Evaluation of oral brush liquid-based cytology for oral squamous cell carcinoma: a comparative study of cytological and histological diagnoses at a single center.

PURPOSE: Liquid-based cytology is highly useful in oral cytology. However, there are only few reports on the accuracy of this method. The current study aimed to compare oral liquid-based cytological and histological diagnoses and to evaluate items that should be considered in oral cytological diagnosis for oral squamous cell carcinoma. METHODS: We included 653 patients who underwent both oral cytological and histological examinations. Data on sex, specimen collection region, cytological and histological diagnoses, and histological images were reviewed. RESULTS: The overall male-to-female ratio was 1:1.18. The tongue was the most common specimen collection region, followed by the gingiva and buccal mucosa. The most common cytological examination result was negative (66.8%), followed by doubtful (22.7%) and positive (10.3%). The sensitivity, specificity, positive predictive value, and negative predictive value of cytological diagnosis were 69%, 75%, 38%, and 92%, respectively. Approximately 8.3% of patients with a negative cytological diagnosis had a histological diagnosis of oral squamous cell carcinoma. Furthermore, 86.1% of histopathologic images of cytology-negative squamous cell carcinomas exhibited well-differentiated keratinocytes lacking atypia on the surface. The remaining patients developed recurrence, or they had low cell counts. CONCLUSION: Liquid-based cytology is useful in screening oral cancer. However, a cytological diagnosis of superficial-differentiated oral squamous cell carcinoma is occasionally inconsistent with the histological diagnosis. Therefore, histological and cytological examinations should be performed if tumor-like lesions are suspected clinically.

A Case of Vascular Malformation in the Buccal Fat Pad.

Vascular anomalies are categorized as vascular tumors or vascular malformations (VMs) based on the system of classification (updated in 2018) established by the International Society for the Study of Vascular Anomalies. In the orofacial region, such anomalies are most likely to occur in the lips or tongue, and only rarely in the buccal fat pad. This report describes a case of a VM in the buccal fat pad. A 47-year-old woman was referred to our hospital with a mass lesion in her left cheek. On palpation, an elastic, hard, painless, and mobile mass was found anterior to the left masseter muscle. Computed tomography, magnetic resonance imaging, and ultrasonography revealed a mass in the left buccal fat pad. The lesion was identified as a benign tumor and surgical excision performed under general anesthesia. Histopathological examination revealed that the lesion was composed of a large number of vascular structures of various sizes covered with endothelial cells. Based on the clinical and histopathological findings, a diagnosis of a venous VM was made. One year has passed since the operation and no recurrence has been observed. Long-term follow-up is planned.

Second Primary Metachronous Malignancies Occurring in Oral Cavity of Young Adult-A Case Report.

The incidence of oral cancer in Japan is increasing. Interestingly, the number of young patients with oral cancer is also rising. A 19-year-old man with no history of smoking or drinking alcohol presented with a 20×15-mm elastic, hard, protruding mass with a white surface on the right-hand margin of the tongue. A biopsy resulted in a diagnosis of a well-differentiated squamous cell carcinoma of the tongue, for which a partial resection was subsequently performed. During regular follow-up, the patient demonstrated no clinical or imaging abnormalities until 4 years and 9 months later, when erosion was observed at the right palatoglossal arch. A malignant tumor of the right palatoglossal arch was diagnosed based on cytology and imaging findings, and total resection of the lesion performed. Histopathological examination of the resected lesion revealed a moderately differentiated squamous cell carcinoma. Epithelial dysplasia on the right-hand margin of the tongue was diagnosed 4 years and 9 months after the second surgery and was subsequently resected. The patient's condition has been favorable for 7 years since the diagnosis of the second cancer, with no noted recurrence. This case emphasizes the importance of follow-up after initial treatment, as even young people, who are likely to have to endure long-lasting consequences from treatment, can develop metachronous cancer in the oral cavity.

Identification of Novel Regulator Involved in Differentiation of Mouse iPS Cells into Odontoblast-like Cells.

Odontoblasts differentiate from dental papilla stem cells, but the genetic changes that occur during this process remain unclear. The aim of this study was to investigate gene expression patterns during differentiation of mouse iPS cells into odontoblast-like cells. Mouse iPS cells were cultured on a collagen type-1 scaffold with bone morphogenetic protein 4 (BMP4) and retinoic acid (RA). The results of immunofluorescence studies for dentin sialoprotein, dentin matrix protein 1 (DMP1), and nestin were positive. A qRT-PCR analysis revealed that mRNA expression levels of neural crest marker sex determining region Y box (Sox)-10, dentin sialophosphoprotein (Dspp), and Dmp1 were up-regulated, but that mRNA expression levels of the mineralization markers bone sialoprotein and osteocalcin were down-regulated. Microarray analysis showed that 2,597 entities were up-regulated and 1,327 down-regulated among a total of 15,330 investigated. Sox11 was among the up-regulated genes identified. The Sox11 mRNA expression level with odontoblast induction after day 11 was higher than that after day 2 (p<0.05). Gene knockdown using small interference RNA (siRNA) silencing was used to characterize the function of Sox11. The Dspp mRNA expression level in Sox11 siRNA-treated cells was significantly lower than that in the control (p<0.05). These results suggest that BMP4 and RA induce mouse iPS cells to differentiate into odontoblast-like cells. The differentiation efficiency is not high, however, and many stem cells remain. The results also suggest that Sox11 is an important factor in odontoblastic differentiation.

Homeobox transcription factor engrailed homeobox 1 is a possible diagnostic marker for adenoid cystic carcinoma and polymorphous adenocarcinoma.

Diagnostic utility of a homeobox transcription factor, engrailed homeobox 1 (En1) in the histopathology of salivary gland neoplasms was studied. The expression of En1 was immunohistochemically examined in 51 cases of adenoid cystic carcinoma (AdCC) and 143 cases of other salivary gland neoplasms. In all 51 AdCCs, En1 was expressed in 30-100% of tumor cells. In eight of nine polymorphous adenocarcinomas (PACs), En1 was expressed in 40-100% of tumor cells. Less than 5% of tumor cells expressed En1 in three of 12 epithelial-myoepithelial carcinomas, one of 17 basal cell adenomas (BCAs), and one of 34 pleomorphic adenomas (PAs). Among 55 other carcinoma cases, 1-30% of tumor cells expressed En1 in three salivary duct carcinomas (SDCs) ex PA. None of the myoepitheliomas and Warthin tumors expressed En1. When the cut-off value of the percentage of En1-expressing cells was set to 25%, all 51 AdCCs, eight of nine PACs and one SDC ex PA were En1-positive and the others were En1-negative. En1 is expressed consistently in AdCCs, frequently in PACs, but rarely in other salivary gland neoplasms. En1 is a possible diagnostic marker for AdCC and PAC in the histopathology of salivary gland neoplasms.

Luminal, Intramural Unicystic Ameloblastoma with Marked Fluid-Fluid Level: Validity of CT and MRI Findings.

We report herein a case of a luminal and intramural unicystic ameloblastoma (UA) with a marked fluid-fluid level. The validity of imaging findings in diagnosing UA in the present case is discussed in reference to the literature. The patient was a 50-year-old woman who presented with swelling of the gingiva in the region of the left mandibular third molar and numbness in the lower lip. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a large mass lesion with a unilocular appearance and a biphasic aspect, suggesting liquid content. Contrast-enhanced MRI (CE-MRI) and dynamic contrast-enhanced MRI (DCE-MRI) demonstrated that the biphasic aspect indicated a fluid-fluid level with no blood pooling/flow; it also revealed a thick rim-enhanced margin with mural protrusion. Postoperatively, the lesion was histopathologically diagnosed as a luminal and intramural UA. In conclusion, extensive imaging including both standard CT and MRI together with CE-MRI and DCE-MRI allowed mural protrusions or nodules on a thick cystic wall and liquid content to be correctly identified. This suggests that such imaging can play an important role in diagnosing a UA, even though the results were at first misleading due to the marked fluid-fluid level.

Evaluation of Liquid Based Cytology for Tongue Squamous Cell Carcinoma: Comparison with Conventional Cytology.

Oral exfoliative cytology is now used by general practitioners in Japan to screen for oral cancer. With conventional cytology, however, the number of cells that can be sampled is small. Moreover, cell deformation and piling of cells when preparing specimens has been reported. The purpose of this study was to compare conventional and liquid based cytology (LBC), which has been employed with increasing frequency in recent years. We believe that identifying potential pitfalls in oral exfoliative cytology will help improve diagnostic accuracy. A total of 153 patients with tongue squamous cell carcinoma who were diagnosed and treated initially at our hospital between January 2000 and December 2010 were included. Of these, 124 underwent conventional cytology, while the remaining 29 underwent LBC. Histopathological and clinical findings were used as criteria. Conventional cytology yielded a positive rate of 54.8% and LBC 79.3%, while values of 28.2% and 13.8% were obtained for a suspected positive rate, respectively. Liquid based cytology yielded a significantly higher percentage of accurate diagnoses and fewer suspected positives (p<0.05) in cases clinically classified as endophytic and those classified as ulcerative in terms of clinical growth pattern. No significant difference was observed between conventional cytology and LBC in cases of an infiltrative growth pattern, however.The present results suggest that LBC is superior to conventional cytology in achieving an accurate diagnosis based on oral exfoliative cytology. The present findings also suggest that exophytic type, and especially leukoderma type clinical growth patterns constitute pitfall cases in oral exfoliative cytology.

Expression of Cytokeratin in Experimentally Created Inflammatory Cyst in Vivo and in Vitro.

The purpose of this study was to investigate the behavior of epithelial lining derived from Malassez's epithelial rest (MER) cells in experimentally created inflammatory cysts in vivo and in vitro. Porcine MER cells were cultured in vitro with or without interleukin (IL)-1ß (1 ng/ml) or IL-6 (1 ng/ml). Cell proliferation was assessed and expression levels of CK19 and CK13 mRNA determined using RT-PCR. In vivo, a cavity was created in the first molar of Sprague-Dawley male rats and tissue repair observed using immunohistochemical methods. In vitro, treatment with IL-1ß or IL-6 increased proliferation of MER cells and decreased expression of CK19 mRNA, but increased CK13 mRNA at day 1 (p<0.05). In vivo, at 2 weeks, CK19-positive epithelial cells were observed adjacent to the cementum, in the cystic lesion, and in connective tissue. At 3 weeks, they were only detected in cells adjacent to the connective tissue. Cells positive for CK13 were observed throughout the epithelium, except in cells adjacent to connective tissue at weeks 2 and 3. Exposure to IL-1ß and/or IL-6 induced proliferation and differentiation of MER cells.

Congenital Epulis: A Case and Review of the Literature.

Congenital epulis is an unusual benign oral mucosal lesion in newborns with no tendency to recur after excision. The histogenesis of the lesion is unknown, but it is believed to be of mesenchymal origin. We describe a case of congenital epulis (20×10 mm) in the mandibular gingiva of a newborn. The mass, which was smooth-surfaced and pedunculated with a healthy color, was surgically removed at 5 months post-birth. Histologically, the tumor consisted mainly of large eosinophilic granular cells. Immunohistochemical studies revealed intense staining for vimentin, STRO-1, and CD44, suggesting that it was derived from mesenchymal cells. The literature and immunohistochemical profile of congenital epulis are also discussed.

Atypical MRI and Histopathological Findings in Dermoid Cyst.

On images, a dermoid cyst is often described as resembling a "sack of marbles" or "marbles in a bag". Typically, it comprises an inhomogeneity filled with multiple nodules in a fluid matrix on both computed tomography and magnetic resonance imaging (MRI). How it appears, however, will vary depending on its histological contents, which may cause confusion in arriving at a diagnosis. This report describes a dermoid cyst in the floor of the mouth of a 55 year-old woman that showed an atypical internal appearance on MRI. Most of the lesion showed homogeneous high signal intensity on T1 - and T2-weighted images, suggesting that it was derived from fat. A small area within the mass, however, showed moderate signal intensity almost equal to that of muscle on T1-weighted images and high signal intensity on fat-suppressed T2-weighted images. Given the location of the lesion, a dermoid cyst was one possible diagnosis. A lipoma or lipoma variants were also considered, however, based on signal intensity. Histopathological section of the excised specimen revealed a dermoid cyst with sebaceous glands in its walls and keratin in its cavity. Dermoid cysts show variation in their internal structures and contents. Since MRI can reflect such histological variation, signal intensity requires careful interpretation.

HSP70 mRNA expression by cells of the epithelial rest of Malassez due to mechanical forces in vitro.

BACKGROUND: The purpose of the present study was to examine the in vitro responses of ERM cells under the combination of centrifugal and compression forces, in terms of their expression of HSP70 mRNA. METHODS: The ERM cells were positive for CK19 indicating that they were derived from the odontogenic epithelium. Cultured ERM cells were applied centrifugal force and compressing force at one to three times as mechanical forces. After addition of forces, cells were observed using scanning electron microscope (SEM) and were measured expression of HSP70 mRNA by RT-PCR. RESULTS: SEM observations showed the cells were flattened immediately after the application of mechanical force, but nuclear protrusions recovered the same as the control 3 h later. A significantly higher expression of HSP70 mRNA was observed in ERM cells under mechanical force compared with the control, but it gradually decreased with time. No accumulation of HSP70 mRNA expression occurred with intermittent force. However, the expression of HSP70 mRNA with intermittent force repeated 3 times was significantly higher compared with intermittent force applied only once or twice. CONCLUSIONS: These findings suggest that ERM cells express HSP70 mRNA in response to mechanical force, and that intermittent force maintains the level of HSP70 mRNA expression.

A case of cystadenoma arising in the upper lip.

Cystadenoma, a common benign tumor derived from glandular tissue, generally occurs in the appendix, ovaries, kidney, or pancreas. While rare in the oral and maxillofacial region, they do sometimes occur in the parotid or minor salivary glands. We report a case of cystadenoma arising in the upper lip region. The patient was a 37-year-old woman referred to our hospital with a painless mass on the left upper lip initially found during treatment at a local dental clinic. The medical history was non-contributory. The 7×5-mm mass was well-defined, elastic, and flexible. The surface of the mucosa appeared healthy. The mass was clinically diagnosed as a benign tumor of the left upper lip. Because the tumor was painless and slow-growing, and magnetic resonance imaging suggested that it was benign, resection was performed under local anesthesia without biopsy. Histopathologically, cystadenoma was diagnosed. No signs of recurrence or metastasis have been seen as of 24 months postoperatively and the progress of the patient has been satisfactory.

A Case of Infratemporal Fossa Abscess with Signs of Chronic Maxillary Osteomyelitis.

The infratemporal fossa is bordered superiorly by the infratemporal surface of the greater wing of the sphenoid bone and part of the temporal bone; medially by the lateral plate of the pterygoid process of the sphenoid bone; and anteriorly by the posterior surface of the maxilla. As it is completely surrounded by bone, it is frequently difficult to determine whether an abscess is present by direct visual observation or palpation alone. We report an extremely rare case of an infratemporal fossa abscess arising from chronic maxillary osteomyelitis developing after extraction of a maxillary molar. Despite drainage during initial oral anti-inflammatory treatment, pus continued to drain from the wound over a long period of time. This drainage ended when the eroded bone of the maxillary tuberosity on the affected side was curetted in a secondary procedure. The harvested bone tissue exhibited histological findings of chronic osteomyelitis. This suggests that the route of infection involved acute transformation of maxillary osteomyelitis by odontogenic infection advancing posteriorly and superiorly.

A case of mucoepidermoid carcinoma with clear cell components occurring in retromolar region.

Mucoepidermoid carcinomas in the minor salivary glands usually originate in the palatine gland, and their occurrence in the retromolar region is rare. We report a rare case of mucoepidermoid carcinoma with clear cell components occurring in the retromolar region. The patient was a 63-year-old woman referred to our hospital with the chief complaint of a painless mass in the right retromolar region initially found during treatment at a local dental clinic. The 20×10-mm mass was well-defined, elastic, and flexible. The surface of the mucosa was healthy. The mass was clinically diagnosed as a gingival benign tumor in the right retromolar region. There were no significant findings in the patient's medical history. The tumor was resected under local anesthesia. Histopathology revealed that squamoid cells, undifferentiated intermediate cells, and clear cells were dominant, with mucus-producing cells in some areas. A mucoepidermoid carcinoma with clear cell components was diagnosed. There were no signs of recurrence or metastasis at 15 months postoperatively and the patient's progress has been satisfactory. Because the tumor was a painless, slow-growing mass, it was clinically diagnosed as a benign tumor of the gingiva, and resection was performed under local anesthesia without performing a biopsy. However, even if a mass in the retromolar region is clinically diagnosed as a benign tumor, the course of treatment should be decided after performing fine-needle aspiration cytology, taking into consideration the possibility of mucoepidermoid carcinoma.

Osseous choristoma in child with strong vomiting reflex.

Osseous lesions within soft tissue such as the tongue are extremely rare. Here, we report an osseous choristoma on the posterior portion of the tongue in a patient with a strong vomiting reflex. The patient was an 11-year-old boy who presented with the chief complaint of swelling on the posterior portion of the tongue. A pedunculated tumor 8-mm in diameter with distinct borders was observed slightly to the right of the midline of the dorsum of the tongue and slightly anterior to the circumvallate papillae. The clinical diagnosis was a right lingual circumvallate papilla fibroma. A further examination conducted under general anesthesia in July 2012 confirmed a pedunculated and solid mass in the area of the circumvallate papillae. As these results suggested a benign tumor, the mass was resected. Histopathological findings on harvested bone and fibrous connective tissue covered with a layer of squamous cells led to a diagnosis of osteoma. At 18 months postoperatively, there were no signs of recurrence.

Clinicopathological evaluation of oral leukoplakia: a single-center study of 676 cases in Japan.

OBJECTIVES: To analyze the clinical and histopathological characteristics of oral leukoplakia (OL) in the Japanese population and investigate the prevalence and risk factors for epithelial dysplasia (ED) and carcinoma within lesions. STUDY DESIGN: Data, including age, sex, lesion site, and histopathological features, of 676 cases diagnosed with OL over the previous 10 years were analyzed. Dysplasia and carcinoma prevalence were determined. RESULTS: In male patients, the most affected site was the gingiva (42.7%), whereas in females, it was the tongue (47.6%). Moreover, ED was more prevalent in males (41.9%), whereas epithelial hyperplasia was more common in females (44.7%). A significant difference was observed between affected sites with regard to the presence of dysplasia. The ED rates by site were 64.6% and 33.7% for the tongue and gingiva, respectively (P < 0.05). The squamous cell carcinoma rates by site were 23.4%, 5.4%, and 3.4% for the tongue, buccal mucosa, and gingiva, respectively (P < 0.05). Logistic regression analysis revealed a higher prevalence of dysplasia in males than it did in females and that the risk for both dysplasia and carcinoma was highest in the tongue. CONCLUSIONS: Dysplasia is common in OL cases, often showing carcinoma. Early biopsy and interventions are key in OL management.

Dentigerous cysts suspected the other odontogenic lesions on panoramic radiography and CT.

Dentigerous cysts are known as the second most common type of cyst in the jaws. The cyst is one of the lesions occurred frequently in the posterior body of the mandible and is often related to the unerupted third molar and forms around the crown of the unerupted tooth attaching at the cementoenamel junction. Such characteristic appearances are the diagnostic points differentiating from ameloblastoma or odontogenic keratocyst. However, it would be hard for us to diagnose it as a dentigerous cyst if the lesion does not show its typical appearance. We experienced two cases of dentigerous cysts which did not form around the crown of the unerupted tooth on radiologically. Both cysts were relatively large and resorbed adjacent teeth roots. Therefore, an ameloblastoma or an odontogenic keratocyst was suspected rather than a dentigerous cyst as the imaging diagnosis. The biopsy revealed that the lesion was a "dentigerous cyst" in one of the cases and "developmental cyst with inflammation" in another case. After the excision, the histopathological diagnosis was a dentigerous cyst with inflammation in both cases. This report shows the two cases of dentigerous cysts focusing on panoramic radiography and CT images. Also, we discuss the differential diagnosis by reconsidering those diagnostic points.

Regenerative capability of dental pulp cells after crown fracture.

The purpose of this study was to evaluate the characteristics of dental pulp cells for tissue engineering derived from the fractured incisal portion of tooth crowns. Thirty Sprague-Dawley rats were used for histological and immunohistochemical analysis of nestin protein expression and to measure levels of mRNAs encoding osteocalcin, osteopontin, bone sialoprotein (BSP), dentin sialoprotein (DSP), heat shock protein (HSP) 27, vascular endothelial growth factor (VEGF), ATP-binding cassette transporter G2 (ABCG2), nestin, and p57(Kip2) . Odontoblasts at the incisal portion in the control group were oriented in a regular pattern, but those in the experimental group were randomly stratified. Immunohistochemically, only a few odontoblasts were positive for nestin at the incisal portion in the experimental group at 2 days. Some cells in the inner area in the control group were positive for nestin, but nestin-positive cells in the experimental group at the incisal portion were not observed. The mRNA expression for osteogenic or odontogenic markers in the experimental group was higher than in the control group. HSP27 mRNA expression in the experimental group at 2 days was higher than in the control group and in the experimental group at 7 days. mRNA expression of stem cell markers, such as ABCG2 and nestin, in the experimental group tended to decrease compared with the control. In conclusion, this study demonstrates that dental pulp stem cells derived from fractured teeth differentiate to osteogenic or odontogenic cells.

Schwannoma derived from lingual nerve occurring in floor of mouth.

A schwannoma is a benign tumor composed of schwann cells which forms on the periphery of nerves. We report a case of a schwannoma derived from a lingual nerve occurring in the floor of the mouth. The patient was a 27-year-old woman who presented with the complaint of a swelling in the floor of the mouth. It is difficult to distinguish a swelling from a sublingual gland tumor, cyst, or malignant tumor by MRI alone. Therefore, a biopsy and cytological examination were performed one week prior to surgery to determine whether the growth represented a malignancy. The results revealed a class II growth which was suspected to be a schwannoma. Intraoperatively, it became clear that the tumor and lingual nerve were inseparable, making excision of the nerve unavoidable. On the other hand, there was a clear border between the tumor and the sublingual gland, so it was possible to preserve the sublingual gland. In the postoperative pathological diagnosis, a definitive diagnosis was difficult based solely on H-E staining. Therefore, immunohistochemical staining was performed, resulting in a diagnosis of schwannoma. Currently, the patient is still being followed up. The results of this case indicate that preoperative aspiration biopsy cytology is useful in deciding the operative method to be employed.

Intraosseous schwannoma originating in inferior alveolar nerve: a case report.

Schwannomas (neurilemmomas) are benign neoplasms derived from Schwann cells of the neurilemma and appear most frequently on the auditory nerve or peripheral nerves of the skin. They arise in the oral and maxillofacial region infrequently, and very rarely in the center of the jaw. We herein present a case of a rare mandibular intraosseous schwannoma derived from the main trunk of the inferior alveolar nerve in a 33-year-old man. Fusiform expansion in the mandibular canal was observed and a mass showing the target sign in the mandibular canal was confirmed on T2-weighted and Gd contrastenhanced T1-weighted MRI. Based on these findings, an inferior alveolar nerve-derived schwannoma or other benign nervous system neoplasm was diagnosed. A buccal side cortical bone flap in the mandibular molar region was removed to expose the mass, which was then peeled away from the nerve fibers and completely removed. Some inferior alveolar nerve fibers that were connected to the mass were removed at the same time, but the remaining nerve fiber bundle was preserved. Histopathology confirmed the diagnosis of a schwannoma with Antoni type A and Antoni type B regions. Although the patient experienced extremely mild paresthesia in the skin over the mental region and mental foramen at immediately after surgery, this had almost entirely disappeared at 7 years and 4 months later, and there has been no tumor recurrence.