Update from the 5th Edition of the World Health Organization Classification of Head and Neck Tumors: Tumours of the Oral Cavity and Mobile Tongue.

The fifth chapter of the upcoming fifth edition of the 2022 World Health Organization Classification of Tumours of the Head and Neck titled Tumours of the oral cavity and mobile tongue, has had some modifications from the 2017 fourth edition. A new section "Non-neoplastic Lesions", introduces two new entries: necrotizing sialometaplasia and melanoacanthoma. The combined Oral potentially malignant disorders and Oral epithelial dysplasia section in the 2015 WHO has now been separated and submucous fibrosis and HPV-associated dysplasia are also discussed in separate sections. Carcinoma cuniculatum and verrucous carcinoma are described in dedicated sections, reflecting that the oral cavity is the most common location in the head and neck for both these entities which have distinct clinical and histologic features from conventional squamous cell carcinoma. This review summarizes the changes in Chapter 5 with special reference to new additions, deletions, and sections that reflect current clinical, histological, and molecular advances.

Endoscopic diagnosis value of narrow band imaging Ni classification in vocal fold leukoplakia and early glottic cancer.

OBJECTIVES: To explore the diagnostic value and the correlation between histological diagnosis and the Ni classification under narrow band imaging (NBI) for vocal fold leukoplakia (VFL) and early glottic cancer. METHODS: A total of 91 patients with 119 vocal fold lesions were selected from January 2017 to May 2020. All these patients were subsequently examined by white light imaging (WLI) and NBI endoscopy, and then all lesions were classified by the Ni classification according to the characteristics of intraepithelial papillary capillary loop (IPCL) observed. The gold standard of diagnosis was histopathological results. Eventually, the chi-square and kappa test were applied, respectively, to evaluate the diagnostic value of NBI endoscopy and the consistency of Ni classification and pathological results. RESULTS: The accuracy and sensitivity of NBI endoscopy were significantly higher than that of WLI endoscopy (P < 0.05). For the diagnosis of precancerous lesions under the NBI, the sensitivity, specificity, positive and negative predictive value were 69.6% (16/23), 90.6% (87/96), 64.0% (16/25) and 92.6% (87/94), which for malignant lesions were 84.4% (65/77), 92.9% (39/42), 95.6% (65/68) and 76.5% (39/51). Moreover, for patients with low-grade intraepithelial neoplasia (mild and moderate dysplasia), type IV lesions accounted for the most (69.6 vs 30.4%; χ2 = 36.961, P < 0.001). For high-grade intraepithelial neoplasia or carcinoma in situ, type Va lesions were predominant (χ2 = 30.526, P < 0.001), while type Vb and Vc lesions were dominant in invasive carcinoma (χ2 = 64.373, P < 0.001). Besides, the kappa test revealed that there was a high consistency between Ni classification and pathological diagnosis (Kappa = 0.667, P < 0.001). CONCLUSIONS: The Ni classification can improve the diagnosis accuracy of vocal fold lesions which enables clear visualization of mucosal microvasculature. This is essential for the early diagnosis of VFL and early glottic cancer during routine endoscopic examination.

Tumor budding score predicts lymph node status in oral tongue squamous cell carcinoma and should be included in the pathology report.

BACKGROUND: The majority of oral cavity cancers arise in the oral tongue. The aim of this study was to evaluate the prognostic value of tumor budding in oral tongue squamous cell carcinoma, both as a separate variable and in combination with depth of invasion. We also assessed the prognostic impact of the 8th edition of the American Joint Committee on Cancer's TNM classification (TNM8), where depth of invasion (DOI) supplements diameter in the tumor size (T) categorization. METHODS: Patients diagnosed with primary oral tongue squamous cell carcinoma were evaluated retrospectively. Spearman bivariate correlation analyses with bootstrapping were used to identify correlation between variables. Prognostic value of clinical and histopathological variables was assessed by Log rank and Cox regression analyses with bootstrapping using 5-year disease specific survival as outcome. The significance level for the hypothesis test was 0.05. RESULTS: One-hundred and fifty patients had available material for microscopic evaluation on Hematoxylin and Eosin-stained slides and were included in the analyses. Reclassification of tumors according to TNM8 caused a shift towards a higher T status compared to the previous classification. The tumor budding score was associated with lymph node metastases where 23% of the patients with low-budding tumors had lymph node metastases, compared with 43% of those with high-budding tumors. T-status, lymph node status, tumor budding, depth of invasion, and the combined tumor budding/depth of invasion score were all significantly associated with survival in univariate analyses. In multivariate analyses only N-status was an independent prognosticator of survival. CONCLUSION: Reclassification according to TNM8 shifted many tumors to a higher T-status, and also increased the prognostic value of the T-status. This supports the implementation of depth of invasion to the T-categorization in TNM8. Tumor budding correlated with lymph node metastases and survival. Therefore, information on tumor budding can aid clinicians in treatment planning and should be included in pathology reports of oral tongue squamous cell carcinomas.

Using weighted gene co-expression network analysis to identify key modules and hub genes in tongue squamous cell carcinoma.

BACKGROUND: Tongue squamous cell carcinoma (TSCC) is one of the most common malignant tumors in head and neck, but its molecular mechanism is not clear. METHODS: Weighted gene co-expression network analysis (WGCNA) combining with gene differential expression analysis, survival analysis to screen key modules and hub genes related to the progress of TSCC. Gene Set Enrichment Analysis (GSEA) was used to identify biological pathways that might be involved. RESULTS: Weighted gene co-expression network was constructed based on dataset GSE34105. The blue module and turquoise module most related to the progress of TSCC were identified by the network. Gene Ontology (GO) enrichment analysis showed that 2 key modules were significantly enriched in apoptosis and immunity related biological processes and pathway. Network topology analysis, gene difference analysis and survival analysis were used to screen 9 hub genes (NOC2L, AIMP2, ANXA2, DIABLO, H2AFZ, MANBAL, PRDX6, SNX14, TIMM23). The expression of hub genes was significantly correlated with the prognosis of TSCC. GSEA showed that the high expression group of hub genes was mainly enriched in olfactory transduction, neuroactive ligand receptor interaction, nicotinate and nicotinamide metabolism, and the low expression group was mainly enriched in base excision repair, cysteine and methionine metabolism, oxidative phosphorylation. CONCLUSION: Two key modules and 9 hub genes screened by WGCNA were closely related to the occurrence and prognosis of TSCC. Hub genes can be used as biomarkers and potential therapeutic targets for the accurate diagnosis and treatment of TSCC in the future.

A Proposal to Revise the Histopathologic Grading System of Early Oral Tongue Cancer Incorporating Tumor Budding.

The World Health Organization (WHO) grading system has a low prognostic value for early-stage oral tongue squamous cell carcinoma; greater prognostic power has been shown with tumor budding analysis. In this study, we combined tumor budding analysis with histopathologic grading according to WHO 2017. In our proposal, a revised grade I tumor is defined as a "well differentiated cohesive tumor"; revised grade II as a "moderately differentiated and/or slightly dissociated tumor"; and revised grade III as a "poorly differentiated and/or dissociated tumor." We evaluated the prognostic value of this proposed grading system in a multicenter cohort of 311 cases of early oral tongue squamous cell carcinoma. The proposed grading system showed significant prognostic value in multivariable analysis for disease-specific survival with a hazard ratio of 3.86 and a 95% confidence interval of 1.36-10.9 (P=0.001). For disease-free survival, the proposed grading system showed good predictive power in multivariable analysis (hazard ratio, 2.07; 95% confidence interval, 1.00-4.27; P=0.009). The conventional WHO grading system showed a low prognostic value for disease-specific survival and disease-free survival (P>0.05). In conclusion, the prognostic power of the WHO histopathologic grading improved significantly with incorporation of tumor budding. Our proposed grading system can be easily included in pathology reports.

Validation of the 8th edition of the AJCC/UICC TNM staging system for tongue squamous cell carcinoma.

BACKGROUND: The revised 8th edition of the AJCC/UICC staging system was released in January 2017, and depth of invasion (DOI) was added to the new criteria for T classification in oral cavity cancer. In this study, we evaluated whether the 8th edition presents the prognosis and risk of nodal metastasis in patients with squamous cell carcinoma of tongue more accurately than did the 7th edition. METHODS: The data for 112 patients were obtained and reclassified based on the criteria presented in the 8th edition. RESULTS: Seven patients previously staged as T1 based on the criteria in the 7th edition were reclassified as T2 based on the 8th edition, while 19 T2 patients were reclassified as T3, and 9 T4a patients were reclassified as T3. T3 in the 8th edition represents a homogenous population showing the same prognosis, while T2 in the 8th edition represents a heterogenous population. Nodal metastasis was significantly correlated with T classification in both editions and DOI. However, neither the T classification in the 7th or 8th edition, nor DOI could predict the probability of potential nodal metastasis in patients with cN0 disease. CONCLUSIONS: The classification on T3 in the 8th edition can be seen as reasonable with regard to prognosis. Nodal metastasis was significantly correlated with T classification and DOI; however, the probability of subsequent nodal metastasis in patients with T2N0 was almost same for the criteria in the 7th and 8th editions, therefore, the same careful management as before is required for patients with N0 disease.

Survival and recurrence of resectable tongue cancer: Resection margin cutoff value by T classification.

BACKGROUND: The purpose of this study was to determine an appropriate cutoff value for the resection margin according to the initial T classification. METHODS: The medical records of 151 patients treated by surgery for tongue cancer were retrospectively reviewed to identify the significant perioperative parameters and appropriate cutoff value associated with disease-specific survival (DSS) and recurrence-free survival (RFS). RESULTS: The posterior resection margin was significantly correlated with survival and local recurrence (P = .020 and .016, respectively), whereas the deep resection margin was correlated with overall recurrence (P = .047). The cutoff values of the posterior and deep resection margins for survival and recurrence were different and larger in the advanced-stage T classification group (0.45 cm vs 0.95 cm and 0.25 cm vs 0.80 cm, respectively). CONCLUSION: Posterior and deep resection margins are significant prognosticators in tongue cancer. A larger resection margin may be needed in advanced-stage T classification.

Granuloma piógeno de localización atípica: reporte de un caso / Atypical location of a pyogenic granuloma: report of a case

El granuloma piógeno es una lesión que se manifiesta con frecuencia en piel y cavidad oral, está relacionado con diversas causas como irritación crónica, trauma y cambios hormonales. Clínicamente se muestra como una lesión hiperplásica altamente vascularizada de tamaño por lo regularmenor de 2 cm, de base pedunculada o sésil y de crecimiento lento. No tiene predilección por edad o sexo, tiende a aparecer sobre todo en la encía, labios y mucosa bucal, con muy pocos casos reportados en la región lingual, motivo por el que se lleva a cabo el presente reporte de caso, a fin de describir esta lesión en el tercio posterior del dorso delengua en un paciente de 85 años de edad.

Piogenyc granuloma is an injury commonly seen in the skin and oralcavity, it is related to several causes such as chronic irritation, traumaand hormonal changes. Clinically, it is presented as a hyperplasicinjury highly vascular-related, with a size generally no bigger than 2cm pedunculated in base or sessile and slow in growth. Without showingany preferece in age or gender, it tends to appear mainly on the gums,lips and oral mucosae, with very few reported cases in the lingual area.Therefore the hereby report is delivered as means to describe this kindof injury with a very unusual location.

Lipoma intraoral: reporte de un caso clínico / Intraoral lipoma: report of a clinical case

Dentro de las neoplasias más frecuentes de tejidos blandos mesenquimáticos, el lipoma es el de mayor frecuencia. A nivel de cabeza y cuello, su incidencia es inferior, siendo de 2 a 4 por ciento. En la cavidad bucal, la ubicación más usual es en la lengua. Histológicamente, se observan adipocitos separados por tabiques fibrosos. El diagnóstico diferencial se realiza con tumor de células granulares, neurofibroma, fibroma traumático y malformaciones de las glándulas salivales. En el siguiente artículo se describirá un caso clínico con su técnica quirúrgica.

Among the most frequent neoplasms of soft mesenchymal tissues, lipoma is the most frequent. At head and neck level, the incidence is lower, being 2 to 4 percent. In the oral cavity, the most usual location is on the tongue. Histologically, adipocytes are seen separated by fibrous septa. The differential diagnosis is made with granular cell tumor, neurofibroma, traumatic fibroma and malformations of the salivary glands. The following article will describe a clinical case with its surgical technique.

Carcinoma epidermoide de la lengua: presentación de un caso / Epidermoid carcinoma of the tongue: report of a case

El carcinoma epidermoide es el cáncer bucal más frecuente que representamás de 90% de todos los tipos de cáncer de la cavidad oral. Se presenta el caso de masculino de 41 años de edad con un carcinoma epidermoide de rápida evolución a nivel de la lengua. Se observó una estomatosis localizada en el borde izquierdo de la lengua caracterizada por una neoformación de bordes elevados indurados, centro ulcerado, de 2 cm de diámetro y friable. Se detectaron adenomegalias del lado izquierdo de 2 cm. El paciente refería dolor a nivel del cuello y a niveldel oído izquierdo. Fumaba hasta dos cajetillas de cigarros al día. El estudio histopatológico reveló un carcinoma epidermoide ulcerado, invasor con áreas moderadamente poco diferenciadas. Se inició tratamientocon radioterapia 25 sesiones y quimioterapia con cisplatino. Se determinó mala tolerancia y respuesta al tratamiento establecido, por lo que éste se suspendió y se optó por tratamientos paliativos. La evolución del paciente fue tórpida y falleció a los 10 meses del diagnóstico. Las neoplasias de la cavidad oral son relativamente poco frecuentes, pero la letalidad alcanza hasta 78 por ciento entre las neoplasias de las vías aerodigestivas superiores y se diagnostican en etapas avanzadasen 65 por ciento de los casos. La prevención es fundamental, sobre todo la supresión del tabaquismo.

Epidermoid carcinoma is the most frequent oral cancer (90% of alloral cancer). We present the case of a 41-year-old man with oralcancer on the tongue. The lesion was localized on the left side of thetongue and was characterized by an ulcerated tumor with induratedborders, 2 cm of diameter. Lymph node metastasis was detected onthe neck. The patient had left ear pain and also a pain in the neck.He smoked two packs of cigarettes per day. The histopathologic studyrevealed an epidermoid carcinoma with poor and well-diff erentiatedareas. Radiotherapy and chemotherapy with cisplatin on were started.The patient did not tolerate and had a poor response, so the treatmentwas suspended. The patient died 10 months after the diagnosis. Oralcarcinoma is not frequent but the mortality is high, 78%, between thecarcinomas of the aerodigestive tract and frequently it is diagnosedwhen in advanced stages in 65% of the cases. The most important arethe prevention, mostly, tobacco consumption.

Update from the 4th Edition of the World Health Organization of Head and Neck Tumours: Tumours of the Oral Cavity and Mobile Tongue.

There have been several additions and deletions in Chapter 4 on Tumours of the oral cavity and mobile tongue in the 2017 fourth edition of the World Health Organization Classification of Tumours of the Head and Neck. This chapter excludes the oropharynx, which now is a stand-alone chapter acknowledging the uniqueness of the oropharynx from the oral cavity. New entries in Chapter 4 include rhabdomyoma, haemangioma, schwannoma, neurofibroma and myofibroblastic sarcoma in the section titled Soft tissue and neural tumours. Discussion of salivary gland entities have been reduced and includes mucoepidermoid carcinoma and pleomorphic adenoma as the other salivary gland types are discussed elsewhere. In the Haematolymphoid tumours section, like the salivary gland section, only tumors that commonly present in the oral cavity are discussed in Chapter 4. Excluded entities in the updated classification include papillary hyperplasia, median rhomboid glossitis, keratoacanthoma, focal oral mucinosis, and secondary tumors. This article will summarize the changes in the new classification since the 2005 edition focusing on selected entities that have had significant changes along with new entries.

Squamous Cell Carcinoma as the Most Common Lesion of the Tongue in Iranians: a 22-Year Retrospective Study.

The tongue has been globally considered as an indicator of general health for millennia. This study aimed to determine the prevalence and distribution of tongue lesions in an Iranian population. In this retrospective study, data from 6,435 oral biopsy reports over a 22-year period (1992-2014) were retrieved from archives of Oral and Maxillofacial Pathology Department, Shahid Beheshti Dental School, Tehran, Iran. These reports were analyzed according to age, sex, type of lesion and location. Prevalence of tongue lesions were reported as percentages. Out of total oral lesions, 238 (3.7%) were found in the tongue, with the incidence peak (42%) being between 41-60 years. Men constituted 53% and women 47%of patients. The youngest patient was a 3-year-old girl with pyogenic granuloma and the oldest one was a 93-year-old man with squamous cell carcinoma (SCC). SCC was the most common (25%) lesion generally found in the lateral border of the tongue with a male predilection. The second and third most prevalent lesions of the tongue were benign keratosis (frictional keratosis) (13.4%) and leukoplakia (13%).White-red lesions (38.6%) were the most frequent subgroup followed by neoplastic lesions (28%). Moreover, irritation fibroma, non-specific ulcers, squamous papilloma, and hemangioma were found as the most frequent lesions in their related subgroups.Given the high rate of SCC of the tongue in Iranian patients, this area should be examined more carefully by dental practitioners and physicians.

MRI in differentiation of benign and malignant tongue tumors.

The differential diagnosis of benign and malignant tongue tumors is crucial to treatment and prognosis. Magnetic resonance imaging (MRI) is the preferred modality for the evaluation of tongue carcinomas. Dynamic contrast-enhanced (DCE)-MRI can reflect the density, integrity, and leakiness of tumor vasculature, and the time-intensity curve (TIC) patterns derived from DCE-MRI results can differentiate benign from malignant tumors based on differences in vascular structure. Diffusion-weighted (DW)-MRI is based on the random thermal motion of water molecules and can provide information on the cellular and tissue microstructure of the tumor. A low apparent diffusion coefficient (ADC) derived from DW-MRIs may indicate a malignant tumor. Thus, ADC values and TIC parameters yield complementary information on tumors that may improve diagnostic accuracy. Indeed, the combination of DCE-MRI and DW-MRI is a comprehensive reflection of the pathological status of the tongue tumor, so utilization of these MRI modalities may facilitate the diagnostic differentiation of benign from malignant tumors of the tongue.

Vital-dye-enhanced multimodal imaging of neoplastic progression in a mouse model of oral carcinogenesis.

In this longitudinal study, a mouse model of 4-nitroquinoline 1-oxide chemically induced tongue carcinogenesis was used to assess the ability of optical imaging with exogenous and endogenous contrast to detect neoplastic lesions in a heterogeneous mucosal surface. Widefield autofluorescence and fluorescence images of intact 2-NBDG-stained and proflavine-stained tissues were acquired at multiple time points in the carcinogenesis process. Confocal fluorescence images of transverse fresh tissue slices from the same specimens were acquired to investigate how changes in tissue microarchitecture affect widefield fluorescence images of intact tissue. Widefield images were analyzed to develop and evaluate an algorithm to delineate areas of dysplasia and cancer. A classification algorithm for the presence of neoplasia based on the mean fluorescence intensity of 2-NBDG staining and the standard deviation of the fluorescence intensity of proflavine staining was found to separate moderate dysplasia, severe dysplasia, and cancer from non-neoplastic regions of interest with 91% sensitivity and specificity. Results suggest this combination of noninvasive optical imaging modalities can be used in vivo to discriminate non-neoplastic from neoplastic tissue in this model with the potential to translate this technology to the clinic.

Automatic upstaging of tongue squamous cell carcinoma with lateral extrinsic muscle involvement is not justified.

The TNM classification for oral malignancies has been criticized for its upstaging to T4a when tumour involves styloglossus, hyoglossus, palatoglossus and genioglossus. The aims of this study were to (1) create an anatomical computer atlas of extrinsic tongue musculature, and (2) reassess the original staging of pre-treatment archived magnetic resonance images (MRI) of tongue carcinomas using the strict extrinsic muscle criteria. The anatomy of the extrinsic tongue muscles was mapped using images from the Visible Human Project (VHP) to create a computer model of the extrinsic tongue muscles. This was co-registered with 87 archived pre-staging MRI scans of tongue carcinomas to assess tumour ingress of the extrinsic tongue muscles. Of the 87 image sets reviewed, 16 were of superficial tumours not visible on MRI. In the remaining 71 cases that showed positive extrinsic muscle tumour ingress, 52% were upstaged from T1/2/3 tumours to cT4a based upon this finding. Extrinsic lateral and genioglossus muscle invasion did not predict occult cervical lymph node invasion or disease-related survival. In conclusion, tumour invasion of styloglossus or hyoglossus would result in the majority of lateral tongue tumours being staged T4a. Such stratification is of little clinical relevance, and an alternative more reliable method is required.

A detailed anatomical assessment of the lateral tongue extrinsic musculature, and proximity to the tongue mucosal surface. Does this confirm the current TNM T4a muscular subclassification?

PURPOSE: The current T4a subclassification of the TNM staging system for oral malignancies has been criticised as based almost exclusively on anatomical data. The aim of this study was to provide anatomical confirmation of the muscular constraints of T4a classification of oral tongue tumours. METHODS: A detailed anatomical study describing and measuring the adjacency of the named extrinsic tongue muscles to the lateral tongue surface was completed on the Visible Human Female (VHF). The distance of styloglossus and hyoglossus to the over lying mucosa were determined. RESULTS: The appearance, position, orientation and anatomical relationships of the lateral tongue extrinsic muscles, with comparison to their classical descriptions are described. The right VHF styloglossus was 1.3 mm (0.33-1.48) and left 2.91 mm (0.66-7.68) from the mucosal surface in the axial plane. The right VHF hyoglossus was 2.93 mm (1.48-4.96) and left 4.33 (1.68-8.71) from the mucosal surface in the axial line. CONCLUSIONS: In the lateral tongue, styloglossus and hyoglossus are very superficial. The inclusion criteria of hyoglossus and styloglossus in the T4a staging does not appear justified based upon their anatomical position.

Gene expression profiling of archival tongue squamous cell carcinomas provides sub-classification based on DNA repair genes.

A subgroup of patients with squamous cell carcinoma of the head and neck (SCCHN) comprise young persons under the age of 40, who have not been heavily exposed to the classical risk factors, smoking and alcohol. The number of SCCHN in young adults, particularly tongue tumours, is increasing in several parts of the world. Here we employed a novel gene expression array methodology specifically developed for analysis of degraded RNA and investigated the expression of 502 cancer-related genes in archival paraffin-embedded SCCHN of the tongue from young (< or =40) and elderly patients (> or =50). Genes detected as de-regulated in tumours compared to non-malignant controls were in concordance with results from earlier studies of fresh frozen material. No genes were detected as significantly differentially expressed between young and old patients suggesting that the overall pathobiology of SCCHN is similar in young and old. Unsupervised clustering divided tumours into three groups, irrespective of age, where several differentially expressed DNA repair genes were a prominent separation factor. High levels of DNA repair genes associated with impaired therapeutic response to radiation, suggesting that DNA repair genes play a role in clinical outcome after radiotherapy.

Malignancy grading is no better than conventional histopathological grading in small squamous cell carcinoma of tongue and floor of mouth: retrospective study in 128 patients.

There is an ongoing debate about the predictive value of histopathological parameters in oral cancer. In the past decades, the emphasis was on the possible added value of the so-called malignancy grading system. In a retrospective study on 128 previously untreated patients with a T1 or T2 squamous cell carcinoma of the tongue and the floor of the mouth, the value of the classical Broders' grading system and the malignancy grading system were compared with regard to various outcome measures such as regional metastasis, local recurrence and 5-year survival. The results show that neither of the histological grading systems has a strong predictive value and that none is superior to the other.