Investigation of Parotid Cancer Cases Diagnosed as Bell's Palsy at Initial Presentation: The 23 Year Experience of a Single Institution.

Objective: Facial nerve paralysis due to parotid carcinoma is sometimes misdiagnosed as Bell's palsy. This study aimed to compare patients with parotid carcinoma with and without accompanying facial nerve paralysis and to capture the features of patients misdiagnosed with Bell's palsy. Methods: Among 209 patients, 42 (20%) had facial nerve paralysis. Of these 42 patients, 14 had received treatment for facial nerve paralysis without being diagnosed with parotid carcinoma (pretreatment group); the remaining 28 patients had not received any pretreatment and were diagnosed with parotid carcinoma at the initial visit to our hospital (no pretreatment group). This study compared patients with and without facial nerve paralysis and the pretreatment and no pretreatment groups. Results: The 42 patients with facial nerve paralysis had a significantly higher frequency of pain/tenderness and adhesion with surrounding tissues, significantly higher proportions of deep lobe tumors, and a significantly higher proportion of high-grade malignancy. In addition, the disease-specific and disease-free 5 year survival rates were significantly poorer in patients with than in those without facial nerve paralysis. The comparison between the pretreatment and no pretreatment groups revealed no significant differences in any factors nor survival rate. Five patients in the pretreatment group complained of palpable masses or pain/tenderness at the time of their initial treatment for paralysis. Conclusion: Patients with parotid carcinoma who present with facial nerve paralysis at the initial visit have a significantly poorer prognosis. The number of cases in the pretreatment group can be reduced by performing a detailed examination, which can potentially improve the prognosis.

Differential expression of TRKB tyrosine kinase in the two histological types of parotid salivary duct carcinoma with cancer aggressiveness.

Parotid salivary duct carcinoma (SDC) is a rare and aggressive parotid gland carcinoma (PGC). SDC has two origins: de novo and ex pleomorphic adenoma (SDC ex PA); however, because of its rarity, the clinical and molecular features of the two types of SDC are not sufficiently understood. Here, we studied the differences in their clinicopathological and molecular features using clinical specimens while comparing them to those of adenoid cystic carcinoma (AdCC), an intermediate-grade PGC. Clinicopathological analysis of tissues from patients with PGC revealed significant associations between histological types and malignant phenotypes, including nodal metastasis, recurrence, vascular invasion, and neural invasion, and revealed more malignant phenotypes of de novo SDC than of SDC ex PA. The de novo SDC showed a significantly higher frequency of intra-neural invasion (intra-NI) and vascular invasion than AdCC and SDC ex PA. PGCs with high intra-NI were significantly correlated with malignant phenotypes and survival rates. Recently, we observed the overexpression of tropomyosin receptor kinase B (TRKB), a receptor tyrosine kinase, in PGC cells. Here, immunohistochemical and clinicopathological analyses showed that TRKB was highly expressed in SDC cells, particularly de novo SDC cells, and was significantly associated with poor survival and highly malignant phenotypes, including intra-NI and vascular invasion. Collectively, these data show that TRKB expression is significantly elevated in PGC, particularly in de novo SDC, and can be one of the biomarkers of their aggressiveness.

Prognostic value of electroneurography using the midline method for predicting the development of synkinesis after peripheral facial palsy.

OBJECTIVE: The prognostic value of electroneurography (ENoG) for predicting the incidence of synkinesis is reportedly about 40 % using the formal standard method (ENoG-SM). However, the prognostic value of ENoG using the newly developed midline method (ENoG-MM) has not been determined. The aim of this study was to demonstrate the optimal prognostic value and advantages of ENoG-MM for predicting the incidence of synkinesis. METHODS: Participants were 573 patients treated for peripheral facial palsy including Bell's palsy or Ramsay Hunt syndrome. We investigated the clinical presence of any oral-ocular or ocular-oral synkinesis from the medical records. ENoG-MM and ENoG-SM were performed 10-14 days after symptom onset. In ENoG-MM, compound muscle action potentials were recorded by placing the anode on the mental protuberance and the cathode on the philtrum. In ENoG-SM, electrodes were placed on the nasolabial fold. Synkinesis was clinically assessed at the end of follow-up or at >1 year after onset. The sensitivity and specificity of ENoG values for predicting the incidence of synkinesis were compared between ENoG-MM and ENoG-SM at every 5 % around 40 % (range, 30-50 %). RESULTS: At every 5 % of ENoG values around 40 %, ENoG-MM provided higher sensitivity and lower specificity for predicting the incidence of synkinesis compared with ENoG-SM. In particular, when the cut-off value was set at 45 %, sensitivity was 100 % and 95.3 % with ENoG-MM and ENoG-SM, respectively. CONCLUSION: In peripheral facial palsy, ENoG-MM offered higher sensitivity than ENoG-SM for predicting synkinesis. ENoG-MM is useful for screening patients at risk of developing synkinesis. In clinical practice, an ENoG-MM cut-off value of 45 % must be the optimal prognostic value because of the 100 % sensitivity.

Evaluation of Vestibular Functions in a Case of Vestibular Migraine With Successful Treatment With Erenumab.

This is the first report of vestibular examinations before and after the successful treatment of vestibular migraine (VM), a common cause of recurrent vertigo, with calcitonin gene-related peptide (CGRP) receptor inhibitor. We evaluated a 42-year-old female with VM and concomitant probable Meniere's disease, whose headache and dizziness have improved promptly with the administration of erenumab, a CGRP receptor inhibitor. The sensorineural hearing loss in pure-tone audiometry, dysfunctions shown in vestibular examinations (cervical and ocular vestibular evoked myogenic potentials), and mild endolymphatic hydrops shown in gadolinium-enhanced inner ear magnetic resonance imaging, all in the right ear, revealed no change compared with those observed before treatment. This case suggests that VM may be treated by blocking CGRP in the trigeminal ganglion, which suppresses the effects on the vestibular nucleus; herein, no effects were observed in the inner ear despite the clear amelioration of dizziness.

Saccular functions differ for Meniere's disease with and without coexisting headaches.

Objectives: To elucidate the differences between the cases of Meniere's disease (MD) with and without coexisting headaches, especially migraine. The clinical characteristics and vestibular functions are compared. Subjects: Fifteen patients with definite unilateral MD without headaches (MD/H-; 10 males and 5 females; mean age of 55.8 years), and 20 patients with definite unilateral MD with headaches (MD/H+; 3 males and 17 females; mean age of 54.4 years; 15 cases of migraine without aura and 5 cases of suspected migraine or tension-type headache) were enrolled. Methods: The medical records, caloric test results, and cervical vestibular evoked myogenic potential (cVEMP) of the patients were reviewed. A monothermal caloric test by injection of cold water was performed, and canal paresis was assessed. cVEMP was recorded using 500 Hz short tone bursts, and the asymmetry ratio using the corrected amplitude of p13-n23 was determined. Results: The patients in the MD/H- group were predominantly male, whereas more female patients were seen in MD/H+ group (p = 0.004). In the MD/H+ group, the frequency of vertigo and the dizziness handicap inventory (DHI) values were significantly higher than those in the MD/H- group (p = 0.045, <0.001, respectively). There was no statistical difference in the ages, duration of illness, or the hearing levels between both groups. The caloric testing results were abnormal for 10 of the 13 MD/H- cases, and 14 of the 16 MD/H+ cases, which revealed no significant difference between both groups. The cVEMP results revealed positive saccular dysfunction based on the asymmetry ratio of 4 of the 15 MD/H- cases, and 14 of the 20 MD/H+ cases; it was significantly more prevalent in the MD/H+ group than in the MD/H- group (p = 0.018). Multivariate analysis of sex, frequency of vertigo, DHI, and cVEMP results showed significant differences only in the cVEMP results (p = 0.049). Conclusion: The present study revealed differences in patients with MD depending on the presence or absence of headaches. MD without headaches showed a significant male preponderance. MD with coexisting headaches was more associated with severe saccular dysfunctions than MD without headaches. Concomitant headache may affect the manifestations of the vestibular function, especially in the sacculus, in MD cases.

Recurrent facial palsy: Characteristics of ipsilateral and alternative palsies of 104 cases.

OBJECTIVE: Recurrent facial palsy is relatively rare and its clinical details of recurrent facial palsy are not well known. We analyzed recurrent facial palsy cases and clarified its characteristics, especially the difference between ipsilateral and alternative palsies. The analysis aimed to obtain information about recurrent facial palsy that would be useful for delivering explanations to patients and help improve recurrent facial palsy treatments based on the etiology. METHODS: We picked up data from the chart and analyzed the clinical characteristics of patients with recurrent facial palsy from 1243 facial palsy patients (Bell's palsy, VZV-related palsy (Ramsay Hunt syndrome and zoster sine herpete [ZSH])) between 2006 and 2020. RESULTS: Recurrent facial palsy was observed in 104 of 1243 patients (8.4%). There were 35 cases (34%) of ipsilateral palsy and 69 cases (66%) of alternative palsy. The mean age at the onset of the first palsy was 38.9 years old in the ipsilateral group and 48.4 years old in the alternative group, and a significant difference was observed between them. The number of recurrences ranged from 1 to 4. Among the ipsilateral group, 6 patients experienced more than second recurrence. In two cases, the condition failed to resolve after the second recurrence. A serological examination confirmed that 4 cases had recurrent VZV-related palsy (both the first and second palsies were VZV-related) and all of them initially had ZSH: no cases had Hunt syndrome as the first palsy. CONCLUSIONS: The VZV-specific immunity obtained with ZSH might be insufficient to suppress VZV reactivation, and VZV vaccination should be recommended for ZSH patients to prevent further recurrence of VZV-related facial palsy. More than 2 ipsilateral recurrent episodes may be a risk factor for incomplete recovery.

Different results of vestibular examinations and blood flow in cases with transient vascular vertigo/dizziness with or without central nervous system symptoms.

BACKGROUND: The condition of vestibular dysfunction and blood flow in the vertebral artery (VA) in transient vascular vertigo/dizziness (TVV) is not well established. OBJECTIVES: To clarify the pathophysiology of TVV, especially the difference between the isolation of vestibular symptoms. MATERIALS AND METHODS: Ten TVV patients with central nervous system symptoms (TVVw) and 12 TVV patients without central nervous system symptoms (TVVo) underwent duplex color-coded ultrasonographic evaluation of VAs, caloric test, and cervical vestibular-evoked myogenic potential (cVEMP). RESULTS: The mean flow velocity (MV) ratio (peak MV of contralateral VA divided by target VA) was significantly higher in TVVw than in TVVo. There was no difference in the occurrence of canal paresis between TVVw and TVVo. Abnormal asymmetry ratios (ARs) of cVEMP were observed only in TVVo cases (6 of 12 cases), revealing a statistically significant difference in the number of cases between TVVw and TVVo. CONCLUSIONS AND SIGNIFICANCE: Measuring VAs using duplex color-coded ultrasonography and cVEMP may help evaluate TVV. Different results of MV ratio and cVEMP between TVV cases with or without central nervous system symptoms may indicate differences in the pathophysiology between TVVw and TVVo.

Development of the Sphenoid Sinus in Japanese Children: A Retrospective Longitudinal Study Using Three-Dimensional Computed Tomography.

Background: The sphenoid sinus (SS) is located close to vital structures, such as the pituitary gland, and it has significant clinical relevance. This study aimed to clarify the growth pattern of the SS in Japanese children using three-dimensional computed tomography (CT). Methods: Seventy-eight participants with congenital, acquired, or external auditory canal cholesteatoma were recruited and underwent CT more than twice during their treatment. Using the volume-rendered images, the size and volume of the SS were measured. Furthermore, on the scout image, the morphological measurements of the cranial base were determined. Results: The size and volume of the SS increased with age, and peaked at the mean age of 15 years. For males, the volume of the SS was smaller than that of females aged <5 years. The growth rate of the SS was significantly higher in males than in females. The maximum growth rate was detected at the age of 12 years for males and 10 years for females. For females, the increase in the length of the anterior cranial base ceased at approximately 10 years of age and remained constant thereafter. In contrast, for males, the length of the anterior cranial base increased gradually until 15 years of age. Conclusions: Considering the similarity of the periods between the adolescent growth spurt and the maximum growth rate of the SS, changes in the size of the SS may be used as an indicator of the physical growth spurt.

BDNF/TRKB axis provokes EMT progression to induce cell aggressiveness via crosstalk with cancer-associated fibroblasts in human parotid gland cancer.

Parotid gland cancer (PGC) is a rare malignancy and its molecular characteristics remain poorly understood, which has precluded the development of effective drug therapies. Given the poor prognosis of many human cancers in which tropomyosin receptor kinase B (TRKB) is highly expressed, we investigated the involvement of brain-derived neurotrophic factor (BDNF)/TRKB pathway in PGC cells using clinical specimens and observed upregulation of TRKB and BDNF. In primary culture systems of patient-derived PGC cells and cancer-associated fibroblasts (CAFs), PGC cells co-cultured with CAFs exhibited significant upregulation of BDNF and epithelial-mesenchymal transition (EMT). Similar results were observed in PGC cells treated with conditioned medium from co-cultures of PGC cells with CAFs. Administration of TRK inhibitors suppressed BDNF-induced cell migration in PGC cells. Immunohistochemical and clinicopathological analyses of tumors from patients with PGC revealed that BDNF and TRKB were highly expressed in both tumor cells and stromal cells such as CAFs, and TRKB expression levels in PGC cells were significantly correlated with aggressive features, including vascular invasion, nodal metastasis, and poor prognosis. Collectively, these data suggest that the BDNF/TRKB pathway regulates PGC cell aggressiveness via crosstalk with CAFs and is a potential therapeutic target for PGC harboring invasive and metastatic features.

Facial Nerve Palsy in a Young Patient With Acute Lymphoblastic Leukemia Possibly Induced by Herpes Virus Reactivation in the Facial Nerve.

Facial palsy in acute lymphoblastic leukemia (ALL) patients is diagnosed as tumor cell invasion of the central nervous system (CNS) following the ALL guidelines. Facial palsy in a 6-year-old ALL patient was diagnosed as leukemia cell invasion into the CNS by hemato-oncologists. Pretreatment magnetic resonance image (MRI) revealed gadolinium enhancement of the first genu and meatal portion of the facial nerve. After chemotherapy, although the ALL tumor cells disappeared from both the blood and the cerebrospinal fluid, and the facial palsy resolved, a posttreatment MRI showed no change in terms of enhancement of the facial nerve. These findings indicated the possibility of herpetic viral reactivation in the geniculate ganglion of the facial nerve. We must be aware and discuss with hemato-oncologists the possibility that not only tumor cell invasion into the CNS, in accordance with the guidelines, but also that herpetic virus reactivation arising in the facial nerve may be causes of facial palsy.

Thyroid tuberculosis diagnosed as papillary thyroid carcinoma with fever of unknown origin.

Thyroid tuberculosis is a rare disease, very few cases have been reported. It is difficult to diagnose because of no typical characteristics. We report on a patient who underwent surgery for suspected thyroid carcinoma, but who was then diagnosed with thyroid tuberculosis. The patient was a woman in her 70s. She had been diagnosed with chronic renal failure and had been on peritoneal dialysis. She complained of fever and a painful left anterior neck swelling. Computed tomography showed thyroid tumor with cervical lymph node swelling, ultrasound-guided fine needle aspiration cytology was suspected for papillary thyroid carcinoma. We performed surgery to confirm the diagnosis and determine treatment. Procedures for thyroid carcinoma were followed, including left lobectomy of the thyroid gland, central lymph node dissection and right cervical lymph node resection. Pathological examination found no malignant findings in the thyroid tissue but did find a granulation layer even in the right cervical lymph node. Tuberculosis-specific IFN-γ assay was positive, we diagnosed thyroid and cervical lymph node tuberculosis. Postoperatively, the neck pain and fever improved, she was treated as an outpatient with antituberculosis drugs therapy. Thyroid tuberculosis must be considered in patients with immunocompromised, such as this patient, who was on peritoneal dialysis.

Characteristics and Outcomes of Parotid Gland Tumors in Adolescents.

OBJECTIVE: Parotid tumors are rare neoplasms in adults but are exceedingly infrequent in adolescents. We aimed to determine the clinical characteristics and outcomes of parotid tumors in adolescents under 20 years old. METHODS: Between 1999 and 2020, 979 cases of benign parotid tumors and 236 cases of malignant parotid tumors were treated surgically in our department. Of these, 12 benign cases (1.2%) and 9 malignant cases (3.8%) were in adolescents. There were no benign or malignant cases for those aged under 10 years. RESULTS: Regarding the histological type, all benign tumors were pleomorphic adenomas. About half of malignant tumors were mucoepidermoid carcinomas, and excluding one high-grade case, the grade of malignancy was all low/intermediate. The accuracy of fine-needle aspiration cytology among adolescents showed no significant difference with that of adults. In contrast to adults, adolescent benign tumor cases showed a markedly high rate of pleomorphic adenomas and no postoperative facial nerve palsy. Malignant tumors in adolescents had a different trend than adults; low/intermediate-grade malignancies were common and thus few symptoms/signs of malignancy could be observed. As well, the accuracy of fine-needle aspiration cytology was poor. All cases had a good prognosis and are disease-free survival. CONCLUSION: Parotid tumors in adolescents are rare but have several characteristics that are distinct from adults. As long-term observation is required posttreatment in adolescent patients, recurrence in benign pleomorphic adenomas and poor long-term prognosis in malignant tumors, especially for those with low/intermediate-grade malignancy, are more likely to be observed.

Optimal current intensity for supramaximal stimulation during electroneurography for facial palsy.

OBJECTIVE: To determine the optimal current intensity for supramaximal stimulation during electroneurography (ENoG) for facial palsy. METHODS: Forty patients with unilateral facial palsy (32 Bell's palsy, 7 Ramsay Hunt syndrome, and 1 temporal bone fracture) were enrolled. All patients were initially treated with intravenous steroid injections and examined using ENoG. Compound muscle action potentials (CMAPs) of the orbicularis oris muscle were measured on the paralyzed and healthy sides. Stimulation current intensity was varied every 5 mA from 20 mA to 50 mA using two recording methods (the midline and standard methods). The CMAPs of both sides were monitored to see whether they would saturate under the high current intensity stimulation or not. RESULTS: No obvious saturation of CMAPs was observed in either side with the midline or standard methods. Statistically, a current of 35 mA and above in the healthy side, and 30 mA and above in the paralytic side, resulted in no difference to each side when using the midline recording method. On the other hand, a current of 35 mA and above in the healthy side, and 25 mA and above in the paralytic side, resulted in no difference to each side when using the standard recording method. CONCLUSIONS: These results indicate that a current intensity of at least 35 mA is required to achieve supramaximal stimulation on the healthy side in a patient with unilateral facial nerve palsy. Clinically, for simplicity or standardization purposes, if the same current intensity is introduced bilaterally for ENoG measurements, adopting 40 mA (35 mA plus 10-20%) stimulation would be appropriate for supramaximal stimulation, while being cognizant of the potential effects of artifacts from other muscles.

Facial nerve course in the temporal bone: Anatomical relationship between the tympanic and mastoid portions for safe ear surgery.

OBJECTIVE: Avoidance of iatrogenic injury to the facial nerve is crucial during ear surgery. The anatomical relationship between the tympanic portion of the facial canal (FC) and the mastoid portion of the facial nerve was analyzed using multi-slice computed tomography (CT) scans to avoid iatrogenic facial nerve injury. METHODS: In total, 364 ears of 351 patients who underwent CT scans were enrolled. The 364 ears were divided into two groups: 281 ears with middle ear inflammation (MEI) and 83 ears without middle ear inflammation (non-MEI). The anatomical relationship between the tympanic portion of the FC and mastoid portion of the facial nerve was analyzed on multi-slice CT images. The ears were categorized into three subgroups based on the course of the mastoid portion of the facial nerve to the tympanic portion of the FC: ("lateral running course", LRC), "on the tympanic line course" (OL), and "medial running course" (MRC). The proportions of ears in each subgroup were compared between the MEI and non-MEI groups. RESULTS: Overall, 15% of ears were categorized as LRC, 30% were OL, and 55% were MRC. In the MEI group, the proportions of LRC, OL, and MRC ears were 17%, 32%, and 51%, respectively, whereas they were 7%, 24%, and 69% in the non-MEI group. The proportion of LRC ears in the MEI group was significantly higher than that in the non-MEI group. CONCLUSIONS: Especially in patients with MEI, a more LRC for the facial nerve increases the risk of facial nerve injury during posterior tympanotomy or canal wall down mastoidectomy. The course of the facial nerve in the temporal bone should be evaluated before surgery on multi-slice CT images.

Latency shift in compound muscle action potentials during electroneurography in facial palsy.

OBJECTIVE: Electroneurography (ENoG) reliably predicts the prognosis of facial palsy. However, the results of ENoG are dependent on the location, where the wave is detected, as a compound muscle action potential (CMAP) arising from the facial muscles. To minimize errors in prognostic prediction, we analysed the latencies of facial CMAPs. MATERIALS AND METHODS: Fifty-seven patients with unilateral peripheral facial palsy and 24 healthy volunteers were enrolled. Amplitudes, negative peak latencies (NPL), and rise latencies (RL) of CMAPs were measured on the paralysed and healthy sides in patients and in healthy volunteers. The relationships of these latencies with ENoG values and the lowest House-Brackmann (H-B) scores were also analysed. RESULTS: The amplitude of CMAP on the paralysed side was smaller, and NPL and RL were longer, than those on the healthy side in patients and healthy volunteers (p < 0.01). In patients, there was no difference in NPL between the ENoG < 40% group and the ENoG ≥ 40% group. Conversely, there was a significant difference in RL between the ENoG < 40% group and ENoG ≥ 40% group (p = 0.03). No relationships were observed between NPL or RL and the lowest H-B score. CONCLUSIONS: NPL and RL of CMAP on the paralysed side were equivalent or longer than those on the healthy side. During ENoG for facial palsy, CMAP should be measured on the healthy side first, and then detected (and the amplitude measured) on the paralysed side with reference to CMAP latency on the healthy side, to reduce errors in detecting facial CMAPs.

Electroneurography value as an indicator of high risk for the development of moderate-to-severe synkinesis after Bell's palsy and Ramsay Hunt syndrome.

Background: The degree of distress caused by the sequelae of peripheral facial nerve palsy usually depends on the severity of synkinesis. Objective: To clarify whether electroneurography (ENoG) can predict the severity of synkinesis after peripheral facial nerve palsy. Materials and methods: One-hundred and fourteen patients treated for facial nerve palsy at our hospital from April 2014-September 2016 were retrospectively reviewed. ENoG was performed 10-16 days after symptom onset. Patients were classified into Groups A (ENoG value 10%-20%, n = 9) and B (ENoG value <10%, n = 21). Eight months after symptom onset, electrophysiological and symptomatic outcomes were evaluated as the aberrant regeneration ratio of the blink reflex and the total synkinesis score of the Sunnybrook facial grading system, respectively. The outcomes of the groups were compared. Results: Group B had a significantly higher median aberrant regeneration ratio (0% versus 87%, p=.015), median total synkinesis score (1 versus 3, p < .001), and incidence of moderate-to-severe synkinesis (0% versus 57.2%, p=.003) than did Group A. Conclusions and significance: Patients with an ENoG value of <10% have higher risks of aberrant regeneration and moderate-to-severe synkinesis than those with an ENoG value of 10%-20%. Patients with ENoG values of <10% may require rehabilitation to prevent synkinesis.

Regulatory T and B cells in peripheral blood of subcutaneous immunotherapy-treated Japanese cedar pollinosis patients.

AIM: The aim of this study was to clarify whether there are more regulatory T (Treg) and regulatory B (Breg) cells, and higher levels of IL-10-related transcription factors in subcutaneous immunotherapy (SCIT)-treated pollinosis patients than in non-SCIT-treated patients. METHODS: Japanese cedar pollinosis patients undergoing SCIT had received treatment for at least 2.8 years. Peripheral blood mononuclear cells were used for flow cytometer analyses and mRNA measurement. RESULTS: The numbers of type 1 regulatory T (Tr1)-like cells and Breg cells, and expression of E4BP4 mRNA by peripheral blood mononuclear cells in SCIT-treated patients were higher than those in non-SCIT-treated patients. CONCLUSION: Tr1-like cells, Breg cells and E4BP4 may be involved in the effectiveness of SCIT.

Clinical features of poorly differentiated thyroid papillary carcinoma.

OBJECTIVE: To investigate the clinical feature of the poorly differentiated thyroid papillary carcinoma. METHODS: We investigate retrospectively 276 thyroid papillary carcinoma patients who underwent initial treatment at our Department who underwent initial treatment at our Department during the 13-year period from 2000 to 2012. We examine the pathological samples of papillary carcinoma retrospectively to investigate the prevalence of a poorly differentiated component in the tumor. Then the disease-specific survival rate, metastasis-free survival rate, and relapse-free survival rate were compared between patients with or without a poorly differentiated component. In addition, well differentiated carcinoma and poorly differentiated carcinoma were compared in relation to the age, sex, TNM stage, and recurrent laryngeal nerve infiltration. RESULTS: It was considered appropriate to define tumors with a poorly differentiated component of 10% or more as poorly differentiated carcinoma. There was a significant difference of the T classification but not the N classification between well and poorly differentiated thyroid papillary carcinomas. The disease-specific survival rate, metastasis-free survival rate, and relapse-free survival rate of patients with poorly differentiated carcinoma was significantly lower than that of patients with well differentiated carcinoma, and we considered that this might be due to the higher frequency of local infiltration in patients with poorly differentiated tumors. CONCLUSION: The higher relapse rate compared with well differentiated carcinoma suggests that careful postoperative follow-up of patients with poorly differentiated carcinoma is important, particularly surveillance of distant metastasis.

TRKB tyrosine kinase receptor is a potential therapeutic target for poorly differentiated oral squamous cell carcinoma.

It has been reported that one of the neurotrophin receptors, tropomyosin receptor kinase B (TRKB), is frequently overexpressed in various tumor tissues including oral squamous cell carcinoma (OSCC), and that its upregulation promotes tumor progression in human cancers. However, the correlation between TRKB overexpression and clinicopathological characteristics is not fully elucidated. Here, we present the correlation between the expression levels of TRKB and/or its secreted ligand, brain-derived neurotrophic factor (BDNF), and clinicopathological characteristics, especially regarding tumor differentiation, tissue invasion, and disease-free survival in patients with OSCC. The results obtained through immunohistochemical analysis of human OSCC tumor specimens showed that the expression levels of TRKB and/or BDNF, were significantly higher in moderately and poorly differentiated OSCC (MD/PD-OSCC) tumor cells than in well differentiated cells (WD-OSCC). Moreover, the OSCC tumors highly expressing TRKB and/or BDNF exhibited promotion in tissue invasion and reduction in disease-free survival in the patients. In an orthotopic transplantation mouse model of human OSCC cell lines, administration of a TRKB-specific inhibitor significantly suppressed the tumor growth and invasion in PD-OSCC-derived tumor cells, but not in WD-OSCC-derived tumor cells. Moreover, the TRKB inhibitor selectively blocked BDNF-induced tumor cell proliferation and migration accompanied with the suppression of TRKB phosphorylation in PD-OSCC but not in WD-OSCC in vitro. Taken together, these data suggest that the BDNF/TRKB signaling pathway may regulate tumor progression in poorly differentiated OSCC. Expression levels of signal molecules may be an accurate prognosis marker for tumor aggressiveness, and the molecules may be an attractive target for new OSCC therapies.