High Risk Of Malignant Transformation Research Articles

Giant hepatic cystadenoma mimicking a hydatid cyst: A challenging preoperative diagnosis

Biliary cystadenoma is a rare cystic tumor of the liver. It has a high recurrence rate and malignant transformation risk in middle-aged women. Pre-operative diagnosis is difficult because of the lack of clinical, biological and radiological specificity. The confirmation of the diagnosis is made by the histopathological examination. Complete surgical resection is preferred because of the high risk of malignant transformation and recurrence.

Predictive Patterns of Glutamine Synthetase Immunohistochemical Staining in CTNNB1-mutated Hepatocellular Adenomas.

Some hepatocellular adenoma (HCA) subtypes are characterized by different CTNNB1 mutations, leading to different beta-catenin activation levels, hence variable immunostaining patterns of glutamine synthetase (GS) expression, and different risks of malignant transformation. In a retrospective multicentric study of 63 resected inflammatory (n=33) and noninflammatory (n=30) molecularly confirmed CTNNB1-mutated b-(I)HCA, we investigated the predictive potential of 3 known GS patterns as markers for CTNNB1 exon 3, 7/8 mutations. Pattern 1 (diffuse homogenous) allowed recognition of 17/21 exon 3 non-S45 mutated b-(I)HCA. Pattern 2 (diffuse heterogenous) identified all b-(I)HCA harboring exon 3 S45 mutation (20/20). Pattern 3 (focal patchy) distinguished 12/22 b-(I)HCA with exon 7/8 mutations. In exon 3 S45 and 7/8 mutations, both b-HCA and b-IHCA showed a GS+/CD34- rim with diffuse CD34 positivity in the center of the lesion. Interobserver reproducibility was excellent for exon 3 mutations. Comparative analysis of GS patterns with molecular data showed 83% and 80% sensitivity (b-HCA/b-IHCA) and 100% specificity for exon 3 non-S45. For exon 3 S45, sensitivity was 100% for b-(I)HCA, and specificity 93% and 92% (b-HCA/b-IHCA). For exon 7/8, sensitivity was 55% for both subtypes and specificity 100% and 96% (b-HCA/b-IHCA). Preliminary data from 16 preoperative needle biopsies from the same patients suggest that this panel may also be applicable to small samples. In surgically resected HCA, 2 distinct GS patterns can reliably predict CTNNB1 exon 3 mutations, which are relevant because of the higher risk for malignant transformation. The third pattern, although specific, was less sensitive for the identification of exon 7/8 mutation, but the GS+/CD34- rim is a valuable aid to indicate either an exon 3 S45 or exon 7/8 mutation.

Intrahepatic Intraductal Papillary Cystic Neoplasm of the Bile Duct: A Case Report

Abstract Introduction and importance Intraductal papillary neoplasm of the bile duct (IPNB) is a tumour with a very low incidence in the Western world, characterised by a high risk of malignant transformation and unknown prognosis. It is a new entity which was adopted by the WHO in 2010 as a precursor lesion of cholangiocarcinoma. Intrahepatic bile duct is the most common site of origin for IPNB. Case presentation Hereby, we present a case of an asymptomatic 63- year-old man, referred to our department after routine ultrasonography showing a multifocal cystic lesion on the left hepatic lobe. Further screening modalities (CT, MRI abdo) confirmed a complex cystic liver lesion with atypical features. The patient underwent left hepatectomy. Histopathology showed a cystic type intrahepatic IPNB, which was completely resected (R0). The follow up in 2 yrs post-operation showed no signs of recurrence. Clinical discussion The diagnosis and management of IPNB remain challenging. A multimodality imaging approach is essential in order to diagnose IPNB, assess tumour location and extent and plan the optimal treatment strategy. Conclusion Complete surgical resection (R0) with close postoperative follow-up offers long-term survival.

Expression of spindle assembly checkpoint proteins BubR1 and Mad2 expression as potential biomarkers of malignant transformation of oral leukoplakia: an observational cohort study.

Background The Spindle Assembly Checkpoint (SAC) is a surveillance mechanism essential to ensure the accuracy of chromosome segregation during mitosis. Our aim was to evaluate the expression of SAC proteins in oral carcinogenesis, and to assess their potential in predicting malignant transformation of oral leukoplakia.Material and Methods We analysed the immunoexpression of BubR1, Mad2, Bub3, and Spindly proteins in 64 oral biopsies from 52 oral leukoplakias and 12 normal tissues. Univariate and multivariate analysis were performed to evaluate predictive factors for malignant transformation (MT).Results We observed that BubR1 and Mad2 were more highly expressed in high dysplasia grade lesions than in low grade or normal tissues (P<0.05). High expression of Spindly was significantly correlated with a high Ki-67 score (P=0.004). Six (11.5%) oral leukoplakias underwent malignant transformation. In univariate analysis, the binary dysplasia grade (high grade) (P<0.001) was associated with a higher risk of malignant transformation as well as high BubR1 (P<0.001) and high Mad2 (P=0.013) expression. In multivariate analysis, high expression of BubR1 and Mad2 when combined showed an increased risk for malignant transformation (P=0.013; HR of 4.6, 95% CI of 1.4-15.1).Conclusions Our findings reveal that BubR1 and Mad2 were associated with an increased risk for malignant transformation independently of histological grade and could be potential and useful predictive risk markers of malignant transformation in oral leukoplakias. Key words:BubR1, Mad2, Spindly, Bub3, Oral Leukoplakia, epithelial dysplasia, Oral squamous cell carcinoma.

Expression of invadopodia markers can identify oral lesions with a high risk of malignant transformation.

Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the oral cavity and is usually preceded by a range of premalignant tissue abnormalities termed oral potentially malignant disorders. Identifying malignant transformation is critical for early treatment and consequently improved survival and decreased morbidity. Invadopodia (INV) are specialized subcellular structures required for cancer cell invasion. We developed a new method to visualize INV in keratinocytes using fluorescent immunohistochemistry (FIHC) and semi‐automated images analysis. The presence of INV was used to determine the risk of malignant transformation. We analyzed 145 formalin‐fixed, paraffin‐embedded (FFPE) oral biopsy samples from 95 patients diagnosed as nondysplastic, dysplastic, and OSCC including 49 patients whose lesions transformed to OSCC (progressing) and 46 cases that did not transform to OSCC (control). All samples were stained for Cortactin, tyrosine kinase substrate with five SH3 domains (Tks5) and matrix metallopeptidase 14 (MMP14) using FIHC, imaged using confocal microscopy and analyzed using a multichannel colocalization analysis. The areas of colocalization were used to generate an INV score. Using the INV score, we were able to identify progressing lesions with a sensitivity of 75–100% and specificity of 72–76%. A positive INV score was associated with increased risk of progression to OSCC. Our results suggest that INV markers can be used in conjunction with the current diagnostic standard for early detection of OSCC.

Fitness Landscape of Clonal Hematopoiesis Under Selective Pressure of Immune Checkpoint Blockade.

Conventional cytotoxic therapies increase the risk of clonal hematopoiesis and select for TP53-mutant clones, which carry a high risk for transformation to therapy-related myelodysplastic neoplasms. In contrast, the effect of immune checkpoint blockade (ICB) on clonal hematopoiesis is unknown. Paired peripheral-blood samples taken before and after treatment with ICB were obtained for 91 patients with either cutaneous melanoma or basal cell carcinoma. Error-corrected sequencing of a targeted panel of genes recurrently mutated in clonal hematopoiesis was performed on peripheral-blood genomic DNA. The average interval between acquisition of the paired samples was 180 days. Forty-one percent of the patients had clonal hematopoiesis at a variant allele frequency (VAF) > 0.01 in the pretreatment sample. There was near-complete agreement in the distribution and burden of clonal hematopoiesis mutations in the paired blood samples, with 87 of 88 mutations identified across the cohort present in paired samples, regardless of the duration between sample collection. The VAF in the paired samples also showed a high correlation, with an R 2 = 0.95 (P < .0001). In contrast to cytotoxic therapy, exposure to ICB did not lead to selection of TP53- or PPM1D-mutant clones. However, consistent with the known effects of DNA-damaging therapy, we identified one patient who had eight unique TP53 mutations in the posttreatment blood sample after receiving two courses of radiation therapy. There was no expansion of hematopoietic clones or selection for clones at high risk for malignant transformation in patients who received ICB, observations that warrant further validation in larger cohorts. These findings highlight an important difference between ICB and conventional cytotoxic therapies and their respective impacts on premalignant genetic lesions.

Endoscopic diagnosis and management of gastric subepithelial lesions.

The purpose of this manuscript is to provide an in-depth review of gastric subepithelial lesions (SELs) and describe the current approach to endoscopic diagnosis and management of these lesions. Gastric SELs are a relatively frequent finding on routine endoscopy (incidence 0.2-3%). A systematic approach to diagnosis and management is key because many SELs are of little consequence, while others carry a high risk of malignant transformation. Because esophagogastroduodenoscopy (EGD) cannot delineate depth of invasion or subepithelial appearance, endoscopic ultrasound (EUS) should be considered a first-line modality. Recent data suggest EUS-guided fine needle biopsy (FNB) may be superior to traditional fine needle aspiration (FNA) for the diagnosis of gastric SELs due to its ability to obtain histologic specimens for immunohistochemical staining. Alternative techniques for tissue sampling (combined with simultaneous resection) include submucosal resection, endoscopic submucosal dissection (ESD), submucosal tunnelling with endoscopic resection (STER) or endoscopic full-thickness resection (EFTR). This review details the endoscopic diagnosis and management of gastric SELs. Although EUS-guided sampling remains a first-line strategy (preferably with FNB), recent techniques including ESD, STER and EFTR have the potential to provide additional diagnostic and therapeutic options.

Biomarkers of progression to oral cancer in patients with dysplasia: A systematic review.

Identifying oral dysplastic lesions with a high risk of malignant transformation may create opportunities for early therapeutic interventions. Several tissue biomarkers have been suggested to date as prognostic indicators of the progression of dysplastic lesions to oral cancer. We herein present a systematic review (PROSPERO CRD42018086476), with the aim of identifying, evaluating and summarizing evidence on prognostic biomarkers of progression to oral cancer in patients with dysplasia. A search through MEDLINE/PubMed and Scopus databases was performed. The review only included primary articles that reported risk values associated with malignancy after a multivariate analysis. The quality of the findings was analyzed using the Reporting Recommendations for Tumor Marker Prognostic Studies, and research trends were established using SciCurve Open. A total of 4 potential biomarkers were identified: Degree of dysplasia, and the proteins retinal dehydrogenase 1, prominin-1 and podoplanin. All 3 protein biomarkers have been recognized as cancer stem cell markers. The studies were of acceptable quality, although none included sample size determinations. Due to the lack of validation and follow-up studies, these biomarkers are considered to be in a discovery phase and require validation by prospective clinical trials. The present analysis indicated that there are currently insufficient data to include these biomarkers in the clinical decision-making process.

Gene Expression Clustering and Selected Head and Neck Cancer Gene Signatures Highlight Risk Probability Differences in Oral Premalignant Lesions.

Background: Oral premalignant lesions (OPLs) represent the most common oral precancerous conditions. One of the major challenges in this field is the identification of OPLs at higher risk for oral squamous cell cancer (OSCC) development, by discovering molecular pathways deregulated in the early steps of malignant transformation. Analysis of deregulated levels of single genes and pathways has been successfully applied to head and neck squamous cell cancers (HNSCC) and OSCC with prognostic/predictive implications. Exploiting the availability of gene expression profile and clinical follow-up information of a well-characterized cohort of OPL patients, we aim to dissect tissue OPL gene expression to identify molecular clusters/signatures associated with oral cancer free survival (OCFS). Materials and methods: The gene expression data of 86 OPL patients were challenged with: an HNSCC specific 6 molecular subtypes model (Immune related: HPV related, Defense Response and Immunoreactive; Mesenchymal, Hypoxia and Classical); one OSCC-specific signature (13 genes); two metabolism-related signatures (3 genes and signatures raised from 6 metabolic pathways associated with prognosis in HNSCC and OSCC, respectively); a hypoxia gene signature. The molecular stratification and high versus low expression of the signatures were correlated with OCFS by Kaplan–Meier analyses. The association of gene expression profiles among the tested biological models and clinical covariates was tested through variance partition analysis. Results: Patients with Mesenchymal, Hypoxia and Classical clusters showed an higher risk of malignant transformation in comparison with immune-related ones (log-rank test, p = 0.0052) and they expressed four enriched hallmarks: “TGF beta signaling” “angiogenesis”, “unfolded protein response”, “apical junction”. Overall, 54 cases entered in the immune related clusters, while the remaining 32 cases belonged to the other clusters. No other signatures showed association with OCFS. Our variance partition analysis proved that clinical and molecular features are able to explain only 21% of gene expression data variability, while the remaining 79% refers to residuals independent of known parameters. Conclusions: Applying the existing signatures derived from HNSCC to OPL, we identified only a protective effect for immune-related signatures. Other gene expression profiles derived from overt cancers were not able to identify the risk of malignant transformation, possibly because they are linked to later stages of cancer progression. The availability of a new well-characterized set of OPL patients and further research is needed to improve the identification of adequate prognosticators in OPLs.

Influence of Internal and External Factors on the Production of Cytokines by Peripheral Blood Cells in Breast Cancer.

The article focuses on the influence of human leukemia differentiation factor (HLDF), carcinoembryonic antigen (CEA), and polyclonal activators (PA) on cytokine production by peripheral blood cells in breast cancer and benign breast diseases. It was found that the influence of internal factors on the production of cytokines by the peripheral blood cells is associated with lymphatic metastasis (CEA: IL-10; HLDF: IL-6, IL-1β, TNF-α, and G-CSF). One special circumstance was that there were no differences between the production of cytokines by peripheral blood cells in the patients with breast cancer compared to the patients with benign breast diseases with a high risk of malignant transformation. This is evidence of the functional similarity of peripheral blood cells in patients with these conditions. Cytokine production under the influence of PA was different only in case of TNF-α in all study groups.

A Shifting Paradigm in Diagnosis and Management of Hepatic Adenoma.

New insights into molecular pathogenesis of hepatocellular adenomas (HCA) have allowed sub-classification based on distinct genetic alterations and a fresh look at characterizations of natural history. Clinically, this is important in understanding risk factors for two feared complications: malignant transformation and hemorrhage. PubMed literature search for hepatocellular adenoma over all years, excluding case reports and articles focusing on multiple adenomas or adenomatosis. The β-catenin exon 3 mutated HCA accounts for about 10% of all HCAs and is associated with the highest risk of malignant transformation. The HF1α subtype accounts for 30-40% of all HCAs and has the lowest risk of malignant transformation. Gender has also emerged as an increasingly important risk factor and males with HCA are at considerably higher risk of malignant transformation, regardless of tumor size. The increasing use of gadoxetic-enhanced MRI has allowed for improved differentiation of HCAs from focal nodular hyperplasia, as well as the identification of specific radiologic features of some subtypes, particularly the inflammatory and HF1α HCAs. Classification of HCA by subtype has important implications for patient counseling and treatment given variable risks of malignant transformation and hemorrhage. Males and those with β-catenin exon 3 mutated HCAs are two groups who should always be counselled to undergo surgical resection. On the other hand, in the lower risk HF1α subtype observation is appropriate in lesions <5cm and may even be considered in larger lesions as longer follow-up data is aggregated and tumorigenesis is better understood.

Long-term follow-up of oral epithelial dysplasia: A hospital based cross-sectional study

Background/purposeOral epithelial dysplasia (OED) is characterized histopathologically by cellular and morphological changes that remain the single most important factor predicting risk for subsequent development of invasive neoplasia. Hence the aims of the present study were to determine the rate of malignant change of OED in a group of patients followed-up for a number of years, and hence determine factors likely to influence this malignant change, and to describe the clinical characteristics of patients who developed recurrence of OED and second dysplastic lesions. Materials and methodsThis is hospital based cross-sectional study of all biopsy reports with histologically confirmed OED between 2012 and 2018 were retrospectivelly reviewed. ResultsA total of 359 patients with histologically confirmed OED were reviewed, twenty (5.5%) of the 359 patients developed an invasive squamous cell carcinoma (SCC) of the oral mucosa over a period of 2 to 274 months with mean transformation time of 3.3 years. ConclusionThe high risk of malignant transformation of OED seems to be related to patients older than 50 years when lesions were on the floor of mouth with severe dysplastic changes.

Ультразвуковые аспекты и скрининг опухолей и опухолевидных образований яичников у пациенток репродуктивного возраста

Ovarian neoplasms can develop at any age, carry a high risk for malignant transformation, reduce the reproductive potential of a woman and are an indication for surgery. The search for optimal screening algorithms for ovarian tumors is still ongoing. The aim of this study was to evaluate the prognostic efficacy of ultrasonography (US) features in differentiating between benign, malignant and borderline tumors in reproductive-age women. We examined 168 reproductive-age women with ovarian masses who underwent surgery in 2012–2015 and compared the results of histopathological examinations with pulsed-Doppler US findings. We did not establish a correlation between the size/volume of the tumor and their morphological structure. We identified the echotexture characteristics associated with malignancy, including the presence of a solid component (р &lt; 0.001); septations (р = 0.029) and projections on the internal surface of the tumor capsule (р &lt; 0.001); moderate or significant buildup of free fluid in the small pelvis (р = 0.007), and the nodular surface of the tumor capsule (р = 0.008). Solid ovarian masses were at increased (31.69-fold) risk of transformation into malignant or borderline tumors, whereas for a mixed (cystic and solid) type the risk of such transformation increased 3.46-fold. We also identified Doppler parameters that can clearly discriminate between benign and malignant growths, including the blood flow rate in the tumor over 1.85 cm/s (р = 0.007) and RMI over 0.16 (р = 0.013). The sensitivity and specificity of our diagnostic model are 87% and 68%, respectively, with a probability threshold of 0.3.

Prognostic Implications of DNA Repair, Ploidy and Telomerase in the Malignant Transformation Risk Assessment of Leukoplakia

Background:Although leukoplakia shows a higher risk for malignant transformation to oral cancer, currently there are no clinically relevant biomarker which can predict the potentially high risk leukoplakia. This study aimed to investigate the genetic alterations such as DNA ploidy, telomerase expression and DNA repair capacity as predictive markers of malignant transformation risk of leukoplakia. Methods:The study was initiated in September 2005 and patients were followed up to March 2014. Two hundred patients with oral leukoplakia, 100 patients with oral cancer and 100 healthy, age and sex matched adults with normal oral mucosa as controls were recruited. The DNA ploidy content was measured by high resolution flow cytometry, level of telomerase expression was identified by TRAP assay and intrinsic DNA repair capacity was measured by mutagen induced chromosome sensitivity assay of cultured peripheral blood lymphocytes. The Chi-square test or Fisher’s Exact test was used for comparison of categorical variables between biomarkers. A p value less than or equal to 0.05 was considered as statistically significant. Analysis was performed with SPSS software version 16. Logistic regression was used to find the association between the dependent and three independent variables. Results:There was significant difference in the distribution of ploidy status, telomerase activity and DNA repair capacity among control, leukoplakia and oral cancer group (p<0.001). When the molecular markers were compared with histological grading of leukoplakia, both DNA ploidy analysis and telomerase activity showed statistical significance (p<0.001). Both aneuploidy and telomerase positivity was found to coincide with high-risk sites of leukoplakia and were statistically significant (p<0.002 and 0.02). All the leukoplakia and oral cancer patients were followed up for 8.5 years. Out of 200 cases of leukoplakia, 19 were found to be malignancy at the time of diagnosis. So for the calculation of risk of malignant transformation only 181 cases of leukoplakia were considered. Out of this 181 cases of leukoplakia, 12 (6.6%) underwent malignant transformation over a period ranging from 6 to 36 months. Univariate analysis showed DNA repair capacity and DNA ploidy as markers having significant risk association whereas multivariate analysis showed DNA repair capacity as the most significant marker to assess malignant transformation risk of leukoplakia (OR 52.9, 95% CI, 6.56 – 426.7). Conclusion:Genomic markers combined with clinical and histopathological evaluation can help identify the potentially high risk leukoplakia which can then be treated based on an individual approach.

Prognostic biomarkers for malignant transformation of oral potentially malignant disorders: a scoping review protocol.

This scoping review aims to identify and systematically map the available evidence concerning the prognostic biomarkers for malignant transformation of oral potentially malignant disorders (OPMDs), and to identify and analyze possible knowledge gaps in this field of literature. It is hypothesized that diagnosis and treatment of oral cancer in its early stages may be the key to improving the prognosis and reducing treatment-related consequences. Oral potentially malignant disorders represent tissue alterations with a higher risk of malignant transformation compared to the normal mucosa. Therefore, the study of prognostic biomarkers for OPMD could represent new diagnosis and therapeutic targets and, consequently, contribute to the reduction of oral cancer burden worldwide. Longitudinal studies investigating prognostic biomarkers regarding the malignant transformation of OPMD will be included. The initial OPMD diagnosis and the malignant transformation must have been confirmed by histopathological analysis. To achieve minimal heterogeneity, studies that assess biomarkers in other locations (blood, plasma or others) will be excluded. Five electronic databases and three grey literature databases will be consulted. No restrictions regarding publication date will be applied. Only studies published in the Latin (Roman) alphabet, which comprises most of the European languages, will be included. Study selection will be performed by two authors in a two-phase process; if any disagreement arises, a third author will be consulted to make a final decision. Data extraction will be performed by two authors using a standardized extraction tool. The results will be described in details accordantly with the aims of this scoping review.

Premalignant and malignant lesions of the esophagus: A single-institutional experience

Background: Esophageal malignancy is a highly aggressive tumor with a poor prognosis. A number of lesions occurring in the esophagus are associated with a high risk of malignant transformation. While the patterns of esophageal cancers have been documented in a number of African countries, there is a limited data on the Nigerian situation. This study was aimed at reviewing the histological patterns of premalignant and malignant lesions of the esophagus. Methods: This was a 10-year retrospective study of histologically confirmed premalignant and malignant lesions of the esophagus seen at the University College Hospital, Ibadan, between January 2009 and December 2018. Data retrieved from the departmental records were analyzed using the SPSS computer software version 20.0. Results: There were 45 cases diagnosed with premalignant lesions and 32 cases diagnosed with malignant lesions out of the 363 biopsies during the study period. The most common premalignant lesion was Barret's esophagus (68.9%). Premalignant lesions were more common in males (64.4%). The mean age for patients with a diagnosis of premalignant lesions was 55 years. The mean age at the diagnosis for esophageal cancer was 61.5 years. Squamous cell carcinoma was the predominant histological subtype seen (65.6%) with adenocarcinomas accounting for the remainder of cases (35.4%). Conclusion: Squamous cell carcinoma is the most common malignancy of the esophagus in our study. Adenocarcinomas of the esophagus were not as rare as documented in previous African studies. This finding may imply a changing pattern in esophageal malignancies in tandem with the pattern in Western countries.

Propranolol Specifically Suppresses the Viability of Tumorous Schwann Cells Derived from Plexiform Neurofibromas In Vitro.

Plexiform neurofibromas (PNFs) are benign tumors of the periph eral nerves sheath, which can damage neighboring organs, impair functions, cause pain and serious maxillofacial disfigurement, and have a high risk of malignant transformation. Complete resection is usually not possible since PNFs often extend through multiple layers of tissue. Therefore, it is necessary and beneficial to find a reasonable drug treatment for PNFs. Propranolol-treatment is the first-line therapy for infantile hemangiomas and the side effects are reversible and mostly benign. The present study aimed to examine the possible effect of propranolol for suppressing PNFs in vitro. Paired primary Schwann-cell-rich cultures and fibroblast-rich cultures were obtained from 4 PNFs of unrelated patients. Human Schwann cells (HSCs) were used as the control. These cultures were treated with propranolol for 7 days at concentrations up to 150 μM. Cells were then measured for their viability and immune-stained with S100 to label the tumorous Schwann cells. Propranolol inhibited the viability of the tumorous Schwann cells in a dose-dependent manner, while did not substantially suppress viability of the non-tumorous fibroblasts derived from the same PNFs. Propranolol may provide a treatment option for suppressing the growth of PNFs.

NEUROFIBROMATOSIS TYPE 1 INVOLVING THE UPPER MAXILLA, CASE REPORT

Von Recklinghausen disease or neurofibromatosis type 1 (NF1) is an autosomal dominant disease with a wide clinical expression, with manifestations ranging from multiple café-au-lait spots to severe functional and aesthetic complications affecting bone tissue and nerve. Oral manifestations of NF1 are rare. The relevance of this case lies in the fact that the disease rarely occurs in oral cavity. The patient was a 12-year-old boy with facial asymmetry caused by a swelling around the upper left jaw causing deformation. Intraorally, a tumor that completely occupies the vestibule was identified. Excisional biopsy of the lesion was performed, and results indicated neurofibroma plexiform and S-100 positivity. At the control, a favorable healing is observed, and the result is correlated with a clinical history: glaucoma causing blindness of left eye, palpebral fibroids, bilateral frontal neurofibromas, multiple periocular neurofibromas, and Von Recklinghausen disease diagnosis. The treatment of NF1 patients is difficult, which may be increased by the complications derived from deformations (and its resulting psychological problem), gliomas of the optic nerves (blindness), or the high risk of malignant transformation. Von Recklinghausen disease or neurofibromatosis type 1 (NF1) is an autosomal dominant disease with a wide clinical expression, with manifestations ranging from multiple café-au-lait spots to severe functional and aesthetic complications affecting bone tissue and nerve. Oral manifestations of NF1 are rare. The relevance of this case lies in the fact that the disease rarely occurs in oral cavity. The patient was a 12-year-old boy with facial asymmetry caused by a swelling around the upper left jaw causing deformation. Intraorally, a tumor that completely occupies the vestibule was identified. Excisional biopsy of the lesion was performed, and results indicated neurofibroma plexiform and S-100 positivity. At the control, a favorable healing is observed, and the result is correlated with a clinical history: glaucoma causing blindness of left eye, palpebral fibroids, bilateral frontal neurofibromas, multiple periocular neurofibromas, and Von Recklinghausen disease diagnosis. The treatment of NF1 patients is difficult, which may be increased by the complications derived from deformations (and its resulting psychological problem), gliomas of the optic nerves (blindness), or the high risk of malignant transformation.

DESCRIPTIVE ANALYSIS: CLINICAL CHARACTERISTICS OF 34 PATIENTS WITH PROLIFERATIVE VERRUCOUS LEUKOPLAKIA

Proliferative verrucous leukoplakia (PVL) is a subtype of oral leukoplakia, which is not commonly associated with risk factors such as alcohol and smoking; it has high rates of recurrence after treatment and has a high risk of malignant transformation. This study described the clinical features of 34 patients with PVL (1991-2016). Of these, the vast majority was female (31%-91.17%) and the mean age was 69.08 years. Regarding risk factors, only 2 patients smoked and 5 consumed alcoholic beverages. The most frequently affected sites were the buccal mucosa and lateral border of the tongue. The average number of site affected with leukoplakia was 3.41 and the development of squamous cell carcinoma occurred in 7 of the patients (20%). PVL starts as an isolated lesion but develops important changes throughout the follow-up period. Therefore, constant clinical monitoring is necessary. Proliferative verrucous leukoplakia (PVL) is a subtype of oral leukoplakia, which is not commonly associated with risk factors such as alcohol and smoking; it has high rates of recurrence after treatment and has a high risk of malignant transformation. This study described the clinical features of 34 patients with PVL (1991-2016). Of these, the vast majority was female (31%-91.17%) and the mean age was 69.08 years. Regarding risk factors, only 2 patients smoked and 5 consumed alcoholic beverages. The most frequently affected sites were the buccal mucosa and lateral border of the tongue. The average number of site affected with leukoplakia was 3.41 and the development of squamous cell carcinoma occurred in 7 of the patients (20%). PVL starts as an isolated lesion but develops important changes throughout the follow-up period. Therefore, constant clinical monitoring is necessary.

SQUAMOUS CELL CARCINOMA ASSOCIATED WITH WHITE LESIONS

An 81-year-old white female, with no history of smoking or drinking, reported persistent pain and increase in lesion size in the last 3 months. Intraoral exam showed an exophytic nodular and ulcerated lesion in the region of left labial commissure, 1.5 cm in size and of soft consistency; next to the lesion, there was an extensive white plaque. A white plaque with striated appearance was also observed on the right buccal mucosa. An incisional biopsy was performed in the nodular area with the histopathologic diagnosis of squamous cell carcinoma. The patient was referred to the head and neck service for treatment. This carcinoma case may have been preceded by oral lichenoid lesions and proliferative verrucous leukoplakia and these lesions should be detected during clinical exam and followed closely, as they carry a higher risk for malignant transformation and carcinoma arising from them and may show better prognosis if detected early. An 81-year-old white female, with no history of smoking or drinking, reported persistent pain and increase in lesion size in the last 3 months. Intraoral exam showed an exophytic nodular and ulcerated lesion in the region of left labial commissure, 1.5 cm in size and of soft consistency; next to the lesion, there was an extensive white plaque. A white plaque with striated appearance was also observed on the right buccal mucosa. An incisional biopsy was performed in the nodular area with the histopathologic diagnosis of squamous cell carcinoma. The patient was referred to the head and neck service for treatment. This carcinoma case may have been preceded by oral lichenoid lesions and proliferative verrucous leukoplakia and these lesions should be detected during clinical exam and followed closely, as they carry a higher risk for malignant transformation and carcinoma arising from them and may show better prognosis if detected early.