A Rare Case of Dual Metachronous Primary Malignancies, Chronic Myeloid Leukemia, and Tongue Carcinoma in a Patient With Long-Standing Systemic Lupus Erythematosus: A Case Report and Review of Literature.

Patients with long-standing autoimmune diseases like systemic lupus erythematosus (SLE) are at a higher risk of developing hematological malignancies. However, chronic myeloid leukemia (CML) has rarely been reported in patients with SLE. Advancements in medical diagnostics and treatment have led to the life expectancy of SLE and CML patients moving closer to that of the general population, and it is not uncommon to encounter more than one malignancy in a cancer survivor. Although squamous cell carcinoma (SCC) of the skin has been reported in CML patients, mucosal SCC of the head and neck has rarely only been reported in CML survivors. The objective of this case report is to share our experience in treating a patient with dual metachronous primary malignancies, CML, and tongue carcinoma, along with long-standing SLE, managed by a multidisciplinary team.

Small Cell Non-keratinizing Neuroendocrine Carcinoma Involving the Larynx and the Base of the Tongue: A Rare Case With a Locally Aggressive Spread.

Squamous cell carcinoma is the most predominant type of malignancy in the head and neck region with neuroendocrine carcinomas (NECs) being a rare occurrence. Here we report a rare case of small cell non-keratinizing NEC (WHO grade 3), TNM (tumor, node, and metastasis) stage T3N1M0, involving the larynx and the base of the tongue, in a 54-year-old male patient, demonstrating its rarity in an uncommon anatomical site and an aggressive and relatively uncommon pattern of spread for this tumor, over a period of two months. NECs in the head and neck region, especially those affecting the larynx and the posterior third of the tongue, remain exceedingly rare, comprising only a small fraction of malignancies in this region. The aggressive nature and distinct pattern of spread observed in this case underscore the importance of recognizing such unusual presentations for appropriate diagnosis and management. Given the rarity of this tumor type, a comprehensive understanding of its clinicopathological features is essential for guiding effective treatment strategies. We also discuss the treatment.

Implementing a deep learning model for automatic tongue tumour segmentation in ex-vivo 3-dimensional ultrasound volumes.

Three-dimensional (3D) ultrasound can assess the margins of resected tongue carcinoma during surgery. Manual segmentation (MS) is time-consuming, labour-intensive, and subject to operator variability. This study aims to investigate use of a 3D deep learning model for fast intraoperative segmentation of tongue carcinoma in 3D ultrasound volumes. Additionally, it investigates the clinical effect of automatic segmentation. A 3D No New U-Net (nnUNet) was trained on 113 manually annotated ultrasound volumes of resected tongue carcinoma. The model was implemented on a mobile workstation and clinically validated on 16 prospectively included tongue carcinoma patients. Different prediction settings were investigated. Automatic segmentations with multiple islands were adjusted by selecting the best-representing island. The final margin status (FMS) based on automatic, semi-automatic, and manual segmentation was computed and compared with the histopathological margin. The standard 3D nnUNet resulted in the best-performing automatic segmentation with a mean (SD) Dice volumetric score of 0.65 (0.30), Dice surface score of 0.73 (0.26), average surface distance of 0.44 (0.61) mm, Hausdorff distance of 6.65 (8.84) mm, and prediction time of 8 seconds. FMS based on automatic segmentation had a low correlation with histopathology (r = 0.12, p = 0.67); MS resulted in a moderate but insignificant correlation with histopathology (r = 0.4, p = 0.12, n = 16). Implementing the 3D nnUNet yielded fast, automatic segmentation of tongue carcinoma in 3D ultrasound volumes. Correlation between FMS and histopathology obtained from these segmentations was lower than the moderate correlation between MS and histopathology.

Transoral Robotic surgery - excision of Tongue base Tumour with the Entire Hyoid bone in a Salvage Setting.

Objectives - Transoral robotic surgery (TORS) is an already well established modality of treatment for early stage oropharyngeal cancer. This case report will throw light on the role of TORS as a treatment option for oropharyngeal cancer in a salvage setting. Methods - This is a case of a 69 year old patient who was a follow up case of carcinoma base of tongue, status - post concurrent chemoradiation who presented with residual disease at the primary site. Results - TORS was used as a successful treatment modality for base of tongue carcinoma in a salvage setting. The surgical procedure included removal of the entire hyoid bone in toto along with the tumour which is not reported in literature. The procedure also helped us in achieving an R0 resection. Conclusion - TORS should be considered as an important management modality for tongue base tumours in upfront as well as salvage setting.

Research on the role of cellular autophagy in the sensitivity of human tongue cancer cells to radiotherapy and chemotherapy.

OBJECTIVE: This paper aims to investigate the role of cisplatin-induced autophagy in human tongue squamous carcinoma Tca8113 cells. METHODS: After inhibiting the expression of autophagic proteins with different autophagy inhibitors (3-methyladenine, chloroquine), the sensitivity of human tongue squamous cell carcinoma (Tca8113) cells to killing by gradient concentrations of cisplatin and gradient doses of radiation was detected using a colony formation assay. Further, the changes of autophagy expression in Tca8113 cells that had been treated with cisplatin and radiation were detected using western immunoblot, GFP-LC3 fluorescence and transmission electron microscopy. RESULTS: The sensitivity of Tca8113 cells to cisplatin and radiation was significantly increased (P < 0.05) after reducing autophagy expression using different autophagy inhibitors. Meanwhile, the expression of autophagy in the cells was significantly increased by cisplatin and radiation treatment. CONCLUSION: Tca8113 cells upregulated autophagy under the effect of either radiation or cisplatin, and the sensitivity of Tca8113 cells to cisplatin and radiation could be improved by inhibiting autophagy using multiple pathways.

Preoperative MRI for oral tongue squamous cell carcinoma: timing and correlation to histopathology.

Magnetic resonance imaging (MRI) is an integral part of the evaluation of local and regional disease in tongue squamous cell carcinoma prior to surgery. The aim of this study was to evaluate the accuracy of MRI in assessing tumour dimensions, as well as the impact of the time-lag from diagnostic biopsy on the accuracy of MRI. The medical records of 64 patients with tongue carcinoma were reviewed retrospectively. Tumour maximum diameter and tumour depth of invasion were compared between pathology and MRI (T1- and T2-weighted). MRI-derived maximum tumour diameter and depth of invasion correlated strongly with histopathology: T1-weighted (r = 0.700 and r = 0.813, respectively) and T2-weighted (r = 0.734 and r = 0.834, respectively). A significant correlation was found between measurements on T1 and T2 MRI for both parameters (P = 0.955 and P = 0.984, respectively). The accuracy rate of MRI for T-staging of early tumours was low: 10% for T1 tumours; 39.3% for T2 tumours. A time-lag of less than 2 weeks between the diagnostic biopsy and MRI adversely affected the correlation of tumour dimensions. MRI is a reliable tool for evaluating tongue carcinoma; however, it overestimates early tumours. A 2-week delay after diagnostic biopsy is desired before completing an MRI. Alternatively, if logistics allow, a pre-biopsy MRI is preferred, especially for T1-T2 tumours.

Tissue Transfer After Tongue Resection: Micro-Vascular Reconstruction Using Radial Artery Free Flap versus Reconstruction by Split Thickness Skin Graft in T2 Lesions of Tongue Carcinoma.

To compare postoperative complications, functional rehabilitation, surgical outcomes of the radial artery forearm free flap (RAFFF) and split thickness skin graft (STSG) reconstruction of postsurgical defect in T2 lesions of cancer oral cavity. Observational Prospective comparative study. Academic tertiary referral centre. In our study of forty four patients, after tumour resection, half underwent reconstruction using RAFFF (Group I) and another half by STSG (Group II). All of the patients were followed postoperatively to determine and compare their functional outcomes related to donor site and recipient site complications, speech, deglutition and mouth opening. The speech intelligibility and deglutition were each assessed using Articulation Handicap Index and Vedio-fluoroscopy using the Functional oral intake scale. Operative time for STSG reconstruction was shorter at 2.2 ± 0.97 SD hours compared to 5.9 ± 1.24 SD hours for RAFFF reconstruction. Hospital stay was 8.3 ± 1.19 SD days for STSG patients and 12.6 ± 1.7 SD days for RAFFF patients. The functional outcomes of speech quality and swallowing were near comparable in both groups but the donor site complications were significant in the RAFFF group. Operative time, hospital stay and donor site complications are both significantly reduced with the STSG as opposed to RAFF. Functional and oncologic results of both methods are near comparable. To conclude, STSG can be used for reconstruction of the post-surgical defects in T2 lesions of the tongue.

Tongue Carcinoma - 20-Year Comparative Survival and Mortality Analysis by Age, Sex, Race, Stage, Grade, Cohort Entry Time-Period and Disease Duration.

Cancer of the tongue is an uncommon cancer site, with only 31,378 cases in the SEER 1975-2017 database, fewer than 1% of all reported cancers. This article updates trends in incidence, prevalence, short and long-term survival and mortality of tongue carcinoma.

Early-Stage Oral Tongue Squamous Cell Carcinoma and a Positive Sentinel Lymph Node Biopsy: Description of a Prognostic Correlation between Pre-Treatment Inflammatory Biomarkers, the Depth of Invasion and the Worst Pattern of Invasion.

The aim of this study was to investigate the correlation between pre-treatment inflammatory biomarkers and the post-operative depth of invasion (DOI) and worst pattern of invasion (WPOI) in early-stage oral tongue squamous cell carcinoma (OTSCC) by means of positive sentinel lymph node biopsy (SLNB). A retrospective analysis of patients affected by cN0 T1-T2 OTSCC who had undergone an SLNB at the National Cancer Institute of Naples was performed. The patients were studied using an evaluation of the pre-treatment neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammatory index (SII), and a histopathological analysis of the DOI and WPOI. The statistical analysis showed that among the prognostic biomarkers, the NLR was a significant predictor of high WPOI values (p = 0.002). The cut-off NLR value was 2.52 with a probability of developing a positive sentinel lymph node biopsy (SLNB) of 30.3%. In contrast, the DOI value was 5.20 with a probability of developing a positive SLNB of 31.82%. Regarding the WPOI, increasing the WPOI class increased the likelihood of a positive SLNB occurrence, and a positive significant correlation was found between the WPOI and SLNB (Csp = 0.342; p < 0.001). Pre-treatment NLR, together with post-surgical DOI and WPOI, can be a reliable predictor of occult neck metastasis in patients affected by early-stage OTSCC with a clinically negative neck. Further prospective studies with a larger series will be needed to confirm the results obtained and to better define the NLR, WPOI and DOI cut-off values in order for elective neck dissection to be recommended in relation to a clinically negative neck.

Application of near-infrared fluorescence imaging in lingual lymph node screening and drainage pattern observation for tongue cancer.

Objective: Lingual lymph node (LLN) metastasis is regarded as an indicator of unfavorable prognosis and a crucial sign of the high degree of primary tumor aggressiveness. However, detecting LLN metastasis is an important but frequently overlooked aspect of diagnosis and surgical treatment planning. The study aims to identify LLNs by intraoperative near-infrared (NIR) fluorescence imaging with indocyanine green absorbed into human serum albumin (ICG: HSA) and describe the presence of lymphatic drainage channels from the floor of the mouth in patients with tongue carcinoma. Materials and Methods: 21 patients diagnosed with cT1-T4 squamous cell carcinoma (SCC) of the tongue margin and scheduled to undergo tumor resection and unilateral neck dissection were enrolled. After exposing the neck, the patients were injected with 0.3 ml of ICG: HSA (500 µM) in three quadrants around the tumor, excluding the mucous membrane of the basal region cavity. Employing a near-infrared fluorescence imaging system, the fluorescence of levels I, II, III, and IV was measured during neck dissection. Results: LLNs were detected in four patients and were identified as metastatic LLNs in all 21 patients. The near-infrared fluorescence imaging system showed the existence of lymphatic drainage channels in the floor of the mouth. In patients receiving peritumoral injection of ICG: HSA, the mean fluorescence intensity (MFI)of metastatic lymph nodes (LNs) (178.4 ± 64.39, mean ± SD) was higher than that in non-metastatic LNs (132.0 ± 76.5, mean ± SD) (p < 0.05). Conclusion: NIR fluorescence imaging with ICG: HSA could be used for intraoperative identification of LLNs and assist in the determination of metastatic lymph nodes for tongue carcinoma patients. Additionally, this finding demonstrates the feasibility of near-infrared fluorescence imaging in defining lymphatic drainage channels in the head and neck.

Comparison between three age-stratified cohorts reveals poor prognosis of young patients with tongue carcinoma.

Objectives: Investigation of the prognosis of young patients with tongue carcinoma has been the focus of several recent studies aimed at improving future precision treatment. Most studies have been two-cohort investigations comparing young and older patients, who have wide discrepancies in prognosis. Older patients, especially those aged >70 years, often have a poor general condition. This affects the prognosis of the older cohort and accounts for the discrepancies observed in two-cohort studies. Accordingly, in this study, older patients (aged ≥71 years) were separated and compared to young and middle-aged patients. Methods: A total of 257 patients with oral tongue carcinoma referred during 2011-2017 were analyzed. Patients were sorted into young (aged ≤40 years), middle-aged (aged ≥41 and ≤70 years), and older (aged ≥71 years) groups. Overall survival (OS) and disease-free survival (DFS) were compared among the groups. Furthermore, patterns of recurrence rates were compared. Results: Compared with young patients, there was no difference in OS or DFS for older patients (hazard ratio [HR]: 1.2, 95% confidence interval [CI]: 0.5-2.7 and HR: 0.7, 95% CI: 0.4-1.2, respectively) in a multivariate analysis. There was also no difference in OS (HR: 0.6, 95% CI: 0.3-1.3) for middle-aged patients. However, middle-aged patients had low recurrence rates (HR: 0.5, 95% CI: 0.3-0.8). With respect to the recurrence type, middle-aged patients had a low local recurrence rate (HR: 0.3, 95% CI: 0.1-0.7). Conclusion: Three-cohort studies should be conducted to evaluate whether the prognosis of young patients with tongue carcinoma is truly poor in terms of future precision treatment.

Neuropsychiatric Symptoms in a p16-Positive Tongue Carcinoma Patient: An Unexpected Diagnosis.

Differential diagnosis of neuropsychiatric symptoms in a patient with an underlying malignancy is exhaustive. 5-fluorouracil (5-FU) is one of the most widely used chemotherapy agents and it is often used as the first-line regimen in head and neck malignancies. We present a case of an elderly female with an underlying locally advanced p16-positive squamous cell carcinoma of the tongue who presented with manic symptoms for one week after cycle 2 of chemotherapy. Multidisciplinary management by otorhinolaryngologists with psychiatrist and oncologist led to the cessation of 5-FU, administration of antipsychotics, and replacement with a different chemotherapy agent, leading to complete resolution of manic symptoms. Possible mechanisms of the 5-FU-induced manic episode with its treatment are discussed in this report.

Is perioperative brachytherapy effective in carcinoma of the tongue?

Purpose: To analyze the results of patients treated with perioperative interstitial brachytherapy (ISBT) in tongue carcinoma (TC). Material and methods: From April 2009 to May 2015, 43 squamous cell carcinoma consecutive patients diagnosed with TC were treated with limited partial glossectomy and perioperative ISBT, using high-dose-rate (HDR). Twenty- seven patients were treated by brachytherapy (BT), and sixteen received BT as a complement to subsequent external beam radiotherapy (EBRT) after results of lymph node dissection. Median age was 66 years. Distribution by stage, included 10 patients stage I, 14 stage II, 10 stage III, and 9 stage IV. Eighteen patients had negative margins, nineteen margin involvement, and in six cases, the margin was < 5 mm. Results: With a median follow-up of 54 months, LC at 3 and 5 years was 87% and 84%, respectively. LC was 95% at five years in patients with clear margins, and 75% with involved margins. LC in N0 patients treated with BT was 83% at 5 years, and in patients N+ with posterior EBRT treatment, LC was 86%. By tumor size, we found one local relapse in 13 cases T1, in 5 of 27 patients T2 was found, and no local relapse T3 with LC of 87%, 70%, and 100% respectively at five years. Regional control (RC) was 81% at 3 and 5 years. We found a metastasis-free survival of 91% at 3- and 5-year. Twenty-three patients have died, 11 of them due to other causes, with overall survival of 56% at three years and 53% at five years. Conclusions: Combined treatment with conservative surgery and ISBT shows similar results to radical surgery or RT alone, allowing a more patient-tailored approach, with good organ function preservation and cosmetic outcomes.

A comparative study between CT, MRI, and intraoral US for the evaluation of the depth of invasion in early stage (T1/T2) tongue squamous cell carcinoma.

OBJECTIVES: This study aimed to clarify the accuracy of intraoral ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI) in preoperative image depth of invasion (DOI) measurement of T1/T2 tongue cancer through comparison with histopathological measurements. METHODS: Imaging of the primary lesions was performed at our hospital; the lesions were classified into T1 and T2 based on the 8th edition of the AJCC/UICC, and surgery performed. There was histopathological confirmation of lesions as squamous cell carcinoma in 48 patients with tongue cancer. T3 and T4 cases, cases in which preoperative chemotherapy and radiation therapy were performed, and cases where biopsy was performed before imaging were excluded. The radiological DOI in US, CT, and MRI and the histopathological DOI as base were comparatively investigated and statistical analyses were performed by Bland-Altman analysis and Spearman's rank correlation coefficient. RESULTS: Bland-Altman analysis showed that the US radiological DOI was overestimated by an average of 0.2 mm compared to the histopathological DOI, while CT and MRI radiological DOI were overestimated by an average of 2-3 mm. The comparison of CT and MRI revealed that the difference between the MRI and histopathological DOI, as well as the 95% limit of agreement, were smaller than those of the CT radiological DOI. CONCLUSIONS: US is the most accurate preoperative diagnostic tool for T1 and T2 squamous cell carcinoma; CT and MRI tend to have an overestimation of about 2-3 mm and so caution is required.

A case of vastus lateralis muscle metastasis of tongue carcinoma.

Distant metastasis is the most important prognostic factor for head and neck cancer. This report presents the case of a 50-year-old man with distant metastasis of tongue carcinoma to the vastus lateralis muscle which presented to Nihon University Itabashi Hospital, Tokyo, Japan. Tumourectomy was performed with a diagnosis of tongue carcinoma (cT2N0M0, Stage II). Seven months later, radical neck dissection was performed for lymph node metastasis to a left supraclavicular lymph node. In addition, metastasis was then detected outside the neck dissection region. Tumourectomy and radiotherapy (50 Gy) were, therefore, added to the treatment regimen. However, left-sided vastus lateralis muscle metastasis was then observed. To the best of our knowledge, this is the first report of distant metastasis of oral squamous cell carcinoma to the vastus lateralis muscle.

Value of [18F]FDG PET-CT in the follow-up of surgically treated oral tongue squamous cell carcinoma: single centre cohort analysis on 87 patients.

BACKGROUND: To evaluate the diagnostic performance of [¹8F]fluorodeoxyglucose positron emission tomography/computed tomography ([¹8F]FDG-PET/CT) scan in detecting local recurrences in patients with surgically treated oral tongue squamous cell cancer (OTSCC). MATERIAL AND METHODS: Eighty-seven patients who had undergone surgery for OTSCC were monitored clinically and [¹8F]FDGPET/CT and magnetic resonance (MR). PET uptakes were classified as functional (Type A), suspicious (Type B), or highly suggestive of local recurrence (Type C). A multidisciplinary team (MDT) evaluated case-by-case the surveillance strategy based on PET uptake. RESULTS: Fifty-nine patients presented FDG-PET uptake during follow-up: this report was significantly more frequent in patients who received flap reconstruction than in those without (73% vs 50%; p = 0.05). In 13 patients with Type A (n = 1), Type B (n = 9), and Type C (n = 3) uptakes an additional MR was considered preferable and discovered recurrence in 12.PET-CT had 9 true positives, 17 false positives, 71 true negatives, and no false-negative, resulting in sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of 100%, 80.7%, 34.6%, and 100%. CONCLUSIONS: The present results demonstrated a change in diagnostic strategy, as decided by the MDT, in about one-fifth of patients. The results should prompt in designing a rational surveillance schedule in surgically treated OTSCC.

Association of IgA Nephropathy with Squamous Cell Carcinoma of the Tongue: - Case Report and Review of Literature.

A 32-year-old habitual tobacco chewer was diagnosed with squamous cell carcinoma of the tongue. He was initiated on chemo-radiation therapy. After completing 23 cycles of radiation and four cycles of cisplatin-based chemotherapy, he presented with acute nephritic syndrome. Renal biopsy showed IgA nephropathy and acute tubular injury. With supportive care, renal function stabilised with a reduction in proteinuria. We wish to highlight the poorly understood association between mucosal malignancies and IgA nephropathy. It is also interesting to note the peculiar temporal profile of glomerular involvement in our patient, where the onset of the glomerulonephritis was after the initiation of chemo-radiotherapy. This is unlike what has been described earlier.

Prognostic Role of Tumor-Infiltrating Lymphocytes and Tumor Budding in Early Oral Tongue Carcinoma.

OBJECTIVES/HYPOTHESIS: Occult lymph metastasis is an important prognosticator for the treatment of early oral tongue squamous cell carcinoma (SCC). The objective of this study was to evaluate the prognostic significance of tumor-infiltrating lymphocytes (TILs) in early oral tongue SCC. The combination of the TIL subtype and intermediate- or high-grade budding scores was investigated as a prognostic marker for occult neck metastases. STUDY DESIGN: Retrospective study. METHODS: Specimens from 62 patients with early oral tongue SCC treated with only primary surgery were analyzed by immunohistochemistry for CD4+, CD8+, FoxP3+, and CD45RO+ T cells and CD163+ macrophages. The highest number of each TIL subtype was counted in two areas of parenchyma and stroma in the tumor (Tumor) and peripheral stroma of the invasion margin. RESULTS: Based on multivariate analysis, a high density of Tumor CD163+ macrophages served as the poorest prognostic factor for regional control (RC) and disease-free survival (DFS). Patients with both a high density of Tumor CD163+ macrophages and an intermediate- or a high-grade budding score had a poor prognosis for RC according to the log-rank test. CONCLUSIONS: In summary, each TIL subtype may use different mechanisms during early and advanced stages of oral tongue SCC. A high density of Tumor CD163+ macrophages was determined to be a risk factor for RC and DFS as well as an additional stratification factor for RC in patients with intermediate- or high-grade budding scores. Therefore, identifying TIL subtypes in daily clinical practice can help determine a more successful and individualized therapeutic approach for early oral tongue SCC. LEVEL OF EVIDENCE: Step 4 (Level 4) Laryngoscope, 131:2512-2518, 2021.