Generative Adversarial Networks in Digital Histopathology: Current Applications, Limitations, Ethical Considerations, and Future Directions.

Generative adversarial networks (GANs) have gained significant attention in the field of image synthesis, particularly in computer vision. GANs consist of a generative model and a discriminative model trained in an adversarial setting to generate realistic and novel data. In the context of image synthesis, the generator produces synthetic images, whereas the discriminator determines their authenticity by comparing them with real examples. Through iterative training, the generator allows the creation of images that are indistinguishable from real ones, leading to high-quality image generation. Considering their success in computer vision, GANs hold great potential for medical diagnostic applications. In the medical field, GANs can generate images of rare diseases, aid in learning, and be used as visualization tools. GANs can leverage unlabeled medical images, which are large in size, numerous in quantity, and challenging to annotate manually. GANs have demonstrated remarkable capabilities in image synthesis and have the potential to significantly impact digital histopathology. This review article focuses on the emerging use of GANs in digital histopathology, examining their applications and potential challenges. Histopathology plays a crucial role in disease diagnosis, and GANs can contribute by generating realistic microscopic images. However, ethical considerations arise because of the reliance on synthetic or pseudogenerated images. Therefore, the manuscript also explores the current limitations and highlights the ethical considerations associated with the use of this technology. In conclusion, digital histopathology has seen an emerging use of GANs for image enhancement, such as color (stain) normalization, virtual staining, and ink/marker removal. GANs offer significant potential in transforming digital pathology when applied to specific and narrow tasks (preprocessing enhancements). Evaluating data quality, addressing biases, protecting privacy, ensuring accountability and transparency, and developing regulation are imperative to ensure the ethical application of GANs.

Oral squamous cell carcinoma: early detection and improved 5-year survival in 102 patients.

The 5-year survival rate for oral cancer remains poor, as a significant number of patients present with advanced disease at the time of diagnosis. The need remains for early detection within the context of routine oral examinations and evaluation of any noted clinical abnormalities. This retrospective study analyzed patient demographics, lesion characteristics, and 5-year survival rates associated with oral squamous cell carcinoma (OSCC) that was initially assessed using computer-assisted, 3-dimensional analysis of a transepithelial oral brush biopsy. Patients with oral lesions were initially assessed by community-based dentists and physicians using an oral brush biopsy. In 102 patients, OSCC was subsequently confirmed by incisional biopsy and histopathologic analysis. The majority of patients were without traditional risk factors. Almost half of the cancers presented as white lesions, and one-third presented as lesions smaller than 5 mm. In about three-fourths of all cases, OSCC initially presented without pain or bleeding. The overall 5-year survival rate for all patients was approximately 94%. Despite barriers to early detection, identification of early, asymptomatic OSCC with innocuous-appearing clinical features is achievable. This earlier detection can be expected to lead to a marked improvement in overall survival patterns.

Oral mucosal precancer and cancer: A helpful discriminating clinical tool.

The authors have collaborated with many colleagues in several countries in formulating a useful and practical clinical tool for evaluating oral mucosal findings on routine examination. Consideration of several factors including history, evolution of positive findings and clinical information allows placement of examination results into one of three categories which are graded by a color scheme along a spectrum of concerns (green to red, or no concern to serious concern). Afforded to the clinician is a straightforward grading system as a starting point for office end clinic use for all patients.

An Update on the Use of Artificial Intelligence in Digital Pathology for Oral Epithelial Dysplasia Research.

INTRODUCTION: Oral epithelial dysplasia (OED) is a precancerous histopathological finding which is considered the most important prognostic indicator for determining the risk of malignant transformation into oral squamous cell carcinoma (OSCC). The gold standard for diagnosis and grading of OED is through histopathological examination, which is subject to inter- and intra-observer variability, impacting accurate diagnosis and prognosis. The aim of this review article is to examine the current advances in digital pathology for artificial intelligence (AI) applications used for OED diagnosis. MATERIALS AND METHODS: We included studies that used AI for diagnosis, grading, or prognosis of OED on histopathology images or intraoral clinical images. Studies utilizing imaging modalities other than routine light microscopy (e.g., scanning electron microscopy), or immunohistochemistry-stained histology slides, or immunofluorescence were excluded from the study. Studies not focusing on oral dysplasia grading and diagnosis, e.g., to discriminate OSCC from normal epithelial tissue were also excluded. RESULTS: A total of 24 studies were included in this review. Nineteen studies utilized deep learning (DL) convolutional neural networks for histopathological OED analysis, and 4 used machine learning (ML) models. Studies were summarized by AI method, main study outcomes, predictive value for malignant transformation, strengths, and limitations. CONCLUSION: ML/DL studies for OED grading and prediction of malignant transformation are emerging as promising adjunctive tools in the field of digital pathology. These adjunctive objective tools can ultimately aid the pathologist in more accurate diagnosis and prognosis prediction. However, further supportive studies that focus on generalization, explainable decisions, and prognosis prediction are needed.

Performance of AI chatbots on controversial topics in oral medicine, pathology, and radiology.

OBJECTIVES: In this study, we assessed 6 different artificial intelligence (AI) chatbots (Bing, GPT-3.5, GPT-4, Google Bard, Claude, Sage) responses to controversial and difficult questions in oral pathology, oral medicine, and oral radiology. STUDY DESIGN: The chatbots' answers were evaluated by board-certified specialists using a modified version of the global quality score on a 5-point Likert scale. The quality and validity of chatbot citations were evaluated. RESULTS: Claude had the highest mean score of 4.341 ± 0.582 for oral pathology and medicine. Bing had the lowest scores of 3.447 ± 0.566. In oral radiology, GPT-4 had the highest mean score of 3.621 ± 1.009 and Bing the lowest score of 2.379 ± 0.978. GPT-4 achieved the highest mean score of 4.066 ± 0.825 for performance across all disciplines. 82 out of 349 (23.50%) of generated citations from chatbots were fake. CONCLUSIONS: The most superior chatbot in providing high-quality information for controversial topics in various dental disciplines was GPT-4. Although the majority of chatbots performed well, it is suggested that developers of AI medical chatbots incorporate scientific citation authenticators to validate the outputted citations given the relatively high number of fabricated citations.

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.

Corrigendum to "The Role of Medications in Causing Dry Eye".

[This corrects the article DOI: 10.1155/2012/285851.].

Oral mucosal diseases in the office setting--part I: Aphthous stomatitis and herpes simplex infections.

This article is an update and review of the most common nontraumatic ulcerative and vesicular lesions of the oral cavity. Details concerning their etiology, pathogenesis, clinical presentation, differential diagnosis, and management are included. Comparisons are made between the various forms of aphthous ulcerations and their viral counterparts. Lesions of herpes simplex origin are described for both primary and recurrent or secondary forms and differentiation from aphthous ulcerations is made. Treatment options for both the chronic and more acute forms of this condition are discussed.

Oral mucosal diseases in the office setting--Part II: oral lichen planus, pemphigus vulgaris, and mucosal pemphigoid.

Oral lichen planus, pemphigus vulgaris, and mucosal pemphigoid represent a triad of oral mucosal diseases that may be first evaluated or examined by a dental practitioner. This article examines the clinical features, etiology, pathogenesis, diagnostic considerations, and therapeutic options of these three conditions. Treatment considerations and the dentist's role in the overall scheme of management or referral are discussed.

Importance of routine evaluation of the thyroid gland prior to open partial laryngectomy.

OBJECTIVES: To determine the incidence and presentation of synchronous thyroid lesions in a patient population undergoing open partial laryngectomy (OPL), and to determine whether routine preoperative evaluation of the thyroid gland prior to OPL is useful to identify synchronous thyroid lesions in order to reduce the need for reoperation in this complex patient population. DESIGN: Retrospective medical chart review. SETTING: Academic institution. PATIENTS: Sixty-seven consecutive patients with laryngeal tumors who had undergone OPL from 1996 to 2005. INTERVENTIONS: Charts of 67 consecutive patients with laryngeal tumors who underwent OPL in 1996 to 2005 have been reviewed for synchronous thyroid lesions. For all patients, reports of (1) complete preoperative examination findings, (2) inpatient course, (3) postoperative follow-up, and (4) postoperative final histopathologic findings were reviewed. For patients with synchronous thyroid lesions, reports of (1) thyroid evaluation and imaging and (2) preoperative (fine-needle aspiration), (3) intraoperative (frozen section), and (4) postoperative (final) histopathologic results for the thyroid lesions were reviewed. MAIN OUTCOME MEASURES: Incidence of synchronous thyroid lesions and laryngeal cancer in patients undergoing OPL. RESULTS: Eight (11.9%) of 67 (95% confidence interval, 5.3%-22.2%) patients with laryngeal tumors who underwent OPL had evidence of synchronous thyroid lesions. All 8 patients had squamous cell carcinoma of the larynx and underwent either supracricoid or supraglottic laryngectomy. In these 8 patients, synchronous thyroid lesions were incidentally detected. Four patients had papillary thyroid carcinoma, 1 had squamous metaplasia, and 3 had follicular thyroid tissue that was negative for malignancy on final pathologic examination. In 2 patients, the thyroid lesions were detected preoperatively (prior to OPL); in another 2 patients, thyroid masses were detected intraoperatively; and in 4 patients, the thyroid disease was identified postoperatively on histopathologic examination of excised cervical lymph nodes. In 2 patients, thyroidectomy was performed as a second operation after the OPL, and 1 of them had transient vocal fold paralysis for 2 months. Thyroid ultrasonography was performed in 4 patients. In 3 patients, the ultrasonography was performed after the OPL final pathologic findings indicated the presence of metastatic thyroid disease in cervical lymph nodes. Ultrasonography revealed intrathyroidal lesions in all 3 patients. CONCLUSIONS: Patients with laryngeal tumors who will be undergoing OPL might have occult synchronous thyroid lesions. Thyroid surgery in patients with previous OPL may have an increased potential for complication owing to postsurgical changes in the central neck region. Routine preoperative evaluation of the thyroid gland, especially with ultrasonography, to screen for occult synchronous thyroid lesions is recommended for all patients with laryngeal tumors who will be undergoing OPL. Eradication of any thyroid cancer detected preoperatively by fine-needle aspiration should be performed at the same time as OPL. Pros and cons of total thyroidectomy for indeterminate thyroid nodules should be discussed with this patient population.

Follicular dendritic cell sarcoma of the head and neck: Case report, literature review, and pooled analysis of 97 cases.

BACKGROUND: Follicular dendritic cell sarcoma (FDCS) is a rare lymphoid neoplasm presenting in the head and neck. There are no pooled analyses of head and neck FDCS cases in the English language literature. METHODS: A MEDLINE and PubMed review of cases from 1978 to February 2014 was performed. Demographics, clinicopathologic data, and outcomes were summarized. RESULTS: We presented 2 patients and analyzed 97 cases. The mean age was 42.7 years (SD = 16.3 years). Outcomes were available for 76 patients. Tumors ≤4 cm had better disease-free survival (63% vs 28% at 5 years; p = .0282). Locoregional recurrence was significantly less likely with surgery and radiation compared to surgery alone (15% vs 45%; p = .019) and in patients receiving a neck dissection (10% vs 43%; p = .046). CONCLUSION: This pooled analysis provides the largest sample size of FDCS of the head and neck to date and suggests that radiation and neck dissection may be beneficial to locoregional oncologic control. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2241-E2249, 2016.

Mucosal dominant pemphigus vulgaris with anti-desmoplakin autoantibodies.

BACKGROUND: Anti-desmoplakin (DP) antibodies are present in paraneoplastic pemphigus (PNP) as a component of a complex humoral autoimmune reaction characterized by antibodies against proteins of the plakin family, desmogleins, and an unidentified 170 kd protein. Anti-DP antibodies have also been rarely identified in other blistering diseases. The significance of anti-DP antibodies in the pathogenesis of bullous diseases is unclear. OBSERVATION: We studied 3 patients with severe and chronic mucosal dominant pemphigus vulgaris (PV). In addition to anti-desmoglein 3 antibodies, these patients had anti-DP autoantibodies, demonstrable by immunofluorescence (IF), immunoprecipitation (IP), and indirect immunoelectromicroscopy (IIEM). This finding suggested these patients may have had PNP and not PV. However, antibodies against periplakin, envoplakin, bullous pemphigoid antigen 1 (BPAG 1), plectin, and 170 kd PNP antigen could not be detected using IP and immunoblotting. Extensive and repeated investigations for an underlying neoplasm throughout the follow-up period were consistently negative for all patients. CONCLUSION: This study demonstrates that anti-DP antibodies without the presence of any other anti-plakin antibodies are not specific for PNP, and are present in some cases of PV. Cellular disadhesion induced by anti-desmoglein antibodies can trigger an epitope-spreading phenomenon with a secondary formation of autoantibodies against desmoplakins, intracellular desmosomal antigens. The role of anti-DP antibodies in the pathogenesis of these PV patients is still unclear. The presence of anti-DP antibodies will produce a false positive serologic interpretation for the diagnosis of PNP especially if one uses only indirect IF on murine bladder, the most commonly employed screening test to identify PNP. More specific immunologic tests are required in this subset of patients with PV.

Oncocytic neoplasms of the parotid gland: a 16-year institutional review.

BACKGROUND: Oncocytic neoplasms of the parotid gland are a rare collection of salivary gland tumors that include oncocytosis, oncocytoma, and oncocytic carcinoma. Mounting evidence has linked the presence of oncocytes to acquired mitochondrial dysfunction. OBJECTIVES: The study goals were to further delineate this poorly understood group of salivary gland tumors and to search for genetic alterations indicative of mitochondrial dysfunction. METHODS: Cases were identified by search of the surgical pathology archival files from 1984 through 2000. Corresponding medical records were reviewed. Tumor mitochondrial DNA (mtDNA) was evaluated for mtDNA mutations within the control region (C-tract). RESULTS: Twenty-one parotid oncocytic neoplasms were identified. Oncocytoma was the most frequent morphology (62%), followed by oncocytosis (28.5%) and oncocytic carcinoma (9.5%). One specimen displayed synchronous oncocytic morphologies (oncocytoma, oncocytosis, and oncocytic metaplasia). One oncocytoma specimen displayed the mtDNA C-tract alteration. CONCLUSIONS: Oncocytic neoplasia of the parotid gland is a rare form of salivary gland disease with obscure etiology. The presence of multiple oncocytic morphologies in a single specimen is suggestive of transition between forms. Although oncocytic tumorigenesis secondary to acquired mitochondrial dysfunction is a plausible mechanism, few of these tumors actually harbor mtDNA alterations within the control region.

Recurrent herpes labialis: current treatment perspectives.

Recurrent herpes simplex infection of the lips and perioral skin is a very common problem in the general population, often leading patients to seek diagnostic and therapeutic intervention from their dental practitioner. Mechanisms for viral reactivation are well known and have led to the development of new classes of systemic and topical drugs that have been shown to be clinically effective in reducing recurrence frequency and duration. This article presents current treatment choices within the context of healthy and immunocompromised patients, as well as more traditional therapies.

Herpes simplex and aphthous ulcerations: presentation, diagnosis and management--an update.

The most common pathologic alterations seen by dentists are oral mucosal ulcerations, particularly those related to the herpes simplex virus and those produced by the autoimmune phenomenon known as recurrent aphthous stomatitis. Because the general frequency and clinical similarity of these conditions often make it difficult to distinguish one from the other, therapeutic intervention may be inappropriate. An improved understanding of the virologic and local immunologic alterations within the oral mucosa has led to a better understanding of these conditions and to the development of improved treatment strategies within the general practice setting for a significant number of otherwise healthy patients.

Comparison of computer-assisted brush biopsy results with follow up scalpel biopsy and histology.

Oral brush biopsy results were compared with scalpel biopsy and histology to determine the positive predictive value of an abnormal brush biopsy finding. Of 243 patients with abnormal brush biopsies, 93 proved positive for dysplasia (79) or carcinoma (14) and 150 were negative for either dysplasia or carcinoma. Therefore, the positive predictive value of an abnormal brush biopsy was 38% (93/243). By using the oral brush biopsy, dentists can inform their patients that abnormal findings have a strong positive predictive value for dysplasia or carcinoma and therefore require follow-up confirmation by scalpel biopsy.

Current management strategies for verrucous hyperkeratosis and verrucous carcinoma.

Proliferative verrucous leukoplakia, a lesion of unknown origin with no strictly defined diagnostic criteria, is worthy of great clinical concern and scrutiny. Treatment options vary, with no consensus regarding the most efficient and effective strategy. Further complicating the unusual biology and behavior of this lesion is its usual multifocal presentation and progression, with lifelong vigilance required after treatment. Verrucous carcinoma is a progressive lesion with high recurrence and 5-year survival rates. Surgery remains the preferred treatment. Further investigation into the combination of surgery and antiviral agents may bring additional improvement in patient care.