Mucosal Soft Tissue Lesions.

Mucosal soft tissue lesions are fairly common in the pediatric population. However, the precise prevalence is unknown. This is the result of the limited number of studies, the use of various diagnostic criteria in those studies, and the transient nature of commonly encountered lesions in this population. In this section, we seek to familiarize the pediatric pathologist with a sampling of mucosal soft tissue lesions encountered in pediatric patients, highlight key diagnostic features and correlations with systemic diseases should they exist.

Dentinogenic ghost cell tumor associated with odontoma: report of a rare case and review of literature.

Dentinogenic ghost cell tumor (DGCT) is an uncommon odontogenic tumor considered to be the solid, tumorous variant of calcifying odontogenic cyst. DGCT is characterized by islands of ameloblastoma-like epithelial cells that resemble the enamel organ, the presence of ghost cells, and dentinoid material. This article reports a rare case of dentinogenic ghost cell tumor associated with an odontoma in an adult patient, with a review of the literature. To the best of the authors' knowledge, there have only been four case reports of DGCT associated with odontoma, all of which occurred in children and adults younger than 30 years old.

Nodule of the Midline Dorsal Tongue.

A 46-year-old man presented for an evaluation of a lesion on the dorsal tongue; he was asymptomatic and unaware of the lesion prior to it being discovered by his dentist. What is your diagnosis?

Ulcerative and Inflammatory Lesions of the Oral Mucosa.

Ulcerated and inflammatory lesions of the oral mucosa are not rare. A detailed patient medical and social history including habits and abuses, as well as the duration, location, focality and presence, or lack of local and/or systemic symptoms is critical in establishing a proper diagnosis. This article discusses the clinical presentation, management, and histopathologic characteristics of a variety of ulcerative and inflammatory lesions seen in the oral cavity.

Sclerosing Odontogenic Carcinoma: Report of a Case and Review of the Literature.

BACKGROUND: Sclerosing odontogenic carcinoma is an exceedingly rare gnathic malignancy first described by Koutlas et al. in 2008, and was only recently designated as a distinct pathologic entity by World Health Organization in the 2017 Classification of Head and Neck Tumors. To date, fewer than fifteen cases of this neoplasm have been reported in the English language literature. This tumor is characterized by thin cords, strands, and small nests of epithelium in a densely sclerotic stroma. In some tumor foci, the density of the stroma may be sufficient to compress the epithelial component beyond detection in the absence of immunohistochemistry, thus rendering this entity a particularly challenging diagnosis in small sample sizes. METHODS: A 55-year-old male presented with an asymptomatic lesion of posterior left maxilla. Cone beam computed tomography (CBCT) demonstrated a large, well-defined bony lesion with scalloped border, spanning from canine to first molar. External root resorption of the adjacent teeth was also noted. Microscopic examination of the biopsy specimen revealed an odontogenic tumor with features consistent with sclerosing odontogenic carcinoma. Immunohistochemical staining was performed to confirm the diagnosis. RESULTS: The tumor was positive for CK5/6, CK19, E-cadherin, p63 and negative for CK20 and CK7. CONCLUSION: Sclerosing odontogenic carcinoma is a rare, low-grade malignancy of odontogenic origin, which represents a diagnosis of exclusion in many cases. An immunohistochemical profile demonstrating positivity for markers including CK5/6, CK19, p63, and E-cadherin, in addition to a set of pertinent negative findings, can aid in the diagnosis of this tumor. This entity appears to lack metastatic potential despite its locally destructive behavior and a common histologic finding of perineural invasion.

Computed tomographic imaging features of maxillary and mandibular melanotic neuroectodermal tumor of infancy: Report of 2 cases and systematic review.

OBJECTIVE: The aim of this systematic review was to determine the computed tomographic (CT) imaging characteristics of maxillary and mandibular melanotic neuroectodermal tumor of infancy (MNTI). Two cases from our institution were also presented. STUDY DESIGN: Full-text case reports and case series of histopathologically proven gnathic MNTI with CT figures of diagnostic quality were searched in PubMed, Scopus, Web of Science, Ovid, and Google Scholar databases from July 2021 to February 2022. Descriptive statistics were used to determine the frequency of each CT feature of gnathic MNTI. RESULTS: Fifty-two published studies met the eligibility criteria, providing a total of 53 maxillary and mandibular MNTIs for analysis. In order of frequency, the CT features of gnathic MNTI that were present in over half of the study sample were bone expansion (53, 100%), a well-defined periphery (49, 92.5%), tooth displacement (45, 84.9%), and a bilocular radiolucent internal pattern (32, 60.4%). CONCLUSIONS: The bilocular radiolucent internal pattern has not been recognized as a common CT feature of gnathic MNTI. When associated with a well-defined, expansile mass in the infantile maxilla or mandible, this imaging characteristic can support a radiologic interpretation of MNTI.

Stathmin as a surrogate marker of phosphatidylinositol-3-kinase pathway activity: Towards precision medicine in HPV-negative head & neck squamous cell carcinoma.

In order to assess Stathmin as an immunohistochemical (IHC) indicator of phosphatidylinositol 3-kinase (PI3K) pathway activity in HPV-negative head & neck squamous cell carcinoma (HNSCC), we compared Stathmin IHC to expression of other pathway components. We also evaluated the relationship between Stathmin IHC and the mutational status of four key pathway genes. Finally, we ascertained whether Stathmin IHC correlates with tumor grade or primary site. Correlation exists between high Stathmin expression and high pAKT1 expression, indicating a role for Stathmin IHC as a marker of pathway activity. Our analysis did not show correlation between Stathmin IHC and mutation of the four genes evaluated. We also observed an association between high Stathmin expression and oropharyngeal primary site. Our results suggest utility of Stathmin IHC as an indicator of PI3K pathway activity, and thereby demonstrate potential relevance of Stathmin IHC in the context of HNSCC.

Decompression of Odontogenic Keratocysts Before Enucleation Reduces the Rate of Recurrence.

BACKGROUND: The purpose of this study was to determine if 2-stage conservative treatment (decompression followed by enucleation) of odontogenic keratocysts reduced the rate of recurrence compared to single-stage conservative treatment. METHODS: This was a pooled cohort study composed of both patients identified at our institution and cases reported in the literature. The primary predictor variable was treatment modality (single versus 2-staged conservative treatment). The outcome variable was the overall recurrence rate. RESULTS: A total of 684 patient cases were included in the final pooled sample. The mean age was 39.80years (range: 7-80 years). The mandible (76.8%) was the most common site, with the rest of the lesions manifesting in the maxilla (23.0%). A total of 58.1% of the lesions were unilocular, whereas the remaining 41.9% were multilocular. Two-stage conservative treatment demonstrated a lower recurrence rate (14.5% versus 22.1%; P = 0.029). CONCLUSIONS: Decompression is known to reduce lesion size and optimize the favorability of conservative treatment. Furthermore, we propose that 2-staged treatment may also be associated with a lower recurrence rate.

Adverse events secondary to cetuximab therapy in head & neck cancer therapy and risk factors for serious outcomes.

OBJECTIVES: The objective of this study is to illustrate the adverse events secondary to cetuximab therapy for head and neck cancer and elucidate risk factors for serious outcomes. MATERIALS AND METHODS: This retrospective study was conducted using the FDA Adverse Event Reporting System (FAERS). The predictor variables were patient characteristics, country of treatment, and adverse events. The outcome variable was the rate of serious outcomes. Multivariate logistic regression was created to identify all significant risk factors of the outcome. P < 0.05 was considered statistically significant. RESULTS: The final sample consisted of 3,086 reports of adverse events from cetuximab therapy in head and neck cancer treatment, of which 2,746 reports were considered serious (89.0%) per the FAERS criteria. Mucosal inflammation was the most common adverse event. The strongest risk factor for a serious outcome was cetuximab therapy in countries outside the US (OR 105.2, P < 0.01). Polytherapy (OR 7.6, P < 0.01) was also a risk factor for serious outcome. CONCLUSIONS: Health-care providers should be aware of potential complications following cetuximab administration, particularly when administered in countries outside the US and in conjunction with other medications.

High-speed light-sheet microscopy for the in-situ acquisition of volumetric histological images of living tissue.

Histological examinations typically require the excision of tissue, followed by its fixation, slicing, staining, mounting and imaging, with timeframes ranging from minutes to days. This process may remove functional tissue, may miss abnormalities through under-sampling, prevents rapid decision-making, and increases costs. Here, we report the feasibility of microscopes based on swept confocally aligned planar excitation technology for the volumetric histological imaging of intact living tissue in real time. The systems' single-objective, light-sheet geometry and 3D imaging speeds enable roving image acquisition, which combined with 3D stitching permits the contiguous analysis of large tissue areas, as well as the dynamic assessment of tissue perfusion and function. Implemented in benchtop and miniaturized form factors, the microscopes also have high sensitivity, even for weak intrinsic fluorescence, allowing for the label-free imaging of diagnostically relevant histoarchitectural structures, as we show for pancreatic disease in living mice, for chronic kidney disease in fresh human kidney tissues, and for oral mucosa in a healthy volunteer. Miniaturized high-speed light-sheet microscopes for in-situ volumetric histological imaging may facilitate the point-of-care detection of diverse cellular-level biomarkers.

Burkitt Lymphoma Masquerading as Osteomyelitis: An Interesting Road to Diagnosis.

ABSTRACT: Sporadic Burkitt lymphoma (BL) is a clinical form of BL that typically presents with abdominal and cervical lymph node involvement in male children. We present a rare case of disseminated sporadic BL of a 37-year-old female diagnosed via the workup in response to nonhealing tooth extraction sockets.

Central giant cell granuloma of the head & neck: A case report and systematic review.

PURPOSE: The purpose of this paper is to describe a recent case of central giant cell granuloma (CGCG) that rapidly progressed post corticosteroid treatment while also providing a review of the existing literature on CGCG of the head and neck (HNCGCG), with particular emphasis on extra-mandibular and maxillary cases. MATERIALS AND METHODS: The investigators designed and implemented a 32-year review of literature, using the online databases: PubMed, Google Scholar, Medline, and Proquest. The total number of cases analyzed was 55 (42 case reports; 3 case series; 8 comparative studies; 1 retrospective cohort). CASE PRESENTATION: We present a case of a CGCG in a 10-year old male. The lesion originated in the right anterior mandibular body and progressed after corticosteroid treatment. Diagnosis was made using a combination of imaging and histology. A timely debulking procedure of the hemi-mandible was performed and there was no recurrence of the lesion at follow up. RESULTS: The average age at the time of diagnosis of CGCG was 27.5 years. HNCGCG was most commonly detected in the jaw (43.1%), but was also found in the temporal bone (33.3%). The most frequently employed treatment modality was complete surgical excision (76.9%). 93.2% of patients were alive with no evidence of disease at follow-up, while 6.8% of patients exhibited recurrence at follow-up. The median follow up was 13 months. CONCLUSION: It is important for clinicians to recognize that CGCGs are capable of manifesting outside of the jaw. CGCG should be considered in the differential diagnosis of non-odontogenic radiolucent lesions, especially in young patients. CGCGs also need to be distinguished from brown tumor of hyperparathyroidism (BTH) and giant cell tumors, which are histologically similar.

Aneurysmal bone cyst of the head & neck: A review of reported cases in the literature.

The aneurysmal bone cyst (ABC) is a benign, blood-filled bony lesion that notoriously affects the vertebral column and long bones of the body. Rarely, ABCs can manifest in the head and neck (HNABC). The purpose of this paper is to provide a comprehensive review of existing literature on HNABC. This review includes: case reports and case series on ABCs manifesting in the head and neck region published in the English language. All cases identified via PubMed were analyzed individually. Articles were included according to specified eligibility criteria. The total number of cases analyzed were 72 (39 case reports; 33 case series). The average age at the time of HNABC diagnosis was 19.1 years (range: 0.42-62 years). The ratio of prevalence by gender affected exhibited an even 1:1 male-to-female split. CT in combination with MRI proved to be the most prevalent imaging modality utilized (37.2%). HNABC was most commonly detected in the mandible (37.1%), followed by the sinus (14.3%) and cranium (11.4%). The most frequently employed single treatment modality was surgical excision (94.1%). 94.4% of patients were alive with no evidence of disease at follow-up, while 5.6% of patients exhibited disease at follow-up. The average follow-up period was 3.59 years (range: 0.17-17.0 years). Aneurysmal bone cyst of the head and neck region is a rare condition that should be considered in the differential diagnosis of bony, vascular lesions presenting in the aforementioned locations. Since aneurysmal bone cyst of the head and neck region can present as a rapidly growing, expansive and destructive lesion, it is crucial that clinicians are aware of this entity so that patients are accurately diagnosed and treated.

The REASON score: an epigenetic and clinicopathologic score to predict risk of poor survival in patients with early stage oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a capricious cancer with poor survival rates, even for early-stage patients. There is a pressing need to develop more precise risk assessment methods to appropriately tailor clinical treatment. Genome-wide association studies have not produced a viable biomarker. However, these studies are limited by using heterogeneous cohorts, not focusing on methylation although OSCC is a heavily epigenetically-regulated cancer, and not combining molecular data with clinicopathologic data for risk prediction. In this study we focused on early-stage (I/II) OSCC and created a risk score called the REASON score, which combines clinicopathologic characteristics with a 12-gene methylation signature, to predict the risk of 5-year mortality. METHODS: We combined data from an internal cohort (n = 515) and The Cancer Genome Atlas (TCGA) cohort (n = 58). We collected clinicopathologic data from both cohorts to derive the non-molecular portion of the REASON score. We then analyzed the TCGA cohort DNA methylation data to derive the molecular portion of the risk score. RESULTS: 5-year disease specific survival was 63% for the internal cohort and 86% for the TCGA cohort. The clinicopathologic features with the highest predictive ability among the two the cohorts were age, race, sex, tobacco use, alcohol use, histologic grade, stage, perineural invasion (PNI), lymphovascular invasion (LVI), and margin status. This panel of 10 non-molecular features predicted 5-year mortality risk with a concordance (c)-index = 0.67. Our molecular panel consisted of a 12-gene methylation signature (i.e., HORMAD2, MYLK, GPR133, SOX8, TRPA1, ABCA2, HGFAC, MCPH1, WDR86, CACNA1H, RNF216, CCNJL), which had the most significant differential methylation between patients who survived vs. died by 5 years. All 12 genes have already been linked to survival in other cancers. Of the genes, only SOX8 was previously associated with OSCC; our study was the first to link the remaining 11 genes to OSCC survival. The combined molecular and non-molecular panel formed the REASON score, which predicted risk of death with a c-index = 0.915. CONCLUSIONS: The REASON score is a promising biomarker to predict risk of mortality in early-stage OSCC patients. Validation of the REASON score in a larger independent cohort is warranted.

Mesenchymal Chondrosarcoma in the Maxilla: A Case Report and Literature Review.

Mesenchymal chondrosarcoma is a rare high-grade variant of chondrosarcoma distinguished by its aggressive nature. Molecular studies aid in establishing the diagnosis. We present a case report of mesenchymal chondrosarcoma in the maxilla of a 39-year-old male patient and a literature review of 42 gnathic cases of mesenchymal chondrosarcoma with a discussion of clinical, imaging, microscopic, immunohistochemical, and molecular features.

MicroRNA-Based Cancer Mortality Risk Scoring System and hTERT Expression in Early-Stage Oral Squamous Cell Carcinoma.

We have previously constructed a novel microRNA (miRNA)-based prognostic model and cancer-specific mortality risk score formula to predict survival outcome in oral squamous cell carcinoma (OSCC) patients who are already categorized into "early-stage" by the TNM staging system. A total of 836 early-stage OSCC patients were assigned the mortality risk scores. We evaluated the efficacy of various treatment regimens in terms of survival benefit compared to surgery only in patients stratified into high (risk score ≥0) versus low (risk score <0) mortality risk categories. For the high-risk group, surgery with neck dissection significantly improved the 5-year survival to 75% from 46% with surgery only (p < 0.001); a Cox proportional hazard model on time-to-death demonstrated a hazard ratio of 0.37 for surgery with neck dissection (95% CI: 0.2-0.6; p=0.0005). For the low-risk group, surgery only was the treatment of choice associated with 5-year survival benefit. Regardless of treatment selected, those with risk score ≥2 may benefit from additional therapy to prevent cancer relapse. We also identified hTERT (human telomerase reverse transcriptase) as a gene target common to the prognostic miRNAs. There was 22-fold increase in the hTERT expression level in patients with risk score ≥2 compared to healthy controls (p < 0.0005). Overexpression of hTERT was also observed in the patient-derived OSCC organoid compared to that of normal organoid. The DNA cancer vaccine that targets hTERT-expressing cells currently undergoing rigorous clinical evaluation for other tumors can be repurposed to prevent cancer recurrence in these high-risk early-stage oral cancer patients.

Association between oral lichen planus and systemic conditions and medications: Case-control study.

OBJECTIVE: The aim of this study is to investigate the association between oral lichen planus (OLP) and a variety of systemic conditions, medication, and supplement usage. MATERIALS AND METHOD: A total of 156 patients diagnosed with OLP and 156 controls at Columbia University Irving Medical Center from 2000 to 2013 were selected as part of the matched (1:1) case-control study. Demographics, systemic conditions, prescription medications and supplements were extracted from the patients' medical records. A univariable conditional logistic regression (CLR) analysis was performed to calculate unadjusted odds ratio, to identify significant variables associated with OLP (p < .10). Significant variables were further tested using multivariable CLR analysis with both forward and backward selection to calculate adjusted odds ratio (aOR) and further distinguish variables associated with OLP (p < .05). RESULTS: This analysis identified six significant variables: thyroid disorder (aOR:5.1,95%CI:2.3-11.2), any form of cancer (aOR:3.4,95%CI:1.4-8.4), type 2 diabetes (aOR:2.8,95%CI:1.2-6.3), hyperlipidemia (aOR:2.3,95%CI:1.3-4.1), oral sedative usage (aOR:6.3,95%CI:1.8-22.5), and vitamin D supplementation (aOR:2.7,95%Cl:1.3-6.0). CONCLUSION: Thyroid disorders, cancer, type 2 diabetes, hyperlipidemia, sedatives, and vitamin D supplementation were found to be associated with OLP. Additional investigation is required to explore these associations, which could shed light on the potential mechanism of OLP and reinforce the idea that oral lesions could be predicative of previously undetected systemic conditions.

Synovial sarcoma of the head & neck: A review of reported cases in the literature.

Synovial sarcoma is a high-grade malignancy that seldom manifests in the head and neck. The purpose of this paper is to provide a comprehensive review of the existing literature on primary HNSS. This review study includes case reports, case series and retrospective cohort studies on primary HNSS published in the English language. All cases identified via PubMed were analyzed individually. Articles were included according to specified eligibility criteria. The total number of cases analyzed was 243 (91 case reports, 53 cases from 16 case series, and 99 cases from 8 retrospective cohort studies). The average age at the time of HNSS diagnosis was 33.5 years. The ratio of male-to-female was 1.64:1. The most frequently occurring histologic subtype was biphasic (59.2%). The most common location was the neck. Hoarseness was the most common presenting symptom. Almost all patients (98.3%) underwent surgical excision. 55.6% of patients received adjuvant radiotherapy. A smaller number of patients (30.7%) received adjuvant chemotherapy. 60.3% of patients were alive with no evidence of disease at follow-up while 28.0% of patients died of HNSS at follow-up. The average follow-up period was 52.0 months. Synovial sarcoma is a rare head and neck malignancy. Surgical excision with adjuvant radiation is the most frequently employed treatment modality. Regardless of treatment modality, the prognosis of the tumor is guarded.