Follicular Lesions

Question 1

Trichoepithelioma / Trichoblastoma

Answer 1

• Benign adnexal tumors
• May show morphologic overlap and recapitulate features of germinative hair bulb epithelium and associated mesenchymal stroma

Sites:
Trichoepithelioma (solitary):
* Face
* Rarely scalp, trunk, extremities, genital area

Trichoepithelioma (multiple / familial):
* Symmetrical distribution over central face
* Rarely other sites as above

Trichoblastoma:
* Scalp, head and neck
* Occasionally trunk, extremities, genital area

Micro:

Trichoepithelioma:
* Usually superficial dermal tumors
* Superficial nests of basaloid cells with keratin horn cysts
* Can show leaf-like or frond-like architectural pattern
* Fibrous cellular stroma closely associated with the epithelial components
* May have papillary mesenchymal bodies and calcifications
* May have epidermal connection
* Ulceration rare
* Can be basaloid cell predominant with few horn cysts making distinction from trichoblastoma or basal cell carcinoma more difficult

Trichoblastoma:
* Well circumscribed, predominantly dermal tumor nodule which may extend to subcutis
* Predominantly basaloid epithelial cells in nests with peripheral palisading
* May have keratin cysts
* Mitoses and apoptosis can be evident but cellular pleomorphism is minimal
* Prominent cellular stromal component with papillary mesenchymal body formation
* Clefting occurs between the epithelial stromal tumor mass and surrounding dermis rather than between epithelial and stromal components
* May show cribriform, rippled or solid patterns
* May contain dendritic melanocytes and appear pigmented
* Typically retains CK20 positive Merkel cells

Molecular:
* Multiple trichoepitheliomas can be associated with Brooke-Spiegler syndrome and multiple familial trichoepithelioma (CYLD mutations)
* Trichoblastomas are not known to be familial but are the most common tumor type found in association with nevus sebaceus

IHC:
Vs BCC

• CD10
  TE positive in stroma
  BCC positive in epithelium
• CD34
  TE positive in stroma
• Androgen receptor
  BCC focally positive

Question 2

Trichilemmoma

Answer 2

• Benign follicular tumor
• Derived from the outer root sheath of the hair follicle
• Typically located on the head and neck
• Predilection for central face
• Associated with nevus sebaceous

Micro:
* Squamoproliferative lesion in continuity with the epidermis
* Hyperkeratosis and stromal clefting are often associated
* Squamous eddies
* Pale eosinophilic or clear cells
* Rounded lobular profile
* Peripheral palisade of cuboidal or columnar cells
* Reverse polarity of peripheral cells (characteristic but uncommon)
* Distinct basement membrane resembling the hair outer root sheath zone below the level of the follicular isthmus
* Basaloid cell predominance may be seen mimicking basal cell carcinoma

Molecular:
* Cowden syndrome:
Autosomal dominant genodermatoses associated with mutation in PTEN tumor suppressor gene

Question 3

Pilomatricoma

Answer 3

• Pilomatricoma is a benign skin adnexal tumor originating from hair matrix and cortex
• Most commonly occurs in head and neck, extremities and trunk in children –> most common adnexal neoplasm in children, favors young age
• Slow growing, dermal based, asymptomatic nodule measuring 0.5 - 3 cm
• Grossly appears as circumscribed hard dermal tumor with cheesy material
• Variants include pigmented and proliferating type

Micro:
* Lobulated and circumscribed dermal based neoplasm
* Islands of basaloid cells exhibiting abrupt keratinization, without intervening granular layer (trichilemmal keratinization)
* Ghost / shadow cells, may predominate
* Basaloid cells show mitotic activity; however, abnormal mitoses are absent
* Intermediary cells progressively more eosinophilic cytoplasm, with pyknotic nucleus
* Tumor keratin may elicit inflammatory response with foreign body giant cells, granuloma, cholesterol clefts and calcification
* Uncommonly metaplastic bone formation is present along with extramedullary hematopoiesis

Molecular:
* May be associted with Gardner syndrome
* mutations in CTNNB1 gene located in the exon 3 region (encoding beta catenin)

Question 4

Trichofolliculoma

Answer 4

• Benign adnexal hamartomatous follicular tumor
• Mostly solitary papule or nodule
• Occurs in adulthood
• No definitive racial or gender predilection
• Rarely occurs as a congenital lesion
• No proven association with any dermatological or systemic diseases
• Solitary, skin colored papule or nodule (approximately 0.2 - 1.5 cm in diameter) with central depression
• Multiple tufts of vellus and thin hairs emerging from the central section

Micro:
* Dilated central cystic follicle with surrounding multiple fully formed vellus or terminal follicles
* The central cystic follicle shows connection / opening to epidermis
* Branched follicles may show varying degree of maturation, including rudimentary structures or epithelial cords and anagen, catagen or telogen hair in older lesions
* Secondary follicles are small with many epithelial strands and abortive pilar formation
* Sebaceous differentiation may be present
* Trichofolliculoma is usually surrounded by well developed connective tissue, which is frequently cellular

Molecular:
* Repeated development of hair follicles with disordered hair cycle; defective sonic hedgehog polarization
* BMP and PYGO2 signaling pathway in experimental studies; not used in clinical setting