[Creation, implementation and objectives of CARADERM, a national network for rare skin carcinomas - Adnexal neoplasm part]. / Développement, mise en œuvre et objectifs de CARADERM, réseau national cancers cutanés rares ­ partie carcinomes annexiels.

INTRODUCTION: CARADERM is a French national network that includes patients with rare skin adnexal neoplasms. The present paper describes only the adnexal neoplasm part of this network. The primary objective of CARADERM is to improve medical care for malignant skin adnexal neoplasms. A multidisciplinary review group and a centralized pathological review group have been set up. PATIENTS AND METHODS: A dual network of clinicians and pathologists has been set up. Data are recorded in a secure database. RESULTS: The CARADERM network comprises of 38 clinical centres and 22 pathology centres. Between 2014 and 2017, 1598 patients with an adnexal neoplasm were included. Data of interest were documented in 80% of cases. Median patient age was 72 years. Major histological subtypes were sweat gland carcinomas (50%), hair follicle carcinomas (37.7%), and sebaceous gland carcinomas (9.8%). Surgery was the first-line treatment for 81% of patients, including 76.9% with standard surgical margin analysis, and 5.5% with exhaustive margin analysis. 920 patients (57.6%) underwent a national pathology review process. DISCUSSION: The CARADERM network aims at providing assistance in difficult situations concerning diagnosis and care in skin adnexal neoplasms. Analysis of the CARADERM data should allow the creation of a prognostic classification of these rare neoplasms together with recommendations. A national multidisciplinary consensus exists. Translational and therapeutic research is ongoing. CONCLUSION: The CARADERM network is currently recruiting and more data should lead to improved knowledge of these tumours in the coming years.

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

BACKGROUND: Classic Kaposi's sarcoma (CKS) occurs predominantly among elderly men and is associated with Kaposi's sarcoma-associated herpesvirus (KSHV). In low-endemic countries, KSHV infects predominantly men having sex with men (MSM). OBJECTIVES: To describe a cohort of classic Kaposi sarcoma in a low-endemic area for KSHV, to highlight the features of CKS in MSM and identify prognostic factors. METHODS: Retrospective single-centre study of CKS cases. We compared MSM to heterosexual patients. Then, we divided the patients into two subgroups, those requiring a systemic treatment and the others, and we performed univariate and multivariate analyses to determine aggressiveness of CKS. RESULTS: Between 2006 and 2015, seventy-four patients were included. Mean age at diagnosis was 68.9 years; sex ratio (M/F) was 6.4, and 28% were MSM; MSM patients were younger (P = 0.02), less often originated from endemic areas (P < 0.0001). KS was less severe (P = 0.04), required more often a local treatment than a systemic one (P = 0.03). On multivariate analysis, CD4 T-cell count > 500/mm3 at baseline was associated with a reduced risk of severe evolution. CONCLUSION: First CKS cohort in low-endemic zone. We describe a fifth subtype of KS: KS in MSM. The CD4 T-cell count was found to correlate with prognosis.

Anaplastic Kaposi's sarcoma: 5 cases of a rare and aggressive type of Kaposi's sarcoma.

BACKGROUND: Anaplastic Kaposi's sarcoma (KS) is a rare form of KS characterized clinically by the development of a tumour mass with unusual local aggressiveness and histologically by a specific architecture and cytological morphology. A very small number of limited series in endemic countries have established characteristics common to these anaplastic forms of KS. We present five patients with an anaplastic form in a context of KS ongoing for several years in a non-endemic country. MATERIALS AND METHODS: We collected 5 cases of anaplastic KS followed in our department over a period of 20years. We describe the main developmental, clinical, virological and histological features. RESULTS: The cases involved 4 men and 1 woman whose mean age at diagnosis of anaplastic KD was 70years, with an average time of 25years between initial diagnosis of KD and anaplastic transformation. Our patients were all treated with chemotherapy and/or radiotherapy (RT) prior to diagnosis of anaplastic transformation. All patients had a tumour mass of the lower limbs developing in classically indolent KS with associated chronic lymphoedema. Progression was very aggressive locally with deep invasion of the soft tissues as well as osteoarticular involvement, without visceral dissemination. At present, three patients are dead, one patient is showing partial response, and one patient is in locoregional progression. Diagnosis of the disease was based on histopathological findings. The tumour cells were undifferentiated, pseudo-cohesive, and chiefly organized in sheets. The mitotic count was high (27 mitoses per 10 fields at high magnification). Necrosis was constant. DISCUSSION: To our knowledge, this is the first series describing anaplastic Kaposi's sarcoma in a non-endemic country. The severity of the prognosis, despite the absence of visceral dissemination, is related to the local aggressiveness of anaplastic KS and to its resistance to radiotherapy and chemotherapy, with amputation being required in certain cases.

Neutrophilic eccrine hidradenitis in two patients treated with BRAF inhibitors: a new cutaneous adverse event.

Neutrophilic eccrine hidradenitis (NEH) is a rare neutrophilic dermatosis, first described in patients undergoing chemotherapy for a malignant haemopathy. It has polymorphous clinical features and the association of both clinical and histological features is necessary to make a diagnosis. We report the first two cases of NEH in patients treated with a BRAF inhibitor (BRAFi), either dabrafenib or vemurafenib, for a stage IV metastatic melanoma. Disseminated erythematous plaques associated with fever and polyarthralgia occurred early after the initiation of treatment and were badly tolerated. Histological analyses confirmed the diagnosis of NEH. Symptoms disappeared a few days after the cessation of treatment and introduction of topical steroids. The replacement of one BRAFi with another is a therapeutic alternative as it is not necessarily associated with a relapse of NEH. NEH can be added to the spectrum of neutrophilic dermatoses induced by BRAFis. It occurs earlier (3-4 days) than previously described drug-induced NEH (9-12 days) and may be an earlier stage of eccrine squamous syringometaplasia, which has already been reported in the context of BRAFi-treated patients.

Management of advanced non-melanoma skin cancers using helical tomotherapy.

BACKGROUND: Helical tomotherapy (HT) is a relatively new method of radiotherapy, the main advantages of which are an increase of irradiation dose on the target tumour volume and best protection of adjacent organs at risk. OBJECTIVE: To provide an accurate evaluation of efficiency and tolerance of HT on different kinds of non-melanoma skin tumours. PATIENTS AND METHODS: We analysed, retrospectively, 25 patients (pts) who were treated with HT for advanced non-melanoma skin cancers. We studied the characteristics of patients and tumours, associated treatments, characteristics, efficacy and tolerance of HT treatment. RESULTS: Eight had basal cell carcinoma, Eight had cutaneous squamous cell carcinoma, five Merkel cell carcinoma and four adnexal carcinoma. The median age was 75 years (range 51-89). The median follow-up was 12 months. HT was used because of incomplete excision (n = 12), lymph node involvement (n = 6), non-operable lesions (n = 4) and high risk of relapse (n = 4). The delivered dose for the tumour bed was between 50 and 70 Gy and for the lymph node it was between 50 and 64 Gy. There was no grade III-IV adverse event, except one grade III mucositis. Fourteen pts suffered from limited toxic effects 6 months after the end of the treatment, mainly loss of eyebrow and teared eye. Complete remission was noticed for 22 pts (88%); one pt had progressive disease and two pts died. CONCLUSION: HT is an effective option for advanced non-melanoma skin cancers as radical treatment or in association with surgery. Early and late toxicity and cosmetic results are acceptable.

High frequency, diversity and severity of skin diseases in a paediatric emergency department.

BACKGROUND: Skin disorders are a major concern in the Paediatric Emergency Department (PED). We provide an accurate evaluation of the incidence, characteristics and severity of skin disorders seen in our PED over a 1-year period. METHODS: A total of 20,652 children's medical notes were reviewed in a single centre, retrospective study in the PED of a University Hospital over a 1-year period. The dermatological disorders were analysed on the basis of different criteria including their incidence, patient age, sex ratio, diagnosis, seasonal variations and hospitalization rates. RESULTS: A total of 1897 (9.2%, F/M: 1.2; mean age: 4.1 ± 3.6 years) children presented with 1999 skin diseases and 69 different diagnoses. This frequency increased in the summer months (more than 14% of all patients). A total of 46.5% of diseases were infectious in nature (27.6% viral and 14.4% bacterial), inflammatory diseases accounted for 26.2% (urticaria and angio-oedema 15.9%, atopic dermatitis 3.5%, Henoch-Schönlein purpura: 2.1%), non-specific focal disease (balanitis, vulvitis, etc.) and insect bites, burns, transient diseases of the newborn and drug reactions for 9.2%, 7.8%, 6.4%, 3.7% and 1.2% respectively. More than 90% of children presented at the hospital for an acute condition and 155 (8.2% of children with skin disorders; F/M: 0.9; age: 4.0 ± 4.0 years) were hospitalized. More than 90% of hospitalizations were for infectious and inflammatory diseases. CONCLUSION: Our data reveal the extremely high frequency, diversity and potential severity of paediatric emergency skin disorders. Specific educational measures and closer co-operation between Dermatologists and Paediatricians are essential if the skin care dispensed to children and teenagers is to be improved.

[Tumour regression is not predictive for higher risk of sentinel node involvement in thin melanomas (Breslow thickness < or = 1 mm)]. / La régression tumorale n'est pas un facteur de risque d'atteinte du ganglion sentinelle dans les mélanomes fins (indice de Breslow < or = 1 mm).

BACKGROUND: Thin melanomas (Breslow thickness < or = 1 mm) are considered highly curable. The aim of this study was to evaluate the correlation between histological tumour regression and sentinel lymph node (SLN) involvement in thin melanomas. PATIENTS AND METHODS: This was a retrospective single-centre study of 34 patients with thin melanomas undergoing SLN biopsy between April 1998 and January 2005. RESULTS: The study included 14 women and 20 men of mean age 56.3 years. Melanomas were located on the neck (n=3), soles (n=4), trunk (n=13) and extremities (n=14). Pathological examination showed 25 SSM, four acral lentiginous melanomas, three in situ melanomas, one nodular melanoma and one unclassified melanoma with a mean Breslow thickness of 0.57 mm. Histological tumour regression was observed in 26 over 34 cases and ulceration was found in one case. Clark levels were as follows: I (n=3), II (n=20), III (n=9), IV (n=2). Growth phase was available in 15 cases (seven radial and eight vertical). Mitotic rates, available in 24 cases, were: 0 (n=9), 1 (n=11), 2 (n=2), 3 (n=1), 6 (n=1). One patient with histological tumour regression (2.9% of cases and 3.8% of cases with regressing tumours) had a metastatic SLN. One patient negative for SLN had a lung relapse and died of the disease. Mean follow-up was 26.2 months. CONCLUSION: The results of the present study and the analysis of the literature show that histological regression of the primary tumour does not seem predictive of higher risk of SLN involvement in thin melanomas. This suggests that screening for SLN is not indicated in thin melanomas, even those with histological regression.

Vemurafenib pharmacokinetics and its correlation with efficacy and safety in outpatients with advanced BRAF-mutated melanoma.

Vemurafenib is a BRAF kinase inhibitor approved for first-line treatment of metastatic BRAF (V600) -mutant melanoma. However, data on the pharmacokinetic/pharmacodynamic (PK/PD) relationship are lacking. The aim of this prospective, multicenter study was to explore the PK/PD relationship for vemurafenib in outpatients with advanced BRAF-mutated melanoma. Fifty-nine patients treated with single-agent vemurafenib were prospectively analyzed. Vemurafenib plasma concentration (n = 159) was measured at days 15, 30, 60, and 90 after treatment initiation. Clinical and biological determinants (including plasma vemurafenib concentration) for efficacy and safety were assessed using Cox's model and multivariate stepwise logistic regression. Median progression-free survival (PFS) and overall survival were 5.0 (95 % confidence interval [95 % CI] 2.0-6.0) and 11.0 (95% CI 7.0-16.0) months, respectively. Twenty-nine patients (49 %) experienced any grade ≥3 toxicity and the most frequent grade ≥2 toxicity was skin rash (37 %). Severe toxicities led to definitive discontinuation in seven patients (12 %). Grade ≥2 skin rash was not statistically associated with better objective response at day 60 (p = 0.06) and longer PFS (hazard ratio 0.47; 95 % CI 0.21-1.08; p = 0.075). Grade ≥2 skin rash was statistically increased in patients with ECOG ≥ 1 (odds ratio 4.67; 95 % CI 1.39-15.70; p = 0.012). Vemurafenib concentration below 40.4 mg/L at day 15 was significantly associated with a shorter PFS (1.5 [0.5-5.5] vs. 4.5 [2-undetermined] months, p = 0.029). Finally, vemurafenib concentration was significantly greater in patients developing grade ≥2 rash (61.7 ± 25.0 vs. 36.3 ± 17.9 mg/L, p < 0.0001). These results suggest that early plasma drug monitoring may help identify outpatients at high risk of non-response or grade ≥ 2 skin rash.

Helical tomotherapy in oncodermatology: case report of circumferential cutaneous lymphoma treated by this optimized radiotherapy.

Helical tomotherapy is a recent modality of intensity-modulated, rotational irradiation being developed for treatment of an increasing number of malignancies. It allows delivering an accurate treatment while sparing critical organs thus optimizing the therapeutic ratio. In particular, it allows treating some tumour locations that could not be efficiently irradiated through more conventional irradiation devices. We report the usefulness of this approach for the treatment of complex lesions such as circumferential cutaneous lymphoma of the trunk.