Increased frequency of oral plasma cell mucositis/plasma cell gingivitis after the COVID-19 pandemic: a 23-year retrospective analysis and review of diagnostic challenges relating to this condition.

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.

Chronic oral diseases secondary to COVID-19 infection or vaccination: clinical cases and a narrative review.

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 (OLP); oral pemphigoid, either bullous pemphigoid (BP) or mucous membrane pemphigoid (MMP) with oral involvement; pemphigus vulgaris (PV) with oral involvement; or Sjögren's 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 OLP, oral BP, MMP, PV and COVID-19 infection/vaccination, with additional cases from the authors' clinical practice presented. Part 2 (non-mucosal conditions): Cases of initiated or flared Sjögren's disease, chronic oral burning, or xerostomia after COVID-19 infection/vaccination from the authors' clinical practice were aggregated. Our literature review discovered 29 cases of OLP following COVID-19 infection/vaccination. For BP, 10 cases were identified after infection/vaccination. The number of PV cases following infection/vaccination were 28. The majority of mucosal cases were reported after vaccination. Most reported initial disease, but a substantial amount included recurrences of existing diseases. Non-mucosal disease: Sjögren's 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.

Reactive and Nonreactive White Lesions of the Oral Mucosa.

White lesions in the oral cavity may be diverse in etiology and may present with significant clinical and sometimes histologic overlap between categories, making accurate diagnosis difficult at times. Although white lesions of immune and infectious etiology are covered in another article, this article discusses the differential diagnosis between developmental, reactive, idiopathic, premalignant, and malignant white lesions focusing on clinical features of each category.

Localization and characterization of human papillomavirus-16 in oral squamous cell carcinoma.

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.

Oral Melanoacanthoma: Case Series of 33 Cases and Review of the Literature.

BACKGROUND: 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. AIM OF THE STUDY: 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. MATERIALS AND METHODS: 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. RESULTS: 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%), followed by palate (n = 11, 33%), tongue and labial mucosa (n = 2 each, 6%), maxillary and mandibular gingiva (n = 1 each, 3%). The lesions were most frequently brown/black in color, and most often described as macular. All cases were asymptomatic and reported duration was ranged from one week to twelve months. Clinical impression in descending order was pigmented macules (n = 15, 45%), melanosis (n = 4, 12%), nevus (n = 3, 9%), melanoma (n = 2, 6%), melanoacanthoma (n = 1, 3%), and racial pigmentation (n = 1, 3%). Ethnicity was only documented in only 6 out of 33 cases, of which 5 cases were African-American and one Caucasian. The majority of cases (n = 28, 84%) demonstrated hyperplastic/acanthotic surface epithelium with less common, atrophic (n = 4, 12.1%) or spongiotic epithelium (n = 2, 6.06%). CONCLUSION: The demographics and clinical presentation of OM in our series was similar to previous findings but encompasses wider variability of histologic presentation. Awareness of OM in the clinical and histologic differential diagnosis of pigmented lesions should be reinforced as many patients are concerned for melanoma and clinicians are often unware of this condition.

Changing Trends in Benign Human Papillomavirus (HPV) Related Epithelial Neoplasms of the Oral Cavity: 1995-2015.

Human papillomavirus (HPV)-related benign papillary epithelial neoplasms are common lesions affecting any region of the oral cavity. This study evaluated the trends in frequency, location, and demographics of these lesions over 20 years in a large biopsy service. Following IRB approval, the archives of UF Oral Pathology Biopsy Service between 1995 and 2015 were queried. Cases diagnosed as squamous papilloma, verruca vulgaris, and condyloma acuminatum were included. Extraoral locations, inconclusive diagnoses, or syndrome-related HPV lesions were excluded. Age, gender, location, clinical presentation, and diagnoses were recorded. Data from one calendar year per 5-year span was assessed including the years 1995, 2000, 2005, 2010, and 2015. A total of 1458 cases were identified over the total 5 calendar years assessed. Papilloma as a percentage of total biopsies per year was as follows: 1995 (2.6%), 2000 (3.3%), 2005 (3.6%), 2010 (4.0%) and 2015 (4.5%), representing a 73% (1.9×) percentage increase. Males (56%) were affected more commonly; however, in patients under 19 years, a female predominance was observed. The overall percentage of lesions in females increased by 30.6% over the time frame. The mean age was 54 years (range 1-93 years) with an increase of 10 years over time. About 1.1% of patients had multifocal lesions and 0.2% had a recurrence. In descending order of frequency, the tongue, soft palate, and mandibular gingiva were most involved. Maxillary gingiva and lower lip were the most common locations in patients under 19. Location varied over time, however, the biggest increase was noted for lesions on the gingiva. Squamous papilloma was the most common histologic variant (93.6%). The incidence of benign HPV-related oral lesions increased substantially over the 2 decades studied. This increase was statistically significant with a p-value <0.00045. Other trends noted included increase in the following: the average age, female involvement, and gingival location. Our results indicate a trend for the overall increase in the prevalence of benign oral HPV lesions in our population.

Buccal bifurcation cyst: A case series and review of the literature.

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.

Essentials of oral manifestations of leukemia for the dental practitioner.

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.

Adenomatoid odontogenic tumor: a series of 28 cases from a biopsy service.

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.

Labial salivary gland assessment in idiopathic pulmonary fibrosis patients with sicca symptoms.

OBJECTIVE: Patients with idiopathic pulmonary fibrosis (IPF) commonly present with sicca symptoms. This study aimed to assess labial minor salivary glands (LMSGs) in those patients to rule out Sjögren's syndrome (SS), in which sicca symptoms are the clinical hallmark. STUDY DESIGN: Cases of patients with IPF with sicca symptoms referred to the oral medicine clinic at the University of Florida within the last 13 years were selected with institutional review board approval. Demographic characteristics, clinical findings, laboratory results, and histomorphologic parameters were retrospectively analyzed. RESULTS: A total of 12 patients (9 men and 3 women, ages 55-76 years) were identified. History of exposure to asbestos or chemicals, smoking, and medication information was obtained. All patients reported sicca symptoms with 57% of those exhibiting objective or borderline dryness. Anti-SSA/Ro and anti-SSB/La were positive in 25% and 8% of the cases, respectively. Microscopically, 1 out of 12 patients was biopsy positive in the absence of anti-SSA/Ro, fulfilling the 2016 SS criteria with positive sialometry. CONCLUSIONS: A LMSG biopsy is critical to identify SS in patients with diagnosed IPF and present sicca symptoms, especially those with negative serology, as revealed in our study.

Calcifying epithelial odontogenic tumor: a case series spanning 25 years and review of the literature.

OBJECTIVE: The calcifying epithelial odontogenic tumor (CEOT) is a rare benign neoplasm that makes up less than 1% of all odontogenic tumors. This study aims to describe a case series of CEOT spanning 25 years and to review and compare our results with the existing literature. STUDY DESIGN: With institutional review board approval, all CEOT archival cases from the University of Florida Oral Pathology Biopsy Service between 1994 and 2019 were retrieved. A total of 20 cases were included. Based on current criteria, 2 cases that stained positively for CD1 a were excluded, because these most likely represented the amyloid-rich variant of central odontogenic fibroma. RESULTS: Average patient age was 40 years. Females and males were affected equally (n = 10). The mandible was more commonly involved (60%, n = 12) than the maxilla (40%, n = 8). CEOT variants included incipient CEOT (10%, n = 2) and peripheral CEOT (10%, n = 2). One case exhibited features of adenomatoid odontogenic tumor in addition to CEOT. Congo red staining for amyloid was performed in 13 cases, all of which were positive. CONCLUSION: Our results align with the literature. Awareness of the different variants of CEOT and of the separate but similar-appearing amyloid-rich variant of central odontogenic fibroma will help to ensure accurate diagnosis and appropriate treatment.

Case of squamous cell carcinoma of the tongue in a pregnant woman, with literature review.

Oral squamous cell carcinoma (OSCC) is an extremely rare occurrence during pregnancy. OSCC accounts for less than 2% of all malignancies in pregnant women, with an average mortality rate of 36%. Understanding the features of this tumor during pregnancy is important; however, the paucity of reports in the literature makes this challenging. Case presentation: The following is a case presentation of a woman who was diagnosed with SCC of the tongue (TSCC) at 13 weeks gestation. The article also provides a review of the literature of TSCC affecting pregnant women aged 30 years and under. Conclusion: Although OSCC in young women of reproductive age is rare, recent literature suggests an increased risk for this age group. The rarity of OSCC in pregnancy may potentially lead to low clinical index of suspicion, misdiagnosis, and delay in treatment. Additionally, treatment modalities, prognosis, and the long-term impact on the developing fetus are not well established, due to rarity of OSCC in pregnancy. Further studies to identify specific etiologic factors are needed to establish the association of OSCC with pregnancy, aid in prevention, and improve treatment and outcome.

Proliferative Verrucous Leukoplakia: An Expert Consensus Guideline for Standardized Assessment and Reporting.

The many diverse terms used to describe the wide spectrum of changes seen in proliferative verrucous leukoplakia (PVL) have resulted in disparate clinical management. The objective of this study was to produce an expert consensus guideline for standardized assessment and reporting by pathologists diagnosing PVL related lesions. 299 biopsies from 84 PVL patients from six institutions were selected from patients who had multifocal oral leukoplakic lesions identified over several years (a minimum follow-up period of 36 months). The lesions demonstrated the spectrum of histologic features described in PVL, and in some cases, patients developed oral cavity squamous cell carcinoma (SCC). An expert working group of oral and maxillofacial and head and neck pathologists reviewed microscopic features in a rigorous fashion, in combination with review of clinical photographs when available. The working group then selected 43 single slide biopsy cases for whole slide digital imaging (WSI) review by members of the consensus conference. The digital images were then reviewed in two surveys separated by a washout period of at least 90 days. Five non-PVL histologic mimics were included as controls. Cases were re-evaluated during a consensus conference with 19 members reporting on the cases. The best inter-observer diagnostic agreement relative to PVL lesions were classified as "corrugated ortho(para)hyperkeratotic lesion, not reactive" and "SCC" (chi-square p = 0.015). There was less than moderate agreement (kappa < 0.60) for lesions in the "Bulky hyperkeratotic epithelial proliferation, not reactive" category. There was ≥ moderate agreement (> 0.41 kappa) for 35 of 48 cases. This expert consensus guideline has been developed with support and endorsement from the leadership of the American Academy of Oral and Maxillofacial Pathology and the North American Society of Head and Neck Pathologists to recommend the use of standardized histopathologic criteria and descriptive terminology to indicate three categories of lesions within PVL: (1) "corrugated ortho(para)hyperkeratotic lesion, not reactive;" (2) "bulky hyperkeratotic epithelial proliferation, not reactive;" and (3) "suspicious for," or "squamous cell carcinoma." Classification of PVL lesions based on a combination of clinical findings and these histologic descriptive categories is encouraged in order to standardize reporting, aid in future research and potentially guide clinical management.

Marginal linear gingival leukoplakia progressing to "ring around the collar"-An ominous sign of proliferative verrucous leukoplakia.

BACKGROUND: Potentially malignant lesions of the gingiva may frequently present as well-demarcated white lesions confined to the marginal gingiva. These lesions often become thick and verrucoid and spread along the marginal gingiva to encircle the tooth. Some cases of marginal gingival leukoplakia, over time, progress to extensively involve the gingiva fulfilling the criteria for proliferative verrucous leukoplakia (PVL). The objective of this study is to raise awareness of this pattern of leukoplakia by reporting a series of cases of marginal gingival leukoplakia. METHODS: An Institutional Review Board approved retrospective search of University of Florida and University of Nebraska Medical Center oral biopsy services was performed for all gingival biopsies. Inclusion criteria included cases exhibiting marginal gingival leukoplakia, and with accompanying clinical images. RESULTS: A total of 30 cases of marginal gingival leukoplakia were included. All cases presented as well-demarcated leukoplakias, either on the buccal or lingual gingival margin, or circumferentially forming a "ring around the collar" of single or multiple teeth. Eight patients had recurrent lesions and 12 had multifocal involvement. Six of the 12 patients with multifocal involvement presented with a "ring around the collar." The histopathologic diagnoses were representative of benign lesions in seven cases, premalignant in 13, and malignant or suggestive of malignancy in 10 cases. Seven patients had carcinoma at the time of first biopsy, whereas 6 cases showed progression at time of follow-up. CONCLUSION: This study aims to raise awareness that marginal gingival leukoplakia may represent potentially malignant lesions, and if circumferential and/or thick, may be the first manifestation of PVL.

Retrospective Study of Buccal Mucosal Salivary Neoplasms.

Salivary gland neoplasms of the buccal mucosa are relatively rare and often present with an unusual histopathologic profile when compared with other intraoral locations. We present a series of minor salivary gland neoplasms of the buccal mucosa and discuss demographics, clinical presentation, and histologic findings. An IRB approved retrospective search of University of Florida Oral Pathology Biopsy Service archive from 1994 to 2018 for all salivary gland neoplasms of the buccal mucosa was undertaken. Data related to age, gender, clinical presentation, diagnosis, and category of neoplasm recorded. Review for consensus of diagnosis and immunohistochemical (IHC) testing on current diagnostic standards was performed and diagnoses updated based on results. Of 66 cases identified majority were females (72.7%) and age mean was 63 years. Benign tumors were 56.06% and 43.94% malignant, with Mucoepidermoid carcinoma (MEC) being commonest (26/66, 39.4%), followed by canalicular adenoma (CLA) (14/66, 21.2%), ductal papilloma (DP) (10/66, 15.2%), cystadenoma (CA) (8/66, 12.1%), basal cell adenoma (BCA) (4/66, 6.1%), and 1(1.5%) each for pleomorphic adenoma (PA), secretory carcinoma (SC), adenoid cystic carcinoma (ACC) and adenocarcinoma not otherwise specified (ACNOS). This study with respect to demographics and percentage of benign and malignant buccal mucosal salivary gland neoplasms is in conformity with the literature. It underscores the fact that both benign and malignant salivary gland neoplasms should be included in the differential diagnosis of submucosal buccal masses. Future larger multicenter studies with detailed treatment and outcomes data may aid and assist in further understanding the behavior, diverse histomorphology and prognosis of these neoplasms.

Oral Verruciform Xanthoma: A Series of 212 Cases and Review of the Literature.

Verruciform xanthoma (VX) of the oral cavity is an uncommon, reactive lesion of unknown etiology. In this study, we present a large series of VX with analysis of demographics, clinical appearance, histologic presentation and extensive review of literature. To the best of our knowledge, this is the largest series of oral VX reported to date. Following IRB approval, all cases diagnosed as VX found in the archives of the University of Florida Oral Pathology Biopsy Service (1994-2018) were included. Patient age, gender, location, clinical appearance, clinical impression, and duration of each lesion was collected. A total of 212 cases were included in our database with a mean age of 61 years (range of 9-94), and a female: male ratio of 1.06:1. The most common location in descending order was the gingiva (n = 110, 51.2%), followed by palate (n = 41, 19.3%), buccal mucosa (n = 18, 8.5%), tongue (n = 20, 9.4%), vestibule (n = 13, 6.1%), lip (n = 4, 1.9%), floor of mouth (n = 3, 1.4%), and unspecified (n = 1, 0.5%). The lesions were most frequently pink in color, and most often described as bumpy, rough, verrucoid and/or papillary. Clinical impression in descending order was papillary (n = 67, 31.6%), not specified or unknown (n = 41, 19.3%), hyperkeratosis (n = 24, 11.3%), fibroma (n = 20, 9.4%), leukoplakia (n = 17, 8.0%), dysplastic lesion (n = 13, 6.1%), pyogenic granuloma (n = 7, 3.3%), granulomatous reaction (n = 5, 2.4%), lichen planus, VX (n = 4 each, 2.0%), pigmented, other lesions (n = 3 each, 1.4%), and salivary and periapical lesions (n = 2 each, 0.9%). Three of the lesions were recurrences. The demographics and clinical parameters of this case series were in concordance with that of previously published reports. In our series, only 4 cases were suspected as VX, demonstrating the lack of familiarity clinicians have with this lesion.

p16INK4a as a proliferation marker unrelated to HPV expression in odontogenic cysts and tumors.

INTRODUCTION: p16INK4a is a tumor suppressor protein that retards cell cycle progression from G1 to S phase. Prior studies have evaluated p16INK4a expression in odontogenic keratocyst and ameloblastoma, but data regarding other odontogenic cysts and tumors have been sparse. METHODS: With IRB approval, cases from the following entities were identified from archives of the UF Oral Pathology Biopsy Service (2005-2015): benign incidental odontogenic rest, dentigerous cyst, lateral periodontal cyst, calcifying odontogenic cyst, glandular odontogenic cyst, odontogenic keratocyst, orthokeratinized odontogenic cyst, adenomatoid odontogenic tumor, calcifying epithelial odontogenic tumor, and ameloblastoma. All cases were submitted for p16INK4a immunohistochemical testing. RESULTS: Results were scored as follows: nuclear and cytoplasmic staining of <5% cells (score 0), 5%-25% (score 1), 25%-50% (score 2), >50% (score 3). No significant difference in p16INK4a staining was noted between odontogenic cysts and the listed odontogenic tumors (chi-square, P = .540). When comparing lesions with higher recurrence rates (over 25% as reported in the literature) versus lesions with low recurrence rates (under 25%), higher recurrence correlated to significantly higher p16INK4a positivity (chi-square, P = .001). Follow-up testing was performed on 18 cases with "2" or "3" p16INK4a expression scores for high-risk HPV strains through HPV in situ hybridization (ISH) messenger RNA testing with no cases exhibiting a positive result. CONCLUSION: This study exhibits an association between increased p16INK4a positivity and odontogenic lesions with higher recurrence rates and highlights the role of p16INK4a as a progression marker unrelated to HPV expression in this group of pathologic entities.

Inter-observer Variability in the Diagnosis of Proliferative Verrucous Leukoplakia: Clinical Implications for Oral and Maxillofacial Surgeon Understanding: A Collaborative Pilot Study.

The use of diverse terminology may lead to inconsistent diagnosis and subsequent mistreatment of lesions within the proliferative verrucous leukoplakia (PVL) spectrum. The objectives of this study were: (a) to measure inter-observer variability between a variety of pathologists diagnosing PVL lesions; and (b) to evaluate the impact of diverse terminologies on understanding, interpretation, and subsequent treatment planning by oral and maxillofacial surgeons (OMFS). Six oral pathologists (OP) and six head and neck pathologists (HNP) reviewed 40 digitally scanned slides of PVL-type lesions. Inter-observer agreement on diagnoses was evaluated by Fleiss' kappa analysis. The most commonly used diagnostic terminologies were sent to ten OMFS to evaluate their resulting interpretations and potential follow-up treatment approaches. The overall means of the surgeons' responses were compared by Student t test. There was poor inter-observer agreement between pathologists on the diagnosis of PVL lesions (κ = 0.270), although there was good agreement (κ = 0.650) when diagnosing frankly malignant lesions. The lowest agreement was in diagnosing verrucous hyperplasia (VH) with/without dysplasia, atypical epithelial proliferation (AEP), and verrucous carcinoma (VC). The OMFS showed the lowest agreement on identical categories of non-malignant diagnoses, specifically VH and AEP. This study demonstrates a lack of standardized terminology and diagnostic criteria for the spectrum of PVL lesions. We recommend adopting standardized criteria and terminology, proposed and established by an expert panel white paper, to assist pathologists and clinicians in uniformly diagnosing and managing PVL spectrum lesions.

Lichenoid reaction with granulomatous stomatitis: A retrospective histologic study of 47 patients.

OBJECTIVES: Lichenoid granulomatous reaction can be subcategorized into lichenoid granulomatous dermatitis or lichenoid granulomatous stomatitis. It is described in the literature as demonstrating a band-like lichenoid infiltration with clusters of histiocytic or granuloma formation. In this study, we presented a large case series of lichenoid granulomatous stomatitis including demographics, histological features, and subcategories and compared findings with current literature. METHODS AND MATERIALS: We retrieved all cases diagnosed with lichenoid reaction with granulomatous inflammation between January 1, 2000, and August 1, 2016, from the University of Florida Oral Pathology Biopsy Service Archives. RESULTS: A total of 47 patients with tissue from 50 biopsy sites were included. The majority of the cases were noted in females (64%) with a mean age of 59 years (range 30-88). Most patients were Caucasian, and the most common sites in descending order were: gingiva, buccal mucosa, vestibule, tongue, lip, palate, and occasional multifocal involvement. Clinical impressions by the treating clinicians included leukoplakia, dysplasia, carcinoma in situ, squamous cell carcinoma, lichen planus, vesiculobullous disease, trauma, and allergy. The histologic features of these cases ranged from lichenoid mucositis with numerous aggregates of histiocytes to well-formed granulomas, in accordance with previous classifications of similar dermatologic lesions. All cases revealed positive CD 68 in the histiocytic infiltrates and were negative for microorganisms utilizing acid-fast bacilli, Grocott methenamine-silver, and periodic acid-Schiff stains. CONCLUSION: Lichenoid granulomatous disease may be more common than previously reported; however, its etiology remains unknown and patients should be kept under long-term clinical follow-up.

Ulcerated Lesions of the Oral Mucosa: Clinical and Histologic Review.

Ulcerated lesions of the oral cavity have many underlying etiologic factors, most commonly infection, immune related, traumatic, or neoplastic. A detailed patient history is critical in assessing ulcerative oral lesions and should include a complete medical and medication history; whether an inciting or triggering trauma, condition, or medication can be identified; the length of time the lesion has been present; the frequency of episodes in recurrent cases; the presence or absence of pain; and the growth of the lesion over time. For multiple or recurrent lesions the presence or history of ulcers on the skin, genital areas, or eyes should be evaluated along with any accompanying systemic symptoms such as fever, arthritis, or other signs of underlying systemic disease. Biopsy may be indicated in many ulcerative lesions of the oral cavity although some are more suitable for clinical diagnosis. Neoplastic ulcerated lesions are notorious in the oral cavity for their ability to mimic benign ulcerative lesions, highlighting the essential nature of biopsy to establish a diagnosis in cases that are not clinically identifiable or do not respond as expected to treatment. Adjunctive tests may be required for final diagnosis of some ulcerated lesions especially autoimmune lesions. Laboratory tests or evaluation to rule out systemic disease may be also required for recurrent or severe ulcerations especially when accompanied by other symptoms. This discussion will describe the clinical and histopathologic characteristics of a variety of ulcerated lesions found in the oral cavity.