Dermatology MCQ - Infiltrative and Neoplastic Disorders - Cutaneous keratocysts

A 15-year-old boy presents with multiple, small, pearly papules on his face and trunk. His medical history is significant for early-onset basal cell carcinomas, palmar pits, and jaw cysts. A biopsy of one of the facial papules reveals a well-circumscribed cystic structure in the dermis lined by a thin, stratified squamous epithelium. The lumen contains keratin, and the basal layer of the cyst wall shows palisading. What is the most likely diagnosis for these cutaneous cysts and the associated genetic mutation?

A. Steatocystoma multiplex caused by a mutation in the KRT17 gene.
B. Epidermoid cysts associated with Gardner syndrome and APC gene mutations.
C. Cutaneous keratocysts (now often called infundibulocystic basal cell carcinomas) associated with Gorlin syndrome and PTCH1 gene mutations.
D. Eruptive vellus hair cysts, which are typically sporadic.
E. Pilar cysts with a familial autosomal dominant inheritance pattern.

Correct Answer: C. Cutaneous keratocysts (now often called infundibulocystic basal cell carcinomas) associated with Gorlin syndrome and PTCH1 gene mutations.

Answer and Explanation

The correct answer is C. This question describes the classic features of Gorlin syndrome (Nevoid Basal Cell Carcinoma Syndrome). The patient has major criteria: early-onset basal cell carcinomas, jaw keratocysts (odontogenic keratocysts), and palmar pits. The "pearly papules" are often early, superficial basal cell carcinomas. However, a specific benign lesion in this syndrome is the cutaneous keratocyst, which histologically appears as described—a thin-walled, keratin-filled cyst whose lining can resemble a basal cell carcinoma or the infundibulum of a hair follicle. The syndrome is caused by a mutation in the PTCH1 gene, a tumor suppressor gene in the Hedgehog signaling pathway.

Why the Other Options are Incorrect:

• A. Steatocystoma multiplex...: While steatocystomas can be multiple, they are characterized by a corrugated cyst lining and sebaceous glands in the wall, not palisading of the basal layer. They are associated with KRT17 mutations, not PTCH1.

• B. Epidermoid cysts associated with Gardner syndrome...: Gardner syndrome (Familial Adenomatous Polyposis) is associated with epidermoid cysts and osteomas, but not with basal cell carcinomas, jaw cysts, or palmar pits. The genetic mutation is in the APC gene.

• D. Eruptive vellus hair cysts...: These cysts contain vellus hairs, which are not mentioned in the histology. They are not associated with the systemic findings described.

• E. Pilar cysts...: Pilar cysts are almost exclusively found on the scalp and have a specific histology showing a wall without a granular layer and compact keratin. They are not associated with this systemic syndrome.

Additional High-Yield Information for Exams:

• Histopathology: The term "cutaneous keratocyst" can be a misnomer, as many dermatopathologists now view these lesions as infundibulocystic basal cell carcinomas or as benign follicular hamartomas. The histology shows a cystic structure lined by a proliferation of basaloid cells with peripheral palisading, resembling a superficial basal cell carcinoma forming a cyst. The lumen is filled with keratin.

• Gorlin Syndrome Diagnostic Criteria: It is crucial to know the major criteria, which include:

  • 2 Basal Cell Carcinations (BCCs) or 1 BCC in a patient <20 years old.

  • Odontogenic keratocyst of the jaw.

  • Palmar or plantar pits.

  • Lamellar calcification of the falx cerebri.

  • Bifid, fused, or markedly splayed ribs.

  • First-degree relative with Gorlin syndrome.

• Differential Diagnosis: The differential for multiple cutaneous cysts is key:

  • Gorlin Syndrome: As above.

  • Gardner Syndrome: Epidermoid cysts, osteomas, fibromas, and familial colon polyps/cancer (APC gene).

  • Steatocystoma Multiplex: Oily cysts on chest/axillae (KRT17 gene).

• Prognosis: Patients with Gorlin syndrome have a major risk of developing numerous BCCs, often starting in adolescence/early adulthood. They also have an increased risk of other tumors, such as medulloblastoma and cardiac fibromas. Lifelong surveillance is essential.

• Management & Rationale:

  • Rationale: Management is multidisciplinary, focusing on cancer surveillance, prevention, and early treatment.

  • Surveillance: Regular skin exams, panoramic dental radiographs (for jaw cysts), and neurological/ cardiac monitoring as indicated.

  • Treatment of BCCs: Standard treatments include surgical excision. For patients with hundreds of lesions, Hedgehog pathway inhibitors (e.g., vismodegib, sonidegib) are used to suppress tumor growth.

  • Prevention: Strict, lifelong sun protection is paramount to reduce the number and aggressiveness of BCCs.