Trichoepithelioma

Description

• A benign cutaneous neoplasm of the hair follicle
• Trichoepithelioma (TE) commonly presents as a solitary skin-colored papule or nodule on the face.
• Multiple lesions are seen in several autosomal dominant disorders including Brooke-Spiegler syndrome, Brooke disease, Rombo syndrome, and Bazex-Dupré-Christol syndrome.
• There are three variants of TE: (i) solitary, (ii) multiple familial TE (MFT), and (iii) desmoplastic TE (DTE).
• Can be mistaken for basal cell carcinoma (BCC) or Gorlin syndrome (multiple BCCs)

Epidemiology

• Predominantly occurs in young adults
• Multiple lesions may occur in children and adolescents with associated autosomal dominant disorders.
• A distinct variation known as giant solitary TE may occur in the elderly.

Incidence
Incidence unknown

Prevalence

• Rare (affects <1 person per 2,000)
• Female > male (2:1)

Etiology and Pathophysiology

• The short arm of chromosome 9 is known to encode proteins that can arrest the cell cycle by binding CDK4/6. Tumorigenesis is believed to occur when deletion or rearrangements near 9p21 inactivates these proteins, causing decreased CDK4 kinase binding and increased phosphorylation of the retinoblastoma tumor suppressor protein.
• Familial cases of TE are due a mutation of CYLD gene, a tumor suppressor gene that plays a role in deubiquitinating proteins. These proteins negatively regulate the nuclear factor-κB (NF-κB) signaling pathway. Loss of CYLD heterozygosity promotes tumor growth through continuous NF-κB activation, unregulated cell division, and resistance to apoptosis.

Commonly Associated Conditions

• Brooke-Spiegler syndrome
• Familial cylindromatosis (FC)
• BCC
• Gorlin syndrome
• Rombo syndrome (atrophoderma, milia, hypotrichosis, TE, BCC, peripheral vasodilatation)

Genetics
TE displays genetic heterogeneity; the two most prevalent mutations have been mapped to the following:

• 9p21 → Autosomal dominant mutation in a tumor suppressor gene gives rise to the familial form of TE (MFT).
• 16q12 to 16q13 (CYLD gene) → results in a spectrum of disease phenotypes including the following:
  • MFT
  • FC
  • Brooke-Spiegler syndrome, which demonstrates features of MFT and FC

Risk Factors

• Female gender (due to increased disease penetrance)
• Family history