Secretory carcinoma of minor salivary glands.

Secretory carcinoma is a malignant salivary gland tumor, which typically presents as an indolent painless mass within the parotid gland. Involvement of minor gland is reported but less common. Secretory carcinoma was often misclassified as other salivary gland mimics and in particular, acinic cell carcinoma prior to 2010. It was first recognized by Skalova et al. as a molecularly distinct salivary gland tumor harboring the same fusion gene as well as histological and cytogenetic features seen in juvenile breast cancer. Secretory carcinoma is generally managed as other low-grade salivary gland neoplasms and has a favorable prognosis; however, high-grade transformation requiring aggressive therapeutic interventions have been documented. Recent studies of biological agents targeting products of this fusion gene offer the promise of a novel therapeutic option for treatment of this malignancy Due to limited number of reported cases, the spectrum of clinical behavior, best practices for management and long-term treatment outcomes for secretory carcinoma remain unclear. We report a long-standing secretory carcinoma involving minor salivary glands of the mucobuccal fold, which was detected years after it was first noted by the patient. This case brings to light the importance of a thorough clinical exam during dental visits and reviews diagnostic differentiation of this malignancy from other mimics and discusses decision making for its management.

Maackia amurensis seed lectin (MASL) and soluble human podoplanin (shPDPN) sequence analysis and effects on human oral squamous cell carcinoma (OSCC) cell migration and viability.

Maackia amurensis lectins serve as research and botanical agents that bind to sialic residues on proteins. For example, M. amurensis seed lectin (MASL) targets the sialic acid modified podoplanin (PDPN) receptor to suppress arthritic chondrocyte inflammation, and inhibit tumor cell growth and motility. However, M. amurensis lectin nomenclature and composition are not clearly defined. Here, we sought to definitively characterize MASL and its effects on tumor cell behavior. We utilized SDS-PAGE and LC-MS/MS to find that M. amurensis lectins can be divided into two groups. MASL is a member of one group which is composed of subunits that form dimers, evidently mediated by a cysteine residue in the carboxy region of the protein. In contrast to MASL, members of the other group do not dimerize under nonreducing conditions. These data also indicate that MASL is composed of 4 isoforms with an identical amino acid sequence, but unique glycosylation sites. We also produced a novel recombinant soluble human PDPN receptor (shPDPN) with 17 threonine residues glycosylated with sialic acid moieties with potential to act as a ligand trap that inhibits OSCC cell growth and motility. In addition, we report here that MASL targets PDPN with very strong binding kinetics in the nanomolar range. Moreover, we confirm that MASL can inhibit the growth and motility of human oral squamous cell carcinoma (OSCC) cells that express the PDPN receptor. Taken together, these data characterize M. amurensis lectins into two major groups based on their intrinsic properties, clarify the composition of MASL and its subunit isoform sequence and glycosylation sites, define sialic acid modifications on the PDPN receptor and its ability to act as a ligand trap, quantitate MASL binding to PDPN with KD in the nanomolar range, and verify the ability of MASL to serve as a potential anticancer agent.

Systemic Factors in Temporomandibular Disorder Pain.

The science of temporomandibular disorder (TMD) pain and its management has gone through significant changes during the last several decades. The authors strongly feel that the effect of systemic factors influencing TMD pain has been largely overlooked and poorly accounted for, even in established pain-management programs and protocols. The hope is that this article will act as a wake-up call for the pain management community to consider the importance of adequate knowledge of the systemic factors that affect the experience of TMD pain by the patient.

Novel treatment approach of localized juvenile spongiotic gingival hyperplasia with use of Nd:YAG laser.

INTRODUCTION: This article describes the management of two patients who presented with localized juvenile spongiotic gingival hyperplasia. This disease entity is poorly understood, and literature regarding successful treatment is scant. However, there are common themes to management including proper diagnosis and treatment via removal of the affected tissue. The biopsy demonstrates intercellular edema and neutrophil infiltrate with epithelial and connective tissue disease components, so surgical deepithelialization may not be adequate to definitively treat the disease. METHODS AND RESULTS: This article presents two cases of the disease and suggests the use of the Nd:YAG laser as an alternative management modality. CONCLUSION: To our knowledge, we present the first cases of localized juvenile spongiotic gingival hyperplasia treated with the Nd:YAG laser. KEY POINTS: Why are these cases new information? To our knowledge, this case series illustrates the first use of an Nd:YAG laser to treat the rare pathology localized juvenile spongiotic gingival hyperplasia. What are the keys to successful management of these cases? To properly manage this rare presentation, proper diagnosis is paramount. Following diagnosis with microscopic evaluation, deepithelialization and treatment of underlying connective tissue infiltrate via the Nd:YAG laser offers an elegant option to treat the pathology and maintain esthetic outcomes. What are the primary limitations to success in these cases? The primary limitations of these cases include the small sample size, which is attributable to the rarity of the disease.

Plasma Cell Mucositis: A Clinical Conundrum.

Plasma cell mucositis (PCM) is an unusual disorder most evident in the accessible mucosa and usually reported in the upper aerodigestive tract, although it is named according to its specific anatomical site of involvement, such as plasma cell cheilitis, plasma cell gingivitis, plasma cell vulvitis, and Zoon's balanitis. PCM reflects a dense polyclonal, rather than a monoclonal, plasma cell proliferation of unclear and unknown etiology. This perplexing disorder tends to be treated by avoiding possible triggers and intralesional and/or systemic steroids. Herein we review and provide an update on PCM, which often represents a clinical conundrum.

Salivary noncoding RNA in the diagnosis of pancreatic cancer: Systematic review and meta-analysis.

BACKGROUND: Pancreatic cancer is considered one of the most deadly malignancies, primarily because of its diagnostic challenges. We performed a systematic review and diagnostic meta-analysis to evaluate the diagnostic value of noncoding salivary RNAs in pancreatic cancer diagnosis. METHODS: Our investigation involved pertinent studies published in PubMed, Scopus, Web of Science, LIVIVO, Ovid and also the Google Scholar search engine. Specificity and sensitivity were calculated, as were positive and negative likelihood ratios (PLR and NLR), and the diagnostic odds ratio (DOR). The summary receiver-operating characteristics and area under the curve were plotted and assessed. RESULTS: This meta-analysis and systematic review involved and examined five studies that contained 145 study units with a total of 2731 subjects (1465 pancreatic cancer patients versus 1266 noncancer controls). The pooled specificity, sensitivity, NLR, PLR and DOR were 0.783 (95% CI: 0.759-0.805), 0.829 (95% CI: 0.809-0.848), 0.309 (95% CI: 0.279-0.343), 3.386 (95% CI: 2.956-3.879) and 18.403 (95% CI: 14.753-22.954), respectively, with the area under the curve (AUC) equal to 0.882. Subgroup analyses were conducted based on the saliva type (unstimulated and stimulated), mean age of patients, sample size, type of control, serum carbohydrate antigen 19-9 (CA19-9) level and type of salivary noncoding RNA (microRNA (miRNA) and long noncoding RNA (lncRNA)). CONCLUSIONS: The results of our systematic review and meta-analysis suggest that noncoding RNA biomarkers in the stimulated saliva could be a promising approach for accurate pancreatic cancer diagnosis in the early stages.

Salivary biomarkers in breast cancer diagnosis: A systematic review and diagnostic meta-analysis.

BACKGROUND: Salivary diagnostics and their utility as a nonaggressive approach for breast cancer diagnosis have been extensively studied in recent years. This meta-analysis assesses the diagnostic value of salivary biomarkers in differentiating between patients with breast cancer and controls. METHODS: We conducted a meta-analysis and systematic review of studies related to salivary diagnostics published in PubMed, EMBASE, Scopus, Ovid, Science Direct, Web of Science (WOS), and Google Scholar. The articles were chosen utilizing inclusion and exclusion criteria, as well as assessing their quality. Specificity and sensitivity, along with negative and positive likelihood ratios (NLR and PLR) and diagnostic odds ratio (DOR), were calculated based on random- or fixed-effects model. Area under the curve (AUC) and summary receiver-operating characteristic (SROC) were plotted and evaluated, and Fagan's Nomogram was evaluated for clinical utility. RESULTS: Our systematic review and meta-analysis included 14 papers containing 121 study units with 8639 adult subjects (4149 breast cancer patients and 4490 controls without cancer). The pooled specificity and sensitivity were 0.727 (95% CI: 0.713-0.740) and 0.717 (95% CI: 0.703-0.730), respectively. The pooled NLR and PLR were 0.396 (95% CI: 0.364-0.432) and 2.597 (95% CI: 2.389-2.824), respectively. The pooled DOR was 7.837 (95% CI: 6.624-9.277), with the AUC equal to 0.801. The Fagan's nomogram showed post-test probabilities of 28% and 72% for negative and positive outcomes, respectively. We also conducted subgroup analyses to determine specificity, sensitivity, DOR, PLR, and NLR based on the mean age of patients (≤52 or >52 years old), saliva type (stimulated and unstimulated saliva), biomarker measurement method (mass spectrometry [MS] and non-MS measurement methods), sample size (≤55 or >55), biomarker type (proteomics, metabolomics, transcriptomics and proteomics, and reagent-free biophotonic), and nations. CONCLUSION: Saliva, as a noninvasive biomarker, has the potential to accurately differentiate breast cancer patients from healthy controls.

Monckeberg's Medial Sclerosis as a Cause for Headache and Facial Pain.

PURPOSE OF REVIEW: Mönckeberg's medial sclerosis (MMS) is a chronic, non-inflammatory degenerative condition affecting primarily the tunica media of muscular arteries resulting in their calcification. The purpose of this comprehensive review is to describe MMS as it appears in the literature, in the context of headache and facial pain. Understanding the etiopathology, the associated conditions, and the differential diagnoses is important in managing MMS. RECENT FINDINGS: Management of MMS primarily depends upon identification of its associated conditions and their treatment. Due to the rare incidence and inadequate literature on MMS presenting with headaches, the diagnosis of the pain and the entity itself is challenging. MMS is characterized by associated systemic conditions and absence of inflammatory markers. It can mimic giant cell arteritis (GCA) and other pain entities. An interdisciplinary approach involving appropriate specialties is recommended.

Cervicofacial actinomycosis.

Cervicofacial actinomycosis is an uncommon, chronic, suppurative, and granulomatous bacterial infection. It is often of dental origin and tends to mimic other dental infections, granulomatous disorders, and cancers. The initial diagnostic workup, predicated upon imaging and tissue biopsies, is frequently nonspecific. A definitive diagnosis is usually rendered only after surgical excision and histologic examination of the cervicofacial mass. We propose a classification of three stages: localized infection without sinus involvement, localized infection with sinus involvement, and disseminated infection, to facilitate recognition, diagnosis, and early aggressive treatment. Untreated infection may be life-threatening. Therapy may require long-term antibiotics; however, many cases may also necessitate complete surgical excision.

HIV Modifies the Effect of Tobacco Smoking on Oral Human Papillomavirus Infection.

BACKGROUND: People living with HIV (PLWH) are more likely to smoke and harbor oral human papillomavirus (HPV) infections, putting them at higher risk for head and neck cancer. We investigated effects of HIV and smoking on oral HPV risk. METHODS: Consecutive PLWH (n = 169) and at-risk HIV-negative individuals (n = 126) were recruited from 2 US health centers. Smoking history was collected using questionnaires. Participants provided oral rinse samples for HPV genotyping. We used multivariable logistic regression models with interaction terms for HIV to test for smoking effect on oral HPV. RESULTS: PLWH were more likely to harbor oral HPV than HIV-negative individuals, including α (39% vs 28%), ß (73% vs 63%), and γ-types (33% vs 20%). HIV infection positively modified the association between smoking and high-risk oral HPV: odds ratios for smoking 3.46 (95% confidence interval [CI], 1.01-11.94) and 1.59 (95% CI, .32-8.73) among PLWH and HIV-negative individuals, respectively, and relative excess risk due to interaction (RERI) 3.34 (95% CI, -1.51 to 8.18). RERI for HPV 16 was 1.79 (95% CI, -2.57 to 6.16) and 2.78 for ß1-HPV (95% CI, -.08 to 5.65). CONCLUSION: Results show tobacco smoking as a risk factor for oral HPV among PLWH.

Primary diffuse large B-cell lymphoma of mandible masquerading as a toothache.

Diffuse large B-cell lymphoma is an aggressive, fast-growing form of non-Hodgkin disease with rare manifestation in mandible as a primary site. Absence of pathognomonic features in this localization often leads to misdiagnosis as an odontogenic process or its delayed diagnosis. The present case report is of a patient in whom non-odontogenic jaw pain mimicked a toothache prompting multiple dental interventions before persistence of pain and atypical findings led to consideration of a primary malignant etiology.

The dentist's role in the prevention and management of necrotizing stomatitis in the immunosuppressed.

Advances in transplant medicine and availability of effective immunosuppressive regimens have dramatically improved survival for patients afflicted with end-stage organ failure. However, chronic immunosuppression predisposes transplant patients to infection caused by a wide spectrum of endogenous or exogenous pathogens as well as necrotizing periodontal conditions. This article reviews clinical features, diagnosis, and management of necrotizing stomatitis in the context of therapeutic immunosuppression and discusses the integral function of dentists in eliminating oral foci of infection in preparation for transplantation as well as life-long maintenance of oral health post-transplant. We also present a renal transplant patient who developed massive soft and hard tissue necrosis in the anterior mandible. Disproportionate periodontal destruction in relation to local factors raised suspicion of iatrogenic overimmunosuppression, and he was hospitalized for management of profound neutropenia.

Podoplanin emerges as a functionally relevant oral cancer biomarker and therapeutic target.

Oral cancer has become one of the most aggressive types of cancer, killing 140,000 people worldwide every year. Current treatments for oral cancer include surgery and radiation therapies. These procedures can be very effective; however, they can also drastically decrease the quality of life for survivors. New chemotherapeutic treatments are needed to more effectively combat oral cancer. The transmembrane receptor podoplanin (PDPN) has emerged as a functionally relevant oral cancer biomarker and chemotherapeutic target. PDPN expression promotes tumor cell migration leading to oral cancer invasion and metastasis. Here, we describe the role of PDPN in oral squamous cell carcinoma progression, and how it may be exploited to prevent and treat oral cancer.

Pleomorphic Adenoma of the Upper Lip: A Rare Case.

Salivary gland tumors account for a small fraction of head and neck tumors. Pleomorphic adenoma, the most common salivary gland neoplasm, frequently arises in major salivary glands; its localization to minor salivary glands is uncommon and typically involves the palate. We describe a patient with an asymptomatic, long-standing mass of the upper lip, which was found to be a pleomorphic adenoma.

Antibody and lectin target podoplanin to inhibit oral squamous carcinoma cell migration and viability by distinct mechanisms.

Podoplanin (PDPN) is a unique transmembrane receptor that promotes tumor cell motility. Indeed, PDPN may serve as a chemotherapeutic target for primary and metastatic cancer cells, particularly oral squamous cell carcinoma (OSCC) cells that cause most oral cancers. Here, we studied how a monoclonal antibody (NZ-1) and lectin (MASL) that target PDPN affect human OSCC cell motility and viability. Both reagents inhibited the migration of PDPN expressing OSCC cells at nanomolar concentrations before inhibiting cell viability at micromolar concentrations. In addition, both reagents induced mitochondrial membrane permeability transition to kill OSCC cells that express PDPN by caspase independent nonapoptotic necrosis. Furthermore, MASL displayed a surprisingly robust ability to target PDPN on OSCC cells within minutes of exposure, and significantly inhibited human OSCC dissemination in zebrafish embryos. Moreover, we report that human OSCC cells formed tumors that expressed PDPN in mice, and induced PDPN expression in infiltrating host murine cancer associated fibroblasts. Taken together, these data suggest that antibodies and lectins may be utilized to combat OSCC and other cancers that express PDPN.

Oral Human Papillomavirus Infection and Oral Lesions in HIV-Positive and HIV-Negative Dental Patients.

We evaluated the risk factors associated with oral human papillomavirus (HPV) infection and oral lesions in 161 human immunodeficiency virus (HIV)-positive patients and 128 HIV-negative patients presenting for oral examination at 2 urban healthcare centers. Patients were interviewed on risk factors and provided oral-rinse samples for HPV DNA typing by polymerase chain reaction. Statistical associations were assessed by logistic regression. Oral HPV was prevalent in 32% and 16% of HIV-positive patients and HIV-negative patients, respectively, including high-risk HPV type 16 (8% and 2%, respectively; P = .049) and uncommon HPV types 32/42 (6% and 5%, respectively; P = .715). Among HIV-negative patients, significant risk factors for oral HPV included multiple sex partners (≥21 vs ≤5; odds ratio [OR], 9.1; 95% confidence interval [CI], 1.7-49.3), heavy tobacco smoking (>20 pack-years vs none; OR, 9.2; 95% CI, 1.4-59.4), and marijuana use (OR, 4.0; 95% CI, 1.3-12.4). Among HIV-positive patients, lower CD4(+) T-cell count only was associated with oral HPV detection (≤200 vs ≥500 cells/mm(3); OR, 4.5; 95% CI, 1.3-15.5). Detection of high-risk HPV was also associated with concurrent detection of potentially cancerous oral lesions among HIV-negative patients but not among HIV-positive patients. The observed risk factor associations with oral HPV in HIV-negative patients are consistent with sexual transmission and local immunity, whereas in HIV-positive patients, oral HPV detection is strongly associated with low CD4(+) T-cell counts.

Metstatic papillary thyroid carcinoma to maxilla: a rare case.

Metastatic involvement of oral osseous and soft tissues constitutes nearly 1% of all oral malignancies. However, maxillary involvement is uncommon and this phenomenon is even less likely when the primary source is thyroid. A rare case of papillary thyroid carcinoma metastatic to maxillary right posterior alveolar process and sinus in a 43-year-old woman is described and the spectrum of metastatic oral disease is reviewed. The importance of including metastasis in the differential diagnosis of jaw lesions is also emphasized.