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B cell mediated lysis
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Complement mediated lysis
Metastatic migration
Spontaneous regression
T cell mediated lysis
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This patient who presents with loss of color in a melanoma lesion after the initiation of treatment most likely is experiencing T-cell mediated destruction of malignant melanocytes. Melanoma is a malignancy of melanocytes that undergoes neoplastic transformation. The most common presentation of this disease is a pigmented lesion with the following characteristics: asymmetry, border irregularity, color variation, diameter ≥ 6 mm, and evolution over time (ABCDE). Treatment consists of wide local excision if the disease is limited or checkpoint immunotherapy (vemurafenib) if there is metastatic disease. This type of therapy causes malignant cells to experience abnormal cell cycle progression that is recognized by killer T-cells. Loss of color or pigmentation in melanoma is a positive prognostic factor demonstrating that T-cells are killing the malignant melanocytes. Fukuda discusses the role of the CD8+ T cell response in the treatment of melanoma. He presents data showing that vitiligo induced by cancer immunotherapy is a favorable prognostic factor in patients with melanoma. Incorrect Answers: Answer 1: B cell mediated lysis is not consistent with the mechanism of melanoma depigmentation. B cells produce antibodies that can neutralize spreading particles and are more effective against viruses and bacteria. Answer 2: Complement mediated lysis is a mechanism of destroying cells that have lost the ability to degrade circulating complement. This alternative pathway of activation can destroy neoplastic cells but is not a major factor in melanoma. Answer 3: Metastatic migration can result in cancer cells that appear in a different location than the primary tumor. Metastasis does not eliminate the original tumor and would not result in depigmentation. Answer 4: Spontaneous regression can occur in some forms of leukemia after they are treated with induction chemotherapy; however, this is not a mechanism of treatment for melanoma. Bullet Summary: Depigmentation of melanoma lesions being treated with immunotherapy is caused by T-cell mediated destruction of malignant melanocytes.
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