Two cases of BRAF‐mutated, bulbar conjunctival melanoma, and review of the published literature

Abstract

Summary We describe two patients with BRAF‐mutated melanoma of the epithelioid cell type arising from primary acquired melanosis with severe atypia of the right bulbar conjunctiva. Patient 1 was a 71‐year‐old Japanese man. After adjuvant cryotherapy and enucleation of the right eyeball, therapy with vemurafenib was administered for a distant metastasis to a lumbar vertebra, accompanied by erythema multiforme and two keratinous tumours. The patient died due to metastases to the liver and multiple vertebrae, despite therapy with nivolumab and combination therapy with dabrafenib plus trametinib. Patient 2 was a 72‐year‐old Japanese man. After adjuvant cryotherapy, periodic mitomycin C eye drops, and excision of the superficial portion of the right parotid gland and the dissection of cervical lymph nodes, he was treated with adjuvant combination therapy with dabrafenib plus trametinib. Dermatologists should be familiar with BRAF‐mutated conjunctival melanoma, which is usually located on the bulbar conjunctiva and associated with more frequent distant metastasis.

<p>Conjunctival Melanoma: Update on Genetics, Epigenetics and Targeted Molecular and Immune-Based Therapies</p>

“…Table 1 summarizes the reported number of cases for each mutation, the percentage of mutations detected as well as any associated clinicopathological features. 11,15,16,20,[22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] BRAF is a serine-threonine kinase responsible for activating the next kinase in the pathway, MEK. BRAF mutations have been found in 29.7% (n=167) of conjunctival melanomas (n=563) reported to date, both primary and metastatic (Table 1).…”

“…36 To date, a total of nine conjunctival melanoma cases have been managed with BRAF and BRAF/MEK inhibitors (Table 2) 28,31,32,34,35,38,40,94 Four cases were treated solely with BRAF inhibitor monotherapy, 28,32,34,94 vemurafenib 32,34,94 or dabrafenib. 94 The remaining five cases received BRAF/MEK inhibitor combination therapy 31,35,38,40 with dabrafenib/trametinib 31,35,38,40 and vemurafenib/cobimetinib. 31 In one case, the anti-PD1 agent pembrolizumab was also used 81 and in another case, the anti-PD1 agent nivolumab was given in combination with dabrafenib and trametinib.…”

“…31 In one case, the anti-PD1 agent pembrolizumab was also used 81 and in another case, the anti-PD1 agent nivolumab was given in combination with dabrafenib and trametinib. 38 Indications for treatment included locally advanced disease in two cases 31,35 and metastatic disease in the remaining seven cases. 28,32,34,38,40,94 Out of the 4 cases that received BRAF inhibitor monotherapy, one patient demonstrated mixed results, with initial improvement followed by disease progression, 28 two patients responded partially to the treatment, 32,94 and one patient with metastatic disease was on complete remission at 52 weeks of follow-up.…”

“…38 Indications for treatment included locally advanced disease in two cases 31,35 and metastatic disease in the remaining seven cases. 28,32,34,38,40,94 Out of the 4 cases that received BRAF inhibitor monotherapy, one patient demonstrated mixed results, with initial improvement followed by disease progression, 28 two patients responded partially to the treatment, 32,94 and one patient with metastatic disease was on complete remission at 52 weeks of follow-up. 34 Out of the 3 cases that received BRAF/MEK inhibitor combination therapy alone, 35,38,40 one patient with metastatic disease demonstrated complete disease remission, 38 while another one showed only partial improvement.…”

“…28,32,34,38,40,94 Out of the 4 cases that received BRAF inhibitor monotherapy, one patient demonstrated mixed results, with initial improvement followed by disease progression, 28 two patients responded partially to the treatment, 32,94 and one patient with metastatic disease was on complete remission at 52 weeks of follow-up. 34 Out of the 3 cases that received BRAF/MEK inhibitor combination therapy alone, 35,38,40 one patient with metastatic disease demonstrated complete disease remission, 38 while another one showed only partial improvement. 40 The third patient, who had presented with locally advanced conjunctival melanoma, responded substantially to BRAF/MEK inhibition as neoadjuvant therapy, which allowed for the subsequent resection of the shrunk lesion.…”