Squamous cell carcinoma of the tongue: subtypes and morphological features affecting prognosis.

Squamous cell carcinoma (SCC) is the most common histological type of mobile tongue carcinoma. The incidence of mobile tongue carcinoma is decreasing in some countries owing to decreasing exposure to risk factors, but it has been reported to be increasing in younger people. The majority of mobile tongue cancers are conventional SCCs. Pathological diagnosis of conventional SCC is relatively easy. However, mobile tongue SCCs involve several subtypes that have distinct pathological features and biological behaviors. Some subtypes are relatively rare, and the pathological subtype influences treatment decision-making. Therefore, the recognition of SCC subtypes is crucial for proper treatment. In this review, we summarize nine SCC subtypes, including conventional SCC and highlight their pathological characteristics. We also report some morphological factors, such as the pattern of invasion, budding, desmoplastic reaction, lymphovascular invasion, and perineural invasion, which could be predictive of prognosis. As some morphological factors are closely associated with prognosis, pathologists may need to evaluate additional factors in pathological reports of near features. In summary, we highlight the basic knowledge of mobile tongue SCC with an emphasis on pathological subtypes, morphological features, and their relationship. We provide information to further elucidate SCC in the oral region.

Expression and significance of laminin receptor in squamous cell carcinoma of the tongue.

BACKGROUND: Laminin receptor is a non-integrin cell-surface receptor that binds laminin present on the basement membrane. It has been reported to be associated with infiltration and metastasis of various malignant tumors. However, no studies regarding tongue cancer have been reported. This study aimed to clarify the role of laminin receptor in squamous cell carcinoma of the tongue. METHODS: We performed immunohistochemical staining of specimens from 66 patients with squamous cell carcinoma of the tongue and assessed laminin receptor expression and clinicopathological factors. As epithelial-mesenchymal transition has been shown to be associated with infiltration and metastasis of malignant tumors, staining for E-cadherin, vimentin, and N-cadherin were also performed. RESULTS: Of 20 patients with postoperative recurrence, 14 exhibited high laminin receptor expression (p = 0.0025). Kaplan-Meier analysis revealed a significantly shorter time to postoperative recurrence for the high laminin receptor expression group than that for the low laminin receptor expression group (p = 0.0008). Based on multivariate analyses for postoperative recurrence, high laminin receptor expression was associated with poor prognosis (high expression vs. low expression; HR =3.19, 95% CI =0.92-11.08; p = 0.0682). There was a correlation between laminin receptor and N-cadherin (p = 0.0089) but not between laminin receptor and E-cadherin (p = 0.369) or vimentin (p = 0.4221). CONCLUSION: These results suggest that high laminin receptor expression is a useful prognostic factor for postoperative recurrence and may be a target for molecular therapy to treat squamous cell carcinoma of the tongue.

Multicenter retrospective study of nivolumab for recurrent/metastatic oral squamous cell carcinoma.

OBJECTIVES: Immunotherapy with nivolumab for patients with recurrent/metastatic oral squamous cell carcinoma has not been evaluated. Here, we aimed to examine the efficacy, safety, and prognostic factors of nivolumab in these patients. MATERIALS AND METHODS: This multicenter retrospective observational study involved patients who received nivolumab between April 2017 and June 2019. The patient characteristics were evaluated for association with progression-free and overall survival. Progression-free and overall survival rates were calculated; parameters that were significant in the univariate analysis were used as explanatory variables. Independent factors for progression-free and overall survival were identified using multivariate analysis. RESULTS: Totally, 143 patients were included. The overall response and disease control rates were 27.3% and 46.2%, respectively. The median, 1- and 2-year progression-free survival rates were 2.7 months, 25.4%, and 19.2%, respectively; those for overall survival were 11.2 months, 47.3%, and 33.6%, respectively. The independent factors affecting progression-free survival were performance status and immune-related adverse event occurrence, whereas those affecting overall survival were performance status, target disease, and number of previous lines of systemic cancer therapy. Eight patients reported grade ≥3 immune-related adverse events. CONCLUSION: Nivolumab was effective for recurrent/metastatic oral squamous cell carcinoma treatment and was well tolerated by patients.

Mast cells can produce transforming growth factor ß1 and promote tissue fibrosis during the development of Sjögren's syndrome-related sialadenitis.

OBJECTIVES: This study investigated the associations of mast cells with immune-mediated inflammation and fibrosis in patients with primary Sjögren's syndrome (pSS); it also explored the underlying pathophysiology of pSS-related sialadenitis. METHODS: Twenty-two patients with pSS and 10 patients with sicca (control individuals) underwent labial salivary gland biopsies. Sections were subjected to staining and immunofluorescence analyses. HMC-1 human mast cells were cocultured with fibroblasts in vitro; fibroblasts were also grown in HMC-1 conditioned medium. mRNA levels of collagen Type I (Col1a) and transforming growth factor (TGF)ß1 were analysed in cultured cells. RESULTS: Mast cell numbers in labial salivary glands were significantly greater in patients with pSS than in control individuals. In salivary glands from patients with pSS, mast cell number was significantly correlated with fibrosis extent; moreover, mast cells were located near fibrous tissue and expressed TGFß1. Col1a and TGFß1 mRNAs were upregulated in cocultured fibroblasts and HMC-1 cells, respectively. Fibroblasts cultured in HMC-1 conditioned medium exhibited upregulation of Col1a mRNA; this was abrogated by TGFß1 neutralizing antibodies. CONCLUSIONS: Mast cell numbers were elevated in patients with pSS-related sialadenitis; these cells were located near fibroblasts and expressed TGFß1. TGFß1 could induce collagen synthesis in fibroblasts, which might contribute to fibrosis.

The potential for facial artery injury during mandibular third molar extraction. An anatomical study using contrast-enhanced computed tomography.

The purpose of this study was to evaluate the risk of injury to the facial (FA) and related arteries during mandibular third molar (MTM) extraction using contrast-enhanced computed tomography (CE-CT). CE-CT images of the MTM region were retrospectively reviewed. The area of the MTM was equally divided into three zones in the coronal images from mesial to distal, that is, zone 1, zone 2, and zone 3. The FA, submental artery (SMA), and sublingual artery (SLA) were identified. The distance from the mandible to FA, SMA, and SLA and the diameter of the FA, SMA, and SLA was measured in three zones, respectively. The thickness of the facial soft tissues and width of the mandible were measured at their maximum. The mean distance from the FA to the buccal cortical bone in zone 1, zone 2 and zone 3 was 2.24 mm, 2.39 mm and 1.67 mm, respectively. The SMA and SLA were found to be distal to the mandible. The mean diameter of the FA was 1.26 mm in males and 1.04 mm in females, respectively (p < 0.0001). The distance between the FA and buccal cortical bone of the mandible, and the patients' weight showed moderate correlation in zones 1 and 2. Based on our findings, the FA can be damaged if the surgical invasion reaches the facial soft tissues during MTM surgery. The patients' weight might be a good predictor for FA injury when CE-CT is not available.

Comprehensive review of lower third molar management: A guide for improved informed consent.

Lower third molar removal is the most commonly performed dental surgical procedure. Nevertheless, it is difficult to ensure that all the informed consent forms given to patients are based on the best evidence as many newer publications could change the conclusions of previous research. Therefore, the goal of this review article is to cover existing meta-analyses, randomized control trials, and related articles in order to collect data for improved and more current informed consent.

An anatomical and histological study of mental nerve branches to the inferior labial glands.

PURPOSE: In this study, we aimed to reveal the detailed anatomy of mental nerve branches to the inferior labial glands. METHODS: Embalmed cadaveric heads were used in this study and the mental nerve branches to the inferior labial glands were dissected. Branches to the glands were then excised for histological observation. RESULTS: On all sides, the inferior labial glands were innervated by small branches arising from mental nerve branches that innervated the lower lip. No nerve branches to the inferior labial gland crossed the midline. Histological observation found that the tissue to the inferior labial gland were composed primarily of nerve fibers with a small number of surrounding vessels. Histological findings in examined specimens were consistent. CONCLUSION: The inferior labial glands were innervated by small branches of the mental nerve to the lower lip.

The mental artery: anatomical study and literature review.

The mental artery is a terminal branch of the inferior alveolar artery arising from the maxillary artery. It often communicates with the submental and inferior labial arteries branching off the facial artery. To our knowledge, few reports have described its anatomy and clinical significance in detail. The aim of this paper was to clarify the anatomy of the mental artery. Ten sides from five embalmed Caucasian cadaveric heads were used. The facial artery was identified at the point passing through a notch for the facial vessels and was traced medially. The mental artery and its anastomoses with other arteries were observed in detail. It was detected on all sides. Fourteen anastomoses were found, eight with the inferior labial artery and six with the submental artery. On one side, the mental artery directly supplied the lower lip with no anastomosis. The inferior labial artery tended to anastomose with the mental artery superior to the mental foramen and was likely to anastomose with the submental artery anterior to the mental foramen. We clarified the detailed anatomy of the mental artery. Our results could provide dentists with information that will help them to make oral surgery safer and more successful.

Three-dimensional ultrastructural analysis and histomorphometry of collagen bundles in the periodontal ligament using focused ion beam/scanning electron microscope tomography.

BACKGROUND AND OBJECTIVE: The periodontal ligament (PDL) is an essential tissue for tooth function. However, the 3-dimensional ultrastructure of these PDL collagen bundles on a mesoscale is not clear. We investigated the 3-dimensional ultrastructure of these collagen bundles and quantitatively analyzed their histomorphometry using focused ion beam/scanning electron microscope (FIB/SEM) tomography. MATERIAL AND METHODS: The PDLs of the first mandibular molar of male C57BL/6 mice were analyzed using FIB/SEM tomography. The serial images of the collagen bundles so obtained were reconstructed. The collagen bundles were analyzed quantitatively using 3-dimensional histomorphometry. RESULTS: Collagen bundles of the PDL demonstrated multiple branched structures, rather than a single rope-like structure, and were wrapped in cytoplasm sheets. The structure of the horizontal fiber of the collagen bundle was an extensive meshwork. In contrast, the oblique and apical fibers of the collagen bundle showed a chain-like structure. The area and the minor and major axis lengths of cross-sections of the horizontal fiber, as determined from 3-dimensional images, were significantly different from those of the oblique and apical fibers. CONCLUSION: These findings indicate that collagen bundles in horizontal fiber areas have high strength and that the tooth is firmly anchored to the alveolar bone by the horizontal fibers, but is not secured evenly to the alveolar bone. The tooth is firmly anchored around the cervical area, creating a "slingshot-like structure." This study has provided further insights into the structure of the PDL and forms the basis for the development of more effective therapies for periodontal tissue regeneration.

Anatomic Study of Accessory Infraorbital Nerves and Foramina: Application for a Better Understanding of Complications of Le Fort Fractures and Osteotomy.

PURPOSE: Neurosensory disturbance of the infraorbital nerve is one of the many complications of the Le Fort osteotomy. An accessory infraorbital foramen (AIOF) can be one reason for such complications. Therefore, the purpose of the present study was to elucidate the distribution of the accessory infraorbital nerve (AION) arising from the AIOF. MATERIALS AND METHODS: We dissected 60 sides from 30 fresh-frozen cadaveric heads. RESULTS: An AIOF was found in 36.7% of the heads examined. When an AIOF was detected, the nerve was traced distally and proximally. The mean horizontal and vertical diameters of the AIOF were 1.64 ± 0.88 and 1.75 ± 0.87 mm, respectively. The largest AIOF was 3.42 × 3.79 mm. All AIOFs were located medial to the infraorbital foramen. Most of the AIONs (87.5%) had branches to the external nose. CONCLUSIONS: The AION should always be remembered by surgeons to allow for improved outcomes and better understanding of the complications such as those occurring after Le Fort osteotomy.

Anatomical Study of the Posterior Auricular Branch of the Facial Nerve: Application to Parotid Surgery.

The posterior auricular nerve (PAN) is the first branch of the facial nerve after it leaves the stylomastoid foramen. The literature describing the anatomy of the PAN is very sparse. Therefore, the purpose of this study was to clarify the detailed anatomical features of the PAN and consider its clinical and surgical applications. The authors examined 10 sides from 6 fresh frozen adult cadaveric Caucasian heads. The PAN was observed as the first branch of the facial nerve in all specimens. During the dissection of the PAN, the posterior auricular artery was constantly near the PAN. Moreover, the PAN was located under the investing layer of deep cervical facia covering the sternocleidomastoid and mastoid process in all specimens. The diameter of the PAN was 0.82 ±â€Š0.21 mm (range from 0.55 to 1.21). The distance from the stylomastoid foramen to where the PAN branched from the facial nerve was 0.40 ±â€Š1.25 mm (range from 0 to 4.35). The distance from the location of this branching point of the PAN to the entering point of the PAN to any muscles was 28.03 ±â€Š5.51 mm (range from 19.71 to 38.75). Understanding the anatomical features of the PAN is essential for performing surgical procedures in this region.

Anatomical study of the supraorbital and supratrochlear nerves: A new classification and application to understanding some migraine headaches.

The frontal nerve is the largest branch of the ophthalmic nerve. This nerve gives rise to two terminal branches, the supraorbital (SON) and supratrochlear nerves (STN). To the best of our knowledge, there are no reports describing the detailed proximal course of these nerves while inside the orbit. Therefore, the goal of this study was to clarify the anatomy of the SON and STN inside and at their exit from the orbit. Twenty sides from ten fresh-frozen cadavers were used in this study. Intra and extra orbital dissections were performed to observe the course of the SON and STN. Additionally, measurements of the nerves were made at these locations. The course of the SON and STN inside the orbit was classified into three groups depending on the STN branching pattern from the SON. The group without any branch from the SON and STN inside the orbit was the most common. The exit points of these nerves were via the supraorbital notch, foramen, or neither a notch nor foramen. A distinct fibrous band was consistently found tethering the nerve except in specimens with nerves traversing a bony foramen. The mean diameters of the SON and STN were 1.3 ± 0.2 and 0.7 ± 0.1 mm, respectively. The results of this study further our knowledge of the course and morphology of the SON and STN and might be useful for better understanding and potentially treating some forms of migraine headache due to SON or STN compression/entrapment. Clin. Anat. 33:332-337, 2020. © 2019 Wiley Periodicals, Inc.

Microsurgical Anatomy of the Superior Wall of the Mandibular Canal and Surrounding Structures: Suggestion for New Classifications for Dental Implantology.

Our goal was to clarify the relationship between the superior wall of the mandibular canal and the presence of teeth. We also sought to study the structural changes of the mandibular canal after tooth loss. Twenty sides from 10 dry mandibles derived from six males and four females were used for this study. The age of the specimens at the time of death ranged from 57 to 91 years. The mandibles were cut in the midline resulting in 20 hemi-mandibles. The presence of teeth (from the second premolar to the third molar) was recorded for each hemi-mandible. The mandibular canal in the body of the mandible was divided into four areas, that is, Areas 1-4. The superior wall of the mandibular canal and a cancellous bone pattern above the mandibular canal were observed. Next, the mandibular canal was horizontally cut at its center and the superior wall of the mandibular canal observed inferiorly. A total of 75 areas (20 dentulous areas and 55 edentulous areas) were produced. The distal view was classified into three groups, Type I (trabecular pattern), Type II (osteoporotic pattern), and Type III (dense/irregular pattern). The Type I pattern was found in 60.0% (12/20) of the dentulous areas and 32.7% of the edentulous areas. While the Type II pattern was found in 15.0% (23/55) of the dentulous areas and 41.8% of the edentulous areas. The inferior view was classified into four groups depending on the surface of the superior wall of the mandibular canal, that is, Class I (trabecular pattern), Class II (osteoporotic pattern), Class III (dense/irregular pattern), and Class IV (smooth).The Class I pattern was seen most frequently (55.0%) in dentulous areas and the Class IV pattern (45.5%) most frequently in edentulous areas. Based on these results, we conclude that the superior wall of the mandibular canal could change following tooth loss. Clin. Anat. 33:223-231, 2020. © 2019 Wiley Periodicals, Inc.

Clinical anatomy of the accessory mandibular foramen: application to mandibular ramus osteotomy.

PURPOSE: An accessory foramen around the mandibular foramen is called an accessory mandibular foramen (AMF). The clinical anatomy of the AMF has not been well described. The aim of this study was to reveal the clinical anatomy of the AMF for a better understanding of its implication during ramus surgeries. METHODS: Twenty-two sides fresh-frozen cadaveric heads with a mean age of 76.2 ± 14.4 years at death underwent dissection. The neurovascular bundles passing through the AMF were observed. Additionally, a hemi-face of a latex injected embalmed cadaver was dissected medially to laterally and the neurovascular bundles of the AMF investigated. RESULTS: A unilateral foramen, bilateral foramina, and absence of foramina were found in 45.4%, 18.2%, and 36.4%, respectively. The origin of the neurovascular bundle entering the AMF was a branch of the maxillary artery in 20% and a tributary of the inferior alveolar vein in 80%. In the latex embalmed cadaver, the AMF was found to contain a branch from the maxillary artery and a tributary of the maxillary vein. CONCLUSION: Given the practical meaning of the specific AMF located in the operative field of the ramus osteotomy, we suggest these be named "foramina for ramus osteotomy."

Anatomical Feasibility Study of the Digastric Branch of the Facial Nerve: A Potential Donor for Facial Nerve Reanimation.

PURPOSE: The digastric branch is the second branch of the facial nerve after emerging from the stylomastoid foramen. To the best of our knowledge, few detailed anatomic studies of the digastric branch have been performed. Moreover, the use of the digastric branch for facial nerve reanimation has not been explored. MATERIALS AND METHODS: Nine sides of 5 fresh frozen cadavers were dissected for anatomic observation of the digastric branch and exploration of the feasibility of the digastric branch as a donor for facial nerve reanimation. The facial nerve trunk (FNT) and digastric branch were readily found by dissection using the tragal cartilage and tragal pointer as landmarks. The length and diameter of the digastric branch were measured, and the digastric branch was repositioned anterior to the FNT and the 2 major extracranial divisions of the FNT. RESULTS: On all sides, the digastric branch existed as a single branch and innervated only the posterior belly of the digastric muscle. The available length of the digastric branch was 13.28 ± 2.47 mm (range, 8.87 to 16.38 mm), and the mean diameter was 0.98 ± 0.31 mm (range, 0.64 to 1.64 mm). The digastric branch reached the FNT and its 2 major divisions without tension. CONCLUSIONS: The results of the present study have clarified the anatomic findings of the digastric branch in detail and the feasibility of using the digastric branch as a potential donor for facial nerve reanimation. The surgeon might consider the use of the digastric branch as a feasible donor for facial nerve reanimation based on the findings from our cadaveric study.

The Feasibility of Using the Posterior Auricular Branch of the Facial Nerve as a Donor for Facial Nerve Reanimation Procedures: A Cadaveric Study.

PURPOSE: Facial nerve paralysis can result in critical complications, including those to the visual, respiratory, and digestive systems. The facial nerve has been reanimated using various nerves, but the posterior auricular nerve (PAN) branching off the facial nerve has not been explored for this purpose. MATERIALS AND METHODS: Ten sides from 6 fresh-frozen adult cadavers were used for dissection of the PAN to explore its potential as a donor for facial nerve reanimation. The facial nerve trunk (FNT) and PAN were consistently and readily identified by deep dissection using the tragal cartilage and tragal pointer as landmarks. The PAN was transected at the point of insertion of its innervated muscles. Its length and diameter were measured, and it was transposed anteriorly to the FNT and its 2 major extracranial divisions. RESULTS: The PAN was observed on all sides. Its available length was 27.11 ± 5.02 mm and its mean diameter was 0.85 ± 0.20 mm. In all specimens, the PAN readily reached the FNT and its 2 major divisions without tension. CONCLUSION: No previous study has explored the use of the PAN as a donor for facial nerve reanimation. Based on the present cadaveric study, surgeons might consider it for this purpose.

A Relationship Between the Supratrochlear Nerve and Trochlea: Anatomical Study and Application to Migraine Headaches.

Supratrochlear nerve (STN) is a terminal branch of the frontal nerve arising from the ophthalmic nerve (V1). Compression of the STN by adjacent structures might result in migraine headaches. The aim of this study was to explore the relationship of the STN and trochlea for a better understanding of potential entrapment of the STN. Nineteen orbits from ten fresh-frozen cadaveric heads were dissected. The relationship of the STN and the trochlea was classified into three types: In type I, the STN passed lateral to the trochlea; In type II, the STN passed through the trochlea; In type III, the STN passed medial to the trochlea. Type I was found in 52.6% (10/19 sides), type II was found in 42.1% (8/19 sides), and type III was seen in 3.4% (1/19 sides). In type III, both the STN and infratrochlear nerve were identified as separate branches. The authors propose a new classification of the pathway of the STN based on its relationship with the trochlea. This study might shed light on headaches emanating from this region.

Supernumerary incisive canals in a cadaver: a rare anatomical variation.

We present a rare anatomical variation in which an additional incisive canal was observed during the routine dissection of the palatal region in a cadaver. The diameter of the incisive and additional incisive canals measured 4.59 mm and 0.91 mm, respectively. Even though this variation is rare, oral surgeons should be aware of such anatomical variations for a better understanding.

Sprouty2 is involved in the control of osteoblast proliferation and differentiation through the FGF and BMP signaling pathways.

Fibroblast growth factor (FGF) and bone morphogenetic protein (BMP) play essential roles in bone formation and osteoblast activity through the extracellular signal-regulated kinase 1/2 (ERK1/2) and Smad pathways. Sprouty family members are intracellular inhibitors of the FGF signaling pathway, and four orthologs of Sprouty have been identified in mammals. In vivo analyses have revealed that Sprouty2 is associated with bone formation. However, the mechanism by which the Sprouty family controls bone formation has not been clarified. In this study, we investigated the involvement of Sprouty2 in osteoblast proliferation and differentiation. We examined Sprouty2 expression in MC3T3-E1 cells, and found that high levels of Sprouty2 expression were induced by basic FGF stimulation. Overexpression of Sprouty2 in MC3T3-E1 cells resulted in suppressed proliferation compared with control cells. Sprouty2 negatively regulated the phosphorylation of ERK1/2 after basic FGF stimulation, and of Smad1/5/8 after BMP stimulation. Furthermore, Sprouty2 suppressed the expression of osterix, alkaline phosphatase, and osteocalcin mRNA, which are markers of osteoblast differentiation. Additionally, Sprouty2 inhibited osteoblast matrix mineralization. These results suggest that Sprouty2 is involved in the control of osteoblast proliferation and differentiation by downregulating the FGF-ERK1/2 and BMP-Smad pathways, and suppresses the induction of markers of osteoblast differentiation.

Adenosquamous Carcinoma in the Midline Dorsum of the Tongue: A Rare Case Report.

Adenosquamous carcinoma (ASC) is a rare malignant tumor of the oral and maxillofacial region that displays histologic features of both adenocarcinoma and squamous cell carcinoma. ASC in the midline dorsum of the tongue is exceedingly rare. We report the case of a 48-year-old man who presented with a painless mass in the midline dorsum of the tongue. Although the case was diagnosed as adenocarcinoma by biopsy, a final diagnosis of ASC was established after surgery. Ten months after the patient's initial visit, no recurrence or metastasis has been noted. ASC in the middle dorsum of the tongue is exceedingly rare, and no examples have been reported hitherto.