High‐risk histopathologic features in local advanced conjunctival melanoma

Purpose To identify high‐risk histopathologic and molecular features of local recurrence, nodal metastasis, distant metastasis (DM) and disease‐specific death (DSD) in conjunctival melanoma (CoM). Methods Ninety patients with pathologically diagnosed CoM between 2008 and 2023 were enrolled. Immunohistochemistry staining of BRAF V600E , NRAS Q61R , CD117, PD‐1 and PD‐L1 was performed in 65 and 45 patients, respectively. Cox regression and Kaplan–Meier survival analysis were conducted to identify risk factors for local recurrence, nodal metastasis, DM and DSD. Results Pathologically, ulceration (hazard ratio [HR]: 3.170; 95% CI: 1.312–7.659; p = 0.01) and regression (HR: 3.196; 95% CI: 1.094–9.335; p = 0.034) were risk factors for DM. Tumour thickness ≥ 4 mm (HR: 4.889; 95% CI: 1.846–12.946; p = 0.001) and regression (HR: 4.011; 95% CI: 1.464–10.991; p = 0.007) were risk factors for DSD. For patients with tumour thickness < 4 mm, the presence of ulceration indicated a higher risk of nodal metastasis (log‐rank p = 0.0011), DM (log‐rank p = 0.00051) and DSD (log‐rank p = 0.02). Patients with regression (+)/tumour‐infiltrating lymphocytes (TILs) (+) had a higher risk for DM (log‐rank p = 0.011) and DSD (log‐rank p = 0.0032). Molecularly, the positive rate of BRAF V600E , NRAS Q61R , CD117, PD‐1 and PD‐L1 was 40.00% (26/65), 43.08% (28/65), 70.77% (46/65), 46.67% (21/45) and 28.89% (13/45), respectively. Positive BRAF V600E was identified as an independent risk factor for DM (HR: 2.533; 95% CI: 1.046–6.136, p = 0.039). The expression level of BRAF V600E was positively correlated with vascular invasion ( p = 0.01), as well as the expression levels of PD‐1 ( p = 0.038) and PD‐L1 ( p = 0.049). Conclusions Tumour thickness ≥ 4 mm, ulceration, the coexistence of regression and TILs, and positive BRAF V600E were risk factors for poor prognosis of CoM patients. Besides, expression level of BRAF V600E was positively correlated with the expression levels of PD‐1 and PD‐L1.