps, and lipomas. The trichilemmomas present as small lichenoid, skin-colored to yellow-tan papules with a smooth surface. They are concentrated on the face, especially around the orifices and the ears. Similar papules may appear on the extremities, including palmoplantar surfaces, and the oral cavity, particularly on the gingiva and the tongue (Figures 123-20 and 123-21). The presentation of these papules usually precedes the appearance of breast cancer²⁸⁸ and, therefore, can serve as a marker of associated cancer.

Figure 123-20

Cowden disease. Multiple trichilemmomas on the upper lip. Similar papules are present on the mucosal surface of the lower lip. (Four-color version of figure on CD-ROM)

Figure 123-21

Cowden disease. Translucent keratotic papules on the palmar surface. Courtesy of R.A. Johnson, MD. (Four-color version of figure on CD-ROM)

Histopathology

The facial papules show evidence of differentiation toward outer root sheath cells of the hair follicles. Multiple biopsies may be required to demonstrate the characteristic histology of trichilemmomas.²⁹³ The oral lesions are fibromatous or fibrovascular nodules.

Genetics

Germ line mutations in the protein tyrosine phosphatase PTEN/MMAC have been linked to multiple families with Cowden disease.²⁹⁴

Treatment

Therapies are directed toward achieving good cosmetic appearance and treatment of the various associated benign and malignant tumors, as indicated. In view of the high incidence of breast cancer in female patients, which may be as high as 50%, frequent breast examination and mammography are indicated.

Definition

Sebaceous adenoma is a rare, benign tumor consisting of incompletely differentiated sebaceous lobules within the dermis. In Muir-Torre syndrome, multiple sebaceous adenomas and carcinomas are associated with multiple visceral malignant neoplasms. These sebaceous tumors are rare enough that the presence of a single lesion in an otherwise healthy patient warrants an investigation for internal neoplasms.

Epidemiology

Solitary sebaceous adenoma is a rare tumor that occurs in elderly patients of both sexes. The multiple type, associated with Muir-Torre syndrome, is familial, with more than 50% of reported patients having an immediate family member with a history of internal cancer, most frequently of the colon.^295–297

Clinical Features

Sebaceous adenoma typically appears as a firm, flesh-colored to waxy-yellow papule or pedunculated lesion, usually less than 1 cm in size. The surface may be smooth or verrucous. Older lesions may be plaque-like or ulcerated. It is usually located on the face or scalp and is usually slow growing.

In Muir-Torre syndrome, multiple sebaceous tumors, including adenomas and carcinomas, and keratoacanthomas are associated with multiple visceral carcinomas, most commonly carcinoma of the colon and carcinoma of the ampulla of Vater.

Histopathology

The tumor is made up of lobules of undifferentiated basaloid cells and cells with varying degrees of sebaceous differentiation. It is situated in the upper dermis and is sharply demarcated. Connection to the epidermis can often be demonstrated.

Genetics

Overlap between Muir-Torre syndrome and kindreds with hereditary nonpolyposis colon cancer allowed the identification of the DNA mismatch repair gene hMSH2 as one of the genes disturbed in Muir-Torre syndrome.²⁹⁸

Treatment

The treatment of choice is surgical excision. The tumor is also radiosensitive.

Definition

Mucosal neuromas present as small, discrete and coalescing, painless nodules, usually involving the lips, and sometimes studding the margins of the tongue. The association of multiple mucosal neuromas, medullary thyroid carcinoma and pheochromocytoma has been established as a familial syndrome.

Epidemiology

Discrete mucosal neuromas are common and often result from direct trauma, as in the typical bite neuroma. More than 150 cases of multiple neuromas associated with endocrine tumors have been described in the literature.²⁹⁹

Clinical Features

In MEN2B, diffusely enlarged lips are an early feature. Diffuse and symmetric fleshy papules and nodules occur on the tongue by the end of first decade. Any mucosal surface may be involved. Patients often develop a marfanoid habitus. Most importantly, medullary thyroid carcinoma may develop in early adulthood. These tumors produce calcitonin and can stimulate parathyroid hyperplasia. Pheochromocytomas are frequently present as well.

Histopathology

The mucosal neuroma associated with the endocrine syndrome are of the intraneural variety,³⁰⁰ consisting of a bulbous hyperplasia of a peripheral nerve forming a nodule in the dermis. The nodules are surrounded by a perineurial sheath. Within the sheath, Schwann cells form interlacing fascicles.

Genetics

In all cases studied to date, mutation in the protooncogene RET, a receptor tyrosine kinase, has been uncovered.^300,301

Course and Prognosis

Medullary thyroid carcinoma is often the cause of death. Routine screening for this tumor with ultrasonography and by measuring serum calcitonin levels is useful, but current recommendations suggest prophylactic thyroidectomy in cases where a RET mutation is documented.³⁰²