Case 40
- Wangpan Shi
- Jan 29
- 2 min read
A 57-year-old female with some discoloration of the vulva mucosal region and here is the excision,
1.Which of the following mutation is most commonly seen in this location for this
entity?
A: KRAS
B: BRAF
C: SF3B1
D: GNAS
Answer
This is a case of vulvar melanoma, a type of mucosal melanoma. The correct answer is C -> SF3B1.
Feature | Cutaneous Melanoma | Mucosal Melanoma |
Common Mutations | - BRAF mutations (~50%) - NRAS mutations (~15-20%) - NF1 mutations | - KIT mutations (~20-30%) - SF3B1 mutations - TERT promoter mutations |
Mutational Burden | High due to UV-induced DNA damage | Lower mutational burden compared to cutaneous melanoma |
Genomic Alterations | - Frequent chromosomal aberrations (e.g., 7q, 1p) - High levels of UV signature mutations | - Distinct copy number variations - Less frequent UV signature mutations |
Associated Pathways | - MAPK/ERK pathway activation - PI3K/AKT pathway alterations | - KIT signaling pathway activation - Alterations in spliceosome machinery |
UV Exposure | Strong association with UV radiation exposure | Not associated with UV exposure; originates from mucosal surfaces |
Immunogenicity | Generally high due to higher mutational load | Lower immunogenicity; fewer neoantigens |
Therapeutic Targets | - BRAF inhibitors (e.g., vemurafenib) - MEK inhibitors - Immune checkpoint inhibitors | - KIT inhibitors (e.g., imatinib) - Emerging targets (e.g., SF3B1) |
Response to Therapy | Often responsive to targeted therapies (BRAF/MEK inhibitors) and immunotherapies | Less responsive to traditional targeted therapies; ongoing research on immunotherapy efficacy |
Prognosis | Variable; generally better with early detection and targeted treatment | Generally poorer prognosis due to late diagnosis and limited treatment options |
Prevalence | More common, accounting for ~90% of melanoma cases | Rare, accounting for ~1-3% of all melanoma cases |
Typical Locations | Sun-exposed skin areas (e.g., back, legs, arms) | Mucosal sites such as the head and neck, anorectal region, and genital tract |
Case credit: UCSD Pathology
Author: Wangpan Jackson Shi, MD
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