A Case Report of Atypical Spindle Cell Lipomatous Tumor of the Tongue.

Herein, we report a case of atypical spindle cell lipomatous tumor (ASCLT) on both sides of the tongue in a 74-year-old male patient. The patient was referred to our department for treatment of the masses in the tongue. Several elastic soft indolent masses were detected during the first examination. The masses were well defined, and their consistency was similar to that of adipose tissues. No signs of induration were observed in the surrounding tissues. The patient was not aware of the masses, which were only detected during his visit at the dental clinic that referred him to our institution. Thus, the onset of the masses remains unknown. ASCLT was identified via histopathological examination. Then, tumor excision was performed under general anesthesia. Thirteen months after surgery, the condition of the patient was good, and signs of local recurrence or postoperative metastasis were not observed.

Associations between Systemic Markers of Bone Turnover or Bone Mineral Density and Anti-Resorptive Agent-Related Osteonecrosis of the Jaw in Patients Treated with Anti-Resorptive Agents.

BACKGROUND: Some previous studies have examined anti-resorptive agent-related osteonecrosis of the jaw (ARONJ) prediction using systemic markers of bone turnover as risk factors. Radiographic imaging is also effective at detecting ARONJ. In this study, computed tomography (CT)-derived bone mineral density (BMD) values and the levels of systemic markers of bone turnover were evaluated, and then each parameter was compared between patients that developed ARONJ and those who did not after treatment with systemic anti-resorptive agents. The aim of this study was to determine whether systemic markers of bone turnover and/or BMD values can be used to predict the risk of ARONJ. METHODS: The subjects' serum levels of cross-linked N-terminal telopeptide of type I collagen (NTX) and bone alkaline phosphatase (BAP) (systemic markers of bone turnover) were measured. BMD was calibrated to CT values using a medical imaging phantom. Then, the subjects' BMD were assessed using quantitative computed tomography. Fifty-six patients who had received systemic anti-resorptive agents were included in this study. Thirty-two of the patients developed ARONJ after receiving the drugs whereas the remaining 24 did not. RESULTS: No correlation was observed between the serum levels of the systemic markers of bone turnover and the incidence of ARONJ. On the other hand, the ARONJ patients exhibited higher mandibular BMD values than the control group. BMD was not associated with healing or the clinical stage of ARONJ. CONCLUSION: These results suggest that increased mandibular BMD values are associated with ARONJ. Furthermore, mandibular BMD might serve as a novel marker for predicting the risk of ARONJ in patients that are taking anti-resorptive agents and are about to undergo tooth extraction. Accordingly, mandibular BMD could be a useful tool for aiding risk assessments and guiding treatment decisions.

PITX1 is a reliable biomarker for predicting prognosis in patients with oral epithelial dysplasia.

Paired-like homeodomain 1 (PITX1) genes are essential in human development. In the present study, PITX1 protein expression was evaluated in human normal oral mucosa, oral epithelial dysplasia and oral squamous cell carcinoma (OSCC), with the aim of examining the expression patterns of these critical genes during the multi-stage transformation of oral epithelial dysplasia to OSCC. PITX1 and Ki-67 expression were assessed by immunohistochemistry in 26 individuals with normal oral mucosa, 106 patients with oral epithelial dysplasia and 97 OSCC patients. The labeling indices (LIs) of PITX1 and Ki-67 were calculated and their correlation with the incidence of malignancy was evaluated. The PITX1 LI of the dysplasia specimens was significantly lower than that of the normal oral mucosa samples, but significantly higher than that of the OSCC samples. The oral epithelial dysplasia patients that exhibited low PITX1 expression showed a significantly higher incidence of malignant transformation than those exhibiting high PITX1 expression, regardless of the histological grades of their oral epithelial dysplasias. On the other hand, no correlation was observed between the Ki-67 LI and the incidence of malignancy. These results suggested that PITX1 suppression is associated with malignant transformation in the oral epithelium and that PITX1 expression may serve as a novel biomarker for predicting prognosis in oral epithelial dysplasia.

Cancer-associated fibroblasts and CD163-positive macrophages in oral squamous cell carcinoma: their clinicopathological and prognostic significance.

BACKGROUND: Stromal cells are believed to affect cancer invasion and metastasis. The purpose of this study was to evaluate the distribution of cancer-associated fibroblasts (CAFs) and the incidence of tumor-associated macrophages (TAMs) in oral squamous cell carcinoma (OSCC), focusing on clinicopathological factors and patient prognosis, as well as cancer invasion. METHODS: The study included 108 patients with OSCC. Anti-α-smooth muscle actin, CD68, and CD163 antibodies were used to identify CAFs and TAMs. CAFs were divided into 4 grades on the basis of staining intensity: negative (0), scanty (1), focal (2), and abundant (3). The most intensive areas of macrophage concentration in each tumor invasive stroma were also evaluated. RESULTS: The cancer specimens were divided into Grade 0/1, Grade 2, and Grade 3 on the basis of CAF grade. In addition, they were divided into low- and high-grade groups on the basis of the number of CD68-positive and CD163-positive macrophages. The latter were significantly increased in the Grade 2 CAF group compared to the Grade 0/1 group (P = 0.009). Kaplan-Meier and multivariate survival analyses revealed that Grade 2 CAFs (P = 0.003) and high CD163-positive macrophage levels (P = 0.007) significantly correlated with a poor outcome in patients with OSCC, and that a high CD163-positive macrophage level was a significant and an independent prognostic factor (P = 0.045). CONCLUSIONS: Cancer-associated fibroblasts and CD163-positive macrophages may be potential prognostic predictors of OSCC.

Zoledronic acid, a third-generation bisphosphonate, inhibits cellular growth and induces apoptosis in oral carcinoma cell lines.

Bisphosphonates (BPs) inhibit bone resorption by preventing osteoclast maturation and apoptosis induction. Recently, BPs have also been shown to have antitumor effects against various types of carcinomas in vitro and in vivo. In this study, we investigated the antitumor effect of zoledronic acid (ZOL), a third generation bisphosphonate, on proliferation, cell cycle and apoptosis of oral cancer cells. Direct antitumor effects of ZOL against four oral carcinoma cell lines (squamous cell carcinoma, HSC3, HSC4, SCCKN; salivary adenocarcinoma, HSY) were measured by WST assay. Apoptosis-related molecules were analyzed by Western blot analysis and cell cycle was analyzed by flow cytometry. ZOL had a dose-dependent antitumor effect in the four oral cancer cell lines. ZOL activated caspase-3, -8 and -9 and induced cellular apoptosis. Western blot analysis showed that ZOL increased cleaved anti-human poly(ADP-ribose) polymerase expression and decreased Bcl-2 and Bid expression. Treatment with ZOL increased the number of cells in apoptosis, sub G1 phase and S phase, and reduced the number of cells in the G0/G1 and G2/M phase in a concentration-dependent manner. ZOL inhibits cell proliferation and induces apoptosis of oral cancer cells in vitro. These findings suggest that ZOL might be beneficial in the treatment of oral carcinoma patients.

Geminin, Ki67, and minichromosome maintenance 2 in gastric hyperplastic polyps, adenomas, and intestinal-type carcinomas: pathobiological significance.

BACKGROUND: Geminin negatively regulates Cdt1 and induces the formation of prereplicative complexes by loading mini-chromosome maintenance proteins (Mcm) onto chromatin and limiting DNA replication to once per cell cycle. Recent studies have suggested that geminin expression is a marker of the S/G2/M phase of the cell cycle and is associated with a poor prognosis in various human malignancies. This study aimed to clarify the pathobiological role of geminin in intestinal-type gastric carcinoma, and its relationships with minichromosome maintenance 2 (Mcm2) and Ki67 expression. METHODS: We performed western blot analysis of seven human gastric cancer cell lines, and immunohistochemical analysis of 72 gastric mucosal lesions and 128 surgically removed advanced intestinal-type gastric carcinomas. Double-labeling immuno-fluorescence was performed to identify the coexpression of geminin and Ki67. RESULTS: Geminin was detected in all cell lines. Geminin labeling indices (LIs) in hyperplastic polyps, low-grade adenomas, high-grade adenomas, and intestinal-type adenocarcinomas were 3.9%, 10.5%, 18.6%, and 27.2%, respectively. The equivalent LIs for Ki67 and Mcm2 were 17.7%, 42.2%, 52.6%, and 59.7%; and 26.7%, 70.0%, 67.8%, and 77.8%, respectively. Double-labeling immunofluorescence revealed coexpression of geminin and Ki67 in both normal and tumor cells. The LI for geminin was significantly correlated with N stage, International Union Against Cancer (UICC) stage, Mcm2 LI, and Ki67 LI. Patients in stages I-IV and stage III with higher LIs for geminin (>25%) had significantly worse prognoses (P < 0.05 and P < 0.04, respectively). Univariate Cox regression analysis indicated that the overall survival of stage I-IV tumors was significantly correlated with high geminin LIs (relative risk [RR] = 1.94; P = 0.04). CONCLUSIONS: Geminin expression might reflect the biological nature of gastric intramucosal neoplasms and could be a possible prognostic marker in advanced intestinal-type gastric carcinomas.

Tubular-trabecular type Basal cell adenoma of the parotid gland: a patient report.

Basal cell adenoma (BCA) is an uncommon benign salivary gland neoplasm that includes isomorphic basaloid cells. We report on a female patient with BCA that developed in the right parotid gland in her 50s. The present patient demonstrated a few tumor nests in the fibrous capsule, and her tumor was larger than usual. These facts made us suspect of malignancy. Histopathologically, the tumor was characterized by multiple duct-like structures and tubular-trabecular masses composed of small isomorphic cells with hyperchromatic, round nuclei and an eosinophilic cytoplasm. It was difficult to determine whether the ductal structures noted in the tumor capsule were invasive. By immunohistochemistry, tumor cells of the tubular nests were positive for cytokeratin 7 and that the outer cells of tubular nests were positive for alpha smooth muscle actin (αSMA) and calponin. Tumor cells were immuno-negative for S-100 protein and glial fibrillary acidic protein. The Ki-67 labeling scores of the cells were extremely low (< 1%). We could achieve an accurate diagnosis of BCA by immunohistochemistry with MIB-1 and other markers.