Julia Zaragoza

A high neutrophil to lymphocyte ratio prior to BRAF inhibitor treatment is a predictor of poor progression-free survival in patients with metastatic melanoma

BackgroundSome studies have shown that a high neutrophil/lymphocyte ratio (NLR) ≥4 before initiating ipilimumab treatment is an independent prognostic indicator of poor survival in patients with metastatic melanoma (MM).ObjectivesTo determine whether the NLR before starting BRAF inhibitor (BRAFi) treatment in patients with (MM) is associated with progression-free survival (PFS).Materials & methodsThis retrospective study included 49 patients consecutively receiving BRAFi for MM between July 2012 and December 2014. Cox proportional hazards regression was used to analyse the relationship between NLR and other factors, such as lactate dehydrogenase (LDH), performance status, BRAFi as firstor second-line therapy, and corticosteroid intake with PFS. The NLR before starting BRAFi was significantly associated with PFS based on univariate analysis and multivariate analysis adjusted for potential confounding factors, such as LDH activity, ulceration, performance status, first-line therapy, and corticosteroid intake. A high NLR (continuous variable) was associated with short PFS (HR: 1.35; 95% CI: 1.07-1.70; p = 0.01), and NLR ≥4 was associated with shorter PFS (HR: 3.24; 95% CI: 1.30-8.12; p = 0.01). Corticosteroid intake was not associated with short PFS based on multivariate analysis.ConclusionAn NLR > 4, before starting BRAFi treatment, is an independent prognostic indicator of poor progression-free survival.

High-frequency ultrasound imaging for cutaneous neurofibroma in patients with neurofibromatosis type I

BackgroundNeurofibromas (NFs) are benign tumours arising from a nerve sheath, which are present in nearly all patients with neurofibromatosis type 1 (NF1). High-frequency ultrasound (HFU) systems, using frequencies over 20 MHz, were developed to improve visualization of skin tumours by means of increased resolution.ObjectivesTo describe NFs by using HFU in patients with NF1.Materials & MethodsAnonymized HFU (25-MHz) images of NFs were randomized. Initially, two dermatologist investigators, with experience in HFU imaging of the skin, together described the ultrasound images and established eight criteria for NFs. The same task was then repeated by two other dermatologists, also with experience in HFU imaging of the skin, independently, to establish inter-observer agreement.ResultsA total of 108 NFs in 29 patients were included. Superficial and subcutaneous NFs were hypoechoic with a round to spindle shape. Plexiform NFs were ill-defined, consisting of multiple hypoechoic linear zones. Good to excellent inter-observer agreement was found for six of the eight criteria (k>0.6).ConclusionThis is the first series describing HFU skin imaging of NFs in patients with NF1. Lateral extension that may correspond to involvement of an adjacent nerve seems to be specific to NFs.

Merkel cell carcinomas infiltrated with CD33+ myeloid cells and CD8+ T cells are associated with improved outcome

Background: Merkel cell carcinoma (MCC) is a rare tumor of the skin that has an aggressive behavior. Immunity is the main regulator of MCC development, and many interactions between lymphocytes and tumor cells have been proven. However, the impact of tumor‐infiltrating myeloid cells needs better characterization. Objective: To characterize tumor‐infiltrating myeloid cells in MCC and their association with other immune effectors and patient outcome. Methods: MCC cases were reviewed from an ongoing prospective cohort study. In all, 103 triplicate tumor samples were included in a tissue microarray. Macrophages, neutrophils, and myeloid‐derived suppressor cells were characterized by the following markers: CD68, CD33, CD163, CD15, CD33, and human leukocyte antigen‐DR. Associations of these cell populations with programmed cell death ligand 1 expression, CD8 infiltrates, and vascular density were assessed. Impact on survival was analyzed by log‐rank tests and a Cox multivariate model. Results: The median density of macrophages was 216 cells/mm2. CD68+ and CD33+ macrophage densities were associated with CD8+ T‐cell infiltrates and programmed cell death ligand 1 expression. In addition, MCC harboring CD8+ T cell infiltrates and brisk CD33+ myeloid cell infiltrates were significantly and independently associated with improved outcomes (recurrence‐free and overall survival). Limitations: Sampling bias and the retrospective design were potential study limitations. Conclusion: Infiltration of CD33+ myeloid cells and CD8+ T lymphocytes defines a subset of MCC associated with improved outcome.

Differentiating Merkel cell carcinoma of lymph nodes without a detectable primary skin tumor from other metastatic neuroendocrine carcinomas: The ELECTHIP criteria

Background: Merkel cell carcinoma (MCC) can present as a cutaneous tumor or a lymph node metastasis without a primary tumor. MCC presenting without a primary tumor (MCCWOPT) can be misinterpreted on histologic examination as lymph node metastasis (LNM) from another neuroendocrine carcinoma (LNMNEC). However, this distinction is crucial for therapeutic management. Objective: To determine the discriminative criteria for the differential diagnosis of MCCWOPT, LNM from cutaneous MCC, and LNMNECs. Methods: Clinical, morphologic, and immunohistochemical data (expression of cytokeratins AE1, AE3, 7, 19, and 20; chromogranin A, synaptophysin, thyroid transcription factor‐1 [TTF‐1]), as well as the presence of Merkel cell polyomavirus (by immunohistochemistry and PCR) were compared in patients with MCCWOPT (n = 17), LNM from a cutaneous MCC (n = 11), and LNMNEC (n = 20; 8 lung, 7 thyroid, 3 digestive tract, 2 other). Results: MCC (including MCCWOPT and LNM from a cutaneous MCC) differed from LNMNEC by 7 discriminative criteria: 1) elderly age, 2) location of the tumor, 3) extent of the disease, 4) cytokeratin expression, 5) TTF‐1 expression, 6) histologic type, and 7) Merkel cell polyomavirus detection, summarized under the acronym ELECTHIP. All MCC patients had ≥5 of the ELECTHIP criteria, whereas all patients with LNMNEC (except 1) had <3 criteria. Limitations: The discriminant ability of the ELECTHIP criteria should be validated in a second independent set. Conclusion: MCCWOPT can be distinguished from other LNMNEC by the ELECTHIP criteria.

High neutrophil-to-lymphocyte ratio before starting anti-programmed cell death 1 immunotherapy predicts poor outcome in patients with metastatic melanoma

From the Sorbonne Universit e, Facult e de M edecine Sorbonne Universit e, Assistance Publiquee Hôpitaux de Paris, Service de Dermatologie et Allergologie, Hôpital Tenon, Paris, France; Service de Dermatologie, Hôpital Saint-Eloi et Hôpital Universitaire de Montpellier, Montpellier, France; Assistance PubliqueeHôpitaux de Paris, Service de Dermatologie Hôpital SaintLouis, Universit e Paris VII, Sorbonne, Paris, France; Facult e de M edecine, Universit e de Strasbourg, et Clinique Dermatologique, Strasbourg, France; Unit e de Dermatologie et M edecine Interne, Universit e des Antilles, Campus Guadeloupe Fouillole et Universit e de Normandie, Universit e de Rouen Normandie, Institut National de la Sant e et de la Recherche M edicale U1234, France; and Service de Rhumatologie, Hôpitaux Universitaires de Strasbourg, Laboratoire d’Immunorhumatologie Mol eculaire, Institut National de la Sant e et de la Recherche M edicale UMR S1109, Universit e de Strasbourg, Strasbourg, France

Multiple “halo nevi” occurring during pembrolizumab treatment for metastatic melanoma

A female in her 30s, with a previous history of acral melanoma (T1aN0M0) treated by excision, presented in 2015 with homolateral ilioinguinal lymph node metastasis. She underwent complete lymph node dissection but presented unresectable regional relapse (T1aN3M0) 3 months later. No BRAF, CKIT, or NRAS mutations were found in tumoral tissue, and the treatment was pembrolizumab (2 mg/kg every 3 weeks). Eight weeks later, an achromic halo appeared around a preexisting nevus of the right