In vivo processing and release into the circulation of GFP fusion protein in arginine vasopressin enhanced GFP transgenic rats: response to osmotic stimulation.

Arginine vasopressin (AVP) is a neurohypophysial hormone synthesized as a part of a prepropeptide precursor containing the signal peptide, AVP hormone, AVP-associated neurophysin II and copeptin in the hypothalamic neurosecretory neurons. A transgenic (Tg) rat line expressing the AVP-eGFP fusion gene has been generated. To establish the AVP-eGFP Tg rat as a unique model for an analysis of AVP dynamics in vivo, we first examined the in vivo molecular dynamics of the AVP-eGFP fusion gene, and then the release of GFP in response to physiological stimuli. Double immunoelectron microscopy demonstrated that GFP was specifically localized in neurosecretory vesicles of AVP neurons in this Tg rat. After stimulation of the posterior pituitary with high potassium we demonstrated the exocytosis of AVP neurosecretory vesicles containing GFP at the ultrastructural level. Biochemical analyses indicated that the AVP-eGFP fusion gene is subjected to in vivo post-translational modifications like the native AVP gene, and is packaged into neurosecretory vesicles as a fusion protein: copeptin1-14 -GFP. Moreover, GFP release into the circulating blood appeared to be augmented after osmotic stimulation, like native AVP. Thus, here we show for the first time the in vivo molecular processing of the AVP-eGFP fusion gene and stimulated secretion after osmotic stimulation in rats. Because GFP behaved like native AVP in the hypothalamo-pituitary axis, and in particular was released into the circulation in response to a physiological stimulus, the AVP-eGFP Tg rat model appears to be a powerful tool for analyzing neuroendocrine systems at the organismal level.

[The use of genetic modification techniques in the fluorescent visualization of oxytocin neurons].

Oxytocin, a neurohypophyseal hormone, is synthesized in the magnocellular neurosecretory cells located in the paraventricular and supraoptic nuclei of the hypothalamus, and is secreted into the systemic blood flow from the axon terminals. It is well known that plasma oxytocin is involved in contraction of the uterus during parturition and milk ejection reflex during lactation. It has recently come to the attention of researchers that oxytocin receptors are abundant in the brain and oxytocin is involved in higher brain functions such as bonding between parent and child and trust. Since it was difficult to identify neurohypophyseal hormones, oxytocin- and vasopressin-producing neurons in a living cell, we tried to generate transgenic animals that express fluorescent proteins as a tag protein to visualize neurohypophyseal hormones. In this paper we review the use of genetic modification techniques in the fluorescent visualization of oxytocin neurons and its application.

[Prognostic factors of IgA nephropathy after tonsillectomy].

Tonsillectomy is one of the prevailing treatments for IgA nephropathy. This retrospective study aimed to elucidate prognostic factors for the postoperative kidney function of tonsillectomized patients with IgA nephropathy. Forty consecutive patients with IgA nephropathy who underwent tonsillectomy in our department between 1999 and 2008 were enrolled. They were 21 men and 19 women with ages ranging 14-52 years with an average age of 25.5 years. The patients were classified into remission and non-remission groups based on their kidney function assessed 1 year after surgery according to the clinical guidelines for IgA nephropathy of the Japanese Society of Nephrology. Patients' profiles and preoperative physical findings/laboratory data in the remission group were then compared with those in the non-remission group. The remission and non-remission groups included 13 and 27 patients, respectively. The remission group showed a significantly shorter interval between onset to surgery (2.3 +/- 2.1 vs. 5.0 +/- 6.7 years; p = 0.032), a lower diastolic blood pressure (66 +/- 13 vs. 75 +/- 17 mmHg; p = 0.040), a higher level of serum total protein (7.6 +/- 0.5 vs. 7.0 +/- 0.7 mg/dl; p = 0.015), and a higher degree of tonsillar hypertrophy (I degrees: II degrees: III degrees = 5 : 8: 0 vs. 21 : 6 : 0; p = 0.033) in comparison with the non-remission group. Multiple logistic regression analysis also revealed that patients with a higher level of serum total protein and those with a higher degree of tonsillar hypertrophy were more likely to recover. We should carefully consider these prognostic factors when indicating tonsillectomy for the treatment of IgA nephropathy.

Expression of the c-fos-monomeric red fluorescent protein 1 fusion gene in the spinal cord and the hypothalamic paraventricular nucleus in transgenic rats after nociceptive stimulation.

We generated transgenic rats expressing the c-fos and monomeric red fluorescent protein 1 (mRFP1) fusion gene in the central nervous system after adequate stimulation. In the present study, the time-course of the induction patterns of mRFP1 fluorescence in the spinal cord and the paraventricular nucleus (PVN) was compared with that of Fos-like immunoreactivity (LI) within 24 h after subcutaneous (s.c.) injection of 0.9% saline and 5% formalin in both hind paws. Control rats were not treated. In the control and saline/formalin injected rats, scattered mRFP1 fluorescence in the spinal cord and the PVN was observed at 0 min, though there was little Fos-LI in the same region. The mRFP1 fluorescence in the spinal cord and the PVN was increased at 3h after formalin. On the other hand, the changes of Fos-LI in the spinal cord and the PVN were relatively shorter than those of the mRFP1 fluorescence after formalin. These results suggest that the c-fos-mRFP1 fusion gene expression is slightly upregulated in normal conditions and nociceptive stimulation-induced induction of the fusion gene may be maintained longer than the endogenous c-fos gene expression in the spinal cord and the PVN. Next, nocifensive behavior and mRFP1 fluorescence and Fos-LI in the spinal cord and the PVN after s.c. injection of formalin, 4α-phorbol 12,13-didecanoate (4α-PDD) and saline were compared. Although the 4α-PDD injected rats seldom displayed nocifensive behaviors like s.c. saline injection, 4α-PDD injection caused mRFP1 fluorescence and Fos-LI significantly in the spinal cord and the PVN unlike s.c. saline injection.

Thyroid gland cutaneous fistula secondary to a migratory fish bone: a case report.

INTRODUCTION: We report an extremely rare case of a migratory fish bone penetrating through the thyroid gland. CASE PRESENTATION: A 56-year-old Japanese woman presented with a two-month history of a painless cutaneous fistula in her anterior neck with pus discharge. Endoscopic examinations showed no abnormality, but computed tomography revealed a bone-density needle-shaped foreign body sticking out anteroinferior from the esophagus wall, penetrating through her left thyroid lobe and extending nearly to the anterior cervical skin. A migratory fish bone was suspected, and the foreign body was removed under general anesthetic, combined with a hemithyroidectomy. The injured esophageal mucosa was sutured and closed. Our patient's postoperative course was uneventful, and she was allowed oral food intake seven days after the surgery. No evidence of recurrence was seen over the postoperative follow-up period of 42 weeks. CONCLUSION: We should be aware that fish bone foreign bodies may migrate out of the upper digestive tract and lodge in the thyroid gland.

Efficacy of intratympanic steroid administration on idiopathic sudden sensorineural hearing loss in comparison with hyperbaric oxygen therapy.

OBJECTIVES/HYPOTHESIS: The efficacy of intratympanic steroid administration was examined in comparison with hyperbaric oxygen (HBO) therapy in patients with idiopathic sudden sensorineural hearing loss (ISSNHL). STUDY DESIGN: Retrospective study. METHODS: Two hundred seventy-six consecutive patients with ISSNHL (average hearing levels at 250, 500, 1,000, 2,000, and 4,000 Hz ≥ 40 dB; time from onset to treatment ≤30 days) were enrolled. All the patients were given intravenous hydrocortisone (400 mg/day) followed by tapered doses. In addition, 174 patients underwent HBO therapy (HBO group), and 102 patients received intratympanic dexamethasone injection (IT group). The hearing outcomes were evaluated by six indices; the cure rate, marked-recovery rate (percent of patients with hearing gains ≥30 dB), recovery rate (percent of patients with hearing gains ≥10 dB), hearing gain, hearing level after treatment, and hearing improvement rate compared to the unaffected contralateral ear. RESULTS: There was no significant difference in the cure rate, marked-recovery rate, hearing gain, hearing level after treatment, or hearing improvement rate between the two groups; however, the recovery rate was significantly higher in the IT group than in the HBO group (79.4% vs. 68.4%; P = .048). Multiple logistic regression analysis also showed that patients in the IT group were significantly more likely to recover than those in the HBO group (odds ratio: 2.045; 95% confidence interval: 1.097-3.812; P = .024). CONCLUSIONS: Systemic plus intratympanic steroid administration is more effective than systemic steroids plus HBO therapy, and can be a useful first-choice treatment for ISSNHL.

Induction of arginine vasopressin-enhanced green fluorescent protein expression in the locus coeruleus following kainic acid-induced seizures in rats.

Seizure causes autonomic, neuroendocrine and stress responses. We examined the effects of kainic acid (KA)-induced seizures on the expression of the arginine vasopressin (AVP)-enhanced green fluorescent protein (eGFP) in the locus coeruleus (LC), an area known to contain noradrenergic cells, in AVP-eGFP transgenic male and female rats, with the rationale to identify stressors which induce AVP synthesis in the LC. Subcutaneous (s.c.) administration of KA caused a progressive development of seizure behavior within 24 h. AVP-eGFP fluorescence in the LC was detected 6, 24, and 48 h and 1 week after administration of KA (12 mg/kg). From a nearly undetectable level, it reached a maximum at 48 h after s.c. administration of KA and returned to the basal levels after 2 weeks. AVP-eGFP fluorescence in the LC after s.c. administration of KA was significantly reduced by the pretreatment with MK-801 (nonselective N-methyl-D-aspartate (NMDA) receptor antagonist). In the KA-administered rats, immunohistochemistry for tyrosine hydroxylase (TH) revealed that the eGFP fluorescence was co-localized with TH-immuno-reactivity in the LC. These results suggest that the synthesis of AVP-eGFP is potentially up-regulated in noradrenergic neurons in the LC after KA-induced seizures through the activation of NMDA receptors.

Upregulation of arginine vasopressin synthesis in the rat hypothalamus after kainic acid-induced seizures.

We examined the effects of kainic acid (KA)-induced seizures on arginine vasopressin (AVP) gene expression in the paraventricular (PVN) and the supraoptic nuclei (SON) of normal rats using in situ hybridization histochemistry. We also investigated the expression of the AVP-enhanced green fluorescent protein (eGFP) fusion gene after KA-induced seizures in transgenic rats. AVP heteronuclear (hn) RNA levels in the PVN and the SON were significantly increased at 3h and 24h after subcutaneous (s.c.) administration of KA in normal rats. AVP mRNA levels in the PVN and the SON did not change significantly at 3h, 24h and 1 week after s.c. administration of KA in normal rats. In KA-administered transgenic rats, AVP-eGFP fluorescence in the magnocellular and parvocellular divisions of the PVN and the SON were significantly stronger compared to vehicle-administered transgenic rats. By pretreatment with MK-801 (nonselective N-methyl-D-aspartate, NMDA, receptor antagonist), AVP-eGFP transgenic rats after administration of KA did not show preconvulsive symptoms or convulsions and AVP-eGFP fluorescence in the magnocellular and parvocellular divisions of the PVN and the SON of these rats was significantly reduced. These results suggested that KA-induced increases in AVP transcripts and AVP were prevented by MK801 because seizure activity was prevented or reduced.

Possible contribution of pannexin channel to ATP-induced currents in vitro in vasopressin neurons isolated from the rat supraoptic nucleus.

Release of arginine vasopressin (AVP) from magnocellular neurosecretory cells (MNCs) of the supraoptic nucleus (SON) is controlled by the electrical activity of these neurons. ATP plays a crucial role in the regulation of SON MNCs by activating the purinergic P2X and P2Y receptors. Recent reports of interaction between P2X receptors and pannexin channels have provided new insights into the physiology of the central nervous system; however, the function of pannexin channels has not been assessed in AVP neurons. In the present study, we examined the possible contribution of the pannexin channel in ATP-induced responses in SON AVP neurons. We used the whole-cell patch-clamp technique in isolated rat SON MNCs that express an AVP-enhanced green fluorescent protein transgene. The ATP-induced current was inhibited in a concentration-dependent manner by pannexin channel blockers carbenoxolone and mefloquine, whereas the connexin channel blockers flufenamic acid and lanthanum had no effect. Multi-cell reverse transcriptase-polymerase chain reaction experiments confirmed the existence of pannexin-1 mRNA in AVP neurons. The involvement of the ATP-activated transient receptor potential vanilloid and acid-sensing ion channels was excluded. These results suggest that pannexin channels in SON AVP neurons are involved in the regulatory mechanisms of neuronal activity.

Highly visible expression of an oxytocin-monomeric red fluorescent protein 1 fusion gene in the hypothalamus and posterior pituitary of transgenic rats.

We have generated rats bearing an oxytocin (OXT)-monomeric red fluorescent protein 1 (mRFP1) fusion transgene. The mRFP1 fluorescence was highly visible in ventral part of the supraoptic nucleus (SON) and the posterior pituitary in a whole mount. mRFP1 fluorescence in hypothalamic sections was also observed in the SON, the paraventricular nucleus (PVN), and the internal layer of the median eminence. Salt loading for 5 d caused a marked increase in mRFP1 fluorescence in the SON, the PVN, the median eminence, and the posterior pituitary. In situ hybridization histochemistry revealed that the expression of the mRNA encoding the OXT-mRFP1 fusion gene was observed in the SON and the PVN of euhydrated rats and increased dramatically after chronic salt loading. The expression of the endogenous OXT and the arginine vasopressin (AVP) genes were significantly increased in the SON and the PVN after chronic salt loading in both nontransgenic and transgenic rats. These responses were not different between male and female rats. Compared with nontransgenic rats, euhydrated and salt-loaded male and female transgenic rats showed no significant differences in plasma osmolality, sodium concentration, OXT, and AVP levels. Finally, we succeeded in generating a double-transgenic rat that expresses both the OXT-mRFP1 fusion gene and the AVP-enhanced green fluorescent protein fusion gene. Our new transgenic rats are valuable new tools to study the physiology of the hypothalamo-neurohypophysial system.

Prediction of hearing outcomes by distortion product otoacoustic emissions in patients with idiopathic sudden sensorineural hearing loss.

OBJECTIVE: To investigate whether distortion product otoacoustic emissions (DPOAEs) can be a prognostic indicator of hearing outcomes in patients with idiopathic sudden sensorineural hearing loss (ISSNHL). METHODS: Seventy-eight consecutive patients with ISSNHL were enrolled. DPOAEs were measured at the first hospital visit. Two primary pure tones with a frequency ratio (f2/f1) of 1.2 were used at non-equal sound pressure levels (L1/L2=80/70dB SPL). The DPOAE amplitude was measured at the 11 frequencies of 2f1-f2 with f2 varying from 593 to 6031Hz. All the patients received steroid administration in combination with hyperbaric oxygen (HBO) therapy. Hearing recovery was evaluated by the improvement in hearing compared to the unaffected contralateral ear. Correlations between the hearing improvement rate and five potential prognostic factors (the DPOAE amplitude, patient's age, days from onset to the start of treatment, initial hearing level, and presence of vertigo) were examined by simple and multiple regression analyses. RESULTS: The net DPOAE amplitude in patients with hearing improvement rate ≥50% was significantly larger than that with hearing improvement rate <50% at f2 frequencies of 3031 and 4812Hz (unpaired Student's t-test, p<0.05). A simple regression analysis showed that the hearing improvement rate significantly correlated with the net DPOAE amplitude at f2 frequencies of 3031 and 4812Hz, but not with that at the other f2 frequencies tested. The correlation coefficients were 0.528 and 0.522 for 3031 and 4812Hz, respectively, with p values <1×10(-6). In a multiple regression analysis, the partial correlation coefficients of the net DPOAE amplitude were 0.308 and 0.246 with p values of 0.008 and 0.036 for 3031 and 4812Hz, respectively. CONCLUSION: The significant correlation between hearing recovery and DPOAEs measured before treatment indicates that DPOAEs are a potentially useful means of predicting hearing prognosis in ISSNHL.

Modulators of BK and SK channels alter electrical activity in vitro in single vasopressin neurons isolated from the rat supraoptic nucleus.

Release of arginine vasopressin (AVP) from magnocellular neurosecretory cells (MNCs) of the supraoptic nucleus (SON) is controlled by the electrical activities of the MNCs. Ca(2+)-activated K(+) channels, such as the BK and SK channels, are K(+)-selective ion channels that are activated in response to increased intracellular calcium concentrations. Intrinsic affinities for Ca(2+) permit these channels to exert a negative feedback effect on cellular excitability. In the present study, we used the whole-cell patch-clamp technique to examine the effects of BK or SK channel modulators on neuronal activity in single isolated rat SON MNCs that express an AVP-enhanced green fluorescent protein (eGFP) transgene. Application of BK or SK channel activators abolished the action potentials and induced hyperpolarization. In contrast, the number of action potentials was significantly increased after application of BK or SK channel blockers. Our results suggest that BK and SK channels in AVP neurons may play a role in the regulatory mechanisms of neural activity.

REVIEW: Oxytocin: Crossing the bridge between basic science and pharmacotherapy.

Is oxytocin the hormone of happiness? Probably not. However, this small nine amino acid peptide is involved in a wide variety of physiological and pathological functions such as sexual activity, penile erection, ejaculation, pregnancy, uterus contraction, milk ejection, maternal behavior, osteoporosis, diabetes, cancer, social bonding, and stress, which makes oxytocin and its receptor potential candidates as targets for drug therapy. In this review, we address the issues of drug design and specificity and focus our discussion on recent findings on oxytocin and its heterotrimeric G protein-coupled receptor OTR. In this regard, we will highlight the following topics: (i) the role of oxytocin in behavior and affectivity, (ii) the relationship between oxytocin and stress with emphasis on the hypothalamo-pituitary-adrenal axis, (iii) the involvement of oxytocin in pain regulation and nociception, (iv) the specific action mechanisms of oxytocin on intracellular Ca²(+) in the hypothalamo neurohypophysial system (HNS) cell bodies, (v) newly generated transgenic rats tagged by a visible fluorescent protein to study the physiology of vasopressin and oxytocin, and (vi) the action of the neurohypophysial hormone outside the central nervous system, including the myometrium, heart and peripheral nervous system. As a short nine amino acid peptide, closely related to its partner peptide vasopressin, oxytocin appears to be ideal for the design of agonists and antagonists of its receptor. In addition, not only the hormone itself and its binding to OTR, but also its synthesis, storage and release can be endogenously and exogenously regulated to counteract pathophysiological states. Understanding the fundamental physiopharmacology of the effects of oxytocin is an important and necessary approach for developing a potential pharmacotherapy.

Centrally administered relaxin-3 induces Fos expression in the osmosensitive areas in rat brain and facilitates water intake.

The expression of the relaxin-3 gene, detected as a new member of the insulin superfamily using human genomic databases, is abundantly present in the brain and testis. Intracerebroventricularly (icv) administered relaxin-3 stimulates food intake. Icv administered relaxin (identical to relaxin-2 in humans) affects the secretion of vasopressin and drinking behavior. Relaxin-3 partly binds relaxin family peptide receptor 1, which is a specific receptor to relaxin. Thus, we hypothesized that relaxin-3 would have physiological effects in the body fluid balance. However, the effects of relaxin-3 in the body fluid balance remain unknown. In the present study, we revealed that icv administered relaxin-3 induced dense Fos-like immunoreactivity (Fos-LI) in the rat hypothalamus and circumventricular organs including the organum vasculosum of the lamina terminalis, the median preoptic nucleus, supraoptic nucleus (SON), the subfornical organ (SFO) and the paraventricular nucleus (PVN), that are related to the central regulation of body fluid balance. Icv administered relaxin-3 (54, 180 and 540 pmol/rat) also induced a significant increase in c-fos gene expression in a dose-dependent manner in the SON, SFO and PVN. Further, icv administered relaxin-3 (180 pmol/rat) significantly increased water intake, and the effect was as strong as that of relaxin-2 (180 pmol/rat). These results suggest that icv administered relaxin-3 activates osmosensitive areas in the brain and plays an important role in the regulation of body fluid balance.

Specific expression of an oxytocin-enhanced cyan fluorescent protein fusion transgene in the rat hypothalamus and posterior pituitary.

We have generated rats bearing an oxytocin (OXT)-enhanced cyan fluorescent protein (eCFP) fusion transgene designed from a murine construct previously shown to be faithfully expressed in transgenic mice. In situ hybridisation histochemistry revealed that the Oxt-eCfp fusion gene was expressed in the supraoptic nucleus (SON) and the paraventricular nucleus (PVN) in these rats. The fluorescence emanating from eCFP was observed only in the SON, the PVN, the internal layer of the median eminence and the posterior pituitary (PP). In in vitro preparations, freshly dissociated cells from the SON and axon terminals showed clear eCFP fluorescence. Immunohistochemistry for OXT and arginine vasopressin (AVP) revealed that the eCFP fluorescence co-localises with OXT immunofluorescence, but not with AVP immunofluorescence in the SON and the PVN. Although the expression levels of the Oxt-eCfp fusion gene in the SON and the PVN showed a wide range of variations in transgenic rats, eCFP fluorescence was markedly increased in the SON and the PVN, but decreased in the PP after chronic salt loading. The expression of the Oxt gene was significantly increased in the SON and the PVN after chronic salt loading in both non-transgenic and transgenic rats. Compared with wild-type animals, euhydrated and salt-loaded male and female transgenic rats showed no significant differences in plasma osmolality, sodium concentration and OXT and AVP levels, suggesting that the fusion gene expression did not disturb any physiological processes. These results suggest that our new transgenic rats are a valuable new tool to identify OXT-producing neurones and their terminals.

Robust up-regulation of nuclear red fluorescent-tagged fos marks neuronal activation in green fluorescent vasopressin neurons after osmotic stimulation in a double-transgenic rat.

The up-regulation in the expression of mRNA or protein encoded by the c-fos gene is widely used as a marker of neuronal activation elicited by various stimuli. To facilitate the detection of activated neurons, we generated transgenic rats expressing a fusion gene consisting of c-fos coding sequences in frame with monomeric red fluorescent protein 1 (mRFP1) under the control of c-fos gene regulatory sequences (c-fos-mRFP1 rats). In c-fos-mRFP1 transgenic rats, 90 min after hypertonic saline ip administration, nuclear mRFP1 fluorescence was observed abundantly in brain regions known to be osmosensitive, namely the median preoptic nucleus, organum vasculosum lamina terminalis, supraoptic nucleus, paraventricular nucleus, and subfornical organ. Immunohistochemistry for Fos protein confirmed that the distribution of Fos-like immunoreactivity in nontransgenic rats was similar to those of mRFP1 fluorescence after ip administration of hypertonic saline in the transgenic rats. Several double-transgenic rats were obtained from matings between transgenic rats expressing an arginine vasopressin-enhanced green fluorescent protein fusion gene (AVP-eGFP rats) and c-fos-mRFP1 rats. In these double-transgenic rats, almost all eGFP neurons in the supraoptic nucleus and PVN expressed nuclear mRFP1 fluorescence 90 min after hypertonic saline administration. The c-fos-mRFP1 rats are a powerful tool that enables the facile identification of activated neurons in the nervous system. Furthermore, when combined with transgenes expressing another fluorophore under the control of cell-specific regulatory sequences, activation of specific neuronal cell types in response to physiological cues can be readily detected.

Exaggerated response of a vasopressin-enhanced green fluorescent protein transgene to nociceptive stimulation in the rat.

Nociceptive stimulation elicits neuroendocrine responses such as arginine vasopressin (AVP) release as well as activation of the hypothalamo-pituitary-adrenal axis. We have generated novel transgenic rats expressing an AVP-enhanced green fluorescent protein (eGFP) fusion gene, and we examined the effects of nociceptive stimulation on transgene expression in the hypothalamus after subcutaneous injection of saline or formalin into the bilateral hindpaws in these rats. We have assessed (1) AVP levels in plasma and the changes of eGFP mRNA and AVP heteronuclear RNA (hnRNA) in the supraoptic nucleus (SON) and the paraventricular nucleus (PVN) using in situ hybridization histochemistry, (2) gene expression changes in distinct magnocellular and parvocellular divisions of the PVN, (3) eGFP fluorescence in the SON, the PVN, the median eminence (ME), and the posterior pituitary gland (PP). Plasma AVP levels were significantly increased 15 min after formalin injection. In the same time period, the AVP hnRNA levels in the PVN were increased, especially in the parvocellular division of the PVN in formalin-injected rats. In the same region, eGFP mRNA levels after formalin injection were also significantly increased to a much greater extent than those of AVP hnRNA. The eGFP fluorescence in the SON, the PVN, the ME, and the PP was markedly increased in formalin-injected rats and especially increased in the parvocellular divisions of the PVN. Together, our results demonstrate robust and rapid changes in the expression of the AVP-eGFP transgene in the rat hypothalamus after acute nociceptive stimulation.

Hyalinizing clear cell carcinoma arising from the base of the tongue.

Hyalinizing clear cell carcinoma is a low-grade indolent and rare salivary gland tumor originally described by Milchgrub et al. in 1994. We herein report a case of this tumor of the base of the tongue. A 66-year-old Japanese woman presented with a large painless mass in the throat. Computed tomography and magnetic resonance imaging revealed a 40x30-mm well-defined ovoid tumor arising from the base of the tongue. She underwent tracheostomy followed by a resection of the tumor via the transmandibular approach combined with a right-sided supra-omohyoid neck dissection. Because the tumor invasion of the surrounding tissue was limited, the surgical defect at the base of the tongue was relatively small, and no reconstructive procedure needed to be performed. The tumor was histopathologically diagnosed as hyalinizing clear cell carcinoma of the minor salivary gland. Her postoperative clinical course was uneventful. No aspiration or difficulty upon deglutition was recognized when she started transoral ingestion on the eighth postoperative day. The patient is currently free from disease 21 months after surgery. The pathology, clinical characteristics, and treatment of hyalinizing clear cell carcinoma are bibliographically reviewed.