Contralateral axillary metastasis (CAM) in breast cancer is presently treated as a stage IV disease. We hypothesized that this disease pattern is a manifestation of direct aberrant lymphatic drainage and would behave more similar to advanced locoregional disease. This is a single-site, retrospective review of patients with biopsy-proven CAM from 2008–2017. Descriptive analysis was performed. Twenty-three patients met the inclusion criteria. The median disease-free interval from primary tumor treatment to diagnosis of CAM was 68 months (range, 36–155 months). This population had aggressive disease (74% local recurrences and 61% clinical evidence of cutaneous or underlying muscular invasion) and extensive locoregional therapy (70% radiated, 57% mastectomy, and 65% axillary lymph node dissection) before their presentation with CAM. Fifteen (65.2%) patients recurred after treatment of CAM; the median recurrence-free interval was 11 months (range, 5–23 months), and 12 (52.2%) patients developed distant metastases. The median distant metastasis-free survival was 14 months (range, 11–23 months), and the median overall survival was 31 months (range, 22–67.5 months). Development of CAM is associated with aggressive disease and extensive prior locoregional surgery and/or radiation. The short recurrence-free interval and high progression to additional stage IV disease suggest these patients behave similar to traditional stage IV patients with resected oligometastatic disease.

Background: Tumoral melanosis clinically resembles metastatic melanoma, occurs in the context of regressed disease, and requires evaluation to rule out underlying melanoma and metastatic disease. Histopathology demonstrates a nodular infiltrate of melanophages in the dermis, subcutaneous tissue, deep soft tissue, or lymph nodes in the absence of viable melanocytes. Recent limited reports of tumoral melanosis in the context of immunotherapy with ipilimumab (monoclonal antibody targeting CTLA-4) as well as nivolumab and pembrolizumab (humanized monoclonal antibodies against programmed death 1 receptor) highlight a unique presentation representative of treatment-related tumor regression and an association with a favorable clinical response.Objective: To describe our experience with tumoral melanosis in the setting of immunotherapy for metastatic melanoma and elucidate the clinical and histopathological features.Methods: Retrospective case series from a single tertiary care institution. Results:We describe 10 cases of patients with metastatic melanoma who received treatment with immunotherapy before the development of tumoral melanosis. Length of time between the initiation of therapy and the onset of tumoral melanosis ranged from 2 to 20 months with a mean time of 10 months. At the end of the follow-up period, 8 patients were classified as having a complete or partial response to treatment with immunotherapy. One patient had progression of visceral and cutaneous disease on ipilimumab despite developing tumoral melanosis, and 1 patient had yet to undergo repeat imaging. Furthermore, at the end of follow-up, 3 patients were alive with no evidence of active disease, 5 patients were alive with disease, and 1 patient was deceased, although this patient died of a cardiovascular event unrelated to his underlying melanoma. Of the patients who were classified as alive with disease, 2 patients had minimal remaining disease, and 2 patients had an almost complete response on immunotherapy with recurrence of visceral metastases after immunotherapy was discontinued. One patient developed new peritoneal and cutaneous metastases on pembrolizumab despite development of tumoral melanosis. Conclusions:The underlying biologic mechanisms and prognostic implications of tumoral melanosis in the setting of immunotherapy remain to be elucidated. Further prospective studies with a larger cohort and prolonged follow-up are necessary to better understand the incidence, prevalence, and oncologic outcomes in patients with tumoral melanosis who receive immunotherapy.

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