Assessment of MDM2 Gene Locus Amplification by Fluorescence In-Situ Hybridization in Juvenile Ossifying Fibroma.

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). MATERIALS AND METHODS: 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. RESULTS: The examined cases were all negative for MDM2 gene locus amplification via FISH testing. CONCLUSION: 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.

Xanthoma of the Jaw Bones: Cases Series and Review of Literature.

BACKGROUND: Intraosseous xanthomas are rare benign lesions sometimes associated with excess lipid production. Xanthoma of the jaw bones (XJB) was first reported in 1964, and fewer than 50 cases have been reported in the English literature to date. The etiopathogenesis of XJB is highly suggestive of a reactive process or a metabolic condition. METHOD: Seven cases of XJBs were retrieved from the archives of 4 oral and maxillofacial pathology services. Clinical, radiographic and histopathologic features of all these cases were retrospectively analyzed. Immunohistochemical (IHC) stains for S100 and CD68 were performed. RESULTS: All seven cases involved the mandible. Patients' age ranged between 13 and 69 years with an evenly distributed female to male ratio. One patient had a medical history of hyperlipidemia, but the medical and dental histories of the others were unremarkable. For most cases, XJB was an incidental finding discovered during routine radiographic examination. Swelling and cortical expansion were noted in a few cases. Radiographically, cases typically presented as either well-defined multilocular or unilocular lesions, which were either radiolucent or mixed radiolucent/radiopaque. All the lesions were treated with surgical curettage and no recurrence was observed during subsequent follow-ups. Each of the seven cases exhibited sheets of foamy macrophages. The diagnosis is established by exclusion of entities with overlapping microscopic features and involved correlation with the clinical, histological, radiographic and IHC profiles. Immunohistochemically, all the cases expressed diffuse positivity for CD68 and were negative for S100. CONCLUSION: XJB is a rare lesion of unknown etiology, which may mimic other benign or reactive jaw lesions. Due to its rarity and the potential diagnostic challenges it presents, clinicians must remain vigilant and consider CXJ in their differential when assessing radiolucent jaw anomalies.

COVID-related mucormycosis mimicking dental infection.

A recent increase in the prevalence of mucormycosis of the head and neck in patients who have recovered from COVID-19 following hospitalization has been reported. A Majority of the cases have been reported from India. Conditions such as diabetes mellitus, use of corticosteroids for other autoimmune conditions, organ transplant, immunosuppression, immunodeficiency, and malignancies especially hematologic ones, are all known risk factors for mucormycosis. Recently, hospitalization for COVID-19 has been added to the list of risk factors for opportunistic mucormycosis infection. This is likely attributable to the high doses and prolonged use of corticosteroids in the treatment of hospitalized COVID-19 patients. Case Description: Two patients with post-COVID-19 associated rhinocerebral mucormycosis presented with profound unexplained dental disease including tooth mobility and dental abscess mimicking periodontal disease. The patients were previously hospitalized for COVID-19 and received prolonged treatment with high doses of corticosteroids. The patients responded well to the surgical debridement with or without antifungal therapy. Conclusion: Oral healthcare providers including oral and maxillofacial surgeons, dentists, dental hygienists, and other dental practitioners can play a vital role in the recognition and early diagnosis of rhinocerebral mucormycosis given the large number of patients with severe COVID-19 infection who have recovered following hospitalization and/or received long-term high doses of immunosuppressive treatment.

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.

A rare case of peripheral adenoid ameloblastoma with dentinoid.

Adenoid ameloblastoma with dentinoid (AAD) is an extremely rare central neoplasm of the gnathic bones with no reported case of peripheral AAD. Adenoid ameloblastoma with dentinoid was first reported by Slabbert et al. in 1992 under the term "dentinoameloblastoma." However, the Armed Forces Institute of Pathology introduced the name "adenoid ameloblastoma with dentinoid" in 1994. Histologically, AAD shows features of ameloblastoma and adenomatoid odontogenic tumor along with a calcified product resembling dentin. The biological behavior of central AAD is not well established, though, in the literature, several reports consider it to be among the more aggressive odontogenic neoplasms, with a propensity for local invasion and recurrence. The demographic characteristics, clinical features, behavior, and prognosis of the peripheral AAD (PAAD) are unknown. To the best of our knowledge, this is the first reported case of PAAD in a 62-year-old woman.

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.

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.

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.

Peripheral ameloblastic fibro-odontoma-Report of 2 cases of a very rare entity.

Ameloblastic fibro-odontoma (AFO) is a rare benign mixed odontogenic tumor that affects children and young adults. AFO occurs mainly intraosseous. Extraosseous AFO is extremely rare. We report 2 cases of rare peripheral ameloblastic fibro-odontoma in 2- and 12-year-old female patients. Microscopic examination revealed a benign proliferation of odontogenic epithelium associated with a dentinoid material distributed within a cell-rich mesenchymal stroma resembling dental papilla. Simple surgical excision of the lesion is usually curative. There was no recurrence after a short period of follow-up. Clinicians should be cognizant of this rare entity, which can be considered in a differential diagnosis of gingival growths that are noted in early childhood.

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.

Central odontogenic fibroma in association with brown tumor of hyperparathyroidism in a patient with neurofibromatosis type 1.

We present a patient with bone abnormalities and a myriad of lesions secondary to his redeveloping renal failure and neurofibromatosis type 1 (NF1). A 21-year-old male renal transplant recipient with NF1 presented with painless masses and large, irregular radiolucent lesions in the maxilla and mandible. After histologic examination, the lesion was diagnosed as a central odontogenic fibroma (COdF) in association with a central giant cell lesion, most consistent with brown tumor of hyperparathyroidism. The bone changes were interpreted to be highly suggestive of renal osteodystrophy. Around 30 cases of hybrid central giant cell granuloma-like lesion in association with central odontogenic fibroma have been reported. This, to our knowledge, is the first reported case of brown tumor in association with COdF. Our case provides further evidence of the giant cell component as the initiating entity in these hybrid lesions.

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.

Secretory Carcinoma of the Oral Cavity: A Retrospective Case Series with Review of Literature.

Secretory carcinoma (SC) is an uncommon salivary gland neoplasm of the oral cavity that microscopically may mimic acinic cell carcinoma (ACC) and mucoepidermoid carcinoma (MEC). This study describes a series of SC in minor glands with a literature review. We performed a retrospective search for oral SC, within the archives of the University of Florida, Oral Pathology and Surgical Pathology Biopsy services from 2010 to 2018. A total of 10 SCs were identified in the oral and maxillofacial region, four of which were in the minor salivary glands. The demographic, clinical, histological, and molecular findings were aggregated for all 4 cases. Patient age varied from 30 to 60 years, with an average of 45 years. Two cases each were in female and male patients. Two cases presented on the labial mucosa, and one each on the hard and soft palate. Immunohistochemical (IHC) staining showed mammaglobin positivity in all cases, GATA3 positivity in two cases, S100 positivity in three cases, and SOX10 positivity in only one case. Fluorescence in situ hybridization demonstrated positivity for ETV6-NTRK3 fusion in 4 cases. Although oral SC is rare, pathologists should be aware of the histologic overlap between the SC and other salivary gland neoplasms such as ACC and MEC. A judicious application of IHC staining would aid in diagnosis. SC should be considered in the differential diagnosis for intraoral salivary gland tumors.

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.

Oral Hairy Leukoplakia in Immunocompetent Patients Revisited with Literature Review.

Oral hairy leukoplakia (OHL) is an Epstein-Barr virus (EBV) related lesion seen in severely immunocompromised patients especially, those with concomitant human immunodeficiency virus (HIV) infection. It has been rarely reported in immunocompetent patients. OHL most often presents on the lateral border of the tongue as an asymptomatic, white, and corrugated plaque that does not rub off. With Institutional Review Board (IRB) approval, the University of Florida Oral & Maxillofacial Pathology Biopsy Service archives spanning 1994-2020 were queried. All cases of OHL affecting immunocompetent patients were identified. Data related to age, gender, clinical presentation, results of Epstein-Barr virus in situ hybridization (EBER-ISH), and periodic acid-Schiff (PAS)-fungus stains were recorded. Medical history and histology of all cases were reviewed for confirmation of diagnosis. A total of 11 cases were identified, the majority of which were males (63.6%) with a mean age of 62 years. All patients were Caucasian. Lesions entirely were located on the lateral borders of the tongue. OHL should not be considered pathognomonic for HIV infection and should be included in the differential diagnoses of keratotic lesions affecting the lateral border of tongue even in immunocompetent elderly patients. The etiology of OHL in this group of patients is not clearly understood.

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.