IgG4-related disease with pseudotumor formation in the larynx

Mikulicz’s disease, an immunoglobulin G4-related disease (IgG4-RD) occurs frequently in the head and neck region but rarely in the larynx. We report a case of IgG4-RD with pseudotumor formation in the larynx. A 50-year-old man presented at our facility for a complete physical examination and diagnostic testing of a left arytenoid tumor. On examination, a large supraglottic mass was noted with signs of dyspnea. Movement disorder of the vocal fold was absent. The patient underwent surgery with general anesthesia to improve respiratory symptoms and a resected specimen was submitted for diagnosis. The pathology findings revealed lymph follicle formation, interstitial follicular fibrosis, angiogenesis, and inflammatory cell infiltration with plasmacytosis. Immunohistologic staining at high magnification revealed one hundred or more IgG4-positive plasma cells and fifty percent IgG4/IgG. In addition, obliterative phlebitis was observed. Medical history was positive for retroperitoneal fibrosis with serum IgG4 levels below the diagnostic criteria of IgG4-RD, but histological characteristics of IgG4-RD were met. The diagnosis of IgG4-RD was established, oral treatment with prednisolone (0.6 mg/kg/day) was initiated, and the tumor reduced in size. IgG4-RD may cause irreversible functional impairment. Early diagnosis and treatment are important in reducing the risk of permanent impairment of vocal fold mobility.     

Synchronous benign and malignant tumors in the ipsilateral parotid gland

Synchronous benign and malignant tumors in the ipsilateral salivary glands are extremely rare. We report a unique case of synchronous unilateral parotid tumors in a 71-year-old man. The main parotid lesion was preoperatively suggested to be adenocarcinoma by fine needle aspiration cytology. A coexisting Warthin's tumor was also diagnosed on microscopic examination of total parotidectomy specimens. We describe this case of rare synchronous salivary gland tumors exhibiting both benign and malignant components with a review of the literature.     

IgG4-related disease presenting as otogenic skull base osteomyelitis

IgG4-related disease (IgG4-RD) is an emerging clinical disease entity characterized by tumefactive lesions at multiple sites with a dense lymphoplasmacytic infiltrate rich in IgG4+ plasma cells. Although almost any organ can be affected, IgG4-RD is most likely to involve the submandibular, lacrimal, or parotid glands in the head and neck region. However, skull base involvement presenting as otogenic skull base osteomyelitis (SBO) is rare. We encountered a 70-year-old male with IgG4-RD presenting primarily with severe otalgia and otorrhea. He had uncontrolled diabetes mellitus and showed clinical manifestations of otogenic SBO. Tissue immunostaining revealed typical features of increased IgG4-positive plasma cells, and hematological examination showed elevated serum IgG4 concentrations. Treatment with corticosteroids significantly improved well-being and partially resolved the lesion based on computed tomography (CT) scan.     

Effects of benign parotid tumors on unstimulated saliva secretion from the parotid gland

Objective

Salivary tumors can manifest as abnormalities of the gland itself and/or changes in salivary flow. However, effects of salivary tumors on saliva secretion have not been studied in much detail. The aim of the present study was to evaluate effects of benign parotid tumors on unstimulated saliva secretion from the affected gland.

Methods

Unstimulated parotid saliva was collected bilaterally using the swab method in patients with unilateral pleomorphic adenoma (n = 14) or Warthin's tumor (n = 6). Pre-weighted cotton rolls were placed at the opening of each parotid duct for 15 min.

Results

The range of salivary flow was similar to that found in studies on unstimulated parotid saliva. Salivary flow did not differ between the involved and non-involved side. No difference was found between the involved and non-involved side when the patients with pleomorphic adenoma or Warthin's tumor were separately analyzed.

Conclusion

The present results suggest that the most common benign parotid tumors do not alter unstimulated salivary flow from the affected gland.     

TcO4 accumulation in scintigraphy and expression of Na/I symporter in salivary gland tumors

Objective

Warthin's tumors and oncocytomas show exceptionally good ^99mTcO₄⁻ (Tc) accumulation images in Tc scintigraphy. However, the mechanism of Tc accumulation in these tumors remains unclear. Sodium-iodide symporter (NIS) is a plasma membrane protein expressed in the thyroid, lactating breast, stomach and salivary glands; it facilitates uptake of I⁻ and Tc. We hypothesized that Warthin's tumor cells and oncocytomas may also express NIS, which would promote uptake of Tc. We examined NIS localization and the mechanism of Tc accumulation in various salivary gland tissues.

Methods

Immunohistological localization of NIS was performed for 19 tumors from 18 patients who underwent preoperative Tc scintigraphy. Expression of mRNA for NIS in the normal salivary gland, Warthin's tumors and pleomorphic adenomas was analyzed by real-time PCR.

Results

In normal salivary glands, striated duct cells were strongly immunostained by anti-NIS antibodies. In Warthin's tumors, eosinophilic epithelial cells exhibited positive immunostaining, but their staining was varied among the cases. Furthermore, all Tc-positive specimens were NIS-positive, and all Tc-negative specimens were NIS-negative. Real-time PCR showed that NIS mRNA expression was detectable in normal salivary glands and Warthin's tumor cells. The expression was significantly higher in normal salivary glands compared with Warthin's tumor cells and pleomorphic adenoma.

Conclusion

Tc-positive salivary glands expressed NIS. Our findings suggest that Tc accumulation in Warthin's tumors and oncocytomas is due to poorer Tc excretory function compared with normal salivary gland tissues, in addition to active uptake of ^99mTcO₄⁻ via NIS.     

Papillary cystadenoma of the larynx

A patient with a tumor of the larynx resembling a Warthin's tumor of the parotid salivary gland is described. A comparison is drawn between this lesion and oncocytoma. A discussion of the morphology and pathogenesis of oncocytic adenomas is presented.     

A novel concept of Mikulicz's disease as IgG4-related disease

Since Morgan's report in 1953, Mikulicz's disease (MD) has been considered part of primary Sjögren'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 Küttner'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.     

Mucosa-associated lymphoid tissue lymphoma of the thyroid with abundant IgG4-positive plasma cells

A case of thyroidal mucosa-associated lymphoid tissue (MALT) lymphoma mimicking IgG4-related disease is described. A 54-year-old male presented with acute swelling of the anterior neck. Anaplastic thyroid carcinoma (ATC), malignant lymphoma (ML), or acute deterioration of Hashimoto's thyroiditis were initially suspected, and an emergent tracheostomy was required for progressive airway obstruction; a simultaneous biopsy from the thyroid tissue was performed. Histopathologically, the lesion consisted of sclerotic fibrosis and diffuse and dense infiltration by small lymphoid cells without atypia and plasma cells, many of which were IgG4-positive. Blood examination also revealed high serum IgG4 levels. Riedel's thyroiditis was suspected. However, despite medical treatments, a firm swelling of the thyroid still remained. In an in situ hybridization study, IgG4-negative plasma cells showed immunoglobulin light-chain restriction (κ-monotype), and immunoglobulin heavy (IgH) chain gene monoclonal re-arrangement was detected by polymerase chain reaction. The lesion was finally diagnosed as MALT lymphoma. When IgG4-related disease is suspected, it is important to thoroughly exclude other possibilities.     

SDHB expression in Warthin's tumour

IntroductionSuccinic dehydrogenase subunit B (SDHB) is an enzyme belonging to the mitochondrial complex II. The aim of this study is to analyse SDHB expression in a series of Warthin's tumours, studying its relationship with oncocytic changes, constantly present in this form of tumour.Material and methodsIn resection tumour specimens from a series of ten Warthin's tumours (all from the parotid gland), immunohistochemical expression of SDHB was analysed using a commercially-available monoclonal antibody.ResultsThe Warthin's tumours studied affected 10 men (mean age: 64.2 yrs, range 40-80), all with smoking habits, and 2 with metachronous bilateral involvement. Two patients presented associated urothelial carcinoma. Our SDHB study showed marked reactivity (++/+++) in all cases in the oncocytic epithelial component and also in striated duct cytoplasm (+) from non-tumorous parotid tissue. Expression was not influenced by age, smoking intensity or bilateral character. One of the tumours showed squamous metaplasia foci with SDHB-negativity at this level.Discussion and conclusionsDue to the constant and intense SDHB reactivity in oncocytic cells in our observations, oncocytic changes are not considered to be associated with defective enzyme activity in the mitochondrial complex II. Strong SDHB reactivity is an additional marker of oncocytic changes in Warthin's tumour. Neither of these facts has been described previously.     

The specific binding of parotin on duct cells of human parotid gland

Summary The relationship between parotin and human parotid gland was investigated using indirect technique of enzyme antibody method. Normal rabbit IgG has non-specific affinity to duct cells of human parotid gland, but it was suppressed by adding bovine serum albumin. Anti-parotin rabbit IgG has no reaction products on the sections of adult human parotid gland. When the sections, initially incubated with parotin solution in PBS, were treated with anti-parotin rabbit IgG containing bovine serum albumin, and then HRPO-labeled anti-rabbit gamma globulin antibodies (swine IgG), intercalated and striated ducts excepting excretory ducts were stained with diaminobenzidine reaction, but also acinar cells did not. These results indicate that parotin is bound specifically on duct cells of human parotid gland.     

The histogenesis of so-called mixed tumor evaluating from parotin binding

Summary We evaluated the histogenesis of so-called mixed tumors of the parotid gland by comparing the tumor cells with normal parotid gland cells. Using the indirect technique of the enzyme antibody method, the paraffin sections of human parotid glands, initially reacted with 0.1 mg/ml of parotin solution in PBS for 20 min at 37° C, were treated for 20 min at 37° C with anti-parotin subunit rabbit IgG (0.01 mg/ml) containing 5 mg/ml BSA, and then with HRPO-labeled anti-rabbit gamma globulin antibodies (swine IgG). After staining for enzyme by Karnovsky's method, DAB reactions were observed on the duct cells of human parotid glands in 12 of 13 cases. We surveyed the parotin binding as a marker of duct cell on the so-called mixed tumors of 11 cases. DAB reactions were recognized on the cells of myxoid portion, along with the polygonal cells of solid sheet, board cord, and ductular formation, but the cells of chondroid portion and the spindle-shaped cells forming trabecular structure did not.Consequently, the predominant cells proliferated in the so-called mixed tumor were closely related to the ductular components. It can therefore be presumed that the tumors may be derived from the duct cells and/or the progenitors with potentiality to differentiate to the duct cell of parotid gland.     

Inflammatory myofibroblastic tumor of the parotid gland: case report and review of the literature

An inflammatory myofibroblastic tumor, previously known as an inflammatory pseudotumor, is an uncommon neoplasm. This tumor, which has characteristic morphological and immunohistochemical features, is mostly seen in the lung. Herein we present a rare case of an inflammatory myofibroblastic pseudotumor of the parotid gland as well as a review of the literature. The patient was a 66-year-old man with recurrent painful swelling of the parotid gland. A total parotidectomy with preservation of the facial nerve branches was performed. The patient showed no signs of recurrence>3 years after surgery. The presence of clonal cytogenic abnormalities supported the neoplastic origin of this process. The treatment consisted of complete resection. Clinicians should however be aware that an inflammatory myofibroblastic tumor may mimic a reactive process.     

Spontaneous regression of lung lesions after excision of the submandibular gland in a patient with chronic sclerosing sialadenitis

Chronic sclerosing sialadenitis, which clinically resembles a salivary gland tumor, is considered a salivary gland lesion of the IgG4-related inflammatory disease. Corticosteroids are effective for the treatment of chronic sclerosing sialadenitis, but the natural clinical course of this disease is not fully understood. We report a 67-year-old man with chronic sclerosing sialadenitis who showed lung lesions, which spontaneously regressed without steroid therapy after excision of the submandibular gland. He presented with several weeks' history of continuous swelling in the right submandibular region. Physical examination showed a hard swelling of the right submandibular gland; the cytological finding was Papanicolaou class III. A chest X-ray demonstrated bilateral infiltration of the right middle and left lower lobes. The right submandibular gland was excised under general anesthesia for definite diagnosis, and histopathological examination revealed an IgG4-positive plasmacytic infiltration accompanied by periductal fibrosis and interlobular sclerosis, consistent with chronic sclerosing sialadenitis. Five months after operation, the lung lesions regressed spontaneously.     

Temporary facial nerve dysfunction after parotidectomy correlates with tumor location

Objective

To investigate the clinical factors associated with temporary facial nerve dysfunction (TFND) following surgery for benign parotid gland tumors.

Methods

We reviewed the records of 175 patients with benign parotid gland tumors who underwent partial parotidectomy at Yokohama City University Medical Center in Japan. TFND was found in 33 patients (18.9%). We used two hypothetical lines in magnetic resonance imaging (MRI) images to define the tumor location (upper/lower or anterior/posterior) in the parotid gland. We then studied the associations of TFND with the following clinical factors: patient age, tumor size, histopathological diagnosis, and the location of the tumor within the parotid gland (superficial lobe/deep lobe; upper part/lower part; and anterior part/posterior part).

Results

Tumors located in the upper parts, anterior parts or the deep lobes of the parotid gland had statistically higher incidences of TFND compared with tumors located in the lower parts, posterior parts or the superficial lobe (P < 0.001, <0.001, <0.01, respectively). The odds ratio for the risk of TFND was significantly high if tumors were located in the upper parts, the anterior parts or the deep lobes with stepwise multivariate regression analysis. The other factors, including patient's age, tumor size, histopathology of the tumor, and inadequate surgeon's experience, were not apparent risks for TFND.

Conclusions

Parotid gland tumors located in the upper parts, the anterior parts or the deep lobes had a higher risk of TFND. The two hypothetical lines we used were shown to be useful to define the tumor location, eventually the risk of TFND.     

Otologic Manifestation in IgG4-Related Systemic Disease

IgG4-related systemic disease, including autoimmune pancreatitis, is a multi-organ disorder characterized by elevated serum immunoglobulin G4 (IgG4) concentration and IgG4-positive plasma cell infiltration. We report a case of a 66-year-old woman with IgG4-related hearing disorder, presenting with fluctuating mixed hearing loss with middle ear effusion. The serum IgG4 level was elevated and pathological examination revealed dense infiltration of IgG4-positive lymphocyte in the renal parenchyma, lung tissue and lacrimal gland. With intravenous methylprednisolone at a dose of 60 mg daily, improvement of hearing loss were observed. No recurrence was observed for 6 months with mainternance of prednisolone and methotrexate.     

Syncronized Warthin's tumor in bilateral parotid gland and nasopharynx

Warthin's tumor is a benign salivary gland tumor of the parotid gland. Although bilateral or multicentric involvement of the parotid gland is common, extraparotid involvement is seen rarely. The nasopharynx is an unusual region for extraparotid involvement. In this article, we present a 52-year-old male case with a synchronized Warthin's tumor in the bilateral parotid gland and nasopharynx, and we discuss the clinical management of the disease.     

Clinicopathological analysis of salivary gland tissue from patients with IgG4-related disease

Conclusion The diagnosis of immunoglobulin G4-related disease (IgG4-RD) should be based on the morphology of tissue biopsy, and this study recommends a submandibular gland (SMG) biopsy for accurate diagnosis and to exclude malignant disease. Objective To clarify which type of biopsy specimen (SMG or labial salivary gland [LSG]) should be taken from patients with IgG4-RD. Methods This study included 33 patients with IgG4-RD (21 women; 12 men) who were subjected to both SMG and LSG biopsies at Sapporo Medical University between 2011–2015. Tissues obtained from the SMG and LSG specimens were evaluated. Results All SMG specimens satisfied the diagnostic criteria for IgG4-RD, whereas 19 (57.6%) LSG specimens satisfied the diagnostic criteria for IgG4-RD. Histological evaluation showed fibrosis in all the SMG specimens and in eight LSG specimens (24.2%). Obliterative phlebitis was seen in nine SMG specimens (27.3%), but it was absent in all the LSG specimens.     

Seltener maligner Tumor der Gl. parotis

A parotid mass in a 62-year-old woman presented intraoperatively as a highly malignant tumor with facial nerve infiltration. Classification by means of rapid section histology was not possible. Immunohistochemical studies were necessary to diagnose this rare case of myoepithelial carcinoma of the parotid gland. We performed a total parotidectomy including partial nerve resection and neck dissection on the tumor side. The patient was referred to radiotherapy postoperatively.     

Warthin's tumor: A 40-year experience at the johns hopkins hospital

Warthin's tumor previously has been thought to occur much more commonly in men than in women and rarely in African Americans. One hundred thirty-two cases of Warthin's tumor treated at The Johns Hopkins Hospital from 1952 to 1992 were retrospectively reviewed. There were 90 (68%) men and 42 (32%) women, with an overall man-to-woman ratio of 2.2:1. The number and percentage of women with Warthin's tumor increased over each consecutive decade: 1952 to 1962, 5 (21%); 1963 to 1972, 6 (29%); 1973 to 1982, 11 (31%); and 1983 to 1992, 20 (39%). A positive smoking history was found in 88% of the men and in 89% of the women with a Warthin's tumor. Eleven (8%) African Americans and 1 (0.75%) Asian American were diagnosed to have a Warthin's tumor. Also, the incidence of African Americans with a Warthin's tumor increased over each decade: 0 (0%), 1 (4.8%), 2 (5.5%), and 8 (16%). This study's results indicate a progressive increase in the occurrence of this tumor in women and in African Americans and a higher overall incidence in African Americans than previously reported.     

Fazialisparese durch einen benignen Parotistumor

Facial nerve palsy is rarely associated with an inflammatory parotid process. We present a case of peripheral facial palsy initiated by infection of a cystadenolymphoma of the parotid gland. The paresis progressed rapidly despite abating inflammation and 48-h antibiotic therapy. Following total parotidectomy the facial nerve paresis persisted for a period of 4 months. Histological work-up yielded a diagnosis of Warthin’s tumor with necrotic changes. This case indicates that even benign processes can be associated with facial nerve palsy.