TERT promoter mutations are associated with poor prognosis in cutaneous squamous cell carcinoma.

BACKGROUND: Telomerase reverse transcriptase gene (TERT) promoter (TERTp) mutations have been reported as potential predictors of poor prognosis in several cancers, but the prognostic value of TERTp mutations for cutaneous squamous cell carcinoma (cSCC) has not been determined. OBJECTIVE: To evaluate the frequency of TERTp mutations and correlate it with clinicopathologic features and patient outcome. METHODS: We performed genetic profiling of TERTp mutations in a retrospective series of cSCCs. The predictive value of TERTp mutations and clinicopathologic parameters were assessed by using logistic regression models. RESULTS: A total of 152 cSCCs from 122 patients were analyzed for TERTp mutations; the mutation rate was 31.6% (48 of 152), and it was higher in invasive cSCC (42 of 121 [34.7%]) than in in situ cSCC (6 of 31 [19.4%]). Age older than 75 years (odds ratio [OR], 14.84; P = .013] and TERTp mutation (OR, 8.11; P = .002) were independent predictors of local recurrence. TERTp mutation (OR, 15.89; P = .022) was independently associated with higher risk of lymph node metastasis. LIMITATIONS: The restricted number of metastatic cases. CONCLUSION: TERTp mutations may prove to be a molecular biomarker with prognostic significance in invasive cSCC, but larger studies are needed.

Spotlight on hTERT Complex Regulation in Cutaneous T-Cell Lymphomas.

As a major cancer hallmark, there is a sustained interest in understanding the telomerase contribution to carcinogenesis in order to therapeutically target this enzyme. This is particularly relevant in primary cutaneous T-cell lymphomas (CTCL), a malignancy showing telomerase dysregulation with few investigative data available. In CTCL, we examined the mechanisms involved in telomerase transcriptional activation and activity regulation. We analyzed 94 CTCL patients from a Franco-Portuguese cohort, as well as 8 cell lines, in comparison to 101 healthy controls. Our results showed that not only polymorphisms (SNPs) located at the promoter of human telomerase reverse transcriptase (hTERT) gene (rs2735940 and rs2853672) but also an SNP located within the coding region (rs2853676) could influence CTCL occurrence. Furthermore, our results sustained that the post-transcriptional regulation of hTERT contributes to CTCL lymphomagenesis. Indeed, CTCL cells present a different pattern of hTERT spliced transcripts distribution from the controls, mostly marked by an increase in the hTERT ß+ variants proportion. This increase seems to be associated with CTCL development and progression. Through hTERT splicing transcriptome modulation with shRNAs, we observed that the decrease in the α-ß+ transcript induced a decrease in the cell proliferation and tumorigenic capacities of T-MF cells in vitro. Taken together, our data highlight the major role of post-transcriptional mechanisms regulating telomerase non canonical functions in CTCL and suggest a new potential role for the α-ß+ hTERT transcript variant.

Extensive Refractory Perineal Pyoderma Gangrenosum Treated with Infliximab, Fecal Diversion, and Negative-Pressure Wound Therapy.

BACKGROUND: Pyoderma gangrenosum (PG) is a rare and difficult-to-diagnose disease that often associates with inflammatory bowel disease. CASE: We present a case of a 57-year-old female with ulcerative colitis receiving 5-ASA who presented with rapidly progressive ulcers in the right foot and on the inside of the thigh, extending from the left large vaginal lip to the perianal area, compatible with PG. She was initially treated with corticosteroids with no response. After multidisciplinary consultation, it was decided to initiate in-fliximab 5 mg/kg, and to perform ileostomy for fecal diversion and negative-pressure wound therapy. The patient presented with marked improvement of the lesions, being discharged after 2 months and demonstrating almost complete resolution of the lesions within 4 months. CONCLUSION: Due to the rarity of PG, there is no evidence of the optimal management. The role of surgery is controversial as PG lesions can demonstrate pathergy and theoretically could worsen with surgical intervention. In this case it was decided based on the extent of the lesions and the experience in other septic/ulcerative perianal conditions.

INTRODUÇÃO: O pioderma gangrenoso (PG) é uma doença rara e de difícil diagnóstico, que frequentemente se associa à doença inflamatória intestinal. CASO: Apresentamos um caso de uma mulher de 57 anos de idade com colite ulcerosa sob 5-ASA que recorreu ao serviço de urgência pelo aparecimento de úlceras rapidamente progressivas no pé direito e no interior da coxa, estendendo-se desde o grande lábio vaginal esquerdo até à área perianal, compatível com PG. A doente foi inicialmente tratada com corticosteroides, sem resposta. Após consulta multidisciplinar, optou-se por iniciar o infliximab 5 mg/kg, realizar ileostomia para desvio fecal e iniciar terapia de vácuo com pressão negativa. A doente apresentou melhoria marcada das lesões tendo tido alta após 2 meses e demonstrando resolução quase completa das lesões aos 4 meses. CONCLUSÃO: Devido à raridade do PG, não há evidências de qual a abordagem ideal. O papel da cirurgia é controverso, pois as lesões do PG podem demonstrar patergiae teoricamente poderiam piorar com a intervenção cirúrgica. Neste caso, a opção cirúrgica foi tomada com base na extensão das lesões e na experiência em outras condições perianais sépticas/ulcerativas.

Prognostic Significance of RAS Mutations and P53 Expression in Cutaneous Squamous Cell Carcinomas.

TP53 is considered the most commonly-altered gene in cutaneous squamous cell carcinoma (cSCC). Conversely, RAS mutations have been reported in a low percentage of cSCC. The objective of our study was to evaluate the frequency of p53 expression and RAS mutations in cSCC and correlate them with clinicopathological features and patient outcome. We performed immunohistochemistry for p53 and genetic profiling for RAS mutations in a retrospective series of cSCC. The predictive value of p53 expression, RAS mutations, and clinicopathological parameters was assessed using logistic regression models. The overall frequency of RAS mutations was 9.3% (15/162), and 82.1% of the cases (133/162) had p53 overexpression. RAS mutations rate was 3.2% (1/31) of in situ cSCCs and 10.7% (14/131) of invasive cSCCs. RAS mutations were more frequently associated with an infiltrative than an expansive pattern of invasion (p = 0.046). p53 overexpression was a predictor of recurrence in the univariate analysis. Our results indicate that RAS mutations associate with features of local aggressiveness. Larger studies with more recurrent and metastatic cSCCs are necessary to further address the prognostic significance of p53 overexpression in patients' risk stratification.

Comparative effectiveness of purpuragenic 595 nm pulsed dye laser versus sequential emission of 595 nm pulsed dye laser and 1,064 nm Nd:YAG laser: a double-blind randomized controlled study.

INTRODUCTION: Erythematotelangiectatic rosacea is a common condition in Caucasians. The most frequently used lasers to treat this condition are pulsed dye laser (PDL) and neodymium:yttrium-aluminum-garnet laser (Nd:YAG). This study compares the treatment efficacy of purpuragenic PDL with that of sequential emission of 595 nm PDL and 1,064 nm Nd:YAG (multiplexed PDL/Nd:YAG). METHODS: We performed a prospective, randomized, and controlled split-face study. Both cheeks were treated, with side randomization to receive treatment with PDL or multiplexed PDL/Nd:YAG. Efficacy was evaluated by spectrophotometric measurement, visual photograph evaluation, the Dermatology Quality of Life Index questionnaire, and a post-treatment questionnaire. RESULTS: Twenty-seven patients completed the study. Treatment was associated with a statistically significant improvement in quality of life (p < 0.001). PDL and multiplexed PDL/Nd:YAG modalities significantly reduced the erythema index (EI; p < 0.05). When comparing the degree of EI reduction, no differences were observed between the two treatment modalities. PDL was associated with a higher degree of pain and a higher percentage of purpura. Multiplexed PDL/Nd:YAG modality was associated with fewer side effects and greater global satisfaction, and 96.3% of the patients would recommend this treatment to a friend. CONCLUSIONS: Both laser modalities are efficacious in the treatment of erythematotelangiectatic rosacea. The multiplexed PDL/Nd:YAG modality was preferred by the patients.

Daylight photodynamic therapy in 25 patients with actinic keratosis and evaluation of efficacy by confocal microscopy.

BACKGROUND: Daylight photodynamic therapy (PDT) has been reported as having similar efficacy to conventional photodynamic therapy in actinic keratosis treatment. METHODS: 25 patients with actinic keratosis of the scalp and/or face were submitted to a daylight photodynamic therapy session. Adverse reactions were evaluated after one week and efficacy after 3 months. Confocal Microscopy was performed in 6 patients, before and one week after the treatment. Our aim was to compare our results with others studies and analyse the changes occurring in the epidermis and upper dermis with confocal microscopy. RESULTS: 76% of the patients were male. The mean age was 74.2 years. In 51.7% of patients the treatment site was the scalp. Mean cure rate at 3 months was 74%. Aesthetic results were excellent in all patients and only one patient reported mild pain during the 2 h exposure. Confocal Microscopy showed a normalization of the honeycomb pattern in all of the patients. CONCLUSIONS: This therapy has similar results to conventional photodynamic therapy and stands out for less discomfort, fewer adverse effects and better cost-effectiveness. Using confocal microscopy it's possible to in vivo demonstrate the efficacy of this method, with normalization of the honeycomb pattern in the epidermis following succcessful PDT.

The genetics of cutaneous squamous cell carcinogenesis.

In this review, the current knowledge of cutaneous squamous cell carcinogenesis (cSCC) is outlined based on an appraisal of the different features of cSCC, with particular emphasis on genetic alterations underlying aetiopathogenesis. When appropriate, diagnostic and/or prognostic biomarkers for cSCC are also considered. This review is intended to aid future investigation into the molecular characterization of cSCC.

Near-total lower lip reconstruction: combined Karapandzic and Bernard-Burrow-Webster flap.

Lip carcinoma is a common cancer of the head and neck region. It more often affects the lower lip (> 90%), and squamous cell carcinoma represents 95% of the cases. The authors present a reconstruction of the lower lip combining two classical flaps: the Karapandzic and Bernard-Burrow-Webster flap. The surgical technique is discussed.

Evaluation of hygiene habits: cross-sectional study.

Introduction: It is well known that adequate hygiene is important for health. Even though this topic has drawn the attention of the media, little or no scientific investigation has been done. Methods: We performed a comparative questionnaire-based cross-sectional study in three groups: patients attending a dermatology outpatient clinic, patients attending an internal medicine consultation, and community members. Results: We analyzed a total of 446 questionnaires (249 from dermatology patients, 98 from internal medicine patients, and 99 from the community group). The three groups did not differ statistically in sex and age (p=0.070). The patients from the dermatology department had a higher education level. The number of weekly baths did not differ among the three groups (p=0.417). Hair hygiene did not differ between the three groups. The dermatology and internal medicine groups washed their hands more frequently than the community group (p=0.028). Conclusions: Comparing our results to the limited data available, we find that the population surveyed has better hygiene habits than those previously reported. We believe that hygiene habits should be discussed during office visits.

Inverse psoriasis treated with ustekinumab.

Inverse psoriasis is characterised by the involvement of flexural skin folds. This form of psoriasis has distinct clinical and therapeutic features. This report refers to the case of a 48-year-old Caucasian man who was observed in our department, with a clinically and biopsy proven diagnosis of inverse psoriasis. For 2 years, the patient was treated with different combinations of corticosteroids, vitamin D analogues and methotrexate, with no satisfactory response. Given the lack of a clinical response and comorbidities, latent tuberculosis was excluded, and we started treatment with ustekinumab. We chose this biological agent because the patient was a long-distance truck driver and refused the possibility of autoinjections. The patient underwent three ustekinumab injections, which resulted in significant improvement of pruritus, erythaematous lesions and quality of life.