Trichilemmoma

Background

In 1962, Headington and French first described trichilemmoma as a benign neoplasm with differentiation toward pilosebaceous follicular epithelium,^[1] or outer root sheath. Although unusual, at times, a central zone of desmoplasia may develop and thus be termed desmoplasia trichilemmoma.^[2] While benign in nature, the significance of trichilemmoma resides in the association with Cowden disease (ie, multiple hamartoma syndrome), nevus sebaceous, and the need to differentiate trichilemmomas from other more aggressive cutaneous tumors, such as trichilemmal carcinoma.

Clinically, trichilemmomas present as well-defined, smooth, asymptomatic papules or verrucoid growths. They may appear as a solitary or multiple lesions, and they usually are found on the head and face (see the image below). These papules often mimic a basal cell carcinoma or a verruca.

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A patient with trichilemmoma papules on the face.

Trichilemmomas are often reported in association with several other neoplasms. Trichilemmoma is most commonly found secondary to nevus sebaceous of Jadassohn.^[3] . Nevus sebaceous is classified as a congenital cutaneous hamartoma that presents on the scalp or face sometime between birth and childhood development.^[2] Several articles have reported trichilemmomas also appearing alongside trichoblastoma, sebaceous adenoma, and syringocystadenoma papilliferum.^{[4, 5]}

When multiple trichilemmomas are present, Cowden disease should be suspected, especially if associated with oral fibromas, goiter, gastrointestinal polyposis, thyroid disease, or a family history of breast cancer.

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Pathophysiology

The underlying cause of trichilemmomas is unknown. Because of its histologic similarity to a wart, some researchers have investigated a viral etiology.^{[6, 7]}

Johnson et al^[8] performed histologic and ultrastructural analyses of 10 hyperkeratotic lesions on the extremities and 2 keratotic lesions on the face in a patient with Cowden disease. They were unable to find evidence of a viral infection in the tissues examined. Leonardi et al^[9] performed a study on 25 trichilemmomas, revealing no evidence of human papillomavirus DNA in the lesions. Most trichilemmomas, therefore, appear to represent a benign tumor with differentiation towards the follicular outer root sheath (trichilemma).^[7]

Stierman et al^[10] were unable to detect human papillomavirus (HPV)–1, HPV-2, or mixed genital-type HPV infection in trichilemmomas using in situ hybridization. It was suggested that the association between HPV infection and the hair follicle is both one of the permanent sources of HPV DNA and the site of origin for trichilemmomas.^[11] The development of trichilemmomas may be independent factors associated with increasing age, rather than HPV being an oncogenic stimulus for trichilemmomas.

Conversely, Rohwedder et al used the polymerase chain reaction (PCR) technique to show 11 cases of HPV-positive trichilemmoma. So far, HPV types 6b, 15, 17, 23, 27, and 28 have been identified in both solitary trichilemmoma lesions and in patients with Cowden syndrome.^{[11, 12]}

Cowden syndrome is a rare autosomal dominant condition characterized by the formation of multiple types of hamartomas and neoplastic growths, which may be found throughout different body systems. This syndrome is thought to be due to the PTEN mutation, a germline mutation in exon 8 of the phosphatase and tensin homolog deleted on chromosome 10.^[13] It is a point mutation of C to T at codon 1003 (CGA → TGA, arginine → stop codon). This defect demonstrates incomplete genetic penetrance with variable expressivity. Loss of heterozygosity may lead to tumor formation.^[14]

The syndrome is allelic to other PTEN -related syndromes such as Lhermitte-Duclos disease (dysplastic cerebellar gangliocytoma) and Bannayan-Riley-Ruvalcaba syndrome, which is characterized by genital lentigines and hamartomatous growths. Families or patients with overlapping features have been described.^{[15, 16]}

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Etiology

The cause of a trichilemmoma is unknown. Because trichilemmoma shares some morphologic and histologic features with a verruca, some researchers have postulated that a virus may induce these lesions. Increased risk has also been found when subjects have a history of long exposure to sunlight.^[17]

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Epidemiology

Frequency

United States

Trichilemmomas are relatively common benign neoplasms of the follicular epithelium. Their true incidence is hard to determine and is probably underestimated. Approximately 40 cases per 100,000 consecutive skin biopsies may be found every year in any given dermatopathologic laboratory. Unlike isolated trichilemmomas, multiple trichilemmomas associated with Cowden disease are very rare.

International

The international frequency is unknown.

Race

Trichilemmomas may occur in any race. They are most common in white females, but they have also been reported in Chinese, Japanese, and black patients.

Sex

The male-to-female ratio of trichilemmomas is 1:1; however, Cowden disease has a female predominance, with a male-to-female ratio of 1:3.

Age

Trichilemmomas predominantly occur in adult patients aged 20-80 years. However, onset may occur as early as age 4 years, with a median age of onset at 30 years.^[14]

Desmoplastic trichilemmomas (a histologic subtype of trichilemmoma) predominantly occur in white men over a wide age range, and the highest frequency is in the fifth decade.

One rare case of a trichilemmoma following a blaschkoid pattern has been noted in a 13-year-old boy. It is the first case seen as such.^[18]

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Prognosis

Trichilemmomas are benign follicular epithelial neoplasms. Of themselves, trichilemmomas are associated with minimal morbidity and no mortality. These tumors usually need to be differentiated clinically from a verruca or a basal cell carcinoma. The only morbidity associated with these tumors occurs if they are treated as a basal cell carcinoma before histologic confirmation is obtained.

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Patient Education

Educate each patient with a trichilemmoma regarding the benign nature of this epithelial neoplasm. Further education regarding its association with Cowden disease may also be provided, particularly if other clinical evidence for Cowden disease exists. Patients should be informed that they are at higher risk for the development of trichilemmoma the more they are subjected to sun exposure. In addition, if nevus sebaceous remains untreated, it has a 10-20% chance of transforming into a malignant form. Appropriate plans and treatment should always be instituted.^[17]

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History

Patients with trichilemmomas usually give a history of a slow-growing, asymptomatic papule and/or plaque on the face. Such lesions may be solitary or multiple. Patients often desire reassurance that they do not have a skin cancer and/or seek an evaluation for cosmetic removal of the lesions.

If presenting in a nevus sebaceous of Jadassohn, a trichilemmoma may appear as a new growth within the lesion. No single feature allows the clinical diagnosis of a trichilemmoma, but rather this diagnosis is usually rendered histologically. However, if multiple lesions are present on the face, trichilemmomas associated with Cowden syndrome may be suspected. Once the diagnosis of trichilemmoma has been given, reevaluating the patient for clinical features of Cowden syndrome may be prudent.

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Physical Examination

Patients with trichilemmomas usually present with either a single papule or multiple, small, flesh-colored papules that are 1-5 mm in diameter on the face or the neck. When these lesions grow in size, small plaques may be found, particularly in the nasolabial fold region. As trichilemmomas slowly enlarge, they often produce a hyperkeratotic surface suggestive of a verruca or a cutaneous horn. Besides the central part of the face, the ears, the forearms, the hands, or within a nevus sebaceous of Jadassohn are other typical sites that are examined for these cutaneous lesions.

Trichilemmoma commonly stems from nevus sebaceous, which usually is found on the face and scalp. However, cases have also been noted on the eyelid and anus.^{[19, 20]}

If a diagnosis of trichilemmoma is rendered, the patient should be completely examined for evidence of Cowden syndrome. (See images below.) Ten key physical features to look for in establishing the diagnosis of Cowden syndrome include the following:

• Adenoid facies with facial trichilemmomas
• Craniomegaly
• High arched palate
• Oral papillomas producing a cobblestone appearance on the lips and the mucosal surfaces
• Goiter or palpable thyroid nodules/tumors
• Gynecomastia in men
• Fibrocystic breast disease and/or palpable breast nodules or tumors in women
• Acral keratoses on the dorsum of the hands and the wrists
• Palmoplantar translucent punctate keratoses
• Sclerotic fibromas on the extremities

In 1983, Salem and Steck^[21] proposed diagnostic criteria for Cowden syndrome. See Cowden Disease (Multiple Hamartoma Syndrome) for a more definitive discussion in this area.

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Clinical image of the face of a patient with Cowden syndrome.

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Clinical image of the oral mucosa of a patient with Cowden syndrome.

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Clinical image of palmar keratoses in a patient with Cowden syndrome.

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Clinical image of sclerotic fibroma in a patient with Cowden syndrome.

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Clinical image of multiple trichilemmomas in a patient with Cowden syndrome.

Patients with desmoplastic trichilemmomas usually present with lesions less than 1 cm in diameter found predominantly on the face, the neck, the scalp, and, sometimes, on the chest or the vulva. Several reports have described desmoplastic trichilemmomas occurring on the upper eyelid.^{[22, 23]} They may be indurated, with a depressed central region and a raised, annular border. Desmoplastic trichilemmomas, although not associated with Cowden disease, have been described arising from a nevus sebaceous.^{[3, 24]}

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Laboratory Studies

If clinical evidence of Cowden syndrome is present, the following tests may be considered in establishing the diagnosis and in searching for potential malignancies:

• Triiodothyronine and thyroxine serum levels
• CBC count with differential
• Electrocardiogram

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Imaging Studies

No imaging studies are needed for the evaluation of a trichilemmoma. However, the following imaging studies may be of use when completing a workup for Cowden syndrome:

• Mammography
• Thyroid scan
• Upper and lower GI imaging series
• Chest radiography
• Radiographs of the long bones, the pelvis, and the skull

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Procedures

A skin biopsy is used to establish the diagnosis of a trichilemmoma. A shave biopsy is most commonly performed (see Histologic Findings). Some practices have used several variant types of antibiotics in attempts to decrease the size of the trichilemmoma.^[25]

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Histologic Findings

The following are histologic features found in a trichilemmoma (see the images below); these features assist in establishing the diagnosis:

• The epidermis usually reveals hyperkeratosis, mild acanthosis, and, occasionally, a cutaneous horn.
• A lobular or platelike epidermal growth projecting downward into the dermis
• Cells high in the epidermis may be vacuolated and contain coarse keratohyaline granules.
• Cells located toward the center of the lobular growth are often pale staining or have clear cytoplasm. These cells contain glycogen and are periodic acid-Schiff (PAS) positive but diastase labile.
• Cells at the periphery of the tumor are more basophilic and exhibit palisading.
• An eosinophilic hyaline basement membrane zone surrounds the tumor. This eosinophilic rim is PAS positive and diastase resistant.
• Foci of epidermal keratinization with formation of squamous eddies may be present.
• A desmoplastic variant demonstrates central sclerotic collagen breaking the center of the tumor into small irregular islands.

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  Low-power histologic view of a trichilemmoma.

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  Mid-power histologic view of a trichilemmoma.

   

  

   

The histologic differential diagnosis includes a hidroacanthoma simplex, which usually demonstrates ductal differentiation. A clear basal cell carcinoma should also be considered but can be excluded based on the presence of mucinous stroma, mitoses, and peripheral palisading with an absence of an eosinophilic hyaline cuticle. In tumor tissue in mice, nestin immunoreactivity was observed in immunoreactivity but not in basal cell carcinoma.^[26]

Other epithelial neoplasms, such as the tumor of the follicular infundibulum (see the image below), may be considered in the differential diagnosis. Trichilemmal carcinoma may be considered, but excluded, based on its invasive growth pattern and many mitoses. An immunohistochemical study of cytokeratins suggests that an absence of cytokeratins 15 and 16 in trichilemmal carcinoma may be related to transformation from trichilemmoma to its trichilemmal carcinoma.^[27]

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Tumor of the follicular infundibulum.

Several reports have stated that the use of CD34 immunostaining in tumors completely or partially differentiated toward the external root sheath of the hair follicle, such as trichilemmoma.^[28]

Desmoplastic trichilemmoma demonstrates a biphasic growth pattern, having features of a lobulated tumor and cells that form narrow, irregular cords, which penetrate into the dermis. The stroma surrounding the tumor cords appears sclerotic. An inflammatory cell infiltrate is often seen surrounding the epithelial strands of the tumor. Because of these features, differentiating this tumor from an invasive squamous cell carcinoma or a sclerosing basal cell carcinoma is important.^[29] CD34 expression has been particularly useful in the differentiation of desmoplastic trichilemmoma from other cutaneous tumors with dense collagenous stroma.^[30]

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Low-power histologic view of a desmoplastic trichilemmoma.

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High-power histologic view of a desmoplastic trichilemmoma.

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Approach Considerations

The best medical treatment of a tricholemmoma is to begin by establishing the correct diagnosis. Because these tumors are benign, no medical treatment is required. However, a few treatment options are available, ranging from simple surgical excision to carbon dioxide laser tissue ablation. Even though most tumors are benign, they always should be continually monitored, as malignant transformation has occurred.^[17] Trichilemmoma may commonly vary in size, and it should be reevaluated should continual growth occur.^[25]

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Surgical Care

A standard surgical approach to a patient with a trichilemmoma is to perform a shave biopsy. This procedure provides a tissue specimen for histologic examination and facilitates removal of the epithelial growth. If the shave biopsy is performed flush to the skin surface, it often produces an excellent cosmetic result. However, performing a shave biopsy does not eliminate the possibility of a recurrence.

Excision is an option but is less commonly performed because of the benign nature of this neoplasm and its common location on the face.

Electrodesiccation may be used to remove a trichilemmoma. However, electrodesiccation followed by curettage is not indicated for this benign neoplasm. This procedure produces unnecessary and unsightly scarring.

One report describes successful treatment of desmoplastic trichilemmoma (a variant of trichilemmoma) with Mohs micrographic surgery.^[31]

Probably the most elegant procedure to date for removing a trichilemmoma is the use of a carbon dioxide laser for tissue ablation. Carbon dioxide laser has been used for removal of a wide range of epidermal and dermal growths or neoplasms. Under local anesthesia, the hypertrophic and hyperkeratotic epithelium characteristic of a trichilemmoma may be rapidly and precisely vaporized.

The coagulated tissue subsequently may be wiped away. This process is repeated until the tissue is flush with the surrounding skin surface and/or the tumor has been destroyed. The remaining tissue and thermal debris is allowed to heal and usually separates from the epidermis in 3-5 days after the procedure. Reepithelialization is usually complete within 4 weeks.

This procedure is particularly useful if multiple trichilemmomas are present (eg, Cowden syndrome).

The carbon dioxide laser has the following advantages: It allows for precise tissue ablation. Multiple lesions can be treated with ease. The procedure can be performed quickly. Morbidity is minimal. Patient recovery time is relatively short. Cosmetic results are usually excellent.

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Consultations

If the diagnosis of trichilemmoma is established and no other clinical features or family history of Cowden syndrome is found, then no further consultation is needed. However, if the medical provider finds evidence of Cowden syndrome, referral to a dermatologist is needed. Secondary referrals to a gastroenterologist, internist, endocrinologist, and a surgeon may be needed.

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