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.

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.

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.

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.

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.

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.

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.

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.

Critical evaluation of diagnostic aids for the detection of oral cancer.

Historically, the screening of patients for signs of oral cancer and precancerous lesions has relied upon the conventional oral examination. A variety of commercial diagnostic aids and adjunctive techniques are available to potentially assist in the screening of healthy patients for evidence of otherwise occult cancerous change or to assess the biologic potential of clinically abnormal mucosal lesions. This manuscript systematically and critically examines the literature associated with current oral cancer screening and case-finding aids or adjuncts such as toluidine blue, brush cytology, tissue reflectance and autofluorescence. The characteristics of an ideal screening test are outlined and the authors pose several questions for clinicians and scientists to consider in the evaluation of current and future studies of oral cancer detection and diagnosis. Although the increased public awareness of oral cancer made possible by the marketing of recently-introduced screening adjuncts is commendable, the tantalizing implication that such technologies may improve detection of oral cancers and precancers beyond conventional oral examination alone has yet to be rigorously confirmed.

Oral mucosal melanoma with unusual clinicopathologic features.

Oral mucosal melanoma (OMM) is an extremely rare malignancy, accounting for < 0.5% of all melanomas and all oral malignancies. The rarity of OMM, the heterogeneity in clinical and histopathologic appearances, and the paucity of molecular and genetic studies to date have limited our knowledge of the etiopathogenesis of these cancers. A 39-year-old Hispanic male presented for evaluation of a large, pigmented, plaque-like and nodular growth of the maxillary gingival and palatal mucosa. On presentation, a presumptive clinical diagnosis of mucosal melanoma was made, which was confirmed by incisional biopsy with subsequent histopathologic evaluation. Macroscopically, the morphology and highly pigmented nature of the tumor was suggestive of a rarer subtype of melanoma known as animal-type melanoma, also referred to as pigmented epithelioid melanocytoma. However, microscopically, the tumor showed histopathologic features consistent with a high-grade acral (mucosal) lentiginous melanoma with overt cytomorphologic features of malignancy in addition to showing prominent pigment synthesis resembling animal-type melanoma. A detailed search of the literature did not identify a previous report of OMM with prominent pigment synthesis resembling animal-type melanoma. Identification of melanoma subtypes has specific implications for therapeutic approach, and thus their recognition is important to successful patient management.

Verruciform xanthoma: immunohistochemical characterization of xanthoma cell phenotypes.

BACKGROUND: Verruciform xanthoma (VX) is a benign lesion that primarily affects the oral cavity, most frequently the gingiva. VX lesions are characterized by xanthoma cells (lipid-laden macrophages or foam cells) found in the superficial connective tissue. To characterize these foam cells further, immunohistochemical techniques were used to investigate the presence of macrophage subpopulations in oral lesions of VX. METHODS: Sixteen biopsy samples of VX lesions from the oral cavity (six from gingiva, three from palate, and seven from other mucosa) were studied. Immunohistochemical analysis was performed using antibody probes to macrophage subpopulations, including RM3/1 (reparative), 25F9 (resident), and 27E10 (inflammatory). The percentage of antibody-labeled foam cells was determined by visual counts of selected fields within lesional connective tissue. RESULTS: The proportion of VX lesions that demonstrated positive xanthoma cell reactivity with antibodies RM3/1, 25F9, and 27E10 was 100%, 88%, and 50%, respectively. Foam cells that stained positively with RM3/1, 25F9, and 27E10 represented 61.5% +/- 19.6%, 51.8% +/- 29.4%, and 10.9% +/- 14.7% of the counted cells, respectively. When results were analyzed based on anatomic location (gingiva, palate, and other mucosa), there was no difference in the percentage of positively stained cells by anatomic site for any of the three antibodies (P >0.05). Similarly, there were no differences between masticatory (gingiva and palate) and other mucosa (P >0.05). CONCLUSIONS: VX lesions contain primarily reparative and resident foam cells, with limited numbers of inflammatory macrophages, consistent with a chronic reactive process. These findings were independent of the anatomic site.

Diffuse pigmentation of maxillary attached gingiva: four cases of the cultural practice of gingival tattoo.

BACKGROUND: Gingival pigmentation is a common finding, may be of endogenous or exogenous origin, and can have diagnostic significance. Diffuse gingival pigmentation may be physiologic in nature or can be due to environmental factors, drugs, endocrine disorders, or genetic conditions. We present four cases of diffuse gingival pigmentation due to traditional gingival tattooing and review the literature on this practice. METHODS: Four black females (aged 19 to 56 years) of West African origin (Mauritania and Senegal), representing three different ethnic groups (Fulani, Mandinka, and Soninke) presented with various chief complaints. All exhibited diffuse pigmentation of the maxillary vestibular gingiva extending to the second premolar areas, without any associated radiographic abnormalities. The color ranged from intense blue gray to light gray or grayish pink. One case was biopsied for histopathologic evaluation. RESULTS: Questioning revealed that the women had had one or more sessions of traditional gingival tattooing. In one case, the procedure was performed in a dental office. The color range appeared to depend on the time that elapsed since the last procedure. The biopsy exhibited dense fibrous connective tissue containing aggregates of foreign material consistent with a foreign body tattoo. CONCLUSIONS: Gingival tattooing, a cultural practice prevalent in certain African ethnic groups, results in diffuse pigmentation. Outside of Africa, it may be misinterpreted as racial pigmentation or pose a diagnostic puzzle. The color and distribution pattern of diffuse gingival pigmentation often are quite suggestive, and the clinical diagnosis should be confirmed by patient history. In selected cases, biopsy may be necessary to exclude other diagnostic considerations.

Narrative [corrected] review: bisphosphonates and osteonecrosis of the jaws.

Osteonecrosis of the jaws is a recently described adverse side effect of bisphosphonate therapy. Patients with multiple myeloma and metastatic carcinoma to the skeleton who are receiving intravenous, nitrogen-containing bisphosphonates are at greatest risk for osteonecrosis of the jaws; these patients represent 94% of published cases. The mandible is more commonly affected than the maxilla (2:1 ratio), and 60% of cases are preceded by a dental surgical procedure. Oversuppression of bone turnover is probably the primary mechanism for the development of this condition, although there may be contributing comorbid factors. All sites of potential jaw infection should be eliminated before bisphosphonate therapy is initiated in these patients to reduce the necessity of subsequent dentoalveolar surgery. Conservative débridement of necrotic bone, pain control, infection management, use of antimicrobial oral rinses, and withdrawal of bisphosphonates are preferable to aggressive surgical measures for treating this condition. The degree of risk for osteonecrosis in patients taking oral bisphosphonates, such as alendronate, for osteoporosis is uncertain and warrants careful monitoring.

Diagnosis and management of oral lichen planus.

Oral lichen planus is a relatively common mucosal autoimmune disease that may be initially detected and diagnosed in the dental office. For asymptomatic patients, clinical characteristics including a generalized involvement of the oral mucosa are often sufficient to establish a working diagnosis. Symptomatic presentations of oral lichen planus, however, can mimic a variety of other potentially serious conditions and scalpel biopsy is recommended to determine an accurate diagnosis. Treatment strategies for the symptomatic patient are discussed.

AAOMP case challenge: a pigmented lesion of the mandibular facial gingiva.

A 55-year-old white male was referred by his dermatologist for evaluation of an asymptomatic dark brown lesion on the mandibular facial attached gingiva.

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.