Facial Sebaceous Hyperplasia in an Adolescent With Hypohidrotic Ectodermal Dysplasia.

We report on a 13-year-old boy diagnosed with hypohidrotic ectodermal dysplasia (HED) due to a pathogenic variant in ectodysplasin A (EDA). He exhibited multiple whitish, millimetric papules clustered on the nasal ala, forehead, temporal, and zygomatic arch areas. Histological examination revealed numerous hyperplastic sebaceous lobules within the upper dermis. The occurrence of sebaceous papules in this distribution among HED patients has rarely been reported. An association with the blockage of the Wnt/ß-catenin pathway due to EDA malfunction has been speculated.

Idiopathic calcinosis cutis in an infant: The importance of a wait-and-see approach.

A healthy 2-year-old girl presented with multiple asymptomatic subcutaneous nodules on both legs. Histologically demonstrated calcium deposition within the dermis and subcutaneous tissue consistent with calcinosis cutis. Laboratory abnormalities, underlying genetic conditions, and potential triggering factors were ruled out. The lesions resolved over an 18-month period without treatment, emphasizing the importance of the wait-and-see approach in idiopathic cases of calcinosis cutis.

Segmental congenital vascular anomaly with atrophy, ulceration, and scarring (SeCVAUS): Case series and review of literature.

BACKGROUND: Next-generation sequencing has greatly increased our understanding of vascular birthmarks. Many port-wine birthmarks are due to somatic mutations in GNAQ/GNA11 exon 183, but other genomic causes have been identified. Most congenital hemangiomas are due to somatic mutations in GNAQ/GNA11 at exon 209. Although genomically distinct, clinical overlap of congenital hemangiomas and port-wine birthmarks has occasionally been described. OBJECTIVE: We report a case series of a unique segmentally distributed vascular anomaly with overlapping characteristics of port-wine birthmarks and congenital hemangiomas with other distinctive features including ulceration, atrophy, and scarring. METHODS: This was a multicenter study with retrospective identification of patients via a detailed review of medical records. We also reviewed previously published cases. RESULTS: The clinical, histological, radiological, and genomic characteristics of 19 new and 13 previously reported cases characterized by segmental distribution, sharply demarcated borders, with variable thickening are presented. All cases had central atrophy with or without episodic ulceration. Those with genomic studies (13 out of 32) had somatic activating missense mutations in GNA11 or GNAQ codon 209. CONCLUSIONS: We describe the features and propose a descriptive name segmental congenital vascular anomaly with atrophy, ulceration, and scarring (SeCVAUS) for this condition.

Molecular and Pathological Features of Paediatric High-Grade Gliomas.

Paediatric high-grade gliomas are among the most common malignancies found in children. Despite morphological similarities to their adult counterparts, there are profound biological and molecular differences. Furthermore, and thanks to molecular biology, the diagnostic pathology of paediatric high-grade gliomas has experimented a dramatic shift towards molecular classification, with important prognostic implications, as is appropriately reflected in both the current WHO Classification of Tumours of the Central Nervous System and the WHO Classification of Paediatric Tumours. Emphasis is placed on histone 3, IDH1, and IDH2 alterations, and on Receptor of Tyrosine Kinase fusions. In this review we present the current diagnostic categories from the diagnostic pathology perspective including molecular features.

Telangiectasia-ectodermal dysplasia-brachydactyly-cardiac anomaly syndrome is caused by de novo mutations in protein kinase D1.

BACKGROUND: We describe two unrelated patients who display similar clinical features including telangiectasia, ectodermal dysplasia, brachydactyly and congenital heart disease. METHODS: We performed trio whole exome sequencing and functional analysis using in vitro kinase assays with recombinant proteins. RESULTS: We identified two different de novo mutations in protein kinase D1 (PRKD1, NM_002742.2): c.1774G>C, p.(Gly592Arg) and c.1808G>A, p.(Arg603His), one in each patient. PRKD1 (PKD1, HGNC:9407) encodes a kinase that is a member of the protein kinase D (PKD) family of serine/threonine protein kinases involved in diverse cellular processes such as cell differentiation and proliferation and cell migration as well as vesicle transport and angiogenesis. Functional analysis using in vitro kinase assays with recombinant proteins showed that the mutation c.1808G>A, p.(Arg603His) represents a gain-of-function mutation encoding an enzyme with a constitutive, lipid-independent catalytic activity. The mutation c.1774G>C, p.(Gly592Arg) in contrast shows a defect in substrate phosphorylation representing a loss-of-function mutation. CONCLUSION: The present cases represent a syndrome, which associates symptoms from several different organ systems: skin, teeth, bones and heart, caused by heterozygous de novo mutations in PRKD1 and expands the clinical spectrum of PRKD1 mutations, which have hitherto been linked to syndromic congenital heart disease and limb abnormalities.

Plaque-like cutaneous mucinosis of childhood.

A healthy 10-year-old boy presented with plaque-like cutaneous mucinosis (PCM) on his back. Cutaneous biopsy was followed by progressive resolution of the skin lesion. Pediatric PCM could differ clinically from the adult form. However, more cases are necessary to draw conclusions.

Penile and scrotal infundibular cysts in an adolescent treated with sorafenib.

Sorafenib is a multikinase inhibitor increasingly used for the treatment of several solid tumors. Different types of keratotic lesions, such as squamous cell carcinoma, actinic keratosis, or infundibular cyst, have been reported in association with this therapy. We present a 15-year-old male diagnosed with desmoid fibromatosis who developed multiple penile and scrotal infundibular cysts while receiving treatment with sorafenib.

Conradi-Hünermann-Happle syndrome with minimal signs.

A 4-year-old girl presented with congenital patches of scalp alopecia, which on physical examination, was consistent with blaschkolinear alopecic patches with mild epidermal atrophy. Similar atrophic hypopigmented patches were seen on the trunk and proximal extremities. With the clinical suspicion of Conradi-Hünermann-Happle syndrome, genetic testing was performed and revealed a mutation in the EBP gene. Despite characteristic cutaneous findings, no skeletal, ocular, or other anomalies were found on further evaluation.

Suspected COVID-19-related reticulated purpura of the soles in an infant.

A growing number of skin lesions during the COVID-19 pandemic are being recognized. Acral ischemic lesions identical to chilblains are most typical in children and young adults. We report an infant girl, aged 1 month and 29 days, with a peculiar reticulated purpuric eruption on her soles, with positive immunohistochemistry for SARS-CoV-2 in the endothelia of dermal blood vessels. The patient had an excellent outcome without specific therapy.

Pigmented purpuric dermatosis in an infant.

Pigmented purpuric dermatoses (PPDs) are a group of idiopathic, chronic, and self-resolving conditions easily recognizable in adults but extremely uncommon in infants. We present the youngest patient with PPD reported to date.

Diffuse reticulate purpura in two adolescents with anorexia nervosa and severe malnutrition.

Anorexia nervosa is an eating disorder frequently associated with cutaneous manifestations. A rare type of purpura, known as diffuse reticulate purpura, has been described in patients with anorexia nervosa and severe malnutrition. Typical characteristics of this condition include a purpuric reticulate rash predominantly affecting the trunk that rapidly resolves with adequate feeding. We report two male adolescent patients with anorexia nervosa and severe malnutrition who developed diffuse reticulate purpura.

Papillary hemangioma in a child and sonographic characterization.

Papillary hemangioma (PH) is a rare, benign, vascular tumor that usually appears on the scalp and face and is reported most frequently in adults. We present a pediatric case of PH and provide sonographic features that may assist in establishing the diagnosis.

Chilblains in children in the setting of COVID-19 pandemic.

BACKGROUND: Different skin manifestations of COVID-19 are being reported. Acral lesions on the hands and feet, closely resembling chilblains, have been recognized during the peak incidence of the COVID-19 pandemic. MATERIAL AND METHODS: A retrospective review of 22 children and adolescents with chilblain-like lesions seen over a short period of time in the Emergency Department of a children's hospital during the peak incidence of COVID-19 in Madrid, Spain. RESULTS: All patients had lesions clinically consistent with chilblains of the toes or feet, with three also having lesions of the fingers. Pruritus and mild pain were the only skin symptoms elicited, and only 10 had mild respiratory and/or GI symptoms. None had fever. Coagulation tests, hemogram, serum chemistry, and lupus anticoagulant were normal in all patients tested. One out of 16 tested cases had elevated D-dimer results, but without systemic symptoms or other laboratory anomalies. SARS-CoV-2 PCR tested in 19 cases was positive in just one case. Skin biopsies obtained in six patients were consistent with chilblains. On follow-up, all cases showed spontaneous marked improvement or complete healing. CONCLUSION: Acute chilblains were observed during COVID-19 pandemic in children and teenagers. It is a mildly symptomatic condition with an excellent prognosis, usually requiring no therapy. Etiopathogenesis remains unknown.

Erythema multiforme-like lesions in children and COVID-19.

During examination of cases of chilblains in children and adolescents, we identified four patients who also showed skin lesions similar to erythema multiforme (EM). They had no other known triggers for EM. One of them had a positive PCR for SARS-CoV-2, while the other three were negative. Skin biopsies from two patients showed features not typical of EM, such as deep perivascular and perieccrine infiltrate and absence of necrosis of keratinocytes. Immunohistochemistry for SARS-CoV/SARS-CoV-2 spike protein showed granular positivity in endothelial cells and epithelial cells of eccrine glands in both biopsies. All patients had an excellent outcome, and had minimal or no systemic symptoms. The coincidence of EM, a condition commonly related to viruses, and chilblains in the setting of COVID-19, and the positivity for SARS-CoV/SARS-CoV-2 spike protein by immunohistochemistry strongly suggest a link between EM-like lesions and SARS-CoV-2.

Hemophagocytic Lymphohistiocytosis Associated With 2 Cases of Pediatric Lymphocyte-depleted Classic Hodgkin Lymphoma.

Hemophagocytic lymphohistiocytosis (HLH) is a rare and often fatal syndrome of abnormal T-cell activation and cytokine production, which can be familial or secondary in nature. Although HLH can occur concomitantly with lymphomas, the development of HLH alongside Hodgkin lymphoma in children is unusual. Here we report the diagnostic evaluation and clinical course of 2 pediatric cases of HLH secondary to lymphocyte-depleted classic Hodgkin lymphoma. These cases highlight the need to be vigilant for this rare presentation and the difficulties in managing these patients.

Cutaneous Mastocytosis With Predominant Infiltration of Promastocytes.

Mastocytosis is a heterogeneous group of disorders with a variable clinical course, ranging from indolent disease with normal life expectancy to highly aggressive disease. In the skin, mast cells may show a spindle-shape appearance or appear as round cells with wide, polygonal cytoplasm. In this study, we present a case series of 4 patients with cutaneous childhood-onset mastocytosis in whom skin mast cells showed striking nuclear pleomorphism with bilobed and multilobed nuclei. Such finding does not seem to represent a malignant phenotype of the disease in the skin, although the true biological significance and the potential prognostic impact remain to be determined.

Focal nevoid hyperkeratosis of the nipple in a prepubertal girl.

Nevoid hyperkeratosis (NH) of the nipple and areola is an extremely uncommon condition in prepubertal children. We report on a prepubertal girl with NH and provide dermoscopic findings that helped to make the diagnosis.

Campbell de Morgan Spots (Cherry Angiomas) Show Endothelial Proliferation.

Campbell de Morgan spots (also known as adult hemangiomas, cherry angiomas, or senile angiomas) show clinical and histopathological features that make them distinct. Despite this, they are not included as benign vascular tumors in the current classification by the International Society for Vascular Anomalies (ISSVA). In the current study, we investigated the proliferation rate (Ki67) of the endothelia of 23 cases of Campbell de Morgan spots, as well as the immunoexpression of Wilms tumor protein 1 (WT1) by these vascular anomalies. The youngest patient was 24 years old (range: 24-80; mean: 52.61). Ten patients were women (43.48%). All cases showed intense cytoplasmic expression of WT1 by the endothelia in 80%-100% of the endothelial cells. Ki67 demonstrated proliferation by the endothelia of all vascular lesions. A mean of 1077.6 nuclei were evaluated per case. Eight cases showed a very low proliferation (less than 0.5% of the nuclei). In the other 15 cases, the proliferation ranged from 0.59% to 3.59% (mean: 1.89%).