Trichilemmoma is a benign tumor of the skin involving the hair follicle infundibulum. It is characterized histologically by cellular differentiation towards the outer root sheath. It commonly appears on the head and neck region. The presence of multiple trichilemmoma is associated with Cowden Syndrome.
Trichilemmoma typically presents in adults, although childhood cases have been reported. It is most common in Caucasians and women. The exact incidence is unknown. Cowden Syndrome has an occurrence of approximately 1:200,000. Average age of diagnosis is around 22 years and it is more commonly found among women. 
Etiology and Pathophysiology
Trichilemmomas have been associated with HPV; several viral subtypes have been isolated by PCR from lesions including 6, 15, 17, 23, 27, 28, and 37.  The fundamental etiology, however, remains unknown.
A rare variety termed desmoplastic trichilemmoma also exists. Approximately 80 cases have been reported in the last thirty years. They have been shown to be more closely correlated with malignant neoplasms.
The presence of multiple facial trichilemmomas is associated with Cowden Syndrome. Cowden Syndrome is an autosomal dominant condition characterized primarily by mucocutaneous lesions, thyroid abnormalities, breast lesions, GI lesions, GU lesions, and a multitude of other cancers (such as squamous cell carcinoma, basal cell carcinoma, liposarcoma, HCC, and RCC). It is due to mutations in the PTEN gene, which predisposes the patient to multiple hamartomas appearing within organs from any of the three embryonic layers (endoderm, mesoderm, ectoderm). The most common location for hamartomas to develop are in the skin, colon, and thyroid tissue.
Trichilemmomas appear as well-demarcated tumors composed of squamous epithelial cells with varying degrees of glycogen vacuolization, central keratinization, and microcysts. Pale pink, glassy cells are often present. They generally appear at the border of the epidermis and dermis, extending into each region. The cells organize and appear as if they are assembling towards differentiation into the outer root sheath of hair follicles.  Peripheral palisading is characteristic. Desmoplastic trichilemmomas appear as above but with a central desmoplastic stroma that contains angular cords and strands; it can appear invasive, mimicking basal or squamous cell carcinomas.
Isolated trichilemmomas do not have systemic manifestations. They most commonly appear on the face and neck, but have been reported to appear on other areas of the body as well.
Systemic manifestations can be seen in Cowden Syndrome in the form of multiple hamartomas throughout the body. The most common site for hamartomas to appear are the skin, colon, and thyroid tissue. They are also at increased risk of malignancy in the thyroid and breast.
Ocular manifestations of trichilemmoma are mainly isolated to a fleshy, painless growth on the upper or lower lids. Misdiagnosis is a high possibility given the variable dermoscopic and histologic appearance. Desmoplastic trichilemmomas are more commonly reported on the lids.
Ocular manifestations of Cowden Syndrome are mostly limited to complications of lid trichilemmomas, although cases have been reported with other findings such as choroidal schwannomas and corneal irregularities (abnormal cornea anterior stromal layers, increased reflectivity, unstructured epithelial layer architecture). 
The diagnosis of trichilemmoma depends upon histologic examination showing peripheral palisading, the appearance of outer root sheath organization, and lobules of epithelial cells with vacuolization.
Trichilemmoma presents as a slow growing, often asymptomatic, fleshy papule/nodule. Other presentations can include a papule with a dome shape and crown vessels, hyperkeratotic central depression or smooth surface, and erythema.  The lesion is typically nontender and varies in size. Sizes reported at presentation vary from one to five millimeters. Multiple such lesions may be present in patients with Cowden Syndrome. Other signs of Cowden Syndrome are neck masses, gastric/colon polyps, or breast masses.
Ocular findings are often limited to the skin of the upper and lower lids. Skin mass/growth, ptosis, ectropion, entropion, and decreased vision are all possible complaints that would bring a patient into the clinic.
Diagnostic procedures include:
- Biopsy of lesions for histologic diagnosis of trichilemmoma
- Staining of samples for CD34 to identify desmoplastic trichilemmoma
- Complete blood count to evaluate for anemia or infection
- Thyroid functions testing for thyroid evaluation
- Urinalysis for renal/urinary symptoms
- Endoscopy, colonoscopy, mammogram, and thyroid scans if there is concern for Cowden Syndrome to evaluate for other masses
- Molluscum contagiosum
- Basal cell carcinoma
- Sebaceous carcinoma
- Cutaneous horns
- Trichilemmal carcinoma
Management of trichilemmoma begins with correct diagnosis. Biopsy and histologic analysis is the gold standard of diagnosis.only reliable method of diagnosis as the clinical presentation and visual appearance may vary considerably.
There are no medical treatments for trichilemmoma. Medical treatments for Cowden Syndrome will focus on controlling symptoms and, most importantly, cancer screenings. The National Comprehensive Cancer Network provides the following guidelines for screening individuals diagnosed with Cowden Syndrome:
- Initial genetic evaluation and testing to confirm diagnosis and type.
- Women: breast self exams at 18, clinical breast exams every 6-12 months, annual mammogram and breast MRI at age 30-35, annual US screening for endometrial cancer at age 30-35, possible prophylactic surgeries depending on risk.
- Men: annual physical beginning at 18, annual thyroid US beginning at 18, colonoscopy at 35 with another every 5 years, possible renal US every 1-2 years beginning at 40
- Children: yearly thyroid US, yearly skin check, yearly neurodevelopmental evaluation
Removal of cutaneous lesions is recommended if pain or symptoms are experienced. Patients often request removal, especially if lesions are present on the face or lid, for cosmetic appearance.
Shave biopsy is generally performed for facial lesions. The cosmetic appearance is more favorable and allows for histologic analysis. There is a chance of recurrence, however.
Excision can be used to remove the trichilemmoma completely. This presents greater risk of bleeding and disfigurement. As the lesion is considered benign, there is little advantage to excisional removal in the place of shave biopsy. Other options for removal include carbon dioxide laser ablation, electrosurgery, dermabrasion, or cryosurgery.
Prognosis and Complications
The prognosis for patients with trichilemmoma is generally good. They are considered benign and nonmalignant. Negative outcomes mainly stem from surgery and can include infection, bleeding, and disfigurement. Particular attention must be paid to lid function and anatomy post-op to avoid ocular complications (dry eye, corneal exposure and ulcers, damage to globe).
The prognosis of Cowden Syndrome is dependent on the development of malignant neoplasms. Complications can be mitigated by early diagnosis, with both primary care and dentistry at the front lines of initial presentation. Close surveillance after diagnosis is crucial to the management of these patients.
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