Background: Next-generation sequencing （NGS） of tumor samples in a clinical setting provides information
regarding cancer-related genetic aberrations, and is therefore expected to be useful in precision medicine. However, the clinical utility of clinical sequencing remains unknown in solid cancers, including recurrent or metastatic head and neck cancer （R/M HNC） in Japan. Here, we conducted a hospital-based study to investigate the clinical utility of tumor-profiling gene panel testing in R/M HNC.
Methods: We examined 18 panel tests from 14 cases of R/M HNC; 15 underwent tumor tissue-based panel testing （FoundationOne CDx® and/or FoundationOne HEME®） and three underwent liquid biopsy （Guardant360®）, with three cases undergoing both investigations.
Results: There were nine men and five women of median age 58 years （38-73 years）. There were ten cases of squamous cell carcinoma （SCC） and four of non-SCC. The most common genetic alteration was inactivation of TP53 followed by TERT promoter and CDKN2A alterations. There was no suspected hereditary neoplastic syndrome. Gene profiling data was obtained for 11 cases （78.6％） that harbored at least one actionable gene aberration. Two cases （14.3％） had undergone molecular targeted therapy. The median value of the tumor mutational burden （TMB） was 6.0 Muts/Mb （0-34） and the disease control rate of the three cases with high TMB （≥10 Muts/Mb） was 66.7％ （partial response: 2, progressive disease: 1） following treatment with an immune-checkpoint inhibitor such as nivolumab or pembrolizumab.
Conclusions: These results indicate the clinical utility of tumor-profiling multiplex gene panel testing in R/M HNC in Japan.
Virtual reality is a rapidly developing technology in the field of computer science and can contribute to surgical care. The mixed reality （MR） technique is the merging of real and virtual worlds and provides the user with a hologram in the real world. Here, we report a new cadaver training technique with holograms called hybrid cadaver training. The MR technique makes it possible to show teaching materials as holograms during cadaver training. The application for the MR was developed by the faculty of engineering, Ehime University. Four otolaryngology-head and neck surgery residents participated in the hybrid cadaver training and answered a questionnaire. All participants rated the usefulness of the training as 5 points out of 5. The hybrid cadaver training with holograms may be a new promising simulation training for otolaryngology-head and neck surgery residents.
The author performed larynx-conserving surgery on a total of 82 patients （59 primary cases and 23 secondary cases） of laryngeal cancer. The disease-specific 5-year survival rate of all 82 patients was 92.6％. The larynx conservation rate was 87.8％ in all 82 cases. In regard to the treatment of early-stage laryngeal cancer （T1, 2）, we suggested that larynx-conserving surgery should be considered as an option for initial treatment because it is not inferior to radiotherapy in terms of clinical outcome and preservation of laryngeal function in daily life. Larynx-conserving surgery as a salvage treatment for recurrence did not present a lower laryngeal preservation rate than for primary cases, and seemed to be an effective method of salvage surgery for recurrent patients.
Larynx-conserving surgery was performed on 16 patients with locally advanced laryngeal cancer （T3, 4）. These cases included 5 cases of paraglottic space （PGS） invasion and 6 cases of thyroid cartilage invasion. Of these 11 cases, 5 cases whose surgical margins were diagnosed as negative on histopathological examination suffered local recurrence. We performed total laryngectomy as a salvage surgery on these 5 cases. Of the 16 cases of locally advanced cancer （T3, 4）, 5 cases （1 case of deep tongue muscle invasion, 3 cases of anterior invasion of the epiglottis, and 1 case of anterior wall invasion of the cricoid cartilage） showed no local recurrence and local control was successfully achieved with surgery alone. Regarding indications, in the case of locally advanced laryngeal cancer involving anterior invasion of the epiglottis, deep tongue muscle invasion, and anterior wall invasion of the cricoid cartilage, larynx-conserving surgery appropriately indicated because the cases were local controlled with surgery alone. However, in the case of recurrence, postoperative radiotherapy should be considered because of the difficulty of preserving the function of the larynx.
It is recommended that elderly cancer patients should be evaluated for geriatric assessment. This study investigated the diagnostic characteristics of two geriatric screening tools, G8 （Geriatric 8） and fTRST （Flemish version of Triage Risk Screening Tool）, in older patients with head and neck cancer and the prognostic value of these screening tools for overall survival, treatment completion and complications. The subjects were 30 patients over 70 years old who were evaluated by G8 and fTRST between March 2017 and October 2019. A Cox regression analysis with G8 and fTRST as the independent variables was conducted for the OS analysis. Univariate analysis showed that only G8, in which we set the cut-off value to 14, was a statistically significant prognostic predictor （hazard ratio 9.64, p＝0.036）. G8 was considered to be a more useful screening tool in predicting the prognosis of elderly patients with head and neck cancer.
Diffuse sclerosing variant of papillary thyroid carcinoma is a rare variant. This variant is characterized by diffuse fibrosis, calcification, abundant lymphocytic infiltration and psammoma bodies. This variant is usually seen in female patients in the second decade and has an associated chronic thyroiditis. The sonographic findings of diffuse involvement without an obvious mass in the thyroid make it often misdiagnosed as chronic thyroiditis. The treatment is total thyroidectomy, which is similar to high-risk papillary cancer, but since there are many cases with lymph node metastasis in the lateral neck, modified neck dissection is often performed. Here, we performed total thyroidectomy and modified neck dissection in two young women and added radioiodine isotope therapy postoperatively. Although the observation period was short, no recurrence was observed in either case.
Malignant peripheral nerve sheath tumors （MPNSTs） are sarcomas derived from peripheral nerves and have high rates of local recurrence and metastasis. We report a case of an MPNST on the cheek that was discovered following trauma. A 75-year-old man experienced a fall while riding a bicycle and injured his face. The swelling of his left cheek did not improve, and he was referred to our department. No bone fracture was observed on image-based examination, and the patient was followed up. Magnetic resonance imaging one month after the injury revealed a solid lesion 40×35×25mm in size in the left masseter muscle, and biopsy revealed a malignant spindle cell tumor. The tumor was resected under general anesthesia, and the histopathological diagnosis was MPNST. Local recurrence was observed 4 months after the surgery. Therefore, recurrent tumor resection was performed, and the tumor was found to infiltrate the facial nerve. External irradiation of 66Gy was performed postoperatively. Eighteen months after the surgery, no local recurrence or distant metastasis was observed. For MPNSTs, wide excision with a sufficient safety margin is the first choice for treatment, but functional preservation and esthetic considerations are required in the head and neck region.
Adenosquamous carcinoma is a rare epithelial cancer with histologic features of both adenocarcinoma and squamous carcinoma. We report a case of laryngeal adenosquamous carcinoma manifesting as a submucosal tumor.
A man in his 60s complained of hoarseness. Laryngeal endoscopy revealed left vocal cord paralysis, but no neoplastic lesion in the larynx. CT showed a submucosal neoplastic lesion with cricoid infiltration from the left vocal cord to the subglottic region. A biopsy was attempted under laryngomicro surgery, but laryngeal expansion was not possible, and a biopsy by extracervical incision revealed squamous cell carcinoma. Total laryngectomy and neck dissection were performed, and the postoperative pathological diagnosis was adenosquamous carcinoma. Two years have passed since the operation, but no metastasis or recurrence has occurred.
Only 18 cases of laryngeal adenosquamous carcinoma have been reported in Japan. It is known that the prognosis is worse than that of squamous carcinoma and that it is resistant to chemotherapy and radiation therapy. As in this case, submucosal lesion was observed in 8 cases, which is a characteristic finding.
Functional preservation is an important issue in surgeries of head and neck malignancies in the adolescent and young adult （AYA） generation. We report two cases of primary synovial sarcoma of the head and neck in the AYA generation. Case 1: An 18-year-old man underwent computed tomography （CT）, which showed a 135-mm mass growing from the hypopharynx or posterior cricoid region. Preoperative biopsy revealed a malignant tumor. We considered total laryngectomy but performed hypopharyngeal tumor resection, bilateral neck dissection, and free jejunal reconstruction. The patient was diagnosed with synovial sarcoma due to permanent pathology, and adjuvant chemotherapy was administered. However, neck recurrence and pulmonary metastasis occurred, and he died of the disease three and a half years after the surgery. Case 2: A 15-year-old girl underwent CT, which showed a 95-mm mass in the right parapharyngeal space. Preoperative examination revealed a paraneuroma with adhesion to the right internal carotid artery. We performed tumor resection, and the right internal carotid artery was preserved. The patient was diagnosed with synovial sarcoma due to permanent pathology, and adjuvant chemotherapy was administered. However, local recurrence was found at the base of the skull, and bone metastasis and meningeal dissemination were observed. She died of the disease five and a half years after the surgery. The first choice for treatment of synovial sarcoma is surgery, but recurrence occurred in the present two cases, suggesting the need for a wider safety margin. It is difficult to select a surgical procedure for malignancies in the AYA generation; more cases need to be accumulated in the future.