RESUMO
Dermal neurofibromas are characteristic of neurofibromatosis type one (NF1), and their developmental origin still unsolved. Although NF1 loss is required for neurofibroma initiation, some features of these benign tumors resemble a skin injury state and cutaneous trauma or other insults might support tumor development. Since adult terminal Schwann cells ensheathing nerve endings are able to dedifferentiate into a progenitor-like state in response to nerve crushing, we hypothesized that dedifferentiation of NF1-/- Schwann cells could be at the origin of human dermal neurofibromas. In support of this, here we show that CDH19 (a marker specific of Schwann cell precursors) and Schwann cell dedifferentiation marker SOX2 are significantly upregulated in NF1 tumors. We posit that onset of nerve regeneration might have a role in dermal neurofibroma initiation via dedifferentiation of NF1-/- Schwann cells.
Assuntos
Desdiferenciação Celular , Neurofibroma/etiologia , Células de Schwann/fisiologia , Neoplasias Cutâneas/etiologia , HumanosRESUMO
BACKGROUND: Facial lesions in frontal fibrosing alopecia (FFA) have been poorly described in published series. OBJECTIVE: We sought to describe facial lesions in FFA. METHODS: We reviewed our series of 55 cases of FFA, selecting 12 cases with clinically significant facial lesions. We performed a histologic study of these lesions. RESULTS: In addition to the observations already described in the literature such as facial papules or follicular red dots, we observed perifollicular and diffuse erythema, sometimes with a reticular pattern, and the gradual appearance of pigmented macules on facial skin. Biopsy specimens from the areas with facial erythema showed perifollicular and interfollicular lymphocytic infiltrate and fibrosis around vellus hair follicles. Histologic evaluation of pigmented macules sometimes exhibited an increased epidermal pigmentation and on occasions, pigmentary incontinence. LIMITATIONS: More patients are needed to determine the prevalence of these lesions in FFA. CONCLUSION: On facial skin of patients with FFA, we can observe papules or perifollicular erythema secondary to vellus hair follicle involvement. We describe diffuse erythema, owing to follicular and interfollicular lichenoid infiltrate, and the gradual appearance of pigmented macules, which could be secondary to an increased epidermal pigmentation or to pigmentary incontinence.
Assuntos
Alopecia/patologia , Dermatoses Faciais/patologia , Folículo Piloso/patologia , Adulto , Fatores Etários , Alopecia/fisiopatologia , Biópsia por Agulha , Progressão da Doença , Dermatoses Faciais/fisiopatologia , Feminino , Fibrose/patologia , Fibrose/fisiopatologia , Humanos , Imuno-Histoquímica , Líquen Plano/patologia , Líquen Plano/fisiopatologia , Pessoa de Meia-Idade , Pós-Menopausa/fisiologia , Doenças Raras , Estudos Retrospectivos , Medição de Risco , Estudos de AmostragemRESUMO
Cetuximab and panitumumab are epidermal growth factor receptor (EGFR) inhibitors used in metastatic colorectal cancer (mCRC). Most patients develop a papulopustular rash that may predict tumor response to treatment. EGFR gene polymorphisms may also determine tumor response and appearance of skin rash. We hypothesized an association between EGFR gene polymorphisms, papulopustular rash and response to anticancer treatment. Four EGFR polymorphisms (-216, -191, CA-SSR, R521K) were analysed in 51 patients with mCRC receiving anti-EGFR. Severity of cutaneous rash and tumor response was measured following standard scales. We report an association between SNP-216 and tumor response (P = 0.003): no tumor progression occurred in TT genotype. Moreover, 92.3% of the responder patients developed skin rash, 62.9% of them presenting a grade ≥2 (P = 0.015). Thus, although underpowered, our preliminary data suggest that SNP-216 polymorphism of the EGFR gene could be useful in predicting tumor response and the appearance of severe skin rash might also be associated.
Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia , Receptores ErbB/antagonistas & inibidores , Exantema/etiologia , Genes erbB-1 , Idoso , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Cetuximab/efeitos adversos , Cetuximab/uso terapêutico , Neoplasias Colorretais/secundário , Receptores ErbB/genética , Exantema/genética , Feminino , Humanos , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade , Modelos Genéticos , Panitumumabe , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , Resultado do TratamentoRESUMO
A 3-month-old boy presented with a congenital atrophic plaque on his right palm. On histopathologic examination, bundles of mature striated muscle were noted replacing the subcutis and extending into the dermis, without any other mesenchymal component seen. We have not been able to find a similar previously reported case. We propose the name nevus of striated muscle for this congenital, well-circumscribed cutaneous lesion composed exclusively of mature skeletal muscle.
Assuntos
Dermatoses da Mão/diagnóstico , Músculo Estriado , Nevo/diagnóstico , Neoplasias Cutâneas/diagnóstico , Dermatoses da Mão/patologia , Humanos , Lactente , Masculino , Nevo/patologia , Neoplasias Cutâneas/patologiaRESUMO
Diltiazem is a calcium channel blocking agent used for the treatment of hypertension. Cutaneous adverse effects are uncommon. The most frequently reported are itching, urticaria, and maculopapular eruption. A peculiar, cutaneous photodistributed reticulated hyperpigmentation secondary to diltiazem has been recently reported. A 66-year-old white woman with a 2 year history of pruritic hyperpigmented lesions on her face was seen in the clinic. Past medical history was remarkable for hypertension, which had been treated with diltiazem. Physical examination showed slate-gray to brown reticulated hyperpigmentation in the photo-exposed areas of the face and neck. Histological examination revealed interface dermatitis with liquefactive degeneration of the basal layer, necrotic keratinocytes, lymphocytic inflammatory infiltrate, and melanophages in the superficial dermis. A diagnosis of diltiazem-induced hyperpigmentation was established and diltiazem was stopped. Gradual resolution of the hyperpigmentation was observed over the following months. Although diltiazem has been marketed for over 20 years, the first cases of this particular type of reticulated hyperpigmentation were described in 2001. Since then, to our knowledge, only 17 cases have been reported in the literature. In all cases, cutaneous lesions appeared at least 6 months after this treatment had been started. Hyperpigmentation was controlled by means of photoprotection and discontinuation of diltiazem. Diltiazem can produce a characteristic lichenoid dermatitis with reticulated hyperpigmentation on sun-exposed areas.