Melanoma

Question 1

Common somatic mutations in melanoma?

Answer 1

BRAF (50-60% of tumors), NRAS (15-20% of tumors). These confer poorer prognosis. Other genes: cKIT (acral, mucosal, lentigo maligna melanoma), GNAQ/GNA11 (uveal)

Question 2

Risk factors for melanoma?

Answer 2

Dysplastic nevi, numerous benign nevi, fam history of melanoma, and fair skin that burns.

Question 3

Common genes that are implicated in hereditary melanoma?

Answer 3

p16/CDKN2A and, much rarer, CDK4. Pancreatic cancer can also be seen in patients with CDKN2A mutations. BRCA2 carriers as well. BAP1 mutations (uveal melanoma)

Question 4

Four subtypes of melanoma?

Answer 4

Superficial spreading, nodular, lentigo maligna, and acral lentiginous

Question 5

Prognostic factors for melanoma?

Answer 5

Tumor thickness, mitotic rate, ulceration. Other poor prognostic factors are increased invasiveness (Clark level), lack of tumor-infiltrating lymphocytes, presence of microscopic satellites. Other factors: location, age, sex, regional nodes. One regional node: 40-50% risk of recurrence; multiple modes: 75% risk.

Question 6

Treatment of melanoma?

Answer 6

Surgical excision. For tumor >= 1 mm thick or with ulceration or high mitotic count or Clark level IV or V, perform sentinel lymph node dissection. If SLN neg and primary = 4 mm, consider adjuvant therapy.

Question 7

Adjuvant therapy for high-risk melanoma?

Answer 7

High dose IFN alpha-2b, clinical trial, or observation. IFN improves relapse free survival but not OS. Other approaches include ipilimumab and chemo/IL-2 in clinical trials.

Question 8

Surveillance strategy for melanoma?

Answer 8

No clear guidelines. For stage one and stage two, regular physical exam and annual skin exam. Chest x-ray and LDH optional. CT or PET can be considered.