Association of Human Papillomavirus and Epstein-Barr Virus Infection with Tonsil Cancer in Northeastern Thailand.

BACKGROUND: Human papillomavirus (HPV) and Epstein-Barr virus (EBV) are associated with head and neck cancer, including tonsil cancer (TC) in the oropharyngeal area. Increasing incidence of HPV and EBV infection in different cancer tissues of oropharynx in both epithelial and lymphoid tissues, have been reported. However, little is known about association of these tumor viruses with TC in the Thai population. Here, we investigated the prevalence of HPV and EBV infection in different histology of TC and their association with TC from Thai patients. METHODS: Eighty-three exfoliated tonsil cells from non-cancer controls (NCC) and 65 formalin-fixed paraffin-embedded TC tissues (TC) that were histologically classified as tonsillar squamous-cell carcinoma (TSCC) or diffuse large B-cell lymphoma (DLBCL) were studied. Prevalence of HPV and EBV infection was determined by real-time PCR. HPV genotyping was performed by reverse line blot hybridization and HPV genome status was investigated by multiplex qPCR. Localization of EBV infection was determined by EBER in situ hybridization. RESULTS: Infection of HPV and EBV in TC cases was 16.9% and 30.8%, whereas in exfoliated tonsil cells was 1.2% and 66.3% respectively. HPV infection was significantly higher in TSCC (30.6%) than DLBCL samples (13.8%). HPV58 was commonly detected and presented as an integrated form in TSCC, whereas only episomal form was found in DLBCL. EBV infection was significantly higher in DLBCL (44.8%) than TSCC samples (19.4%), and detected in both lower than among exfoliated tonsil cell samples (66.3%). By EBER in situ hybridization in TSCC, EBV infection localized both in epithelial cells and infiltrating lymphocytes. The co-occurrence of HPV and EBV infection was 11.11% and 13.79% of TSCC and DLBCL, respectively, was associated with well-differentiated TSCC. CONCLUSION: HPV and EBV infection was significantly involved in a specific TC tissue, and associated with a good clinical outcome in TSCC.

COVID-19 Incidentally Detected on PET/CT During Work-up for Locally Advanced Head and Neck Cancer.

AIM: To describe the incidental detection of COVID-19 disease on positron-emission tomography/computed tomography (PET/CT) in a patient with cancer despite initial negative swab by polymerase chain reaction (PCR). CASE REPORT: Clinical and radiographic data were obtained from the electronic medical record. Nasopharyngeal swabs were obtained and evaluated for COVID-19 by the Food and Drug Administration-approved reverse transcription-PCR assays. On radiographic examination, PET/CT was consistent with COVID-19-related pneumonia not seen on prior imaging. Initial nasopharyngeal swab 2 days after PET/CT imaging was negative for COVID-19. Subsequent repeat swab 10 days later was positive for COVID-19, while the patient was febrile on screening assessment. The patient remained COVID-19-positive until 1 month after abnormal PET/CT imaging. CONCLUSION: PET/CT can be sensitive for early COVID-19 detection, even in the setting of a negative confirmatory PCR test. This highlights the importance of continued patient surveillance and use of appropriate personal protective equipment to minimize COVID-19 transmission.

Left atrial tumor thrombus with emboli to the brain and distal extremities: A case report.

Cardiac metastases are an uncommon phenomenon associated with neoplasms from a variety of primary sites. Pulmonary involvement often accompanies metastases involving the left atrium or ventricle and clinical presentation may be associated with stroke or emboli involving distal sites. We report a patient who presented acutely to the Emergency Department with symptoms of a cerebrovascular accident and bilateral cold pulseless lower extremities. Computerized Tomographic (CT) angiogram of the chest, abdomen, pelvis and lower extremities disclosed pulmonary veins with large filling defects in the right superior and inferior vessels as well as the left atrium and atrial appendage. Mediastinal and hilar adenopathy was detected. The patient had a history of tonsillar squamous cell carcinoma eighteen months prior. The patient underwent operative intervention with removal of a large left intra-atrial mass, histologic evaluation of which demonstrated groups of malignant squamous cells meshed in fibrin clot. The patient died three days post operatively due to multiple brain infarctions.

Pediatric Tonsillar Synovial Sarcoma- Very Rare Localization: A Case Report and Review of the Literature.

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.

Radiotherapy versus transoral robotic surgery and neck dissection for oropharyngeal squamous cell carcinoma (ORATOR): an open-label, phase 2, randomised trial.

BACKGROUND: Transoral robotic surgery (TORS) with concurrent neck dissection has supplanted radiotherapy in the USA as the most common treatment for oropharyngeal squamous cell carcinoma (OPSCC), yet no randomised trials have compared these modalities. We aimed to evaluate differences in quality of life (QOL) 1 year after treatment. METHODS: The ORATOR trial was an investigator-initiated, multicentre, international, open-label, parallel-group, phase 2, randomised study. Patients were enrolled at six hospitals in Canada and Australia. We randomly assigned (1:1) patients aged 18 years or older, with Eastern Cooperative Oncology Group scores of 0-2, and with T1-T2, N0-2 (≤4 cm) OPSCC tumour types to radiotherapy (70 Gy, with chemotherapy if N1-2) or TORS plus neck dissection (with or without adjuvant chemoradiotherapy, based on pathology). Following stratification by p16 status, patients were randomly assigned using a computer-generated randomisation list with permuted blocks of four. The primary endpoint was swallowing-related QOL at 1 year as established using the MD Anderson Dysphagia Inventory (MDADI) score, powered to detect a 10-point improvement (a clinically meaningful change) in the TORS plus neck dissection group. All analyses were done by intention to treat. This study is registered with ClinicalTrials.gov (NCT01590355) and is active, but not currently recruiting. FINDINGS: 68 patients were randomly assigned (34 per group) between Aug 10, 2012, and June 9, 2017. Median follow-up was 25 months (IQR 20-33) for the radiotherapy group and 29 months (23-43) for the TORS plus neck dissection group. MDADI total scores at 1 year were mean 86·9 (SD 11·4) in the radiotherapy group versus 80·1 (13·0) in the TORS plus neck dissection group (p=0·042). There were more cases of neutropenia (six [18%] of 34 patients vs none of 34), hearing loss (13 [38%] vs five [15%]), and tinnitus (12 [35%] vs two [6%]) reported in the radiotherapy group than in the TORS plus neck dissection group, and more cases of trismus in the TORS plus neck dissection group (nine [26%] vs one [3%]). The most common adverse events in the radiotherapy group were dysphagia (n=6), hearing loss (n=6), and mucositis (n=4), all grade 3, and in the TORS plus neck dissection group, dysphagia (n=9, all grade 3) and there was one death caused by bleeding after TORS. INTERPRETATION: Patients treated with radiotherapy showed superior swallowing-related QOL scores 1 year after treatment, although the difference did not represent a clinically meaningful change. Toxicity patterns differed between the groups. Patients with OPSCC should be informed about both treatment options. FUNDING: Canadian Cancer Society Research Institute Grant (#701842), Ontario Institute for Cancer Research Clinician-Scientist research grant, and the Wolfe Surgical Research Professorship in the Biology of Head and Neck Cancers grant.

Hypoglycemia associated with disseminated metastatic tonsillar squamous cell carcinoma producing insulin-like growth factor-I in a Pomeranian dog.

A 13-year-old spayed female Pomeranian dog was presented for persistent, severe hypoglycemia (37 mg/dL; reference interval [RI] 75-128 mg/dL). Progressive nonregenerative anemia (hematocrit 23.3%-15.9%; RI 37.0%-55.0%) and severe thrombocytopenia (36 000/µL; RI 200-500 000/µL) were also noted. The serum insulin concentration was low (0.24 ng/mL; RI 0.302-1.277 ng/mL). Computed tomography revealed multiple splenic nodules (1-6 mm in diameter) and several hepatic nodules (7.6, 12 mm in diameter). Ultrasound-guided fine-needle aspiration of the splenic and hepatic nodules revealed low numbers of epithelial cells with mild cellular atypia, suggestive of a metastatic epithelial tumor, but the primary site was unknown at that time. On careful oral examination under general anesthesia, an enlarged right tonsil was noted grossly, and histopathologic examination of the tonsil diagnosed squamous cell carcinoma. Bone marrow aspirates and biopsies of the splenic and hepatic nodules were performed; all samples were diagnosed as metastatic carcinoma on histopathologic examination. No nodules were present in the pancreas, despite careful palpation during exploratory laparotomy. On immunohistochemistry, the neoplastic cells were positive for cytokeratin AE1/3 and insulin-like growth factor (IGF)-I but were negative for chromogranin A, PGP9.5, insulin, and inconclusive for IGF-II. This is the first report of a primary IGF-I-producing squamous cell carcinoma in the tonsil of a dog with metastases to bone marrow, liver, and spleen, resulting in hypoglycemia.

Cerebellar Hypermetabolism in a Case of Paraneoplastic Cerebellar Syndrome With the Primary Lymphoepithelial Carcinoma in Tonsil.

A 70-year-old man with cerebellar syndromes was clinically diagnosed as paraneoplastic cerebellar degeneration and underwent whole-body F-FDG PET/CT imaging for screening primary tumor. Intensely elevated tracer uptake in both cerebellar hemispheres was revealed, whereas no abnormality was found in MRI. Increased tracer uptake and swelling of the left tonsil and a cervical lymph node were found at the same time, suggesting neoplasm in tonsil with lymph node metastasis. Pathological examination demonstrated lymphoepithelial carcinoma of the left tonsil.

Naloxegol for opioid-induced sphincter of Oddi spasm/dysfunction.

The paper describes a case report of a patient with a significant history of opioid-induced dysfunction of the sphincter of Oddi, who required morphine sulfate to manage oral mucositis pain, and who was successfully treated with concomitant oral naloxegol (Moventig: Kyowa Kirin, Galashiels, UK).

Association Between Fibroblast Growth Factor Receptor 1 Gene Amplification and Human Papillomavirus Prevalence in Tonsillar Squamous Cell Carcinoma With Clinicopathologic Analysis.

Amplification of fibroblast growth factor receptor 1 ( FGFR1) has been reported in many squamous cell carcinomas, and human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma has been characterized as a distinct subset with favorable prognosis. Here, we investigated the FGFR1 amplification and HPV status in tonsillar squamous cell carcinoma (TSCC) and analyzed the clinical characteristics. HPV in situ hybridization (HPV ISH) and FGFR1 fluorescence in situ hybridization (FISH) were performed using tissue microarray from 89 cases of TSCC. Fourteen of 89 (15.7%) TSCC cases had FGFR1 amplification, and HPV was detected in 59 of 89 (66.3%) cases. FGFR1 amplification status was not associated with HPV positivity ( p=0.765). Outcomes were not significantly different between FGFR1 amplified and non-amplified patients. Although FGFR1 amplified patients ( n=4) in the HPV ISH-negative group ( n=30) had a tendency for poorer overall survival, no statistical significance was identified ( p=0.150, log-rank). FGFR1 protein overexpression showed better disease-free survival ( p=0.031, log-rank) in HPV-negative TSCC. This study suggests FGFR1 amplification may be important in the pathogenesis of TSCC regardless of HPV status.

Radiation and chemotherapy with no excessive toxicity in a patient with human papillomavirus-related tonsillar cancer and porphyria cutanea tarda: Case report and literature review.

BACKGROUND: Porphyria is a condition of cutaneous photosensitivity. It is unclear if radiotherapy (RT) is safe in patients with porphyria. METHODS: We report a patient case with uncontrolled porphyria cutanea tarda treated with chemoradiation for p16-positive oropharyngeal cancer. Given the scarcity of data on this subject, we also conducted a literature review on the topic of radiation in patients with porphyria. RESULTS: The patient in our study did not experience any unusual acute or late toxicity, despite receiving a high dose of cutaneous radiation. We also found the majority of the literature supports the safe use of therapeutic radiation in patients with porphyria. CONCLUSION: In this patient, and in the majority of the literature, radiation seems safe in patients with porphyria; however, there are few reports on the subject in the literature, therefore, caution is warranted.

When dizziness becomes sinister: oropharyngeal carcinoma presenting as a paraneoplastic neurological disorder.

Paraneoplastic neurological disorders are uncommon presentations of head and neck cancers. We present a case of a 68-year-old male patient who presented with dizziness, nausea and memory problems. MRI of his brain showed bilateral cerebellar leptomeningeal enhancing signal abnormality with cervical lymphadenopathy. CT imaging of his neck raised the suspicion of a tonsillar primary, which was later confirmed on biopsy. His poorly differentiated HPV positive squamous cell carcinoma was treated with chemoradiotherapy. Subsequent MRI imaging showed progressive cerebellar atrophy and his presenting symptoms persisted, but he remained disease free 6 months post-treatment for his primary malignancy.

Intratonsillar metastasis of EBV-positive nasopharyngeal carcinoma.

We present the case of a 47-year-old man with a history of Epstein-Barr-virus-positive nasopharyngeal carcino- ma who developed a metastasis to the palatine tonsil. To the best of our knowledge, this is the first reported case of an intratonsillar metastasis of a nasopharyngeal carcinoma. The aim of this report is to emphasize the importance of vigilant surveillance in patients with nasopharyngeal carcinoma. This case also demonstrates that an atypical metastatic pattern can raise suspicion of a local disease recurrence.

Post-transplant lymphoproliferative disorders with naso- and oropharyngeal manifestation.

The nasopharyngeal/oropharyngeal lymphatic tissues represent the anatomical site of Epstein-Barr virus (EBV) entry. Post-transplant lymphoproliferative disorders (PTLD) are often associated with EBV, but little is known about the characteristics of nasopharyngeal/oropharyngeal mass-forming PTLD. Retrospective evaluation of our own PTLD database (n = 79) and the PubMed(®) database (n = 61) has been performed. Sinonasal/oro-/nasopharyngeal lymphatic masses were early lesions (n = 54/140, 38.5%), polymorphic PTLD (n = 32/140, 23%), monomorphic B-PTLD (n = 47/140, 33.5%) and T-PTLD (n = 7/140, 5%). One-fourth of lesions manifested as masses in the Waldeyer's ring, and in two-thirds of cases, swelling of tonsils was related to manifestation of benign early lesions. Tonsil infiltration by polymorphic PTLD and monomorphic PTLD was present in one-third of cases. Extratonsillar masses were mainly monomorphic PTLD. Meta-analysis of our data in combination with previously published data revealed that lung transplantation and young patients are at a higher risk for earlier manifestation of monomorphic PTLD. Therapy is similar to PTLD therapy strategies, in general reduced immunosuppression and chemotherapy for polymorphic and monomorphic PTLD, and diagnostic and therapeutic surgical gross tumour resection of tonsillar/adenoid lesions. In summary, it is relevant for the clinical differential diagnosis that oro-/nasopharyngeal aggressive PTLD manifested in ~30% as tonsillar masses and >90% at extratonsillar sites.