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Lipomas of the palatine tonsil are rare benign neoplasms in clinical practice. We present a case of palatine tonsillar fibroangiolipoma in a 50-year-old Chinese male with a history of multiple lipomas on the back and extremities. It was diagnosed based on histological examination and integrated analysis. Good wound healing and no evidence of recurrence were noted within 6 months follow-up after tonsillectomy. This article also puts a spotlight on the differential diagnosis of benign tonsillar tumors and reviewed recent relevant literature., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Extranodal natural killer/T-cell lymphoma (ENKTL) with tonsil involvement is not common, especially in children., Case Presentation: A 13-year-old girl presented with an unexplained sore throat for more than 2 months, together with intermittent fever and suppurative tonsilitis. Nasopharyngoscopy revealed a pharyngeal mass. Enhanced computed tomography (CT) scan showed tonsillar hypertrophy and punctate calcification. Chronic pyogenic granulomatous inflammation with pseudoepithelial squamous epithelial hyperplasia was observed in left tonsil, and pyogenic granulomatous inflammation and a small number of T-lymphoid cells were detected in the right tonsil. The immunohistochemical results showed CD2 + , CD3 + , CD4 + , CD5 + , CD8 + , granzyme B + , and TIA-1 + . The Ki-67 proliferation index was 20%. The case showed T cell receptor gene rearrangement. Finally, the case was diagnosed as ENKTL of stage II with tonsil involvement. The patient received 6 cycles of chemotherapy with SMILE regimen, and showed complete response with no recurrence in the follow-up., Conclusion: We presented a rare case of ENKTL with tonsil involvement in a child. The patient showed complete response to the SMILE chemotherapy with no recurrence., (© 2024. The Author(s).)

Background: Synovial sarcoma is a rare soft tissue malignancy, occasionally found in the head and neck region. The diagnosis necessitates a multidisciplinary approach involving the clinical presentation, proper imaging studies and histological confirmation, with molecular testing for definitive identification. Treatment entails surgical resection with adjuvant therapies as needed., Case Presentation: A 33-year-old male patient presented with globus sensation concomitant with right-sided neck swelling. He was clinically found to have right tonsil enlargement with posterior extension. Therefore, he underwent right tonsillectomy with pharyngoplasty. Histopathological examination revealed a biphasic tumor consistent with synovial sarcoma, confirmed by immunohistochemistry and fluorescence in situ hybridization., Conclusions: Tonsillar synovial sarcoma represents a diagnostic challenge, requiring a high index of suspicion and comprehensive evaluation. With only twenty previously published cases documented in the literature, awareness of this rare presentation is crucial for prompt diagnosis and appropriate management. Collaboration among multidisciplinary healthcare teams and ongoing research efforts are essential for optimizing diagnostic accuracy, treatment efficacy, and patient outcomes in this rare malignancy., (© 2024. The Author(s).)

Background: This study aimed to compare the diagnostic value of [ 68  Ga]Ga-DOTA-FAPI-04 and [ 18 F]FDG PET/CT imaging for primary lesions and metastatic lymph nodes in patients with tonsil cancer., Method: Twenty-one tonsil cancer patients who underwent [ 68  Ga]Ga-DOTA-FAPI-04 and [ 18 F]FDG PET/CT scans within two weeks in our centre were retrospectively enrolled. The maximum standardized uptake value (SUVmax) and tumor-to-background ratio (TBR) of the two tracers were compared by using the Mann‒Whitney U test. In addition, the sensitivity, specificity, and accuracy of the two methods for diagnosing metastatic lymph nodes were analysed., Results: In detecting primary lesions, the efficiency was higher for [ 68  Ga]Ga-DOTA-FAPI-04 PET/CT (20/22) than for [ 18 F]FDG PET/CT (9/22). Although [ 68  Ga]Ga-DOTA-FAPI-04 uptake (SUVmax, 5.03 ± 4.06) was lower than [ 18 F]FDG uptake (SUVmax, 7.90 ± 4.84, P = 0.006), [ 68  Ga]Ga-DOTA-FAPI-04 improved the distinction between the primary tumor and contralateral normal tonsillar tissue. The TBR was significantly higher for [ 68  Ga]Ga-DOTA-FAPI-04 PET/CT (3.19 ± 2.06) than for [ 18 F]FDG PET/CT (1.89 ± 1.80) (p < 0.001). In lymph node analysis, SUVmax and TBR were not significantly different between [ 68  Ga]Ga-DOTA-FAPI-04 and [ 18 F]FDG PET/CT (7.67 ± 5.88 vs. 8.36 ± 6.15, P = 0.498 and 5.56 ± 4.02 vs. 4.26 ± 3.16, P = 0.123, respectively). The specificity and accuracy of [ 68  Ga]Ga-DOTA-FAPI-04 PET/CT were higher than those of [ 18 F]FDG PET/CT in diagnosing metastatic cervical lymph nodes (all P < 0.05)., Conclusion: The availability of [ 68  Ga]Ga-DOTA-FAPI-04 complements the diagnostic results of [ 18 F]FDG by improving the detection rate of primary lesions and the diagnostic accuracy of cervical metastatic lymph nodes in tonsil cancer compared to [ 18 F]FDG., (© 2024. The Author(s).)

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 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., Competing Interests: None

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., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Shin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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.

The incidence of human papillomavirus-positive (HPV + ) tonsillar cancer has been sharply rising during the last decades. Myeloid cells represent an appropriate therapeutic target due to their proximity to virus-infected tumor cells, and their ability to orchestrate antigen-specific immunity, within the tonsil. However, the interrelationship of steady-state and inflammatory myeloid cell subsets, and their impact on patient survival remains unexplored. Here, we used single-cell RNA-sequencing to map the myeloid compartment in HPV + tonsillar cancer. We observed an expansion of the myeloid compartment in HPV + tonsillar cancer, accompanied by interferon-induced cellular responses both in dendritic cells (DCs) and monocyte-macrophages. Our analysis unveiled the existence of four DC lineages, two macrophage polarization processes, and their sequential maturation profiles. Within the DC lineages, we described a balance shift in the frequency of progenitor and mature cDC favoring the cDC1 lineage in detriment of cDC2s. Furthermore, we observed that all DC lineages apart from DC5s matured into a common activated DC transcriptional program involving upregulation of interferon-inducible genes. In turn, the monocyte-macrophage lineage was subjected to early monocyte polarization events, which give rise to either interferon-activated or CXCL-producing macrophages, the latter enriched in advanced tumor stages. We validated the existence of most of the single-cell RNA-seq clusters using 26-plex flow cytometry, and described a positive impact of cDC1 and interferon-activated DCs and macrophages on patient survival using gene signature scoring. The current study contributes to the understanding of myeloid ontogeny and dynamics in HPV-driven tonsillar cancer, and highlights myeloid biomarkers that can be used to assess patient prognosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jimenez, Altunbulakli, Swoboda, Sobti, Askmyr, Ali, Greiff and Lindstedt.)

Background: Human papillomavirus (HPV)-positive tonsil cancer has a better prognosis than HPV-negative tonsil cancer. Deintensification strategies to reduce or avoid radiotherapy (RT) for patients with HPV-associated tonsil cancer have been suggested. This study investigated the treatment outcomes of patients with HPV-associated tonsil cancer and suggested RT deintensification strategies., Methods: A cohort of 374 patients with HPV-associated tonsil cancer treated with primary surgery or RT between 2008 and 2020 was retrospectively evaluated. Survival and locoregional control rates after primary surgery or RT were analyzed, and propensity score matching was performed to adjust for clinical factors. Pearson's chi-square or Fisher's exact test was used to compare categorical variables, and Student's t-test was used to compare continuous variables. The Kaplan-Meier method and log-rank test were used to assess overall survival, progression-free survival, and locoregional failure (LRF)., Results: No significant differences in survival or LRF were observed between the primary surgery and RT groups. Subgroup analysis was conducted for patients who underwent primary surgery. Advanced pathological N stage, negative contralateral nodes at diagnosis, abutting or positive surgical margins, and no adjuvant RT were independent risk factors for LRF. Advanced pathological T stage was an independent risk factor for LRF in patients who underwent primary surgery without subsequent adjuvant RT. None of the patients with pathological complete remission (CR) after induction chemotherapy died or experienced LRF., Conclusions: Our study revealed that the outcomes of primary surgery and primary RT in HPV-positive tonsil cancer were similar after adjusting for clinical factors. Primary RT might be considered instead of surgery in patients with advanced pathological T stage. In the case of pathological CR after induction chemotherapy, deintensification for adjuvant RT should be considered., (© 2022. The Author(s).)

Background: 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.

Backgroud: Primary tonsil diffuse large B cell lymphoma (PT-DLBCL) is an uncommon disease entity. The role of radiation therapy (RT) in PT-DLBCL is debatable in both the pre- and post- rituximab era. The purpose of this study was to evaluate the treatment outcome and establish a prognostic model in PT-DLBCL based on the Surveillance, Epidemiology, and End Results (SEER) database., Materials and Methods: Data of 1214 PT-DLBCL patients diagnosed between 1975 and 2016 were extracted from SEER 18. The effect of RT was assessed for the entire cohort and subgroups by stages using univariate, multivariate Cox regression analyses and propensity score matching (PSM)., Results: The entire cohort included 1043 patients with early-stage (ES) PT-DLBCL and 171 patients with advanced-stage (AS) disease. A decreasing trend of RT utilization in the ES cohort after 2002 was observed. 47.4% of patients in ES received RT, whereas 25.1% in AS underwent RT. RT significantly improved overall survival in both univariate (P < 0.001) and multivariate (P = 0.002) analyses. PSM analysis further validated the survival advantage of RT (P = 0.002). A nomogram was established to predict the potential survival benefit. Subgroup analysis revealed RT was significantly associated with overall survival in ES patients of PT-DLBCL (P = 0.001) and in the rituximab era (P = 0.001) but not in those with AS disease (P = 0.241)., Conclusions: This population-based study encloses the largest sample of PT-DLBCL to date and demonstrates a favorable survival role of RT in early stages rather than advanced stages. The established nomogram helps to identify high risk patients to improve prognosis., (© 2021. The Author(s).)

We describe the heretofore unreported case of an HPV-related carcinoma of the palatine tonsil with distinct areas of squamous cell- and adenoid cystic carcinoma-like differentiation in a 54-year old patient. The morphological, immunophenotypic and molecular findings of the tumor are illustrated. We discuss the parallels between the tumor and HPV-related multiphenotypic sinonasal carcinoma (HMSC) which is well-known to exhibit adenoid cystic carcinoma-like features. A review of the literature of high-risk HPV-associated non-squamous carcinomas of the oropharynx is presented., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Extragonadal non-gestational choriocarcinoma is a rare but well-described phenomenon occurring in patients with midline germ cell tumors. Choriocarcinoma (ChC) is an aggressive neoplasm usually developing in women as a rare complication of pregnancy. In male patients ChC occurs in the testes, usually as a component of mixed germ cell tumors. Very few patients develop extragonadal choriocarcinoma with the tumor occurring in midline locations, such as the mediastinum, retroperitoneum, and central nervous system (mostly pineal gland). Non-midline choriocarcinoma can occur in the lung, gastrointestinal tract, and breast, sometimes blended with another primary malignancy. A midline choriocarcinoma manifesting as a head and neck malignancy is exceptional. During an evaluation of multiple enlarged cervical lymph nodes suspected to be lymphoma in a 72-year-old man, a core biopsy was taken from one of the left neck lymph nodes which histologically showed a necrotic malignancy with strong diffuse pancytokeratin staining. After an initial interpretation of metastatic carcinoma, further samples were taken from both tonsils and from a right level 5 neck lymph node. Histologically, all samples contained the same tumor, showing profound pleomorphism and multinucleated syncytial-type giant cells. A panel of immunohistochemistry studies were performed, including β-human chorionic gonadotropin, with positive findings leading to a diagnosis of extragonadal non-gestational choriocarcinoma., (© 2020. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Nasopharyngeal carcinomas (NPC) are non-keratinizing squamous cell carcinomas of the nasopharynx associated with Epstein-Barr virus (EBV). When occurring outside of the nasopharynx, they are referred to as lymphoepithelioma-like carcinomas (LELCs) and present the same morphology as NPC. LELC have been described in other head and neck regions such as the salivary glands and the soft palate. LELC can also occur in the oropharynx, are associated with human papillomavirus (HPV) and are typically negative for EBV. We herein present a unique case of a 78-year-old Chinese male with EBV-positive, HPV-negative NPC of the left tonsil. His presenting symptom was a left-sided lymph node. There was no evidence of nasopharyngeal lesion seen on physical examination, PET and MRI. The patient was treated with curative-intent external beam radiotherapy which delivered 70 Gy (Gy) to the gross tumour and lymph nodes, and 56 Gy electively to the ipsilateral neck using a volumetric modulated arc therapy technique. This is the first case of primary tonsil EBV-positive NPC described in the literature., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

The purposes of the study were to determine whether there are differences in texture analysis parameters between tonsil cancers and normal tonsils, and to correlate texture analysis with 18F-FDG PET/CT to investigate the relationship between texture analysis and metabolic parameters. Sixty-four patients with squamous cell carcinoma of the palatine tonsil were included. A ROI was drawn, including all slices, to involve the entire tumor. The contralateral normal tonsil was used for comparison with the tumors. Texture analysis parameters, mean, standard deviation (SD), entropy, mean positive pixels, skewness, and kurtosis were obtained using commercially available software. Parameters were compared between the tumor and the normal palatine tonsils. Comparisons were also performed among early tonsil cancer, advanced tonsil cancer, and normal tonsils. An ROC curve analysis was performed to assess discrimination of tumor from normal tonsils. Correlation between texture analysis and 18F-FDG PET/CT was performed. Compared to normal tonsils, the tumors showed a significantly lower mean, higher SD, higher entropy, lower skewness, and higher kurtosis on most filters (p<0.001). On comparisons among normal tonsils, early cancers, and advanced tonsil cancers, SD and entropy showed significantly higher values on all filters (p<0.001) between early cancers and normal tonsils. The AUC from the ROC analysis was 0.91, obtained from the entropy. A mild correlation was shown between texture parameters and metabolic parameters. The texture analysis parameters, especially entropy, showed significant differences in contrast-enhanced CT results between tumor and normal tonsils, and between early tonsil cancers and normal tonsils. Texture analysis can be useful as an adjunctive tool for the diagnosis of tonsil cancers., Competing Interests: The authors have declared that no competing interests exist.

Head and neck lymphomas can present with a wide range of symptoms. Timely and accurate diagnosis is often challenging. The blastoid variant of mantle cell lymphoma (MCL) accounts for less than one-third of all MCL cases. Isolated primary presentation on the palatine tonsils is rare, and prognosis and outcome are seemingly unfavorable. An 81-year-old man presented with persistent odynophagia, dysphagia, and obstructive hypertrophic palatine tonsils with purulent exudate. The signs and symptoms were non-responsive to antibiotic therapy, and the tonsils were biopsied. The cellular morphology, immunophenotype, and genotype supported a diagnosis of the blastoid variant of MCL. After staging, the patient underwent chemotherapy with Rituximab-Bendamustine (R-Benda). The patient is in clinical remission more than two years after therapy. We report an exceedingly rare case of blastoid MCL that is prone to be misdiagnosed as tonsillitis. We review the literature and discuss treatment options of this uncommon malignancy.

Follicular dendritic cell sarcoma (FDCS) is a rare entity which can share morphologic features with non-keratinizing squamous cell carcinoma. Recent reports suggest that up to half of FDCSs show immunohistochemical positivity for p16 (Zhang et al., in Hum Pathol 66:40-47, 2017), a stain that is conventionally used in the risk stratification of oropharyngeal squamous cell carcinoma (OPSCC). Herein, we report a case of p16-positive FDCS with clinical and histomorphologic overlap with human papilloma virus (HPV)-related OPSCC.

Background: To analyze the prevalence proportions and prognostic factors of synchronous distant metastases in patients with tonsil squamous cell carcinomas (TSCC)., Methods: TSCC patients were extracted from the Surveillance, Epidemiology and End Results (SEER) database between 2010 and 2014. We examined the association between clinical manifestations and distant metastases using Chi-squared tests. Predictors of 5-year survival were assessed using univariate and multivariate analyses., Results: A total of 6193 patients were analyzed and lung was the most common site of distant metastases. Poorly/undifferentiated differentiation was found to be significantly correlated with lung metastasis (p=0.033) and liver and bone metastases were associated with African American (p=0.000 and p=0.000, respectively). A higher T classification was associated with higher prevalence of lung, liver, bone and brain metastasis (p=0.000, p=0.000, p=0.000 and p=0.007, respectively). The same results were found in N classification in lung, liver, and bone metastasis (p=0.000, p=0.000, and p=0.000, respectively). Worse prognosis was associated with older age, Blacks, lower grade, higher T and N classification, no surgery therapy and more metastatic sites., Conclusion: Lung was the most frequent lesion of synchronous distant metastases and liver and bone metastases were associated with African American. Higher T and N classification were independent prognostic parameters for higher prevalence of lung, bone, liver and brain metastasis. Worse prognosis was associated with older age, African Americans, lower grade, higher T and N classification, no surgery therapy and more metastatic sites., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Double-hit lymphoma (DHL) is a unique subtype of non-Hodgkin lymphoma characterized by atleast two rearrangements involving MYC, BLC2, and/or BCL6. These lymphomas are uncommon and aggressive, responding poorly to typical chemotherapy regimens. Lymphomas rarely arise from the oral cavity or tonsils, and those presenting as a neck mass are predominantly diffuse large B-cell lymphoma. To date, primary DHL of the tonsils has yet to be described in the literature. Here, we report a case of a 44 year-old male patient with well-controlled human immunodeficiency virus (HIV) who presented with a sore throat. He subsequently developed acute respiratory compromise due to a rapidly enlarging tonsillar mass. Pathologic and genetic analysis confirmed the presence of BCL6 and MYC rearrangements suggestive of DHL of the tonsils. In a young patient with HIV and a neck mass, it is essential that lymphoma remains on the list of differential diagnoses as prompt diagnosis and treatment may prevent complications from its rapid expansion.

HPV-infection in patients with HNSCC is reportedly correlated with sexual behavior, age, and tobacco/alcohol-consumption. HPV-infections of the oral cavity are regarded as sexually transmitted. Comparable data of patient populations outside the U.S. are sparse or missing. Questionnaires regarding sexual behavior, education tobacco- and alcohol-consumption, were given to 28 patients with tonsillar hyperplasia (H) and 128 patients with tonsillar carcinomas (CA), all with tissue-typed HPV-DNA-status performing PCR. Answers were correlated among groups and HPV-status. 106 questionnaires were analyzed. Comparisons between H- (n = 25) and CA- (n = 81) patients showed that CA-patients were older (61.1yrs ± 9.3) than H-patients (45.2yrs ± 11.9; p < 0.0001; Student's t-test); had a lower educational level (p = 0.0095); and lower number of sexual partners (p = 0.0222; Fisher's exact test). All groups showed a significant correlation between smoking and lack of HPV-DNA-positivity (p = 0.001). Further Fisher's exact tests and logistic regression analysis revealed in all 106 patients no significant correlations between tissue-HPV-status and the analyzed parameters. Despite the limited sample size, we were able to confirm the established correlation between smoking and tissue-HPV-status. The correlation between sexual behavior and HPV-infection was not confirmed. No consensus exists in the literature about the latter. Our data does not support the strict classification of oral HPV-infections and HPV-driven HNSCCs as STDs., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Goal: To evaluate transoral robotic surgery (TORS) for isolated previously untreated squamous cell carcinoma (SCC) of the tonsillar fossa classified as T1-2., Method: Retrospective analysis of two cohorts of isolated untreated T1-2 tonsillar fossa SCC consecutively operated on by a transoral approach, with (R=21) and without (NR=24) robotic assistance, in the period 2006-2014. Three main (survival, local control, and operative morbidity) and three secondary (pathologic data, incidence and duration of tracheotomy and nasogastric intubation, and hospital stay) endpoints were compared between groups. The significance threshold was set at P< .005., Results: Three- and five-year actuarial survival estimates were 80.2% and 74.5% respectively in group R, and 91.5% and 82.5% respectively in group NR (NS: P=.34). Three- and five-year actuarial local control estimates were 90% and 90% respectively in group R, and 95.8% and 91% respectively in group NR (NS: P=.81). There were no significant differences in morbidity, tracheotomy/nasogastric intubation time, or hospital stay. Positive resection margins (R1) were noted in 38.1% and 16.7% in groups R and NR, respectively (NS: P=.05) without significant impact on 5-year actuarial local control (P=0.78)., Conclusion: Robotic assistance in transoral lateral oropharyngectomy for T1-2 tonsillar fossa SCC did not significantly impact oncologic or functional outcome., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

This study aimed to establish and validate a comprehensive nomogram for predicting the cause-specific survival (CSS) probability in tonsillar squamous cell carcinoma (TSCC). We screened and extracted data from the SEER (Surveillance, Epidemiology, and End Results) database for the period 2004 to 2016. We randomly divided the 7243 identified patients into a training cohort (70%) for constructing the model and a validation cohort (30%) for evaluating the model using R software. Multivariate Cox stepwise regression was used to select predictive variables. The concordance index (C-index), the area under the time-dependent receiver operating characteristics curve (AUC), the net reclassification improvement (NRI), the integrated discrimination improvement (IDI), calibration plotting, and decision-curve analysis (DCA) were used to evaluate the model. The multivariate Cox stepwise regression analysis successfully established a nomogram for the 1-, 3-, and 5-year CSS probabilities for TSCC patients. The C-index, AUC, NRI, and IDI were all showed that the model has good discrimination. The calibration plots were very close to the standard lines, indicating that the model has a good degree of calibration, and the DCA curve further illustrated that the model has good clinical validity. We have established the first nomogram for predicting the 1-, 3-, and 5-year CSS probabilities for TSCC based on a large retrospective sample. Our rigorous validation and evaluation indicated that the model can provide useful guidance to clinical workers making clinical decisions about individual patients.

Tonsillar synovial sarcoma is an extremely rare entity and only 9 adult patients have been reported up to now. Here, we describe the first pediatric tonsillar synovial sarcoma of the literature in a patient who presented with a 2-month history of dysphagia and snoring. Clinical and radiological examinations showed that the tumor arose from the right palatine tonsil and narrowed the parapharyngeal space. An incisional biopsy from the palatine tonsil revealed the diagnosis of synovial sarcoma. The patient has underwent total tonsillectomy and received radiotherapy and chemotherapy because of the positive surgical margins. The patient is clinically in good condition and free of tumor 30 months after the initial diagnosis. We achieved a long-term complete remission with a combination of surgery, radiotherapy and chemotherapy in our case. Tonsillar synovial sarcoma should be kept in mind while dealing with tonsillar masses. We can conclude that a multidisciplinary approach is warranted while treating synovial sarcoma with this localization.

Oropharyngeal squamous cell carcinomas associated with high risk HPV show a wide morphological spectrum, including papillary, adenosquamous, lymphoepithelioma-like and sarcomatoid. We report an interesting case of ciliated HPV-related carcinoma arising from tonsillar tissue in a 55-year-old man which was associated with HPV33. This rare variant has been described in only a handful of cases in the literature, and to our knowledge this is the first case specifically associated with HPV33. The presence of cilia is a potential diagnostic problem as it has been traditionally considered a feature of benignancy, and could pose a particular challenge on frozen section. The diagnostic challenges, differential diagnosis of this tumor and the association with HPV33 are discussed.

We present a 52 years old male with a left tonsillar follicular dendritic cell sarcoma with prominent epithelioid features that on light microscopical examination bore a striking resemblance to a lymphoepithelial or undifferentiated carcinoma. The tumor was immunohistochemically positive for CD21 and CD35 and negative for cytokeratins. Two distinct histopathological features (both present in our case) that may serve as clues to the correct diagnosis on light microscopical examination were formation of ectatic pseudovascular spaces lined by malignant cells and the presence of non-neoplastic multinucleated giant cells. Familiarity with the above-mentioned morphological clues, and awareness that this tumour may occur in anatomical sites outside the lymph node, are essential for accurate diagnosis.

Rationale: Human papillomavirus (HPV)-related oropharyngeal cancer is becoming more common, the primary cancer AQ4 usually occult and appearing only as cystic cervical lymph node (LN) metastasis. Distinguishing between a benign cystic lesion and cystic LN metastasis is challenging given their similar radiologic and histologic appearances., Patient Concerns: A 54-year-old man presented with a bulging cystic mass measuring 6.4cm on the right side of neck., Diagnoses: Postexcision diagnosis was second branchial cleft cyst. After 2 years, the cystic mass recurred, and HPV-related tonsillar squamous cell carcinoma with cystic metastatic LNs was confirmed after wide tonsillectomy and neck dissection. The previous cystic lesion proved to be a cystic metastatic LN from the same malignancy with additional p16 immunostain., Interventions: The patient was treated with adjuvant concurrent chemoradiation therapy., Outcomes: The patient was followed up in the outpatient department with no evidence of recurrence after 1 year., Lessons: When an adult has a cystic mass in the upper neck, we must rigorously exclude it as a cystic metastatic LN of occult HPV-related oropharyngeal cancer. Additional p16 staining might be helpful.

Surgical oncologists depend heavily on visual field acuity during cancer resection surgeries for in-situ margin assessment. Clinicians must wait up to two weeks for results from a pathology lab to confirm a post-operative diagnosis, potentially resulting in subsequent treatments. Currently, there are no clinical tools that can visualize diagnostically pertinent tissue information in-situ. Here, we present the first microscopy capable of non-contact label-free visualization of human cellular morphology in a reflection-mode apparatus. This is possible with the recently reported imaging modality called photoacoustic remote sensing microscopy which enables non-contact detection of optical absorption contrast. By taking advantage of the 266-nanometer optical absorption peak of DNA, photoacoustic remote sensing is efficacious in recovering qualitatively similar nuclear information in comparison to that provided by the hematoxylin stain in the gold-standard hematoxylin and eosin (H&E) prepared samples. A photoacoustic remote sensing system was employed utilizing a 266-nanometer pulsed excitation beam to induce photoacoustic pressures within the sample resulting in refractive index modulation of the optical absorber. A 1310-nanometer continuous-wave interrogation beam detects these perturbed regions as back reflected intensity variations due to the changes in the local optical properties. Using this technique, clinically useful histologic images of human tissue samples including breast cancer (invasive ductal carcinoma), tonsil, gastrointestinal, and pancreatic tissue images were formed. These were qualitatively comparable to standard H&E prepared samples.

Benign tumours of the tonsils are rare. Majority of these lesions are diagnosed as squamous papilloma. Hamartoma is a benign tumor-like malformation. Hamartoma in tonsils is unique and only a few anecdotal cases are reported until now. Tonsillar hamartoma usually presents as unilateral or bilateral polyp with clinical features of dysphagia or foreign body sensation. Histopathologically, normal tissues are noted in a haphazard or disorganised way. We hereby present a case of 31-year-old male patient with tonsillar hamartomatous polyp presenting with the symptom of a foreign body sensation in the throat. The diagnosis of this entity and its distinction from other clinico-pathological mimickers require histopathological examination and awareness. A complete surgical excision is curative without any evidence of disease recurrence., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: There are no conflicts of interest

Rationale: Palatine tonsil is an extremely rare site for metastatic disease, accounting for 0.8% of malignant tonsillar neoplasms. To the best of our knowledge, this is the first report of metastatic adenocarcinoma in the tonsil treated with wide excision and targeted therapy, with no local recurrence 6 months postoperatively., Patient Concerns: A 75-year-old man presented hemoptysis and mild productive cough for 2 weeks., Diagnoses: Palatine tonsil metastasis from lung adenocarcinoma, pT2bN0M1b, stage IVA, was confirmed., Interventions: Wide excision of primary lung tumor and metastatic tonsil carcinoma has been performed, and the patient was undergoing targeted therapy with the epidermal growth factor receptor inhibitor afatinib., Outcomes: There was no local recurrence in the oropharynx 6 months postoperatively., Lessons: We aim at highlighting the importance of a thorough evaluation for suspicion of tonsillar enlargement, which might be a sign of a primary malignancy elsewhere.

Rationale: Extranodal natural killer T-cell lymphoma nasal type (ENKL) is an extremely rare tumor with a very low survival rate. In recent decades, only a few ENKL cases have been published. Presenting a special ENKL case lead the authors to emphasize the primary features of ENKL in early diagnosis and therapy. Here we report an unusual ENKL case which was initially found in the eyes and presented as masqueraded uveitis PATIENT CONCERNS:: A 55 years old female, with vision loss in the right eye for approximately 6 months, and vision blurry, redness and pain in the left eye for 2 weeks, was referred to our hospital., Diagnosis: Clinical examinations and images demonstrated bilateral anterior uveitis, retinal and choroidal detachment, and secondary glaucoma. After 3 months, the patient began to present a sore throat, fever, and headaches. The computed tomography (CT) and magnetic resonance imaging (MRI) of her skull demonstrated nothing positive. One month later, a neoplasm was found in her nasopharynx and tonsil, which was confirmed, by histopathology, as ENKL INTERVENTIONS:: This patient was prescribed with steroid for 3 months because of the first diagnosis by the ophthalmologist. After the other symptoms like a sore throat, fever and headaches occurred, symptomatic treatment was given. Unfortunately, when the real cause was found, the patient could not tolerate the other treatment for ENKL., Outcomes: Since the patient was treated with steroid without improvement, she died due to the septic shock and multiple organ failure., Lessons: Clinicians should always be cautious to ENKL which can be easily be misdiagnosed in the early stage. Early diagnosis and appropriate treatment are keys to raise the survival rate of ENKL patients.

Competing Interests: None

Chronic lymphocytic leukemia (CLL) patients are at an increased risk for developing more aggressive lymphomas via Richter's transformation and of developing secondary malignancies. Despite the known association for secondary cancers, oropharyngeal cancers occur rarely. We present a case of a woman with a history of CLL who presented to our facility via transfer for impending airway compromise. Her initial workup was consistent with CLL; however, biopsies were taken of the neck mass because of its aggressive nature. She was treated with rituximab with good response. Final pathology showed evidence of CLL and tonsillar squamous cell carcinoma (SCC). Direct laryngoscopy and further biopsies yielded a diagnosis of unresectable oropharyngeal SCC. She was to be treated with chemotherapy and radiation for her SCC while holding treatment for CLL. This case demonstrates a rare and unexpected concurrent diagnosis.

Recently, an in situ hybridization (ISH) and immunohistochemical study demonstrated that Epstein-Barr virus (EBV) infection may be involved in tonsillar hypertrophy and recurrent tonsillitis in children and young adolescents. The present study was based on 630 consecutive specimens from tonsillectomies performed at the Dokkyo University School of Medicine between 2002 and May 2017. Clinical findings were obtained from hospital records. Histologically, a "pale clear zone" was characterized by hyperplastic germinal centers with ill-defined borders and interfollicular expansion. Immunohistologically, the majority of immunoblasts were CD20-positive, whereas medium to large lymphoid cells usually expressed CD3. Among 14 lesions, numerous EBV-encoded small RNA (EBER)-positive cells were detected in 10. In 7 of these 10 lesions, EBER-positive cells were detected in germinal centers as well as in the interfollicular area. Based on our results, the "pale clear zone" suggests asymptomatic EBV infection of the tonsil. The present study demonstrated that "pale clear zones" should be taken into consideration when diagnosing asymptomatic EBV-associated LPDs in the tonsils of children and young adolescents as well as in middle-aged patients.

Osteonecrosis of the jaw is a significant complication secondary to radiation therapy or drug therapy, most commonly bisphosphonates. Safety data regarding the administration of bisphosphonates in bone metastatic head and neck cancer patients with history of jaw irradiation are almost non-existent. In this paper, we report the case of a Head and Neck (HNC) patient, with history of radiation therapy to the mandible region, treated with intravenous bisphosphonates for bone metastases that resulted in gross, life threatening mouth hemorrhage secondary to advanced, locally invasive ONJ.

Background/aim: Human papillomavirus-positive (HPV + ) tonsillar and base of tongue squamous cell carcinoma (TSCC/BOTSCC) have better outcome than corresponding HPV - cancers. To better individualize treatment, additional predictive markers are needed. Previously, we have shown that mutated fibroblast growth factor receptor 3 protein (FGFR3) was correlated to poorer prognosis and here FGFR3 expression was further analyzed., Patients and Methods: One-hundred-fifteen HPV + TSCC/ BOTSCC biopsies were analyzed for FGFR3 by immunohistochemistry (IHC), and 109/115 were analyzed for FGFR3 mutations by Ion Proton sequencing, or by Competitive Allele-Specific Taqman PCR (CAST-PCR). Disease-free survival (DFS) was then calculated according to FGFR3 IHC expression., Results: CAST-PCR was useful for detecting the three most common FGFR3 mutations. Focusing especially on the 98/115 patients with HPV + TSCC/BOTSCC and wild-type FGFR3, high FGFR3 expression correlated to significantly better 3-year DFS, p=0.043., Conclusion: In patients with HPV + TSCC/BOTSCC and wild-type FGFR3, overexpression of FGFR3 was correlated with better DFS., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)