Genetics of adnexal tumors: An update.

Cutaneous adnexal tumors form a vast heterogeneous group that include frequent entities that are mostly benign, as well as rare tumors that are occasionally malignant. In contrast to cutaneous tumors arising from the interfollicular epidermis that develop as a result of accumulation of UV-induced DNA damage (basal cell carcinoma, squamous cell carcinoma), the oncogenesis of adnexal tumors is related to a broad spectrum of genetic mechanisms (e.g., point mutation, fusion genes, viral integration, etc.). In this setting, specific and recurrent genetic alterations have been progressively reported, and these allow better classification of these entities. For certain of them, immunohistochemical tools are now available, enabling precise integrated histological and molecular diagnosis since certain entities are linked to well-defined alterations. In this context, we aim in this review to summarize the main molecular tools currently available for the classification of adnexal tumors.

Adcitmer® , a new CD56-targeting monomethyl auristatin E-conjugated antibody, is a potential therapeutic approach in Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive skin cancer, whose tumour cells often express CD56. While immune checkpoint inhibitors constitute a major advance for treating patients with MCC with advanced disease, new therapeutic options are still urgently required. OBJECTIVES: To produce and evaluate the therapeutic performance of a new antibody-drug conjugate (Adcitmer® ) targeting CD56 in preclinical models of MCC. METHODS: CD56 expression was evaluated in a MCC cohort (immunohistochemistry on a tissue microarray of 90 tumour samples) and MCC cell lines. Interaction of an unconjugated CD56-targeting antibody with CD56+ MCC cell lines was investigated by immunohistochemistry and imaging flow cytometry. Adcitmer® product was generated by the bioconjugation of CD56-targeting antibody to a cytotoxic drug (monomethyl auristatin E) using the McSAF Inside® bioconjugation process. The chemical properties and homogeneity of Adcitmer® were characterized by hydrophobic interaction chromatography. Adcitmer® cytotoxicity was evaluated in vitro and in an MCC xenograft mice model. RESULTS: Similar to previous reports, CD56 was expressed by 66% of MCC tumours in our cohort, confirming its relevance as a therapeutic target. Specific binding and internalization of the unconjugated CD56-targeting antibody was validated in MCC cell lines. The high homogeneity of the newly generated Adcitmer® was confirmed by hydrophobic interaction chromatography. The CD56-mediated cytotoxicity of Adcitmer® was demonstrated in vitro in MCC cell lines. Moreover, Adcitmer® significantly reduced tumour growth in a MCC mouse model. CONCLUSIONS: Our study suggests that Adcitmer® should be further assessed as a therapeutic option in patients with MCC, as an alternative therapy or combined with immune checkpoint inhibitors.

[Dual localisation of ischaemic fasciitis with local relapse at one site]. / Une double localisation de fasciite ischémique avec récidive locale sur un des sites.

INTRODUCTION: Ischaemic fasciitis (IF) is a rare pseudosarcomatous proliferation initially described on the pressure points of long-term bedridden patients. Healing is the rule after surgical excision. No multifocal localisations have been reported to date. Herein, we describe the case of a patient with FI affecting two sites and having recurred at one of them. OBSERVATION: A 50-year-old woman with scoliosis and mental retardation consulted for a hard skin lesion next to her right scapula. Elastofibroma was diagnosed on the basis of a surgical biopsy sample. Early local recurrence led to a second resection four months later. Histologically, central fibrinoid necrosis was observed, surrounded by collagenous tissue containing occasionally atypical fibroblasts and numerous capillaries. The diagnosis of ischaemic fasciitis was made by a national expert. Six months later, we observed a 13-cm purplish erythematous infiltrated mass with a 6-cm ulceration at the surgical site. A second 6-cm non-ulcerated indurated purplish lesion was visible next to the right greater trochanter. The scan showed deep soft-tissue infiltration with subfascial extension and contact with the greater trochanter. Superficial biopsies of both lesions showed only an appearance of granulation tissue. MRI performed after five months showed an extension of lesions at the two sites with an appearance evocative of ischaemic fasciitis. Surgical excision was refused by the patient and her family. DISCUSSION: We report a rare case of ischaemic fasciitis at two separate sites with local relapse after surgical excision.

[Hypocomplementaemic urticarial vasculitis with bullous lesions and pericardial involvement]. / Vascularite urticarienne hypocomplémentémique avec lésions bulleuses et péricardite spécifique.

BACKGROUND: Hypocomplementemic urticarial vasculitis syndrome (HUVS) is a rare disease involving urticarial cutaneous vasculitis, hypocomplementaemia and systemic manifestations. Pericardial involvement occurs in very rare cases. We report a case of HUVS associated with specific pericarditis and bullous lesions. PATIENTS AND METHODS: A 63-year-old woman consulted for chronic urticaria that had appeared ten months earlier. Her skin lesions were associated with weight loss of 10 kg, deterioration of respiratory function and abdominal pain. Leukocytoclastic vasculitis was seen in the skin biopsy sample. Hypocomplementaemia and anti C1q antibodies were present and a diagnosis of HUVS was made. During hospitalisation, extensive compressive pericardial effusion was identified, and histological examination of the biopsy revealed specific pericardial lymphocytic vasculitis. During follow-up, four episodes of infectious pneumonitis were noted. Bullous skin lesions were also observed. DISCUSSION: HUVS is a disease caused by an antibody against C1q complement responsible for urticarial lesions and vasculitis antibodies. To our knowledge, there have been only five reports in the literature of pericardial injury associated with HUVS. In our case, histological examination of the pericardium demonstrated lymphocytic vasculitis.