Kazuto Hoshi

Cancers of unknown primary origin (CUPs) are reported to be the 3-4th most common causes of cancer death. Recent years have seen advances in mutational analysis and genomics profiling. These advances could improve accuracy of diagnosis of CUPs and might improve the prognosis of patients with CUPs. A 76-year old male with an adenocarcinoma of unknown primary origin in the lung presented with another tumor of the palate mucosa. The tumor cells in the pleural effusion were all negative for immunohistochemical markers (TTF-1 and Napsin A) and lung-specific oncogenic driver alterations (EGFR mutation and ALK translocation). The tumor of the palate mucosa was likewise identified as an adenocarcinoma, and the cells showed cytological similarities with the tumor cells in the pleural effusion; TTF-1, Napsin A, EGFR mutation and ALK translocation were all negative. This result suggested that origins of the tumors of the palate mucosa and in the lung were the same, even though the origin had not yet been determined. Next, we addressed whether the tumor of the palate mucosa was a primary tumor or not. Secretory carcinoma (SC), which is a common type of minor salivary gland tumor (MSGT), was suspected; however, mammaglobin was negative and ETV6-NTRK3 (EN) fusion was not observed. Other MSGTs were excluded based on histological and immunohistochemical findings. Furthermore, an additional examination demonstrated an oncogenic KRAS mutation at codon 12 (p.G12D) in both palate tumor and in pleural effusion. KRAS mutation is known to exist in one-third of lung adenocarcinomas (LUADs), but quite rare in MSGTs. The possibility of metastasis from other organs was considered unlikely from the results of endoscopic and imaging studies. This result indicated that the primary site of the CUP was indeed the lung, and that the tumor of the palate mucosa was a metastasis of the LUAD. A tumor of the palate mucosa that showed diagnostic difficulties was determined to be a metastatic LUAD by genomic alterations and histopathological findings.

Background: Infections in the oral and maxillofacial region can sometimes extend beyond the oral cavity, with serious consequences. Most oral infections are odontogenic, occurring through the root apex of the tooth or the periodontal pocket. It thus makes sense that edentulous patients have a much lower risk of oral bacterial infection. For this reason, while there are many reports on systemic infections caused by oral infections, few of these describe such infections in edentulous patients. Case presentation: We present a case of oral and maxillofacial cellulitis followed by sepsis due to Streptococcus pyogenes infection in an 89-year-old Japanese edentulous woman. S. pyogenes was detected in the wound of left maxilla and the blood sample. S. pyogenes has been reported to be one of the most common and influential aerobic bacteria associated with deep neck infection and subsequent systemic infection. Left maxillary sinusitis was observed, and this could be the origin of the S. pyogenes infection. S. pyogenes derived from the sinusitis and leaked to the oral cavity might have caused systemic infection through wounding of the oral mucosa. Fortunately, intensive antibiotic therapy was effective, and the patient recovered without any surgical procedures. Conclusions: We experienced a rare case of oral and maxillofacial cellulitis followed by sepsis due to a Streptococcus pyogenes infection in an old edentulous woman. This result indicated that, while edentulous patients are considered to have no risk of odontogenic infection, they still carry a risk of bacterial infection.

Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. The long-term complications arising from standard therapy with surgery, chemotherapy and radiotherapy lower the quality of life (QOL) due to eating disorders, speech problems and cosmetic issues. Recently the importance of antibody therapy has increasingly come to be recognized for its capacity to enhance QOL. Robo1, an axon guidance receptor, has been received considerable attention as a monoclonal antibody target in various cancers. Methods and findings: We checked the expression of Robo1 and the cytotoxic effect of saporin-conjugated anti- Robo1 immunotoxin (IT) against several HNSCC cell lines. The Robo1 cell surface expression level estimated by flow cytometry using the antibody B5209B was approximately 220,000 copies in Robo1 over-expressed CHO (Robo1/ CHO) cells, and in HNSCCs, 22,000 copies in HSQ-89 cells, 3,000 copies in Sa3 cells, and few copies inSAS cells. Conventional IT treatment exhibited an inadequate cytotoxic effect even in HSQ-89 cells. When we added a photosensitizer and LED light illumination (650 nm), the cytotoxic effect was remarkably improved in HSQ89. With longer exposure, significant cytotoxicity was observed, even in Sa3 cells. Conclusion: These results suggest that the photochemical internalization (PCI) is a promising method for augmenting the cytotoxicity of IT against tumors. The drug delivery system shown in this study should be applicable to other targets with low level expression on cancer cells, thus widening the therapeutic window in rare cancers.

Odontogenic myxoma is a benign odontogenic tumor with locally aggressive behavior, and is relatively rare in the oral cavity. There are currently no clear surgical management guidelines for odontogenic myxoma, and a variety of approaches may be used. This study evaluated the literature concerning the surgical management of odontogenic myxoma, and reports the long-term outcome of a case managed by using a more conservative surgical approach. We managed a 40-year-old Japanese man with odontogenic myxoma in the right mandible by enucleation and curettage, a relatively conservative approach that has proved to have been justified by a lack of recurrence over 10 years. Our strategy was compared with others reported in the literature, which was identified by a PubMed search using the term “odontogenic myxoma”. Articles without full text or with missing data were excluded. The age and sex of patients, the tumor location (maxilla/mandible), treatment (conservative/radical), recurrence, and follow-up period were compared in the reported cases that we evaluated. From the initial 211 studies identified, 20 studies qualified as mandibular cases of odontogenic myxoma. Recurrence was reported in three cases that had been treated with a more conservative surgical approach. Enucleation and curettage has proved an effective approach in several cases in ours there has been no recurrence more than 10 years after surgery but the risk of recurrence appears to be higher. We discuss the important factors that must be considered when determining the correct management approach to odontogenic myxoma.