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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.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.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%).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.

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.

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.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.The tumor was positive for CK5/6, CK19, E-cadherin, p63 and negative for CK20 and CK7.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.

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.

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.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.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.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.

BACKGROUND: For early-stage oral squamous cell carcinoma (OSCC), there is no existing risk-stratification modality beyond conventional TNM staging system to identify patients at high risk for cancer-specific mortality. METHODS: A total of 568 early-stage OSCC patients who had surgery only and also with available 5-year clinical outcomes data were identified. Signature microRNAs (miRNAs) were discovered using deep sequencing analysis and validated by qRT-PCR. The final 5-plex prognostic marker panel was utilized to generate a cancer-specific mortality risk score using the multivariate Cox regression analyses. The prognostic markers were validated in the internal and external validation cohorts. RESULTS: The risk score from the 5-plex marker panel consisting of miRNAs-127-3p, 4736, 655-3p, TNM stage and histologic grading stratified patients into four risk categories. Compared to the low-risk group, the high-risk group had 23-fold increased mortality risk (hazard ratio 23, 95% confidence interval 13-42), with a median time-to-recurrence of 6 months and time-to-death of 11 months (vs >60 months for each among low-risk patient; p < .001). CONCLUSION: The miRNA-based 5-plex marker panel driven mortality risk score formula provides clinically practical and reliable measures to assess the prognosis of patients assigned to an early-stage OSCC.

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.

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.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.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).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.

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.

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.

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.

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.

We have developed and validated a novel microRNA (miRNA)-based prognostic model to predict survival outcome in oral squamous cell carcinoma (OSCC) patients who are already categorized into ‘early-stage’ by the TNM 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 and low mortality risk categories. Within the high-risk group, surgery with neck dissection significantly improved the 5-year survival to 75% from 46% (p

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 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.

Esophageal cancers comprise adenocarcinoma and squamous cell carcinoma, two distinct histologic subtypes. Both are difficult to treat and among the deadliest human malignancies. We describe protocols to initiate, grow, passage, and characterize patient-derived organoids (PDO) of esophageal cancers, as well as squamous cell carcinomas of oral/head-and-neck and anal origin. Formed rapidly (

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

The PI3K signaling pathway is frequently mutated in head and neck squamous cell carcinoma (HNSCC), often via gain-of-function (GOF) mutations in the PIK3CA gene. Here, we present novel genetically engineered mouse models (GEMM) carrying a GOF allele Loxp-STOP-Loxp(LSL)-PIK3CAH1047R (E20) alone or in combination with heterozygous LSL-p53+/R172H (p53) mutation with tissue-specific expression to interrogate the role of oncogenic PIK3CA in transformation of upper aerodigestive track epithelium. We demonstrated that the GOF PIK3CA mutation promoted progression of 4-nitroquinoline 1-oxide–induced oral squamous cell carcinoma (OSCC) in both E20 single mutant and E20/p53 double mutant mice, with frequent distal metastasis detected only in E20/p53 GEMM. Similar to in human OSCC, loss of p16 was associated with progression of OSCC in these mice. RNA-seq analyses revealed that among the common genes differentially expressed in primary OSCC cell lines derived from E20, p53, and E20/p53 GEMMs compared with those from the wild-type mice, genes associated with proliferation and cell cycle were predominantly represented, which is consistent with the progressive loss of p16 detected in these GEMMs. Importantly, all of these OSCC primary cell lines exhibited enhanced sensitivity to BYL719 and cisplatin combination treatment in comparison with cisplatin alone in vitro and in vivo, regardless of p53 and/or p16 status. Given the prevalence of mutations in p53 and the PI3K pathways in HNSCC in conjunction with loss of p16 genetically or epigenetically, this universal increased sensitivity to cisplatin and BYL719 combination therapy in cancer cells with PIK3CA mutation represents an opportunity to a subset of patients with HNSCC. Implications: Our results suggest that combination therapy of cisplatin and PI3K inhibitor may be worthy of consideration in patients with HNSCC with PIK3CA mutation.

Lipoid proteinosis (LP) is a rare autosomal recessive disorder characterized by the deposition of amorphous hyaline material in the dermis and submucosal connective tissue. Here, we present a case of LP with significant oral, dermatologic, and neurologic manifestations occurring in a 10 year-old female of Asian descent. In addition to the more typical oral findings of restricted tongue movement and labial and buccal mucosal involvement, this case highlights an unusual pattern of gingival enlargement infrequently reported in the literature. As LP almost always involves the oral cavity, often before the onset of cutaneous lesions, it is important for dental providers to be familiar with the oral manifestations of this disease. Early detection and diagnosis of LP by the dental practitioner can help expedite proper multidisciplinary care and lead to significant reductions in patient morbidity and mortality.

The Stafne bone defect (SBD) classically presents as a well-defined, radiolucent lesion in the molar-mandibular angle region beneath the level of the mandibular canal. Due in large part to this prototypical appearance, most cases of SBDs are radiographically diagnostic without the need for tissue biopsy. A diagnostic challenge may arise, however, when the SBD occurs in other locations in the mandible. The authors report a case of a 57-year-old male who presented with a SBD of the left ascending ramus. The lesion was found incidentally on a panoramic radiograph. Additional imaging studies confirmed a lingual concavity of the mandibular bone consistent with a SBD, and a retrospective study of the patient's records revealed the presence of the lesion 5 years prior without any radiographic alterations. To date, only 10 documented cases of an SBD involving the ascending ramus have been reported. The rarity of such a presentation may obscure the diagnosis and lead to unwarranted surgical procedures. It is important to recognize atypically located SBDs, because unlike other radiolucent lesions, imaging studies are diagnostic. With proper diagnosis, additional surgical procedures and any associated morbidities can be avoided.

Alveolar soft part sarcoma (ASPS) is a rare neoplasm constituting less than 1% of all soft tissue sarcomas. It tends to occur in the deep soft tissues of the lower extremities, however approximately 5-12% of cases are primary to the head and neck region. ASPS metastatic to the oral cavity is rare, with only four documented cases in the literature. Here, we present the case of a 29-year-old woman with ASPS metastatic to the mandible. To the best of our knowledge, this represents only the 5th documented case of ASPS metastatic to the oral cavity, and more specifically, the 3rd documented case of mandibular metastasis.

Langerhans cell histiocytosis (LCH) is a clonal neoplastic proliferation of Langerhans-type dendritic cells, with more than 50% of cases of LCH seen in children younger than 15 years of age. The most common clinical presentation of LCH is solitary or multiple bony lesions. The jaws are affected in approximately 10%–20% of cases, with a strong predilection for the mandible. The maxilla is involved in only 1% of head and neck cases. When the jaws are involved, lesions of LCH may mimic periapical pathology as seen in patients requiring endodontic therapy or bone loss as seen in periodontal disease. We report the case of a 39-year-old man with LCH involving the posterior maxilla. This is a rare presentation of LCH with respect to both location and patient age. Clinicians should consider LCH when developing a differential diagnosis of an apical radiolucency of vital teeth or teeth that fail to respond to endodontic therapy and be aware of its clinical and radiographic mimics.

There are a multitude of oral manifestations of human immunodeficiency virus (HIV), many of which have decreased in frequency following the introduction of combination antiretroviral therapy (cART) in 1996. Atypical periodontal disease is an example of an oral manifestation that is infrequently seen yet strongly associated with HIV infection. HIV-associated periodontal disease can be classified into three categories, linear gingival erythema, necrotizing ulcerative gingivitis (NUG), and necrotizing ulcerative periodontitis (NUP), which vary based on disease severity. When this disease process extends beyond the alveolar ridges and causes massive tissue destruction, it is termed necrotizing ulcerative stomatitis (NUS). Herein, we report a case of a 20-year-old male patient with undiagnosed HIV in whom necrotizing ulcerative stomatitis was the first presenting sign of underlying disease.

Pseduomyogenic hemangioendothelioma (PMH) is a vascular neoplasm of intermediate biological potential first described by Hornick and Fletcher (Am J Surg Pathol 35:190–201, 2011). Despite its initial categorization as a malignant entity, PMH often demonstrates an indolent behavior profile, and thus was classified as a rarely metastasizing endothelial neoplasm in the 2013 WHO Classification of Tumors of Soft Tissue and Bone. It is a tumor primarily of skin and soft tissue, with most reported cases involving the trunk or extremities. To date, only one case of PMH involving the oral cavity has been reported. Herein, we present a case of PMH involving the mandibular gingiva and vestibule of a 33-year-old female and discuss the salient features of this entity.

Purpose The purpose of this study was to present the characteristics and survival outcomes of primary gingival squamous cell carcinoma (SCC). Materials and Methods We performed a retrospective cohort study using data from the Surveillance, Epidemiology, and End Results (SEER) tumor registry. Patients who received a diagnosis of primary gingival SCC were included in the analyses. The predictor variables were chosen from baseline demographic and tumor characteristics. The outcome of interest was survival, and Kaplan-Meier analyses were used to estimate rates of overall survival (OS) and disease-specific survival (DSS). Cox proportional hazards regression models were used for multivariate analyses. Results In total, 4,345 patients (mean age, 70.2 years) with primary gingival SCCs were identified. There was a significantly positive association between T category and both nodal and distant metastases. The 2-, 5-, and 10-year OS rates were 63.1%, 46.5%, and 28.1%, respectively, whereas the DSS rates were 78.2%, 70.7%, and 62.2%, respectively. Multivariate Cox proportional hazards regression showed that the independent predictors of overall and disease-specific death were older age, intermediate and high histologic grade, tumor size, nodal disease, and the absence of surgery. T4 classification was significantly associated with only DSS. Race, gingival location (maxillary vs mandibular), verrucous histology, and the presence of distant metastases did not significantly affect survival when all other predictors were controlled for. Conclusions Older age at diagnosis, higher grade, increased tumor size, nodal disease, and the absence of surgery were each individually associated with lower OS and DSS. Because of low nodal disease rates, both T1N0M0 lesions and verrucous subtypes may be candidates for neck observation.

Subacute necrotizing sialadenitis (SANS) is an unusual inflammatory condition known to primarily affect the minor salivary glands of the palatal region. Patients usually present with a localized, often erythematous palatal swelling accompanied by an abrupt onset of pain. The disease usually resolves between 2 days and a week with few extrapalatal reports lasting longer than 1 week. We report a series of three cases of SANS involving the palate.

Introduction: Heavy alcohol (EtOH) drinking and tobacco smoking increase the risk for upper digestive (e.g. oral and esophageal) squamous cell carcinomas (SCC) in individuals with polymorphic mutations in aldehyde dehydrogenase 2 (Aldh2). Mutant Aldh2E487K protein delays mitochondrial clearance of acetaldehyde, the chief metabolite of EtOH and constituents of tobacco smoke, aka a major human carcinogen. The role of Aldh2 in tumor biology remains elusive. Methods: Single cell-derived three-dimensional (3D) organoids were generated from murine oral and esophageal preneoplastic and SCC lesions carrying wild-type Aldh2WT or mutant Aldh2E487K as well as human SCC cell lines with Aldh2E487K, the latter subjected to xenograft transplantation in immunodeficient mice. 3D organoids and xenograft tumors were analyzed by morphology and flow cytometry to determine CD44, autophagy (cyto-ID), proliferation (EdU), and reactive oxygen species (ROS) following EtOH exposure ex vivo (0.1-2% EtOH) or in vivo (10% EtOH in drinking water) along with or without inhibitors of alcohol metabolism (4-methylpyrazole; 4MP, siRNA against Adh1B and Cyp2E1), and autophagy flux (chloroquine; CQ or siRNA against Atg7). Flow cytometry was performed to determine cancer stem-like cells with high CD44 expression (CD44H cells). Results: EtOH stimulated xenograft tumor growth and increased highly proliferative intratumoral CD44H cells with increased autophagy. EtOH-stimulated tumor growth and induction of CD44H cells were sharply suppressed by concurrent 4MP treatment, indicating that EtOH is directly metabolized in SCC cells to promote tumor growth via CD44H cells. These EtOH-induced effects were recapitulated in 3D organoids where Aldh2E487K augmented EtOH-mediated induction of CD44H cells and organoid formation with increased cellular atypia. EtOH induced mitochondrial superoxide and ROS-dependent autophagy activation in CD44H cells. Inhibition of autophagy prevented EtOH from enriching CD44H cells in 3D organoids, suggesting that autophagy may limit alcohol-induced oxidative stress as a cytoprotective mechanism. Conclusions: These studies provide not only mechanistic insights into the role of Aldh2 mutation in oral and esophageal SCC pathogenesis but also establish the utility of the 3D organoid system to test the functional interplay between genetic and environmental factors which may subsequently be targeted for pharmacological intervention in the setting of personalized medicine. Citation Format: Masataka Shimonosono, Takashi Kijima, Hisatsugu Maekawa, Satoshi Takada, Koji Tanaka, Varun Sahu, Manti Guha, Andres J. Klein-Szanto, J. Alan Diehl, Adam J. Bass, Anil K. Rustgi, Elizabeth Philipone, Angela J. Yoon, Hiroshi Nakagawa. Aldh2 mutation promotes oral and esophageal cancer stem cells via autophagy-mediated redox homeostasis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 501.

Head and neck angiosarcomas (HN-AS) are rare malignancies with a poor prognosis relative to other soft tissue sarcomas. To date, the HN-AS literature has been limited to short reports and single-institution experiences. This study evaluated patients registered with the Surveillance, Epidemiology, and End Results (SEER) program who had been diagnosed with a primary HN-AS. Predictors were drawn from demographic and baseline tumor characteristics. Outcomes were survival months and cause of death. Kaplan–Meier analyses were used to estimate overall (OS) and disease-specific survival (DSS) rates. Cox proportional hazards regression models were used for multivariate analyses. A total of 1250 patients (mean age 73.3 years) were identified, and nearly all lesions (93.5%) were cutaneous. Two- and 5-year OS rates were 47.3% (95% CI 44.3–50.3) and 26.5% (95% CI 23.7–29.3), while 2- and 5-year DSS rates were 66.6% (95% CI 63.6–69.6) and 48.3% (95% CI 44.5–52.1). In the univariate analyses, age, race, tumor grade, tumor size, AJCC stage, SEER historic stage, and surgery were significant predictors of both OS and DSS. Multivariate regression revealed that independent predictors of poor OS and DSS were older age [OS: HR 1.04 (95% CI 1.02–1.05), p

Ameloblastic fibro-odontoma (AFO) is a rare benign odontogenic tumor with the histologic features of ameloblastic fibroma (AF) but also contains enamel and dentin. It is most commonly observed in the pediatric population. Distinction between AFO and AF becomes important as ameloblastic fibromas are associated with higher recurrence rates of up to 18%, and 35% of these recurrent lesions can undergo malignant transformation to ameloblastic fibrosarcoma. Hence, for amelobastic fibroma, conservative curettage is recommended for the initial lesion and marginal resection is considered for recurrent cases. In contrast, AFO can be treated with simple curettage and the recurrence rate is approximately seven percent. Malignant transformation of AFO is exceedingly rare. Therefore, the treatment and prognosis differs for these two histologically similar neoplasms. We present a case of a 17-year-old boy who was initially diagnosed with ameloblastic fibroma upon biopsy, with subsequent curettage specimen showing AFO, which carries a better prognosis.

Pyogenic granuloma, also called lobular capillary hemangioma, is a benign vascular lesion of the skin and mucous membranes. While the majority of pyogenic granulomas in the oral cavity involve the gingiva, they also infrequently present at other sites including lips, oral mucosa, palate, and tongue. We report a case of a pyogenic granuloma of the tongue in a five-year old female patient.

Medication-induced ulcerative stomatitis can be a complication of immunosuppressive therapy in a post-transplant patient. A 54-year-old African-American female patient presented with significant, recalcitrant oral ulcers 5 months after renal transplant as a result of mucosal toxicity and severe leucopenia caused by her immunosuppressive maintenance regimen of tacrolimus (US Pharmacopeia, Rockville, MD) and mycophenolate mofetil (Santa Cruz Biotechnology, Santa Cruz, CA). The patient was also prescribed fluconazole as an antifungal, which likely contributed to the patient's increase in tacrolimus blood levels. Altering the medication dosages ultimately reduced blood tacrolimus levels, allowing for resolution of her oral ulcers. This report indicates that medication-induced oral ulcerations are a potential sequela of post-transplant immunosuppressive therapy.