Excisional biopsy was performed on a small tumor and immune staining suggested lung cancer as the primary source.
Metastatic cancer of an unknown primary source accounts for 3% to 5% of invasive cancers.1 Poorly differentiated SCC, as in this case, may arise from skin, lung, or head and neck SCC. Risks of metastatic disease in cutaneous SCC include size greater than 2 cm, depth greater than 2 mm, and location on the ear, hand, lip, or within a burn.2 Recurrent tumors, poorly differentiated tumors, and tumors demonstrating perineural invasion also increase the risk of metastasis.
Having failed both previous treatments, further tissue characterization offered some hope of effective immunotherapy. Specifically, SCC from lung cancer as a primary source may express programmed-death ligand 1 (PD-L1), a transmembrane protein that suppresses adaptive immune responses. Pembrolizumab inhibits this molecule leading to a more aggressive immune response to tumor cells. Additionally, tumor profiling of specific oncogenes can highlight potentially beneficial therapies.
In this case, gene profiling identified several active tumor oncogenes, but PD-L1 was not strongly expressed. Despite the effort, this process did not uncover practical or novel treatment options. The patient was offered an empiric trial of immunotherapy but opted to pursue palliative therapy alone and passed away 2 months later.
This case highlights the role of multidisciplinary care of metastatic disease to the skin and the potential role, and limitations, of skin biopsy in tumor profiling and treatment guidance. Even though the most likely primary site was lung, cutaneous metastases can be equally devastating.
Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).