Scleredema diabeticorum in a patient: un uncommon etiology of restrictive lung pattern Escleredema diabeticorum en un paciente: una etiología infrecuente de patrón restrictivo pulmonar.

Scleredema adultorum of Buschke is a rare skin disease characterized by skin thickening and tightening typically at the neck and the upper part of the body. This thickening results from increased mucin deposition in the reticular dermis. Three variants are recognized. Scleredema diabeticorum is one subtype associated with diabetes mellitus. We report a man with a history of poorly controlled diabetes presenting with extensive scleredema adultorum of the trunk in a "cuirasse" pattern associated with restrictive lung disease. Cutaneous ultrasonography revealed a marked thickening of the dermis as well as various echogenic spots in the dermis. Cutaneous hardness secondary to scleredema may cause limited mobility. Therefore, respiratory manifestations may be associated and assessed, mainly in cases of extensive scleredema involving trunk and shoulders. Moreover, cutaneous ultrasonography may be useful to monitor the evolution of scleredema and confirm the diagnosis.

Prognostic and Clinicopathological Significance of CCND1/Cyclin D1 Upregulation in Melanomas: A Systematic Review and Comprehensive Meta-Analysis.

Our objective was to evaluate the prognostic and clinicopathological significance of cyclin D1 (CD1) overexpression/CCND1 amplification in melanomas. We searched studies published before September 2019 (PubMed, Embase, Web of Science, Scopus). We evaluated the quality of the studies included (QUIPS tool). The impact of CD1 overexpression/CCND1 amplification on overall survival and relevant clinicopathological characteristic were meta-analyzed. We performed heterogeneity, sensitivity, small-study effects, and subgroup analyses. Forty-one studies and 3451 patients met inclusion criteria. Qualitative evaluation demonstrated that not all studies were performed with the same rigor, finding the greatest risk of bias in the study confounding domain. Quantitative evaluation showed that immunohistochemical CD1 overexpression had a statistical association with Breslow thickness (p = 0.007; OR = 2.09,95% CI = 1.23-3.57), significantly higher frequency of CCND1/cyclin D1 abnormalities has been observed in the primary tumor compared to distant metastases (p = 0.004), revealed also by immunohistochemical overexpression of the protein (p < 0.001; OR = 0.53,95% CI = 0.40-0.71), while the CCND1 gene amplification does not show association (p = 0.43); while gene amplification, on the contrary, appeared more frequently in distant metastases (p = 0.04; OR = 1.70,95% CI = 1.01-2.85) and not in the primary tumor. In conclusion, CCND1/cyclin D1 upregulation is a common molecular oncogenic alteration in melanomas that probably favors the growth and expansion of the primary tumor. This upregulation is mainly consequence to the overexpression of the cyclin D1 protein, and not to gene amplification.

Lupus miliaris disseminatus faciei with complete response to isotretinoin.

Lupus miliaris disseminatus faciei is an uncommon type of granulomatous rosacea characterized by a papular eruption in the central regions of the face. A 43-year-old woman presented with an asymptomatic papular eruption on the face that had developed over a period of five months. Physical examination revealed multiple, small, reddish-brown papules, distributed symmetrically on the central area of the face. A biopsy was taken, showing dermal epithelioid cell granulomas with central necrosis and surrounding lymphocytic infiltrate with multinucleate giant cells. No foreign bodies were found in granulomas and no mycobacterial or fungal components were detected. On the basis of these findings, the diagnosis of lupus miliaris disseminatus faciei was made. The patient was given oral isotretinoin 20mg/day with initial slow response. After 6 months' treatment the lesions completely disappeared. Many authors consider this entity to be a variant of granulomatous rosacea. It is a chronic condition that primarily affects young adults. Treatment is usually unsatisfactory. Therapies with corticosterois, tetracyclines, retinoids, clofazimine or topical tacrolimus have been described but there is a lack of controlled studies and convincing results. Our success with a 6-month course of low dose isotretinoin suggests consideration of a longer trial prior to abandoning this as treatment.

Worldwide prevalence of oral lichen planus: A systematic review and meta-analysis.

The objective was to assess the global oral lichen planus prevalence. We searched PubMed, EMBASE, Web of Science, and Scopus for studies published before September 2019. We evaluated the quality of studies and carried out several meta-analyses. The global pooled prevalence was 1.01%, with a marked geographical difference (p < .001). The highest prevalence was reported from Europe (1.43%) and the lowest in India (0.49%), where tobacco-associated keratosis appears to mask oral lichen planus resulting in attenuation of its prevalence. From the age of 40 years, the prevalence increases significantly and progressively (OR = 3.43, 95% CI = 2.48-4.73, p < .001). Studies that define diagnostic criteria report a higher prevalence (1.31% vs. 0.70%, p = .03), although the application of the WHO criteria (year 1978-2007) does not increase the ability to diagnose the disease compared with other criteria (p = .11). The studies performed by oral medicine/oral pathology specialists report significantly higher prevalence (1.80%) than dentists (0.61%) and dermatologists (0.33%; p < .001). In conclusion, we propose that reliable diagnostic criteria should be defined, which should include a set of essential criteria including the presence of white reticular lesions in any location of the oral mucosa. The impact of histopathological confirmation with defined diagnostic criteria must be researched in the future, although its main use should be to determine the presence or absence of epithelial dysplasia. The necessity to improve the knowledge of oral lichen planus among dentists and dermatologists through continuing education is apparent in the results of this meta-analysis.

Clinicopathological and prognostic significance of PD-L1 in oral cancer: A preliminary retrospective immunohistochemistry study.

OBJECTIVE: To evaluate the relation between PD-L1 expression in oral cavity squamous cell carcinomas and clinicopathological features as well as survival outcomes. METHODS: A retrospective immunohistochemical study was carried out on 55 archived tumours from 55 patients. Tumours were stained for PD-L1 and scored by the proportion of tumour cells with positive membranous staining. PD-L1 scores were compared to the patient's clinicopathological characteristics for any significant associations. Kaplan-Meier curves were constructed for PD-L1 positive and negative tumours to investigate any advantage to survival. RESULTS: Positive PD-L1 staining was found in 58% of tumours and was significantly more likely in non-smokers, non-drinkers and in tongue squamous cell carcinomas. Increased PD-L1 was also associated with increased lymphocyte infiltration as well as PD-L1 staining in lymphocytes and the epithelium adjacent to tumour invasion. No survival benefit was seen from PD-L1 expression in tumour cells. CONCLUSIONS: PD-L1 expression is more common in non-smokers and non-drinkers, and its presence in the adjacent non-tumour epithelium suggests it may be involved in early oncogenesis.

Prognostic and Clinicopathological Significance of FADD Upregulation in Head and Neck Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.

Fas-associated death domain (FADD) upregulation, i.e., gene amplification, protein phosphorylation and/or overexpression, has shown promising prognostic implications in head and neck squamous cell carcinoma (HNSCC). This systematic review and meta-analysis aims to evaluate the clinicopathological and prognostic significance of FADD upregulation in HNSCC. We searched studies published before February 2020 through PubMed, Embase, Web of Science, Scopus and Google Scholar. We evaluated the quality of the studies included using the QUIPS tool. The impact of FADD upregulation on survival and clinicopathological variables was meta-analysed. We explored heterogeneity and their sources, conducted sensitivity analyses and investigated small-study effects. Thirteen studies (1,923 patients) met inclusion criteria. FADD immunohistochemical overexpression was statistically associated with worse overall survival (hazard ratio [HR] = 1.52, 95% confidence intervals [CI] = 1.28-1.81, p < 0.001), disease-specific survival (HR = 2.52, 95% CI = 1.61-3.96, p < 0.001), disease-free survival (HR = 1.67, 95% CI=1.29-2.15, p < 0.001), higher clinical stage (odds ratio [OR] = 1.72, 95% CI = 1.17-2.51, p = 0.005) and a large magnitude of effect with N+ status (OR = 2.36, 95% CI = 1.85-3.00, p < 0.001). FADD phosphorylation in ser-194 demonstrated no prognostic value, while no conclusive results can be drawn for FADD gene amplification. In conclusion, our findings indicate that immunohistochemical assessment of FADD overexpression could be incorporated into the prognostic evaluation of HNSCC.

Clinicopathological and prognostic characteristics of oral squamous cell carcinomas arising in patients with oral lichen planus: A systematic review and a comprehensive meta-analysis.

OBJECTIVES: To evaluate current evidence in relation to the prognostic and clinicopathological significance of oral squamous cell carcinomas arising in patients with oral lichen planus (OLP-OSCC). MATERIAL AND METHODS: We searched PubMed, Embase, Web of Science and Scopus for studies published before May-2019. We evaluated the quality of studies (QUIPS tool). We carried out meta-analyses to fulfill our objective. We examined the between-study heterogeneity and small-study effects, and conducted sensitivity and subgroup analyses. RESULTS: Inclusion criteria were met by 27 studies (10,505 patients with OLP, of whom 205 developed a total of 247 OSCCs). The combined 5-year mortality rate was 15.48% for OLP-OSCC (95%CI  =  7.34-25.19), clearly lower than the 34.70-50.00% mortality rate for conventional oral cancer communicated in previous official reports. Also, 14.67% (95%CI  =  6.34-24.81) of OLP-OSCC developed N+ status, compared to 47.00% of conventional oral carcinomas. Likewise, most of the OSCCs in the study were T1/T2 (93.57%, 95%CI  =  82.20-99.88) and presented at stage I/II (81.51%, 95%CI = 68.32-92.38) at the time of diagnosis, which contrasts with 50.00% of conventional carcinomas diagnosed in stages I/II. Furthermore, most of the cases were grade I (well differentiated OSCC) (67.79%; 95%CI = 43.50-88.65), in comparison to conventional OSCCs, which present typically in grade II in 90.00% of cases. Our results also show an 11.21% of the OLP-OSCC patients in this study developed multiple tumors. CONCLUSIONS: Oral squamous cell carcinomas that developed in oral lichen planus show favorable prognostic parameters, especially with regard to the mortality rate. Around 11% of OLP-OSCC patients develop multiple tumors, which confirms that OLP can lead to field cancerization.

Prognostic and clinicopathological significance of PD-L1 overexpression in oral squamous cell carcinoma: A systematic review and comprehensive meta-analysis.

BACKGROUND: The presence of Programmed Death-Ligand 1 protein (PD-L1) in oral squamous cell carcinoma (OSCC) may indicate an ability to evade immune response and has been suggested as a prognostic marker, but there is controversy in the literature. OBJECTIVE: To review the scientific evidence of a prognostic role for PD-L1 levels in OSCC. METHODS: PubMed, Embase, Web of Science, and Scopus were searched for studies published on or before March 02, 2019. Studies measuring PD-L1 levels by immunohistochemistry (IHC) in OSCC were included. Study quality was assessed using the QUIPS tool. Meta-analysis was performed for survival outcomes and clinic-pathological parameters. RESULTS: 26 articles were included comprising 2532 patients. Analysis of studies measuring PD-L1 expression in the cell membrane showed a worse prognosis for disease-specific survival (HR = 1.74, 95% CI = 1.14-2.66, p = 0.01) and disease-free survival (HR = 1.56, 95% CI = 1.16-2.09, p = 0.003). PD-L1 overexpression was more likely in females (OR = 0.69, 95% CI = 0.53-0.91, p = 0.008), non-smokers (OR = 0.45, 95% CI = 0.27-0.75, p = 0.002), non-drinkers (OR = 0.40, 95% CI = 0.16-0.97, p = 0.04), advance stage tumours (OR = 1.63, 95% CI = 1.00-2.64, p = 0.05) and in tumours with high levels of PD-1 (OR = 33.36, 95% CI = 1.88-591.69, p = 0.02), CD4+ (OR = 3.25, 95% CI = 1.36-7.76, p = 0.008) and CD8+ (OR = 3.63 , 95% CI = 1.20-10.99, p = 0.02). CONCLUSION: This meta-analysis found a worse prognosis in OSCCs overexpressing PD-L1 in the cell membrane as measured by disease specific survival and disease-free survival. We also found positive correlations between PD-L1 overexpression and advanced tumours, females, non-smokers, non-drinkers and high levels of tumour PD-1, CD4, and CD8.

An update on the implications of cyclin D1 in melanomas.

Cyclin D1 is a protein encoded by the CCND1 gene, located on 11q13 chromosome, which is a key component of the physiological regulation of the cell cycle. CCND1/cyclin D1 is upregulated in several types of human tumors including melanoma and is currently classified as an oncogene that promotes uncontrolled cell proliferation. Despite the demonstrated importance of CCND1/cyclin D1 as a central oncogene in several types of human tumors, its knowledge in melanoma is still limited. This review examines data published on upregulation of the CCND1 gene and cyclin D1 protein in the melanoma setting, focusing on the pathways and molecular mechanisms involved in the activation of the gene and on the clinical and therapeutic implications.

Cutaneous lupus erythematosus, morphea profunda and psoriasis: A case report. / Lupus eritematoso cutáneo, morfea profunda y psoriasis en una paciente.

Psoriasis is a common inflammatory dermatosis that may be associated with a number of diseases. Recent studies provide evidence that there is a greater frequency of autoimmune diseases, but association with autoimmune connective tissue diseases is uncommon. The coexistence of psoriasis and lupus erythematosus is rare. Besides, the occurrence of morphea has rarely been reported in patients with lupus or psoriasis. We report a woman with cutaneous lupus and morphea profunda associated with psoriasis, with an excellent response to methotrexate, and review the literature.

Report of a man with heterotopic ossification of the legs. / Osificación heterotópica de las piernas en un varón.

Heterotopic ossification is an uncommon disorder that consists of deposition of ectopic bone outside the extraskeletal tissues. In the skin, it can be primary, in association with genetic syndromes, or be secondary to different disorders. The latter include subcutaneous ossification of the legs in chronic venousinsufficiency, an infrequent and unrecognized complication. We report the case of a patient with subcutaneous ossification of both legs secondary to venous insufficiency and review the literature.

An update of knowledge on PD-L1 in head and neck cancers: Physiologic, prognostic and therapeutic perspectives.

Programmed cell death-ligand 1 (PD-L1) is a transmembrane protein that acts as a co-inhibitory factor in the immune response. Its receptor, programmed cell death protein 1 (PD-1), is found on immune cells, where binding to PD-L1 can reduce the proliferation of PD-1-positive cells, inhibit their cytokine secretion and induce apoptosis. PD-L1 in immune-privileged tissue plays a crucial role in peripheral tolerance. PD-L1 can be overexpressed in various malignancies, including oral squamous cell carcinoma, where it can attenuate the host immune response to tumour cells and has been associated with a worse prognosis. Monoclonal antibody therapies targeting the PD-1:PD-L1 axis have shown initial promise, but further research is needed to identify which patients will benefit. We provide an update of knowledge on PD-L1, including its structure, function and regulation. We also review studies on the overexpression of PD-L1 in cancer, specifically oral squamous cell carcinoma, and explore its potential value as a therapeutic target.

Malignant transformation risk of oral lichen planus: A systematic review and comprehensive meta-analysis.

OBJECTIVES: To evaluate current evidence on the malignant transformation of oral lichen planus (OLP), oral lichenoid lesions (OLLs), and oral lichenoid reactions (LRs) and to determine the variables with greatest influence on cancer development. MATERIAL AND METHODS: We searched PubMed, Embase, Web of Science, and Scopus for studies published before November 2018. We evaluated the quality of studies (QUIPS tool). We carried out meta-analyses to fulfill our objectives. We examined the between-study heterogeneity and small-study effects, and conducted sensitivity studies and subgroup analyses. RESULTS: Inclusion criteria were met by 82 studies (26,742 patients. The combined malignant transformation rate was 1.14% for OLP (95% CI = 0.84-1.49), 1.88% for OLLs (95% CI = 0.15-4.95) and 1.71% for LRs (95% CI = 0.00-5.46). Subgroup analysis revealed a higher malignant transformation rate in studies when the presence of epithelial dysplasia was not an exclusion criterion (p = 0.001), when both clinical and histopathological criteria were used for diagnosis (p < 0.001), when the follow-up was at least 12 months (p = 0.048), and when there was lower risk of potential bias (p = 0.002). Malignant transformation risk factors were: tongue localization (RR = 1.82, 95% CI = 1.21-2.74, p = 0.004), presence of atrophic-erosive lesions (RR = 4.09, 95% CI = 2.40-6.98, p < 0.001), tobacco use (RR = 1.98, 95% CI = 1.28-3.05, p = 0.002), alcohol consumption (RR = 2.28, 95% CI = 1.14-4.56, p = 0.02), and hepatitis C virus infection (RR = 4.46, 95% CI = 0.98-20.22, p = 0.053). CONCLUSIONS: The malignant transformation rates of OLP, OLLs and LRs are underestimated due essentially to restrictive diagnostic criteria, inadequate follow-up periods, and/or low quality of studies.

Delayed hypersensitivity to palladium dichloride: 15-year retrospective study in a skin allergy unit.

BACKGROUND: Metal allergies are the most frequent causes of allergic contact dermatitis. Although the use of palladium is increasing, it is not included in any baseline series. OBJECTIVE: To assess the prevalence of hypersensitivity to palladium and to describe the clinical and demographic characteristics of patients who are sensitized to palladium dichloride (PdCl2 ). METHODS: A single-centre, retrospective study of 15 years of patch testing with the Spanish baseline series supplemented with PdCl2 2% pet. was performed. We collected clinical and demographic data and data on co-sensitization among the metals studied, and we compared patients who were sensitized to palladium, with or without co-sensitization to nickel, with the rest of the study population. RESULTS: Among the 3678 included patients, 730 (19.9%) were sensitized to nickel sulfate. The prevalence of sensitization to PdCl2 (n = 316, 8.6%) was higher than the prevalence of sensitization to potassium dichromate (n = 240, 6.5%) and similar to the prevalence of sensitization to cobalt chloride (n = 353, 9.6%). Only 26 (8.2%) of the patients sensitized to palladium were not co-sensitized to nickel. The percentage of men and patients aged ≥40 years was higher in this subgroup than in the patients with nickel co-sensitization. CONCLUSIONS: Given the high prevalence of hypersensitivity to PdCl2 , this metal salt should be included in the Spanish baseline series, notwithstanding the frequency of co-sensitization to nickel.