Identification of three clinical neurofibromatosis 1 subtypes: Latent class analysis of a series of 1351 patients.

BACKGROUND: Neurofibromatosis 1 (NF1) is one of the most common inherited disorders characterized by mutations in the tumour suppressor gene NF1. Its clinical manifestations are highly variable and unpredictable. A specific NF1 mutation does not predict the severity or complications of the disease. OBJECTIVE: The objective of this study was to build an empirical classification scheme without any a priori hypotheses to identify the underlying NF1 subtypes that best explain the observed heterogeneity. METHODS: We performed latent class analysis (LCA) of 1351 consecutive NF1 patients aged >17 years seen between 2002 and 2014. Data and phenotypic features were collected prospectively on a standardized form. RESULTS: The median age was 36.8 (17-81) years. A three-class model showed the best fit: 706 (52%) belonged to the LC1 'Cutaneous neurofibromas' class having preferentially cutaneous neurofibromas (99%), plexiform neurofibromas (63%) and blue-red macules (29%); 593 (44%) belonged to the LC2 'Subcutaneous neurofibromas' class characterized by the presence of at least 10 subcutaneous neurofibromas (21%) and a familial form (77%) and 52 (4%) belonged to the LC3 'Dysmorphic phenotype' class characterized by dysmorphic features (78%) and learning difficulties (87%). Patients in LC1 had a higher likelihood of developing scoliosis (RR = 1.7, 95% confidence interval (CI) [1.2-2.4]). Patients in LC2 were more likely to be men (RR = 1.4, 95% CI [1.1-1.7]). Patients in LC3 were at higher risk of having an optic pathway glioma (RR = 4.8, 95% CI [1.9-11.8]) and epilepsy (RR = 4.5, 95% CI [1.8-11.6]). CONCLUSION: Our findings invite the performance of a larger cohort study to test whether the various latent classes reflect different underlying genetic modifiers of these phenotypic traits.

[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.

Oesophageal involvement in 26 consecutive patients with mucous membrane pemphigoid.

BACKGROUND: Oesophageal involvement of mucous membrane pemphigoid (MMP) has not yet been thoroughly described. OBJECTIVES: To characterize systematically the endoscopic lesions of a series of patients with oesophageal symptoms seen at a referral centre for autoimmune bullous diseases. METHODS: Clinical, endoscopic and immunological findings of consecutively referred patients with MMP with oesophageal involvement, systemic and endoscopic treatments, and follow-up are described. RESULTS: Of 477 consecutive patients with MMP consulting between 2002 and 2012, 26 (5·4%) had symptomatic oesophageal involvement. Dysphagia, observed in 23 (88%) patients, was the most frequent symptom. Oesophageal symptoms could be the first sign of MMP. Patients with oesophageal involvement had a mean of three other involved sites. At initial oesophageal endoscopy, 17 of 26 patients had active lesions (intact bullae, erosions and/or erythema), 15 had stricture(s) and 12 had other cicatricial lesions. Systemic therapy alone achieved oesophageal symptom relief for five patients. Dilatation was combined with systemic therapy for 12 patients and was successful in nine; one perforation occurred. CONCLUSIONS: Symptomatic oesophageal involvement affected 5·4% of patients with MMP. Dermatologists and gastroenterologists should be aware of these mucocutaneous diseases and their oesophageal involvement, as it could lead to earlier diagnosis and better care. Oesophageal dilatation could be a therapeutic option for symptomatic stricture not relieved by optimized systemic therapy alone.

Cold-associated perniosis of the thighs histopathologically mimicking lupus. Six observations.

BACKGROUND: Equestrian cold panniculitis has been described since 1980 in horse riders or in stable employees. Histological aspect is underdescribed. PATIENTS AND METHODS: We describe clinical and histological features of six horse riding or stable employees patients presenting with upper lateral thigh lesions during the winter months between 2014 and 2016 in our dermatological department. RESULTS: Six horse riding or stable employees ladies without any known disease presented with similar symptoms. They had urticarial or violaceous, slightly pruritic, sometimes necrotic lesions of the upper lateral thighs. Clinically, equestrian cold panniculitis, insect bite or a caustic dermatitis was suspected. Four of these patients had a cutaneous biopsy. They all showed a similar histological appearance resembling lupus erythematosus, combining dermo-epidermal lesions, with foci of interface dermatitis, an abundant dermal lymphocytic infiltrate and a dermal mucinosis. Hypodermal infiltration was present on samples including subcutis. Laboratory workup for systemic disease was unremarkable for two patients and not performed for the four others, having no other clinical sign of lupus. All patients improved rapidly with very high potent topical steroids. CONCLUSION: Cold-associated perniosis of the thighs should be considered whenever a histopathological appearance of lupus is associated with lesions of the upper lateral thighs in patients practicing horse riding. This disease belongs to the spectrum of miscellaneous cold-induced dermatoses in which histopathological lesions identical to lupus can be encountered.

[Infectious cellulitis of the face complicating injection for esthetic nasolabial sulcus by hyaluronic acid: report of seven cases]. / Dermohypodermite infectieuse de la face compliquant l'injection à visée esthétique des sillons nasogéniens par de l'acide hyaluronique : à propos de sept cas.

We report a case series of seven patients with bacterial cellulitis of the face complicating a filler injection for cosmetic reason, treated in a university hospital from 2005 to 2012. There were seven women aged 34 to 57 years. Two patients had a deep collection requiring surgical excision combined with antibiotics. Five patients were treated with antibiotics only. In two cases the bacteria was found streptococcus A and in one case Staphylococcus aureus. One patient required hospitalization in an intensive care unit. Only patients who needed surgical treatment showed moderate aesthetic sequelae.

Neurofibromatosis 1 phenotype associated to malignant peripheral nerve sheath tumours: a case-control study.

BACKGROUND: Malignant peripheral nerve sheath tumours (MPNSTs) are the main cause of death in neurofibromatosis 1 adult patients. OBJECTIVES: To determine the clinical type of neurofibromas associated to MPNSTs. METHODS: Case-control study. Cases were neurofibromatosis 1 adults with MPNSTs and controls were patients without MPNSTs individually matched by age and sex (1 : 3). Both were recruited from our database. The following variables were studied: clinical presence of cutaneous, subcutaneous or plexiform neurofibromas and of internal neurofibromas. Internal neurofibromas were confirmed by clinical imaging. Multivariate odds ratios (aORs) were estimated with their 95% confidence interval (CI). RESULTS: From January 1995 to December 2007, 52 patients (cases) were identified with a MPNSTs, 155 controls could be recruited. In the multivariate analysis, MPNSTs were significantly associated with the presence of internal NFs (aOR: 7.5; 95% CI: 3.2-17.4), a trend for an association was observed for the presence of subcutaneous neurofibromas (aOR: 2.11; 95% CI: 0.89-5). CONCLUSIONS: This study confirms the association between the MPNSTs and the internal neurofibromas. The later are indeed associated with a high risk of malignant transformation.

[Neglected skin tumors. Three cases]. / Tumeurs "historiques": tumeurs négligées. Trois observations.

BACKGROUND: Giant skin tumours are defined as greater than 10 cm in size and are frequently a consequence of neglect. We report three cases of giant skin tumours and discuss possible factors associated with delayed diagnosis and treatment. OBSERVATIONS: Two men and one woman, aged 52, 62 and 78 years, presented with giant skin tumours. One was mentally retarded, one had a borderline personality and another was presenting a major depressive disorder. Pain, smell, bleeding and/or loss of function forced the patients to seek medical care. Tumour sizes were 11 to 30 cm and were present for between six months and 20 years. All patients had hidden their lesion from their doctor and families. In one case, a sebaceous carcinoma of the right shoulder required amputation of the right upper limb. In a second, palliative surgery and medical care was given for a metastatic porocarcinoma. The last patient received neoadjuvant chemotherapy for an undifferentiated carcinoma. DISCUSSION: Neglected skin tumours continue to be encountered even in 2011. Consultation was delayed due to fear of the diagnosis and/or lack of corresponding physicians, resulting in worsening of the prognosis. A larger scale study could help us to identify the factors associated with neglected giant tumours and to improve their management.