Case Report
73-year-old white male presented with large right shoulder soft tissue mass (17x5 cm) near the scapula, and was subsequently sent for surgical resection by his primary care. Pathology showed nodular melanoma with positive margin, lymphovascular invasion and neurotropism present with high mitosis. PET-CT scan showed positive uptake in axillary and supraclavicular lymph nodes as well as uptake in the left proximal tibia. Biopsy of the bone was also positive for melanoma. Molecular study showed BRAF mutation at L597, high tumor mutation burden (24 mutations/Mb), and PD-L1 positive in 60% of tumor cells and PD-1 was positive in immune cells, but not in tumor cells. One other distinct feature of this clinical presentation was the abundance of macrophages (CD68+) in the tumor microenvironment. Patient was initiated therapy with pembrolizumab. However, three weeks after his second cycle, he was admitted to hospital due to severe weakness in both upper extremities and pain at night. He also experienced a new onset of polyarthralgia in both hands, unable to play musical instruments. He was started on steroid treatment and showed significant improvement. Once steroid was tapered off, the sensation of pain substantially decreased but persisted. EMG showed right median motor neuropathy and left median sensory neuropathy. Blood test detected ANA positive, and as TSH was high, levothyroxine was initiated.
Outcome
His PET-CT scan showed improvement after only two cycles of treatment and has remained stable for over ten months without any treatment (patient elected to stop pembrolizumab treatment due to frequent traveling). We have performed a more detailed study of the macrophages in his tumor sample and interestingly, the majority of macrophages were type-1 (CD 80+), with some, type-2 macrophages (CD163+). It is known that type-1 macrophages are pro-inflammatory and have antitumor effect, while type-2 macrophages have opposite effect and often promote tumor growth and metastasis. This could explain the side effect and long duration of response despite only two cycles of pembrolizumab treatment. Characteristics of macrophages in melanoma tumor samples may be an important parameter to predict side effect and tumor response beyond PD1 or PD-L1 expression.