Oral pseudoperineurioma (OPP) is a recently recognized peripheral nerve–associated lesion characterized by pseudo–onion bulb–like perineurial cell proliferations surrounding axon–Schwann cell units. Although now is included in the current World Health Organization (WHO) Classification of Head and Neck Tumors within the spectrum of neuromas, it remains underrecognized and is frequently misdiagnosed as other neural lesions, particularly traumatic neuroma. The full histopathologic spectrum of OPP has not yet been well defined. Following Institutional Review Board approval, a retrospective review of University of Florida Oral Pathology Biopsy Service archives was performed to identify lesions meeting WHO-defined diagnostic criteria for OPP. Cases were retrieved through re-evaluation of lesions originally diagnosed as traumatic neuroma, intraneural perineurioma, or related peripheral nerve lesions. Hematoxylin and eosin–stained slides were reviewed and immunohistochemical studies (EMA, GLUT-1, CD56, and S-100) were performed. Clinical and pathologic data were recorded, and lesions were subclassified based on architectural growth patterns. Descriptive statistics were used for analysis. Twenty-one cases of oral pseudoperineurioma were identified. Patients ranged in age from 14 to 73 years (mean 36 years), with a slight female predominance (52

Background Warty dyskeratoma (WD), also called isolated follicular keratosis, is a benign self-limiting lesion regarded as either a follicular part of actinic keratosis or a follicular neoplasm. The etiology of WD remains largely unknown. It typically appears as an isolated small papulonodular lesion in the head and neck area. Intraorally, it usually appears as a white papule with central depression on keratinized mucosa, predominantly on alveolar ridges of both arches and hard palate. Clinically WD may resemble entities such as squamous papilloma, squamous cell carcinoma, or verrucous carcinoma, hence a biopsy is usually required as the standard of care. Case Report A 69-year-old man presented with a tiny white, papillary soft tissue lesion on the right lateral border of the tongue. The clinical impression was papilloma. The lesion was completely excised, and microscopic examination revealed a cup-shaped, keratin filled, characteristic acantholytic dyskeratosis with suprabasilar clefting and subjacent connective tissue with adherent basal cells. A diagnosis of WD was rendered. No recurrence has been reported. Discussion We present a case of isolated Darier's disease/warty dyskeratoma in an unusual location such as the tongue. Given the rarity of occurrence in this location, WD may not be initially considered by unsuspecting clinicians. Therefore, it is crucial for oral health care providers to be sentient of this entity and consider WD in the differential diagnosis when encountering punctate, papillary, keratotic, or umbilicated lesions of the tongue.

INTRODUCTION:Chronic hyperplastic candidiasis (CHC) has a controversial potential role in the carcinogenesis of oral epithelium. In addition, histological overlap between CHC and atypical epithelial proliferation with Candida (AEPC) may cause a diagnostic dilemma. In this pilot study, potential premalignant markers including tumor suppressor gene proteins p53 and p16, and cancer stem cell markers CD44 and OCT4, were investigated in CHC and AEPC with benign and malignant validation groups. MATERIALS AND METHODS:A total of 20 tongue lesions were identified, with 5 cases of each: benign validation group of traumatic fibroma, CHC without dysplasia, AEPC, and malignant validation group of moderately differentiated squamous cell carcinoma (SCCA). IHC staining was performed with p53, p16, CD44, and OCT4. Inter-observer variability between two pathologists' independent scores was determined using Cohen's kappa (k). A third pathologist served as tiebreaker for disagreement. Chi-square testing was performed between diagnostic groups and staining results. RESULTS:Overall agreement of staining for all stains was good (κ = 0.614) for intensity, moderate (κ = 0.544) for percentage, and good (κ = 0.612) for p53 wild or atypical pattern analysis (based on prior studies). p53 and CD44 staining showed statistically significant differences between the fibroma/CHC cases and the AEPC/SCCA cases. The most diagnostic measures were p53 pattern, which categorized 100% of fibroma/CHC cases as wild type and 90% of AEPC/SCCA groups as atypical (p < 0.001), and CD44 staining above 50%, which diagnosed 70% of AEPC/SCCA cases versus 0% of fibroma/CHC cases (p = 0.004). Using these two together, all AEPC/SCCA cases were diagnosed. p16 and OCT4 were not significant in differentiating between diagnoses in this study. CONCLUSIONS:In this pilot study, p53 pattern and CD44 percentage showed significant potential to serve as useful diagnostic aids. Future studies with larger sample sizes are necessary to validate these findings and explore the potential of these markers in determining the transformation risk of CHC and AEPC.

Juvenile ossifying fibroma (JOF) is an uncommon benign fibro-osseous lesion (BFOL) of the maxillofacial bones with a locally aggressive nature and a high recurrence rate. Murine Double Minute 2 (MDM2) is an oncogene located at chromosome 12 (12q13-15) that inhibits the tumor suppressor gene TP53. The presence of MDM2 gene locus amplification is a useful molecular adjunct in the evaluation of some sarcomas, including low-grade intramedullary osteosarcoma (LGIOS). JOF and LGIOS have some overlapping clinical and histopathological features. The aim of this study is to evaluate a series of JOF for the presence of MDM2 gene locus amplification using fluorescence in-situ hybridization (FISH). With IRB approval, a search of the institutional files of the archives of the Oral Pathology and Surgical Pathology biopsy services at the University of Florida Health was performed. The cases were re-evaluated by an oral pathology resident, an oral and maxillofacial pathologist, and a bone and soft tissue pathologist. Cases with consensus in diagnosis were selected (n = 9) for MDM2 testing. Testing by FISH for MDM2 gene locus amplification was applied to all retrieved cases. The examined cases were all negative for MDM2 gene locus amplification via FISH testing. In our small series, JOF did not demonstrate MDM2 gene locus abnormality, a characteristic of LGIOS. This finding suggests that JOF has a distinct underlying pathogenesis. If confirmed in a larger series, these findings may be useful in distinguishing these two entities in cases with overlapping features or when minimal biopsy material is available.

OBJECTIVES:Autoimmune activation by COVID-19 infection/vaccination has been postulated to be responsible for initiating or reactivating multiple types of oral mucosal immune disorders. These include: oral lichen planus; oral pemphigoid; either bullous pemphigoid or mucous membrane pemphigoid with oral involvement; pemphigus vulgaris with oral involvement; and Sjögren disease. In addition, chronic conditions such as oral burning, xerostomia, or changes in taste and/or smell have also been linked to COVID-19 infection/vaccination. DATA SOURCES:Part 1 (mucosal conditions): an English-language literature review of Pubmed, Web of Science, Scopus, and Embase was performed searching cases of oral lichen planus, oral bullous pemphigoid, mucous membrane pemphigoid, pemphigus vulgaris, and COVID-19 infection/vaccination, with additional cases from the authors' clinical practice presented. Part 2 (nonmucosal conditions): Cases of initiated or flared Sjögren disease, chronic oral burning, or xerostomia after COVID-19 infection/vaccination from the authors' clinical practice were aggregated. RESULTS:The literature review discovered 29 cases of oral lichen planus following COVID-19 infection/vaccination. For bullous pemphigoid, 10 cases were identified after infection/vaccination. The number of pemphigus vulgaris cases following infection/vaccination was 28. The majority of mucosal cases were reported after vaccination. Most reported initial disease, but a substantial amount included recurrences of existing diseases. Nonmucosal disease: Sjögren disease, chronic oral burning, or xerostomia after COVID-19 infection/vaccination cases totaled 12 cases identified from the authors' clinical practice, with the majority occurring after infection. CONCLUSIONS:Chronic conditions after infection with COVID-19 or vaccination remain relatively rare and self-limited, yet reinforce the importance of comprehensive history taking involving COVID-19 to differentiate potential etiologic factors for these conditions.

Objectives The role of Human papillomavirus (HPV) in the oral squamous cell carcinoma (OSCC) has not been completely elucidated. The purpose of the present study was to investigate the prevalence and localization of HPV-16 virus in OSCC and to correlate HPV-16 positivity and p16INK4A expression with the clinical and pathological features of OSCC. Methods The archives of Oral Pathology at the University of Florida, College of Dentistry were accessed for demographic, clinical, histopathological data, and slides of 114 OSCC patients. HPV-16 positivity of OSCC was evaluated by p16INK4A immunohistochemistry (IHC) and HPV-16 E6/E7mRNA by in situ hybridization (ISH). Results Out of 114 consecutive pathological slides of OSCC, 16 samples (14%) showed positivity for p16INK4A by IHC and 14 samples (12%) were positive for HPV-16 E6/E7mRNA ISH and the Positivity showed a significant correlation with the patients' age, alcohol consumption, and the degree of OSSC differentiation. The hard palate showed the highest positivity of p16INK4A IHC and HPV-16 mRNA ISH (38%, 36% respectively). Conclusion HPV-16 is a significant factor in oral carcinogenesis. We recommend using p16INK4A as a surrogate marker for HPV detection in OSCC, which can be complemented by RNA ISH for the identification of HPV subtypes.

White lesions within the oral cavity represent some of the most commonly encountered types of oral pathologic entities and may frequently cause diagnostic difficulty both clinically and his-tologically due to overlapping features between conditions. Consideration of both clinical history and appearance of the lesions is important in dis-tinguishing benign from potentially malignant or malignant lesions. Warning signs include high -risk location, sharply demarcated borders, thick-ened, plaque-like, papillary, or verrucous lesions, erythroplakia, asymmetry, or the presence of iso-lated lesions with no apparent source of trauma, large or enlarging size, multiple recurrences, or a pattern of marginal linear gingival leukoplakia (ring around the collar) are all important and must be recognized to provide appropriate management.

OBJECTIVE:Oral plasma cell mucositis (PCM) or localized plasma cell gingivitis (PCG) is an idiopathic inflammatory condition often associated with hypersensitivity reactions. This study aimed to evaluate the frequency and features of PCM/PCG in a large biopsy service over a time period of more than 20 years.STUDY DESIGN:The biopsy archives at University of Florida College of Dentistry were searched from 2000 through the first quarter of 2023 for cases of oral PCM or PCG. Case data were aggregated and analyzed.RESULTS:A total of 107 cases were included. Between 2000 and 2019, PCM/PCG was diagnosed in 0.03% of all biopsy cases. Starting in 2020 through 2023, the percentage of biopsies diagnosed as PCM/PCG increased threefold to 0.10% of all biopsy cases, and the mean patient age increased by 3 years. There were no statistically significant differences between cases diagnosed from 2000 to 2019 and those from 2020 to 2023 regarding age, sex, location, or histology.CONCLUSIONS:A significant increase in PCM/PCG was identified in this study at one institution coinciding with the start of the COVID-19 pandemic. Further investigation is recommended to determine if this is a widespread phenomenon and identify possible etiologic mechanisms.

Background: Oral squamous cell carcinoma (OSCC) is a disease typically seen in the elderly, with an established relationship with tobacco and/or alcohol abuse. However, the incidence of OSCC among young adults (defined in this study as ≤ 30 years old) is on the rise. Materials and Methods: With IRB approval, a retrospective search was performed at the University of Florida College of Dentistry Oral Pathology Biopsy Service database from 1994-to 2019 for all cases of OSCC affecting patients aged ≤ 30 years. Demographic data were recorded, and the slides were reviewed for diagnostic consensus. Results: Thirty-one of 3971 OSCC cases (0.76%) were identified. The data show a prominent increase over time. Male patients (54.83%) were more commonly affected. Their ages ranged from 8 to 30 years, with a mean age of 25 years. The lateral border of the tongue is the most frequent site of involvement. A wide spectrum of differential diagnoses were obtained, mostly consisting of reactive lesions. Symptoms were reported in 65.6% of the cases. The histological grades ranged from well to poorly differentiated. Conclusion: This study underscores the rarity of OSCC in children and young adults. This may potentially lead to a low clinical suspicion, misdiagnosis, and delay in treatment. Further longitudinal multicenter studies with detailed medical history, treatment, genotyping, and prognostic data may help to better understand the etiology of OSCC in young patients, aid in prevention, and improve outcomes.

Buccal bifurcation cyst is an inflammatory odontogenic cyst and constitutes up to 5% of all odontogenic cysts. The aim of this study was to report a series of cases, review the recent literature, and facilitate recognition and proper treatment of this entity.With institutional review board approval, the authors retrieved all archival cases of buccal bifurcation cyst from the oral pathology biopsy service from 1994 through 2018. Patient age and sex, cyst location, clinician's impression, radiographic appearance, diagnosis, and treatment data were recorded.A total of 10 cases were identified. Average patient age was 9 years. A slight male predilection was observed (n = 6, 60%). One hundred percent of cases were in the mandible, including 3 (30%) bilateral cases.Mandibular buccal bifurcation cyst is an important entity in pediatric patients but may be less likely to be recognized by clinicians not regularly treating children. The results of this study are mostly consistent with the literature. Treatment is typically via enucleation or even more conservative modalities, and extraction should be avoided if possible.Buccal bifurcation cysts should be treated via enucleation or even more conservative methods. If possible, the affected teeth should be preserved.

Oral lesions may be the initial or only manifestation of leukemia and can be the key to early diagnosis. The varied nature of presenting signs and dentists' general lack of familiarity with oral presentations makes diagnosis challenging. This retrospective review reports a series of cases of leukemia to familiarize dentists with the oral manifestations and facilitate earlier diagnosis or recognition of relapse of this life-threatening disease. Following institutional review board approval, the University of Florida Oral Pathology Biopsy Service archive from 1994 to 2018 was queried for all oral biopsies resulting in a diagnosis of leukemia. Cases with insufficient diagnostic information or extraoral manifestations were excluded. Demographic, clinical, and histologic findings were tabulated. Ten cases with 12 biopsy sites were identified. Men (n = 6) were affected more commonly. The mean age of the patients was 58.4 years (range of 17 to 88 years). The gingiva was the most frequently biopsied site (n = 6; 50%). Importantly, 40% of the patients (n = 4) had no prior diagnosis of leukemia. A wide spectrum of clinical impressions was rendered, pyogenic granuloma being the most common, and the reported duration of lesions ranged from several weeks to 6 months. The rarity of patients presenting with leukemia may lead to low levels of clinical suspicion, misdiagnosis, and delays in treatment. However, oral lesions may be the first and only manifestation of leukemia, and clinicians should be aware of the clinical characteristics of these oral presentations to ensure early diagnosis and treatment, thereby helping to reduce disease-related morbidity and mortality.

Introduction. Buccal bifurcation cyst is an inflammatory odontogenic cyst and constitutes up to 5% of all odontogenic cysts. The aim of this study was to report a series of cases, review the recent literature, and facilitate recognition and proper treatment of this entity. Methods. With institutional review board approval, the authors retrieved all archival cases of buccal bifurcation cyst from the oral pathology biopsy service from 1994 through 2018. Patient age and sex, cyst location, clinician's impression, radiographic appearance, diagnosis, and treatment data were recorded. Results. A total of 10 cases were identified. Average patient age was 9 years. A slight male predilection was observed (n = 6, 60%). One hundred percent of cases were in the mandible, including 3 (30%) bilateral cases. Conclusions. Mandibular buccal bifurcation cyst is an important entity in pediatric patients but may be less likely to be recognized by clinicians not regularly treating children. The results of this study are mostly consistent with the literature. Treatment is typically via enucleation or even more conservative modalities, and extraction should be avoided if possible. Practical Implications. Buccal bifurcation cysts should be treated via enucleation or even more conservative methods. If possible, the affected teeth should be preserved.

Oral melanoacanthoma (OM) is a rare, reactive, and benign proliferation of two cell types: keratinocytes and melanocytes. Biopsy is mandatory to not only confirm the diagnosis but also, rule out other entities, as clinical correlation simply, is not definitive. We present a large series of OM with analysis of demographics, clinical appearance, histologic presentation, and review of the literature. To the best of our knowledge, this is the largest series of oral OM reported to date. Following IRB approval, cases diagnosed as OM within the archives of the University of Florida Oral Pathology Biopsy Service (1998–2020) were included. Patient age, gender, location, clinical appearance, clinical impression, and duration of each lesion was collected. A total of 33 cases were included with a mean age of 38.7 years (range of 5–73), and a female: male ratio of 2.6:1. The most common location in descending order was the buccal mucosa (n = 16, 48

OBJECTIVE Adenomatoid odontogenic tumor (AOT) is a benign odontogenic tumor with an excellent prognosis, often seen in children and young adults. The aim was to examine the spectrum of clinical, radiographic, and histologic attributes of AOT and assess clinician recognition of this entity. In addition, diagnostic considerations and treatment modalities were explored. METHOD AND MATERIALS With Institutional Review Board approval, archival cases of AOT from the University of Florida Oral Pathology Biopsy Service (1994-2019) were examined. Clinical and demographic data along with accompanying radiographs and original slides were reviewed. RESULTS A total of 28 cases of AOT were identified. These were all solitary in nature, with a mean age of 20.6 years (range 12-67 years). Most patients were under 20 (75.0%) with a definite female predilection (64.3%). Anterior jaws remained the most common location (85.2%), with a higher maxillary predilection (57.1%). Clinical impression included odontogenic lesions such as dentigerous cyst, lateral periodontal cyst, and odontogenic keratocyst. CONCLUSION The spectrum of features of AOT is described. As clinicians were unfamiliar with AOT, highly characteristic features of AOT and more unique variants are discussed extensively to improve diagnostic aptitude. Clinicians must remain aware of this entity, as treatment is minimal compared to other odontogenic entities.