[Time course of changes in gustatory function test results and subjective symptoms, and predictive factors for response in patients with taste disorder receiving 24-week zinc replacement treatment].

In a taste disorder, an agreement between patients' complaints and gustatory function test results is not necessarily found both at the initial hospital visit and during the course of treatment; therefore, it is difficult to assess treatment responses and review treatment strategies based on the assessed treatment responses. The present study investigated the time course of changes in disc gustometry results and subjective symptom scores measured at 4-week intervals in 44 patients with a taste disorder who were considered eligible for zinc replacement treatment and who received polaprezinc at a dose of 150 mg/day (equivalent to a 34 mg/day dose of zinc) for up to 24 weeks. The study also examined the potential differences in treatment outcomes according to the predictive factors for response such as patient background and assessed disc gustometry results during the course of treatment. Results indicated that disc gustometry results and subjective symptom scores showed different time courses of changes. The response rate as measured by disc gustometry was 47.7% at week 12 of treatment, and showed a subsequent slow increase to 56.8% at week 24. On the other hand, subjective symptom scores showed a time-proportional improvement up to week 24. Among the patients included in the present study, a clear difference was found according to the presence or absence of an improving trend as determined by disc gustometry at week 12 of treatment, although there were no differences in ultimate treatment responses, including categories of taste disorder, according to patient background. Patients showing a trend toward improvement had significantly better treatment responses in terms of both ultimate response rates and subjective symptom scores, whereas patients showing no trend toward improvement were less likely to respond to the subsequent 12-week continued treatment.

Laryngeal granuloma in experimental rats with gastroesophageal reflux disease and mechanically injured vocal cord mucosa.

OBJECTIVE: This study was undertaken to elucidate the mechanisms underlying laryngeal granuloma formation in a rat model of gastroesophageal reflux disease (GERD) with mechanically injured vocal cord mucosa. METHODS: The rat model of GERD was surgically created by tying the pyloric sphincter and ligating the transitional region between the forestomach and the glandular portion (limiting ridge). The control rats received only a midline incision. In all the animals, a plastic bar was inserted into the trachea, and moved vertically thrice in 3 seconds to cause mechanical injury of the vocal cord mucosa. The rats were sacrificed 2 weeks postsurgically, and their pharynx and larynx were observed histologically. RESULTS: Granulomas were observed in the vocal cord mucosa of the GERD group (3 of 5 animals); they presented a similar pathological structure to that of human laryngeal granulomas. In contrast, only abrasions and blisters were observed on the vocal cord mucosa in the control group (all 5 animals). CONCLUSIONS: The development of laryngeal granuloma may involve both mechanical injury and gastric acid reflux.

[The effect of zinc agent in 219 patients with zinc deficiency-inductive/ idiopathic taste disorder: a placebo controlled randomized study].

Diagnosis and treatment of taste disorders are challenging because the disorder can only be determined by the awareness of the patient. Hence, these disorders still require comprehensive evidence. We conducted a randomized, placebo-controlled double-blind study to investigate the effect of polaprezinc, a zinc-containing agent, in 219 patients with either zinc deficiency-inductive or an idiopathic taste, disorder. As a result, the zinc-treated arm experienced a statistically significant improvement against the placebo-treated arm in the perceptible threshold scores of the filter-paper disk method 8 weeks after the administration of the investigational drug. Moreover, the effect lasted for 4 weeks after discontinuation of the drug. However, the effective ratios based on the initial criteria were 55.6% in the treatment group and 43.2% in the placebo, where no statistical significance was recorded. Sex and degree of depression could be two of the potential factors to explain this discrepancy. Furthermore, the effect was not significant among male patients and patients with a high depression score based on the Self-rating Depression Scale (SDS) test. These results indicate that determining the symptom among such patients remains undisclosed. Whereas, in approximately 77%, or 168 patients with "normal" SDS scores and with completely impaired taste qualities, the ratio of effective cases reached 60.9% in the zinc-treated group, the ratio of the placebo-treated group reached 39.5%, resulting in a statistical significance. This may be partly because of a problem in the adaption of male subjects to the gustatory analyses, especially to the identification of saltiness and sourness. Care must also be taken regarding the depressive state of patients when diagnosing and treating taste disorders. Taste disorders caused by depression may not be cured by zinc supplementation due in part to the fact that the symptom is based on a mental issue, and due in part to the conservative responding bias generated by the depression itself, which may inhibit accurate and precise diagnosis of the disorder. In conclusion, administration of a zinc agent is effective for patients with taste disorders, provided selection of appropriate patients is performed, and that proper examination and evaluation are conducted. The present study also indicated that examining depressiveness based on the SDS scores and investigating disturbance of each taste quality using the filter-paper disk method are recommended for the diagnosis and determination of the treatment effect of a taste disorder.

Innate immune reactions in locally limited tonsillar cancer.

Tonsillar cancers often present as locally limited tumors but with cervical metastases. When the primary tumors of tonsillar cancers with cervical metastases are as small as clinically occult, the clinical features are diagnosed as primary-unknown cervical metastases. However, little is known as to why small tonsillar cancers establish cervical metastases. The aim of this study was to investigate a possibility that innate immune reactions might suppress the growth of tumors arising in the palatine tonsils, because the palatine tonsils contain various immune effector cells. Infiltration of natural killer (NK) cells and macrophages, which are major innate immune cells, in surgically removed tumors from patients with locally limited tonsillar cancers and tongue cancers was immunohistochemically studied by using anti-CD57 and anti-CD68 antibodies. Phagocytosis of the tumor cells by macrophages was also studied by dual immunofluorescence labeling. The number of infiltrating CD57+ NK cells and CD68+ macrophages was significantly increased in locally limited tonsillar cancers in comparison to normal tonsils and tongue cancers. The phagocytosis of tumor cells by CD68+ macrophages was observed significantly more frequently in tonsillar cancers than in tongue cancers. These results indicated that the innate immune reactions were more strongly induced in locally limited tonsillar cancers than in tongue cancers, and might therefore suppress the growth of primary tumors in palatine tonsils. The innate immune reactions against cancers in palatine tonsils were suggested to be one of the possible etiologies for the developing of primary-unknown cervical metastases.

A case of typical carcinoid of the larynx.

We report herein a rare case of typical carcinoid occurring primarily in the epiglottis. The patient was a 70-year-old man. On initial examination, a polypoid lesion with irregular surface near the center right-hand side of the laryngeal surface of the epiglottis was observed, and a biopsy was performed. Pathological examination of the specimen suggested the possibility of adenocarcinoma. Surgical excision was performed by means of laryngomicrosurgery. A Weerda-type laryngoscope was used to open the larynx, supplemented by rigid nasal sinus surgery endoscopes, and the right-hand half of the epiglottis were excised was ensured using a CO(2) laser. Postoperative pathological diagnosis was negative for adenocarcinoma and squamous cell cancer; typical carcinoid was diagnosed according to the World Health Organization criteria. Aspiration occurred postoperatively, swallowing training was therefore provided, and the patient was discharged from hospital 2 months after surgery when he was able to eat normally. As of 4 years after surgery, the patient remains under follow-up observation by means of PET-CT and neck, thoracic, and abdominal CT administered at appropriate intervals, but no findings indicating obvious recurrence or metastasis have been observed, and the patient displays good swallowing function.

Pathological characteristics of the epiglottis relevant to acute epiglottitis.

OBJECTIVE: The characteristic swelling of acute epiglottitis is thought to be caused by histological factors in the epiglottis. We investigated the relationships between histological findings and the pathology of acute epiglottitis. METHODS: We examined 23 autopsy cases. For 16 of these, histological assessments were performed. In the remaining 7 subjects, physiological saline was injected at the lingual tonsil. RESULTS: These histological findings revealed abundant laryngeal glands on the laryngeal surface compared with the lingual surface. With regard to the blood vessels and lymphatic vessels, more of these vessels tended to be apparent on the lingual surface compared with the laryngeal surface. In each of the physiological saline injected subjects, almost no swelling of the lingual tonsil occurred, but the lingual surface of the epiglottis was swollen, and morphological changes had occurred that resembled those in acute epiglottitis. CONCLUSION: Periepiglottic tissues are rich in lymphatic tissues, and it appears easy for inflammation to spread to the epiglottis itself via the gland's own rich networks of blood and lymphatic vessels. In addition, according to the video observation, it appeared that the liquid ingredient that exudes at the inflamed the lingual tonsil may cause swelling the lingual surface of the epiglottis.

[A comparative study of concurrent chemoradiotherapy with S-1 or CDDP for pharyngeal or laryngeal cancer].

Adverse events and therapeutic effects were analyzed in patients with pharyngeal or advanced laryngeal squamous cell carcinomas(SCCs)receiving concurrent chemoradiotherapy (CCRT) with S-1 or weekly CDDP between 2004 and 2007. Low-dose CDDP (25 mg/m2) was administered once a week and S-1 (65 mg/m2) was administered for 3 weeks with one-week rest during conventional radiation with 2 Gy/fraction. Both of the two CCRT regimens showed little toxicity with grade 4 toxicities in less than 5%of the patients. However, CCRT with S-1 more frequently induced grade 3 and 4 oral mucositis than CCRT with CDDP. As a result, the completion rate of CCRT with S-1 was lower than that of CCRT with CDDP. The two regimens achieved a similar complete response rate of the primary sites, local control rate(LCR)and larynx preservation rate; the LCR for T1 and 2 disease was more than 70%. However, the LCR for T3 or 4 disease by the two regimens was less than 50%. CCRT with S-1 showed significantly higher LCR in patients with poorly or undifferentiated SCCs than those with well or moderately-differentiated SCCs. It is suggested that the two CCRT regimens are useful treatment modalities for patients with locally(primary site)non-advanced pharyngeal or laryngeal SCCs, and that CCRT with S-1 is highly sensitive to poorly or undifferentiated SCCs. In order to achieve local control and larynx preservation, more intensive CCRT might be necessary for patients with locally(primary site)advanced pharyngeal or laryngeal SCCs.

Endotoxin tolerance attenuates airway allergic inflammation in model mice by suppression of the T-cell stimulatory effect of dendritic cells.

Prior exposure of dendritic cells (DCs) and monocytes/macrophages to LPS causes unresponsiveness to subsequent LPS stimulation, a phenomenon called endotoxin tolerance (ET). ET impairs antigen presentation of these cells to T cells by down-regulating expression of MHC class II and co-stimulatory molecules such as CD86 and CD40. Some epidemiological studies have shown that endotoxin acts as a protective factor for allergic diseases. Accordingly, LPS has beneficial effects on the onset of airway allergic inflammation in model animals by T(h)1 skewing or induction of regulatory T cells. However, results derived from asthma model animals are controversial, probably due to the difficulty of handling LPS. We previously generated a monoclonal agonistic antibody against Toll-like receptor (TLR) 4, named UT12, which mimics the biological activities of LPS, exhibiting more potent and sustained ET than does LPS. In this study, we took advantage of UT12 to generate prolonged ET to explore the possibility that ET is involved in the inhibitory effects of the TLR4 signals on asthma model mice. Induction of ET by UT12 inhibited the capacity of DCs to expand ovalbumin (OVA)-specific T(h)2 and T(h)17 cells, without inducing T(h)1 cell or regulatory T-cell populations or producing inhibitory cytokines. Accordingly, administration of UT12 before the OVA sensitization significantly suppressed airway allergic inflammation by OVA inhalation. Taken together, these results demonstrate that ET induced by activating TLR4 signals attenuates airway allergic inflammation through direct suppression of the T-cell stimulatory effect of DCs in asthma model mice.

Relationship between squamous cell carcinoma antigen and the clinical severity of allergic rhinitis caused by Dermatophagoides farinae and Japanese cedar pollen.

OBJECTIVES: Allergic rhinitis is known to be related to the Th2-type immune response, but no sensitive biomarker of severity yet exists. Serum squamous cell carcinoma antigen (SCCA) is clinically used as a popular tumor biomarker. We have demonstrated that SCCA is related to allergic diseases such as asthma. The purpose of the present study was to clarify the relationship between allergic rhinitis and SCCA, which had not yet been investigated. METHODS: We compared the serum SCCA levels in patients with allergic rhinitis due to Japanese cedar pollen and Dermatophagoides farinae with those in normal subjects. Thereafter, the correlations between the clinical severity of allergic rhinitis and the serum levels of SCCA were investigated. Furthermore, the influence of 8 variables (serum levels of SCCA, immunoglobulin E, eosinophil cationic protein, and eosinophils; age; gender; oral administration of antiallergic or antihistaminic agents; and use of nasal drops) in regard to the severity of allergic rhinitis was studied by a multiple regression analysis. RESULTS: The SCCA levels of the D farinae group were statistically higher than those of the control group, and they correlated with the severity of rhinitis. Among the 8 variables, only the SCCA level was found to be a predictive factor of severity on a multiple regression analysis. No relationship between SCCA level and Japanese cedar pollen allergy was demonstrated. CONCLUSIONS: These results suggest that the serum SCCA level may be a useful biomarker to evaluate the severity of allergic rhinitis caused by D farinae.

Coccoid Helicobacter pylori exists in the palatine tonsils of patients with IgA nephropathy.

PURPOSE: Helicobacter pylori infection is acquired by oral ingestion. H. pylori has been reported to be present in the palatine tonsils. To clarify the route and mode of infection, the prevalence of tonsillar H. pylori was evaluated, and an attempt was made to culture tonsillar H. pylori. METHODS: In a prospective study, 55 patients with recurrent pharyngotonsillitis or IgA nephropathy underwent a tonsillectomy. The carbon 13-urea breath test and enzyme-linked immunosorbent assay for the detection of H. pylori IgG antibodies in the serum were performed. Tonsillar H. pylori was cultured under conventional culture conditions for gastric H. pylori with or without the following shock methods; heat shock, hydrogen-peroxide-degrading compounds, or parasitizing amoebae. Immunofluorescence and immunoelectron microscopy using antibodies against H. pylori and cytotoxin-associated antigen A were used to identify tonsillar H. pylori. RESULTS: H. pylori in the coccoid form was present in tonsillar crypts. Of 55 patients, 43 (78.2%) had tonsillar H. pylori, and 15 (27.3%) were infected with gastric H. pylori. All patients with gastric H. pylori also had tonsillar H. pylori (p < 0.01). Cytotoxin-associated antigen A was observed in 38 (88.4%) of 43 tonsillar H. pylori. Tonsillar H. pylori could not be cultured in any culture conditions. All patients with IgA nephropathy had tonsillar H. pylori (p < 0.01). CONCLUSIONS: The present research might provide some insight into clarifying the route and mode of H. pylori infection. Our findings may indicate that tonsillar H. pylori is one of the antigens causative of IgAN.

[Cepharanthin effect on radiation-induced xerostomia and taste disorder in patients with head and neck cancer].

In evaluating the effect of cepharanthin on xerostomia and taste disorder in 40 patients undergoing radiotherapy for head and neck cancer, we administered cepharanthin intravenously during chemoradiotherapy to 22 patients, with 18 others as a control group. Cepharanthin did not significantly affect salivary secretion during and after chemoradiotherapy, although taste disorder and oral discomfort were alleviated. Cepharanthin may thus be effective in maintaining the quality of life of patients with head and neck cancer.

Amelioration of experimental allergic rhinitis with suppression of topical immune responses by lack of IL-27/WSX-1 signaling.

BACKGROUND: Allergic rhinitis is 1 of the most common atopic diseases with strong similarity to asthma. Interleukin (IL) 27 is an immunosuppressive cytokine, and lack of the IL-27 receptor (WSX-1) resulted in exacerbation of allergic airway hyperresponsiveness. OBJECTIVE: To address the role of IL-27/WSX-1 in the rhinitis model compared with the asthma model. METHODS: Wild-type or WSX-1(-l-) female mice were immunized intraperitoneally 4 times with ovalbumin adsorbed to aluminum potassium sulfate at a 1-week interval. The sensitized mice were then challenged for 14 days with ovalbumin intranasally from days 22 to 35. Clinical scores, serum antigen specific IgE levels, and cytokine production in the nasal lavage fluid were examined. Cytokine and chemokine expression in the cervical lymph nodes, nasopharynx-associated lymphoid tissues, and nasal mucosa was also examined. RESULTS: WSX-1(-l-) mice developed augmented immune responses in the serum (IgE production), cervical lymph nodes (cytokine and chemokine expression), and nasopharynx-associated lymphoid tissues (cytokine and chemokine expression), whereas local responses, such as clinical scores and nasal lavage fluid cytokine production, were reduced in WSX-1(-l-) mice. Expression of some chemokines was also reduced in the nasal mucosal tissues of WSX-1(-l-) mice. CONCLUSION: In contrast to the immunosuppressive role observed in the asthma model, IL-27/WSX-1 topically plays an exacerbating role in the pathogenesis of allergic rhinitis, presumably through differential expression of chemokines.

A zinc-containing compound, Polaprezinc, is effective for patients with taste disorders: randomized, double-blind, placebo-controlled, multi-center study.

CONCLUSIONS: The effect of a zinc-containing compound, Polaprezinc, was shown to clinically improve the disease conditions of idiopathic taste disorders with no serious side effects in a well controlled double-blinded clinical study. OBJECTIVES: The purpose of the present study was to evaluate the efficacy and safety of a zinc-containing compound in the treatment of patients with idiopathic taste disorders, including patients with low serum zinc, by a Good Clinical Practice (GCP)-compliant, randomized, placebo-controlled, double-blind, multi-center clinical study. SUBJECTS AND METHODS: A group of 109 patients suffering from taste disorders was assigned into placebo and three treatment groups. Each group of patients was given either placebo (n=28), or 17 mg (n=27), 34 mg (n=26) or 68 mg (n=28) of oral zinc, Polaprezinc preparations, daily for 12 weeks. RESULTS: The group of patients given 68 mg zinc showed a significant improvement in their gustatory sensitivity compared with the placebo group. The most common side effects observed were increase in serum triglyceride and serum alkaline phosphatase, decrease in serum iron, and some gastrointestinal incidents, although they were not serious.

Histological changes of the pharynx and larynx in rats with chronic acid reflux esophagitis.

CONCLUSIONS: The histological changes of the pharynx and the larynx associated with surgically induced chronic acid reflux esophagitis were observed in rats. Chronic inflammatory change due to gastric acid reflux was found microscopically in the pharynx and larynx. This indicated that inflammatory changes due to gastric acid reflux are associated with the pathogenesis of laryngopharyngeal reflux disease (LPRD). OBJECTIVE: To clarify the pathological mechanism of LPRD by studying the histological changes of the pharynx and the larynx in rats with chronic acid reflux esophagitis. MATERIALS AND METHODS: An experimental rat model of chronic acid reflux esophagitis was created surgically. The pharynx, larynx, trachea, lung, and esophagus of these rats were observed histologically every 2 weeks until 20 weeks after the operation. RESULTS: At 8 weeks after the operation, mucosal thickening and inflammatory cell infiltration were observed in the hypopharynx of the rat model. Moreover, chronic inflammation with proliferation of fibroblasts, deposition of collagen fibers, and proliferation and dilatation of the capillaries were found as time progressed. However, little macroscopic change was observed in the hypopharyngeal mucosa. In addition, at 16 weeks post-operation, inflammatory cell infiltration was identified in the nerve cells around the thoracic esophagus, the arytenoid region, and the lung.

Serum concentrations of laminin gamma2 fragments in patients with head and neck squamous cell carcinoma.

BACKGROUND: The laminin (LN) gamma2 chain expression has been linked to tumor invasion and prognosis. To provide a convenient clinical use, procedures that analyze LNgamma2 expression by using the serum and/or urine of patients should be developed. METHODS: The serum concentrations of the N-terminal fragments of the LNgamma2 chain in 73 patients with head and neck squamous cell carcinomas were measured by immunoassay. RESULTS: The concentrations of the LNgamma2 fragments ranged between 14.5 and 324.2 ng/mL, and the normal upper limit was estimated to be 50 ng/mL. The LNgamma2 fragment concentrations increased according to the T classification. The amount of elevated LNgamma2 fragment concentrations decreased after the use of curative treatments. Three patients displayed a continuous increase of the concentrations and subsequently died of the diseases. CONCLUSIONS: The serum concentrations of the LNgamma2 fragments may prove useful in assessing the treatment results and clinical courses of patients with head and neck squamous cell carcinomas.

Helicobacter pylori in the palatine tonsils of patients with IgA nephropathy compared with those of patients with recurrent pharyngotonsillitis.

Helicobacter pylori infection is acquired by oral ingestion. However, the morphology and microscopic localization of H pylori in the human oral cavity and pharynx are unknown. In the present study, we performed immunohistochemistry, immunoelectron microscopy, in situ hybridization, and polymerase chain reaction to identify H pylori in the palatine tonsils of 32 patients with immunoglobulin A nephropathy (IgAN) and 141 patients with recurrent pharyngotonsillitis (RPT). H pylori in coccoid form was present in bacterial colonies and horny layers of the stratified squamous epithelium in tonsillar crypts. We described for the first time the morphology of H pylori in palatine tonsils. Most bacterial colonies were sulfur granules with Actinomyces israelii (A israelii), and A israelii showed significant coexistence with H pylori (P=.011). The prevalence of H pylori in palatine tonsils of the RPT group increased steeply with age, but one fourth of the patients were found not to have tonsillar H pylori in adulthood. All patients with IgAN had H pylori in palatine tonsils. The prevalence of H pylori was greater in the IgAN group than in the RPT group, and the difference was statistically significant (P<.001). In contrast, A israelii was unrelated to age and clinical diagnosis (P=.722). In conclusion, our results demonstrate that H pylori in coccoid form is present in palatine tonsils and may indicate that H pylori in palatine tonsils is among the antigens causative of IgAN.

[A case of follicular carcinoma of thyroid gland with concurrent tuberculous lymphadenitises].

We report a case of follicular carcinoma of the thyroid gland with concurrent tuberculous lymphadenitises as neck lymph node metastases of thyroid carcinoma. A 71-year-old woman presented with multiple painless masses in the thyroid gland and painless lymphadenopathies in the right neck. She and her family had no previous history of tuberculosis. A diagnosis of thyroid cancer with lymph node metastases was made, and the patient underwent total thyroidectomy with neck dissection. Lymph nodes were hard and severely adhered to the internal jugular vein. The histopathological diagnosis was follicular carcinoma and multiple nodes of adenomatous goiter of the thyroid gland, and tuberculous lymphadenitises of lymph nodes in the right neck. There was no findings of coexisting pulmonary tuberculosis. The possibility of coexisting tuberculous lymphadenitis must thus be ruled out when we find painless lymph node swelling in aged patients with head and neck cancer including thyroid cancer.

Hypopharyngeal squamous cell carcinoma bordering ectopic gastric mucosa "inlet patch" of the cervical esophagus.

OBJECTIVE: Ectopic gastric mucosa of the cervical esophagus, referred to as inlet patch (IP), is considered to be a common development abnormality of the esophagus. We report here a case of hypopharyngeal squamous cell carcinoma bordering on IP of the cervical esophagus. METHODS: A 44-year-old female underwent partial pharyngectomy, total laryngectomy, cervical esophagectomy, and bilateral neck dissection under the diagnosis of hypopharyngeal carcinoma. RESULTS: Resected specimens of the hypopharynx revealed a well-differentiated squamous cell carcinoma in the ulcerative tumorous lesion (3.5 cm x 0.5 cm). A brown patch (2 cm x 1.5 cm) bordering the anal aspect of the tumor comprised ectopic gastric mucosa of fundic type epithelium. Immunohistochemistry revealed the surface mucosal cells of this lesion were strongly positive for human gastric mucin (HGM) and the fundic cells were positive for gastrin. CONCLUSION: The hypopharyngeal squamous cell carcinoma likely developed in association with chronic irritation due to gastric acid from the IP. To our knowledge, this is the first reported case of squamous cell carcinoma related to IP.

Squamous cell carcinoma arising from Stensen's duct.

We report a case of squamous cell carcinoma presumably arising from the left Stensen's duct. The tumor was discovered during management of recurrent left parotitis. Ultrasonography, computed tomography, and magnetic resonance imaging were useful for estimating the tumor and coexisting obstructive parotitis. Relapsing symptoms and the presence of parotitis seemed to be characteristic of tumors of Stensen's duct. For a mass accompanied by obstructive parotitis or relapsing parotitis without salivary calculus, a tumor of Stensen's duct should be included in the differential diagnosis.

Spindle epithelial tumor with thymus-like differentiation (SETTLE): youngest reported patient.

Spindle epithelial tumor with thymus-like differentiation (SETTLE) is a very rare thyroid tumor. It is one of a family of tumors arising either from ectopic thymus or remnants of branchial pouches that retain the potential to differentiate along the thymic line. Herein is reported a case of SETTLE in a 2-year-old girl. The patient underwent right thyroid lobectomy for a tumor of the right thyroid lobe. The resected specimen of this tumor revealed a whitish and solid mass. On microscopy, the tumor exhibited an area of spindle cells, glandular epithelium, and mucinous cystic lesions. The following findings were obtained on immunohistochemistry: the spindle cell area was diffusely positive for cytokeratin AE1/3 and vimentin, and partially positive for alpha-smooth muscle-specific actin. The glandular structures consisted of columnar cells and the cystic area was also positive for cytokeratin AE1/3. All three components of the tumor were negative for thyroglobulin, thyroid transcription factor-1, S-100 protein, carcinoembryonic antigen, somatostatin, synaptophysin, and chromogranin A. On the basis of the aforementioned findings, SETTLE was diagnosed. The patient remains disease free to date, 2 years after surgery with no additional treatment. To the best of the authors' knowledge the present SETTLE patient is the youngest yet reported.