Berta Ferrer

Blastic plasmacytoid dendritic cell neoplasm in a child

A total of 512,085 prescriptions for the transdermal methylphenidate patch were written in the first year on the market, with an imminent increase in its use because of the recently expanded age indications. While it is conceivable that the patient in this report may develop generalized vitiligo in the future as the observed depigmentation may represent vitiligo induced by a Koebner phenomenon, the fact that his disease was solely localized to the areas of drug application and did not spread elsewhere suggests that the depigmentation was most likely directly related to patch application. Because the patch was not applied to the same location on a daily basis, the areas lacked the typical angulated appearance of other cases of contact vitiligo. Given the prevalent use of this transdermal patch, we recommend the close observation of treated patients to prevent chemical leukoderma.

A Mouse Model Uncovers LKB1 as an UVB-Induced DNA Damage Sensor Mediating CDKN1A (p21WAF1/CIP1) Degradation

Exposure to ultraviolet (UV) radiation from sunlight accounts for 90% of the symptoms of premature skin aging and skin cancer. The tumor suppressor serine-threonine kinase LKB1 is mutated in Peutz-Jeghers syndrome and in a spectrum of epithelial cancers whose etiology suggests a cooperation with environmental insults. Here we analyzed the role of LKB1 in a UV-dependent mouse skin cancer model and show that LKB1 haploinsufficiency is enough to impede UVB-induced DNA damage repair, contributing to tumor development driven by aberrant growth factor signaling. We demonstrate that LKB1 and its downstream kinase NUAK1 bind to CDKN1A. In response to UVB irradiation, LKB1 together with NUAK1 phosphorylates CDKN1A regulating the DNA damage response. Upon UVB treatment, LKB1 or NUAK1 deficiency results in CDKN1A accumulation, impaired DNA repair and resistance to apoptosis. Importantly, analysis of human tumor samples suggests that LKB1 mutational status could be a prognostic risk factor for UV-induced skin cancer. Altogether, our results identify LKB1 as a DNA damage sensor protein regulating skin UV-induced DNA damage response.

Tufted Angioma Associated with Kasabach-Merritt Phenomenon: A Therapeutic Challenge

Fig. 1. (A) Tufted angioma involving the chin in a one-month-old child. (B) The patient at 2 months of age showing a subtle increase in tumour size and decrease in platelet count

Microarray study reveals a transforming growth factor-β-dependent mechanism of fibrosis in discoid lupus erythematosus†

Discoid lupus erythematosus (DLE) is characterized by scarring lesions that develop and perpetuate fibrotic lesions. These are not observed in subacute cutaneous lupus erythematosus (SCLE). The pathophysiological basis of this is currently unknown.

Genetic profile of GNAQ-mutated blue melanocytic neoplasms reveals mutations in genes linked to genomic instability and the PI3K pathway.

Melanomas arising in association with a common or cellular blue nevus (MABN) comprise a relatively rare and heterogeneous group of lethal melanomas. Although GNAQ is known to be frequently mutated in common blue nevus, cellular blue nevus (CBN) and MABN and these malignant lesions present gross chromosome alterations harboring BAP1 mutations, little is known about other mutations that contribute to the development and progression of these neoplasms. Thus, the genetic profile of these tumors is important to increase the number of intervention and treatment modalities. Here, we characterized and genetically profiled two different sections of a rare MABN and two CBNs from three different patients. All of the samples harbored a GNAQ mutation, exhibited RAS pathway activation, and harbored additional mutations in genes associated with genomic instability and epigenetic regulation (KMT2C, FANCD2, ATR, ATRX, NBN, ERCC2, SETD2, and WHSC1). In addition, all neoplasms harbored mutations that directly or indirectly affected either the regulation or activation of the PI3K pathway (PIK3CA, NF1, INPP5B and GSK3B). Our results not only help understand the genetic complexity of these blue melanocytic lesions but provide a rationale to use the combination of PI3K/MTOR and MEK1/2 inhibitors against these types of tumors.

Genetic Evolution of Nevus of Ota Reveals Clonal Heterogeneity Acquiring BAP1 and TP53 Mutations

Melanoma presents molecular alterations based on its anatomical location and exposure to environmental factors. Due to its intrinsic genetic heterogeneity, a simple snapshot of a tumors genetic alterations does not reflect the tumor clonal complexity or specific gene–gene cooperation. Here, we studied the genetic alterations and clonal evolution of a unique patient with a Nevus of Ota that developed into a recurring uveal‐like dermal melanoma. The Nevus of Ota and ulterior lesions contained GNAQ mutations were c‐KIT positive, and tumors showed an increased RAS pathway activity during progression. Whole‐exome sequencing of these lesions revealed the acquisition of BAP1 and TP53 mutations during tumor evolution, thereby unmasking clonal heterogeneity and allowing the identification of cooperating genes within the same tumor. Our results highlight the importance of studying tumor genetic evolution to identify cooperating mechanisms and delineate effective therapies.

Prognostic value of skin lesions in sarcoidosis: clinical and histopathological clues

BackgroundAlthough tremendous advances have been made, a significant gap exists between the vast knowledge accumulated concerning sarcoidosis in recent years and our understanding of this disease.ObjectiveDescribe the main clinical and histopathological findings associated with cutaneous sarcoidosis and to investigate the relationship of these skin lesions with systemic involvement.Materials and MethodsAretrospective review of 41 patients who were diagnosed with cutaneous sarcoidosis was done.ResultsThe study included 34 females and 7 males. Systemic disease occurred frequently in patients with lupus pernio and nodulo-plaque type lesions. Systemic symptoms were observed more commonly in patients with raised serum ACE levels (84.6% vs. 40%; p<0.05). Our study also indicated that patients with skin lesions that were associated with systemic symptoms had a more chronic form of the disease than patients with only cutaneous lesions (91.6% vs. 29.4%; p<0.001). Additionally, complete resolution of cutaneous lesions was observed more frequently in patients with no associated systemic symptoms (66.6% vs. 23.5%; p<0.05). Interestingly, we found that patients with a moderate/severe granulomatous infiltrate in their biopsies had a more severe clinical presentation during the course of the disease, with a more generalized skin involvement (65.6% vs. 30%) as well as a more chronic course of the disease (56.3% vs. 30%). Another interesting histopathological finding observed was the presence of a grenz zone in 20 cases (47.6%).ConclusionsA correct and methodical clinicopathological correlation is important for our clinical practice because it can give us useful clues to the diagnosis and prognosis of this disease.

Atypical scleromyxedema with prominent nodular lesions associated with immune thrombocytopenia: An unusual presentation

To the Editor: Scleromyxedema (SM) is a rare cutaneous mucinosis that usually occurs with monoclonal gammopathy ([83.2%), predominantly an IgG lambda subtype. SM may show a great variety of extracutaneous manifestations ( gastrointestinal, musculoskeletal, neurologic, pulmonary, cardiac, and renal involvement) leading to significant morbidity and mortality. We report a case of SM with prominent scalp involvement, presence of nodular lesions, and immune thrombocytopenia. A 69-year-old woman presented with a 2-week history of facial edema and progressive eruption. The patient also reported severe scalp pruritus and increased hair loss. On physical examination, skin-colored firm papules, nodules, and edema of the face and both hands were observed. The papules were initially located on the scalp, neck, and back of the auricular area, then gradually involved upper aspect of the trunk and the surrounding skin showed scleroderma-like induration in these areas. Several nodules, 4 to 10 mm in size, were present on the scalp, forehead (Fig 1), and side portions of the chin. Pathological examination of biopsy specimens from a nodular scalp lesion and of a neck papule (Fig 2) revealed an increase in fibroblasts, collagen, and deposits of mucin in the papillary and midreticular dermis. Laboratory analysis showed a progressive low platelet count (60-10 10/ L, normal range 150-400 10/ L, platelet count within normal limits 6 months earlier), with a normal peripheral blood smear result and a normocellular bone marrow with trilineage hematopoiesis. Serum protein electrophoresis, immunofixation electrophoresis of serum and urine, and immunoglobulin free light chain assays did not show paraproteinemia. Other laboratory examination findings including thyroid function were within normal limits and autoantibody screening produced negative results. Computed tomographic scans of the chest, abdomen, and pelvis showed no relevant abnormalities. Electromyography detected signs consistent

Enfermedad del injerto contra el huésped crónica liquenoide con patrón blaschkoide

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Cutaneous infections by dematiaceous opportunistic fungi: Diagnosis and management in 11 solid organ transplant recipients

The incidence of cutaneous infections by dematiaceous fungi is rising in our environment due to the high number of solid organ transplant recipients (SOTR).