Lymph node metastasis is the leading factor determining the outcome of mucosal cancer, and the factors associated with lymph node metastasis—and thus with disease outcome—are the depth and invasion patterns of the primary tumor. The General Rules for Clinical and Pathological Studies on Oral Cancer specify clinical growth patterns as the principal method for clinical classification. This method re-categorized oral cancer into superficial, exophytic, and endophytic types because of their universality and reproducibility, based on conventional observation-based classification and on the concept that “classification is possible and useful”. Because a subgroup of lesions in the endophytic group is strongly associated with poor prognosis, this growth pattern-based classification is currently under debate as to whether this subgroup should be reclassified as an independent lesion type with characteristic gross and histological images and pathological features. Because this issue will be addressed by the Scientific Committee's Working Group 1, here I will discuss, as the next-generation method of clinical classification, a novel classification method that reflects tumor invasion patterns.
It is my belief that the current clinical classification method needs to be updated to reflect the patterns of tumor invasion. Owing to advances in surgical pathology, clinical classification of gastrointestinal lesions is performed using silhouette classification. This classification is based on the morphology of the mucosal surface as well as the patterns of tumor invasion. The Yamamoto-Kohama mode of invasion (YK classification), which has been used to determine the degree of malignancy of oral squamous cell carcinoma, is an equivalent version of the silhouette classification and can be used as the next-generation classification method. Macroscopic and imaging evaluation should not be performed with the eyes alone, but should be accompanied by a knowledge base for surgical pathology. Clinical classification should reflect the knowledge accumulated on all types of oral cancer.

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Cancer progression and dissemination are the outcome of a complex interplay between cancer cells and the surrounding microenvironment. Therefore, the three-dimensional features of tumor parenchyma-stroma architecture should be integrated in the histopathological diagnosis of solid tumor malignancy. In order to elucidate the diversity of tumor invasion patterns in the 3D microenvironment of tongue squamous cell carcinoma (SCC), we routinely conducted histology-based 3D reconstruction using 100-250 serial histological sections (4-μm thick). The basic procedure for 3D reconstruction is the preparation of serial sections using a paraffin tissue microarray in combination with immuno-staining of tissues, computer-assisted color segmentation of tumor parenchyma and stroma, and alignment and superposition of digitized images. The resulting 3D constructs provided sufficient spatial resolution to segregate individual cells and to validate the continuity or separation of carcinoma cells at the deepest invasion front. Observations in the 3D space revealed discrete SCC architectures that were classified into several categories from bulky masses with pushing border to infiltrating islands or clusters. Of particular importance in the malignancy grading assessment based on the histopathological characteristics of the deep invasive front of SCC, an anastomosing network of tumor strands in tissue volume may appear in 2D histological sections as discontinuous segments of small foci. Indeed, our experience proved that 3D reconstruction is an essential tool to validate the nature of continuity or sequestration of carcinoma cells and to collect quantitative information as to the number and size distribution of invading carcinoma foci into the surrounding microenvironment.

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Tumor blood vessels play an important role in tumor progression and metastasis. Thus, targeting the tumor blood vessels is an important strategy in cancer therapy. Tumor blood vessels generally arise from pre-existing vessels and have been thought to be genetically normal. However, they have been shown to differ from their normal counterparts e.g., with regard to morphological changes. We isolated tumor endothelial cells (TECs) from mouse tumor xenografts and showed that they were abnormal. TECs up-regulate many genes, proliferate more rapidly, and migrate more than normal endothelial cells (NECs). Furthermore, the TECs in our study were cytogenetically abnormal. TECs were drug resistant to paclitaxel with upregulation of multidrug resistance 1 (MDR1) mRNA, compared to NECs. Tumor-conditioned medium treatment caused drug resistance in NEC. We concluded that TECs can acquire cytogenetic abnormalities while in the tumor microenvironment.
In order to develop ideal antiangiogenic therapies, it is important to understand the crosstalk between blood vessels and the tumor microenvironment.
This review considers the current studies on TEC abnormalities, and discusses the possible mechanism by which the tumor microenvironment produces abnormal TECs.

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In cancer clinical practice, metastasis is an important prognostic factor, and so elucidation of the mechanism of metastasis at the molecular level is desirable. Cell motility is intricately related to metastasis, and dynamic change in the actin cytoskeleton is one of the most important factors regulating motility. Actinin-4 (gene name: ACTN4), which is a novel actin bundling protein, has been identified by our laboratory. Expression of actinin-4 protein leads to the formation of cell processes and increases motility. Clinicopathologically, increased expression of actinin-4 protein not only affects the prognosis in invasive ductal carcinoma of the breast, but also correlates with lymph node metastasis in colon cancer. In small cell lung cancer, a splice variant has been isolated as a cancer/testis antigen, and may also serve as a diagnostic marker. Recently, increases in actinin-4 protein were found to be attributable to ACTN4 gene copy number amplification. ACTN4 gene amplification has been identified in ovarian and pancreatic cancer. This review discusses the biological role of actinin-4 in cancer metastasis and invasion.

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As the aging society is advancing in our country, it is expected that the opportunity to treat oral cancer in elderly patients is increasing. In this report, 64 patients (23 male and 41 female) aged 75 and older with oral squamous cell carcinoma (OSCC) were clinically evaluated as compared with 60 patients (32 male and 28 female) aged 65-74 years old, and 63 patients (46 male and 17 female) aged 64 and younger with OSCC who were treated at our clinic between 2000 and 2008.
The ratio of Performance Status (PS) grade 0·1 patients in the group aged 75 and older was significantly lower than that in the groups aged 65-74 and those aged 64 and younger. The number of patients aged 75 and older are divided into the radical cure treatment group, palliative treatment group and no treatment group, which accounts for 45 (70.3%), 9 (14.1%), and 10 (15.6%) cases, respectively. The ratio of the radical cure treatment patients in the group aged 75 and older was lower than that in the group aged 65-74. The 5-year cause-specific survival rates of radical cure treatment in the groups aged 75 and older, 65-74 and 64 and younger were 81.3%, 88.6% and 80.9%, respectively. The survival rate of the group aged 75 and older was lower than that aged 65-74. We could not follow up with the patients who underwent no treatment. Therefore, it is necessary to consider a solution to this problem in the future.

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Myoepithelial carcinoma (MEC), a rare malignant salivary gland tumor, was first classified as a separate neoplasm by the World Health Organization (WHO) in 1991. The tumor represents less than 1% of all salivary gland neoplasms. MEC occurs most frequently in the parotid gland (75%), and approximately 10% in the submandibular gland, and there have been no previous reports of MEC arising from the sublingual gland. Herein, we report a case of MEC occurring in the sublingual gland.
A 67-year-old male came to our hospital in January of 2006, complaining of a swelling on the left side of the floor of the mouth. Clinical examination revealed a 30 × 20 × 10mm elastic, hard, non-tender, submucosal mass on the left side of the floor of the mouth. The mass had poor mobility, but no ulceration was seen on the surface of the mucosa.
Magnetic resonance imaging (MRI) showed an ovoid form mass with a bright mixture of hyper- and hypo-intense signals on T1-weighted images. No signs of mandibular bone invasion were detected. The resected specimen showed a lobulated shape and it extended from the sublingual gland into the surrounding tissues. Immunohistochemical analysis indicated that the tumor cells were positive for S-100 protein, SMA, pan-keratin, CK19, MUC-I, Calponin, and Vimentin. The pathological diagnosis was myoepithelial carcinoma of the sublingual gland. During the follow-up for 2 years and 9 months, there was no clinical or radiological evidence of loco-regional recurrence or distant metastasis.

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Dentinogenic ghost cell tumor (DGCT) has been defined as a solid type of calcifying odontogenic cyst, however, according to the most recent WHO classification, it is now divided into two categories: type 2 of CCOT (cystic type) and DGCT (solid type). In this report, we present a case of DGCT originating in the right maxillary molar region.
Because DGCT is characterized microscopically by odontogenic epithelial proliferation, presence of ghost cells, dentinoid-like material and dystrophic calcification, biopsy specimens must include calcified lesion for a correct histopathological diagnosis.
Surgical removal is the primarily recommended option for DGCT, but post-operative recurrence is not uncommon. In the present case, recurrence occurred after the initial surgical therapy.
In the case of surgical removal, preoperative planning of the resected area with sufficient normal margins is extremely important, hence, maxillectomy might be considered. In the present case, the recurrent lesion showed characteristic findings on CT and MRI.
In conclusion, careful follow-up after surgical therapy is important, with periodical imaging diagnosis by CT and MRI.

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