Oral cancer is a rare cancer that accounts for 1％ of all cancers, or about 6 per 100,000 people. In 2014, the Japanese Ministry of Health, Labour, and Welfare （MHLW） created the “10-Year Strategy for Cancer Research” and designated “oral cancer” as a priority research area as a rare cancer that is difficult to study. Since there are limitations in conducting high-quality clinical research at individual institutions, multi-institutional research is becoming increasingly important. The Japanese Society of Oral Oncology has established a joint research committee, and various studies are being conducted. This study is a prospective, multi-institutional, non-randomized observational study. The choice of whether to perform elective neck dissection （END） for clinically node-negative （cN0） oral tongue squamous cell carcinoma （OTSCC） at the same time as resection of the primary tumor is based on institutional policy and patient preference. The primary endpoint of this study is 3-year overall survival. The secondary endpoints are 3-year disease-specific survival, 3-year relapse-free survival, and the impact on patient quality of life （QoL）. The impact of QoL is assessed by using the Functional Assessment of Cancer Therapy-Head and Neck （Version 4; FACT-H&N） and the Disabilities of the Arm, Shoulder, and Hand （DASH） questionnaire. Confounding factors will be adjusted to reduce selection bias. The results of this study may provide new outcome-oriented insights into the efficacy of END for cN0 OTSCC in terms of patient QoL in Japan.

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S-1 is an anticancer agent comprising tegafur as a 5-FU prodrug, gimeracil, and oteracil potassium. It has been suggested that the effectiveness of S-1 depends on the expression of enzymes stimulating fluoropyrimidine anticancer agents, such as thymidylate synthase （TS）, dihydropyrimidinede hydrogenase （DPD）, and orotate phosphoribosyl transferase （OPRT）. The goal of this study was to investigate the regimen, dosage, and correlation between the response and adverse events to S-1 and the expression of TS, DPD, and OPRT in elderly patients with oral squamous cell carcinoma. Three CR cases, one PR case, and three SD instances were reactions to S-1. The final dosing schedule in 5 patients was a 2-week administration period followed by a 1-week break; the dose was 67-80％ of the recommended amount in 5 patients, and 6 patients had some adverse event. The low expression of TS enzyme in cytoplasm was associated with the effect of S-1. Low dosage of S-1 with 2-week administration followed by 1-week rest was efficient and safe for the elderly patients with oral squamous cell carcinoma. In addition, it was suggested that TS expression in the cytoplasm might be helpful in the selection of S-1 therapy using immunohistochemistry.

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Carcinoma cuniculatum is a subtype of squamous cell carcinoma that histopathologically shows a sinus-like invasion resembling a rabbit hole. We report a case of carcinoma cuniculatum of the mandibular gingiva.
A 65-year-old man with a history of chronic myelogenous leukemia visited our hospital with a complaint of a white spot in the mandible. A white lesion was recognized on the buccal side of the left mandibular alveolar region, which rapidly progressed to the lingual side. Imaging revealed a flat mass lesion. We suspected a malignant lesion and performed a biopsy, but could not obtain a definitive pathological diagnosis. Because of the aggressive progression of the lesion, resection was planned according to malignant lesions, and a mandibular marginal resection was performed one month after the initial visit. The histopathological diagnosis was carcinoma cuniculatum. There was no recurrence or metastasis four years after surgery.
Carcinoma cuniculatum is a rare histological type of oral squamous cell carcinoma and is underreported due to the difficulty of histopathological diagnosis and lack of recognition. As the accumulation of cases is needed for further clinical and histopathological analysis, we report the present case as a typical one.

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Invasive fungal infection （IFI） is a systemic fungal infection that develops due to immune depression, and superior vena cava syndrome （SVCS） is a syndrome caused by obstruction of the superior vena cava. We experienced a case of IFI due to the treatment of SVCS caused by tongue cancer.
A 67-year-old man with tongue squamous cell carcinoma, cT3N2bM0, was surgically treated by partial hemiglossectomy and modified radical neck dissection. Five months after postoperative adjuvant therapy, nivolumab was started because metastatic lymph nodes were found in the cervical region. Two years thereafter, metastatic lymph nodes were found in the superior mediastinal region, and chemotherapy was planned, but edema in the head and neck and malaise appeared because of stenosis of the superior vena cava. The patient’s symptoms improved with radiotherapy and steroid administration, but two months after the start of chemotherapy, he developed a persistent fever that did not respond to antibiotics. Although no fungi were detected in the blood culture, we diagnosed IFI （probable diagnosis） based on long-term steroid administration, nodular lesions in the lungs, and elevated β-D glucan levels. Voriconazole was administered, which resulted in an improvement in the symptoms. Chemotherapy was resumed, but his general condition worsened, and he died five months after the onset of IFI.

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Carcinoma ex pleomorphic adenoma （Ca-ex-PA） mainly arises from the major salivary glands （i.e., parotid gland）, and adenocarcinoma not otherwise specified and salivary duct carcinoma are common histological types. Here, we report a case of a patient with Ca-ex-PA, with myoepithelial cancer derived from the minor salivary glands of the cheek. A 74-year-old woman was admitted to our hospital with swelling of her left cheek. MRI revealed a lobular mass lesion that surrounded the anterior margin of the left masseter muscle. A biopsy revealed the coexistence of malignant components with pleomorphic adenoma, which led to the diagnosis of Ca-ex-PA. Tumor resection and supraomohyoid neck dissection were performed, followed by anterolateral thigh flap transplantation. The patient had a good postoperative course, but about five months after the operation, died from another illness. As Ca-ex-PA is a rare disease in the minor salivary gland, it is desirable to establish preoperative diagnostic methods and treatment strategies by accumulating cases from multiple institutions.

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