PMC9707535_01
Early tumor flare. CT scan at W12 (A) and PET scan at W18 (B) showed enlarged (A; red arrow) and hypermetabolic cervical lymph nodes (B; red arrow) and in the left palatine tonsil (B; grey arrow).
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At the end of the induction phase (W12), tumour assessment with computed tomography (CT) scan and Fluorodeoxyglucose (FDG)-Positron Emission Tomography (PET) identified enlarged, FDG-positive, bilateral cervical lymph nodes and left palatine tonsil (Figure 1A and B).
Late tumor flare. CT scan performed at W60 (A) detected a single lung nodule with morphologic feature of an inflammatory lesion (A; arrow) that disappeared at a follow-up CT at W72 (B; arrow).
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On May 2011, the W60 follow-up CT scan revealed a single lung nodule (37.9 x 34 mm) with radiologic features suggestive for an inflammatory lesion (Figure 2A). In view of the full radiologic recovery of this inflammatory lung event on August 2011 (Figure 2B), treatment was resumed and completed in June 2013, when the patient entered the study follow-up phase.
Radiologic features of lung melanoma metastasis. CT scan showed a lung lesion with irregular shape (A; arrow) and density (B, arrow) that had progressed compared to a previous CT scan (not shown).
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On January 2017, a control CT scan detected a single pulmonary nodule (7x6 mm) that significantly increased (12.5 x 8.5 mm) 4 months later; thus, also based on its morphologic features (Figure 3A and B) suspicious for a metastatic lesion, a wedge pulmonary resection was performed on June 2017.
Histopathologic features of lung melanoma metastasis. Histopathologic examination of the surgical specimen, (A; HE) revealed melanoma cells surrounded by a very abundant mononuclear inflammatory cells infiltrate (arrow) and plentiful necrosis (star). The mononuclear cell infiltrate consisted predominantly of CD4+ T cells intermingling neoplastic cells in the non-necrotic area (B; anti-CD4, Ventana Roche) and surrounding the necrotic area (C; anti-CD4, Ventana Roche); CD8+ T cells were identified both in the non-necrotic (D; Fuchsin/anti-CD8, Ventana Roche) and in the necrotic (E; anti-CD8, Ventana Roche) portion of the lesion. Scale bar: (A), 600 micron; (B and C), 250 micron; (D and E), 120 micron.
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Notably, histopathologic report depicted scattered residual melanoma cell nests surrounded by a rich mononuclear cell infiltrate and plentiful necrosis; immunohistochemistry revealed a T cell infiltration mostly composed of CD4+ and CD8+ cells (Figure 4A-D).  