Salivary gland tumor is one of the most common tumors in oral and maxillofacial regions. The diagnosis and treatment of salivary gland tumors had been a clinical characteristic project in Peking University School and Hospital of Stomatology since long time ago. Here we introduced the research progress in diagnosis and treatment of salivary gland tumors during the past 10 years. Among 7 190 cases of salivary gland tumors treated in this institution, 4 654 cases (64.7%) were benign, and 2 536 (35.3%) were malignant, with benign ∶ malignant ratio of 1.84 ∶ 1. Parotid was the most common location, followed by minor salivary gland and submandibular gland, while sublingular gland tumor was seldom seen. The proportion of minor salivary gland tumor was relatively high. Among 1 874 cases with primary malignant tumors, the cases with T3 and stage Ⅲ accounted for only 9.6% and 10.3%, respectively, which indicated that there was shortcoming in the T classification and clinical stage formulated by Union for International Cancer Control (UICC), and further revision was required. The 5, 10, and 15 year survival rates of 1 637 cases with postoperative follow-up were 93.1%, 87.2% and 79.3%, respectively, which were much higher than those we reported 30 years ago. The improvement of treatment results was related to more widely used combined treatment with surgery and postoperative radiotherapy, and the increase in patients with early stage. Adenoid cystic carcinoma was the malignant tumor with high rate of distant metastasis. The 5 and 10 year survival rates of the patients with pulmonary metastasis were 76.2% and 51.8%, respectively, which indicated that the pulmonary metastatic carcinomas developed slowly. Recurrent rate of carcinoma ex pleomorphic adenoma was 46.7% after single treatment of sur-gery, while it decreased to 27.5% after combined theraphy with surgery and radiotherapy, indicating that postoperative radiotheraphy could reduce the recurrent rate effectively. The normal myoepithelial cells had the inhibiting role in the invasion and metastasis of carcinoma ex pleomorphic adenoma. The evaluation of integrity of myoepithelial cells surrounding the tumor mass is helpful to understand the invasiveness of the tumors. The new surgical modalities such as extracapsular resection and partial sialoadenectomy were used in treatment of benign tumors of parotid gland and submandibular gland with advantages of decreased tissue damage and preservation of glandular function. Application of digital surgical techniques such as mixed reality combined with surgical navigation and real-time three-dimensional holograms in the surgical treatment of parotid gland tumors showed the benifits of more safety and precision, and less tissue da-mage.
Humans ; Salivary Gland Neoplasms/pathology* ; Carcinoma, Adenoid Cystic/therapy* ; Adenoma, Pleomorphic/therapy* ; Neoplasm Staging

Objective: To investigate the expression of TRPS1 in salivary gland-type breast carcinoma and its clinical application. Methods: A total of 30 cases of salivary gland-type breast carcinoma diagnosed from May 2015 to November 2022 at the Department of Pathology of the First Affiliated Hospital of Nanjing Medical University were collected. The expression of TRPS1 was detected by immunohistochemistry and compared with that of GATA3. TRPS1 and GATA3 expression in 24 cases of primary salivary gland carcinoma. Results: There were 10 cases of breast secretory carcinoma, aged 21-61 years (median 53.5 years), with the size ranging from 0.9-2.2 cm (median 1.6 cm), 2 of which were accompanied by axillary nodal macrometastasis. All patients were alive after 2-55 months of follow-up (median 29.5 months, mean 29.7 months). There were 20 cases of breast adenoid cystic carcinoma, aged 36-77 years (median 53.5 years), with the size ranging from 1.2-5.5 cm (median 2.5 cm), 3 of which were accompanied by axillary nodal macrometastasis. All patients were alive after 3-92 months of follow-up (median 22.5 months, mean 31.7 months), and 1 patient had lung metastasis 15 months after surgery. The medium/high expression ratio of TRPS1 in breast secretory carcinoma was 10/10, which was higher than that of GATA3 (7/10). TRPS1 was also positive in the 2 cases with lymph node metastases. The medium/high expression rate of TRPS1 in breast adenoid cystic carcinoma was 20/20, which was significantly higher than that of GATA3 (2/20). TRPS1 was highly expressed in both classic and solid subtypes, while GATA3 was only expressed in a few cases of the classic subtype. TRPS1 was also positive in 3 cases with lymph node metastases and 1 case of the pulmonary metastases. The expression level of TRPS1 was the same in 1 case before and after neoadjuvant chemotherapy. In addition, TRPS1 was positive in parotid secretory carcinoma and adenoid cystic carcinoma. The medium/high expression rate of TRPS1 in parotid secretory carcinoma (6/6) was higher than that of GATA3 (2/6), and the medium/high expression rate of TRPS1 in parotid adenoid cystic carcinoma (17/18) was higher than that of GATA3 (2/18). Conclusions: The expression of TRPS1 is highly sensitive to salivary gland-type breast carcinoma, especially in GATA3-negative solid subtype of adenoid cystic carcinoma, which plays an important role in clinical practice.
Humans ; Female ; Carcinoma, Adenoid Cystic/pathology* ; Lymphatic Metastasis ; Salivary Gland Neoplasms/pathology* ; Parotid Neoplasms ; Lung Neoplasms ; Breast Neoplasms ; Parotid Gland ; Repressor Proteins

Objective: To investigate the clinicopathological, immunophenotypic, and molecular genetic features of bronchial sialadenoma papilliferum (BSP). Methods: Four cases of BSP collected at the Shanghai Pulmonary Hospital from May 2018 to June 2021 were retrieved and analyzed. These cases were evaluated for their clinical, histological, immunohistochemical (IHC) and genomic features. The patients were followed up and relevant literature was reviewed. Results: All four patients were male, aged from 55 to 75 years (mean 62 years), with tumor diameter of 6 to 21 mm (mean 13.5 mm), and lesions were located in the left lower lobe (n=2), right lower lobe (n=1), and trachea (n=1). They were characterized by a combination of surface exophytic endobronchial papillary proliferation and an endophytic two-cell layered ductal structure. IHC staining showed that CK7 and EMA were strongly positive in ductal epithelium; p63, p40, CK5/6 were positive in ductal and papillary basal cells; SOX10 was positive in ductal epithelium and basal cells; S-100 was positive in basal cells and ductal epithelium in two cases. Next generation sequencing showed that two cases harbored BRAF V600E mutation. Conclusions: BSP is an extremely rare primary lung tumor arising from the salivary gland under bronchial mucosa. The primary treatment choice of this tumor is complete surgical resection. The diagnosis and differential diagnosis of this tumor depend on classic histomorphologic and IHC features, and BRAF V600E gene mutation can be detected.
Aged ; China ; Epithelium/pathology* ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Neoplasms, Glandular and Epithelial/pathology* ; Salivary Gland Neoplasms/surgery*

Adenoma, Pleomorphic/surgery* ; Brain/pathology* ; Cell Transformation, Neoplastic/pathology* ; Humans ; Lung/pathology* ; Salivary Gland Neoplasms/pathology*

Warthin tumor is a benign salivary gland tumor comprising ductal epithelium and lymphoid stroma. To date, reports about the malignant transformations of intraepithelial and lymphoid components in Warthin tumor are extremely rare; lymphoid malignant transformation into B-cell lymphoma is particularly rare in combination with T-cell lymphoma. The case of Warthin tumor complicated with T-lymphoblastic lymphoma is reported to emphasize the importance of a careful light microscopic evaluation of lymphoid tissue in Warthin tumor for identifying occult lymphoma presence, reducing misdiagnosis and missed diagnosis, and determining a timely treatment.
Humans ; Adenolymphoma/pathology* ; Parotid Neoplasms/pathology* ; Salivary Gland Neoplasms ; Epithelium/pathology* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications*

Interferon-γ (IFN-γ), a key effector molecule in anti-tumor immune response, has been well documented to correlate with the intratumoral infiltration of immune cells. Of interest, however, a high level of IFN-γ has been reported in salivary adenoid cystic carcinoma (SACC), which is actually a type of immunologically cold cancer with few infiltrated immune cells. Investigating the functional significance of IFN-γ in SACC would help to explain such a paradoxical phenomenon. In the present study, we revealed that, compared to oral squamous cell carcinoma cells (a type of immunologically hot cancer), SACC cells were less sensitive to the growth-inhibition effect of IFN-γ. Moreover, the migration and invasion abilities of SACC cells were obviously enhanced upon IFN-γ treatment. In addition, our results revealed that exposure to IFN-γ significantly up-regulated the level of programmed death ligand 1 (PD-L1) on SACC cell-derived small extracellular vesicles (sEVs), which subsequently induced the apoptosis of CD8⁺ T cells through antagonizing PD-1. Importantly, it was also found that SACC patients with higher levels of plasma IFN-γ also had higher levels of circulating sEVs that carried PD-L1 on their surface. Our study unveils a mechanism that IFN-γ induces immunosuppression in SACC via sEV PD-L1, which would account for the scarce immune cell infiltration and insensitivity to immunotherapy.
B7-H1 Antigen/metabolism* ; CD8-Positive T-Lymphocytes/pathology* ; Carcinoma, Adenoid Cystic/pathology* ; Carcinoma, Squamous Cell/pathology* ; Cell Line, Tumor ; Humans ; Immunosuppression Therapy ; Interferon-gamma/pharmacology* ; Mouth Neoplasms/metabolism* ; Programmed Cell Death 1 Receptor/metabolism* ; Salivary Gland Neoplasms/pathology*

Breast/pathology* ; Humans ; Salivary Gland Neoplasms/pathology* ; Salivary Glands/pathology*

Pathological diagnosis of salivary gland tumors is one of the most challenging areas in all head and neck surgical pathology. The classification of salivary gland tumors was updated in the 5th edition of the World Health Organization Classification of Head and Neck Tumours, most of which were based on their molecular pathological characteristerics. This new classification features a description of several new entitiesamong benign and malignant neoplasms, salivary gland tumors with updated naming or diagnostic criteria, and lesions deleted from this section, etc.This present review focuses on the updates and changes in the new classification of salivary gland tumors, and provides some reference for head and neck surgeons and pathologists.
Humans ; Head and Neck Neoplasms ; Salivary Gland Neoplasms/pathology* ; Salivary Glands ; World Health Organization

Objective: To investigate the clinical and pathological features of salivary secretory carcinoma (SSC). Methods: Ten cases of SSC confirmed in the Department of Pathology,Capital Medical University School of Stomatology from January 2014 to December 2021 were retrospectively included, including 5 males and 5 females, with a median age of 46.5 years. The microscopic morphology, immunophenotype, special staining and clinical follow-up of 10 cases of salivary secretory carcinoma were observed. Ten patients were tested with S-100, vimentin, mammaglobin, Dog-1, p63 and Ki-67, 9 cases with cytokeratin (CK) 8/18, 8 with CK7, 6 with calponin, 5 with smooth muscle actin (SMA) and GCDFP15, 4 with CK5/6 and 1 with SOX10. The ETV6-NTRK3 fusion gene was detected by fluorescence in situ hybridization. Results: Seven of the 10 SSC were located in the parotid gland and 3 were located in the cheeks. Histomorphology showed solid, papillary-cystic, follicular, microcystic, and macrocystic types. In 7 cases, tumor cells were dominated by single arrangement type, while certain mixed arrangements existed in some areas. The cytoplasm of the tumor cells was rich in eosinophilic, fine granular or vacuolar shapes, and clear cytoplasm was seen in 2 cases. The nuclei were mostly oval-shaped vesicular nuclei, with nucleoli in the center. Immunohistochemistry showed CK7 (8/8) positive, CK8/18 (9/9) positive, S-100 (10/10) positive, vimentin (5/10) positive, (4/10) partially positive and (1/10) less partially positive, mammaglobin (7/10) positive, (1/10) partially positive and (2/10) some individual cells positive, Dog-1 (10/10) negative, CK5/6 (4/4) negative, p63 (7/10) negative and (3/10) partially positive, SMA (5/5) negative, calponin (6/6) negative, and Ki-67 index was 5%-20%. Secretions of 5 cases showed periodic acid-Schiff (PAS) and PAS with diastase (PAS-D) staining positive. All 10 cases showed ETV6-NTRK3 fusion positive. Six cases were successfully followed up for 32-91 months, of which 2 cases recurred after 28 and 74 months and underwent surgical resection again. All cases followed up are alive and disease-free. Conclusions: The salivary secretory carcinoma is a rare low-grade malignant tumor. In certain cases, morphology is atypical and mammaglobin is immunohistochemically positive in only individual tumor cells. Therefore, the diagnosis should be supported with morphology, immunohistochemical staining, and molecular feature preferably.
Female ; Male ; Biomarkers, Tumor ; Carcinoma/pathology* ; In Situ Hybridization, Fluorescence ; Ki-67 Antigen/genetics* ; Neoplasm Recurrence, Local ; Retrospective Studies ; S100 Proteins ; Salivary Gland Neoplasms/pathology* ; Vimentin

Objective: To study the clinicopathologic and genetic features of papillary cystic low-grade mucoepidermoid carcinoma (LG-MEC) and cystadenoma. Methods: A retrospective review was performed on salivary gland tumor patients with papillary cystic architecture who presented to department of oral pathology, Peking University School and Hospital of Stomatology between January 2010 and June 2022. Among this cohort, there were 17 males and 17 females with a range age of 23-82 years [(55.6±14.6) years]. Diagnosis was confirmed by histological, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) analysis. Finally, 15 papillary cystic LG-MEC and 19 cystadenoma patients were included in the present study. All patients were followed clinically and radiologically, and the duration of follow-up ranged from 1 to 141 months. Results: All neoplasms showed papillary proliferation with multilocular or giant cystic tumors. Papillary cystic LG-MEC was characterized by epidermoid cells, intermediate cell and mucous cells with multiple lining-layers. Papillary cystic LG-MEC had mild cellular atypia and a pushing infiltration. Cystadenoma was characterized by cuboidal, columnar and ciliated pseudostratified columnar lining epithelium. Squamous metaplasia, mucinous metaplasia and acidophilic degeneration could also be observed focally in cystadenoma. For IHC staining, papillary cystic LG-MEC showed diffusely and strongly positive for mucin 4 (MUC4) (15/15) and mucin 5 Subtype AC (MUC5AC) (4/15) in the epidermoid cells, intermediate cell and mucous cells. The epidermoid cells and intermediate cells were diffusely positive for p40 and p63. The Ki-67 index was about 10%-15% in LG-MEC. As a contrast, p40 (17/19) and p63 (14/15) were only detected in the basal cells of cystadenoma. Cystadenoma showed focal MUC5AC (4/19)expression and MUC4 (19/19)diffuse expression. In addition, the Ki-67 index was 5%-10% in cystadenoma. The MAML2 gene translocation was detected in 11 LG-MEC patients, but none in cystadenoma. Conclusions: The differential diagnosis points between papillary cystic LG-MEC and cystadenoma included the specific epidermoid cells, intermediate cells and mucus cells in LG-MEC, cell atypia, the pushing-infiltration pattern, diffuse expression of p40 and p63 in the lining epithelium, and a MAML2 gene rearrangement. The molecular test of MAML2 should be recommended to reduce missed LG-MEC diagnoses.
Male ; Female ; Humans ; Carcinoma, Mucoepidermoid/pathology* ; In Situ Hybridization, Fluorescence ; Ki-67 Antigen/genetics* ; Biomarkers, Tumor/analysis* ; Salivary Gland Neoplasms/diagnosis* ; Transcription Factors/metabolism* ; Cystadenoma ; Metaplasia