Head-to-head comparison of [68Ga]Ga-DOTA-FAPI-04 and [18F]FDG PET/CT for the evaluation of tonsil cancer and lymph node metastases: a single-centre retrospective study.

BACKGROUND: This study aimed to compare the diagnostic value of [68 Ga]Ga-DOTA-FAPI-04 and [18F]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 [18F]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 [18F]FDG PET/CT (9/22). Although [68 Ga]Ga-DOTA-FAPI-04 uptake (SUVmax, 5.03 ± 4.06) was lower than [18F]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 [18F]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 [18F]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 [18F]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 [18F]FDG by improving the detection rate of primary lesions and the diagnostic accuracy of cervical metastatic lymph nodes in tonsil cancer compared to [18F]FDG.

[Analysis on the ultrasonic characteristics of tonsillar lymphoma].

Objective: To analyze the ultrasonic features of tonsillar lymphoma to improve the diagnostic accuracy. Methods: The clinical, pathological and ultrasonic data of nine patients with tonsillar lymphoma confirmed by pathology at Tianjin Medical University Cancer Institute and Hospital during June 2015 and June 2022 were analyzed retrospectively, and the characteristics of their ultrasonic images were summarized. Results: All 9 cases of tonsil lymphoma were unilateral tonsil disease, including 4 cases on the left side and 5 cases on the right side. The average maximum diameter of tonsil lymphoma in 9 cases was 4.32 cm. There were 3 cases with simultaneous involvement of tonsil and cervical lymph nodes, all of which were ipsilateral lymph nodes. Gray scale ultrasound showed that the lesions were hypoechoic, with clear boundaries in 7 cases and unclear boundaries in 2 cases. The shape was full and irregular in 5 cases and oval in 4 cases. The echo was uniform in 7 cases and uneven in 2 cases. Color Doppler ultrasonography showed abundant internal blood flow signal in 1 case, a little dotted linear internal blood flow signal in 5 cases, and no obvious internal blood flow signal in 3 cases. Conclusions: The ultrasonic features of tonsillar lymphoma include hypoechoic area, clear boundary, full shape, irregular and uniform internal echo, no or low linear signal of internal blood flow. Ultrasonography is of great value in the diagnosis of this disease and can help clinical decision-making.

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

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

Impact of metal artifact reduction algorithm on gross tumor volume delineation in tonsillar cancer: reducing the interobserver variation.

BACKGROUND: Patients with tonsillar cancer (TC) often have dental fillings that can significantly degrade the quality of computed tomography (CT) simulator images due to metal artifacts. We evaluated whether the use of the metal artifact reduction (MAR) algorithm reduced the interobserver variation in delineating gross tumor volume (GTV) of TC. METHODS: Eighteen patients with TC with dental fillings were enrolled in this study. Contrast-enhanced CT simulator images were reconstructed using the conventional (CTCONV) and MAR algorithm (CTMAR). Four board-certified radiation oncologists delineated the GTV of primary tumors using routine clinical data first on CTCONV image datasets (GTVCONV), followed by CTCONV and CTMAR fused image datasets (GTVMAR) at least 2 weeks apart. Intermodality differences in GTV values and Dice similarity coefficient (DSC) were compared using Wilcoxon's signed-rank test. RESULTS: GTVMAR was significantly smaller than GTVCONV for three observers. The other observer showed no significant difference between GTVCONV and GTVMAR values. For all four observers, the mean GTVCONV and GTVMAR values were 14.0 (standard deviation [SD]: 7.4) cm3 and 12.1 (SD: 6.4) cm3, respectively, with the latter significantly lower than the former (p < 0.001). The mean DSC of GTVCONV and GTVMAR was 0.74 (SD: 0.10) and 0.77 (SD: 0.10), respectively, with the latter significantly higher than that of the former (p < 0.001). CONCLUSIONS: The use of the MAR algorithm led to the delineation of smaller GTVs and reduced interobserver variations in delineating GTV of the primary tumors in patients with TC.

Post-Treatment Neck Dissection of Tonsillar and Base of Tongue Squamous Cell Carcinoma in the Era of PET-CT, HPV, and p16.

Human-papillomavirus (HPV)-positive tonsillar and base of tongue carcinomas (TSCC/BOTSCC) are rising in incidence and treatments with radiotherapy, chemoradiotherapy (RT/CRT), and neck dissections (NDs) have several side effects. Therefore, an improved selection of patients needing salvage NDs would be beneficial. We examined the prevalence and localisations of viable tumour cells in neck lymph nodes in patients post-RT/CRT, identified by fluorodeoxyglucose positron-emission tomography with computer-tomography (FDG PET-CT), with a focus on HPV-associated tumours. Patients with 217 TSCC/BOTSCC with tumours assessed for HPV-DNA and p16INK4a undergoing FDG PET-CT 12 weeks after treatment and/or an ND were included. The FDG PET-CT data were compared with the findings in the pathology report after the ND. In total, 36/217 (17%) patients were selected for an ND due to positive findings in post-treatment FDG PET-CT. Of these, 35/36 were HPV-associated, 10/36 (28%) had viable tumour cells in the pathology reports of the neck specimen, and 8/10 (80%) were consistent with the FDG PET-CT findings, while 2/36 (5%) were missed by FDG PET-CT. We conclude that FDG PET-CT 12 weeks after RT/CRT is useful, but not completely reliable for finding all the metastases of HPV-associated TSCC/BOTSCC. Nonetheless, our data indicate that an ND could be more selectively guided by FDG PET-CT.

Unilateral Radiation Therapy for Tonsillar Cancer: Treatment Outcomes in the Era of Human Papillomavirus, Positron-Emission Tomography, and Intensity Modulated Radiation Therapy.

PURPOSE: The goal of this study was to evaluate disease, survival, and toxic effects after unilateral radiation therapy treatment for tonsillar cancer. METHODS AND MATERIALS: A retrospective study was performed of patients treated at our institution within the period from 2000 to 2018. Summary statistics were used to assess the cohort by patient characteristics and treatments delivered. The Kaplan-Meier method was used to determine survival outcomes. RESULTS: The cohort comprised 403 patients, including 343 (85%) with clinical and/or radiographic evidence of ipsilateral cervical nodal disease and 181 (45%) with multiple involved nodes. Human papillomavirus was detected in 294 (73%) tumors. Median follow-up time was 5.8 years. Disease relapse was infrequent with local recurrence in 9 (2%) patients, neck recurrence in 13 (3%) patients, and recurrence in the unirradiated contralateral neck in 9 (2%) patients. Five- and 10-year overall survival rates were 94% and 89%, respectively. Gastrostomy tubes were needed in 32 (9%) patients, and no patient had a feeding tube 6 months after therapy. CONCLUSIONS: For patients with well-lateralized tonsillar tumors and no clinically evident adenopathy of the contralateral neck, unilateral radiation therapy offers favorable rates of disease outcomes and a relatively low toxicity profile.

Incidence of synchronous contralateral tonsillar malignancy in a known case of unilateral tonsillar carcinoma.

OBJECTIVE: The literature is divided with regards to contralateral tonsillectomy in a known/suspected case of ipsilateral tonsillar malignancy. In this study, we evaluate the incidence of indolent synchronous contralateral tonsillar malignancy (SCTC) in patients with known ipsilateral tonsillar malignancy. METHODS: All patients diagnosed with ipsilateral tonsillar carcinoma (TC) at a tertiary teaching center between January 2016 and December 2019 were screened. None of the patients were suspected to have bilateral TC. All patients underwent appropriate imaging in the form of Magnetic resonance imaging and computed tomography of head and neck region and then underwent bilateral tonsillectomy. The prevalence of bilateral tonsillar malignancy and the factors predicting them were analyzed. RESULTS: In all 59 patients were included in the study. The mean and median age of the patient population was 60.8 and 59 years, respectively, with a male to female ratio of 3.2:1. The incidence of bilateral tonsillar malignancy in carcinoma of unknown primary (CUP) was 3/10 (33.3%). Among the remaining 49 patients, incidence of synchronous contralateral tonsillar carcinoma (SCTC) was 2/49 (4.08%). Overall, 5/59 (8.5%) patients had synchronous bilateral tonsillar malignancy. Furthermore, dysplasia was found in the contralateral tonsil in 4/10 (40%) CUP patients. Among the remaining 49 patients, dysplasia was seen in the contralateral tonsil in 20/49 (40.8%) patients. The absence of p16 expression predicted higher probability of SCTC. Factors like gender, T stage, nodal status or smoking did not predict SCTC. CONCLUSION: We recommend bilateral tonsillectomy in all patients with suspected or proven TC (unilateral or bilateral) and CUP as it helps identify indolent SCTC and it does not add any significant morbidity to the patients. LEVEL OF EVIDENCE: III.

Tonsillar actinomycosis that mimics tonsillar neoplasm.

Actinomycosis is a chronic suppurative infection that can develop almost anywhere in the body. Cervicofacial actinomycosis is the most common form of the disease. We report a case of tonsillar actinomycosis that causes massive, asymmetric enlargement of tonsil and mimics the neoplasia. The most common cause of asymmetric tonsil hypertrophy is tonsillar squamous cell carcinoma and lymphomas. Tonsillar actinomycosis is a rare entity that should be kept in mind, if cases cannot be clarified with clinical and laboratory findings, when radiological findings are suspicious about malignancy.

Determination of posterolateral oropharyngeal wall thickness and the potential implications for transoral surgical margins in tonsil cancer.

BACKGROUND: Margins in transoral surgery for tonsil cancer can be limited by oropharyngeal wall thickness (OWT), but the normal range is not well established. METHODS: In 240 noncancer subjects, OWT was measured bilaterally in the vicinity of the tonsils with MRI. Statistical analysis was performed to assess for interaction of age, sex, location, and obesity. RESULTS: Mean(SD) OWT measured 3.4(0.6) mm posteriorly, 3.7(2.0) mm between the styloglossus and stylopharyngeus, and 5.3(0.8) mm laterally. OWT was greater in men, correlated with obesity, decreased posteriorly and laterally in the 60-80 versus 40-59 year age groups, and increased when styloglossus/stylopharyngeus were closer. OWT was <5 mm in 36.7%-97.9% of locations, with the largest percentage below this threshold located posteriorly. CONCLUSIONS: OWT is frequently <5 mm, particularly in the posterior and intermuscular areas, suggesting that a smaller surgical margin may need to be accepted in transoral tonsil cancer surgery for anatomic reasons.

Technical feasibility of radiomics signature analyses for improving detection of occult tonsillar cancer.

Diagnosis of occult palatine tonsil squamous cell carcinoma (SCC) using conventional magnetic resonance imaging (MRI) is difficult in patients with cervical nodal metastasis from an unknown primary site at presentation. We aimed to establish a radiomics approach based on MRI features extracted from the volume of interest in these patients. An Elastic Net model was developed to differentiate between normal palatine tonsils and occult palatine tonsil SCC. The diagnostic performances of the model with radiomics features extracted from T1-weighted image (WI), T2WI, contrast-enhanced T1WI, and an apparent diffusion coefficient (ADC) map had area under the receiver operating characteristic (AUROC) curve values of 0.831, 0.840, 0.781, and 0.807, respectively, for differential diagnosis. The model with features from the ADC alone showed the highest sensitivity of 90.0%, while the model with features from T1WI + T2WI + contrast-enhanced T1WI showed the highest AUROC of 0.853. The added sensitivity of the radiomics feature analysis were 34.6% over that of conventional MRI to detect occult palatine tonsil SCC. Therefore, we concluded that adding radiomics feature analysis to MRI may improve the detection sensitivity for occult palatine tonsil SCC in patients with a cervical nodal metastasis from cancer of an unknown primary site.

Tonsillar Metastasis From Colon Cancer Detected on 18F-FDG PET/CT Imaging.

A 54-year-old woman with smoking history who was diagnosed with invasive adenocarcinoma of the rectosigmoid colon with subsequent surgical resection and chemotherapy was presented. The patient developed local recurrence and pulmonary metastases that required further chemotherapy and surgical resection. During follow-up, the patient had F-FDG PET/CT scan showing asymmetric hypermetabolic tonsils with activity greater on the right compared with the left. The patient underwent bilateral tonsillectomy, and pathology revealed moderately to poorly differentiated adenocarcinoma in the right tonsil, consistent with metastasis from known colonic primary.

MRI-Based Assessment of the Pharyngeal Constrictor Muscle as a Predictor of Surgical Margin after Transoral Robotic Surgery in HPV-Positive Tonsillar Cancer.

BACKGROUND AND PURPOSE: Transoral robotic surgery is an emerging strategy for treating human papillomavirus-positive cancers, but the role of MR imaging in predicting the surgical outcome has not been established. We aimed to identify preoperative MR imaging characteristics that predispose the outcome of transoral robotic surgery toward an insecure (positive or close) surgical margin in human papillomavirus-positive tonsillar squamous cell carcinoma. MATERIALS AND METHODS: Between December 2012 and May 2019, sixty-nine patients underwent transoral robotic surgery at our institution. Among these, 29 who were diagnosed with human papillomavirus-positive tonsillar squamous cell carcinoma, did not receive neoadjuvant treatment, underwent preoperative 3T MR imaging, and had postoperative pathologic reports and were included in this retrospective study. Two neuroradiologists evaluated the preoperative MR imaging scans to determine the tumor spread through the pharyngeal constrictor muscle using a 5-point scale: 1, normal constrictor; 2, bulging constrictor; 3, thinning constrictor; 4, obscured constrictor; and 5, tumor protrusion into the parapharyngeal fat. The risk of an insecure surgical margin (involved or <1 mm) according to the MR imaging scores was predicted using logistic regression with the Firth correction. RESULTS: The interobserver agreement for the MR imaging scores was excellent (κ = 0.955, P < .001). A score of ≥4 could predict an insecure margin with 87.5% sensitivity and 92.3% specificity (area under the curve = 0.899) and was the only significant factor associated with an insecure margin in the multivariable analysis (OR, 6.59; 95% CI, 3.11-22.28; P < .001). CONCLUSIONS: The pre-transoral robotic surgery MR imaging scoring system for the pharyngeal constrictor muscle is a promising predictor of the surgical margin in human papillomavirus-positive tonsillar squamous cell carcinoma.

A metastatic histiocytic sarcoma case with primary involvement of the tonsil.

Histiocytic sarcoma (HS) is an extremely rare and aggressive hematopoietic tumor. Although it can be seen at any anatomic location, the most common primary sites are skin as extranodal region, locations including the lymph nodes and gastrointestinal tract. To the best of our knowledge, in light of PubMed search, this is the first primary tonsillar HS case presented with disseminated metastases at the time of diagnosis. A 58-year-old male patient applied with swelling on the right side of the neck, difficulty in swallowing, and weight loss. Positron emission tomography computed tomography was performed and increased pathological 18F fluorodeoxy D glucose uptake was detected in the right palatine tonsil, bilateral cervical multiple lymph nodes, liver masses, intra abdominal lymph nodes, and nodular lesion in the left adrenal gland. Tonsillectomy was performed and the pathological result was reported as HS. The patient did not respond to any treatment and had died after 5 months from the date of diagnosis. In conclusion, HS is generally diagnosed at advanced stage, it has limited chemotherapy response and high mortality rates. To understand this rare disease's pathophysiological and clinical features, further investigations are needed.

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.

Periodontitis in tonsil cancer patients-A comparative study in accordance with tumour p16 status.

OBJECTIVES: We assessed the periodontal situation radiologically according to tumour p16 status. MATERIALS AND METHODS: Patients with a diagnosis of tonsillar cancer and availability of a digital panoramic radiograph (DPR) during a 5-year period were included in this retrospective study. The predictor variables were periodontal stability, marginal bone loss, marginal bone loss without periodontal stability and total number of teeth. Periodontal status was compared with p16 status, age, gender, smoking and alcohol use. RESULTS: Among 115 patients included in the analyses (p16-negative, n = 24; p16-positive, n = 91), smoking (p < .0001), heavy alcohol use (p < .0001) and total number of teeth (p = .0001) were significantly associated with p16 status. Current smoking (OR = 7.3) and heavy alcohol use (OR = 10.1) increased the risk of p16-negative cancer. CONCLUSIONS: Patients with p16-negative tonsillar carcinoma had less teeth than patients with p16-positive tumours. Other periodontal findings were common in both groups without statistical significance. Heavy alcohol use and smoking were the most important risk factors for p16-negative tonsillar carcinoma.

Lacrimal sac primary squamous cell carcinoma with synchronous tonsillar primary squamous cell carcinoma.

A gentleman with recurrent epiphora after two failed endonasal dacryocystorhinostomies was found to have a squamous cell carcinoma of the lacrimal sac at his third operation via an external approach. CT showed contralateral nodal involvement; however, biopsy of the node found it to be histologically distinct from the lacrimal sac lesion. A PET-CT revealed a second primary lesion located at the contralateral palatine tonsil. We discuss the histological features of squamous cell carcinomas and the impact on prognosis. This case highlights the importance of nasoendoscopy prior to lacrimal surgery. There should be a low threshold for lacrimal sac biopsy, and any anatomical or histological inconsistency should prompt further investigation.

All-optical Reflection-mode Microscopic Histology of Unstained Human Tissues.

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.

Targeted Intervention to Improve the Quality of Head and Neck Radiation Therapy Treatment Planning in the Netherlands: Short and Long-Term Impact.

PURPOSE: To benchmark and improve, through means of a targeted intervention, the quality of intensity modulated radiation therapy treatment planning for locally advanced head and neck cancer (HNC) in the Netherlands. The short and long-term impact of this intervention was assessed. METHODS AND MATERIALS: A delineated computed tomography-scan of an oropharynx HNC case was sent to all 15 Dutch radiation therapy centers treating HNC. Aims for planning target volume and organ-at-risk (OAR) dosimetry were established by consensus. Each center generated a treatment plan. In a targeted intervention, OAR sparing of all plans was discussed, and centers with the best OAR sparing shared their planning strategies. Impact of the intervention was assessed by (1) short-term (half a year after intervention) replanning of the original case and (2) long-term (1 and 3 years after intervention) planning of new cases. RESULTS: Benchmarking revealed substantial difference in OAR doses. Initial mean doses were 22 Gy (range, 15-31 Gy), 35 Gy (18-49 Gy), and 37 Gy (20-46 Gy) for the contralateral parotid gland, contralateral submandibular gland, and combined swallowing structures, respectively. Replanning after targeted intervention significantly reduced mean doses and variation, but clinically relevant differences still remained: 18 Gy (14-22 Gy), 28 Gy (17-45 Gy), and 29 Gy (18-39 Gy), respectively. One and 3 years later the variation remained stable. CONCLUSIONS: Despite many years of HNC intensity modulated radiation therapy experience, initial treatment plans showed surprisingly large variations. The simple targeted intervention used in this analysis improved OAR sparing, and its impact was durable; however, fairly large dose differences still continue to exist. Additional work is needed to understand these variations and to minimize them. A national radiation oncology platform can be instrumental for developing and maintaining high-quality planning protocols.