Identification of Epstein-Barr virus after topical treatment for oral hairy leukoplakia: A preliminary study.

BACKGROUND: This study evaluated the presence of Epstein-Barr virus type 1 (EBV-1) DNA in patients living with HIV, before and after three different topical therapy protocols for oral hairy leukoplakia (OHL). METHODS: The sample consisted of five patients treated with topical solution of 25% podophyllin resin; six with 25% podophyllin resin plus 5% acyclovir cream; and four with 25% podophyllin resin plus 1% penciclovir cream. DNA was extracted from OHL scrapings and amplified by the PCR using specific primers for EBV-1 (EBNA-1). RESULTS: Clinical healing of OHL lesions was observed across all treatment groups over time. At baseline, EBNA-1 was detected in all OHL lesions. After treatment, OHL samples from three patients treated with 25% podophyllin resin plus 5% acyclovir cream and from one patient treated with 25% podophyllin resin plus 1% penciclovir cream exhibited negative EBNA-1 viral gene encoding. Despite the clinical resolution of OHL, 11 patients (73.3%) showed EBNA-1 positivity immediately after the lesion disappeared. Three patients (20%) treated with podophyllin resin displayed both EBNA-1 positivity and a recurrence of OHL, in contrast to no recurrence in the other two groups. CONCLUSIONS: These findings suggest potential associations between treatment formulations, EBNA-1 persistence, and the recurrence of OHL lesions.

Mast cells in oral lichen planus and oral lichenoid lesions related to dental amalgam contact.

The aim of this study was to analyze the expression of mast cell markers toluidine blue, c-kit, and tryptase and presence of mononuclear inflammatory cells in oral lichen planus (OLP) and oral lichenoid lesions related to dental amalgam. Nineteen specimens of OLP, OLLC, and healthy oral mucosa were selected. Mononuclear inflammatory cells were analyzed. Histochemical and immunohistochemical analyses were performed using toluidine blue, anti-c-kit and anti-tryptase reagents, and the results were quantified in areas A and B of connective tissue. Mast cells of all OLP and OLLC samples were positive for toluidine blue, c-kit, and tryptase. The density of toluidine blue+, c-kit+ and tryptase+ mast cells was higher in tissue with OLP and OLLC compared with healthy controls (p < 0.05). No difference was noted in mast cells density between OLP and OLLC (p > 0.05). The density of tryptase+ mast cells was higher in the subepithelial region (area A) than the region below it (Area B) in OLLC (p = 0.047). The mononuclear inflammatory cell density was higher in OLLC compared to OLP, but without statistical significance (p > 0.05). A positive statistical correlation was found between mononuclear immune cells and density of c-kit+ and tryptase+ mast cells in OLP (r = 0.943 and r = 0.886, respectively). Our data demonstrate that the etiopathogenesis process of OLP and OLLC modulates the expansion and degranulation of mast cells; mast cells density, however, was similar between OLP and OLLC. The distribution of mast cells appears to vary along the lamina propria.

Subgemmal neurogenous plaque: a series of six cases and a literature overview.

The study aims to describe six subgemmal neurogenous plaque (SNP) cases and compile the previously available data on SNP. Searches on PubMed, Web of Science, Embase, Scopus, and a two-step study selection were performed to compile data from case reports/series of SNP published in English literature. Our six patients (range 29-63 years) had SNP in the posterior lateral border of the tongue. Four of them were associated with lymphoepithelial cysts. A total of 15 studies, comprising 116 patients, were included in this overview. There was a slight predilection for female patients (56.0%) in the 5th (22.4%) and the 7th (23.9%) decades. The lateral border of the tongue (66.4%) was the most common anatomical location. The major manifestation was nodule/papule. Histologically, the presence of taste buds (n = 40/ 34.5%), superficial neural plexus (n = 32/ 27.6%), deep nerve fascicles (n = 32/ 27.6%), ganglion cells (n = 41/ 35.3%), and lymphoid tissue (n = 22/ 19.0%) was mainly reported. Surgical removal was the primary approach, with a low recurrence rate. Although largely unknown, SNP is a regular and likely frequent structure located in the tongue. The findings emphasize the importance of describing clinicopathological patterns of SNP as a differential diagnosis of neural lesions that affect the tongue.

Oral carcinoma in situ in a middle-aged woman with systemic sclerosis: Report of a rare case and literature review.

Systemic sclerosis (SSc) is a rare multisystem rheumatic autoimmune disease involving the skin, connective tissue, and internal organs. Individuals with SSc are at increased risk of cancer. We herein contribute by reporting a case of carcinoma in situ affecting the lower lip and labial mucosa of a 56-year-old Brazilian female patient, which apparently represents the first case reported in Latin America. Surgical resection of the lesion was performed. After a 2-year follow-up, the patient has shown no evidence of recurrence. According to a literature review in PubMed, Web of Science, Scopus, and Embase databases on SSc-related oral and oropharyngeal cancer, 11 cases have been documented hitherto. Reports of oral carcinoma in individuals with SSc are rare. Clinicians should conduct regular examinations of the oral mucosa of these individuals to permit an early diagnosis, as done in the present case.

Mast cells in oral lichen planus and oral lichenoid lesions related to dental amalgam contact

Abstract The aim of this study was to analyze the expression of mast cell markers toluidine blue, c-kit, and tryptase and presence of mononuclear inflammatory cells in oral lichen planus (OLP) and oral lichenoid lesions related to dental amalgam. Nineteen specimens of OLP, OLLC, and healthy oral mucosa were selected. Mononuclear inflammatory cells were analyzed. Histochemical and immunohistochemical analyses were performed using toluidine blue, anti-c-kit and anti-tryptase reagents, and the results were quantified in areas A and B of connective tissue. Mast cells of all OLP and OLLC samples were positive for toluidine blue, c-kit, and tryptase. The density of toluidine blue+, c-kit+ and tryptase+ mast cells was higher in tissue with OLP and OLLC compared with healthy controls (p < 0.05). No difference was noted in mast cells density between OLP and OLLC (p > 0.05). The density of tryptase+ mast cells was higher in the subepithelial region (area A) than the region below it (Area B) in OLLC (p = 0.047). The mononuclear inflammatory cell density was higher in OLLC compared to OLP, but without statistical significance (p > 0.05). A positive statistical correlation was found between mononuclear immune cells and density of c-kit+ and tryptase+ mast cells in OLP (r = 0.943 and r = 0.886, respectively). Our data demonstrate that the etiopathogenesis process of OLP and OLLC modulates the expansion and degranulation of mast cells; mast cells density, however, was similar between OLP and OLLC. The distribution of mast cells appears to vary along the lamina propria.

Clinicopathologic analysis of oral dermoid and epidermoid cysts: a Brazilian multicenter study.

Dermoid cysts (DCs) and epidermoid cysts (ECs) are uncommon developmental cysts affecting the oral cavity. This study aims to evaluate patients with oral DCs and ECs and their demographic and clinicopathologic features. A retrospective descriptive cross-sectional study was performed. A total of 105,077 biopsy records of oral and maxillofacial lesions from seven Brazilian oral pathology centers were analyzed. All cases diagnosed as oral DCs and ECs were reviewed, and clinical, demographic, and histopathological data were collected. The series comprised 32 DCs (31.4%) and 70 ECs (68.6%). Most of the DCs occurred on the floor of the mouth (n = 14; 45.2%) of women (n = 17; 53.1%) with a mean age of 34.6 ± 21.6 years. All DCs were lined partially or entirely by stratified squamous epithelium (100%). Chronic inflammatory cells, melanin pigmentation, multinucleated giant cell reaction, and cholesterol clefts were observed in the fibrous capsule . Most of the ECs affected the labial mucosa (n = 20; 31.7%) of men (n = 39; 56.5%) with a mean age of 48.0±19.8 years. Microscopically, most ECs (n = 68; 97.1%) were lined entirely by stratified squamous epithelium. Two cysts (2.9%) showed areas of respiratory metaplasia. Chronic inflammatory cells, melanin pigmentation, multinucleated giant cell reaction, and cholesterol clefts were also observed in the fibrous capsule. Conservative surgical excision was the treatment of choice in all cases. Oral DCs and ECs are uncommon and often clinically misdiagnosed lesions. Clinicians should consider DCs and ECs in the differential diagnosis of soft tissue lesions in the oral cavity, mainly located on the floor of the mouth and labial mucosa.

Can SARS-CoV-2 screening in oral biopsies aid epidemiological surveillance?

BACKGROUND: Three years after the first confirmed COVID-19 case in Brazil, the outcomes of Federal government omissions in managing the crisis and anti-science stance heading into the pandemic have become even more evident. With over 36 million confirmed cases and nearly 700 000 deaths up to January 2023, the country is one of the hardest-hit places in the world. The lack of mass-testing programs was a critical broken pillar responsible for the quick and uncontrolled SARS-CoV-2 spread throughout the Brazilian population. Faced with this situation, we aimed to perform the routine SARS-CoV-2 screening through RT-qPCR of oral biopsies samples to aid in the asymptomatic epidemiological surveillance during the principal outbreak periods. METHODS: We analyzed 649 formalin-fixed paraffin-embedded oral tissue samples from five important oral and maxillofacial pathology laboratories from the north, northeast, and southeast geographic regions of Brazil. We also sequenced the whole viral genome of positive cases to investigate SARS-CoV-2 variants. RESULTS: The virus was detected in 9/649 analyzed samples, of which three harbored the Variant of Concern Alpha (B.1.1.7). CONCLUSION: Although our approach did not value aiding asymptomatic epidemiological surveillance, we could successfully identify a using FFPE tissue samples. Therefore, we suggest using FFPE tissue samples from patients who have confirmed diagnosis of SARS-CoV-2 infection for phylogenetic reconstruction and contraindicate the routine laboratory screening of these samples as a tool for asymptomatic epidemiological surveillance.

Fine-needle aspiration cytology for the diagnosis of plasma cell neoplasms in the head and neck region: A systematic analysis of the literature.

BACKGROUND: Cytopathologic analysis is feasible and provides detailed morphological characterisation of head and neck lesions. AIMS: To integrate the available data published on fine-needle aspiration cytology (FNAC) used for the diagnosis of plasma cell neoplasms (PCN) of the head and neck region. MATERIALS AND METHODS: Searches on PubMed, Web of Science, Embase, and Scopus were performed to compile data from case reports/case series published in English. The Joanna Briggs Institute tool was used for the critical appraisal of studies. RESULTS: A total of 82 studies comprising 102 patients were included in this review. There was a predilection for men (68.6%) (male/female ratio: 2.1:1). Individuals in their 50s (29.4%), 60s (22.5%), and 70s (22.5%) were more often affected. The thyroid gland (26.2%) was the main anatomical location, followed by scalp (15.5%), neck/cervical region (15.5%), jaws (13.6%), and major salivary glands (13.6%). For FNAC analysis, a smear was employed in 41 (40.6%) cases and a cell block was used in four (3.9%). In 56 (55.4%) reports, no cytological methods were available. Morphologically, 34 (56.7%) cases had a diagnosis of PCN with agreement between cytopathology and histopathology. The rate of wrong diagnoses when using cytology was 27.5%. Immunophenotyping was performed in 49 (48%) of the cases. The 69-month disease-free survival rate was 60.2%, while the 27-month overall survival rate was 64.1%. CONCLUSION: This study reinforces that FNAC can be an ancillary tool in the first step towards the diagnosis of PCN of the head and neck region, especially when applying a cell block for cytological analysis.

Interrogation of TERT promoter hotspot mutations in ameloblastoma and ameloblastic carcinoma.

BACKGROUND: TERT promoter mutations increase telomerase activity, conferring cell immortality. The coexistence of TERT promoter mutations with BRAFV600E is associated with aggressiveness. Ameloblastoma and ameloblastic carcinoma are infiltrative neoplasms that harbor BRAFV600E; however, it remains unknown if these odontogenic tumors also show TERT promoter mutations. METHODS: Genomic DNA of paraffin-embedded ameloblastomas (n = 6) and ameloblastic carcinomas (n = 3) were Sanger-sequenced to assess the hotspot TERT promoter mutations C228T and C250T. BRAFV600E status was screened by TaqMan allele-specific quantitative polymerase chain reaction. RESULTS: None of the samples harbored TERT promoter mutations. The BRAFV600E mutation was positive in 3 of 6 of ameloblastomas and in 1 of 3 of ameloblastic carcinomas. CONCLUSION: The absence of TERT promoter mutation in the samples indicates that this molecular event is not relevant to the tumors' pathogenesis. Further studies are necessary to explore undefined genetic or epigenetic mechanisms related to TERT-upregulation in ameloblastoma, and the telomerase activity in ameloblastic carcinoma.

Clinicopathologic analysis of oral dermoid and epidermoid cysts: a Brazilian multicenter study

Abstract Dermoid cysts (DCs) and epidermoid cysts (ECs) are uncommon developmental cysts affecting the oral cavity. This study aims to evaluate patients with oral DCs and ECs and their demographic and clinicopathologic features. A retrospective descriptive cross-sectional study was performed. A total of 105,077 biopsy records of oral and maxillofacial lesions from seven Brazilian oral pathology centers were analyzed. All cases diagnosed as oral DCs and ECs were reviewed, and clinical, demographic, and histopathological data were collected. The series comprised 32 DCs (31.4%) and 70 ECs (68.6%). Most of the DCs occurred on the floor of the mouth (n = 14; 45.2%) of women (n = 17; 53.1%) with a mean age of 34.6 ± 21.6 years. All DCs were lined partially or entirely by stratified squamous epithelium (100%). Chronic inflammatory cells, melanin pigmentation, multinucleated giant cell reaction, and cholesterol clefts were observed in the fibrous capsule . Most of the ECs affected the labial mucosa (n = 20; 31.7%) of men (n = 39; 56.5%) with a mean age of 48.0±19.8 years. Microscopically, most ECs (n = 68; 97.1%) were lined entirely by stratified squamous epithelium. Two cysts (2.9%) showed areas of respiratory metaplasia. Chronic inflammatory cells, melanin pigmentation, multinucleated giant cell reaction, and cholesterol clefts were also observed in the fibrous capsule. Conservative surgical excision was the treatment of choice in all cases. Oral DCs and ECs are uncommon and often clinically misdiagnosed lesions. Clinicians should consider DCs and ECs in the differential diagnosis of soft tissue lesions in the oral cavity, mainly located on the floor of the mouth and labial mucosa.

Hydrochlorothiazide use is associated with the risk of cutaneous and lip squamous cell carcinoma: A systematic review and meta-analysis.

PURPOSE: The aim of this study is to investigate the association between hydrochlorothiazide (HCTZ) use and the risk of cutaneous and lip squamous cell carcinoma development. METHODOLOGY: We performed a systematic review and meta-analysis of case-control studies. We searched the Cochrane Library, PubMed, Scopus, Web of Science and LILACS. This study was registered in PROSPERO under protocol CRD42019129710. The meta-analysis was performed using the software Stata (version 12.0). RESULTS: A total of 2181 published studies referring to the theme were identified, from which six were included in this systematic review. Men were more frequently affected by cutaneous and lip squamous cell carcinoma than women, with a 1.42:1 ratio. The mean age for cutaneous and lip squamous cell carcinoma development was 73.7 years. This meta-analysis demonstrated a chance of developing cutaneous and lip squamous cell carcinoma in any region of the body in hydrochlorothiazide users of 1.76-fold higher than in non-users. In addition, a risk factor of 1.80 higher (CI 95% = 1.71-1.89) of cutaneous squamous cell carcinoma in the head and neck region was observed in HCTZ users. Moreover, in the analysis of the dose used, the chance of developing squamous cell carcinoma was 3.37-fold lower when the concentration of HCTZ used was less than 50,000 mg. CONCLUSIONS: Our results confirm the association between the use of hydrochlorothiazide and the cutaneous and lip squamous cell carcinoma development.

Biomarkers involved in the proliferation of the odontogenic keratocyst, glandular odontogenic cyst and botryoid odontogenic cyst.

INTRODUCTION: Odontogenic cysts are a heterogeneous group of lesions with varied clinical behavior. OBJECTIVE: To analyze the expression of the epidermal growth factor receptor (EGFR), Cyclin D1, and transcription factor SOX2 in the odontogenic epithelium evaluating the cell cycle control and cystic expansion. METHODS: This was a cross-sectional study including 40 cases, 20 odontogenic keratocysts (OKC), 10 botryoid odontogenic cysts (BOC), and 10 glandular odontogenic cysts (GOC). RESULTS: All cases of OKC, BOC, and GOC were positive for EGFR in all layers of the cyst lining. The highest expression of nuclear Cyclin D1 was observed in the suprabasal layer of OKCs and in the basal and suprabasal layers of GOC and BOC (p < 0.001). In addition, SOX2 was only expressed in the suprabasal layer of OKCs. CONCLUSION: The high expression of EGFR in the cyst membrane suggests that EGF stimulates epithelial proliferation in BOCs, and the high expression of SOX2 in OKCs may be related to the presence of stem cells in the lesion. Cyclin D1 is related to cell cycle disruption in G1-S contributing to stimulates epithelial proliferation of OKCs and GOCs and BOCs.

Survival-related epithelial-mesenchymal transition proteins in oropharyngeal squamous cell carcinoma: A systematic review and meta-analysis.

OBJECTIVE: To aim of this systematic review was to explore the relationship between Human papillomavirus (HPV) and epithelial-mesenchymal transition (EMT) related to the prognosis of oropharyngeal squamous cell carcinoma (OPSCC). DESIGN: For this systematic review, searches were performed in PubMed, Web of Science, Scopus, Science Direct, and Cochrane, and a random-effects model was used for meta-analysis. The presence of EMT was confirmed by the loss of E-cadherin immunoexpression and overexpression of vimentin. RESULTS: In summary, EMT-related proteins were expressed regardless of HPV status; however, overall survival was better in HPV-positive OPSCC cases, with a 5.88 times lower death risk compared to HPV-negative patients (OR=0.17; 95%CI=0.10-0.30). Likewise, the maintenance of E-cadherin in OPSCC was associated with an 11.11 times lower risk of death due to the disease (OR=0.09; 95%CI=0.01-0.88). CONCLUSIONS: More advanced clinical stages (III/IV) and the presence of lymph node metastases (N1-3) were common in OPSCC but were not significantly associated with HPV status.

Osteomyelitis of the jaws in patients with pycnodysostosis: a systematic review.

INTRODUCTION: Pycnodysostosis is a rare autosomal recessive syndrome that provides the abnormal bone metabolism that increases the susceptibility of patients to develop osteomyelitis. OBJECTIVE: This systematic review was conducted to analyze the risk factors associated with the development of complications in the jaws (fractures and osteomyelitis), as well as their clinical-pathological characteristics and therapeutic approaches in patients with pycnodysostosis. METHODS: Searches were performed in the PubMed, Web of Science, Scopus, Lilacs, and Cochrane databases. Case reports or case series that met the eligibility criteria according to the PRISMA statement were included. The full texts of 31 articles were retrieved. Twenty of these articles published between 1969 and 2018 were selected, which described 26 cases of osteomyelitis in patients with pycnodysostosis. RESULTS: The mean age of the patients was 37.84 years; the male-to-female was 1.36:1. The mandible was the most affected site (76.9%). Tooth extraction was the main risk factor for osteomyelitis (61.5%), followed by infection (26.8%) and mandibular fracture (23.0%). Antibiotic therapy alone or combined with some surgical procedure was the treatment used in most cases (80.7%). CONCLUSION: The findings of this review showed that patients with pycnodysostosis are more likely to develop osteomyelitis of the jaws after surgical procedures, especially tooth extraction which remains the main risk factor for its establishment. In addition, prophylactic antibiotic-therapy in the pre- and postoperative periods may prevent the development of osteomyelitis in pycnodysostosis.

A rare case of a metastatic giant cell-rich osteosarcoma of the mandible: Update and differential diagnostic considerations.

A metastatic giant cell-rich osteosarcoma (GCRO) to the jaws is an exceedingly rare neoplasm. To date, fewer than 10 cases have been reported in the English language literature. In this article, we describe an additional case of a metastatic GCRO that presented the diagnostic challenge of a painless mass in the posterior mandible of a 19-year-old girl who exhibited rapid and aggressive local growth. The lesion was confirmed radiologically as an ill-defined expansive osteolytic mass showing cortical perforation. Microscopically, the presence of osteoclast-like giant cells permeated with atypical oval and rounded mesenchymal cells in a fibrovascular stroma, cellular atypia, and scarce osteoid formation were observed. Immunohistochemistry revealed the Ki-67 proliferative index in 50% of positive cells, positivity for vimentin and CD68, as well as scarce positivity for CDK4. The patient's medical history involved a GCRO in the proximal ulna. This report highlights the aggressive behavior of GCRO and its high capacity for metastasis to different parts of the body. Clinicians, pathologists, and surgeons should be aware of the giant cell-rich variant of osteosarcoma of the jaws, an imminent "wolf in a sheep's skin", because its indolent but unrelenting growth and dissemination, with radiographic and histologic characteristics that may represent a diagnostic pitfall regarding aggressive central giant cell lesions of the jaws.

DNA base excision repair and nucleotide excision repair proteins in malignant salivary gland tumors.

OBJECTIVE: To analyze the immunohistochemical expression of the base excision repair (BER) proteins apurinic/apyrimidinic endonuclease 1 (APE1) and X-ray repair cross-complementing protein 1 (XRCC1) and nucleotide excision repair (NER) protein xeroderma pigmentosum group F (XPF) in malignant salivary gland tumors (MSGTs). DESIGN: Sixty-two cases of MSGTs were selected, including 14 acinic cell carcinomas (AcCC), 15 polymorphous adenocarcinomas (PAC), 16 adenoid cystic carcinomas (ACC), and 17 mucoepidermoid carcinomas (MEC). The specimens were submitted to quantitative immunohistochemical analysis. RESULTS: All MSGTs exhibited nuclear or nucleo-cytoplasmic immunostaining of APE1, XRCC1 and XPF, with a high percentage of positive cells (median = 78.31, 70.48 and 75.46, respectively). XRCC1 expression was higher in PAC compared to MEC (p = 0.032). Nuclear APE1 immunostaining was significantly higher than nucleo-cytoplasmic expression in the selected MSGTs (p < 0.0001). APE1 expression was significantly associated with T1-T2 tumors in ACC (p = 0.006). Increased expression of XPF was associated with age older than 60 years in MEC (p = 0.015) and with ACC involving the minor salivary gland (p = 0.012), while a lower expression was found in AcCC and ACC patients treated by surgery combined with adjuvant therapy (p = 0.036 and p = 0.020, respectively). Low expression of XRCC1 in the nucleus (p = 0.028) and concomitant expression of this protein in the nucleus/cytoplasm were associated with a lower overall 5-year survival rate (p = 0.017). CONCLUSIONS: This study showed that BER and NER proteins evaluated are highly expressed in the MSGTs studied, indicating mechanisms of genotoxic control in these tumors. In addition, the dysregulation of XRCC1 expression was a prognostic predictor in MSGTs analyzed.

YouTube™ and oral lichen planus: an appraisal of the educational quality of information.

The objective of this study was to analyze the quality of videos on oral lichen planus (OLP) available in YouTube™. A cross-sectional analytical study was conducted by searching the video sharing platform YouTube™. Videos aimed at clarifying the etiological and clinical characteristics, diagnostic criteria, treatment, and prognosis of OLP were included. A total of 481 videos were retrieved and 37 were included in the study according to the selection criteria established. Most of the videos evaluated (86.5%; n = 32) were produced by independent users. The average reliability was 1.8 and quality assessment classified only three videos (8.1%) as having good/excellent quality. A significant correlation was observed between the length of the video analyzed and its quality and reliability (p < 0.05), as well as between the reliability and usefulness of the video (p = 0.03). YouTube™ has become a leading source of information for the general population. However, a significant number of these videos have a low quality. Students, professionals, and healthcare providers must be more actively involved in providing clear, accurate, and reliable evidence-based information in an accessible language in order to enable significant improvement in patient care delivery.