Johan Chanal

Mature Cytotoxic CD56bright/CD16+ Natural Killer Cells Can Infiltrate Lymph Nodes Adjacent to Metastatic Melanoma

Melanomas are characterized by high metastatic potential, with regional lymph node representing the most frequent site of early dissemination in this disease. These regional lymph nodes also represent the primary site for differentiation of natural killer (NK) cells. Although blood-derived NK cells can efficiently lyse melanoma cells isolated from metastatic lymph node (M-LN), there has been no study of the properties of the most disease-relevant NK cells isolated from M-LN in patients with melanoma. Here, we report that M-LN contains 0.5% to 11% of CD56(bright) NK cells among CD45(+) hematopoietic cells present and that this cell population surrounds tumor cell clusters in M-LN. This NK cell population was characterized by expression of CD62L, chemokine receptors, and high levels of natural cytotoxicity receptors (NCR), NK group 2 D (NKG2D), and DNAX accessory molecule 1 (DNAM-1). Expression of NCR-NKp30 and NKG2D correlated negatively with percentages of tumor cells in M-LN. Interestingly, M-LN contained a unique subset of mature CD56(bright)CD16(+) NK cells displaying coregulated expression of NCR and NKG2D activating receptors. Ex vivo analyses suggested that M-LN-derived NK cells were inactive but could be activated by appropriate cytokine signals [interleukin (IL)-2 or IL-15], and could lyse metastatic melanoma cells in a highly efficient manner compared with blood-derived NK cells. Taken together, the results offer evidence that adjuvant immunotherapy that targets NK cells in M-LN for activation may improve treatment of patients with sentinel lymph node-positive melanoma.

Molecular subtyping of Treponema pallidum in Paris, France.

Two major Treponema pallidum subtypes, 14 d/g and 14 d/f, were identified in a population of 119 patients with syphilis in Paris, France, characterized by a high proportion of men who have sex with men. A new subtype named 11 q/j was characterized, and a reinfection case was determined in 1 patient having consecuitve syphilis infection at 19-month interval.

Phenotypic and functional characteristics of blood natural killer cells from melanoma patients at different clinical stages.

Melanomas are aggressive skin tumors characterized by high metastatic potential. Immunotherapy is a valuable alternative for metastatic melanoma patients resistant to chemotherapy. Natural Killer (NK) cells are efficient anti-tumor cytotoxic effectors. We previously showed that blood NK cells from stage IV metastatic melanoma patients display decreased NK receptors and that chemotherapy modifies the functional status of blood NK cells. To investigate the role of NK cells along melanoma progression, we have here studied NK cells from patients at different stages of the disease. First, we showed that ex vivo NK cells from certain stage III–IV patients displayed low degranulation potential. Using a dynamic label-free assay, we found that immunoselected IL-2 activated blood NK cells from patients efficiently lysed melanoma cells through NKp46 and NKG2D receptors, independently to the clinical stage. Moreover, the ex vivo phenotype of circulating NK cells from 33 patients (stage I to IV) was extensively analyzed. NK cells from patients displayed higher variability in the percentages of Natural Cytotoxicity Receptors (NCR) and Natural Killer Group 2D (NKG2D) receptor expression compared to donor NK cells. The main defect was the decreased expression of NCR1 (NKp46) by NK cells from metastatic patients. Interestingly, we found a positive correlation between the NK cell percentages of NKp46 and the duration of stage IV in melanoma patients. Finally, we showed that NK cells infiltrated primary melanomas and displayed a predominant peritumoral distribution. These results are new arguments for the development of NK-based therapies in melanoma patients.

Chronic Meningococcemia Cutaneous Lesions Involve Meningococcal Perivascular Invasion Through the Remodeling of Endothelial Barriers

Chronic meningococcemia is a form of sepsis with frequent polymorphous skin lesions. Both in vivo and in vitro data suggest that, in these lesions, meningococci gain access from the capillary lumen to the peripheral extravascular compartment, in the absence of vascular dislocation, through a paraendothelial route.

Lipschütz Genital Ulceration Associated with Mumps

Lipschütz ulcers are characterised by a first flare of non-sexually related acute genital ulcers (AGU) occurring in adolescent girls. Epstein-Barr primary infection is the most frequently reported aetiology but other infectious agents are probably implicated. We report the first case of mumps associated with an AGU in a 21-year-old girl. She presented a bilateral parotitis with genital ulcers, and serology confirmed she had mumps. As in our case, most Lipschütz ulcers heal spontaneously within a couple of weeks and the diagnosis should be reconsidered in case of recurrence.

Actualités diagnostique et thérapeutique des infections à Neisseria gonorrhoeae

Bacterial culture remains the gold standard for symptomatic infection. Nucleic Acid Amplification Tests (NAATs) have better sensitivity and specificity for rectal and pharyngeal specimens. A bacterial culture with antibiogram must be done for all NAAT positive specimens in order to modify antibiotics prescription if needed. We must fear a diffusion of extensively drug-resistant Neisseria gonorrhoeae in the future. Nevertheless, ceftriaxone 500 mg intramuscular with 1 g of azithromycin against Chlamydia trachomatis remains the treatment of N. gonorrhoeae infections. Screening of partners of identified cases and other STDs is the main measure to add to the treatment of gonorrhea.

Age and clear eyes are associated with an increased risk of cutaneous squamous cell carcinomas in vemurafenib-treated melanoma patients.

Cutaneous squamous cell carcinoma (cSCC) is a frequent side-effect of vemurafenib treatment. The main aim of this study was to identify the clinical risk factors associated with the development of cSCC in melanoma patients treated with vemurafenib. We carried out a retrospective study, including 63 consecutive melanoma patients treated with vemurafenib for BRAF-mutant metastatic melanoma in an oncodermatological department. Clinical and follow-up data were collected and analysed, and a comparison of the subgroups who did and did not develop cSCC was performed. A total of 42.9% of patients (n=27) treated with vemurafenib developed one or more cSCC. Patients with cSCC were significantly older (P=0.01). Clear eyes were also associated with a higher risk of developing cSCC (odds ratio=3.50; 95% confidence interval: 1.08–12.43). Three patients developed cSCC more than 1 year after the initiation of treatment (12, 16 and 18 months, respectively). Clinicians should be vigilant in older patients undergoing vemurafenib therapy as well as patients with clear eyes as they seem to be at increased risk of developing cSCC, even late after the initiation of treatment.

BRAFV600 inhibitor discontinuation after complete response in advanced melanoma. A retrospective analysis of 16 patients

BRAF inhibitors (BRAFi) improve progression-free survival and overall survival in patients with advanced melanoma (1,2), with 3 to 6% of patients experiencing complete remission (CR)(1,3). Nevertheless, this efficacy comes at a cost with 90% of patients experiencing at least one adverse event and 45% grade 3 or 4 adverse events (4). Management of long-term responders is not yet well delineated: safety argues for treatment continuation, because evolution after discontinuation is unknown. This article is protected by copyright. All rights reserved.

Locally Advanced Unresectable Vaginal Melanoma: Response With Anti-Programmed Death Receptor 1.

CASE REPORT Mucosal melanoma is rare. We report an impressive partial response to pembrolizumab, an anti–programmed death receptor 1 (PD-1) in a patient with locally advanced and unresectable vaginal mucosal melanoma after failure of imatinib and ipilimumab. A 72-year-old woman attended in July 2012 for a mucosal vaginal melanoma of the anterior vaginalwall, described as a large infiltration of 2.5 mm in Breslow thickness and an 8-mm thick polypoid lesion. She underwent full colpectomy with bilateral adnexectomy and pelvic lymph node dissection. Pathological report showed residual mucosal vaginal melanoma of 1.5 mm in thickness whose resection was incomplete laterally and without any lymph node involvement among 9 resected bilateral iliac lymph nodes. The tumor harbored neither BRAF nor NRASmutations. There was no mutation of the c-kit gene but amplification. Immunostaining was negative for PD-1 or PD-L1 (program death receptor ligand). An additional treatment was discussed. Interferon alpha was contraindicated because of the depressive mood of the patient, already treated by paroxetine. Imatinib was also considered but did not seem appropriate at that stage because of the absence of an evaluable target either clinically or radiologically. Finally, the surgeons were asked for an additional resection but judged that it was not appropriate. Therefore, a close followup both clinical every 3 months and by imaging every 6 months was proposed to the patient. Ten months later, new melanocytic lesions developed on the colpectomy scar. Progression was confirmed by a PET scan and by a biopsy. Surgical treatment consisted in resection of the entire residual vagina, resection of a 5-mm portion of distal urethra, and resection of a left inguinal lymph node and a right superficial lymph node dissection that provided 3 lymph nodes. Urethra and lymph nodes were disease free. Excision of the melanoma was again incomplete pathologically. Surgeons were asked to reoperate but were reluctant to perform a pelviectomy with colic derivation. Imatinib was not considered in the absence of any radiological target lesion. The situation was explained to the patient who refused a mutilating operation. Therefore, a follow-up without additional treatment was restarted. Six months later, pelvic magnetic resonance imaging (MRI) identified a recurrent nodule of the vaginal wall measuring 35 26 mm in diameters. Imatinib (400 mg daily) was initiated. Two months later, the treatment was stopped because of neutropenia

A fifth subtype of Kaposi's sarcoma, classic Kaposi's sarcoma in men who have sex with men: a cohort study in Paris

Classic Kaposis sarcoma (CKS) occurs predominantly among elderly men and is associated with Kaposis sarcoma‐associated herpesvirus (KSHV). In low‐endemic countries, KSHV infects predominantly men having sex with men (MSM).