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IgG4-related disease (IgG4-RD) is a chronic inflammatory disorder, characterized by elevated serum IgG4 levels as well as abundant infiltration of IgG4-positive plasmacytes and fibrosis in various organs, including the head and neck region. In particular, the salivary glands, orbit, and thyroid are common sites of disease involvement. IgG4-RD is diagnosed based on various clinical, serological, and histopathological findings, none of which are pathognomonic. Hence, various differential diagnoses, which exhibit elevated serum IgG4 levels and infiltration of IgG4-postive cells into tissues, need to be excluded, especially malignant diseases and mimicking disorders. Systemic corticosteroids are generally effective in inducing IgG4-RD remission; however, recurrent or refractory cases are common. In addition, although the pathogenic mechanisms of IgG4-RD remain unclear, an antigen-driven inflammatory condition is believed to be involved. Recent studies have indicated the important pathogenic role of B cell/T cell collaboration and innate immunity in this disease. Nevertheless, additional research and discussions are needed to resolve many remaining questions. In this review, we provide an overview of the recent insights on the history, clinical features, diagnosis, and treatment of IgG4-RD in the head and neck region. Furthermore, we have also addressed the pathogenesis of this disease.

Objective In northern Japan, birch pollen is the major allergen in pollinosis, while oral allergy syndrome (OAS) is caused primarily by apple and peach, and is almost exclusively related to birch pollinosis. To clarify the clinical benefit of allergen-based component-resolved diagnosis (CRD) in Japanese birch-allergic patients with OAS, we present an analysis of IgE profiles in response to crude extracts and recombinant component-resolved allergen to birch pollen and Rosaceae fruits allergens. Methods The sera of 30 patients with birch pollen-related OAS to apple or peach were analyzed for specific IgE reactivity to pathogenesis-related class 10 (PR-10) family (birch: rBet v 1, apple: rMal d 1, and peach: rPru p 1), profilin (birch: rBet v 2 and peach: rPru p 4), and lipid transfer protein (LTP) (apple: rMal d 3 and peach: rPru p 3) allergens, as well as to conventional crude, unfractionated extracts (birch: T3, apple: f49, and peach: f95) using the ImmunoCAP System™. Allergen-specific IgE values Results Of the 30 sera CAP-positive for natural birch pollen extract, 28 (93.3%) exhibited specific IgE against Bet v1, and two (6.7%) contained specific IgE against Bet v2. Of the 26 sera of OAS to apple patients, only 17 were positive for specific IgE against f49 extract (65.4%); however, 24 were positive for specific IgE against rMal d 1 (92.3%). Similarly, only 17 of the 23 sera of OAS to peach patients contained specific IgE against the f95 extract (73.9%); however, 22 were positive for specific IgE against rPru p 1 (95.7%). Conclusion Our data suggest that CRD constitutes a reliable tool for the diagnosis of birch pollen-related OAS.

Objective Patients with multiple sensory deficits, including hearing loss and visual impairment, present a unique problem. We evaluated the clinical outcomes of cochlear implantation in patients with severe to profound sensorineural hearing loss and visual impairment. Methods We retrospectively reviewed eight patients with severe sensorineural hearing loss and visual impairment who underwent cochlear implantation at our institution between 1993 and 2014. The follow-up period was between 2 and 20 years. We evaluated the case histories, etiologies of hearing loss and visual impairment, pre- and postoperative pure-tone thresholds, speech perception rates after CI using the Japanese CD speech discrimination scoring system (CI-2004 test) for words and sentences, and pre- and postoperative communication means. Postoperative speech discrimination scores were compared between patients with and without visual impairment who underwent cochlear implantation. Results The outcomes of cochlear implantation were good in all patients, with seven showing the ability to hold a conversation with others. The average proportion of correct answers for words and sentences in the CI-2004 test was 72.3 ± 19.1% and 86.0 ± 16.1%, respectively, for the patients with visual impairment and 62.1 ± 21.7% and 78.5 ± 20.9%, respectively, for those without visual impairment (based on auditory senses only). There were no significant differences in results between the patients with and without visual impairment. Conclusions Cochlear implantation is important for the rehabilitation of patients with severe auditory loss and visual impairment. Medical staff members require additional skills to perform auditory evaluations and rehabilitate patients with multiple sensory deficits.

Progressively transformed germinal centers (PTGC), a lymph node process unfamiliar to most otolaryngologists, is a morphological variant of reactive lymphofollicular hyperplasia of lymph nodes. Immunoglobulin (Ig)G4-related disease (IgG4-RD) is a newly identified condition, characterized by hyper-IgG4-γ-globulinemia and mass-forming or hypertrophic lesions associated with infiltration of IgG4 + plasma cells in the affected organs. Recently, a case study of PTGC was reported that fulfilled the diagnostic criteria of IgG4-RD (IgG4 + PTGC) [1] . A 68-year-old male was referred to our hospital with swelling in the left submandibular region. Palpation revealed swollen lymph nodes, the largest of which measured 5 cm in diameter. 18 F-fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography identified lymphadenopathy with high 18 F-FDG uptake in the left submandibular region. We strongly suspected malignant lymphoma, and excisional biopsy of the submandibular lymph node was performed under general anesthesia. Pathological findings were consistent with IgG4 + PTGC, and serological examination demonstrated elevated levels of IgG4. These findings were consistent with IgG4-RD. The patient did not have systemic lesions; therefore, he has not undergone corticosteroid therapy. IgG4 + PTGC should be considered as a differential diagnosis for cervical lymphadenopathy by otolaryngologists as well as pathologists.

Since Morgan's report in 1953, Mikulicz's disease (MD) has been considered part of primary Sjogren's syndrome (SS). However, MD has a unique presentation, including persistent swelling of the lacrimal and salivary glands, and is characterized by good responsiveness to glucocorticoids, leading to recovery of gland function. Recently, it has been revealed that MD patients show elevated serum immunoglobulin G4 (IgG4) levels and prominent infiltration of IgG4-positive plasmacytes. The complications of MD include autoimmune pancreatitis, retroperitoneal fibrosis, tubulointerstitial nephritis, autoimmune hypophysitis, and Riedel's thyroiditis, all of which show IgG4 involvement in their pathogenesis. Thus, MD is a systemic ''IgG4-related disease.'' In addition, recent analyses have revealed that Kuttner's tumor (KT), a chronic sclerosing sialadenitis that presents with asymmetrical firm swelling of the submandibular glands, is also associated with prominent infiltration of IgG4-positive plasmacytes. MD and KT differ from SS and are thought to be singular systemic IgG4-related plasmacytic diseases. Here we discuss the results of recent studies and provide an overview of MD as an IgG4-related disease. # 2011 Elsevier Ireland Ltd. All rights reserved.

Objective Mikulicz's disease (MD) is differentiated from Sjogren's syndrome as an immunoglobulin G4 (IgG4) systemic disease. MD patients often report olfactory dysfunction (OD). To analyze cases of OD associated with MD, we studied clinicopathological and serological findings of MD patients. Methods A total of 44 MD patients (17 males and 27 females) were examined for OD. We evaluated clinicopathological and serological findings of these patients by dividing them into OD (+) and OD (−) groups. Results The mean IgG4 concentration (SD) in such cases was 950.5 (797.5) mg/dl. Of the 44 patients, 20 (45%) had OD even though no abnormalities, such as obstructive and inflammatory disease, were detected in their nasal cavities and sinuses. The two groups did not show significant differences in background characteristics, such as age, sex, IgG4 concentration, presence or absence of allergic rhinitis, and presence or absence of extrasalivary gland lesions. We found abundant IgG4-positive plasmacytes in the nasal mucosa specimens of the OD (+) group but not in that of the OD (−) group. Conclusions Nasal mucosa in the MD patients with OD was infiltrated with IgG4-positive plasmacytes. We concluded that OD may be associated with infiltration by IgG4-positive cells.

Objective To analyze the clinical characteristics, 5-year survival, and prognostic factors of squamous cell carcinoma (SCC) of the external and middle ear. Methods A multi institutional study. Ninety five cases of patients from 10 institutions were reviewed on their age and sex distribution, initial complaints, stages, tumor locations, treatments, and outcomes. Prognostic factors were discussed based on the Pittsburgh staging system. Results This disease seems to appear in the elderly with a peak age of 50–69 years. Males appear to be more predisposed than females with an odd ratio of 1.7. The initial complaints were not typical, while 12.6% of patients presented a history of recurrent otitis externa or chronic otitis media. Regional metastasis was recognized in 13.7% of patients, while no distant metastasis was confirmed. SCC located in the external ear could be detected in an earlier stage than that in the middle ear. The overall 5-year survival was 66.8% in total, and decreased significantly with stage. SCC in stages I and II was susceptible to each therapeutic strategy with a 5-year survival of 100%. Operation combined with radiotherapy and/or chemotherapy was the major treatment for stages III and IV SCC, while radiotherapy and chemotherapy were applied mainly for those who had been considered inappropriate for operation. The overall survival was 67.2% for stage III and 29.5% for stage IV, and operation with pathologically tumor free margin could improve the survival to 72.7% when combined with radio- and chemotherapy. Stage, completeness of operation with tumor free margin, recurrence, and metastasis have significant influence on survival. Conclusion Local infiltration seems to be the main behavior of SCC in the external and middle ear. Early diagnosis and treatment were important because SCC in the earlier stage is susceptible to be cured. For tumors of advanced stage, operation should be performed with pathologically tumor free margin, and operation combined with radiotherapy and chemotherapy could improve the survival. Tumor stage adds more influence on survival than its location. Recurrence and metastasis mainly occur in advanced stages and result in a poor survival.

A case of columnar-cell carcinoma of the thyroid gland occurring in a 77-year-old female is described. Tracheal deviation and calcified anterior neck lesion were showed in X-ray examination. A computed tomography (CT) scan revealed a soft tissue density mass with calcification of the right thyroid lobe and isthmus. A 99m Tc scintiscan showed a ‘cold’ nodule, whereas a 201 Tl scintiscan showed a ‘hot’ in the right thyroid lobe and isthmus. Subtotal thyroidectomy and dissection of paratracheal adipose tissue were performed after fine needle aspiration cytology (FNA) of the thyroid mass had been done. On the FNA smears, there were many papillary fragments, which contained pseudostratified columnar cells. Histopathologically, the tumor had three different types of neoplasm including papillary carcinoma of usual feature, columnar-cell carcinoma and follicular carcinoma. Transitional changes were observed between columnar-cell carcinoma and follicular carcinoma. The patient has been followed up for 3 years, with no evidence of recurrence or metastasis.

Schwannomas of the submandibular gland have only been documented sporadically throughout the medical literature. We describe a case of schwannoma of the submandibular gland originating from the submandibular branch of the lingual nerve, which carries the preganglionic parasympathetic nerve fibers. The clinical aspect of this tumor is discussed, followed by a brief literature review.

Primary cartinoid tumors in the middle ear and mastoid are rare. They are also very difficult to distinguish from adenomas and adenocarcinomas, using conventional histological stains. We present clinical, histological, immunohistochemical and ultrastructural findings of a cartinoid tumor in the middle ear and mastoid in a 40-year-old male. A soft tumor was revealed in the posterior mesotympanum and mastoid cavity, and a radical tympanomastoidectomy was performed. The tumor cells were stained by chromogranin A, and neurosecretory granules were confirmed with electron microscopy. We also review 20 previously reported cases in regard to their presentation, symptoms, signs, tumor extension, treatments, and histopathology.

To our knowledge, this is the first description of the histopathology of the temporal bone from a case of craniodiaphyseal dysplasia. The air spaces of the mastoid, external auditory canal, and middle ear cavity are reduced by hyperostotic bone. The ossicles are also deformed by the bony overgrowth. Anomalous ossicles with hyperostosis could affect the air conduction. Even though the internal auditory canal is somewhat elongated and narrow, no labyrinthine abnormalities can be attributed to the abnormal bone. Facial nerves run through abnormal courses but the geniculate ganglion cells are not involved. The VIIIth nerve dysfunction in this case could be due to mechanical damage of the nerve fibers and/or impaired vascular supply by the hyperostosis.

The purpose of this study was to clarify the mechanism of the chronicity of otitis media with effusion (OME). The levels of the IgG-immune complexes (IC) in middle ear effusions (MEE) were determined by using anti-C3 solid phase ELISA. The clinical significance of IC in OME was investigated, and the results were as follows: 1) IgG-IC levels in MEE were found to be significantly elevated in patients with OME and positive rates of IgG-IC in MEE were 58.3% in acute cases, 54.5% in subacute cases, and 52.5% in chronic cases. 2) There was no correlation between IgG-IC levels and IgG levels in MEE which were determined by single radial immunodiffusion method. These results suggested that immune complexes formed in the middle ear cavity might play an important role in the prolonged inflammatory process of OME.