A 72-year-old man was treated with voriconazole for pulmonary aspergilloma after surgical treatment for lung cancer. Two years later he developed a rapidly growing skin tumor on his left cheek. He was diagnosed as squamous cell carcinoma and he soon developed a metastasis to the infra-auricular lymph node. He underwent resection surgery with superficial parotidectomy and lymph node resection, and post-operative radiotherapy. He also presented with hyperpigmentation and keratotic macules on his face and arms, which resided after discontinuing voriconazole therapy. Histopathologically the keratotic macules revealed dyskeratosis of the keratinocytes. There are increasing reports on association of phototoxicity and cutaneous squamous cell carcinoma with long-term voriconazole treatment, an adverse drug reaction of importance dermatologists should be aware of.
A 73-year-old woman underwent surgery for a black macule on the right forearm when she was 70-year-old. Histopathological analysis revealed malignant melanoma. She underwent extended resection and biopsy of the sentinel lymph node. The sentinel lymph node was negative for melanoma (tumor thickness 1.4 mm, pT2aN0M0, Stage IB). After the surgery, local injection of interferon-β followed 3 months. When she was 73-year-old, chest X-ray revealed multiple nodular shadows on her both lungs. She had undergone partial resection of lung. Histopathological analysis was consistent with lung metastasis of malignant melanoma. She underwent 8 courses of chemotherapy of dacarbazine. However, she had new metastases in brain, liver, and bone. Thereafter, she received treatment of nivolumab (2 mg/kg was administered every 3 weeks). After the third nivolumab, lung and liver metastases decreased the size by over 30%. After the fifth nivolumab, brain metastasis decreased the size by 38%. After the sixth nivolumab, she had severe interstitial pneumonias due to nivolumab, leading to discontinuation of nivolumab. However, lung and liver metastases decreased the size even more 12 weeks after discontinuation and brain metastasis also decreased 16 weeks after discontinuation. Positron emission tomography (PET) revealed improvement of bone metastasis. Thus, nivolumab was effective to every metastasis lesion including brain, lung, liver, and bone in this patient. While there is no clear evidence of effectiveness of nivolumab on brain metastasis, nivolumab could be a useful choice for patients with multiple metastases including brain lesion.
In this review article, the author discusses possible surgery-driven interruption of tumor dormancy in melanoma. He also discusses the critical appraisal of the Multicenter Selective Lymphadenectomy Trial-1 data, which reveals the low quality of the trial due to the risk of bias and imprecision of the estimated effects. Based on these considerations, the author emphasizes the importance of combining surgery with systemic therapies using a number of newly developed drugs, such as kinase inhibitors and immune check point inhibitors.