Depth of resection predicts loss of tongue tip sensation after partial glossectomy in oral tongue cancer: A pilot study.

OBJECTIVE(S): To characterize the change in sensory function following partial glossectomy for oral tongue cancer (OTC) and to identify predictors of loss of tongue-tip sensation (LoTTS). MATERIALS AND METHODS: Patients with at least three months follow-up after partial glossectomy for primary OTC were included. All patients underwent a qualitative tongue sensation assessment and an objective tongue sensory exam of the native tongue tip. Additional details regarding the oncologic resection, surgical reconstruction, and pathological stage were collected. Multiple linear and logistic regressions were used for statistical analysis. RESULTS: Sixty-four patients were enrolled, including 34 (53%) men with a median age of 65 at enrollment. Ten (15%) patients reported LoTTS. Increased depth of resection (DOR) was an independent predictor of LoTTS on multivariate analysis, with an increased risk at a threshold of 1.3 cm. LoTTS was also associated with worse subjective quality of life and perceptive speech performance in our qualitative tongue assessment. CONCLUSIONS: In this pilot study, we found that DOR is a critical prognostic factor in predicting post treatment function. Patients with an increased DOR, particularly above 1.3 cm, are at greatest risk of LoTTS and associated morbidity. These findings may be used to predict post-operative sensory deficits, manage patients' expectations, and optimize the reconstructive approach. Future studies are needed to validate and replicate our results.

Glossectomy for the treatment of oral cavity carcinoma: Quantitative, functional and patient-reported quality of life outcomes differ by four glossectomy defects.

OBJECTIVE: The goal was to characterize four clinically distinct glossectomy defects to establish significant quantitative cut points using functional metrics, the MD Anderson Dysphagia Index (MDADI) and speech intelligibility. METHODS: Population included 101 patients treated with surgery, adjuvant radiation per NCCN guidelines, and ≥ 12 months follow-up. RESULTS: Defect groups: subtotal hemiglossectomy (1), hemiglossectomy (2), extended hemiglossectomy (3) and oral glossectomy (4) were compared: All outcomes supported a four defect model. Intergroup comparison of outcomes with subtotal hemiglossectomy as reference (p value): Tongue Protrusion <0.001,<0.001,<0.001; Elevation <0.001,<0.001,<0.001; Open Mouth Premaxillary Contact Elevation <0.001,<0.001,<0.001; Obliteration 0.6,<0.001,<0.001; Normalcy of Diet, <0.3,<0.001,<0.001; Nutritional Mode, <0.9,<0.8,<0.001; Range of Liquids, <0.4,<0.016,<0.02; Range of Solids, <0.5,<0.004,<0.001; Eating in Public, <0.2,<0.002,<0.03; Understandability of Speech, <0.9,<0.001,<0.001; Speaking in Public, <0.4,<0.03,<0.001; MDADI, <0.4,<0.005,<0.01; Single Word Intelligibility, <0.4,<0.1,<0.001; Sentence Intelligibility, <0.5,<0.08,<0.001; Words Per Minute Intelligibility, <0.6,<0.04,<0.001; Sentence Efficiency Ratio, <0.4,<0.03,<0.002. Proportion of patients by 4 defect groups who underwent: tissue transplantation, 51%,93.9%,100%,100%.Radiation,24%,67%,88%,80%.Between hemiglossectomy and extended hemiglossectomy, the defect extends into the contralateral floor of the mouth and/or the anterior tonsillar pillar; resection of these subunits limits tongue mobility with an impact on functional outcome and MDADI. Between extended hemiglossectomy and oral glossectomy, the defect extends to include the tip of the tongue and appears to impact functional outcome and MDADI. CONCLUSIONS: Subtotal hemiglossectomy, hemiglossectomy, extended glossectomy and oral glossectomy are associated with quantitative (elevation, protrusion, open mouth premaxillary contact and obliteration), qualitative (speech and swallowing) and MDADI differences, suggesting that these 4 ordinal defect groups are distinct.

Association of CASC18/miR-20a-3p/TGFB2 ceRNA axis with occult lymph node metastasis in tongue squamous cell carcinoma.

BACKGROUND: Tongue squamous cell carcinoma (TSCC) ranks as the most prevalent malignancy in the oral cavity. TSCC patients with occult lymph node metastasis (OLNM) are thought to be at risk of worse outcome. However, regulatory mechanisms underlying OLNM remain less investigated. METHODS: In the present study, CASC18/miR-20a-3p/TGFB2 axis was identified and evaluated by bioinformatic and qRT-PCR analyses. Effects of CASC18 knockdown on cell migration and invasion were determined by wound healing and transwell assays. Western blot, ELISA, RNA pulldown and luciferase reporter assays were performed for mechanism verification. RESULTS: CASC18 was identified up-regulating in TSCC tumours, and especially in those from patients with OLNM. Importantly, we found higher CASC18 expression was positively correlated with the presence of OLNM and worse outcome of TSCC patients. Furthermore, we demonstrated that CASC18 knockdown repressed cell migration and invasion through inhibiting epithelial-mesenchymal transition, which could be partly rescued by miR-20a-3p inhibitor. Regarding the molecular mechanism, we further confirmed that CASC18 functioned as a ceRNA to sponge miR-20a-3p to enhanceTGFB2 expression and secretion. CONCLUSION: In conclusion, we have reported a novel CASC18/miR-20a-3p/TGFB2 ceRNA axis in OLNM of TSCC. Our findings will contribute to a deeper understanding of the molecular mechanism of OLNM in TSCC, and facilitate the development of diagnostic methods for assisting treatment decision-making.

P16-positive secondary tongue squamous cell carcinoma following allogeneic hematopoietic stem cell transplantation: A case report and literature review.

As a method to improve the survival rate of patients with hematological malignancies, allogeneic hematopoietic stem cell transplantation (allo-HSCT) has increasingly been used for treatment. However, some potentially serious complications after allo-HSCT, including graft-versus-host disease, graft failure, infection, end-organ toxicity, and secondary malignancies, will determine the success of hematopoietic reconstitution. Here, we describe a case of a patient with p16-positive tongue squamous cell carcinoma (TSCC) following allo-HSCT. A 62-year-old man who had previously received allo-HSCT due to acute lymphocytic leukemia (AML) presented with erosions on the back of the tongue surrounded by multiple white patches, which were compatible with oral chronic graft-versus-host disease (cGVHD). During follow-up, a circular-like erosive lesion appeared on the right dorsal surface of the tongue. Biopsy of this lesion confirmed early invasive TSCC (T2N0M0). Partial glossectomy and tongue reconstruction were performed after cessation of immunosuppressants. Immunohistochemical (IHC) staining was positive for p16 and ki-67, suggesting a probable active human papillomavirus (HPV) infection. Six months after surgery, the patient showed no signs of metastasis or recurrence nor progression of oral GVHD.

Prognostic Markers and Driver Genes and Options for Targeted Therapy in Human-Papillomavirus-Positive Tonsillar and Base-of-Tongue Squamous Cell Carcinoma.

The incidence of Human-papillomavirus-positive (HPV+) tonsillar and base-of-tongue squamous cell carcinoma (TSCC and BOTSCC, respectively) is increasing epidemically, but they have better prognosis than equivalent HPV-negative (HPV-) cancers, with roughly 80% vs. 50% 3-year disease-free survival, respectively. The majority of HPV+ TSCC and BOTSCC patients therefore most likely do not require the intensified chemoradiotherapy given today to head and neck cancer patients and would with de-escalated therapy avoid several severe side effects. Moreover, for those with poor prognosis, survival has not improved, so better-tailored alternatives are urgently needed. In line with refined personalized medicine, recent studies have focused on identifying predictive markers and driver cancer genes useful for better stratifying patient treatment as well as for targeted therapy. This review presents some of these endeavors and briefly describes some recent experimental progress and some clinical trials with targeted therapy.

Vaping the Venom: Oral Cavity Cancer in a Young Adult With Extensive Electronic Cigarette Use.

Squamous cell carcinoma (SCC) of the oral cavity is one of the most common malignancies of the head and neck. Risk factors for the development of SCC include infection with human papillomavirus (HPV), tobacco use, and alcohol use. HPV-positive SCC of the oral cavity is more commonly seen in young adult patients, whereas HPV-negative disease is more prevalent in older patients with histories of alcohol and tobacco use. We describe the case of a young adult with an extensive history of vaping using nicotine-delivery systems who was diagnosed with HPV-negative SCC that was rapidly progressive and fatal.

Differences in gene expression between high-grade dysplasia and invasive HPV+ and HPV- tonsillar and base of tongue cancer.

BACKGROUND: Human papillomavirus (HPV) is a causative agent for tonsillar and base of tongue squamous cell carcinoma (TSCC/BOTSCC), as well as for cervical cancer. Premalignant stages in cervical cancer have been studied extensively, while little is known about premalignant stages in TSCC/BOTSCC and the role of HPV. Here we analyzed differences in gene and protein expression between high-grade dysplasia and invasive cancer in both HPV-positive (HPV+ ) and HPV-negative (HPV- ) TSCC/BOTSCC. METHODS: High-grade dysplasia and invasive carcinoma were laser microdissected from HPV+ and HPV- TSCC/BOTSCC tumor sections. Differential gene expression was studied utilizing nanoString RNA-panels and genes of interest were validated on the protein level by immunohistochemistry. RESULTS: Forty genes in the HPV+ tumors showed significantly different expression between high-grade dysplasia and invasive cancer and 33 genes in the HPV- tumors. Five out of the nine most significant pathways showed similar increased activity in invasive cancer as compared to high-grade dysplasia in both HPV+ and HPV- tumors. Lastly, significant differences in protein expression was confirmed for SPARC, psoriasin, type I collagen and galectin-1 in both HPV+ and HPV- tumors. CONCLUSIONS: This is to our knowledge the first study disclosing differences and similarities in gene expression between dysplastic and invasive HPV+ and HPV- TSCC/BOTSCC.

Three Synchronous Primary Extranodal Mantle Cell Lymphomas Involving Torus Tubarius, Posterior Nasopharynx, and Base of the Tongue 65 Years After Treatment of Chronic Sinusitis with Nasopharyngeal Radium Irradiation.

BACKGROUND Radiation, specifically ionizing radiation, causes broad-spectrum gene damage, including double-strand DNA breaks, single DNA strand breaks, cross links, and individual base lesions, thus causing chromosomal translocations, deletions, point mutations, and, consequently, various types of cancer. Radiation also causes genomic instability in cells, which enhances the rate of mutations in the descendants of the irradiated cell after many generations of normal replications. CASE REPORT We report the first case of mantle cell lymphoma of the torus tubarius, and the first CD10-positive mantle cell lymphoma of the Waldeyer's ring. Mantle cell lymphoma appeared 65 years after treatment of chronic sinusitis with nasopharyngeal radium irradiation. CONCLUSIONS On the basis of the medical literature about atomic bomb survivors, nuclear plant workers, and radiologists exposed to radiation, and our case, we conclude that radiation can, in a very small percentage of exposed individuals, cause non-Hodgkin lymphoma: in 0.24% of atomic bomb survivors and in at least 0.13% of the patients treated with nasopharyngeal radium irradiation. Non-Hodgkin lymphoma can occur many decades after radiation exposure, and individuals treated with nasopharyngeal radium irradiation, usually in their childhood, need continuing follow-up.

Maternal folic acid depletion during early pregnancy increases sensitivity to squamous tumor formation in the offspring in mice.

Gestational nutrition is widely recognized to affect an offspring's future risk of lifestyle-related diseases, suggesting the involvement of epigenetic mechanisms. As folic acid (FA) is a nutrient essential for modulating DNA methylation, we sought to determine how maternal FA intake during early pregnancy might influence tumor sensitivity in an offspring. Dams were maintained on a FA-depleted (FA(-)) or normal (2 mg FA/kg; FA(+)) diet from 2 to 3 days before mating to 7 days post-conception, and their offspring were challenged with chemical tumorigenesis using 7,12-dimethylbenz[a)anthracene and phorbol 12-myristate 13-acetate for skin and 4-nitroquinoline N-oxide for tongue. In both squamous tissues, tumorigenesis was more progressive in the offspring from FA(-) than FA(+) dams. Notably, in the skin of FA(-) offspring, the expression and activity of cylindromatosis (Cyld) were decreased due to the altered DNA methylation status in its promoter region, which contributed to increased tumorigenesis coupled with inflammation in the FA(-) offspring. Thus, we conclude that maternal FA insufficiency during early pregnancy is able to promote neoplasm progression in the offspring through modulating DNA methylation, such as Cyld. Moreover, we propose, for the first time, "innate" utero nutrition as the third cause of tumorigenesis besides the known causes-hereditary predisposition and acquired environmental factors.

Dyskeratosis Congenita and Oral Cavity Squamous Cell Carcinoma: Report of a Case and Literature Review.

Dyskeratosis congenita is a rare genetic condition of telomerase dysfunction in which patients are at an increased risk of squamous cell carcinoma (SCCa) of the oral cavity. We present here the youngest patient in the literature with a diagnosis of SCCa. We discuss the literature and management of this advanced presentation of SCCa in a child, stressing the importance of palliative care involvement in facilitating medical decision making.

Oral tongue cancer in a patient with hereditary nonpolyposis colorectal cancer: A case report and review of the literature.

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disorder characterized by mutations of mismatch repair genes leading to the early development of multiple malignancies. The most common malignancy is colorectal cancer but there is a strong association with malignancies of the ovary, endometrium, small intestine, stomach, skin, brain, and pancreas. We report a case of a 35-year-old female with a history of known HNPCC who presented with adenocarcinoma of the small intestine as well as a synchronous oral tongue squamous cell carcinoma. The patient underwent a combined oncologic surgery involving a hemiglossectomy, selective neck dissection, and partial small bowel resection. Despite the wide range of malignancies seen in patients with HNPCC, no cases of oral cavity cancer have previously been reported. This represents the first case in the literature of oral cavity cancer in a patient with HNPCC.

Cutaneous malignant melanoma of the oral cavity following skin graft reconstruction: Case report.

BACKGROUND: Malignant melanomas on skin graft recipient sites are rare, with few cases reported in the literature. METHODS: We present a case report of a patient with recurrent cutaneous melanoma in the grafted anterolateral thigh flap of the tongue. RESULTS: A patient underwent hemiglossectomy with free flap reconstruction for squamous cell carcinoma of the tongue. Five years later the patient was seen with a 1-cm nodule and surrounding erythroplakia at the recipient site of the graft. Analysis revealed cutaneous malignant melanoma. Patient then related a remote history of a suspected skin melanoma of the donor leg that had been treated with excision, with unknown histology. CONCLUSION: This may be the first reported case of a cutaneous malignant melanoma in the oral cavity following an anterolateral thigh free flap reconstruction, emphasizing the importance of obtaining a comprehensive history of skin cancers and closely inspecting the donor site prior to graft harvesting.

Early onset oral tongue cancer in the United States: A literature review.

The incidence of early onset oral tongue squamous cell carcinoma (OTC) has been increasing in the United States, and no clear etiology has been identified. Studies on this topic have generally been small and presented varied results. The goal of this review is to analyze and synthesize the literature regarding early onset OTC risk factors, outcomes, and molecular analyses within the US. To date, studies suggest that early onset OTC patients tend to have less heavy cigarette use than typical onset patients, but there may be an association between early onset OTC and smokeless tobacco (chewing tobacco and snuff) use. Early onset OTC is associated with similar or possibly improved survival compared to typical onset OTC. There has been no evidence to support a significant role for human papillomavirus in development of early onset OTC. Further research with larger cohorts of these patients is needed to better characterize this disease entity.

Hemangiomas of the tongue and the oral cavity in a myotonic dystrophy type 1 patient: A case report.

RATIONALE: Myotonic dystrophy type 1 (DM1) is an autosomal dominant disease caused by a cytosine, guanine, thymine (CTG) trinucleotide repeat expansion in the non-coding region of dystrophia myotonica protein kinase gene, causing a multisystem involvement. To date, few studies have been performed to evaluate skin features in DM1 patients, but none reported on the possible association between the disease and tongue hemangiomas. PATIENTS CONCERNS: We report a case of a 63-year-old woman affected by DM1 and presenting, at the intraoral examination, several swelling and buish lesions occurring on buccal and palatal mucosa, and in the anterior two-thirds and margins of the tongue. DIAGNOSIS: Multiple tongue hemangiomas in DM1 patient. INTERVENTIONS: Color Doppler ultrasound revealed hypoechoic lesions with intermittent color picking suggestive of vascular lesion. Surgical excision was performed under general anesthesia. Histopathological examination was compatible with the diagnosis of cavernous hemangiomas. OUTCOMES: At 6 months follow-up, a part from the cosmetic deformity, patient's hemangiomas did not bleed, but caused functional problems with speaking, mastication, and deglutition, in addition to the same symptoms induced by DM1. LESSONS: This case may add new details to better characterize the DM1 phenotype, suggesting that even tongue hemangiomas may be part of the DM1 multisystem involvement.

Clinical analysis of second primary gingival squamous cell carcinoma after radiotherapy.

INTRODUCTION: Clinically, we have observed that some oral cancer patients have a history of radiotherapy for head and neck cancer; we have named this condition radiotherapy-associated cancer (RAC). Gingival cancer, which is usually juxtaposed with other oral cancer subtypes, is seldom reported individually, and there are few reports on the association between the incidence of oral cancer and history of radiation therapy. Therefore, this study aimed to elucidate the clinicopathological features and prognosis of second primary gingival squamous cell carcinoma after head and neck radiotherapy. MATERIALS AND METHODS: The data collected included 450 patients diagnosed with gingival squamous cell carcinoma from 1964 to 2012 at Sun Yat-sen University Cancer, among whom 52 patients had a history of radiotherapy for head and neck cancer. We retrospectively analysed the differences in the clinicopathological characteristics and prognosis between sporadic gingival squamous cell carcinoma and radiation-associated gingival carcinoma, with an emphasis on gingival carcinoma. RESULTS: Sporadic gingival squamous cell carcinoma is less likely to have more advanced T stage, and the second primary tumour is more likely to be located in the molar area of the maxillary gingiva than in the mandibular gingiva (75.6% vs 24.4%, P < 0.05). The 5-year overall survival of patients with second primary gingival carcinoma was influenced by age distribution, T classification, N classification, clinical TNM stage, histological grade and radiation history in head and neck. Mandibular gingival carcinoma was more likely to have an increased neck lymph node metastasis than maxillary gingival carcinoma (P = 0.001), but there was no significant difference in 5-year overall survival between these two groups (P = 0.828). The main therapy for gingiva carcinoma is surgery or comprehensive treatment based on surgery. CONCLUSIONS: Second primary gingival squamous cell carcinoma after radiotherapy demonstrated particular clinicopathologic features, such as prominent sites and TNM stage; and there was statistically significant difference in 5-year overall survival and prognosis between second primary gingival carcinoma after radiotherapy and sporadic gingival carcinoma.

Oral tongue carcinoma among young patients: An analysis of risk factors and survival.

INTRODUCTION: The incidence of oral tongue squamous cell carcinoma (OTSCC) in younger adults has rapidly increased over the past two decades. While tobacco and alcohol use may be less likely to cause these tumors, it remains controversial whether differences also exist in their prognosis. Our aim is to examine the risk factors for cancer among young (<45 years old) OTSCC patients at our institution, and to compare their recurrence and survival with older patients in a matched cohort. MATERIALS AND METHODS: All OTSCC patients seen at our institution between 2000 and 2015 were reviewed. Patients under 45 who with sufficient treatment information were matched 1:1 on race, T-stage, and N-stage with patients 45 and older. Three-year recurrence and survival were determined in stratified and adjusted Cox regression models. RESULTS: Of 397 OTSCC patients were seen at our institution, 117 (29%) were less than 45 years old. Younger patients were significantly more likely to be female, (50% vs. 39%; p = 0.04) and to abstain from tobacco (51% vs. 39%; p < 0.01). Young patients in the matched cohort were significantly more likely to have a recurrence (HR 3.9 95% CI 1.4-10.5). There was no difference in overall survival. CONCLUSION: Younger OTSCC patients in a matched cohort were more likely to recur within 3 years, although there was no difference in overall mortality. Differences in risk factors and recurrence between older and younger patients suggest that some cancer among younger patients may be distinct from traditional OTSCC.