Senescence is one of the main barriers against tumor progression. Oncogenic signals in primary cells result in oncogene-induced senescence (OIS), crucial for protection against cancer development. It has been described in premalignant lesions that OIS requires DNA damage response (DDR) activation, safeguard of the integrity of the genome. Here we demonstrate how the cellular mechanisms involved in oncogenic transformation in a model of glioma uncouple OIS and DDR. We use this tumor type as a paradigm of oncogenic transformation. In human gliomas most of the genetic alterations that have been previously identified result in abnormal activation of cell growth signaling pathways and deregulation of cell cycle, features recapitulated in our model by oncogenic Ras expression and retinoblastoma (Rb) inactivation respectively. In this scenario, the absence of pRb confers a proliferative advantage and activates DDR to a greater extent in a DNA lesion-independent fashion than cells that express only HRasV12. Moreover, Rb loss inactivates the stress kinase DDR-associated p38MAPK by specific Wip1-dependent dephosphorylation. Thus, Rb loss acts as a switch mediating the transition between premalignant lesions and cancer through DDR modulation. These findings may have important implications for the understanding the biology of gliomas and anticipate a new target, Wip1 phosphatase, for novel therapeutic strategies.

Vemurafenib has proved to be useful in the treatment of patients with unresectable or metastatic melanoma harboring the BRAF-V600E mutation, with better rates of overall and progression-free survival than previous treatments. Adverse cutaneous effects, such as alopecia, pruritus, photosensitivity reactions, verrucous keratosis, keratoacanthomas, or squamous cell carcinomas, have been described. Thirty cases of vemurafenib-associated panniculitis are available in the literature with variable clinical relevance. Only 9 of them exhibited definitive evidence of neutrophilic panniculitis. They all consist of multiple lesions, usually located in the lower limbs. Histopathologically, they have been described as predominantly neutrophilic, lymphocytic, or mixed, more commonly with lobular location. We report an additional case of neutrophilic panniculitis in a 45-year-old woman treated with vemurafenib for metastatic melanoma, presenting as a single lesion on his right leg. The lesion resolved spontaneously and did not need treatment reduction. The presentation of this condition with a single lesion is particularly challenging. Recognition of this association is important given the increasing use of vemurafenib and the potential implications of treatment withdrawal.

Linear dermatoses are unusual entities whose distribution reflects cutaneous mosaicism, even when they occur in adult life. Adult blaschkitis (AB) and lichen striatus (LS) always follow this peculiar distribution. Although usually referred to as distinct entities, the clinical and histopathological presentation of lichen striatus in adults may be similar to those of adult blaschkitis. Moreover, some cases with overlapping features between lichen striatus and linear lichen planus have been published, making precise diagnosis very difficult. Recently, the concept of a wide spectrum of blaschkolinear dermatoses with AB and LS located somewhere within it has been proposed but it has not gained general recognition. We report three cases of dermatoses following the lines of Blaschko in adults (two women and one male, ages 35, 50 and 56, respectively). They involved the upper extremity in two cases and the lower in the third. Clinically, they were interpreted as linear lichen planus or blaschkitis but, histopathologically, they showed features consistent with lichen striatus. Lesions subsided with topic steroids and/or tacrolimus ointment, they are an example of the significant overlapping between these three entities, demonstrating that they may exist on a spectrum both clinically and histopathologically and clinico-pathologic correlation is essential to achieve an accurate final diagnosis. A detailed review of previously published cases has also been made.

We investigated the clinicopathological features and prognostic factors of patients with peripheral T-cell lymphoma (PTCL) in 13 sites across Spain. Relevant clinical antecedents, CD30 expression and staining pattern, prognostic indices using the International Prognostic Index and the Intergruppo Italiano Linfomi system, treatments, and clinical outcomes were examined. A sizeable proportion of 175 patients had a history of immune-related disorders (autoimmune 16%, viral infections 17%, chemo/radiotherapy-treated carcinomas 19%). The median progression-free survival (PFS) and overall survival (OS) were 7Á9 and 15Á8 months, respectively. Prognostic indices influenced PFS and OS, with a higher number of adverse factors resulting in shorter survival (P < 0Á001). Complete response (CR) to treatment was associated with better PFS (62Á6 vs. 4 months; P < 0Á001) and longer OS (67Á0 vs. 7Á3 months; P < 0Á001) compared to no CR. CD30 was expressed across all subtypes; >15% of cells were positive in anaplastic lymphoma kinase-positive and-negative anaplastic large-cell lymphoma and extranodal natural killer PTCL groups. We observed PTCL distribution across subtypes based on haematopathological re-evaluation. Poor prognosis, effect of specific prognostic indices, relevance of histopathological subclassification, and response level to first-line treatment on outcomes were confirmed. Immune disorders amongst patients require further examination involving genetic studies and identification of associated immunosuppressive factors.

Laser use for biopsy of suspicious lesions may simulate cytological atypia at the margin of the incisions, challenging pathological diagnosis. Erbium, chromium: yttrium-scandium-gallium-garnet (Er,Cr:YSGG) laser has shown promising results in experimental models by inducing fewer artifacts. The aims of this study were to examine the thermal wounds induced by Er,Cr:YSGG laser in a short series of oral leukoplakias in terms of cytological and epithelial architectural changes and also to assess the width of the thermal damage lateral to the incision. Four oral leukoplakia patients entered the study and underwent complete surgical excision of their lesions by using Er,Cr:YSGG laser. Patients were weekly controlled until complete healing was accomplished. The patients were included on the existing follow-up program for these lesions thereafter. Study samples were routinely processed by the same technician and double-blindedly studied by two pathologists until a consensus was reached for each case. The pathological analysis of the samples revealed no autolysis and no fixation- or handling-related artifacts. However, cellular and nuclear polymorphism could be observed in two samples. Loss of intercellular adherence was the most frequent thermal artifact in this series; all pseudodysplastic artifacts recognized in the study were of low intensity and located at the basal and suprabasal layers of the leukoplakias' epithelium. The width of the thermal damage at the edge of the incision scored an average of 26.60 ± 25.3 μm. It is concluded that irradiation with Er,Cr:YSGG laser induces a minimal amount of thermal artifacts at the surgical margins of oral leukoplakias and avoids diagnostic interferences with real dysplastic borders.