Publications by authors named "Sook Bin Woo"

139 Publications

A Bronchogenic Cyst Masquerading as a Tongue Mass.

Head Neck Pathol 2021 Feb 27. Epub 2021 Feb 27.

Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, 188 Longwood Avenue, Boston, MA, 02115, USA.

Bronchogenic cysts are foregut-derived developmental anomalies found along the developmental pathway of the foregut. The putative theory of pathogenesis is abnormal budding or branching of epithelial cells during the development of tracheobronchial tree. Over 99 % of cases occur in the mediastinum and lung while the head and neck area is affected in less than 1 % of cases with only rare cases reported in the oral cavity. This is a report of a case of a bronchogenic cyst arising in a 6-year-old male. The lesion presented as a painless swelling of the left underside of the tongue. Microscopically, the cyst was lined by pseudostratified columnar epithelium exhibiting many ciliated and mucous cells. A focus of cartilage and discontinuous bundles of smooth muscle were present adjacent to the lining. Where there was cyst rupture, there was granulation tissue associated with many foamy macrophages and acute and chronic inflammation. Four other cases, three in the tongue and one in the lower lip vestibule with cutaneous extension, all in the midline, have been reported in a 1 day-old male, 4 year-old male, 6 year-old female and 3 year-old male. There was no recurrence after excision and this is in keeping with the behavior in previous reports. Other developmental cysts including foregut cysts may be focally lined with respiratory epithelium but the presence of cartilage is the sine qua non for the diagnosis of a bronchogenic cyst.
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http://dx.doi.org/10.1007/s12105-021-01303-xDOI Listing
February 2021

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

Head Neck Pathol 2021 Jan 7. Epub 2021 Jan 7.

Department of Oral and Maxillofacial Diagnostic Sciences, University of Florida College of Dentistry, Gainesville, FL, USA.

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.
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http://dx.doi.org/10.1007/s12105-020-01262-9DOI Listing
January 2021

Calcifying synovial sarcoma of the tongue with SS18 rearrangement: a rare variant in a rare location.

Oral Surg Oral Med Oral Pathol Oral Radiol 2020 Aug 20. Epub 2020 Aug 20.

Department of Oral Medicine Infection and Immunity, Harvard School of Dental Medicine, Boston, MA, USA; Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Synovial sarcoma is a soft tissue malignancy harboring t(X;18) resulting in fusion of two genes SS8 (at 18q11) and SSX (1, 2 or 4 at Xp11) forming the gene fusion product SS18-SSX. It affects adults in their 3rd-4th decades, most frequently in the para-articular regions of the extremities. Less than 10% of the cases occur within the head and neck region and of these, 60% occur in the neck and only 10% occur in the oral cavity. We report a synovial sarcoma of the tongue in a 14-year-old female patient with unusual histology. The patient presented with a mass occupying most of the tongue with extension into the floor of mouth and the lingual gingiva of the anterior mandibular teeth. The tumor was composed of a highly cellular proliferation of spindle cells in a herringbone pattern with many small vessels but without glandular structures, and with extensive calcifications throughout the tumor. Tumor cells were positive for epithelial membrane antigen and transducin-like enhancer of split-1, and fluorescence in situ hybridization studies identified SS18 gene rearrangement. The patient was managed with two debulking procedures followed by chemoradiation and is currently alive with disease.
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http://dx.doi.org/10.1016/j.oooo.2020.08.016DOI Listing
August 2020

Architectural Alterations in Oral Epithelial Dysplasia are Similar in Unifocal and Proliferative Leukoplakia.

Head Neck Pathol 2020 Sep 16. Epub 2020 Sep 16.

Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA, USA.

The current WHO histopathologic criteria for oral epithelial dysplasia (ED) are based on architectural and cytologic alterations, and do not address other histopathologic features of ED. Here we propose new diagnostic criteria including architectural, organizational, and cytologic features for oral ED. Cases of unifocal leukoplakia (UL) and proliferative leukoplakia (PL) with clinical photographs and follow-up information were identified. Only cases that showed minimal cytologic atypia or mild ED were used to demonstrate critical architectural changes as defined in this study. Eight biopsies from eight UL patients and 34 biopsies from four PL patients were included. The biopsies showed (a) corrugated, verrucous or papillary architecture, (b) hyperkeratosis with epithelial atrophy, (c) bulky squamous epithelial proliferation, and (d) demarcated hyperkeratosis and "skip" segments. The architectural alterations defined here are as important as the currently used criteria for the diagnosis of ED. Clinicopathologic correlation when diagnosing oral ED is also of the utmost importance in accurate diagnosis.
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http://dx.doi.org/10.1007/s12105-020-01216-1DOI Listing
September 2020

Adverse Drug Events in the Oral Cavity.

Dermatol Clin 2020 Oct 11;38(4):523-533. Epub 2020 Aug 11.

Division of Oral Medicine and Dentistry, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA; Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, 188 Longwood Avenue, Boston, MA 02115, USA.

Adverse reactions to medications are common and may have a variety of clinical presentations in the oral cavity. Targeted therapies and new biologic agents have revolutionized the treatment of cancers, autoimmune diseases, and inflammatory and rheumatologic diseases but have also been associated with adverse events in the oral cavity. This review describes the most common clinical presentations of oral mucosal reactions to medications, namely hyposalivation, lichenoid reactions, ulcers, bullous disorders, pigmentation, fibrovascular hyperplasia, reactive keratosis, dysesthesia, osteonecrosis, infection, angioedema, and malignancy.
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http://dx.doi.org/10.1016/j.det.2020.05.012DOI Listing
October 2020

Benign Alveolar Ridge Keratosis: Clinical and Histopathologic Analysis of 167 Cases.

Head Neck Pathol 2020 Dec 16;14(4):915-922. Epub 2020 Mar 16.

Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, 188 Longwood Avenue, Boston, MA, 02215, USA.

Benign alveolar ridge keratosis (BARK), the intraoral counterpart of cutaneous lichen simplex chronicus, is a reactive hyperkeratosis caused by trauma or friction that presents as a poorly demarcated white papule or plaque on the keratinized mucosa of the retromolar pad or alveolar ridge mucosa (often edentulous). This is a clinical and histopathologic analysis of BARK including evaluation of p53 expression in selected cases. One hundred and sixty-seven cases of BARK were identified from 2016 to 2017 and 112 (67.1%) occurred in males with a median age of 56 years (range 15-86). The retromolar pad was affected in 107 (64.1%) cases and the edentulous alveolar mucosa in 60 (35.9%) cases, with 17.4% of the cases presenting bilaterally. BARK showed hyperkeratosis often with wedge-shaped hypergranulosis and occasional focal parakeratosis. The epithelium exhibited acanthosis and surface corrugation with tapered rete ridges often interconnected at the tips. The study for p53 performed in 12 cases showed less than 25% nuclear positivity. BARK is a distinct benign clinicopathologic entity caused by friction, which should be clearly distinguished from true leukoplakia, a potentially malignant disorder.
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http://dx.doi.org/10.1007/s12105-020-01151-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7669959PMC
December 2020

Corrigendum to "Intralesional Triamcinolone Acetonide Therapy for Inflammatory Oral Ulcers". Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Volume 128, Issue 5, 485 - 490.

Oral Surg Oral Med Oral Pathol Oral Radiol 2020 05 6;129(5):549. Epub 2020 Mar 6.

Division of Oral Medicine and Dentistry, Brigham and Women's Hospital, Boston, MA, USA; Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA, USA.

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http://dx.doi.org/10.1016/j.oooo.2020.02.007DOI Listing
May 2020

Biallelic PTCH1 Inactivation Is a Dominant Genomic Change in Sporadic Keratocystic Odontogenic Tumors.

Am J Surg Pathol 2020 04;44(4):553-560

Department of Pathology, Brigham and Women's Hospital, Harvard Medical School.

Keratocystic odontogenic tumors (KCOTs) are locally aggressive odontogenic neoplasms with recurrence rates of up to 60%. Approximately 5% of KCOTs are associated with nevoid basal cell carcinoma (Gorlin) syndrome and 90% of these show genomic inactivation of the PTCH1 gene encoding Patched 1. Sporadic KCOTs reportedly have PTCH1 mutations in 30% of cases, but previous genomic analyses have been limited by low tumor DNA yield. The aim of this study was to identify recurrent genomic aberrations in sporadic KCOTs using a next-generation sequencing panel with complete exonic coverage of sonic hedgehog (SHH) pathway members PTCH1, SMO, SUFU, GLI1, and GLI2. Included were 44 sporadic KCOTs from 23 female and 21 male patients with a median age of 50 years (range, 10 to 82 y) and located in the mandible (N=33) or maxilla (N=11). Sequencing identified PTCH1 inactivating mutations in 41/44 (93%) cases, with biallelic inactivation in 35 (80%) cases; 9q copy neutral loss of heterozygosity targeting the PTCH1 locus was identified in 15 (34%) cases. No genomic aberrations were identified in other sequenced SHH pathway members. In summary, we demonstrate PTCH1 inactivating mutations in 93% of sporadic KCOTs, indicating that SHH pathway alterations are a near-universal event in these benign but locally aggressive neoplasms. The high frequency of complete PTCH1 loss of function may provide a rational target for SHH pathway inhibitors to be explored in future studies.
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http://dx.doi.org/10.1097/PAS.0000000000001407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7071995PMC
April 2020

Burning mouth syndrome: a diagnostic challenge.

Oral Surg Oral Med Oral Pathol Oral Radiol 2020 Feb 12;129(2):120-124. Epub 2019 Oct 12.

Harvard School of Dental Medicine, Boston, MA, USA; Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, MA, USA.

Objectives: The aim of this study was to characterize the diagnostic process that patients with burning mouth syndrome (BMS) undergo and to identify the potential pitfalls encountered in the workup and management of BMS.

Study Design: A retrospective chart review of patients with BMS seen at the Oral Medicine clinic at Brigham and Women's Hospital (Boston, MA) was conducted from January 2014 to April 2017. Abstracted data focused on the period from onset of symptoms to referral to the Oral Medicine clinic for definitive diagnosis and included providers consulted, symptom characteristics, diagnostic tests performed, and provisional diagnoses and treatments offered.

Results: One hundred and two patients (86.3% females) were included (median age 60 years). Median time from onset of symptoms to referral to the Oral Medicine clinic was 12 months (range 4-370 months). Patients saw a median of 3 providers (range 1-7); 30.4% had undergone a diagnostic test; 63.7% had been given a provisional diagnosis; and 78.4% had received treatment. Candidiasis was the most common misdiagnosis (25.5%), and antifungal medication was the most frequently prescribed therapy (27.5%).

Conclusions: Patients with BMS experience delay in diagnosis and management despite seeking and receiving professional care. Many undergo unnecessary tests and tend to be misdiagnosed or receive no diagnosis at all. Even those correctly diagnosed with BMS often receive inappropriate or ineffective treatment.
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http://dx.doi.org/10.1016/j.oooo.2019.09.015DOI Listing
February 2020

Oral immune-related adverse events associated with PD-1 inhibitor therapy: A case series.

Oral Dis 2020 Mar 9;26(2):325-333. Epub 2020 Jan 9.

Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA, USA.

Objective: The aim of this study was to characterize clinical and histopathological features, and management outcomes of patients with oral immune-related adverse events (irAEs) secondary to programmed cell death-1 (PD-1) inhibitors.

Methods: This was a case series of cancer patients receiving PD-1 inhibitor therapy who were referred to oral medicine for the development of oral irAEs. Demographic, clinical, and histopathological data were collected from electronic medical records.

Results: There were 13 patients (7 males) with a median age of 68 years (range: 39-82) who were treated with nivolumab (n = 7) or pembrolizumab (n = 6). Oral irAEs included lichenoid lesions (n = 10), erythema multiforme (EM) (n = 2), and acute graft-versus-host disease reactivation (n = 1), with or without ulcerations (n = 8). Four patients (31%) presented with only oral irAEs. Oral biopsies showed lichenoid mucositis (n = 4). Management with topical and systemic steroids led to complete symptomatic response in most patients (n = 12). PD-1 inhibitor therapy was temporarily discontinued (n = 3) and discontinued indefinitely (n = 2) due to severe oral irAEs.

Conclusion: Patients receiving PD-1 inhibitors may develop oral irAEs characterized by lichenoid lesions, ulcers, or EM. Topical and systemic steroids appear to be effective in managing oral lesions although the severity of irAEs may necessitate PD-1 inhibitor therapy dose modification.
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http://dx.doi.org/10.1111/odi.13218DOI Listing
March 2020

Intralesional triamcinolone acetonide therapy for inflammatory oral ulcers.

Oral Surg Oral Med Oral Pathol Oral Radiol 2019 Nov 13;128(5):485-490. Epub 2019 Aug 13.

Division of Oral Medicine and Dentistry, Brigham and Women's Hospital, Boston, MA, USA; Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA, USA.

Objectives: The aim of this study was to report on the clinical indications and treatment outcomes of intralesional steroid therapy (IST) for oral ulcerative conditions in an oral medicine practice.

Study Design: This was a retrospective single-center study of patients with oral ulcerative conditions treated with IST. Demographic data, clinical diagnosis of the oral condition, size of the ulcer, and pain were abstracted from patients' electronic medical records.

Results: Ninety-three patients (51 females [54.8%]) were treated for persistent traumatic oral ulcers (n = 38 [40.8%]), ulcers in oral chronic graft-versus-host disease (n = 23 [24.7%]), oral lichen planus (n = 19 [20.4%]), and other conditions (14%). Complete resolution was achieved in 81.7% of patients in a median of 96 days (range 10-357 days), with 80% fully healed in a median of 84 days (range 10-140 days). Overall, patients received a median of 2 injections (range 1-5 injections) and a median dose of 12 mg per injection (range 2-36 mg). Nearly half the patients were also treated with concomitant topical steroid therapy. After the first injection, the median pain score reduced from 5 (range 1-10) to 1 (range 0-10; P < .001) and the median size of ulcers reduced from 1 cm (range 0.1-5 cm) to 0.3 cm (range 0-2 cm; P < .001).

Conclusions: IST may be an effective treatment for inflammatory and immune-mediated oral ulcers.
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http://dx.doi.org/10.1016/j.oooo.2019.07.024DOI Listing
November 2019

Direct immunofluorescence is of limited utility in patients with low clinical suspicion for an oral autoimmune bullous disorder.

Oral Dis 2020 Jan 31;26(1):81-88. Epub 2019 Oct 31.

Division of Oral Medicine and Dentistry, Brigham and Women's Hospital, Boston, MA, USA.

Objectives: Oral autoimmune bullous disorders show clinical overlap with diseases such as lichen planus and others that may cause desquamative gingivitis. As direct immunofluorescence is expensive, we sought to determine if routine histology alone would be sufficient to distinguish between oral autoimmune bullous disorders and mimics.

Methods: We searched the records for patients with a suspected oral autoimmune bullous disorder who underwent biopsies for concurrent routine histologic evaluation and direct immunofluorescence and who had at least one follow-up visit. Cases were separated into high and low suspicion subgroups based on clinical findings.

Results: Within 148 cases, the sensitivity of routine histology alone was 0.810, with a negative predictive value of 0.889. However, the specificity was 0.989 with a positive predictive value of 0.979. Of the high suspicion cases, 57 (47.1%) were found to be consistent with an oral autoimmune bullous disorder, with a total of 11 histologic false negatives. 8 cases, all in the high suspicion subgroup, showed indeterminate direct immunofluorescence results. There were no histologic false negatives or inconclusive direct immunofluorescence results in the low suspicion subgroup.

Conclusions: In patients with a low clinical suspicion for an oral autoimmune bullous disorder, it is reasonable and more cost-effective to evaluate the lesion with routine histology alone.
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http://dx.doi.org/10.1111/odi.13159DOI Listing
January 2020

Oral keratosis of unknown significance shares genomic overlap with oral dysplasia.

Oral Dis 2019 Oct 23;25(7):1707-1714. Epub 2019 Jul 23.

Division of Oral Medicine and Dentistry, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts.

Objectives: To identify molecular characteristics of keratosis of unknown significance and to nominate pathways of molecular progression to oral cancer. Our work could provide a rationale for monitoring and treating these lesions definitively.

Methods: Patients with oral leukoplakia were eligible for our prospective observational study. We correlated alterations in cancer-associated genes with clinical and histopathologic variables (keratosis of unknown significance vs. moderate-to-severe dysplasia) and compared these alterations to a previously molecularly characterized oral cancer population.

Results: Of 20 enrolled patients, 13 (65%) had evidence of keratosis of unknown significance, while seven (35%) had dysplasia. Nine patients (45%) developed oral cancer (4/13 with keratosis of unknown significance, 5/7 with dysplasia). At a median follow-up of 67 (range 22-144) months, median overall survival was significantly shorter for patients with dysplasia (hazard ratio 0.11, p = .02). KMT2C and TP53 alterations were most frequent (75% and 35%, respectively). There were molecular similarities between keratosis of unknown significance and dysplasia patients, with no significant differences in mutational frequency among genes with ≥15% rate of alteration.

Conclusions: Among patients with leukoplakia, both patients with keratosis of unknown significance and patients with dysplasia developed oral cancer. Molecular alterations between these two groups were similar at this sample size.
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http://dx.doi.org/10.1111/odi.13155DOI Listing
October 2019

World Workshop of Oral Medicine VII: A systematic review of immunobiologic therapy for oral manifestations of pemphigoid and pemphigus.

Oral Dis 2019 Jun;25 Suppl 1:111-121

School of Dentistry, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Objective: To assess the evidence for treatment of oral involvement of pemphigus and pemphigoid with biologics.

Study Design: This systematic review used a comprehensive search strategy to identify literature describing oral involvement of pemphigus or pemphigoid treated with a biologic agent. The primary outcome measures were efficacy and safety of biologic therapy.

Results: Inclusion criteria were met by 154 studies including over 1200 patients. Treatment of pemphigus with a total of 11 unique biologic agents and 3 unique combinations of agents is reported. Five randomized controlled trials (RCT) were included in the final analysis that investigated infliximab, IVIg, rituximab, and autologous platelet-rich plasma therapy for pemphigus vulgaris. Three non-RCT studies reported on successful rituximab or IVIg therapy for mucous membrane pemphigoid. Studies demonstrated considerable heterogeneity in agent, methods, and quality.

Conclusions: Evidence clearly describing oral tissue response to biologic therapy is sparse. Two RCTs support use of rituximab, one supports use of IVIg, and one pilot study suggests intralesional injection of autologous platelet-rich plasma aids healing of oral PV lesions. As oral lesions of pemphigus and pemphigoid can be refractory to systemic therapy, drug trials including biologic therapies should document details regarding response of the oral lesions to therapy.
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http://dx.doi.org/10.1111/odi.13083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6544168PMC
June 2019

World Workshop on Oral Medicine VII: Immunobiologics for salivary gland disease in Sjögren's syndrome: A systematic review.

Oral Dis 2019 Jun;25 Suppl 1:102-110

School of Dentistry, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Objective: This systematic review evaluated the efficacy of immunobiologics for the management of oral disease in Sjögren's syndrome (SS).

Materials And Methods: MEDLINE , Embase, Scopus, and the Cochrane Library were searched for evidence on the use of immunobiologics for management of glandular disease in SS. Primary outcomes were xerostomia and salivary gland dysfunction, assessed via visual analogue scales, disease-specific scales for SS, measurement of salivary flow, ultrasound data, and quality of life measures.

Results: Seventeen studies (11 randomized controlled trials and 6 observational studies) met inclusion criteria. Rituximab showed efficacy in improving salivary gland function but not xerostomia. Abatacept showed promise in improving both xerostomia and salivary flow. Belimumab exhibited long-term improvement of salivary flow and subjective measures. The novel agent CFZ533 improved both disease activity and patient-reported indexes.

Conclusions: There is strong evidence pointing to the efficacy of rituximab in the management of oral disease in SS. Future controlled trials may elucidate the efficacy of belimumab and abatacept. The new drug CFZ533 is a promising alternative for the management of SS and its salivary gland involvement. In considering these agents, the promise of efficacy must be balanced against the harmful effects associated with biologic agents.
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http://dx.doi.org/10.1111/odi.13062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6544171PMC
June 2019

Persistent Pain and Gingival Swelling in a Middle-aged Woman.

JAMA Otolaryngol Head Neck Surg 2019 07;145(7):676-677

Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts.

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http://dx.doi.org/10.1001/jamaoto.2019.0606DOI Listing
July 2019

Oral Epithelial Dysplasia and Premalignancy.

Authors:
Sook-Bin Woo

Head Neck Pathol 2019 Sep 18;13(3):423-439. Epub 2019 Mar 18.

Harvard School of Dental Medicine, Boston, MA, USA.

Leukoplakia and erythroplakia are two entities under the moniker of "oral potentially malignant disorders" that are highly associated with the presence of oral epithelial dysplasia (OED) at first biopsy, while lesions of submucous fibrosis develop OED after being present for years. Importantly, traumatic/frictional keratoses are often mistaken clinically for leukoplakia and it is important for the pathologist to recognize and report them as such. The features of OED have been well-described and other architectural features will be discussed here, in particular verrucous and papillary architecture, bulky epithelial proliferation and epithelial atrophy. Proliferative leukoplakia, verrucous or otherwise, often show only hyperkeratosis in early lesions, with development of OED occurring over time, and squamous cell carcinoma developing in the majority of cases over time. The concept of hyperkeratosis without features of OED and that is not reactive, is likely a precursor to the dysplastic phenotype. Many cases of leukoplakia exhibiting OED are associated with a band of lymphocytes at the interface and these should not be mistaken for oral lichen planus.
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http://dx.doi.org/10.1007/s12105-019-01020-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6684678PMC
September 2019

Evaluation of a community-based dental screening program prior to radiotherapy for head and neck cancer: a single-center experience.

Support Care Cancer 2019 Sep 7;27(9):3331-3336. Epub 2019 Jan 7.

Division of Oral Medicine and Dentistry, Brigham and Women's Hospital, Boston, MA, USA.

Purpose: Oral toxicities following radiation therapy (RT) for head and neck (HN) cancer can be profound and are associated with poor health outcomes. The Division of Oral Medicine and Dentistry at Brigham and Women's Hospital and Dana-Farber Cancer Institute therefore implemented a dental evaluation program designed for community-based (CB) dentists to evaluate and treat patients scheduled for HN RT. The aim of this retrospective single-center cohort study was to assess the compliance of CB dentists with this pre-RT dental evaluation program.

Methods: A retrospective analysis of dental evaluations completed by CB dentists from December 2013 to December 2015 was performed. Descriptive statistics were used to determine compliance.

Results: A total of 186 dental evaluations were received. Compliance with completion of dental treatment was as follows: scaling and prophylaxis: 94.5% (172/182); dental restorations: 78.7% (48/61); endodontic therapy: 76.9% (10/13); and dental extractions: 76.9% (30/39). Compliance of CB dentists with all requested components of the pre-RT evaluation and treatment was 77.4% (144/186). The median distance traveled by patients to the CB dentist and to the hospital was 5.2 miles (range 0.03-66.0) and 46.5 miles (range 0.8-1457; p < 0.01), respectively.

Conclusion: In this study, the majority of patients completed their necessary dental treatment in a timely manner by their CB dentist in collaboration with an oral medicine specialist. Given the high compliance of CB dentists, this program could serve as a model for other cancer centers to optimize oral and dental health prior to RT.
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http://dx.doi.org/10.1007/s00520-018-4626-yDOI Listing
September 2019

Integrated genomic characterization of oral carcinomas in post-hematopoietic stem cell transplantation survivors.

Oral Oncol 2018 06 10;81:1-9. Epub 2018 Apr 10.

Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, USA.

Objectives: Secondary oral squamous cell carcinoma (OSCC) is a late complication in allogeneic hematopoietic stem cell transplantation (HSCT) patients, but little is known about long-term outcomes and prognostication. Additionally, molecular alterations and immunologic insights unique to this disease remain largely unexplored.

Methods: We present a cohort of 31 patients with post-HSCT OSCC and reported on clinicopathologic predictors of survival. Whole-exome sequencing was performed on 6 (19%) matched pairs of peripheral blood (post-conditioning, pre-HSCT) and tumor samples. The entire cohort had archival tumor available for immunoprofiling with PD-1/L1 immunohistochemistry.

Results: Five-year overall survival (OS) was 57% (95% CI: 46.1-69.8) with a median disease-free survival (DFS) of 13.3 months. Advanced initial staging, a buccal or oral tongue subsite, chronic oral graft-versus-host disease (GVHD) and smoking all negatively impacted survival. High tumor mutational burden (TMB) (median 11.3 vs. 5.0) and unique mutational signatures were noted between unrelated and related donor groups - with a strong correlation between infiltrating PD-1+ lymphocytes and TMB (R = 0.98, p < 0.01). Some differences were observed when comparing commonly mutated genes among our cohort and TCGA, with a predominance of TP53 events.

Conclusion: Survival outcomes appear similar in HSCT survivors with OSCC compared with non-HSCT OSCC populations. We identified somatic alterations in genes with therapeutic potential unique to this subpopulation of oral cancers.
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http://dx.doi.org/10.1016/j.oraloncology.2018.04.007DOI Listing
June 2018

Lipomas of the Oral Cavity: Utility of MDM2 and CDK4 in Avoiding Overdiagnosis as Atypical Lipomatous Tumor.

Head Neck Pathol 2019 Jun 10;13(2):169-176. Epub 2018 May 10.

Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA, USA.

Traumatized lipomas with degenerative change may demonstrate histopathologic features that mimic atypical lipomatous tumor (ALT). Previously reported series of ALT involving the oral cavity preceded routine use of MDM2 and CDK4 immunohistochemistry. Our aim is to evaluate MDM2 and CDK4 immunohistochemical expression in adipocytic tumors arising in this site, in conjunction with the histiocytic marker PU.1, to determine whether MDM2 and CDK4 impacts classification. 17 cases originally diagnosed as ALT were retrieved and immunohistochemical studies for MDM2, CDK4 and PU.1 were performed. FISH analysis for MDM2 amplification was performed in select cases. For this study group, the male:female ratio was 9:8 and the median age was 62 (range 41-88). All 17 cases presented as well- or predominantly well-circumscribed proliferations of variably sized, mature adipocytes exhibiting uni- or multi-vacuolation with occasional scalloped nuclei and mild nuclear atypia. Variable amounts of fibrous stroma with focal myxoid change and bland spindle cells were identified in 14/17 cases. Lipoblasts or atypical hyperchromatic stromal cells were not identified in any cases. 14 of 17 cases were negative for MDM2 and CDK4 in tumor cells and 11 of these 14 showed weak nuclear positivity for MDM2 in histiocytes. 3 of 17 cases showed weak, multifocal immunohistochemical expression of MDM2 and CDK4. PU.1 highlighted histiocytes in all 17 cases. FISH analysis for MDM2 amplification was negative in all 3 cases with weak MDM2/CDK4 expression. All cases were reclassified as lipoma with degenerative changes. ALT, in all likelihood, is less common than previously thought in this anatomic location and best diagnosed with ancillary studies. MDM2 expression in histiocytes is best interpreted in conjunction with CDK4 immunohistochemistry and confirmatory FISH for MDM2 amplification.
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http://dx.doi.org/10.1007/s12105-018-0928-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6513928PMC
June 2019

Primordial odontogenic tumour: report of two cases.

Histopathology 2018 Jun 15;72(7):1221-1227. Epub 2018 Mar 15.

Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA, USA.

Aims: Primordial odontogenic tumour (POT) is a rare mixed odontogenic neoplasm that is composed of primitive ectomesenchyme resembling dental papilla, surfaced by odontogenic epithelium resembling inner enamel epithelium, without hard tissue formation. Most reported cases have presented in the posterior mandible as a well-demarcated radiolucency associated with an unerupted tooth in the first two decades of life. The aim of this report is to describe the clinicopathological features of two more cases of POT.

Methods And Results: Each presented as an asymptomatic well-delineated radiolucency in the mandible in a 15-year-old female and an 18-year-old male, respectively. Both tumours were composed of a proliferation of plump spindle and stellate cells in delicately collagenous and myxoid stroma, surfaced by columnar-squamous epithelial cells with reverse nuclear polarisation at the tumour periphery. In one case, the formation of abortive tooth germ-like structures was noted. This has not been reported previously and supports the hypothesis of the primordial nature of this tumour. Both patients showed no recurrence at 3- and 20-month follow-up, respectively.

Conclusion: This report describes two additional cases of POT for a total of 11 cases reported in the English language literature.
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http://dx.doi.org/10.1111/his.13488DOI Listing
June 2018

A well-circumscribed lobulated tumor on the hard palatal mucosa in a child.

Oral Surg Oral Med Oral Pathol Oral Radiol 2019 Jan 11;127(1):3-7. Epub 2017 Dec 11.

Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, Massachussetts, USA. Electronic address:

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http://dx.doi.org/10.1016/j.oooo.2017.12.002DOI Listing
January 2019

Oral health status and risk of bacteremia following allogeneic hematopoietic cell transplantation.

Oral Surg Oral Med Oral Pathol Oral Radiol 2017 Sep 16;124(3):253-260. Epub 2017 Jun 16.

Division of Oral Medicine and Dentistry, Brigham and Women's Hospital, Boston, MA, USA; Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA, USA.

Objectives: The aim of this study was to evaluate the impact of oral health status on bacteremia risk in a cohort of patients with acute myeloid leukemia (AML) who underwent chemotherapy followed by myeloablative allogeneic hematopoietic cell transplantation (allo-HCT).

Study Design: A retrospective study was conducted in patients with AML from 2007 to 2011. Oral health status was determined from a pre-allo-HCT dental evaluation. Positive blood cultures were recorded from AML induction to post-allo-HCT day +60. Organisms that caused bacteremia were classified as "of possible oral source" by a blinded microbiologist. Two-sided Fisher's exact test was used to compare the oral health status of the entire cohort with that of patients with blood cultures of potential oral source.

Results: Pre-allo-HCT dental evaluations were completed in 91 (99%) of 92 patients. Of these 91 patients, 13 (14%) with dental pathology (13 of 13 [100%]) completed all required dental treatment before allo-HCT. Bacteremias occurred in 63 of 92 patients (68%), and 12 (19%) of 63 patients had positive blood cultures of potential oral source. Of these, 1 of 12 patients developed bacteremia during AML induction, and 11 of 12 developed bacteremia during allo-HCT.

Conclusions: Oral health status was not associated with risk of bacteremia of potential oral source either at AML induction or consolidation or at allo-HCT.
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http://dx.doi.org/10.1016/j.oooo.2017.06.003DOI Listing
September 2017

HPV-16 in a distinct subset of oral epithelial dysplasia.

Mod Pathol 2017 12 11;30(12):1646-1654. Epub 2017 Aug 11.

Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA, USA.

Human papillomavirus (HPV) 16 is the most common high-risk HPV type identified in oropharyngeal and cervical neoplasia. Recently, HPV-associated oral epithelial dysplasia with specific histopathologic features and demographics similar to HPV-oropharyngeal carcinoma has been identified. The objective of this study was to evaluate histopathologically all cases of HPV-oral epithelial dysplasia seen in one center and identify HPV types in a subset of cases. Cases with specific histopathology for HPV-oral epithelial dysplasia that were positive both by immunohistochemical studies for p16 and by in situ hybridization for high-risk types of HPV were further analyzed using QIAamp DNA Tissue Kits (Qiagen, Hilden, Germany). DNA was extracted, amplified, and digested with restriction enzymes and run on a polyacrylamide gel. Digestion patterns were visually compared with a database of known HPV digestion patterns for identification. There were 53 specimens included in the analysis. There were 47 males and six females (7.8:1), with a median age of 55 years (range 41-81). The most common site of involvement was the tongue/floor of mouth (77% of cases). Of the 53 cases, 94% exhibited parakeratosis and/or hyperkeratosis. All the cases featured karyorrhexis, apoptosis, and characteristics of conventional carcinoma in situ. The quantity of DNA extracted was sufficient for analysis in 22 cases. HPV-16 was identified in 20/22 (91%) cases. One case was associated with HPV-33 and one with HPV-58 (5% each). Eight of the 53 cases (15%) were associated with invasive squamous cell carcinomas.
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http://dx.doi.org/10.1038/modpathol.2017.71DOI Listing
December 2017

Biological significance of 5-hydroxymethylcytosine in oral epithelial dysplasia and oral squamous cell carcinoma.

Oral Surg Oral Med Oral Pathol Oral Radiol 2018 Jan 16;125(1):59-73.e2. Epub 2017 Jun 16.

Department of Oral Medicine and Dentistry, Brigham and Women's Hospital, Harvard School of Dental Medicine, Boston, MA, USA. Electronic address:

Objectives: The aim of this study was to determine the levels of 5-hydroxylmethylcytosine (5-hmC) in oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC) compared with those in benign, reactive inflammatory lesions and to explore whether DNA hydroxymethylation may serve as a novel biomarker for early diagnosis and prognosis of OSCC.

Study Design: The study included normal mucosa from uninvolved margins of 9 fibromas, 10 oral lichen planus, 15 OED, and 23 OSCC. Cultured human keratinocyte lines from benign oral mucosa, OED, and OSCC, as well as a murine model in which OSCC was induced with 4-nitroquinoline-1-oxide, were also evaluated.

Results: Progressive loss of 5-hmC from benign oral mucosal lesions to OED and OSCC was documented in patient samples. Decreased levels in 5-hmC that typify OED and OSCC were also detectable in human cell lines. Moreover, we characterized similar alterations in 5-hmC in an animal model of OED/OSCC.

Conclusions: This study demonstrated that 5-hmC distinguishes OED and OSCC from benign lesions with high sensitivity and specificity. Consequently, loss of 5-hmC may be useful for the diagnosis of OED with potential implications for therapy of OSCC.
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http://dx.doi.org/10.1016/j.oooo.2017.06.006DOI Listing
January 2018

Topical Clonazepam Solution for the Management of Burning Mouth Syndrome: A Retrospective Study.

J Oral Facial Pain Headache 2017 Summer;31(3):257-263

Aims: To evaluate and compare the effectiveness of two concentrations of topical clonazepam solution in improving symptoms of burning mouth syndrome (BMS).

Methods: A retrospective chart review was conducted of patients diagnosed with BMS and managed with topical clonazepam solution between 2008 and 2015. A 0.5-mg/mL solution was prescribed until 2012, when this was changed to a 0.1 mg/mL solution. Patients were instructed to swish with 5 mL for 5 minutes and spit two to four times daily. The efficacies of the two concentrations were compared using patient-reported outcome measures at the first follow-up, including the reported percentage of improvement in burning symptoms and the change in burning severity from baseline ranked on an 11-point numeric rating scale (NRS). Response to treatment was compared between the two concentrations using Wilcoxon rank sum test.

Results: A total of 57 subjects were included, 32 in the 0.1-mg/mL cohort and 25 in the 0.5-mg/mL cohort, and evaluated at a median follow-up of 7 weeks. The median overall percentage improvement was 32.5% in the 0.1-mg/mL cohort and 75% in the 0.5-mg/mL cohort. The median reduction in NRS score was 0.5 points in the 0.1-mg/mL cohort and 6 points in the 0.5-mg/mL cohort. The use of either outcome measure revealed that the response to treatment with the 0.5-mg/mL solution was superior to that of the 0.1 mg/mL solution (P < .01).

Conclusion: These findings suggest that a 0.5-mg/mL topical clonazepam solution is effective in the management of BMS. Future randomized clinical trials are warranted.
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http://dx.doi.org/10.11607/ofph.1754DOI Listing
November 2017

Safety and tolerability of topical clonazepam solution for management of oral dysesthesia.

Oral Surg Oral Med Oral Pathol Oral Radiol 2017 Aug 11;124(2):146-151. Epub 2017 May 11.

Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA, USA; Division of Oral Medicine and Dentistry, Brigham and Women's Hospital, Boston, MA, USA.

Objectives: The aim of the study was to determine the absolute and relative safety of treatment with 2 concentrations of topical clonazepam solution (0.1 mg/mL, 0.5 mg/mL) for management of oral dysesthesia.

Study Design: The study was a retrospective chart review of patients diagnosed with oral dysesthesia and managed with topical clonazepam solution (swish and spit) between 2008 and 2015. The relative safety of the 2 concentrations was evaluated in terms of occurrence of adverse drug reactions (ADRs) and occurrence of change to treatment plan secondary to ADRs.

Results: For the study, 162 patients were included-84 patients in the 0.1 mg/mL cohort and 78 in the 0.5 mg/mL cohort, who were evaluated for a median follow-up period of 6 weeks. Thirty-eight (23%) patients developed ADRs. The most frequently reported ADR was sedation (62% of ADRs), followed by altered mental status and dizziness (7% each). Dose adjustments were required in 9 patients (6%) and treatment discontinuation in 13 (8%). ADRs were more frequently reported in the 0.5 mg/mL cohort, but no significant difference was found in terms of occurrence of ADRs, change to treatment plan secondary to ADRs, or types of ADRs (P > .05).

Conclusions: Treatment with topical clonazepam solution in either 0.5 mg/mL or 0.1 mg/mL concentration appears to be safe and well-tolerated. Future prospective studies are needed to confirm this finding.
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http://dx.doi.org/10.1016/j.oooo.2017.05.470DOI Listing
August 2017

An asymptomatic diffuse palatal mass.

Oral Surg Oral Med Oral Pathol Oral Radiol 2018 09 14;126(3):208-213. Epub 2017 Mar 14.

Division of Oral Medicine and Dentistry, Brigham and Women's Hospital, Boston, MA, USA; Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA, USA.

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http://dx.doi.org/10.1016/j.oooo.2017.03.005DOI Listing
September 2018

Intraoral Salivary Duct Cyst: Clinical and Histopathologic Features of 177 Cases.

Head Neck Pathol 2017 Dec 27;11(4):469-476. Epub 2017 Mar 27.

Center for Oral Pathology, StrataDx Inc., Lexington, MA, 02421, USA.

The salivary duct cyst (SDC) is a reactive ductal ectasia most frequently seen in major salivary glands, and likely caused by obstruction. The aim of this study is to define the clinical and histopathologic spectrum of intraoral SDCs. Cases were retrieved from the archives of Harvard School of Dental Medicine/StrataDx, Inc. from January 2012 to August 2014. There were 177 cases of which 103 (58.2%) occurred in females, with a median age of 56 (range 2-95). Approximately half of cases (45.8%) presented in the area of the buccal mucosa, lower lip mucosa, or mandibular vestibule, and 23.2% presented in the floor of mouth. SDCs were lined at least focally by 1-2 layers of cuboidal/columnar epithelium in 85.3% of cases and showed varying degrees of metaplasia (oncocytic, mucous cell, squamous, ciliated, apocrine-like) in 68.4% of cases. Intraluminal mucous stasis was present in 41.8% of SDCs, incipient calcification was present within 4.5% of SDCs, and chronic obstructive sialadenitis was seen in 90.2% of cases. No cysts showed adenomatous ductal proliferations or true papillary structures with fibrovascular cores, although 41.2% exhibited reactive undulation of cyst lining. Thirty-nine 'papillary oncocytic cystadenoma-like' SDCs (22.0%) demonstrated complete oncocytic metaplasia and marked undulation. An additional seven such cysts (4.0%) had a 'Warthin tumor-like' lymphoplasmacytic infiltrate. Intraoral SDCs occur most commonly in the sixth decade of life in locations distinct from extravasation mucoceles, likely secondary to intraluminal obstruction. SDCs show diverse histopathology and certain phenotypic variants may be mistaken for papillary oncocytic cystadenoma or Warthin tumor.
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http://dx.doi.org/10.1007/s12105-017-0810-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5677068PMC
December 2017