[Analysis of clinical, pathological and molecular genetic characteristics of conjunctival melanoma]

Objective: To investigate the clinical, pathological and molecular genetic characteristics of conjunctival melanoma (CoM). Methods: A retrospective case series study was conducted. The clinical, imaging and pathological data of patients diagnosed with CoM from January 2004 to June 2025 at Shaanxi Eye Hospital of Xi'an People's Hospital (Xi'an Fourth Hospital) and Xi'an First Hospital were analyzed. Some patients were detected for the BRAF V600E mutation. The χ² test or the χ² correction test was used for statistical analysis. Results: A total of 70 patients (70 eyes) with CoM were enrolled, aged (60.8±10.6) years, including 40 males (57.1%) and 30 females (42.9%). There were 33 cases (47.1%) in the left eye and 37 cases (52.9%) in the right eye. The tumor was located at the bulbar conjunctiva in 37 cases (52.9%), at the vault conjunctiva in 24 cases (34.2%), and at the palpebral conjunctiva in 9 cases (12.9%), involving the orbit in 13 cases (18.6%), the eyeball in 3 cases (4.3%), and the lacrimal sac in 6 cases (8.6%). Most patients presented with black nodules or cauliflower-like masses in the conjunctival area. Some tumors were accompanied by superficial vascular hyperplasia and pigmentation of adjacent tissues, while some invaded the cornea or orbit, resulting in clinical manifestations such as visual field defects, exophthalmos and limited movement. Imaging showed irregular soft tissue density shadows at the conjunctival site. According to the criteria of the American Joint Committee on Cancer, the tumor was at the T1 stage in 10 cases (14.3%), T2 stage in 41 cases (58.6%), and T3 stage in 19 cases (27.1%), with superficial ulcers in 6 cases (8.6%). Histopathology results disclosed that 67 cases (95.7%) were of the nodular type, 3 cases (4.3%) were of the superficially diffuse type, 47 cases (67.1%) were of the epithelial cell type, and 23 cases (32.9%) were of the mixed cell type. Sixty-three cases (90.0%) were accompanied by melanin, 32 cases (45.7%) were accompanied by primary acquired melanosis, including 23 cases (32.9%) with atypical primary acquired melanosis and 2 cases (2.9%) with conjunctival nevus, and 48 cases (68.6%) had tumor infiltrating lymphocytes. Immunohistochemistry demonstrated positive melanin markers such as human melanoma-associated antigen 45, melanocyte antigen A, S-100 protein and sex-determining region Y-frame protein 10. Thirty cases (42.9%) completed the detection of BRAF V600E mutations, of which 11 had BRAF V600E point mutations, with a positive rate of 36.7%. Sixty-two patients (88.6%) were followed up, with a recurrence rate of 27.4% (17/62), a metastasis rate of 19.4% (12/62), and a case fatality rate of 54.8% (34/62). The recurrence rate was 4/5 among patients with ulcers, versus 22.8% (13/57) among patients without ulcers (χ²=4.96, P=0.026); it was 8/13 among patients with orbital invasion, versus 18.3% (9/49) among patients without orbital invasion (χ²=9.62, P=0.002). Thirty-four patients (48.5%) underwent complete resection of the ocular mass, 16 (22.9%) underwent partial resection, and 20 (28.6%) underwent ocular or intraorbital enucleation. Ten patients (14.3%) received BRAF inhibitor-targeted therapy. Seven patients had a significant reduction of the residual mass and no tumor progression, and 3 patients did not respond to the treatment and died from the disease progression. Conclusions: CoM mostly occurs in the unilateral eye of middle-aged and elderly patients, more common at the bulbar conjunctiva and fornix conjunctiva, and histopathological epithelial cell types are the main types, with a high recurrence and metastasis rate.