[Preliminary outcomes of neoadjuvant chemoimmunotherapy combined with transoral robotic surgery for locally advanced oropharyngeal squamous cell carcinoma].

Objective: To evaluate the efficacy of neoadjuvant chemoimmunotherapy (NACI) combined with transoral robotic surgery (TORS) in the treatment of locally advanced oropharyngeal squamous cell carcinoma (OPSCC). Methods: This was a retrospective study of 15 patients with locally advanced OPSCC who underwent TORS after neoadjuvant therapy (NAT) at the Department of Otolaryngology-Head and Neck Surgery of Sun Yat-sen Memorial Hospital of Sun Yat-sen University from April 2019 to February 2023. There were 12 males and 3 females, aged 31 to 74 years. Twelve cases were tonsil cancer, and 3 cases were tongue base cancer. There were 11 cases in stage Ⅲ and 4 cases in stage Ⅳ. Two patients received neoadjuvant chemotherapy and 13 patients received NACI, with 2 to 3 cycles, and all patients underwent TORS after multidisciplinary team consultation. The clinicopathological characteristics, surgical outcomes, and oncological results were summarized. Results: All surgeries were successfully completed with negative surgical margins, and no case was required conversion surgery. All patients were fed via nasogastric tubes postoperatively, with a median gastric tube stay of 7 days (range: 2-60 days). No tracheotomy was applied. There were no major complications such as postoperative bleeding. Pathological complete response (pCR) was found in 10 cases (76.9%) among the 13 patients with NACI. The follow-up time was 21 months (range: 10-47 months), and there was no death or distant metastasis. One patient with rT0N3M0 tonsil cancer had local recurrence 5 months after surgery. The 2-year overall survival and 2-year disease-free survival were respectively 100.0% and 93.3% in the 15 patients. Conclusion: NACI combined with TORS provides a safe, effective and minimally invasive treatment for patients with locally advanced oropharyngeal squamous cell carcinoma.

Extranodal follicular dendritic cell sarcoma of the tonsil: An extremely rare clinical entity.

Follicular dentritic cell sarcomatous neoplasms originate from dendritic cells contained within the lymph nodes. In extranodal location, these neoplasms, are rare clinical entities, and even more so, their location in the head-neck region is extremely rare. Only 17 cases of primary dendritic cell sarcoma of the tonsil are reported in the literature at present. Being such a rare entity, histopathological diagnosis can be complex and requires great expertise and proper immunohistochemical analysis [1]. We present a case of a 48-year-old young man diagnosed with follicular dendritic cell sarcoma of the tonsil who underwent, probably for the first time in the literature, transoral robotic surgical resection.

Very rare tumour of the palatine tonsil: a molecular approach.

Mucoepidermoid cancer (MEC) is extremely rare in the palatine tonsil with only three adequately described cases in the literature.We describe a woman in her late 70s with vague pharyngeal discomfort who underwent tonsillectomy, lymph node dissection of the neck and radiotherapy for MEC with loco-regional lymph node metastasis of the palatine tonsil. To confirm this extremely rare diagnosis and to gain deeper insight in the molecular oncogenesis, an extensive molecular study including next-generation sequencing and immunohistochemistry was performed. Immunoreactivity for p16 protein and real-time PCR showed high-risk oncogenic human papillomavirus 16 DNA and mutations in the BRAF, BARD and DNMT3A genes. Tumour mutational burden was low. After a follow-up of 7 years the patient is still alive and well without any residual or disseminated disease.

Neoadjuvant chemotherapy followed by surgery for HPV-associated tonsillar cancer: Does imaging reflect the pathological response?

OBJECTIVES: The purpose of this study was to present our evaluation of the outcome of tonsillar cancer managed with neoadjuvant chemotherapy followed by surgery as definitive treatment. MATERIALS AND METHODS: Thirty-eight patients with human papilloma virus (HPV)-associated tonsillar cancer were treated with neoadjuvant chemotherapy followed by surgery. The volume reduction response of the tumor to neoadjuvant chemotherapy was evaluated and verified by histopathology. RESULTS: The complete pathologic response (pCR) rates at primary and nodal sites were 60 % and 45 %. Tumor volume reduction ≥78.8 % following neoadjuvant chemotherapy predicted pCR of the cervical node. In addition, the optimal cut-off value to predict pCR at the primary tumor site was 83.4 % volume reduction but was not a significant result. For pCR, neoadjuvant chemotherapy decreased the pathological adverse features, significantly reducing the need for adjuvant therapy. The overall survival of the adjuvant group was 79.2 %, and that of the non-adjuvant group was 87.5 %, with disease-free survival of 65.9 % and 54.2 %. There was no significant difference between the two groups. CONCLUSION: Neoadjuvant chemotherapy followed by surgery proved to be a good therapeutic option for management of HPV-associated tonsillar cancer. A greater reduction in tumor volume in post-neoadjuvant chemotherapy imaging predicts a complete pathologic response.

A two-centre experience of tonsil biopsies in the investigation of patients with tonsillar asymmetry.

INTRODUCTION: We aim to evaluate our experience of tonsil biopsies in the investigation of patients presenting with asymmetrical tonsils. METHODS: A two-centre retrospective analysis of all patients who underwent histology sampling of the palatine tonsils between 1 January 2013 and 31 December 2018 was completed. Data collected included patient demographics, method of obtaining tonsil tissue, histological diagnosis and need for repeat tissue sampling. A follow-up period of 36 months was allowed to establish whether any patients re-presented with missed diagnoses. RESULTS: In total, 937 patients were included for analysis: 375 (40.0%) had a biopsy, of which 191 (50.9%) were performed in clinic. The mean duration from initial appointment with the ear, nose and throat clinic to tissue sample collection was 17.6 days (range 0-327 days) for all biopsies, reducing to 0.2 days (range 0-17 days) for biopsies performed in clinic. This was significantly shorter than for tonsillectomies (mean 38.9 days, range 0-444 days; p<0.05). Of the patients who underwent tonsil biopsy, six (1.6%) had malignancy that was not unequivocally diagnosed on initial biopsy. In all six patients, prior clinical suspicion was high, and repeat tissue sampling was undertaken on receipt of negative histology results. CONCLUSIONS: Tonsil biopsy is a viable alternative to tonsillectomy for histology in the assessment of tonsil asymmetry. Tonsil biopsy in the outpatient setting has reduced surgical morbidity, significantly less delay in diagnosis, less inconvenience for patients and lower healthcare costs compared with formal tonsillectomy. Although tonsil biopsies should not be used in isolation, they can be useful in the investigation of patients presenting with tonsillar asymmetry.

A Patient with a History of Tonsillar Cancer Presents for Evaluation of Exposed Alveolar Bone in the Mouth.

Osteoradionecrosis (ORN) is a rare but serious late complication of head and neck radiation therapy. The mandible, proximity of the primary tumor to the jawbones, radiation dose, poor oral hygiene, and smoking history are risk factors of ORN. ORN manifests as a chronic infection with exposed jawbone, which typically occurs in the first 3 years after radiotherapy; however, the risk for ORN development occurring in the patients who have undergone head and neck radiation therapy may be indefinite. Surgery has an important role in the management of cases of ORN, ranging from sequestrectomy, debridement, and extensive extirpative procedures with reconstructive surgery.

Tonsillectomy as Prevention of Tonsil and Base of Tongue Cancer: Systematic Review and Meta-analysis on the Immuno-Oncological Effect of One Among the Most Common Surgeries in the World.

Otorhinolaryngology tradition is that tonsillectomy (TE) is conducted among children and adolescents for obstructive sleep apnea secondary to adenotonsillar hypertrophy and in adults for chronic disease of the tonsils and adenoids (recurrent tonsillitis). Nevertheless, over the last 50 years, we have observed a decline in TE worldwide. As a result, there is an emerging concern of a correlated possible increased risk of tonsil cancer (TC) and other subtypes of oropharyngeal squamous cell carcinoma. Since the available data on such topics are limited and controversial, our aim was to elucidate the impact of TE on the incidence mainly of TC through a systematic review of the literature and a meta-analysis of the studies. After a thorough search, 7 retrospective studies were considered eligible for review and meta-analysis (MA). At MA, patients with a history of TE seem to show a reduced risk of TC but a higher predisposition for base of tongue (BOT) cancer (p<0.001): however, the elevated heterogeneity of the studies hampers drawing firm and convincing conclusions (statistical inconsistency >95%). In future, randomized control trials will be welcome to elucidate the prophylactic role of TE against TC and its real impact on BOT cancer.

Oncologic and functional outcomes of neoadjuvant chemotherapy followed by surgery in human papillomavirus-positive tonsillar cancer.

BACKGROUND: Functional outcomes of neoadjuvant chemotherapy in human papillomavirus (HPV)-positive tonsillar cancer remained unclear. METHODS: We retrospectively reviewed the medical records of HPV-positive patients with tonsillar cancer. Of 112 patients, 38 were assigned to a neoadjuvant chemotherapy group and 74 were assigned to an upfront surgery group. RESULTS: Pathological analyses showed that the risks of close or positive resection margins and lymphovascular invasion were lower in patients who received neoadjuvant chemotherapy. The 5-year disease-free survival was significantly higher in the neoadjuvant chemotherapy group than in the upfront surgery group, but the 5-year overall survival was not. The time to commencement of oral feeding and the mean hospital stay were significantly shorter in the neoadjuvant chemotherapy group. The neoadjuvant chemotherapy group was more likely than the upfront surgery group to resume a regular diet. CONCLUSIONS: Compared with upfront surgery, neoadjuvant chemotherapy improved the functional outcomes and 5-year disease-free survival.

Leiomyoma of the palatine tonsil - report of a rare and unusual tumor at this site.

A leiomyoma is a remarkably rare cause of a benign, one-side tonsillar enlargement. The diagnosis is essentially histologic and will not normally be suspected clinically. Immunohistochemistry is needed for substantiation of the morphology and confirmation. We submit this illustrative case report.

Predictive factors of distant metastasis in surgically treated HPV-positive tonsil cancer.

BACKGROUND: Human papilloma virus (HPV)-related tonsil cancer is associated with favorable outcomes. OBJECTIVE: The purpose of this study was to define factors affecting distant metastasis in patients with surgically treated HPV-positive tonsil cancer. METHODS: The present study enrolled 76 patients diagnosed with HPV-positive tonsil cancer who underwent primary surgery between January 2010 and December 2021. RESULTS: Twelve (15.7%) patients experienced a distant failure with a median follow-up time of 43 months. Sites of distant metastasis included the lung (n = 10), liver (n = 1), and brain (n = 1). Upon multivariate analysis, an advanced T stage (odds ratio [OR]: 13.94, 95% confidence interval [CI]: 1.29-149.863, p = 0.003) and margin involvement (OR: 5.96, 95% CI: 1.33-26.76, p = 0.02) were independent predictors of distant metastases. The five-year disease-specific survival for the entire cohort was 85%. The multivariate analysis confirmed that distant metastasis (hazard ratio [HR]: 12.688, 95% CI: 3.424-47.016; p < 0.001) and margin involvement (HR: 6.243; 95% CI: 1.681-23.191; p = 0.006) were significant factors associated with the five-year disease-specific survival. CONCLUSION: HPV-positive tonsil cancer patients with an advanced T stage and a positive surgical margin have a substantial risk of distant metastases. Distant metastasis and margin involvement are factors that affect their survival.

Association of Unilateral Radiotherapy With Contralateral Lymph Node Failure Among Patients With Squamous Cell Carcinoma of the Tonsil: A Systematic Review and Meta-analysis.

Importance: Ipsilateral neck radiotherapy (RT) is controversial in some patients with tonsil cancer due to concern for nodal failure within the contralateral nonirradiated neck (hereinafter referred to as contralateral neck failure [CNF]). Objective: To determine the rate of CNF following ipsilateral neck RT in patients with tonsil cancer. Data Sources: Databases including PubMed, Embase, Web of Science, and Cochrane Library were queried for peer-reviewed, English language articles published between January 1, 1980, and December 31, 2021. Study Selection: Studies reporting rates of CNF from at least 20 patients treated with ipsilateral neck RT. Studies were excluded if they lacked full text, reported results from databases or systematic reviews, or did not provide RT details. Data Extraction and Synthesis: Data were extracted following the PRISMA reporting guideline. Study quality was assessed using criteria from a methodological index for nonrandomized studies. Pooled outcomes were estimated using random-effects models. Main Outcomes and Measures: Primary outcome was the pooled rate of CNF following ipsilateral neck RT. Secondary outcomes were the pooled rates of CNF by tumor and nodal staging categories from the 7th edition of the AJCC Cancer Staging Manual and rates of toxic effects. Results: A total of 17 studies (16 retrospective and 1 prospective) including 1487 unique patients were identified. The pooled risk of CNF was 1.9% (95% CI, 1.2%-2.6%). The rate of CNF by tumor (T) category was as follows: 1.3% (95% CI, 0.3%-2.3%) for T1; 3.0% (95% CI, 1.6%-4.4%) for T2; 11.3% (95% CI, 3.3%-19.2%) for T3; and 16.0% (95% CI, -7.8% to 39.8%) for T4. Patients with T3 to T4 tumors had a significantly higher rate of CNF than those with T1 to T2 tumors (11.5% [95% CI, 3.9%-19.1%] vs 1.8% [95% CI, 1.0%-2.6%]; P < .001). The rate of CNF by nodal (N) category was 1.2% (95% CI, 0.1%-2.2%) for N0; 4.8% (95% CI, 2.4%-7.2%) for N1; 3.1% (95% CI, 0.4%-5.8%) for N2a; 3.1% (95% CI, 1.2%-4.9%) for N2b; and 0 (95% CI, not applicable) for N3. Rates of CNF were similar for patients with N2b to N3 and N0 to N2a disease (3.0% [95% CI, 1.2%-4.7%] vs 1.7% [95% CI, 0.6%-2.8%], respectively; P = .07). Compared with bilateral RT, ipsilateral RT was associated with increased risk of CNF (log odds ratio, 1.29 [95% CI, 0.09-2.48]; P = .04). The crude rates of xerostomia of grade 3 or greater and feeding tube use were 0.9% (95% CI, -0.2% to 1.9%) and 13.3% (95% CI, 8.3%-18.3%), respectively. Conclusions and Relevance: In this systematic review and meta-analysis, ipsilateral neck RT was associated with a low rate of CNF in patients with small, lateralized tonsil cancers. Bilateral neck RT was associated with lower risk of CNF compared with ipsilateral neck RT. Patients with tumors of a higher T category were at increased risk for CNF following ipsilateral neck RT, and advanced nodal stage was not associated with CNF. Rates of toxic effects appeared favorable in patients treated with ipsilateral neck RT.

Hamartomatous Polyp of the Palatine Tonsil: A Case Report and Critical Literature Review.

BACKGROUND: Hamartomatous polyp of the palatine tonsil is a rare benign tumor poorly recognized by clinicians and pathologists. We present a novel case report and provide a literature review about this diagnosis, highlighting its clinicopathological features and treatment modalities. METHODS: We herein report a case of a 22-year-old female patient who complained of a foreign body sensation in her throat. She presented with a pedunculated polyp attached to her right palatine tonsil, which was noticed 15 years ago. An excisional biopsy was performed under local anesthesia, and the microscopic aspect confirmed the diagnosis of the hamartomatous polyp of the palatine tonsil. The literature review was performed using the "palatine tonsil polyps" term in PubMed and Google Scholar. Only English-language publications showing clinical and microscopic descriptions were selected as inclusion criteria. RESULTS: As in our case report, this poorly understood lesion usually presents as a solitary, unilateral pedunculated mass attached to the palatine tonsil surface with nonspecific symptoms. The literature shows less than 100 cases reported, which reveals a lesion preference for male and young adult patients. Microscopically, it is characterized by disorganized proliferation of the connective tissue components indigenous to the involved site, with variable lymphangiectasia, which accounts for the diversity of the diagnostic term and its unknown incidence. Its treatment consists of excision of the polyp with or without tonsillectomy, and no recurrence or malignant transformation of these polyps has been reported. CONCLUSION: The hamartomatous polyp of the palatine tonsil is challenging due to its rarity and lack of standardization of the terminology used in the literature. Including this diagnosis in the 5th edition of the World Health Organization Classification for Head and Neck Tumors is expected to contribute to a better understanding of this pathology.

Spontaneous regression of an human papillomavirus-positive oropharyngeal squamous cell carcinoma.

BACKGROUND: Spontaneous regression (SR) of cancer is an exceedingly rare phenomenon. While SR is well-documented for some cancers, very few reports exist in oropharyngeal squamous cell carcinomas (OPSCCs) and none in human papillomavirus (HPV)-positive OPSCCs. METHODS: A 67-year old man presented with a left-sided neck mass. Neck CT, PET, and biopsies showed a SCC in a left-sided lymph node without a primary lesion. Immunohistochemistry confirmed HPV16. Six weeks after biopsy, the patient underwent left selective tonsillectomy and neck dissection. RESULTS: Surgery revealed a left tonsillar SCC and no lymph nodes with tumor. Histology revealed homogenous fibrosis and intermixed immune cells indicative of tumor regression analogous to reports of immune-related pathologic responses. AE1/AE3 immunostain was also negative for tumor. All lymph nodes remained negative at 1 year follow-up. CONCLUSION: We described a spontaneously regressed lymph node in a tonsillar HPV-positive SCC. The unique immune environment of HPV-positive OPSCCs, and unknown environmental or host factors, may have played a role in our patient's SR which requires future studies to elucidate.

Patient- and Clinician-Reported Outcomes in Human Papillomavirus-Associated Tonsillar Carcinoma Treated With Unilateral and Bilateral Intensity Modulated Radiation Therapy-A Substudy From TROG 12.01.

PURPOSE: The aim of this TROG 12.01 substudy was to report longitudinal variations in patient- (PRO) and clinician-reported outcomes based on receipt of unilateral (URT) or bilateral radiation therapy (BRT). METHODS AND MATERIALS: Patients with lateralized T1-2 N1-2b human papillomavirus-associated tonsillar carcinoma (AJCC7) enrolled on TROG 12.01 were eligible. The primary endpoint was patient-reported radiation symptom severity score (MDASI-RSS) at 2 years, a composite of 9 MDASI-Head and Neck (HN) symptom items. Secondary endpoints included patient-reported symptom burden and interference (MDASI-HN), quality of life (FACT-HN), emotional distress (HADS), return to work (RTW), clinician-reported performance status scale (PSS-HN), and late adverse events (CTCAE). Mean MDASI-RSS, symptom severity (MDASI-SS), symptom interference (MDASI-SI) and selected single items were compared 1 week, 3 months, and 2 years post-RT. RESULTS: Seventy-four patients were eligible for analysis (26 URT, 48 BRT). Median follow-up was 3.7 years (1.8-5.2 years). Sociodemographic, staging, and treatment variables were mostly balanced, with larger primaries observed in the BRT group. Four regional failures were reported (3 URT, 1 BRT), including one isolated contralateral regional failure in the URT cohort. Mean MDASI-RSS scores did not differ at 2 years (URT vs BRT, 1.1 vs 1.3; difference 0.1 [95% CI: -0.7 to 0.9], P = .75) or at any other time points for the MDASI-RSS, MDASI-SS, and MDASI-SI scores, except for worse MDASI-SI 1 week after treatment in the BRT group (4.7 vs 5.6). Fatigue (6.6 vs 5.4) at 1 week and dry mouth (3.5 vs 2.0) at 2 years were also worse in the BRT group. FACT-HN, HADS, RTW, PSS-HN, and CTCAE results were similar across the follow-up period. CONCLUSIONS: In this favorable-risk cohort, treatment laterality resulted in fewer differences than anticipated in patient-reported or clinician-reported outcomes. Two years after treatment patients treated with BRT reported significantly worse dry mouth. Longer follow-up is needed to determine the impact of treatment laterality on late effects.

Unilateral tonsil enlargement in children and adults: is routine histology tonsillectomy warranted? A multi-centre series of 323 patients.

BACKGROUND: This study aimed to establish whether histology tonsillectomy is justified for unilateral tonsil enlargement. METHODS: A retrospective review was conducted of histology tonsillectomies in three health organisations over five years, with strict exclusion criteria, focusing on benign-appearing unilateral tonsil enlargement. RESULTS: Ninety paediatric and 233 adult cases were included. No paediatric cases and five adult cases of malignancy were detected. All malignant cases presented with other symptoms. Using binary logistic regression, a history of rapid unilateral tonsil enlargement was the only factor found to be significantly associated with malignant outcome. Thirty-three per cent of subjectively larger tonsils were smaller on post-operative histological measurement. Of the cases, 12.1 per cent re-presented with post-tonsillectomy bleeding. CONCLUSION: The authors recommend avoiding histology tonsillectomy for unilateral tonsil enlargement unless 'red flag' signs of malignancy are present, with particular attention to rapid unilateral tonsil enlargement. This study demonstrated discrepancy between clinical examination findings and true tonsil asymmetry; there may be a role for cross-sectional imaging prior to histology tonsillectomy in high-risk patients.

Role of local flaps in the prevention of soft tissue necrosis after transoral robotic surgery for tonsillar cancer.

OBJECTIVE: Soft tissue necrosis (STN) can occur after transoral robotic surgery (TORS) with radiation therapy (RT). We investigated the usefulness of local flap reconstruction for preventing STN after TORS in patients with tonsillar cancer. METHODS: This case-control study retrospectively reviewed clinicopathological data of patients who underwent TORS for tonsillar cancer at a tertiary referral center. The incidence of STN was compared in patients who underwent secondary intention healing or local flap reconstruction, and factors predicting STN were identified. RESULTS: STN occurred in 20 (25%) of 80 patients in the study. The incidence of STN was higher in the secondary intention healing than the flap reconstruction group. Mucositis grade (odds ratio [OR] 3.694, p = 0.02), RT dose (OR 4.667, p = 0.001), and secondary intention healing (OR 14.985, p = 0.035) were predictive factors for STN. CONCLUSION: Flap reconstruction can prevent STN after TORS with RT in patients with tonsillar cancer. The use of local flaps preserves the minimally invasive nature of TORS.

The isolated symptom of unilateral tonsillar enlargement has limited value in adults with a suspected head and neck cancer pathway.

OBJECTIVE: Given the uncertainty regarding the predictive value of unilateral tonsillar enlargement and/or lesion in malignancies, this study aimed to evaluate the efficacy of unilateral tonsillar enlargement and/or lesion referral criterion in the adult suspected head and neck cancer pathway. METHODS: All two-week wait referrals received in 2018-2019 were reviewed. All patients referred with unilateral tonsillar enlargement and/or lesion were included and analysed for patient demographic data, presenting symptoms, initial clinic outcomes and final diagnoses. RESULTS: A total of 4934 urgent head and neck cancer referrals were analysed, and 1.9 per cent of these had unilateral tonsillar enlargement and/or lesion. Only 10 patients were diagnosed with tonsil cancer. All the positive tonsil cancer cases had at least one additional head and neck red flag symptom. CONCLUSION: The referral criterion for unilateral tonsillar enlargement and/or lesion may be of limited benefit in an already economically challenged National Health Service. Further multicentre studies should be undertaken to refine conclusions on the value of unilateral tonsillar enlargement and/or lesion alone as a criterion for the head and neck cancer two-week wait pathway.