PURPOSE: To investigate the difference of expression of autophagy and reactive oxygen species (ROS) related proteins in adenoid cystic carcinoma (ACC) of lacrimal gland in comparison with ACC of salivary gland. MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded tissue samples from patients pathologically diagnosed as lacrimal gland ACC (n=11) and salivary gland ACC (n=64) were used. Immunochemistry was used to measure expression of autophagy related proteins [beclin-1, light chain (LC) 3A, LC3B, p62, and BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3)] and ROS related proteins [catalase, thioredoxinreductase, glutathione S-transferasepi (GSTpi), thioredoxin interacting protein, and manganese superoxide dismutase (MnSOD)]. The prognostic factors related to disease-free and overall survival (OS) in lacrimal gland ACC by log-rank tests, were determined. RESULTS: GSTpi in stromal cells was more highly expressed in lacrimal gland ACC (p=0.006), however, MnSOD in epithelial cells was expressed more in salivary gland ACC (p=0.046). LC3B positivity and BNIP3 positivity in epithelial component were associated with shorter disease-free survival (both p=0.002), and LC3A positivity in stromal component was the factor related to shorter OS (p=0.005). CONCLUSION: This is the first study to demonstrate the expression of autophagy and ROS related proteins in lacrimal gland ACC in comparison with the salivary gland ACC, which would provide a basis for further study of autophagy and ROS mechanism as novel therapeutic targets in lacrimal gland ACC.
Adult ; Aged ; *Autophagy ; Beclin-1 ; Biomarkers, Tumor/metabolism ; Carcinoma, Adenoid Cystic/*metabolism/pathology ; Carrier Proteins ; Disease-Free Survival ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lacrimal Apparatus/metabolism/pathology ; Lacrimal Apparatus Diseases/*metabolism/pathology ; Male ; Membrane Proteins ; Middle Aged ; Proto-Oncogene Proteins ; Reactive Oxygen Species/*metabolism ; Salivary Gland Neoplasms/metabolism/*pathology ; Salivary Glands/pathology

OBJECTIVETo study the clinicopathologic features and possible molecular mechanisms of adenoid cystic carcinoma with high-grade transformation.

METHODSFour cases of adenoid cystic carcinoma with high-grade transformation were enrolled into the study. Immunohistochemical study for smooth muscle actin, p63, p53 and Ki-67 was carried out. C-myc gene status was analyzed by fluorescence in-situ hybridization.

RESULTSThere were altogether 3 males and 1 female. The mean age of the patients was 55.5 years. Two patients died 17 months and 29 months after operation, respectively. One patient had distant metastasis 23 months after operation and was still alive at 26-month follow up. The remaining patient remained tumor free at 3-month follow up. High-grade transformation in adenoid cystic carcinoma presented either as poorly differentiated adenocarcinoma or undifferentiated carcinoma. Histologic examination showed sheets of pleomorphic tumor cells occupying more than one low-power field. The high-grade carcinoma cells showed increased nuclear-cytoplasmic ratio, prominent eosinophilic nucleoli and active mitosis (ranging from 8 to 25 per high-power field). Comedo necrosis was observed in 2 cases and multiple foci of calcifications in 3 cases. Immunohistochemical study demonstrated loss of myoepithelial differentiation, overexpression of p53 and high proliferative index by Ki-67. No c-myc translocation or copy-number changes were observed.

CONCLUSIONSHigh-grade transformation in adenoid cystic carcinoma is rare. The histopathologic features are rather distinctive and the biologic behavior is aggressive. C-myc gene mutation does not seem to play a key role in the pathogenesis.

Actins ; metabolism ; Adenocarcinoma ; genetics ; metabolism ; pathology ; Adult ; Aged ; Carcinoma ; genetics ; metabolism ; pathology ; Carcinoma, Adenoid Cystic ; genetics ; metabolism ; pathology ; Cell Transformation, Neoplastic ; Eye Neoplasms ; genetics ; metabolism ; pathology ; Female ; Follow-Up Studies ; Genes, myc ; Humans ; Ki-67 Antigen ; metabolism ; Lacrimal Apparatus ; Lacrimal Apparatus Diseases ; genetics ; metabolism ; pathology ; Lung Neoplasms ; genetics ; metabolism ; pathology ; Male ; Maxillary Sinus Neoplasms ; genetics ; metabolism ; pathology ; Membrane Proteins ; metabolism ; Middle Aged ; Mutation ; Parotid Neoplasms ; genetics ; metabolism ; pathology ; Survival Rate ; Tumor Suppressor Protein p53 ; metabolism

Chronic sclerosing sialadenitis, also known as Kuttner tumor, is a chronic inflammatory disease of the salivary glands that is reported in a few cases in medical literature. Recent reports suggest that certain aspects of sclerosing diseases, including chronic sclerosing sialadenitis or dacryoadenitis, should be classified under immunoglobulin G4 (IgG4)-related sclerosing disease based on immunohistochemical studies. This study reports an unusual case of IgG4-related sclerosing disease appearing simultaneously in the lacrimal glands, submandibular glands, and extraocular muscles. A 56-year-old male presented with complaints of bilateral eyelid swelling and proptosis that began two years ago. Computed tomography confirmed that bilateral submandibular enlargements also existed five years ago in the subject. Orbital computed tomography and magnetic resonance imaging revealed bilateral lacrimal gland enlargement and thickening of extraocular muscles. Typical findings of chronic sclerosing dacryoadenitis were revealed upon pathologic exam of the right lacrimal gland. Immunostaining revealed numerous IgG4-positive plasma cells. Through these clinical features, we make a diagnosis of IgG4-relataed sclerosing disease in the subject.
Biopsy, Fine-Needle ; Diagnosis, Differential ; Facial Muscles/*immunology/pathology/radiography ; Follow-Up Studies ; Humans ; Immunoglobulin G/*immunology/metabolism ; Immunohistochemistry ; Lacrimal Apparatus/*immunology/metabolism/pathology ; Lacrimal Duct Obstruction/complications/diagnosis/*immunology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Sclerosis ; Submandibular Gland/*immunology/pathology/radiography ; Submandibular Gland Diseases/complications/diagnosis/*immunology ; Tomography, X-Ray Computed

BACKGROUNDImmunoglobulin G4-related disease (IgG4-RD) is a newly recognized systemic disease that can involve multiple organs and various clinical phenotypes. The purpose of this study was to analyze different types of organ involvement in IgG4-RD patients in China.

METHODSWe conducted a prospective cohort study on IgG4-RD patients to analyze the clinical manifestations and rare features of IgG4-RD. Patients were grouped into different types according to organ involvement regarding organ number and organ site. The constituent ratio in different types was also analyzed.

RESULTSA total of 200 IgG4-RD patients, with a male:female ratio of 2.08:1, were grouped into different types. Cases having involvement of two or three organs were the most common whereas the fewest number of patients had multi-organ (≥4) involvement. Serum IgG4 and IgE levels, IgG4/IgG ratio, and percentage of eosinophils increased as the number of involved organs increased. In addition, constituent ratio analysis revealed that patients with salivary gland/lacrimal gland swelling, who also constituted the largest number of IgG4-RD patients, had higher serum IgG4 concentrations and IgG4/IgG values, had higher percentage of Eos, and were more likely to have had a history of allergies relative to patients with internal organ involvement.

CONCLUSIONSThe characteristic feature of IgG4-RD is multiple organ involvement with various clinical manifestations and different types. Although serum IgG4 levels increased with the number of involved organs, serum IgG4 levels were higher for those patients with salivary gland/lacrimal gland swelling compared with those with internal organ involvement. Thus, valuable clues to the differential diagnosis of IgG4-RD could be obtained by examining the clinical patterns of organ involvement.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Autoimmune Diseases ; complications ; pathology ; Eosinophils ; metabolism ; Female ; Humans ; Immunoglobulin E ; blood ; Immunoglobulin G ; blood ; Kidney ; pathology ; Lacrimal Apparatus ; pathology ; Lung ; pathology ; Male ; Middle Aged ; Pituitary Gland ; pathology ; Prospective Studies ; Prostate ; pathology ; Salivary Glands ; pathology ; Thyroid Gland ; pathology ; Uterus ; pathology ; Young Adult