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BACKGROUND: Mycosis fungoides (MF) has usually an indolent course. However, some patients develop a more aggressive disease and few prognostic parameters have been identified. Isolated cases of pustular MF (pMF) suggest an unfavourable prognosis. OBJECTIVES: We aim to describe the clinico-pathological characteristics and prognostic value of pMF. METHODS: We retrospectively collected data of all cases of MF with histological pustules diagnosed from 2009 to 2020. The outcomes and clinico-pathological characteristics of pMF at diagnosis (pMFD) were compared to those of a cohort of non-pustular MF (NpMF). RESULTS: 33 pMF (including 22 pMFD) and 86 NpMF cases were included. The median age at diagnosis of pMF was 61 years [IQR=50-75]. The median follow-up of pMFD was 32 months [IQR=14-49]. Clinically, 33% of pMF had pustules. Large-cell transformation (LCT) occurred in 17 cases. pMFD were at a significantly more advanced-stage and more showed LCT at diagnosis than NpMF (50% vs 7%, p<0.001 and 23% vs 0%, p<0.001, respectively). In multivariate Cox analysis, the presence of histological pustule at diagnostic was associated with shorter OS in all patients (HR=13.90, CI95%[2.43-79]; p=0.003), and in early-stage patients (HR=11.09, CI95%[1.56-78.82]; p=0.02). In multivariate Fine and Gray model analysis, pMFD was associated with a higher cumulative incidence of LCT (SHR=13.90, CI95% [2.43-79]; p=0.003) in all patients. Median OS after the occurrence of histological pustules during follow-up of all pMF patients was 37 months, with a five-year OS of 25% (CI95% [0.06-0.5]). CONCLUSION: pMF often follows an aggressive course, with a high risk of LCT and shorter survival, even for early-stage patients. Histological pustules at diagnostic of MF might represent an independent poor prognostic factor, to be confirmed by further studies. Because pustules are not always clinically identified, histological pustules should be mentioned in pathology reports of MF and prompt discussion of a closer follow-up.
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This case report describes a woman in her 20s who presented with an itchy erythematous-papulo-pustular eruption of the scalp for 3 months with progressive centrifugal extension to the face and was diagnosed with Ofuji disease.
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Anticorpos Monoclonais Humanizados , Eosinofilia , Foliculite , Dermatopatias Vesiculobolhosas , Humanos , Eosinofilia/diagnóstico , Eosinofilia/tratamento farmacológico , Foliculite/diagnóstico , Foliculite/tratamento farmacológico , Dermatopatias Vesiculobolhosas/diagnóstico , Dermatopatias Vesiculobolhosas/tratamento farmacológicoRESUMO
BACKGROUND: Ultrasound imaging has recently benefited from the introduction of a new 70â MHz transducer able to provide high-resolution images, i.e. ultra-high-frequency ultrasound (UHFUS). AIM: To study the morphological features of basal cell carcinomas (BCCs) and measure BCC thickness by means of UHFUS examination. METHODS: In this retrospective multicentric study, 171 consecutive patients underwent UHFUS examination between November 2018 and May 2019 for suspected BCC. Diagnosis was confirmed by histopathology. A series of morphological parameters including echogenicity, structure, borders, shape composition (presence of intralesional structures) were investigated along with objective measurements such as thickness (maximum distance between the surface of the epidermis and the deepest part of the tumour) and width. RESULTS: In total, 117 BCCs from 93 patients were examined, including superficial (n = 13; 11.1%), nodular (n = 64; 54.7%), infiltrative (n = 18; 15.4%), mixed subtypes (n = 20; 17.1%) and other subtypes (n = 2; 1.7%). The most frequently observed UHFUS parameters included: hypoechoic signal (n = 80; 68.4%, P < 0.001), homogeneous structure (n = 76, 65.0%, P = 0.01), well-defined borders (n = 77, 65.8%, P < 0.001) and elongated shape (n = 71, 60.7%, P < 0.001). An excellent correlation was found between the BCC thickness measured by UHFUS and the value estimated by histology (interclass correlation ≥ 0.80). CONCLUSION: UHFUS is a new rapid and easy noninvasive skin imaging technique able to provide data on the dimensions and morphology of BCCs in real time and at the bedside. These characteristics mean UHFUS has a number of possible applications, ranging from presurgical mapping to the detection of disease recurrence and treatment monitoring.
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Carcinoma Basocelular , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/patologia , Projetos Piloto , Estudos Retrospectivos , Carcinoma Basocelular/patologia , Ultrassonografia/métodosRESUMO
Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous neuroendocrine cancer. Management of advanced MCC is mainly based on immune-checkpoint inhibitors. The high failure rate warrants an investigation of new therapeutic targets. The recent identification of BRCA1 or BRCA2 (BRCA1/2) mutations in some MCC raises the issue of the use of poly-(ADP-Ribose)-polymerase inhibitors in selected advanced cases. The main objective of our study is to determine the accurate frequency of BRCA1/2 pathogenic variants. We studied a series of 30 MCC and performed a meta-analysis of BRCA1/2 variants of published cases in the literature. In our series, we detected only one BRCA2 pathogenic variant. The low frequency of BRCA1/2 pathogenic variants in our series of MCC (3%) was confirmed by the meta-analysis of BRCA1/2 variants in the literature. Among the 915 MCC from 13 published series studied for molecular alterations of BRCA1/2, only 12 BRCA1/2 pathogenic mutations were identified (1-2% of MCC), whereas many other BRCA1/2 variants were variants of unknown significance or benign. BRCA1/2 pathogenic variants are uncommon in MCC. However, in BRCA-mutated MCC, poly-(ADP-Ribose)-polymerase inhibitors might be a valuable therapeutic option requiring validation by clinical trials.
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Carcinoma de Célula de Merkel , Neoplasias Ovarianas , Neoplasias Cutâneas , Humanos , Feminino , Proteína BRCA1/genética , Carcinoma de Célula de Merkel/genética , Carcinoma de Célula de Merkel/tratamento farmacológico , Proteína BRCA2/genética , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/genética , Adenosina Difosfato Ribose/uso terapêutico , Mutação em Linhagem Germinativa , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Predisposição Genética para DoençaRESUMO
This case report describes a 78-year old woman with a stage IIA BRAF wild-type melanoma on the left leg who experienced a grade 2 vitiligo, a marked skin thickening, and painful swelling of the limbs.
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Esclerodermia Localizada , Humanos , Esclerodermia Localizada/induzido quimicamente , Esclerodermia Localizada/tratamento farmacológico , Inibidores de Checkpoint Imunológico , Anticorpos Monoclonais Humanizados/efeitos adversos , NivolumabeRESUMO
Psoriasis is a chronic inflammatory disease whereby long-term disease control remains a challenge for the patients. Latest evidence suggests that combined topical treatment with steroids and vitamin D analogue foam (Calcipotriol/Betamethasone) is efficient in long-term management of the disease and reducing the number of relapses. Its effects on cellular inflammation and cytokine production remain to be explored. We set out to examine the effect of topical therapies on cellular infiltrate and cytokine profile in the lesional skin of psoriasis patients. This was a monocentric, double-blind, randomized trial with 30 patients. Patients were treated with the combined Calcipotriol/Betamethasone foam, Betamethasone foam alone, Clobetasol Propionate ointment or placebo. 4 mm skin biopsies from lesional and non-lesional sites were taken before and 4 weeks after treatment. Cellular infiltrate, IFNγ and IL-17 were studied by immunofluorescence. Each patient was their own control. Evolution in skin inflammation was studied in parallel with changes in patient's epidermal thickness and their tPASI clinical score. Lesional skin was characterized by increased epidermal thickness, increased number of IL-17 and IFNγ producing CD8+ T cells, NK cells and neutrophils. All treatment reduced epidermal thickness and improved patients tPASI scores. Only the combined Calcipotriol/Betamethasone foam completely abolished epidermal and dermal influx of CD8+ T cells, reduced number of CD8 + IFNγ+ cells (but not CD8 + IL-17+ cells) and significantly reduced the number of MPO+ neutrophils which were predominantly IL-17+. None of the treatments had effect on NK cells. We have shown the combined topical treatment with Calcipotriol/Betamethasone foam to be effective in reducing cellular influx into lesional skin of psoriasis patients and this effect to be superior to emollient or Betamethasone alone. Its previously described efficacy in the clinic may be attributed to its unique and rapid ability to inhibit both adaptive CD8+ T cell and innate immune neutrophilia influx into the skin, which was not observed for the other treatments.
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Interleucina-17 , Psoríase , Humanos , Emolientes/uso terapêutico , Pomadas/uso terapêutico , Calcitriol , Psoríase/tratamento farmacológico , Betametasona/uso terapêutico , Inflamação/tratamento farmacológicoRESUMO
Pigmentation of the human skin is a complex process regulated by many genes. However, only a few have a profound impact on melanogenesis. Transcriptome analysis of pigmented skin compared with analysis of vitiligo skin devoid of melanocytes allowed us to unravel CLEC12B as a melanocytic gene. We showed that CLEC12B, a C-type lectin receptor, is highly expressed in melanocytes and that its expression is decreased in dark skin compared with that in white skin. CLEC12B directly recruits and activates SHP1 and SHP2 through its immunoreceptor tyrosine-based inhibitory motif domain and promotes CRE-binding protein degradation, leading to the downregulation of the downstream MITF pathway. CLEC12B ultimately controls melanin production and pigmentation in vitro and in a model of reconstructed human epidermis. The identification of CLEC12B in melanocytes shows that C-type lectin receptors exert function beyond immunity and inflammation. It also provides insights into the understanding of melanocyte biology and regulation of melanogenesis.
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Lectinas Tipo C , Melanócitos , Receptores Mitogênicos , Pigmentação da Pele , Epiderme/metabolismo , Humanos , Lectinas Tipo C/genética , Lectinas Tipo C/metabolismo , Melaninas/metabolismo , Melanócitos/metabolismo , Receptores Mitogênicos/metabolismo , Pele/metabolismo , Pigmentação da Pele/genéticaRESUMO
The potential role of CLEC12B, a gene predominantly expressed by skin melanocytes discovered through transcriptomic analysis, in melanoma is unknown. In this study, we show that CLEC12B expression is lower in melanoma and melanoma metastases than in melanocytes and benign melanocytic lesions and that its decrease correlates with poor prognosis. We further show that CLEC12B recruits SHP2 phosphatase through its immunoreceptor tyrosine-based inhibition motif domain, inactivates signal transducer and activator of transcription 1/3/5, increases p53/p21/p27 expression/activity, and modulates melanoma cell proliferation. The growth of human melanoma cells overexpressing CLEC12B in nude mice after subcutaneous injection is significantly decreased compared with that in the vehicle control group and is associated with decreased signal transducer and activator of transcription 3 phosphorylation and increased p53 levels in the tumors. Reducing the level of CLEC12B had the opposite effect. We show that CLEC12B represses the activation of the signal transducer and activator of transcription pathway and negatively regulates the cell cycle, providing a proliferative asset to melanoma cells.
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Lectinas Tipo C/metabolismo , Melanoma/genética , Proteína Tirosina Fosfatase não Receptora Tipo 11/metabolismo , Receptores Mitogênicos/metabolismo , Fator de Transcrição STAT3/metabolismo , Neoplasias Cutâneas/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células/genética , Conjuntos de Dados como Assunto , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Melanoma/mortalidade , Melanoma/patologia , Camundongos , RNA-Seq , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Annular lipoatrophy of the ankle is a rare and unique acquired lipoatrophic panniculitis that mainly affects children. There is no consensus on treatment, and the long-term course is not well known. We present four new pediatric cases that contribute to the understanding of this rare disease.
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Lipodistrofia , Paniculite , Tornozelo , Atrofia/patologia , Criança , Humanos , Lipodistrofia/diagnóstico , Paniculite/patologia , Gordura Subcutânea/patologiaRESUMO
Importance: Chilblain-like lesions have been reported during the coronavirus 2019 (COVID-19) pandemic. The pathophysiology of such manifestations remains largely unknown. Objective: To perform a systematic clinical, histologic, and biologic assessment in a cohort of patients with chilblain-like lesions occurring during the COVID-19 pandemic. Design, Setting, and Participants: In this prospective case series carried out with a COVID-19 multidisciplinary consultation group at the University Hospital of Nice, France, 40 consecutive patients presenting with chilblain-like lesions were included. Main Outcomes and Measures: Patients underwent a thorough general and dermatologic examination, including skin biopsies, vascular investigations, biologic analyses, interferon-alpha (IFN-α) stimulation and detection, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) and serologic analysis. Results: Overall, 40 consecutive patients with chilblain-like lesions were included. Most patients were young, with a median (range) age of 22 (12-67) years; 19 were male and 21 were female. The clinical presentation was highly reproducible with chilblain-like lesions mostly on the toes. Bullous and necrotic evolution was observed in 11 patients. Acrocyanosis or cold toes were reported in 19 (47.5%) cases. Criteria compatible with COVID-19 cases were noted in 11 (27.5%) within 6 weeks prior to the eruption. The real-time PCR (rt-PCR) testing results were negative in all cases. Overall, SARS-CoV-2 serology results were positive in 12 patients (30%). D-dimer concentration levels were elevated in 24 (60.0%) cases. Cryoglobulinemia and parvovirus B19 serologic results were negative for all tested patients. The major histologic findings were features of lymphocytic inflammation and vascular damage with thickening of venule walls and pericyte hyperplasia. A significant increase of IFN-α production after in vitro stimulation was observed in the chilblain population compared with patients with mild-severe acute COVID-19. Conclusions and Relevance: Taken together, our results suggest that chilblain-like lesions observed during the COVID-19 pandemic represent manifestations of a viral-induced type I interferonopathy. Trial Registration: ClinicalTrials.gov Identifier: NCT04344119.