PMC8481697_01
Pathology findings. (A, B) pre-treatment histology showing the presence of atypical neoplastic clones at high cellularity in the same sample: (A) field with melanocytic clone of cells rich in cytoplasmatic melanic pigment; (B) other field with an amelanotic clone displaying intense mitotic activity. (C, D) histologic sampling at complete response: (C) absence of neoplastic cells replaced by loose and dense fibrotic tissue with histiocytes; (D) histiocytes show cytoplasm intensely filled with melanic pigment.
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In October 2019, the patient noted the onset of a pigmented cutaneous nodulation of about 2 cm in diameter at the left parietal skin of the scalp which was surgically removed resulting in a relapse of malignant melanoma, 3.1 mm in thickness, non-ulcerated, with 11 mitoses/mm2 and negative surgical margins (Figures 1A, B). A biopsy performed at this time showed the absence of vital neoplastic cells, with wide areas of histiocytes filled with melanotic pigment, associated to fibrosis in correspondence to the ECT-treated areas (Figures 1C, D).
Evolution of the lesions. (A) Basal evaluation; (B) 2 weeks after the first ECT; (C) 2 months after the first ECT and 1 month after 1 cycle of anti-PD1; (D) 3 months after the first ECT and 1 month after 2 cycles of anti-PD1; (E) 1 week after the second ECT; (F) 2 months after second ECT and completion of 5 cycles of anti-PD1; (G) 3 months after second ECT and anti-PD1 temporary suspension for toxicity; (H) 17 months after the second ECT and after 15 cycles of anti-PD1.
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The patient complained of frequent bleeding from the ulcerated lesions, continuous, severe pain at his scalp and was in serious concern for his life (Figure 2A). Nevertheless, after a few days, new lesions appeared in the proximity of the treated area (Figure 2B). Unfortunately, independently of treatment, the lesions increased in dimension, extension and number with some of them becoming ulcerated and bleeding (Figures 2C, D). As expected, the lesions treated with ECT started to reduce but other new lesions rapidly appeared (Figure 2E). After 2 further cycles of nivolumab, we observed an initial slow shrinkage of all lesions (Figure 2F). Immunotherapy was then started again (Figure 2G) and is currently ongoing. At present, after 18 months from the first ECT and after 14 months from the beginning of anti-PD-1 immunotherapy, the patient is in good clinical condition with complete remission of disease (Figure 2H).
Trends of neutrophil-lymphocyte ratio (A) and platelet-lymphocyte ratio (B) during treatment.
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NLR and PLR progressively increased until clinical response, then they both fell to a minimum value while maintaining a constant plateau level. NLR, and at a minor degree also PLR, presented an increase in their value over the last 2 months of treatment, concomitantly with the appearance of the superinfected pemphigoid lesions of the skin (Figure 3).
Treatment, response and toxicity. Red dots: electrochemotherapy. Blue dots: anti-PD-1 treatments. C: cycle of anti-PD-1. G: grade of toxicity according to Common Terminology Criteria for Adverse Events (CTCAE) classification, 5.0 version.
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The clinical case is visually summarized in Figure 4.