Expression of Programmed Cell Death-L1 (PD-L1) Protein and Mismatch Repair Mutations in Orbital Tumours-a Pilot Study

Purpose Programmed cell death protein 1 (PD-1) and DNA mismatch repair (MMR) deficiency play an important role in tumour progression and response to treatment. Both markers have been studied in some ocular tumours but little is known about these markers in orbital tumours. This pilot study reports on PD-L1 expression and MMR mutations using next generation sequencing (NGS) in specific orbital tumours. Methods We reviewed surgical specimens from patients with rhabdomyosarcoma, adenoid cystic carcinoma (ACC), pleomorphic adenoma (PA) and biopsy negative tissue from orbital tumours used as a control. immunohistochemistry (IHC) was performed on Formalin fixed paraffin embedded tissue using a PD-L1 antibody. DNA was extracted for targeted gene panel NGS of the MMR genes PMS2, MLH1, MSH6 and MSH2. Results The study included 17 orbital specimens. Scattered membrane PD-L1 staining was noted in 3/6 rhabdomyosarcoma specimens without an accompanying lymphocytic infiltrate. PD-L1 immunostaining was absent in 3/3 ACC, and 5/6 PA specimens. PD-L1 immunostaining was not detected in 2/2 control specimens. 4/17 samples shared the same pathogenic mutation in the MLH1 gene, including 3/6 rhabdomyosarcoma and 1/3 ACC samples. 1/6 PA samples had a mutation in MSH6. Conclusions Our study demonstrated scattered, non-quantifiable or absent PD-L1 staining in a limited sample of orbital tumours suggesting that PD-1/PD-L1 inhibitor therapy may not be useful in treatment of malignant orbital tumours (rhabdomyosarcoma and ACC) when refractory to conventional therapy. Our pilot study suggest that PD-L1/MMR axis might not play a major role in the pathogenesis of primary orbital tumour.

Hypertricosis overlying plexiform neurofibroma in a female patient: a rare presentation

Periorbital neurofibromas can occur either in isolation or in association with neurofibromatosis (NF). Neurofibromas in the periorbital region account for 0.5-2.4% of orbital tumours. Hypertrichosis overlying neurofibromas are rarely reported cases in literature. We report a case of localized hypertrichosis overlying neurofibroma in a 27 year old female with no other features of neurofibromatosis. Neurofibromas can occur as solitary lesions or in association with neurofibromatosis. Our patient had diffuse hypertrichosis on a hyperpigmented macule overlying and around the periorbital neurofibroma.

Intraorbital Tumours, Schwannoma, Neurofibroma

Schwannomas are rare benign tumours arising from neuroectodermal Schwann cells. They can arise from cranial, intraspinal, peripheral and autonomic nerve sheaths. Schwannomas represent 1 - 8 % of head and neck tumours. They constitute 25 – 40 % of extracranial tumours in head and neck region.1 Among the schwannomas arising in head and neck region those arising intraorbitally are very rare. The most common benign intra orbital tumours are haemangiomas. They can arise as localised forms or in association with Neurofibromatosis-1 (NF1). In patients with neurofibromatosis-type 1 or in patients with family history of NF, the risk of developing orbital schwannoma is 1.5 %. Schwannomas constitute 1 - 6.5 % of intra orbital tumours.2-6 Of these tumours those undergoing cystic changes are still rare. The most common cystic lesions in the orbit are dermoid cysts or mucoceles.