Lauriane Depaepe

Melanoma Patients under Vemurafenib: Prospective Follow-Up of Melanocytic Lesions by Digital Dermoscopy

Second primary melanomas (SPMs) induced by vemurafenib have been recently described. The aim of this study was to define the dermoscopical signs of melanoma in this context. Patients underwent a total body examination before receiving vemurafenib. Each single melanocytic lesion was registered before therapy by digital dermoscopy (DD), and then repeated monthly until therapy disruption. Forty-two patients were included, the mean duration of follow-up was 6.7 months, and a mean number of 51 lesions per patients were captured and followed. A total number of 2,155 lesions were recorded, of which 56.1% presented at least one change during the study. More common changes concerned the color of the lesions (up to 15%) and appearance or disappearance of globules (14.6%). Thirty-six of the melanocytic lesions were surgically excised, 21 were classified as a nevus, 1 was a lentigo, and 14 as a second new primary melanoma (occurring in 21% of our patients). DD allowed us to excise only 36/2,155 (1.6%) of the lesions and permitted us to detect 14 SPM in the 42 patients with a highly efficient malignant/benign ratio of 63.6%. Although vemurafenib is now tested in an adjuvant setting DD should be systematically used in order to accurately detect SPM and reduce the number of unnecessary excisions.

ZEB1-mediated melanoma cell plasticity enhances resistance to MAPK inhibitors

Targeted therapies with MAPK inhibitors (MAPKi) are faced with severe problems of resistance in BRAF‐mutant melanoma. In parallel to the acquisition of genetic mutations, melanoma cells may also adapt to the drugs through phenotype switching. The ZEB1 transcription factor, a known inducer of EMT and invasiveness, is now considered as a genuine oncogenic factor required for tumor initiation, cancer cell plasticity, and drug resistance in carcinomas. Here, we show that high levels of ZEB1 expression are associated with inherent resistance to MAPKi in BRAFV600‐mutated cell lines and tumors. ZEB1 levels are also elevated in melanoma cells with acquired resistance and in biopsies from patients relapsing while under treatment. ZEB1 overexpression is sufficient to drive the emergence of resistance to MAPKi by promoting a reversible transition toward a MITFlow/p75high stem‐like and tumorigenic phenotype. ZEB1 inhibition promotes cell differentiation, prevents tumorigenic growth in vivo, sensitizes naive melanoma cells to MAPKi, and induces cell death in resistant cells. Overall, our results demonstrate that ZEB1 is a major driver of melanoma cell plasticity, driving drug adaptation and phenotypic resistance to MAPKi.

Reflectance confocal microscopy characteristics of eight cases of pustular eruptions and histopathological correlations

Reflectance confocal microscopy (RCM)s interest has been well established for the non‐invasive diagnosis of skin cancers, especially melanocytic, and in the differential diagnosis between benign and malignant cutaneous lesions. However, its diagnostic interest in inflammatory skin diseases still needs to be demonstrated. Our purpose was to evaluate the correlation between RCM and conventional histopathology in a series of pustular eruptions of different pathogeny.

Tracking of second primary melanomas in vemurafenib-treated patients

influence whether one would have a more successful mentoring relationship. Effective mentors should be supportive, available, and experienced. Willingness to discuss salary, debt, level of autonomy, and promotions may facilitate understanding of key issues for those physicians who might lose interest in a career in academic dermatology. Future studies in mentoring should focus not only on residents but on mid-level faculty members as well.

Reflectance confocal microscopy accurately discriminates between benign and malignant melanocytic lesions exhibiting a 'dermoscopic island'.

Background  The ‘dermoscopic island’ is a term that was recently proposed to design an area of a pigmented lesion with a uniform dermoscopic pattern different from the remainder of the lesion. The positive predictive value of this sign for the diagnosis of melanoma is about 50%.

Drug reaction with eosinophilia and systemic symptoms (DRESS): clinicopathological study of 45 cases

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare and severe adverse drug reaction. Large detailed studies of histopathological features of DRESS are sparse and suggest an association between keratinocyte damage and the severity of visceral involvement.

Extramammary Paget's disease of the scalp: examination by in vivo and ex vivo reflectance confocal microscopy.

Extramammary Paget’s disease of the scalp: examination by in vivo and ex vivo reflectance confocal microscopy S. Debarbieux, S. Dalle, L. Depaepe, P. Y. Jeanniot, N. Poulalhon and L. Thomas Department of Dermatology, Centre Hospitalier Lyon Sud, Claude Bernard Lyon 1 University, Pierre B enite Cedex, France, Department of Pathology, Centre Hospitalier Lyon Sud, Lyon 1 University, Pierre B enite Cedex, France and Department of Maxillo-facial Surgery, Centre Hospitalier Lyon Sud, Pierre B enite Cedex, France

Histological features and treatment approach of trichoblastic carcinomas: from a case report to a review of the literature.

BACKGROUND Trichoblastic carcinoma (or malignant trichoblastoma) is a rare malignant cancer of adnexal structures with morphological features that in some cases are reminiscent of a trichoblastoma. Trichoblastic carcinoma is underdiagnosed as it is a rather recent entity which is still not recognized as such by all pathologists. The differential diagnosis with basal cell carcinoma is often difficult to make and the optimal treatment has not yet been established. CASE REPORT We report the case of a 43-year-old patient who underwent surgical excision and adjuvant radiotherapy for a growing mass of 40 × 48 mm located in the lumbar right paraspinal skin. The pathological findings demonstrated a trichoblastic carcinoma. The clinicopathological profile, the histogenesis, and the difficulties related to the histopathological diagnosis and treatment of this rare entity are discussed in this article. CONCLUSION Although the published reports on this disease are few, surgery should be considered the standard therapeutic approach for trichoblastic carcinomas. Selected cases presenting clinical features of local aggressiveness can safely be treated with adjuvant irradiation to improve local control. However, acute and particularly late toxicities need to be taken into account in the decision.

Comparative histological analysis of drug-induced maculopapular exanthema and DRESS

Cutaneous adverse drug reactions frequently present as a benign maculopapular exanthema (MPE) with a rapid healing. Sometimes systemic signs are present, which could represent a more severe or systemic MPE (sMPE) or even be the initial phase of a drug reaction with eosinophilia and systemic symptoms (DRESS). Histopathology associated with MPE, sMPE and DRESS has not been well characterized.

Cutaneous indeterminate cell histiocytosis: two new observations including a case with paraneoplastic-like evolution.

We report two new cases of cutaneous indeterminate cell histiocytosis (ICH), clinically characterized by a profuse papular eruption, without systemic involment. The first patient, a 59-year-old man, was evaluated for a diffuse, mildly pruritic papular rash of 6 months duration, associated with an impaired general condition. His clinical history was remarkable for a hepatocellular carcinoma (HCC) on NASH treated by hepatic chemoembolization 4 months before the first consultation. No new drug had been [...]