KEY TAKEAWAYS
- The study aimed to investigate the utility of UV signature mutations as a diagnostic tool in metastatic HNCUP patients.
- Researchers noticed UV mutational signature testing is crucial in HNCUP next-gen sequencing, informing distinct management strategies for metastatic cutaneous carcinomas.
Metastatic carcinoma of unknown primary origin to the head and neck lymph nodes (HNCUP) poses unique diagnostic challenges, especially with the potential presence of HR-HPV indicating occult oropharyngeal squamous cell carcinoma (SCC). The consideration of HR-HPV-independent carcinomas necessitates the exploration of alternative primary sites, notably cutaneous malignancies that may mimic HR-HPV-associated SCC.
Karina Colossi Furlan and her team aimed to assess the ultraviolet (UV) signature mutations, characterized by ≥ 60% C→T substitutions and ≥ 5% CC→TT substitutions at dipyrimidine sites, prevalent in tumors from sun-exposed areas, emerge as attractive yet underused diagnostic tool for metastatic HNCUP.
Researchers performed an inclusive analysis through a retrospective review of institutional records, concentrating on cases of HR-HPV negative HNCUP. All identified cases underwent next-generation sequencing analysis to assess the presence of UV signature mutations systematically.
About 14 cases of HR-HPV negative metastatic head and neck carcinoma of HNCUP to cervical or parotid gland lymph nodes were identified in the retrospective analysis. Among these cases, 11 (79%) displayed UV signature mutations, including 4 (40%) with positive p16 status. Notably, all cases positive for UV signature mutations exhibited at least one significant TP53 mutation, along with more than 20 unique gene mutations.
The study concluded that routine incorporation of high C→T with CC →TT substitutions observation in next-generation sequencing reports for HNCUP is crucial. UV mutational signatures testing emerges as a robust diagnostic tool with practical applicability in daily clinical practice.
Source: https://pubmed.ncbi.nlm.nih.gov/38393464/
Furlan KC, Saeed-Vafa D, Mathew TM, et.al (2024). Utility of UV Signature Mutations in the Diagnostic Assessment of Metastatic Head and Neck Carcinomas of Unknown Primary. Head Neck Pathol. 2024 Feb 23;18(1):11. doi: 10.1007/s12105-024-01620-x. PMID: 38393464; PMCID: PMC10891032.
