Salivary gland carcinosarcoma ex pleomorphic adenoma; a case report with molecular characterization.

True malignant mixed tumors, also known as salivary gland carcinosarcoma (SCS), are uncommon yet highly aggressive lesions associated with a poor prognosis. These tumors exhibit a distinctive biphasic structure characterized by both epithelial and mesenchymal components. Recent research has shown that the majority of SCS cases stem from pre-existing pleomorphic adenomas (PAs), suggesting a stepwise developmental pattern. In this report, we present a case of a 73-year-old female with SCS and describe the clinical, radiographic, and pathologic observations. Notably, the SCS was associated with a residual PA. The SCS displayed a CTNNB1::PLAG1 gene rearrangement, providing a molecular basis for its origin from the PA. Further DNA genomic analysis exposed mutations in BAP1, PER1, and LRPB1. Our findings provide support to the theory that SCS emerges from a pre-existing PA while highlighting the multiple genetic changes that could contribute to malignant transformation.

Fungal Otitis Externa (Otomycosis) Associated with Aspergillus Flavus: A Case Image.

A 48-year-old man presented with a chief complaint of intermittent right ear otorrhea of several-month duration, occasional otalgia and progressive unilateral hearing impairment. He also reported frequent episodes of headache and pressure in the sinuses and maxilla. Previous systemic treatment with antibiotics failed to alleviate the symptoms. A head/neck CT showed completely normal mastoid, middle ear and external auditory canal regions without any evidence of opacification or bone erosion. Otoscopic examination of the right ear disclosed aggregates of dried, brown, fibrillar material and debris occluding the external auditory canal and obstructing the otherwise intact tympanic membrane. Dilation of the external auditory canal or thickening of the tympanic membrane were not appreciated. The canal was debrided and the fibrillar material was placed in formalin. Histopathologic examination revealed numerous branching, septated fungal hyphae organized in densely-packed clusters. In other areas, the fungal hyphae abutted or were attached to lamellated collections of orthokeratin. As highlighted by GMS staining, the fungi were morphologically compatible with Aspergillus species. The clinicopathologic findings supported a diagnosis of fungal otitis externa, while the numerous anucleate squamous cells were compatible with colonization of an underlying, probably developing, cholesteatoma. Culture of material isolated from the external auditory canal confirmed the presence of Aspergillus flavus. In this illustrative case, we present the main clinical and microscopic characteristics of Aspergillus-related otomycosis developing in the setting of a tautochronous cholesteatoma.

Pearls and pitfalls in the diagnosis of small oral biopsies.

Pathologic processes affecting the oral and maxillofacial region include a heterogenous group of diseases with widely variable biologic behaviors. Proper patient management begins with the establishment of an accurate diagnosis, which often relies on histopathologic interpretation of small tissue samples from oral lesions. While confident diagnosis of small oral biopsies can be challenging, an understanding of oral and maxillofacial disease and consistent clinicopathologic correlation can help pathologists recognize inflammatory confounders and overcome common errors in specimen management, including insufficient sample size and non-representative biopsy samples.

Microsecretory Adenocarcinoma of Salivary Glands: An Expanded Series of 24 Cases.

Microsecretory adenocarcinoma (MSA) is a recently described salivary gland tumor with a characteristic histologic and immunophenotypic profile and recurrent MEF2C-SS18 fusions. Because only six cases of MSA have been published, its complete clinicopathologic spectrum is unclear, and its biologic behavior has not been documented. Here, we present an updated and expanded experience of 24 MSA cases. All cases of MSA were obtained from the authors' files. Immunohistochemistry for S100, SOX10, p63, p40, SMA, calponin, and mammaglobin was performed. Molecular analysis was performed by targeted RNA sequencing, SS18 break apart fluorescence in situ hybridization, and/or reverse transcriptase polymerase chain reaction for MEF2C-SS18 fusion. Clinical follow-up was obtained from medical records. A total of 24 MSA cases were collected, from 13 women and 11 men, ranging from 17 to 83 years (mean 49.5 years). The vast majority (23 of 24) arose in the oral cavity, with the palate (n = 14) and buccal mucosa (n = 6) as the most frequent subsites. Tumors showed consistent histologic features including: (1) microcystic tubules, (2) flattened intercalated duct-like cells, (3) monotonous oval hyperchromatic nuclei, (4) abundant basophilic luminal secretions, (5) fibromyxoid stroma, and (6) circumscribed borders with subtle infiltration. The tumors were very consistently positive for S100 (24 of 24), p63 (24 of 24), and SOX10 (14 of 14) and negative for p40 (0 of 21), calponin (0 of 12) and mammaglobin (0 of 16), while SMA (4 of 20) was variable. MEF2C-SS18 fusion was demonstrated in 21 of 24 cases; in the remaining 3 cases with insufficient RNA, SS18 break apart FISH was positive. Treatment information was available in 17 cases, all of which were managed with surgery only. In 14 cases with follow-up (1-216 months, mean 30), no cases recurred or metastasized. MSA is a distinct salivary gland neoplasm with remarkably consistent clinical, histologic, immunophenotypic, and genetic features that generally behaves in an indolent manner following surgery alone. These observations solidify MSA as a unique, low-grade salivary gland carcinoma that warrants inclusion in the next version of the WHO classification of head and neck tumors.

Unique Oral Presentations of Deep Fungal Infections: A Report of Four Cases.

Deep fungal infections rarely involve the oral cavity and most commonly affect immunocompromised patients. Oral deep fungal infections typically manifest as chronic mucosal ulcerations or granular soft tissue overgrowths. Since these lesions are non-specific and can mimic malignancy, it is crucial to obtain a thorough clinical history and an adequate biopsy to render the appropriate diagnosis. We report four new cases of deep fungal infections, diagnosed as histoplasmosis, blastomycosis and chromoblastomycosis, exhibiting unique oral and perioral presentations. Awareness of these unusual entities can help dental and medical practitioners expedite proper multidisciplinary care and minimize morbidity and mortality.

Expression of cornulin in oral premalignant lesions.

OBJECTIVE: The aim of this study was to evaluate expression of cornulin in oral mucosa as an adjunct to histopathologic grading of oral epithelial dysplasia (OED). STUDY DESIGN: Biomarker expression was assessed in normal oral mucosa, low-grade OED (LD), high-grade OED (HD), and oral squamous cell carcinoma (OSCC) by using immunohistochemistry. Photomicrographs were evaluated with Aperio Imagescope using a positive-pixel-counting algorithm. A histo-score (H-score) was calculated on the basis of staining intensity and the percentage of positive cells (%-staining). Intrarater reliability for H-score and %-staining was determined by calculating interclass correlation coefficients. Mean differences in H-scores and %-percent staining values were each analyzed by using an analysis of variance and Tukey's post hoc procedure. RESULTS: Cornulin expression progressively diminished with increasing grades of dysplasia and OSCC. Interclass correlation coefficients for H-score and %-staining were each greater than 0.99. Except for OSCC versus HD, all other pairwise comparisons were statistically significant (P < .0001) for H-score and %-staining. CONCLUSIONS: Cornulin expression helped differentiate between low-grade and high-grade oral epithelial dysplasia, making it a potential adjunct for grading oral OEDs and a potential biomarker for risk of lesion progression. Longitudinal studies evaluating risk stratification based on cornulin expression may be warranted.

Erythematous and Vascular Oral Mucosal Lesions: A Clinicopathologic Review of Red Entities.

Erythematous lesions of the oral mucosa are common and can reflect a variety of conditions, ranging from benign reactive or immunologically-mediated disorders to malignant disease. Together with vascular abnormalities, which can vary from reddish to bluish-purple in color, the differential diagnosis for erythematous oral mucosal change is quite diverse. This review focuses on salient clinical features and histopathologic findings of selected conditions which clinically present as red or vascular-like oral mucosal alterations, including oral vascular malformations and neoplasms, pyogenic granuloma, localized juvenile spongiotic gingival hyperplasia, denture stomatitis, benign migratory glossitis (geographic tongue), orofacial granulomatosis, granulomatosis with polyangiitis (Wegener granulomatosis), megaloblastic anemia, and erythroplakia. Recognition of the characteristic clinical features of these conditions, in conjunction with thorough patient history, will allow clinicians to narrow the differential diagnosis and guide appropriate clinical decision making, including the need for tissue biopsy, in order to complete the diagnostic process and initiate optimal patient care.

Non-calcifying Langerhans Cell-Rich Variant of Calcifying Epithelial Odontogenic Tumor: A Distinct Entity with Predilection for Anterior Maxilla.

Calcifying epithelial odontogenic tumor (CEOT) is an uncommon locally invasive epithelial odontogenic tumor of the jaws associated with amyloid production. Intraosseous presentations are most common and they frequently occur in the posterior mandible. A non-calcifying Langerhans cell-rich variant of CEOT (NCLC CEOT) has been described with predilection for the anterior maxilla. Interestingly, all reported cases of NCLC CEOT have occurred in Asian population. We present a case of a 43-year old Caucasian female with a large radiolucent lesion involving the left anterior maxilla with histologic features of NCLC CEOT. This is the first reported case of this rare variant of CEOT in a Caucasian individual.

Adjuncts for the evaluation of potentially malignant disorders in the oral cavity: Diagnostic test accuracy systematic review and meta-analysis-a report of the American Dental Association.

BACKGROUND: Oral squamous cell carcinoma is the most common manifestation of malignancy in the oral cavity. Adjuncts are available for clinicians to evaluate lesions that seem potentially malignant. In this systematic review, the authors summarized the available evidence on patient-important outcomes, diagnostic test accuracy (DTA), and patients' values and preferences (PVPs) when using adjuncts for the evaluation of clinically evident lesions in the oral cavity. TYPES OF STUDIES REVIEWED: The authors searched for preexisting systematic reviews and assessed their quality using the Assessing the Methodological Quality of Systematic Reviews tool. The authors updated the selected reviews and searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials and DTA and PVPs studies. Pairs of reviewers independently conducted study selection, data extraction, and assessment of the certainty in the evidence by using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: The authors identified 4 existing reviews. DTA reviews included 37 studies. The authors retrieved 7,534 records, of which 9 DTA and 10 PVPs studies were eligible. Pooled sensitivity and specificity of adjuncts ranged from 0.39 to 0.96 for the evaluation of innocuous lesions and from 0.31 to 0.95 for the evaluation of suspicious lesions. Cytologic testing used in suspicious lesions appears to have the highest accuracy among adjuncts (sensitivity, 0.92; 95% confidence interval, 0.86 to 0.98; specificity, 0.94; 95% confidence interval, 0.88 to 0.99; low-quality evidence). CONCLUSIONS AND PRACTICAL IMPLICATIONS: Cytologic testing appears to be the most accurate adjunct among those included in this review. The main concerns are the high rate of false-positive results and serious issues of risk of bias and indirectness of the evidence. Clinicians should remain skeptical about the potential benefit of any adjunct in clinical practice.

Evidence-based clinical practice guideline for the evaluation of potentially malignant disorders in the oral cavity: A report of the American Dental Association.

BACKGROUND: An expert panel convened by the American Dental Association (ADA) Council on Scientific Affairs and the Center for Evidence-Based Dentistry conducted a systematic review and formulated clinical recommendations to inform primary care clinicians about the potential use of adjuncts as triage tools for the evaluation of lesions, including potentially malignant disorders (PMDs), in the oral cavity. TYPES OF STUDIES REVIEWED: This is an update of the ADA's 2010 recommendations on the early diagnosis of PMDs and oral squamous cell carcinoma. The authors conducted a systematic search of the literature in MEDLINE and Embase via Ovid and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials and diagnostic test accuracy studies. The authors used the Grading of Recommendations Assessment, Development and Evaluation approach to assess the certainty in the evidence and to move from the evidence to the decisions. RESULTS: The panel formulated 1 good practice statement and 6 clinical recommendations that concluded that no available adjuncts demonstrated sufficient diagnostic test accuracy to support their routine use as triage tools during the evaluation of lesions in the oral cavity. For patients seeking care for suspicious lesions, immediate performance of a biopsy or referral to a specialist remains the single most important recommendation for clinical practice. In exceptional cases, when patients decline a biopsy or live in rural areas with limited access to care, the panel suggested that cytologic testing may be used to initiate the diagnostic process until a biopsy can be performed (conditional recommendation, low-quality evidence). CONCLUSIONS AND PRACTICAL IMPLICATIONS: The authors urge clinicians to remain alert and take diligent action when they identify a PMD. The authors emphasize the need for counseling because patients may delay diagnosis because of anxiety and denial.

The prevalence of pseudoxanthoma elasticum-like connective tissue changes in an oral biopsy service and review of the literature.

OBJECTIVE: The objective of this pilot study is to determine the prevalence of pseudoxanthoma elasticum (PXE)-like connective changes in an oral biopsy service and compare it with the estimated prevalence of PXE as well as to the prevalence of the mutated PXE gene ABCC6. STUDY DESIGN: This prevalence study utilized 500 oral mucosal biopsy specimens received from the biopsy service of the Oral Pathology Consultants at the Ohio State University. Each specimen was microscopically evaluated using hematoxylin and eosin, Verhoeff-van Gieson and von Kossa stains. RESULTS: A prevalence of 9.8% was identified for PXE-like changes in the connective tissue of oral biopsy specimens submitted to this service. CONCLUSIONS: The overall prevalence of PXE-like connective tissue changes found in routine oral mucosal biopsy specimens (9.8%) was much higher than either the suspected prevalence of PXE (0.001%-0.004%) or the estimated prevalence of the mutated gene ABCC6 (0.625%-1.25%).

Oral atypical cellular blue nevus: an infiltrative melanocytic proliferation.

The atypical cellular blue nevus is an extremely rare nevomelanocytic lesion which lacks precise histologic characterization in the current literature. Given the potential for significant architectural and cytologic overlap with melanoma, further study, including molecular analysis, is needed. This is the first description of an atypical cellular blue nevus of the oral cavity.

The role of direct visual fluorescent examination (VELscope) in routine screening for potentially malignant oral mucosal lesions.

OBJECTIVE: Direct visual fluorescent examination (DVFE) is a proposed adjunct to conventional oral examination (COE). We evaluate the benefit of DVFE in screening for potentially malignant mucosal lesions in a general population of patients presenting for dental care. STUDY DESIGN: A total of 130 patients were evaluated by COE followed by DVFE. Areas clinically suspicious by COE or with positive DVFE (visual fluorescence loss [VFL]) underwent surgical biopsy. Association between COE and DVFE was assessed and compared with histopathology. RESULTS: A total of 42 subjects had one or more areas of VFL, yet histologic evidence of premalignancy/malignancy was only identified in a single individual. Further, one lesion negative by DVFE exhibited epithelial dysplasia. DVFE was statistically different from scalpel biopsy (P = .0001). No difference was found between COE and scalpel biopsy (P = 1.0). CONCLUSIONS: Results suggest that COE is more valid than DVFE at discriminating benign mucosal alterations from premalignancy and do not support use of DVFE as an oral cancer screening adjunct.

Evidence-based clinical recommendations regarding screening for oral squamous cell carcinomas.

BACKGROUND: This article presents evidence-based clinical recommendations developed by a panel convened by the American Dental Association Council on Scientific Affairs. This report addresses the potential benefits and potential risks of screening for oral squamous cell carcinomas and the use of adjunctive screening aids to visualize and detect potentially malignant and malignant oral lesions. TYPES OF STUDIES REVIEWED: The panel members conducted a systematic search of MEDLINE, identifying 332 systematic reviews and 1,499 recent clinical studies. They selected 5 systematic reviews and 4 clinical studies to use as a basis for developing recommendations. RESULTS: The panel concluded that screening by means of visual and tactile examination to detect potentially malignant and malignant lesions may result in detection of oral cancers at early stages of development, but that there is insufficient evidence to determine if screening alters disease-specific mortality in asymptomatic people seeking dental care. CLINICAL IMPLICATIONS: The panel suggested that clinicians remain alert for signs of potentially malignant lesions or early-stage cancers while performing routine visual and tactile examinations in all patients, but particularly in those who use tobacco or who consume alcohol heavily. Additional research regarding oral cancer screening and the use of adjuncts is needed.

Lymphomatoid granulomatosis presenting with gingival involvement in an immune competent elderly male.

Lymphomatoid granulomatosis (LYG) represents a B cell lymphoproliferative disorder that appears to be driven by infection of the lesional cells by Epstein-Barr virus (EBV). Although not a common condition, the overwhelming majority of cases affect the lungs and mediastinal lymph nodes. Oral mucosal involvement has been documented in only one other report. We describe an 82-year-old man who developed a chronic oral ulcer following extraction of a mandibular molar tooth. Biopsy of the ulcer identified large atypical mononuclear cells that had a B cell immunophenotype and were associated with the walls of several arterioles in the sample. In situ probes for EBV-encoded small RNA showed prominent labeling of these large cells, suggesting the possibility of LYG. Imaging studies identified mediastinal and hilar lymphadenopathy on CT imaging, while PET scans showed hypermetabolic activity in the lymph nodes as well as the left mandible. Based on these findings, a diagnosis of LYG was made and the patient was treated with rituximab, an anti-CD20 monoclonal antibody, combined with a chemotherapeutic regimen consisting of etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin. After three cycles of therapy, the oral ulcer resolved significantly, as well as the areas of hypermetabolic nodal activity. Remission continued for 3 years, however the patient eventually developed non-small cell carcinoma of the lung and expired as a result of that tumor.

Intraoral phaeohyphomycosis.

Phaeohyphomycosis is an infection caused by pigment-producing saprophytic fungi. Systemic infections may occur in the immunocompromised patient. Infection in healthy individuals may result in subcutaneous abscess formation. Oral lesions appear to be rare. A case of intraoral phaeohyphomycosis presenting as a well-demarcated, painful nodule of the anterior hard palate in a 12-year-old healthy male is described. The mass was excised and the diagnosis was established following histopathologic examination of the tissue.

Managing the care of patients receiving antiresorptive therapy for prevention and treatment of osteoporosis: executive summary of recommendations from the American Dental Association Council on Scientific Affairs.

BACKGROUND: This narrative review of osteonecrosis of the jaw in patients with low bone mass receiving treatment with antiresorptive agents is based on an appraisal of the literature by an advisory committee of the American Dental Association Council on Scientific Affairs. It updates the committee's 2008 advisory statement. METHODS: The authors searched MEDLINE for literature published between May 2008 (the end date of the last search) and February 2011. RESULTS: This report contains recommendations based on the findings of the literature search and on expert opinion that relate to general dentistry; periodontal disease management; implant placement and maintenance; oral and maxillofacial surgery; endodontics; restorative dentistry and prosthodontics; orthodontics; and C-terminal telopeptide testing and drug holidays. CONCLUSIONS: The highest reliable estimate of antiresorptive agent-induced osteonecrosis of the jaw (ARONJ) prevalence is approximately 0.10 percent. Osteoporosis is responsible for considerable morbidity and mortality. Therefore, the benefit provided by antiresorptive therapy outweighs the low risk of developing osteonecrosis of the jaw. CLINICAL IMPLICATIONS: An oral health program consisting of sound hygiene practices and regular dental care may be the optimal approach for lowering ARONJ risk. No validated diagnostic technique exists to determine which patients are at increased risk of developing ARONJ. Discontinuing bisphosphonate therapy may not lower the risk but may have a negative effect on low-bone-mass-treatment outcomes.