Warthin’s tumor is the second most frequent neoplasm next to pleomorphic adenoma in the salivary gland. The tumor contains the epithelial oncocyte cells with the presence of rich-mitochondria and their surrounding abundant lymphocytes. A relatively new disease entity of IgG4-related disease frequently occurs in the salivary gland. However, the coexistence of Warthin’s tumor and IgG4-related disease is scarcely observed. We have recently experienced a rare case of Warthin’s tumor with IgG4-related sialadenitis. A 51-year-old man presented to our hospital, complaining of a mass with right submandibular tenderness and spontaneous pain. A computed tomography scan of the cervical region revealed a suspicion of lymph node proliferative disease, including malignant lymphoma. Elevated serum levels of IL-2R: 1843 U/ml (reference value 122 - 496 U/ml), IgG: 3430 mg/dl (reference value 861 - 1747 mg/dl), and IgG4: 3140 mg/dl (reference value 11 - 121 mg/dl) were observed. Other laboratory data showed within normal ranges. The cervical tumor was diagnosed as Warthin’s tumor by the findings of fine-needle aspiration cytology and biopsy examination. Immunohistochemistry revealed numerous IgG4- and IgG-positive cells with fibrosis surrounding the epithelial component of Warthin’s tumor, suggesting IgG4-rerated sialadenitis. Finally, we diagnosed the cervical tumor as Warthin tumor with IgG4-related sialadenitis. This is the second report describing a case of Warthin’s tumor with possible involvement of IgG4-related sialadenitis.
References
[1]
Kuzenko, Y.V., Romanuk, A.M., Dyachenko, O.O. and Hudymenko, O. (2016) Pathogenesis of Warthin’s tumors. Interventional Medicine and Applied Science, 8, 41-48. https://doi.org/10.1556/1646.8.2016.2.2
[2]
Teymoortash, A., Krasnewicz, Y. and Werner, J.A. (2006) Clinical Features of Cystadenolymphoma (Warthin’s Tumor) of the Parotid Gland: A Retrospective Comparative Study of 96 Cases. Oral Oncology, 42, 569-573. https://doi.org/10.1016/j.oraloncology.2005.10.017
[3]
Schwalje, A.T., Uzelac, A. and Ryan, W.R. (2015) Growth Rate Characteristics of Warthin’s Tumours of the Parotid Gland. International Journal of Oral and Maxillofacial Surgery, 44, 1474-1479. https://doi.org/10.1016/j.ijom.2015.07.019
[4]
Teymoortash, A., Schrader, C., Shimoda, H., Kato, S. and Werner, J.A. (2007) Evidence of Lymphangiogenesis in Warthin’s Tumor of the Parotid Gland. Oral Oncology, 43, 614-618. https://doi.org/10.1016/j.oraloncology.2006.07.006
[5]
Karthikeya, P., Mahima, V.G. and Shalini, K. (2005) Papillary Cystadenoma Lymphomatosum: Case Report and Review of Literature. Indian Journal of Dental Research, 16, 153-158. https://doi.org/10.4103/0970-9290.29904
[6]
Aoki, R. and Tanaka, T. (2024) Pathogenesis of Warthin’s Tumor: Neoplastic or Non-Neoplastic? Cancers (Basel), 16, Article 912. https://doi.org/10.3390/cancers16050912
[7]
Bishop, J.A., Thompson, L.D.R., et al. (2021) Tumors of the Salivary Glands. American Registry of Pathology, No. 5, 152-166.
[8]
Daguci, L., Simionescu, C., Daguci, C., Bataiosu, M. and Dragomir, L.P. (2009) Clinical and Morphological Aspects of Warthin’s Tumor. Current Health Sciences Journal, 35, 115-118.
[9]
Pusztaszeri, M., Rossi E.D. and Faquin, W.C. (2023) Update on Salivary Gland Fine-Needle Aspiration and the Milan System for Reporting Salivary Gland Cytopathology. Archives of Pathology & Laboratory Medicine. https://doi.org/10.5858/arpa.2022-0529-RA
[10]
Seethala, R.R. (2023) New Entities and Concepts in Salivary Gland Tumor Pathology: The Role of Molecular Alterations. Archives of Pathology & Laboratory Medicine. https://doi.org/10.5858/10.5858/arpa.2023-0001-RA
[11]
Fisher, R. and Ronen, O. (2022) Cytologic Diagnosis of Parotid Gland Warthin’s Tumor: Systematic Review and Meta-Analysis. Head Neck, 44, 2277-2287. https://doi.org/10.1002/hed.27099
[12]
Hamano, H., Kawa, S., et al. (2001) High Serum IgG4 Concentrations in Patients with Sclerosing Pancreatitis. The New England Journal of Medicine, 344, 732-738. https://doi.org/10.1056/NEJM200103083441005
[13]
Zahran, M., Alsedra, S., Cope, D., Youssef, A. (2021) The Role of FNAC in the Diagnosis and Management of Warthin’s Tumour: Analysis of 74 Cases. International Archives of Otorhinolaryngology, 25, e379-e382. https://doi.org/10.1055/s-0040-1715148
[14]
Aga, M., Kondo, S., et al. (2013) Warthin’s Tumor Associated with IgG4-Related Disease. Auris Nasus Larynx, 40, 514-517. https://doi.org/10.1016/j.anl.2012.11.005
[15]
Seifert, G., Bull, H.G. and Donath, K. (1980) Histologic Subclassification of the Cystadenolymphoma of the Parotid Gland. Analysis of 275 Cases. Virchows Archiv A, Pathological Anatomy and Histopathology, 388, 13-38. https://doi.org/10.1007/BF00430674
[16]
Sucic, M., Ljubic, N.L. et al. (2020) Cytopathology and Diagnostics of Warthin’s Tumour. Cytopathology, 31, 193-207. https://doi.org/10.1111/cyt.12830
[17]
Deshpande, V., Zen, Y., et al. (2012) Consensus Statement on the Pathology of IgG4-Related Disease. Modern Pathology, 25, 1181-1192. https://doi.org/10.1038/modpathol.2012.72
[18]
Vasaitis, L. (2016) IgG4-Related Disease: A Relatively New Concept for Clinicians. European Journal of Internal Medicine, 27, 1-9. https://doi.org/10.1016/j.ejim.2015.09.022
[19]
Miyabe, K., Zen, Y., et al. (2018) Gastrointestinal and Extra-Intestinal Manifestations of IgG4-Related Disease. Gastroenterology, 155, 990-1003. https://doi.org/10.1053/j.gastro.2018.06.082
[20]
Uchida, K., Masamune, A., Shimosegawa, T. and Okazaki, K. (2012) Prevalence of IgG4-Related Disease in Japan Based on Nationwide Survey in 2009. International Journal of Rheumatology, 2012, Article ID: 358371. https://doi.org/10.1155/2012/358371
[21]
Aga, M., Kondo, S., et al. (2014) Immunoglobulin Class Switching to IgG4 in Warthin’s Tumor and Analysis of Serum IgG4 Levels and IgG4-Positive Plasma Cells in the Tumor. Human Pathology, 45, 793-801. https://doi.org/10.1016/j.humpath.2013.11.012
[22]
Bushara, O., Escobar, D.J., Weinberg, S.E., Sun, L., Liao, J. and Yang, G.Y. (2022) The Possible Pathogenic Role of IgG4-Producing Plasmablasts in Stricturing Crohn’s Disease. Pathobiology, 89, 187-197. https://doi.org/10.1159/000521259
[23]
Kamisawa, T. (2022) Immunoglobulin G4-Related Disease: A New Systemic Disease Emerging in Japan. Japan Medical Association Journal, 5, 23-35. https://doi.org/10.31662/jmaj.2021-0113
[24]
Steplewski, Z., Sun, L.K., Shearman, C.W., Ghrayeb, J., Daddona, P. and Koprowski, H. (1988) Biological Activity of Human-Mouse IgG1, IgG2, IgG3, and IgG4 Chimeric Monoclonal Antibodies with Antitumor Specificity. Proceedings of the National Academy of Sciences of the United States of America, 85, 4852-4856. https://doi.org/10.1073/pnas.85.13.4852
[25]
Abd-Elhamid, E.S. and Elshafei, M.M. (2009) Immunohistochemical Localization of mdm-2, p27Kip1 and bcl-2 in Warthin’s Tumor of the Parotid Gland. Diagnostic Pathology, 4, Article No. 14. https://doi.org/10.1186/1746-1596-4-14
[26]
Rivlin, N., Brosh, R., Oren, M. and Rotter, V. (2011) Mutations in the p53 Tumor Suppressor Gene: Important Milestones at the Various Steps of Tumorigenesis. Genes Cancer, 2, 466-474. https://doi.org/10.1177/1947601911408889
[27]
Arida, M., Barnes, E.L. and Hunt, J.L. (2005) Molecular Assessment of Allelic Loss in Warthin’s ’s Tumors. Modern Pathology, 18, 964-968. https://doi.org/10.1038/modpathol.3800379
