Resumo O síndrome de CLOVES é um síndrome de hipercrescimento raro, causada por uma mutação somática ativadora no gene PIK3CA. Relatamos o caso de um menino de seis meses, que se apresentou com uma dermatose complexa, de evolução congénita. O exame físico revelou uma mancha eritematosa reticulada ocupando a parede torácica anterior à direita, onde apresentava demarcação muito bem delimitada na linha média. Apresentava ainda gigantismo nas mãos e nos pés, com aspecto “furrowed” acral. Posteriormente, desenvolveu lesões em placa papilomatosas na região cervical, sugestivas de nevo epidérmico. O estudo genético realizado na pele lesional confirmou a mutação PIK3CA, estabelecendo o diagnóstico de síndrome CLOVES. O presente caso destaca-se pela raridade desta entidade. A diferenciação precoce com outros síndromes de hipercrescimento é importante, principalmente por causa do pior prognóstico de Proteus. Além disso, realçamos a importância dos achados cutâneos e do papel do dermatologista na abordagem diagnóstica inicial destes casos.

Abstract CLOVES syndrome is a rare overgrowth syndrome caused by an activating somatic mutation in the PIK3CA gene. We report the case of a six-month-old male that presented with a complex dermatosis with evolution since birth. Physical examination revealed a reticulated erythematous patch that affected the right anterior chest wall, where it showed sharp demarcation at the midline. He also had gigantism of the hands and feet, with an acral furrowing of the skin. Later on, he developed papillomatous plaque lesions in the cervical region, suggestive of epidermal nevi. Genetic study performed on lesional skin confirmed the PIK3CA mutation, establishing the diagnosis of CLOVES syndrome. The present case stands out given the rarity of this entity. Early differentiation between other overgrowth syndromes is important, namely because of the worse prognosis of Proteus. Moreover, we emphasize the importance of cutaneous findings and the dermatologist’s role in the diagnostic approach to such cases.

Resumo A Capillary malformation-arteriovenous malformation syndrome (CM-AVM) é uma doença autossómica dominante rara causada por mutações heterozigóticas nos genes RASA1 e EPHB4. Há malformações capilares (MCs) multifocais associadas a um risco aumentado de malformações vasculares de alto fluxo que podem causar complicações ameaçadoras de vida. Uma menina de 6 anos apresentou-se com telangiectasias labiais e múltiplas (>10) máculas e manchas irregulares eritematosas-acastanhadas na face, pescoço, tronco e extremidades superiores, com início aos 18 meses de idade. Não havia queixas locais ou sistémicas associadas. O pai, irmão mais novo, a tia e avô paternos tinham lesões cutâneas semelhantes. O teste genético revelou uma mutação heterozigótica no gene EPHB4, confirmando o diagnóstico CM-AVM tipo 2. A doente foi avaliada por cardiologia e neurologia que excluíram malformações arteriovenosas (MAVs) associadas, e a doente mantem seguimento dermatológico e neurológico regulares, sem complicações até ao momento. O pai e o irmão foram também avaliados, tendo sido confirmada a mutação do gene EPHB4 e excluídas MAVs. O presente caso é uma apresentação clássica de CM-AVM tipo 2, com aparecimento gradual de MCs multifocais, telangiectasias labiais e história familiar positiva, sem MAVs extracutâneas associadas. Com este caso pretendemos chamar a atenção que um número crescente de MCs cutâneas atípicas pode ser o único sinal de CM-AVM, que deve alertar o médico para a exclusão de MAVs potencialmente fatais.

Abstract Capillary malformation-arteriovenous malformation syndrome (CM-AVM) is a rare autosomal dominant disorder caused by heterozygous mutations in RASA1 and EPHB4 that associates multifocal capillary malformations (CMs) with an increased risk for fast-flow vascular malformations (FFVMs) which can cause life-threatening complications. We report the case of a 6-year-old girl with lip telangiectasia as well as multiple (>10) erythematous to brownish irregular macules and patches on the face, neck, trunk, and superior extremities from the age of 18 months with no local or systemic complaints. Several family members had similar lesions. Genetic testing revealed a heterozygous mutation in the EPHB4 gene, confirming the diagnosis of CM-AVM type 2. EPHB4 gene mutation was also present in her father and brother. No associated arteriovenous malformations (AVMs) were found after a thorough evaluation by cardiology and neurology, neither in the patient nor in the closest relatives. The present case is a characteristic presentation of CM-AVM type 2 syndrome, with gradually appearance of multifocal CMs, lip telangiectasias, and a positive family history, without associated extracutaneous FFVMs. An increasing number of atypical CMs on the skin may be the only sign of CM-AVM and should alert the clinician to further investigate the presence of AVMs which can be life-threatening.

RESUMO Fundamentos: A mastocitose é um grupo de doenças raras caracterizada pela expansão e acumulação excessiva de mastócitos clonais, de que resulta o envolvimento cutâneo e/ou sistémico. Nas idades pediátricas, a forma mais comum de mastocitose é a mastocitose cutânea. Objetivos: O presente trabalho tem como objetivo avaliar as características demográficas e os achados clínicos em crianças com diagnóstico de mastocitose. Métodos: Foram revistos os processos clínicos, desde janeiro de 2014 a junho de 2019, de todos os doentes com diagnóstico de mastocitose no Hospital Pediátrico de Coimbra. Resultados: Os 14 doentes foram diagnosticados com mastocitose cutânea. A idade média de início das lesões foi de 15,1 meses, sendo a mediana de 5 meses. A idade média de diagnóstico foi de 22,5 meses e a mediana de 9,5 meses. Dos 14 doentes, 8 eram do sexo masculino. 12 doentes tinham mastocitose cutânea maculopapular e 2 tinham mastocitoma cutâneo. No que diz respeito à subclassificação das variantes da MC maculopapular, 11 foram classificadas como polimórficas e 1 como monomórfica. O sinal de Darier foi positivo em 12 doentes, 10 tinham prurido, 2 apresentavam dor abdominal e 3 diarreia. Não foi constatado nenhum episódio de anafilaxia. Em todos os doentes foi realizado um estudo analítico inicial, a destacar o doseamento da triptase sérica, que variou entre 1,3‑15,9 ng/mL na primeira avaliação. Em 8 doentes, o diagnóstico foi confirmado através de biópsia cutânea. A terapêutica baseou‑se na evicção dos fatores desencadeantes, em anti‑histaminicos H1 e corticosteroide tópico de potência moderada a forte. O curso das lesões permanece estável em 12 doentes. Conclusões: O presente trabalho corrobora o que está descrito na literatura corrente sobre o tema. Realça a importância do conhecimento das características da doença em idade pediátrica para a prevenção de fatores desencadeantes, diagnóstico, investigação e tratamento dirigidos.

ABSTRACT Background: Mastocytosis is a group of rare diseases, characterized by the excessive clonal mast cell proliferation and accumulation, having cutaneous and/or systemic involvement. During pediatric age, cutaneous mastocytosis is the most common presentation. Aim: This descriptive analysis of children diagnosed with mastocytosis has the purpose of evaluating their demographic characteristics and clinical findings. Methods: The clinical files of patients diagnosed with mastocytosis from January 2014 to June 2019 at Hospital Pediátrico de Coimbra were reviewed. Results: Cutaneous mastocytosis was the final diagnosis for all 14 patients. The mean age for the starting lesions was 15.1 months, with a median of 5 months. The mean age for diagnosis was 22.5 months and the median 9.5 months. 8 patients were male, 12 had maculopapular cutaneous mastocytosis and 2 had mastocytoma. Regarding the subclassification of maculopapular cutaneous mastocytosis, 11 were classified as polymorphic and 1 as monomorphic. Darier’s sign was positive in 12 patients, 10 had pruritus, 2 had abdominal pain and 3 diarrhea. None of the patients had an anaphylactic episode. Every patient had an initial evaluation with tryptase dosage measurement, varying between 1.3‑15.9 ng/mL at this point. 8 patients had the diagnosis confirmed through a skin biopsy. As medical therapy was included avoidance of triggers, H1 antihistamine and moderate to strong strength topical corticosteroid. The lesions progression remains stable in 12 patients. Conclusions: This analysis reaffirms what is written about the theme in current literature. It emphasizes the importance of knowing the disease’s pediatric characteristics to ensure the prevention of triggers and an accurate diagnosis, investigation and treatment.

Abstract: Benign follicular tumors comprise a large and heterogeneous group of neoplasms that share a common histogenesis and display morphological features resembling one or several portions of the normal hair follicle, or recapitulate part of its embryological development. Most cases present it as clinically nondescript single lesions and essentially of dermatological relevance. Occasionally, however, these lesions be multiple and represent a cutaneous marker of complex syndromes associated with an increased risk of visceral neoplasms. In this article, the authors present the microscopic structure of the normal hair follicle as a basis to understand the type and level of differentiation of the various follicular tumors. The main clinicopathological features and differential diagnosis of benign follicular tumors are then discussed, including dilated pore of Winer, pilar sheath acanthoma, trichoadenoma, trichilemmoma, infundibuloma, proliferating trichilemmal cyst/tumor, trichoblastoma and its variants, pilomatricoma, trichodiscoma/fibrofolliculoma, neurofollicular hamartoma and trichofolliculoma. In addition, the main syndromes presenting with multiple follicular tumors are also discussed, namely Cowden, Birt-Hogg-Dubé, Rombo and Bazex-Dupré-Christol syndromes, as well as multiple tumors of follicular infundibulum (infundibulomatosis) and multiple trichoepitheliomas. Although the diagnosis of follicular tumors relies on histological examination, we highlight the importance of their knowledge for the clinician, especially when in presence of patients with multiple lesions that may be the cutaneous marker of a cancer-prone syndrome. The dermatologist is therefore in a privileged position to recognize these lesions, which is extremely important to provide further propedeutic, appropriate referral and genetic counseling for these patients.

Abstract Cutaneous meningiomas are rare tumors most commonly located on the scalp. We report the case of a 55-year-old male who presented with a 2x3 cm tumoral lesion on the forehead. The lesion was hard, adherent and covered by normal skin. Incisional biopsy revelead a proliferation of monomorphic round cells, organized in nests and focally forming pseudovascular spaces. Immunohistochemical study revealed positivity for epithelial antigen membrane and vimentin. Vascular markers, cytokeratins and S100 protein were negative. A brain CT scan did not show any evidence of intracranial meningioma. The authors describe the case of a cutaneous frontal meningioma in probable relation with previous cranioencephalic trauma.

Abstract Squamous cell carcinoma of the lower lip is frequent, and radical excision sometimes leads to complex defects. Many lip repair techniques are aggressive requiring general anesthesia and a prolonged post-operative period. The nasolabial flap, while a common flap for the repair of other facial defects, is an under-recognized option for the reconstruction of the lower lip. We describe the use of nasolabial flap for the repair of a large defect of the lower lip in a ninety year-old male, with good functional results and acceptable cosmetic outcome. We believe the nasolabial flap is a good alternative for intermediate-to-large lower lip defects in patients with impaired general condition.