The Molecular Landscape of Primary Acral Melanoma: A Multicenter Study of the Italian Melanoma Intergroup (IMI).

Acral melanoma (AM) is a rare and aggressive subtype of melanoma affecting the palms, soles, and nail apparatus with similar incidence among different ethnicities. AM is unrelated to ultraviolet radiation and has a low mutation burden but frequent chromosomal rearrangements and gene amplifications. Next generation sequencing of 33 genes and somatic copy number variation (CNV) analysis with genome-wide single nucleotide polymorphism arrays were performed in order to molecularly characterize 48 primary AMs of Italian patients in association with clinicopathological and prognostic features. BRAF was the most commonly mutated gene, followed by NRAS and TP53, whereas TERT promoter, KIT, and ARID1A were less frequently mutated. Gains and losses were recurrently found in the 1q, 6p, 7, 8q, 20 and 22 chromosomes involving PREX2, RAC1, KMT2C, BRAF, CCND1, TERT, and AKT3 genes, and in the 6q, 9, 10, 11q and 16q chromosomes including CDKN2A, PTEN, and ADAMTS18 genes, respectively. This study confirmed the variety of gene mutations and the high load of CNV in primary AM. Some genomic alterations were associated with histologic prognostic features. BRAF mutations, found with a higher rate than previously reported, correlated with a low Breslow thickness, low mitotic count, low CNV of the AMs, and with early-stage of disease.

Dermatofibrosarcoma Protuberans on Tattooed Skin: A Case Report.

Dermatofibrosarcoma protuberans is an uncommon indolent fibroblastic skin tumor with a tendency for local recurrence. Its etiology is unknown, but there may be a link with vaccination sites, burn scars, and previous skin traumas. This report describes a curious case of dermatofibrosarcoma protuberans occurring secondary to a 16-year-old tattoo.

Prevalence of ALK gene alterations among the spectrum of plexiform spitzoid lesions.

BACKGROUND: ALK receptor tyrosine kinase gene (ALK) rearrangements have been described in spitzoid lesions with a plexiform growth pattern. OBJECTIVE: To investigate the prevalence of ALK alterations in a large series of spitzoid lesions. METHODS: ALK immunohistochemical and fluorescence in situ hybridization analyses of 78 spitzoid plexiform lesions including 41 Spitz nevi, 29 atypical Spitz tumors (ASTs), and 8 spitzoid melanomas. RESULTS: ALK immunohistochemical staining was observed in 14.6% of Spitz nevi (6 of 41) and 13.8% of ASTs (4 of 29); the spitzoid melanomas were ALK negative. Fluorescence in situ hybridization confirmed ALK translocation in 9 cases and amplification in 1 case. In 2 of the translocated cases it was possible to determine the fusion partner gene (ie, tropomyosin 3 gene [TPM3] or dynactin 1 gene [DCTN1]). Of the 4 cases of AST examined, 2 carried the B-Raf proto-oncogene, serine/threonine kinase gene (BRAF) V600E mutation. The 10 patients had a mean age of 18.7 years (range, 1-39) and a female predominance (female-to-male ratio, 7:3). Seven lesions arose on the extremities; the 2 lesions occurring in infants were located on the face. The lesions' mean diameter was 6.2 mm (range, 3-13), and their mean Breslow thickness was 1.83 mm (range, 0.6-3.6). The results of sentinel node biopsy were negative in 2 ASTs. LIMITATIONS: BRAF status was tested in only 4 of 10 samples because of the limited amount of material. CONCLUSION: ALK alterations characterize a significant subset of spitzoid lesions.

Extraskeletal Myxoid Chondrosarcoma of the Foot Clinically Mimicking Plantar Fibromatosis.

Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft tissue sarcoma usually presenting in proximal extremities of middle-aged men. The authors discuss a unique case of EMC, localized in the plantar foot of a 76-year-old woman, clinically suspected as plantar fibromatosis. It is important to avoid misdiagnosis of EMC because of their propensity for late recurrence and their metastatic potential.

"Double trouble" or an amplification of the triploidy phenotype?

Triploidy occurs in about 1 to 3% of clinically recognizable pregnancies and is typically associated with growth restriction, craniofacial dysmorphisms and congenital anomalies. We report the case of a female fetus with prenatal diagnosis of complete triploidy, polysplenia, bilateral cleft-palate, horseshoe-kidneys and bilateral club-feet. Whereas bilateral cleft-palate, horseshoe-kidneys and bilateral club feet are known to be part of the triploidy-associated malformation spectrum, polysplenia, which usually occurs as part of the heterotaxia spectrum, has never been associated with triploidy. An amplification of the triploidy phenotype or a "double trouble".

DRESS syndrome in a patient undergoing stem cell transplantation: Can sirolimus be involved?

We present a case of sirolimus-induced drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome in a stem cell transplant patient. Sirolimus is an immunosuppressive drug that inhibits the mammalian target of rapamycin (mTOR) pathway. A 24-year-old male with a history of acute lymphoblastic leukemia (ALL) underwent testicular extraction followed by hematopoietic stem cell transplantation (HSCT). He presented with pruritic eczematous lesions, which were initially treated with topical steroids. However, he later developed diffuse xerosis, fever, chills, generalized edema, weight gain, eosinophilia, and leukopenia. Skin biopsy showed spongiotic dermatitis with eosinophils, suggesting a drug or atopic reaction. Investigations ruled out infections, and the RegiSCAR score indicated drug reaction syndrome with eosinophilia and systemic symptoms (DRESS). Sirolimus, an immunosuppressive drug, was suspected as the cause. Sirolimus was discontinued, and oral steroids were initiated. After 3 weeks of therapy, the patient showed improvement with resolution of symptoms. Although no cases of sirolimus-induced DRESS syndrome have been reported, allergic reactions with eosinophilia induced by everolimus have been documented. In our case, the patient's history characterized by stem cell transplantation and multiple immunosuppressive therapies may have contributed to the development of DRESS syndrome after beginning sirolimus therapy. This case may be the first evidence of sirolimus-induced DRESS syndrome in a stem cell transplant patient.

A Case of Lip Psoriasis in a 14-Year-Old Boy Successfully Treated with Adalimumab.

Psoriasis is a common chronic skin disease mainly located in areas of friction. Psoriasis of the lips as an exclusive presentation is rare and often misdiagnosed. Different anti-psoriatic therapies have been proposed, but the literature is limited to case studies with partial results. Biologic therapies have revolutionized the management of many dermatologic conditions, including psoriasis, and they are approved for pediatric use. We report the case of a 14-year-old boy with a 2-year history of white-yellowish scaling lesions on his lips, without intraoral involvement. Lip biopsy showed a psoriasiform pattern. Treatment with adalimumab 40 mg every other week was started, and after 6 months of therapy, we obtained a complete remission of the patient's lip psoriasis.

Paraviral bullous eruption in a 7-year-old child during acute Epstein-Barr virus infection: A case report.

We present the case of a child developing widespread vesicle-bullous lesions during an acute and symptomatic Epstein-Barr Virus infection. Antibody serology, biopsy, and direct immunofluorescence allowed the diagnosis of a paraviral bullous eruption. To our knowledge, this is the first report of bullous eruption following Epstein-Barr virus infection in childhood.

L-citrulline prevents alveolar and vascular derangement in a rat model of moderate hyperoxia-induced lung injury.

BACKGROUND: Moderate normobaric hyperoxia causes alveolar and vascular lung derangement in the newborn rat. Endogenous nitric oxide (NO), which promotes lung growth, is produced from the metabolism of L-arginine to L-citrulline in endothelial cells. We investigated whether administering L-citrulline by raising the serum levels of L-arginine and enhancing NO endogenous synthesis attenuates moderate hyperoxia-induced lung injury. METHODS: Newborn rats were exposed to FiO(2) = 0.6 or room air for 14 days to induce lung derangement and then were administered L-citrulline or a vehicle (sham). Lung histopathology was studied with morphometric features. Lung tissues and bronchoalveolar lavage fluid (BALF) were collected for analysis. Lung vascular endothelial growth factor (VEGF), nitric oxide synthase (eNOS), and matrix metalloproteinase 2 (MMP2) gene and protein expressions were assessed. RESULTS: Serum L-arginine rose in the L-citr + hyperoxia group (p = 0.05), as well as the Von Willebrand factor stained vessels count (p = 0.0008). Lung VEGF immune staining, localized on endothelial cells, was weaker in the sections under hyperoxia than the L-citr + hyperoxia and room air groups. This pattern was comparable with the VEGF gene and protein expression profiles. Mean alveolar size increased in the untreated hyperoxia and sham-treated groups compared with the groups reared in room air or treated with L-citrulline under exposure to hyperoxia (p = 0.0001). Lung VEGF and eNOS increased in the L-citrulline-treated rats, though this treatment did not change MMP2 gene expression but regulated the MMP2 active protein, which rose in BALF (p = 0.003). CONCLUSIONS: We conclude that administering L: -citrulline proved effective in improving alveolar and vascular growth in a model of oxygen-induced pulmonary damage, suggesting better lung growth and matrix regulation than in untreated groups.

Congenital pulmonary airway malformation (CPAM) [congenital cystic adenomatoid malformation] associated with tracheoesophageal fistula and agensesis of the corpus callosum.

Congenital pulmonary airway malformations (CPAM) are a family of hamartomatous disorders due to the uncontrolled overgrowth of the terminal bronchioles. Congenital pulmonary airway malformations can co-exist with cardiovascular and/or urogenital malformations, but their association with thoracopulmonary malformations is extremely rare. We report the first case of CPAM type I, co-existing with tracheo-esophageal fistula and corpus callosum agenesis.

Apert syndrome with fused thalami.

Apert syndrome (Acrocephalosyndactyly type I; AS) is a rare but well-known autosomal dominant disorder characterized by craniosynostosis, midface hypoplasia, bony/cutaneous syndactyly of fingers and toes as well as a variety of associated congenital anomalies involving the brain, heart, limbs and other organ systems. We report the case of a fetus with molecularly confirmed Apert syndrome and additional fusion of the thalamic nuclei. Various central nervous system anomalies, have been reported in patients with AS. However, as far as we know cases of fused thalami in Apert syndrome have never been reported so far.

Can erythema multiforme be an immune sequela of IgM nephropathy? A case report.

A 13-year-old Chinese girl attended to our Pediatric Dermatology Unit for the appearance of itchy targetoid lesions on the trunk, face and upper limbs. A skin biopsy showed histological findings typical of erythema multiforme minor. A month earlier she was admitted for the onset of a nephrotic syndrome and the renal biopsy showed an IgM nephropathy with a diffuse mesangial cell proliferation. There was no medical history of recent infections, fever, muscle or joint pain, drugs intake related to erythema multiforme and viral serology were negative.The role of antibodies in erythema multiforme could be more relevant than suspected and the severity of erythema multiforme was reported to be proportional to the antibody-mediated complement-dependent cytotoxicity, supporting the potential pathogenetic role for humoral immunity in this subtype of erythema multiforme.We reported the first association of erythema multiforme and IgM nephropathy in a pediatric patient providing an additional hint that an antibody-mediated process, rather than T-cell cytotoxicity, might represent the main pathogenetic mechanism in certain subtypes of erythema multiforme.