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.

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.

Predictive Value of 18F-Fluorodeoxyglucose Positron-Emission Tomography Metabolic and Volumetric Parameters for Systemic Metastasis in Tonsillar Cancer.

Although the prognosis of tonsillar cancer (human papillomavirus-positive oropharyngeal squamous cell carcinoma) is improving, disease control failure (distant metastasis) still occurs in some cases. We explored whether several 18F-fluorodeoxyglucose (FDG) positron-emission tomography (PET) parameters can predict metastasis. We retrospectively reviewed the medical records of 55 patients with tonsil squamous cell carcinoma who underwent pretreatment 18F-FDG positron-emission tomography/computed tomography (PET/CT) followed by primary surgery. During the follow-up period, systemic metastases were found in 7 of the 55 patients. The most common sites were the lungs (33%), bone (22%), brain/skull base (22%), small bowel (11%), and liver (11%). Pathologically, P53 mutation was less common in patients with systemic metastasis (41.7% vs. 14.3%, p = 0.054) than without systemic metastasis. In terms of PET parameters, the metabolic tumor volume (MTV2.5) and total lesion glycolysis (TLG2.5) values were lower in the primary tumor, and higher in the metastatic lymph nodes, of human papillomavirus (HPV)-positive compared to HPV-negative patients (all p < 0.05). The MTV2.5, TLG2.5, and tumor−to−liver uptake ratio were 36.07 ± 54.24 cm3, 183.46 ± 298.62, and 4.90 ± 2.77, respectively, in the systemic metastasis group, respectively; all of these values were higher than those of the patients without systemic metastasis (all p < 0.05). The MTV2.5 value was significantly different between the groups even when the values for the primary tumor and metastatic lymph nodes were summed (53.53 ± 57.78 cm3, p = 0.036). The cut-off value, area under the curve (95% confidence interval), sensitivity, and specificity of MTV2.5 for predicting systemic metastasis were 11.250 cm3, 0.584 (0.036−0.832), 0.571, and 0.565, respectively. The MTV2.5 of metastatic lymph nodes and summed MTV2.5 values of the primary tumor and metastatic lymph nodes were significantly higher in tonsillar cancer patients with than without systemic metastases. We suggest PET/CT scanning for pre-treatment cancer work-up and post-treatment surveillance to consider additional systemic therapy in patients with a high risk of disease control failure.

Prophylactic contralateral neck dissection has no advantage in patients with early stage HPV-positive tonsil cancer.

BACKGROUND: Patients with locally advanced HPV-positive tonsil cancer would benefit from prophylactic contralateral neck dissection (pCND). AIMS/OBJECTIVES: The aim of this study was to analyze rates of contralateral lymph node metastases (LNM) and their prognostic effects on locally advanced HPV-positive tonsillar squamous cell carcinoma. MATERIALS AND METHODS: Medical records of 54 patients who underwent upfront primary surgery and pCND were retrospectively reviewed. RESULTS: Six (11.1%) patients had contralateral LNM in 54 locally advanced HPV-positive tonsil cancer. Of these, five patients had contralateral level II LNM and one patient had contralateral level II and III LNM. Contralateral LNM showed significant positive correlations with advanced T stage (p = .017) and the presence of extracapsular spread (p = .007). Contralateral lymph node metastasis had no significant association with five-year disease-specific survival. CONCLUSIONS AND SIGNIFICANCE: This study demonstrated no advantage in performing pCND in early stage HPV-positive tonsil cancer.

A CT-based radiomics nomogram for differentiation of squamous cell carcinoma and non-Hodgkin's lymphoma of the palatine tonsil.

OBJECTIVES: Accurate preoperative differentiation between squamous cell carcinoma (SCC) and non-Hodgkin's lymphoma (NHL) in the palatine tonsil is crucial because of their different treatment. This study aimed to construct and validate a contrast-enhanced CT (CECT)-based radiomics nomogram for preoperative differentiation of SCC and NHL in the palatine tonsil. METHODS: This study enrolled 135 patients with a pathological diagnosis of SCC or NHL from two clinical centers, who were divided into training (n = 94; SCC = 50, NHL = 44) and external validation sets (n = 41; SCC = 22, NHL = 19). A radiomics signature was constructed from radiomics features extracted from routine CECT images and a radiomics score (Rad-score) was calculated. A clinical model was established using demographic features and CT findings. The independent clinical factors and Rad-score were combined to construct a radiomics nomogram. Performance of the clinical model, radiomics signature, and nomogram was assessed using receiver operating characteristics analysis and decision curve analysis. RESULTS: Eleven features were finally selected to construct the radiomics signature. The radiomics nomogram incorporating gender, mean CECT value, and radiomics signature showed better predictive value for differentiating SCC from NHL than the clinical model for training (AUC, 0.919 vs. 0.801, p = 0.004) and validation (AUC, 0.876 vs. 0.703, p = 0.029) sets. Decision curve analysis demonstrated that the radiomics nomogram was more clinically useful than the clinical model. CONCLUSIONS: A CECT-based radiomics nomogram was constructed incorporating gender, mean CECT value, and radiomics signature. This nomogram showed favorable predictive efficacy for differentiating SCC from NHL in the palatine tonsil, and might be useful for clinical decision-making. KEY POINTS: • Differential diagnosis between SCC and NHL in the palatine tonsil is difficult by conventional imaging modalities. • A radiomics nomogram integrated with the radiomics signature, gender, and mean contrast-enhanced CT value facilitates differentiation of SCC from NHL with improved diagnostic efficacy.

Decreased CD1a + and CD83 + cells in tonsillar squamous cell carcinoma regardless of HPV status

Abstract Dendritic cells (DCs) are specialized antigen-presenting cells that play a critical role in the immune response against human papillomavirus (HPV) infection, and represent a therapeutic target in cancer. Objective: To identify and quantify DCs in tonsillar squamous cell carcinoma (TSCC) under the influence of HPV infection. Methodology: CD1a and CD83 antibodies were used to identify immature dendritic cells and mature dendritic cells by immunohistochemistry in 33 primary TSCC and 10 normal tonsils (NTs), respectively. For the TSCC samples, the number of DCs per area was evaluated in the intra- and peritumoral compartments. For the NTs, the quantification of DCs was evaluated in the intra- and peritonsillar compartments. HPV detection methods were determined according to the ASCO Clinical Practice Guidelines from the College of American Pathologists Guideline (2018). Results: There were fewer intratumoral CD1a+ DCs in the HPV-positive and HPV-negative TSCC groups than in the NT group (p<0.05). In the peritumoral compartment, there were fewer CD83+ DCs in the HPV-positive and HPV-negative TSCC groups than in the NT group (p<0.001). The quantification of DCs subtypes showed no statistical differences between HPV-positive and HPV-negative TSCC groups (p>0.137). Patients with HPV-positive TSCC had significantly better overall survival rate than those with HPV-negative TSCC (p=0.004). Conclusion: Tumor activity contributes to DC depletion regardless of intralesional HPV positivity. An improved prognosis has been reported in patients with HPV-positive TSCC.

Linfoma de amígdala: reporte de un caso pediátrico / Palatine tonsil lymphoma: a pediatric case report

El linfoma es la neoplasia maligna de cabeza y cuello más común en la población pediátrica. Las anifestaciones clínicas de linfoma en amígdala palatina son generalmente asimetría amigdalina, alteración en la apariencia de la mucosa y adenopatías cervicales. Ante una hipertrofia amigdalina unilateral, se debe diferenciar de cuadros infecciosos, procesos crónicos, otros tumores o simplemente una hiperplasia amigdalina benigna. El seguimiento estricto de la asimetría amigdalina es un pilar importante a la hora del diagnóstico de los pacientes con linfoma amigdalino, debido a que un tratamiento temprano es fundamental para el pronóstico. Se presenta una niña de 14 años con hipertrofia amigdalina unilateral y odinofagia, de aproximadamente 21 días de evolución sin respuesta al tratamiento antibiótico, con diagnóstico de linfoma de Burkitt. Presenta remisión completa de la enfermedad al año del diagnóstico.

Lymphoma is the most common childhood malignancy in the head and neck. The most common clinical manifestations of lymphoma in palatine tonsil are the tonsils asymmetry, alteration in the appearance of the mucous and cervical lymphadenopathy. The unilateral tonsillar hypertrophy must be differentiated with infectious processes, with chronic processes, other tumors or benign tonsillar hyperplasia. The monitoring of tonsillar hypertrophy is strict, because early diagnosis and treatment are of great importance in the prognosis of tonsillar lymphoma patients. A 14 year-old girl presents unilateral tonsillar enlargement and odynophagia. After 21 days of antibiotic treatment, she has not clinical improvement. The diagnosis is Burkitt's lymphoma. One year after diagnosis, she presents complete remission of the disease.

Palatine tonsil metastasis of cecal mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN): A unique case.

This case demonstrates the importance of understanding that patients with malignant neoplasms may exhibit metastases in unexpected sites and illustrates the necessity of a thorough clinical examination and pathologic correlation.

[Palatine tonsil lymphoma: a pediatric case report]. / Linfoma de amígdala: reporte de un caso pediátrico.

Lymphoma is the most common childhood malignancy in the head and neck. The most common clinical manifestations of lymphoma in palatine tonsil are the tonsils asymmetry, alteration in the appearance of the mucous and cervical lymphadenopathy. The unilateral tonsillar hypertrophy must be differentiated with infectious processes, with chronic processes, other tumors or benign tonsillar hyperplasia. The monitoring of tonsillar hypertrophy is strict, because early diagnosis and treatment are of great importance in the prognosis of tonsillar lymphoma patients. A 14 year-old girl presents unilateral tonsillar enlargement and odynophagia. After 21 days of antibiotic treatment, she has not clinical improvement. The diagnosis is Burkitt's lymphoma. One year after diagnosis, she presents complete remission of the disease.

El linfoma es la neoplasia maligna de cabeza y cuello más común en la población pediátrica. Las manifestaciones clínicas de linfoma en amígdala palatina son generalmente asimetría amigdalina, alteración en la apariencia de la mucosa y adenopatías cervicales. Ante una hipertrofia amigdalina unilateral, se debe diferenciar de cuadros infecciosos, procesos crónicos, otros tumores o simplemente una hiperplasia amigdalina benigna. El seguimiento estricto de la asimetría amigdalina es un pilar importante a la hora del diagnóstico de los pacientes con linfoma amigdalino, debido a que un tratamiento temprano es fundamental para el pronóstico. Se presenta una niña de 14 años con hipertrofia amigdalina unilateral y odinofagia, de aproximadamente 21 días de evolución sin respuesta al tratamiento antibiótico, con diagnóstico de linfoma de Burkitt. Presenta remisión completa de la enfermedad al año del diagnóstico.

Feasibility of Free Flap Reconstruction Following Salvage Robotic-Assisted Resection of Recurrent and Residual Oropharyngeal Cancer in 3 Patients.

INTRODUCTION: Human papilloma virus (HPV)-positive oropharyngeal cancer carries a good prognosis when managed with primary chemoradiotherapy. However, the dramatically increasing rate of this disease means more patients are now developing recurrence, with surgery remaining the mainstay of treatment. Despite this, there is no agreed technique for excision of recurrent oropharyngeal cancer. OBJECTIVE: We describe the transoral robotic technique employed by our head and neck multidisciplinary team (MDT) in the management of patients with recurrent HPV positive oropharyngeal cancer and assess their symptom severity using quality of life and swallowing questionnaires. METHOD: Three (2 males:1 female, mean age 60.7 years) patients with recurrent or residual p16 positive oropharyngeal cancer following radical chemoradiotherapy were identified. All patients underwent selective neck dissection, tracheostomy, and transoral robotic surgery (TORS)-assisted partial oropharyngeal resection with the resultant defect closed with a robotic assisted radial forearm free flap (RFFF). Patient quality of life, symptom severity, and swallowing were assessed pre- and postoperatively using the University of Washington Quality of Life score and MD Anderson Dysphagia Index (MDADI). RESULTS: Histopathological examination revealed complete clearance of the primary lesion in all cases. Two patients made uneventful recoveries, while one patient developed a chest infection and tracheocutaneous fistula managed conservatively. Mean inpatient stay was 15 days (range 8-27). University of Washington Quality of Life and MDADI scores showed a mild improvement in symptoms following surgery. CONCLUSION: Surgical management of recurrent oropharyngeal cancer remains a technical challenge; however, MDT discussion and judicious use of TORS oropharyngeal resection and RFFF can result in good oncological and quality of life outcomes with acceptable postoperative complications and symptoms.

Prognostic impact of resection margin involvement in surgically managed HPV-positive tonsil cancer.

OBJECTIVES: To find out the role of resection margin involvement in surgically managed HPV-positive tonsil cancer. MATERIALS AND METHODS: The study included 94 subjects with HPV-positive tonsil cancer undergoing surgical treatment. We evaluated the relationships between the resection margin status, clinicopathological factors, and oncological outcome. RESULTS: The rate of resection margin involvement was 22.3% (21/94) after ablative surgery. Margin involvement, lymphatic invasion, and extracapsular spread were associated with the 5-year disease-free survival (DFS) and disease-specific survival (DSS) rate in univariate analysis. Multivariate Cox regression analysis confirmed a significant association between the margin involvement and 5-year DFS rate (HR = 4.602; 95% CI = 1.202-17.620; p = 0.026) and 5-year DSS rate (HR = 12.826; 95% CI = 1.399-117.593; p = 0.024). The incidence of resection margin involvement was significantly higher in patients with larger tumors (35.19 ± 15.07 mm vs. 25.53 ± 10.32 mm, p = 0.011) and more invasive tumors (17.84 ± 7.90 mm vs. 13.46 ± 6.88 mm, p = 0.037). The cutoff value of tumor size and depth of invasion for resection margin involvement was 29.5 mm (74% sensitivity and 63% specificity) and 14.5 mm (74% sensitivity and 61% specificity), respectively. CONCLUSION: Resection margin involvement was significantly correlated with tumor size and the depth of invasion in HPV-positive tonsil cancer. Furthermore, resection margin involvement was associated with adverse outcomes.

Isolated pituitary fossa metastasis from a primary tonsillar squamous cell carcinoma: case report.

OBJECTIVE: This paper presents a case of an isolated pituitary fossa metastasis on a background of a previously treated tonsillar squamous cell carcinoma. CASE REPORT: A 64-year-old male, diagnosed with a primary p16-negative squamous cell carcinoma in the right tonsil, was treated with a course of chemoradiotherapy with curative intent. Positron emission tomography/computed tomography, performed at six months post-treatment, revealed a good local response and no distant metastases. The patient was placed on routine follow up at two-monthly intervals. Two months into follow up, he presented with a right-sided oculomotor nerve palsy and partial Horner's syndrome. Imaging and biopsy revealed a pituitary fossa metastasis (p16-negative squamous cell carcinoma), and a further positron emission tomography/computed tomography visualised this lesion. He was deemed unsuitable for further intervention and underwent palliative radiotherapy for symptom control. CONCLUSION: This case represents the first reported isolated pituitary fossa metastasis from a tonsillar squamous cell carcinoma. A high degree of clinical suspicion is recommended, along with a low threshold for biopsy and a cautioned use of positron emission tomography/computed tomography, when investigating such patients.

[A case of tonsil sarcomatoid carcinoma].

Sarcomatoid carcinoma, a malignant tumor containing both epithelial-derived malignant cells and malignant mesenchymal cells. Microscopically, cancer cells and sarcoma cells migrate to each other, and CK and Vimentin are simultaneously expressed. A rare case of tonsillar sarcomatoid carcinoma is discussed in our department with dysphagia as the first symptom.

A case of tonsil sarcomatoid carcinoma / 临床耳鼻咽喉头颈外科杂志

Summary@#Sarcomatoid carcinoma, a malignant tumor containing both epithelial-derived malignant cells and malignant mesenchymal cells. Microscopically, cancer cells and sarcoma cells migrate to each other, and CK and Vimentin are simultaneously expressed. A rare case of tonsillar sarcomatoid carcinoma is discussed in our department with dysphagia as the first symptom.

A case of tonsil sarcomatoid carcinoma / 临床耳鼻咽喉头颈外科杂志

Sarcomatoid carcinoma, a malignant tumor containing both epithelial-derived malignant cells and malignant mesenchymal cells. Microscopically, cancer cells and sarcoma cells migrate to each other, and CK and Vimentin are simultaneously expressed. A rare case of tonsillar sarcomatoid carcinoma is discussed in our department with dysphagia as the first symptom.

Delayed Metastatic Melanoma to the Pharyngeal Tonsil in an African American Female.

Background: Metastatic melanoma to the mucosa of the upper aerodigestive tract is extremely rare, accounting for <0.6% of known metastasis to the head and neck region. We present a case of delayed metastatic melanoma to the pharyngeal tonsil. Case Report: A 57-year-old African American female presented for evaluation of a rapidly enlarging unilateral tonsil mass. Three years prior to presentation, she had undergone primary resection of and systemic therapy for cutaneous melanoma on the sole of her right foot. Tonsillectomy confirmed the diagnosis of metastatic melanoma. Because of the poor prognosis of the disease, the patient was referred for palliative chemotherapy but died shortly after beginning treatment. Conclusion: Metastatic melanoma is a rare disease in African Americans, and the presence of metastatic lesions is a significant prognostic indicator for long-term patient survival. Meticulous head and neck examinations should be performed during the follow-up period, and any pigmented lesion should have a high suspicion for metastasis in any patient with a history of cutaneous melanoma.

[Clinicopathological features of long-term tumor-free survival of patients with untreated primary tonsillar diffuse large B-cell lymphoma].

Objective: To investigate the clinicopathological features of long-term tumor-free survival in patients with untreated primary diffuse large B-cell lymphoma (DLBCL) of the tonsil. Methods: The study included 80 consultation cases of primary tonsillar DLBCL from April 2006 to July 2017 in the Department of Pathology, Beijing Friendship Hospital, Capital Medical University. The patients were divided into two groups: experimental groups of 10 untreated patients with long-term tumor-free survival, and 70 patients who had been treated (control group). The clinical data, histopathological features, immunohistochemical staining, and molecular biology test results of the patients were analyzed retrospectively. Results: Patients who had long-term tumor-free survival with untreated primary diffuse large B-cell lymphoma had the disease mostly confined to the tonsil. Biopsy showed that the tonsil structure was only partially effaced and the lesions were relatively "fresh". EBER and FISH test for t (14;18) results were negative. Gene rearrangement detection showed monoclonality. There was statistically significant difference between the age, bcl-2 expression, CMYC protein expression and co-expression of CMYC and bcl-2 between the untreated group and the treated group(P<0.05). Patient gender, tumor site, histological type and clinical stage showed no difference between the untreated group and the treated group (P>0.05); The median overall survival of the untreated group and treated group was 81 months and 20 months, respectively, and the difference was not statistically significant (P>0.05).In patients younger than 40 years of age, the untreated group had a statistically significant difference in primary site and CMYC protein expression compared with the treated group (P<0.05), and there was no statistical significance in other aspects. Conclusions: Long-term tumor-free survival patients with untreated tonsillar primary DLBCL have relatively unique clinical characteristics. There is no significant difference in the prognosis between the untreated and treated groups, indicating radiotherapy and chemotherapy may not be required and therefore, avoiding related side effects.

Survival outcome of tonsillar squamous cell carcinoma (TSCC) in the context of human papillomavirus (HPV): A systematic review and meta-analysis.

OBJECTIVE: The objective of our study was to assess whether HPV-positive TSCC had better survival and prognosis rates, when compared to HPV-negative TSCC. METHOD: A systematic review and meta-analysis was performed comparing HPV status in TSCC patients. TSCC was confirmed with histopathology and HPV status was confirmed with PCR, immunohistochemistry and/or in-situ-hybridisation. The primary endpoints were overall survival (OS) and disease free survival (DFS). RESULTS: Twenty-four studies were identified, involving 1921 TSCC cases, of which 56.2% (1079) were HPV positive. OS was significantly higher in patients with HPV-positive compared to HPV-negative TSCC in years 1-5 (OR 2.54, P < 0.01; OR 2.93 P < 0.01; OR 2.74 P < 0.01; OR 2.20 P < 0.01, and OR 2.14 P < 0.01 respectively). Similarly, DFS was also significantly higher in patients with HPV-positive compared to HPV-negative TSCC in years 1-3 (OR 2.86, P < 0.01; OR 2.60 P < 0.02; and OR 2.60 P < 0.01 respectively), which was attenuated in years 4 and 5 (OR 1.83, P = 0.10 and OR 1.50, P = 0.12). CONCLUSION: This is the largest meta-analysis with 1921 patients, comparing non-HPV induced TSCC and HPV induced TSCC, looking at outcome and survival. HPV-positive had better OS and DFS.

Clinicopathological features of long-term tumor-free survival of patients with untreated primary tonsillar diffuse large B-cell lymphoma / 中华病理学杂志

Objective@#To investigate the clinicopathological features of long-term tumor-free survival in patients with untreated primary diffuse large B-cell lymphoma (DLBCL) of the tonsil.@*Methods@#The study included 80 consultation cases of primary tonsillar DLBCL from April 2006 to July 2017 in the Department of Pathology, Beijing Friendship Hospital, Capital Medical University. The patients were divided into two groups: experimental groups of 10 untreated patients with long-term tumor-free survival, and 70 patients who had been treated (control group). The clinical data, histopathological features, immunohistochemical staining, and molecular biology test results of the patients were analyzed retrospectively.@*Results@#Patients who had long-term tumor-free survival with untreated primary diffuse large B-cell lymphoma had the disease mostly confined to the tonsil. Biopsy showed that the tonsil structure was only partially effaced and the lesions were relatively "fresh". EBER and FISH test for t (14;18) results were negative. Gene rearrangement detection showed monoclonality. There was statistically significant difference between the age, bcl-2 expression, CMYC protein expression and co-expression of CMYC and bcl-2 between the untreated group and the treated group(P<0.05). Patient gender, tumor site, histological type and clinical stage showed no difference between the untreated group and the treated group (P>0.05); The median overall survival of the untreated group and treated group was 81 months and 20 months, respectively, and the difference was not statistically significant (P>0.05).In patients younger than 40 years of age, the untreated group had a statistically significant difference in primary site and CMYC protein expression compared with the treated group (P<0.05), and there was no statistical significance in other aspects.@*Conclusions@#Long-term tumor-free survival patients with untreated tonsillar primary DLBCL have relatively unique clinical characteristics. There is no significant difference in the prognosis between the untreated and treated groups, indicating radiotherapy and chemotherapy may not be required and therefore, avoiding related side effects.