Cutaneous adnexal carcinomas are very rare and represent only 0.005% of all skin tumors.¹ These neoplasms have a heterogeneous origin from different adnexal hair follicle structures and originate from a variety of undifferentiated stem cells.² Hair follicle malignancies comprise only 1% of all skin adnexal carcinomas.³

Anatomically, the mature hair follicle is divided into several segments distinguished by their vertical position and by their cellular organization and morphology.⁴ The deepest portion of the follicle is the bulb, consisting of a central dermal papilla of mesenchymal tissue. This is surrounded by the hair matrix cells of rapidly proliferating keratinocytes that produce the hair shaft. The stem and isthmus are the lowermost and lower portions of the follicle between the bulb and the upper portion called the infundibulum. An inner root sheath is continuous along the bulb and the stem, disappearing at the isthmus, and forms a channel for the growing hair shaft. The outer root sheath is an extension of the epidermal basal layer and envelopes the entire hair follicle. Its lower segment serves as a reservoir of stem cells.

Hair follicle adnexal tumors constitute a large variety of rare benign and malignant neoplasms that arise from the various segments and cellular components of the hair follicle. Trichoblastoma and trichoblastic carcinoma arise from hair germ cells. The hair matrix gives rise to pilomatrixoma (calcifying epithelioma of Malherbe) and pilomatrix carcinoma. Trichilemmoma, proliferating trichilemmal tumors (PTTs), and trichilemmal carcinoma (TC) derive from the outer hair root sheath. Trichofolliculomas are considered to be hamartomas with follicular differentiation, although some authors consider them to represent an abortive differentiation of pluripotent skin cells toward hair follicles.⁵

Currently, there is no generally accepted classification of hair follicle tumors. In 1976, Headington first proposed a classification based on histogenetic features.⁶ Mehregan⁷ later simplified this into three subgroups: hyperplasias, adenomas, and epitheliomas. More recently, Sia et al⁸ published a basic classification of benign and malignant hair follicle tumors according to their cellular origin, as hair germ tumors, hair matrix tumors, and external hair root sheath tumors. In that same report, the authors reviewed 19 previously published case reports of malignant hair follicle tumors occurring in the periorbital region, and among these, there were nine cases of pilomatrix carcinoma, six cases of TC, three cases of malignant proliferating trichilemmal tumor (MPTT), and one case of trichoblastic carcinoma.⁸

The pathogenesis of hair follicle malignant tumors is largely unknown, and it is unclear whether they arise de novo or from preexisting benign lesions. One of the lesions derived from the outer hair root sheath is the trichilemmal (pilar) cyst,⁹ which is believed to give rise to PTT with solid/cystic trichilemmal differentiation. Ninety percent of PTTs occur on the scalp, but they have also been found on the forehead, nose, back, chest, abdomen, buttocks, elbow, wrist, mons pubis, and vulva.¹⁰,¹¹ Most patients are female (84%), with a mean age of 65 and a range of 28 to 88 years, and most cases occur in the sixth and seventh decades of life.⁹ Malignant transformation of PTT to MPTT occasionally occurs, heralded by sudden rapid growth,¹²,¹³ an aggressive biologic behavior, and a high rate of recurrence and metastasis. MPTTs are closely related to TCs and occur more commonly in areas with excess hair growth, such as lanugo hair follicles of the bald scalp, and less commonly in areas devoid of nonterminal hair.¹⁴ The gross appearance can range from a smooth mobile nodule to a large lobular or multiple cystic lesion and tends to have more extensive hyperkeratosis and a greater number of cysts compared to TC.

The trichilemmoma is another benign lesion of the outer hair root sheath that is believed to be a precursor of TC.¹⁵ Trichilemmoma is more commonly found on sun-exposed areas of the skin, particularly the face, forehead, and scalp. This distribution is likely related to the higher concentration of skin appendages in these areas.¹⁶ Malignant degeneration may result in TC, first described by Headington in 1976⁶ as
“a histologically invasive, cytologically atypical clear cell neoplasm of adnexal keratinocytes that is in continuity with the epidermis and/or follicular epithelium.” The existence of TC has been a subject of debate because of its resemblance to clear cell squamous cell carcinoma, but more recent investigations have confirmed its existence as a distinct entity.¹⁷

Although TC is characterized histologically with features characteristic of malignancy, more benign-appearing lesions can behave aggressively, and malignant-appearing ones can show a relatively benign course.¹⁸ In general, these tumors run an indolent course with a low rate of recurrence following surgical excision and a low metastatic potential. However, despite being commonly regarded as having an indolent clinical course, metastases and multiple recurrences have been reported.¹⁵,¹⁹,²⁰,²¹,²²,²³,²⁴