[The role of new molecular tests in the diagnosis of melanoma in a setting of congenital nævus in an infant]. / Apport des nouveaux tests moléculaires dans le diagnostic d'un mélanome sur nævus congénital chez un nourrisson.

INTRODUCTION: Congenital and infantile melanomas are extremely rare. We report a case of a child presenting at birth with a giant congenital nevus complicated by melanoma and on long-term follow-up with exploration using new immunohistochemistry and molecular biology tools. OBSERVATION: A new-born girl presented at birth with a large congenital cervico-mandibular tumour with para-pharyngeal extension and underlying osteolysis. At 7 months, histology and immunohistochemistry of the operative specimen revealed nodules with atypical features (mitotic figures, necrosis and positive expression of KI67 and P53 in approximatively 50 % of the melanocytic nuclei). A diagnosis was made of infantile melanoma associated with congenital nevi. Repeated surgery and monitoring (clinical and imaging) were performed. At the age of 7 years, as there was no evidence of metastatic lesions, further analyses were performed on the initial operative specimen. Investigation of transcription factor expression using immunohistochemistry, comparative genomic hybridization and histology-guided mass spectrometry, although suspect, did not in itself support a diagnosis of melanoma. Finally, at the age of 7 years, hepatic and pulmonary metastases were reported. Despite combined immunotherapy with ipilimumab and nivolumab, the child died 5 months later. CONCLUSION: This case illustrates the complexity of diagnosis of infantile melanoma and the risk of metastatic involvement long after the initial diagnosis. Diagnosis may be difficult and necessitates expert advice and the application of several recent methods to reach a conclusion and initiate appropriate treatment.

Frequency of isolated cutaneous involvement in adult mastocytosis: a cohort study.

BACKGROUND: Mastocytosis is characterized by the accumulation/proliferation of abnormal mast cells. The frequency of isolated cutaneous involvement in adults with mastocytosis has not been fully determined. The main objective of our study was to assess the frequency of isolated cutaneous mastocytosis (CM) in adults with mastocytosis skin lesions. The second objective was to compare the clinical, histological, biological and imaging features in patients with isolated CM and patients with systemic mastocytosis (SM). METHODS: We included all patients with histology-proven mastocytosis skin lesions between January 2009 and December 2017. The mastocytosis diagnosis was made according to the international diagnostic criteria. All data were collected from a dedicated specific case report. RESULTS: Among 160 patients with mastocytosis skin lesions, 25 patients had isolated CM (15.6%), 105 had SM and 30 (18.7%) patients had undetermined mastocytosis. Skin KIT mutation (OR: 51.9, 95% CI: 3.9-678, P = 0.001) and high bone marrow tryptase (OR: 97.4, 95% CI: 10.3-915, P = 0.001) were strong predictors of SM. The prevalence of osteoporosis was higher in the SM population than in the isolated CM population. Moreover, a decrease in bone mineral density over a short period of follow-up (1-2 years) was associated with SM. There were no differences between the two groups regarding the frequency of mast cell activation symptoms, the presentation of skin lesions, the number of mast cells in the dermis and the level of serum tryptase. We propose considering the KIT mutation status and bone marrow tryptase levels to aid the diagnosis of isolated CM in adult mastocytosis patients. CONCLUSION: Only a small minority of adults with mastocytosis skin lesions has isolated cutaneous involvement. In 18.7% of mastocytosis cases, even complete workup does not allow for a precise classification of patients.

[Dermatologic toxicities of immune checkpoint inhibitors]. / Toxicités dermatologiques des inhibiteurs de checkpoint immunologiques.

The development of immune checkpoint inhibitors (monoclonal antibodies targeting PD-1/PD-L1 or CTLA-4) represents a significant advance in the treatment of multiple cancers. Given their particular mechanism of action, which involves triggering CD4+/CD8+ T-cell activation and proliferation, they are associated with a specific safety profile. Their adverse events are primarily immune-related, and can affect practically all organs. In this context, dermatological toxicity is the most common, though it mostly remains mild to moderate and does not require discontinuation of treatment. More than a third of patients are faced with cutaneous adverse events, usually in the form of a maculopapular rash, pruritus or vitiligo (only in patients treated for melanoma). Much more specific dermatologic disorders, however, may occur such as lichenoid reactions, induced psoriasis, sarcoidosis, auto-immune diseases (bullous pemphigoid, dermatomyositis, alopecia areata), acne-like rash, xerostomia, etc. Rigorous dermatological evaluation is thus mandatory in the case of atypical, persistent/recurrent or severe lesions. In this article, we review the incidence and spectrum of dermatologic adverse events reported with immune checkpoint inhibitors. Finally, a management algorithm is proposed.

Efficacy of anti-programmed cell death-1 immunotherapy for skin carcinomas and melanoma metastases in a patient with xeroderma pigmentosum.

Xeroderma pigmentosum (XP) is an orphan disease of poor prognosis. We report one case of parallel efficacy with anti-programmed cell death-1 (PD-1) antibody on both melanoma and skin carcinoma in a patient with XP. A 17-year-old patient presented with metastatic melanoma and multiple nonmelanoma skin cancers. He was treated with pembrolizumab, a monoclonal anti-PD-1 antibody, at a dose of 2 mg kg-1 , every 3 weeks. Parallel therapeutic efficacy of anti-PD-1 was observed in metastatic melanoma and skin carcinomas, and maintained at week 24. This observation suggests anti-PD-1 may be considered in patients with XP and metastatic melanoma in addition to advanced nonmelanoma skin cancer.

[Uncommon dermatologic disorders triggered by radiation therapy of breast cancer: A case-series]. / Dermatoses réactionnelles rares après radiothérapie : une série de cas avec cancer du sein.

Radiotherapy's main skin toxicities are now well-separated, acute (acute radiation dermatitis) or chronic complications (chronic radiation dermatitis, induced cutaneous carcinoma, aesthetic sequelae). Exceptionally, radiotherapy may induce, by isomorphic reaction or Koebner's phenomenon, some specific dermatosis. In this article, we report five new observations of these unusual complications of radiation therapy, occurring in very variable time after breast irradiation and remaining strictly localized in the irradiated field (cutaneous mastocytosis, Sweet syndrome, lichen planus, vitiligo). These cases emphasize the need to realize a systematic histological exam if any atypical skin lesion appears after radiotherapy, even long after.

Bone marrow tryptase as a possible diagnostic criterion for adult systemic mastocytosis.

BACKGROUND: Mastocytosis is difficult to diagnose, especially when systemic mast cell activation symptoms are not present or involve only one extracutaneous organ. OBJECTIVE: The main objective was to evaluate the accuracy of the bone marrow tryptase level in the diagnosis of systemic mastocytosis in patients with a clinical suspicion of mastocytosis. METHODS: We included all adult patients evaluated in our centre between December 2009 and 2013 for suspected mastocytosis as part of a standardized procedure and who had a bone marrow and serum tryptase assay on the same day. The diagnosis of systemic mastocytosis was established on the basis of the World Health Organization criteria as the gold standard. The accuracy of the bone marrow tryptase level in the diagnosis of systemic mastocytosis was assessed by a receiver operating characteristics curve analysis. The different sensitivity and specificity values, corresponding to the set of possible bone marrow tryptase level cut-off values, were estimated with 95% confidence intervals. RESULTS: Seventy-three patients were included. The diagnosis of systemic mastocytosis was established in 43 patients (58.9%). The median bone marrow tryptase level was 423 µg/L [95% CI: 217-868] in the systemic mastocytosis group and 7.5 µg/L [95% CI: 4.6-17.1] in the non-systemic mastocytosis group (P < 0.001). A cut-off value of 50 µg/L for bone marrow tryptase identified systemic mastocytosis with a sensitivity of 93.0% [95% CI: 80.9-98.5%] and a specificity of 90.0% [95% CI: 73.5-97.9%]. CONCLUSION AND CLINICAL RELEVANCE: The bone marrow tryptase level appears to be a valuable diagnostic criterion for confirming systemic mastocytosis. If this diagnosis can reliably be excluded by evaluation of the bone marrow tryptase level, there would be no need to perform a bone marrow biopsy.

Late epidermal growth factor receptor inhibitor-related papulopustular rash: a distinct clinical entity.

We report four patients developing a late form of papulopustular rash induced by epidermal growth factor receptor inhibitors. These patients presented an unusual presentation of acneiform rash, characterized by late development (several months after treatment commenced), localization to the limbs with sparing of the face, and association with severe pruritus and Staphylococcus aureus superinfection in all cases. These clinical symptoms may suggest a distinct mechanism from the early acne-like rash frequently observed with these targeted anticancer therapies. Clinicians should be aware of this delayed adverse event, and we suggest the term 'late acneiform toxicity of EGFR inhibitors (LATE) syndrome' to permit better characterization of this clinical picture.