Pathologic complete response to intralesional interleukin-2 therapy associated with improved survival in melanoma patients with in-transit disease.

PURPOSE: Melanoma patients with in-transit disease have a high mortality rate despite various treatment strategies. The aim of this study was to validate the role of intralesional interleukin (IL)-2, to understand its mechanism of action, and to better understand factors that may influence its response. METHODS: We retrospectively collected the clinicopathological data of 31 consecutive patients who presented to a tertiary care cancer center for treatment of in-transit melanoma with intralesional IL-2. Kaplan-Meier survival curves and multivariable Cox regression analysis were performed. Immunohistochemistry (IHC) was used to better understand the immune response to localized IL-2 therapy. Targeted next-generation sequencing was performed to genomically characterize the tumors. RESULTS: Ten patients (10/31, 32 %) achieved a pathologic complete response (pCR), 17/21 (55 %) had a partial response, and 4/21 (19 %) had progressive disease on treatment. pCR to IL-2 therapy was associated with overall survival (log-rank p = 0.004) and improved progression-free survival (PFS) [adjusted hazard ratio (HR) 0.11; 95 % CI 0.02-0.47; p = 0.003). A higher CD8+ T cell infiltrate was identified in in-transit lesions with a pCR compared with the other lesions (mean IHC score 3.78 vs. 2.61; p = 0.01). Patients with an elevated CD8+ infiltrate demonstrated an improved PFS (unadjusted HR 0.08; 95 % CI 0.01-0.52; p = 0.008). CONCLUSIONS: Thirty-two percent of patients achieved pCR with intralesional IL-2 therapy and had a significantly improved PFS compared with the rest of the cohort, which may be explained by a systemic CD8+ T-cell response.

Primitive nonneural granular cell tumor (so-called atypical polypoid granular cell tumor). Report of 2 cases with immunohistochemical and ultrastructural correlation.

Primitive nonneural granular cell tumors (so-called atypical cutaneous granular cell tumors) were first described in 1991, followed by few case reports, and 2 recent larger series. We report here 2 additional cases in 2 women aged 73 and 74, who presented with 0.6- and 0.4-cm skin nodules on the right side of the jaw and the forearm, respectively. Biopsies showed cutaneous granular cell neoplasms with epithelioid morphology. The cells exhibited nuclear pleomorphism and brisk mitotic activity with atypical mitoses. Immunohistochemically, the tumor cells expressed vimentin and PGP 9.5 but lacked S-100 and CD34 expression. Ultrastructurally, both cases showed primitive cells packed with large secondary lysosomes. Primitive nonneural granular cell tumors seem to consist of neoplastic proliferating cells that fail to break down uncharacterized cellular material within the lysosomes. They are, however, different from classic granular cell tumor by lacking neural differentiation. Despite reported worrisome cellular atypia, these rare tumors seem to pursue a favorable outcome.