Prognostic value of TERT promoter mutations in conjunctival melanomas in addition to clinicopathological features.

AIMS: To evaluate the prognostic value of clinical, histopathological and molecular features and to relate different treatment modalities to clinical outcome in conjunctival melanomas (CM). METHODS: Retrospective review of clinical, histopathological and BRAF V600E and telomerase reverse transcriptase (TERT) promoter mutation status and treatment modalities, correlated to recurrence and metastasis in 79 patients with CM, diagnosed between 1987 and 2015 in three tertiary referral centres in the Netherlands and Belgium. RESULTS: Out of 78 evaluable patients, recurrences occurred in 16 patients and metastasis in 12 patients (median follow-up time 35 months (0-260 months)). Tumour thickness >2 mm, pT status, the presence of epithelioid cells, ulceration and mitoses was significantly correlated with metastasis (p value 0.046, 0.01, 0.02, 0.001 and 0.003, respectively). Furthermore, CM frequently harbour BRAF V600E and TERT promoter mutations (29% and 43%, respectively). TERT promoter mutations were correlated to shorter metastasis-free survival (p value 0.002). No significant correlation was found for clinical parameters and metastatic disease. Palpebral, forniceal and caruncular melanomas were more prone to develop recurrences (p value: 0.03). Most CM were treated with excision with adjuvant therapy. CONCLUSION: In line with the recommendations in the Eighth Edition of the American Joint Committee on Cancer Staging for CM, the pathology report should include information about pT status, tumour thickness, presence of epithelioid cells, ulceration and mitoses. Furthermore, information about the presence of a TERT promoter mutation and BRAF V600E mutation is of interest for therapeutic decision making. The presence of a TERT promoter mutation is correlated to metastatic disease.

A nation-wide epidemiological study on the risk of developing second malignancies in patients with different histological subtypes of nasopharyngeal carcinoma.

OBJECTIVE: Risk assessment of second head/neck and Epstein Barr Virus (EBV)-related malignancies in patients with different nasopharyngeal carcinoma (NPC) subtypes. METHODS: This is a cross-sectional study. Pathology records were retrieved from PALGA (a Dutch pathology registry database) between 1995 and 2013. Second primary malignancy (SPM) data was extracted from PALGA. Odds ratios (OR) for SPM in the head/neck, and the upper/lower airways were calculated using logistic regression. Pearson X(2)-test and Fisher's exact test were used to assess the relationship between NPC (and EBV-status) with SPM. Standardized incidence rates (SIR) were calculated. RESULTS: Histologically diagnosed NPC (keratinizing and undifferentiated and differentiated non-keratinizing subtypes) (n=1175) were identified. NPC patients have an increased risk of second head/neck malignancies (SIR 4.7 95% CI 3.3-6.5). Keratinizing NPCs have an OR of 1.947 (95% CI 1.362-2.782) for SPM, an OR of 4.026 (95% CI 2.308-7.023) for carcinomas of the upper/lower airways, an OR of 4.306 (95% CI 2.299-8.066) for head/neck malignancies, an OR of 5.289 (95% CI 2.740-10.211) for HNSCC with a SIR of 4.7 (95CI 3.3-6.5). Non-keratinizing NPCs also have an increased risk of head/neck malignancies with a SIR of 3.2 (95% CI 1.8-5.1), but less than keratinizing NPCs (p=<0.001). Positive EBV-status is not associated with (EBV-related) SPM. CONCLUSION: NPCs have a higher risk of SPM regardless of EBV status. SPM (especially HNSCC and malignancies of the upper aerodigestive tract) are more prevalent in keratinizing NPC compared to non-keratinizing NPC. Close clinical follow-up of NPC patients, with specific attention on SPM, is justified.