Malignant development of proliferative verrucous/multifocal leukoplakia: A critical systematic review, meta-analysis and proposal of diagnostic criteria.

BACKGROUND: Proliferative verrucous/multifocal leukoplakia (PVML) is an oral potentially malignant disorder (OPMD) that exhibits high rates of malignant development (MD). This study aimed to analyse the risk of MD of PVML, as well as to investigate the possible risk factors associated with its malignization. METHODS: A bibliographical search of the PubMed, Embase, Web of Science, and Scopus databases was conducted. PVML MD rates were calculated as a pooled proportion, and the risk factors were calculated as risk ratios, using fixed and random models based on the presence of heterogeneity. RESULTS: From a total of 417 records, 16 articles were retrieved for inclusion. The subgroup analysis revealed a higher MD rate in the studies that were conducted in America, and, likewise, said studies involved a longer follow-up time (>6 years). There was a non-significant lower risk of malignization among males. A negative correlation was observed between MD and the year in which the studies were published. CONCLUSIONS: The pooled MD of PVML was 65.8% (95% CI: 55.3-76.2, p < 0.001). Prospective studies of PVML must be designed using simple and universal clinical diagnostic criteria to be able to make an early diagnosis of this important OPMD and acknowledge the frequency of MD.

[Abnormal gut microbiota-induced hypoestrogenemia as a possible risk factor for malignancy in endometrioid heterotopia]. / Gipoéstrogenemiia, vyzvannaia narusheniem kishechnoi mikrobioty, kak vozmozhnyi faktor riska malignizatsii éndometrioidnoi geterotopii.

This paper reveals the pathogenetic impact of the abnormal gut microbiota on the development of female reproductive system diseases. A dynamic imbalance between the altered microbiota and the macroorganism has many manifestations as hormonal homeostatic disorders, one of which is dysbiosis-induced hypoestrogenemia. Using endometrioid heterotopia as an example, the authors trace the possibility of its progression and malignancy due to the occurrence of primary breakdown of the PTEN tumor-suppressor gene with subsequent genetic abnormalities in the ARID1A and TP53 genes. PTEN mutation in both endometriosis itself and its malignancy indicates that dysbiosis-induced hypoestrogenemia may be implicated in the pathogenesis of endometriosis. Thus, the relationship between female reproductive system diseases and gut microbiome disorders may be more significant; and the possibility of correcting the gut microbiota with prebiotics and probiotics opens new horizons not only in the prevention, but also in the treatment of many gynecological diseases associated with hormone disorders.

Changes in the genetic landscape during the malignization of high grade squamous intraepithelial lesion into cervical cancer.

In 5 patients, a change in the genetic landscape from HPV16 positive high-grade squamous intraepithelial lesion (HSIL) to squamous cervical cancer was traced, which occurred in these patients within the period from 7 months to 5 years after diagnosing HSIL. MATERIALS AND METHODS: The DNA from paraffin blocks of dysplasia tissue and the tumor that emerged afterwards was used for the study, which was analyzed using the OncoScan FFPE microarray Assay Kit Affymetrix (USA) for genome-wide determination of gene abundance and 65 key somatic driver mutations of oncogenes and tumor suppressor genes. RESULTS: In the study of HSIL material, somatic mutations were observed in 4/5 cases, 18 different somatic driver mutations of the NRAS, EGFR, BRAF, KRAS, IDH2 oncogenes and TP53 suppressor genes were found and almost no CNA-Copy Number Aberration was identified. HSIL malignization is associated with the appearance of secondary driver mutations in oncogenes and tumor suppressor genes and a large number of structural and numerical CNA, the frequency of which correlates with the time of dysplasia malignization into cancer with a very high correlation coefficient r = 0.98, P = 0.004. The trees of dysplasia evolution into tumor were constructed for each patient. CONCLUSION: According to the results of the work, it is assumed that the initiation of the development of mucosa dysplastic changes is due to primary driver mutations. The formation of secondary driver mutations and CNA are genetic mechanisms of malignant transformation, while the scenarios of the evolution of dysplasia into a tumor are individual and very diverse.

Therapeutic approaches for actinic cheilitis: therapeutic efficacy and malignant transformation after treatment.

Actinic cheilitis (AC) is a sun-induced premalignant lesion. AC is a clinical term housing a wide pathological spectrum ranging from hyperkeratosis to invasive squamous cell carcinoma. The aim of this systematic review was to examine the therapeutic efficacy of different approaches in clinical, histological, and cosmetic terms, and the malignization rate after treatment. A systematic search was undertaken in October 2016 and updated in April 2019 at MEDLINE (from 1966), Embase (from 1980), and Proceedings Web of Science (Conference Proceedings Citation Index-Science (CPCI-S) from 1990) databases. The search strategy was (("actinic" or "solar") AND ("cheilitis")) using both medical subject headings (MeSH) and freetext. A total of 392 potentially eligible reports were identified. After the selection procedure, 20 articles were included. It was concluded that surgical treatment is the first line of treatment for AC and has proved useful for the clinical and pathological control of the disorder. However, there was no evidence of effective treatment in preventing malignant transformations. Non-surgical procedures showed less consistent results, although drug therapy may improve the results obtained by other therapeutic approaches.

Is Visible Aminolevulinic Acid-Induced Fluorescence an Independent Biomarker for Prognosis in Histologically Confirmed (World Health Organization 2016) Low-Grade Gliomas?

BACKGROUND: Approximately 20% of low-grade gliomas (LGG) display visible protoporphyrin fluorescence during surgery after 5-aminolevulinic acid (5-ALA) administration. OBJECTIVE: To determine if fluorescence represents a prognostic marker in LGG. METHODS: Seventy-four consecutive patients with LGG (World Health Organization 2016) were operated on with 5-ALA. Fluorescent tissue was specifically biopsied. Tumor size, age, Karnofsky index, contrast-enhancement, fluorescence, and molecular factors (IDH1/IDH2-mutations, Ki67/MIB1 Index, 1p19q codeletions, ATRX, EGFR, p53 expression, and O6-methylguanine DNA methyltransferase promotor methylation), were related to progression-free survival (PFS), malignant transformation-free survival (MTFS) and overall survival (OS). RESULTS: Sixteen of seventy-four LGGs (21.6%) fluoresced. Fluorescence was partially related to weak enhancement on magnetic resonance imaging and increased (positron emission tomography)PET-FET uptake, but not to Karnofsky Performance Score, tumor size, or age. Regarding molecular markers, only EGFR expression differed marginally (fluorescing vs nonfluorescing: 19% vs 5%; P = .057). Median follow-up was 46.4 mo (95% confidence interval [CI]: 41.8-51.1). PFS, MTFS, and OS were shorter in fluorescing tumors (PFS: median 9.8 mo, 95% CI: 1.00-27.7 vs 45.8, 31.9-59.7, MTFS: 43.0 [27.5-58.5] vs 64.6 [57.7-71.5], median not reached, P = .015; OS: 51.6, [34.8-68.3] vs [68.2, 62.7-73.8], P = .002). IDH mutations significantly predicted PFS, MTFS, and OS. In multivariate analysis IDH status and fluorescence both independently predicted MTFS and OS. PFS was not independently predicted by fluorescence. CONCLUSION: This is the first report investigating the role of ALA-induced fluorescence in histologically confirmed LGG. Fluorescence appeared to be a marker for inherent malignant transformation and OS, independently of known prognostic markers. Fluorescence in LGG might be taken into account when deciding on adjuvant therapies.

Secreted protein acidic and rich in cysteine-like 1 suppresses metastasis in gastric stromal tumors.

BACKGROUND: Malignant growth and metastasis of gastrointestinal stromal tumors (GIST) occur in some patients even during the course of treatment, but their mechanisms remains poorly understand at the molecular level so far. METHODS: Profiles of protein expression in gastric GIST tissues were explored using protein microarray analysis, down-regulation of SPARCL1 (secreted protein acidic and rich in cysteine-like protein 1) was validated by RT-qPCR, western blot and immunohistochemistry. The effect of specific shRNA-induced SPARCL1 downregulation on the biological traits of GIST 882 cell was investigated. We then employed a mouse xenograft model to investigate whether the low-expression of SPARCL1 impact the metastasis ability of GIST cells in vivo. RESULTS: SPARCL1 was significantly downregulated in the gastric GIST with high-grade malignance as compared with low-grade malignance, its expression was closely correlated with tumor size, mitotic index, distant metastasis at the time of initial diagnosis and tumor progression of GIST (P < 0.05). Moreover, results of the Cox analysis showed that expression of SPARCL1 is an independent prognostic predictors for gastric GIST (P = 0.008; HR 0.157, 95% CI 0.040~ 0.612). Downregulation of SPARCL1 promoted cell migration and invasion, but did not affect proliferation, cell cycle and apoptosis of GIST 882 cells. In mouse xenograft model, GIST cells with the decreased expression of SPARCL1 presented an enhanced ability of liver metastasis (P < 0.05). CONCLUSIONS: Taken together, our present study demonstrated that SPARCL1 have a certain degree of malignancy-suppressing potential through inhibiting the metastasis of gastric GIST.

[Oral lichen planus. Case report and literature review]. / Liquen plano bucal. Reporte de un caso y revisión de la literatura.

BACKGROUND: Oral lichen planus is a chronic inflammatory skin disease of autoimmune nature, with infiltration of T lymphocytes that destroy the basal stratum, which causes white striae, erosions, ulcers and breaks in epithelial continuity. CASE REPORT: 54-year-old woman with multiple reticular and erosive lesions in the region of the buccal mucosa and lateral borders of the tongue, as well as desquamative gingivitis. Treatment with mometasone was started thrice daily for 20 days and intermittently with miconazole gel to prevent iatrogenic mycosis by the corticosteroid. The patient was examined at 20 days, after which 80 % improvement of the lesions that had central ulcerations was observed, which allowed the ingestion of food and fluids without pain and improved the quality of life. CONCLUSIONS: In autoimmune diseases, clinical-histopathological correlation is important for a definitive diagnosis to be established. Clinical follow-up of these patients should be carried out in the long term, in order to achieve remission of the lesions, control of the disease and avoid future complications.

Antecedentes: El liquen plano bucal es una enfermedad dermatológica inflamatoria crónica de base autoinmune, con infiltración de linfocitos T que destruyen el estrato basal, lo que ocasiona estrías blancas, erosiones, úlceras y diluciones epiteliales de continuidad. Reporte de caso: Mujer de 54 años con múltiples lesiones reticulares y erosivas en región de la mucosa yugal y bordes laterales de la lengua, así como gingivitis descamativa. Se inició tratamiento con mometasona tres veces al día por 20 días e intermitentemente con miconazol en gel, para prevenir micosis iatrogénica por el corticosteroide. La paciente fue revisada a los 20 días, al cabo de los cuales se observó mejoría de 80 % de las lesiones con ulceraciones centrales, lo que permitió la ingesta de alimentos y líquidos sin dolor y mejoró la calidad de vida. Conclusiones: En las enfermedades autoinmunes es importante la correlación clínico-histopatológica para establecer el diagnóstico definitivo. El seguimiento clínico de estos pacientes se debe realizar a largo plazo, para lograr la remisión de las lesiones, control de la enfermedad y evitar futuras complicaciones.

Expresiones clínicas de los desórdenes potencialmente malignos en cavidad oral. Revisión integrativa de la literatura / Clinical expressions of potentially malignant disorders in oral cavity. integrative review of literature

Antecedentes: Los desórdenes potencialmente malignos (DPM) son aquellas situaciones clínicas en la cavidad bucal que presentan un riesgo aumentado de malignización neoplásica, debido a la exposición a factores de riesgo o alteraciones genéticas. Es necesario realizar revisiones de la evidencia de este tipo de desórdenes para desarrollar o actualizar guías de práctica clínica idóneas. Objetivo: Identificar, a través de una revisión integrativa de la literatura, la evidencia reciente sobre DPM de la cavidad bucal y su transformación maligna, con el fin de proporcionar recomendaciones de manejo diagnóstico y terapéutico. Métodos: Se realizó una búsqueda de literatura en las bases de datos PubMed, Elsevier, SciELO y EMBASE, utilizando la combinación de seis descriptores. Resultados: La búsqueda inicial arrojó 1743 títulos y la muestra consistió en 67 artículos después de aplicar los criterios de inclusión y exclusión. Las DPM identificadas fueron liquen plano oral, palatitis nicotínica, hábito de fumar invertido, queilitis actínica, eritroplasia y leucoplasia oral y úlcera traumática crónica. Conclusión: Cada tipo de lesión tiene distinto potencial de malignización, entre los cuales la eritroplasia, el liquen plano oral variante erosivo y la queilitis actínica poseen el mayor riesgo.

Background: Potentially malignant disorders (PMD) are clinical oral cavity conditions that pose an increased risk of neoplastic malignization due to exposure to risk factors or genetic alterations. It is necessary to conduct evidence-based reviews of this type of disorders to develop or update adequate clinical practice guidelines. Purpose: Identify, through an integrative review of literature, recent evidence on PMDs in the oral cavity and their malignant transformation, in order to provide diagnostic and treatment recommendations. Methods: A literature search was carried out in the PubMed, Elsevier, SciELO, and EMBASE, using a combination of six descriptors. Results: The initial search showed 1743 titles and the sample, after applying the inclusion and exclusion criteria, consisted of 67 articles. The PMDs identified were oral lichen planus, nicotinic palatitis, inverted smoking habit, actinic cheilitis, oral erythroplakia and leukoplakia, and chronic traumatic ulcer.

Factors affecting Clinical Outcomes after Treatment of Oral Leukoplakia with CO2 and Diode Laser.

INTRODUCTION: To analyze factors that may affect recurrence, development of new lesions, and malignant transformation in patients with oral leukoplakia (OL) following surgical treatment with lasers. MATERIALS AND METHODS: A total of 40 patients were enrolled in this study, 17 females (mean age of 64.5 years; 33-88 years) and 23 males (mean age of 56.6 years; 28-84 years) with an overall mean age of 60.5 years. A total of 49 lesions were diagnosed and treated; 9 patients had more than one site affected. Mean time of follow-up was 22 months (6-71 months). Data were assessed by univariate Cox and multivariate Cox regression analyses. RESULTS: Recurrence (OL at the same site of the initial lesion) was observed in 11 patients (27.5%) while 4 patients (10%) developed new lesions, and 2 patients (5%) experienced malignant transformation. Only two clinical factors were statistically associated with the outcome for the development of new lesions: patients ≥ 60 years and female gender (p < 0.1). Neither of the outcomes of recurrences and malignant transformations was significantly correlated with any of the risk factors analyzed. CONCLUSION: Surgical laser is not a deterrent for the outcomes evaluated; additionally, the design of this study did not allow us to determine whether the laser treatment had provided a great benefit by significantly reducing the rate of malignant transformation among the patients. CLINICAL SIGNIFICANCE: It is highly important to inform patients with OL that their condition can be treated, when possible, by surgical laser, and that this treatment may be helpful in bringing down the odds of malignant transformation of their lesions. In addition, the patients should also be brought to the attention of the necessity of a continued clinical monitoring regardless of the outcome following a surgical intervention.

Aggressive inverted papilloma with intracranial invasion and short malignization time.

Inverted papillomas (IP) are considered benign lesions with a prevalence up to 4% among all sinunasal tumors; however, invasive growth and varying tendency for malignization are reported in literature. We report the case of a 69-year-old woman suffering from a large, aggressively growing IP invading the orbit, skull base, and frontal lobe of the brain. Within only 3 months' time the papilloma showed transformation into an invasive carcinoma, leaving surgical therapy in vain due to explosive recurrence. Intracranial and intraorbital expansion by IP is possible despite histology not showing signs of malignancy initially. In "regular" IP close endoscopic follow-up is mandatory to not overlook recurrence harboring malignancy.

Polipose juvenil: relato de 2 casos / Juvenile polyposis: case two report

A Polipose Juvenil é uma afecção rara e faz parte do grupo das poliposes hamartomatosas familiares (PHF). É uma síndrome autossômica dominante que pode ser desencadeada por mutações no gene SMAD4/DPC4 (que codifica um sinalizador intermediário de TGF-b). Caracteriza-se pelo aparecimento de 10 ou mais pólipos hamartomatosos (juvenis) no trato gastrintestinal, predominando no cólon. Costuma manifestar-se entre 4 e 14 anos de idade. Alguns pólipos adquirem focos adenomatosos apesar da natureza hamartomatosa das lesões e há chance de malignização. Relato de 2 casos de pacientes portadores de Polipose Juvenil colônica associada a focos de adenoma com displasia e revisão da literatura.

Juvenile Polyposis Syndrome is a rare disease and is included in the Hamartomatous Familial Polyposis's (HFP) group. It's an autosomal dominant syndrome which can be determinated by SMAD4/DPC4 germline mutations (which codifies an intermediary mediator of TGF-b). It's characterized by 10 or more hamartomatous polyps (juveniles) throughout the gastrointestinal tract, especially in the colon. The symptoms usually appears between the ages of 4 and 14 years old. Some polyps can acquire adenomatous changes despite the lesion's hamartomatous nature and there's chance of colorectum malignization. Case report of two patients with Juvenile Polyposis coli associated to adenomatous changes with dysplasia and literature review.