Oncocytic Lesions of the Thyroid, Kidney, Salivary Glands, Adrenal Cortex, and Parathyroid Glands

First Published January 9, 2014 Research Article Find in PubMed

Authors

, BSc, PhD12
 
Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal
 
Medical Faculty of the University of Porto, Porto, Portugal
by this author
, , MD123
 
Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal
 
Medical Faculty of the University of Porto, Porto, Portugal
 
Centro Hospitalar S. João, Porto, Portugal
by this author
, , MD, PhD123
 
Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal
 
Medical Faculty of the University of Porto, Porto, Portugal
 
Centro Hospitalar S. João, Porto, Portugal
by this author
First Published Online: January 9, 2014

Oncocytic cell represents a special phenotype of neoplastic cells reflecting a unique biologic process characterized by the huge proliferation of morphologically abnormal mitochondria in the cytoplasm of neoplastic cells. This phenotype is driven by quite specific molecular mechanisms that interfere with mitochondrial function and metabolism. The oncocytic phenotype is more common in tumors arising in tissues presenting low proliferative rate, such as thyroid, kidney, salivary glands, adrenal cortex, and parathyroid glands, and it is superimposed on the genotypic and conventional histologic features of the tumors. In this short review, we address the similarity of the molecular alterations and of the biological features of the neoplastic cells in the oncocytic tumors of the different organs. We also discuss the differential diagnosis of benign and malignant oncocytic tumors as well as the prognosis of the malignant ones. We conclude that this rather unique phenotype, which is observed in tumors from different organs, indicates common metabolic alterations that may represent a useful target for therapeutic purposes.

1. Máximo, V, Sobrinho-Simões, M. Hurthle cell tumours of the thyroid. A review with emphasis on mitochondrial abnormalities with clinical relevance. Virchows Arch. 2000;437:107-115.
Google Scholar | Crossref | Medline | ISI
2. Sobrinho-Simões, M, Máximo, V, Castro, IV. Hurthle (oncocytic) cell tumors of thyroid: etiopathogenesis, diagnosis, and clinical significance. Int J Surg Pathol. 2005;13:29-35.
Google Scholar | SAGE Journals | ISI
3. Máximo, V, Lima, J, Prazeres, H, Soares, P, Sobrinho-Simões, M. The biology and the genetics of Hurthle cell tumors of the thyroid. Endocr Relat Cancer. 2012;19:R131-R147.
Google Scholar | Crossref | Medline | ISI
4. Moreira, S, Correia, M, Soares, P, Máximo, V. GRIM-19 function in cancer development. Mitochondrion. 2011;11:693-699.
Google Scholar | Crossref | Medline | ISI
5. Máximo, V, Botelho, T, Capela, J. Somatic and germline mutation in GRIM-19, a dual function gene involved in mitochondrial metabolism and cell death, is linked to mitochondrion-rich (Hurthle cell) tumours of the thyroid. Br J Cancer. 2005;92:1892-1898.
Google Scholar | Crossref | Medline | ISI
6. Máximo, V, Soares, P, Lima, J, Cameselle-Teijeiro, J, Sobrinho-Simões, M. Mitochondrial DNA somatic mutations (point mutations and large deletions) and mitochondrial DNA variants in human thyroid pathology: a study with emphasis on Hurthle cell tumors. Am J Pathol. 2002;160:1857-1865.
Google Scholar | Crossref | Medline | ISI
7. Gasparre, G, Porcelli, AM, Bonora, E. Disruptive mitochondrial DNA mutations in complex I subunits are markers of oncocytic phenotype in thyroid tumors. Proc Natl Acad Sci U S A. 2007;104:9001-9006.
Google Scholar | Crossref | Medline | ISI
8. Pereira, L, Soares, P, Máximo, V, Samuels, DC. Somatic mitochondrial DNA mutations in cancer escape purifying selection and high pathogenicity mutations lead to the oncocytic phenotype: pathogenicity analysis of reported somatic mtDNA mutations in tumors. BMC Cancer. 2012;12:53.
Google Scholar | Crossref | Medline | ISI
9. Attardi, G, Yoneda, M, Chomyn, A. Complementation and segregation behavior of disease-causing mitochondrial DNA mutations in cellular model systems. Biochim Biophys Acta. 1995;1271:241-248.
Google Scholar | Crossref | Medline | ISI
10. Wallace, DC . Diseases of the mitochondrial DNA. Annu Rev Biochem. 1992;61:1175-1212.
Google Scholar | Crossref | Medline | ISI
11. Herbst, A, Johnson, CJ, Hynes, K, McKenzie, D, Aiken, JM. Mitochondrial biogenesis drives a vicious cycle of metabolic insufficiency and mitochondrial DNA deletion mutation accumulation in aged rat skeletal muscle fibers. PLoS One. 2013;8:e59006.
Google Scholar | Crossref | Medline | ISI
12. Máximo, V, Lima, J, Soares, P, Sobrinho-Simões, M. Mitochondria and cancer. Virchows Arch. 2009;454:481-495.
Google Scholar | Crossref | Medline | ISI
13. Lima, J, Máximo, V, Soares, P, Portugal, R, Guimarães, S, Sobrinho-Simões, M. Mitochondria and oncocytomas. In: Singh, KK, Costello, LC, eds. Mitochondria and Cancer. New York, NY: Springer; 2009:193-210.
Google Scholar
14. Máximo, V, Sobrinho-Simões, M. Mitochondrial DNA ‘common’ deletion in Hurthle cell lesions of the thyroid. J Pathol. 2000;192:561-562.
Google Scholar | Crossref | Medline | ISI
15. Aral, C, Akkiprik, M, Kaya, H. Mitochondrial DNA common deletion is not associated with thyroid, breast and colorectal tumors in Turkish patients. Genet Mol Biol. 2010;33:1-4.
Google Scholar | Crossref | Medline | ISI
16. Bonora, E, Evangelisti, C, Bonichon, F, Tallini, G, Romeo, G. Novel germline variants identified in the inner mitochondrial membrane transporter TIMM44 and their role in predisposition to oncocytic thyroid carcinomas. Br J Cancer. 2006;95:1529-1536.
Google Scholar | Crossref | Medline | ISI
17. Máximo, V, Lima, J, Soares, P, Botelho, T, Gomes, L, Sobrinho-Simões, M. Mitochondrial D-Loop instability in thyroid tumours is not a marker of malignancy. Mitochondrion. 2005;5:333-340.
Google Scholar | Crossref | Medline | ISI
18. Kovacs, G, Welter, C, Wilkens, L, Blin, N, Deriese, W. Renal oncocytoma. A phenotypic and genotypic entity of renal parenchymal tumors. Am J Pathol. 1989;134:967-971.
Google Scholar | Medline | ISI
19. Welter, C, Kovacs, G, Seitz, G, Blin, N. Alteration of mitochondrial DNA in human oncocytomas. Genes Chromosomes Cancer. 1989;1:79-82.
Google Scholar | Crossref | Medline | ISI
20. Brooks, JD, Marshall, FF, Isaacs, WB, Johns, DR. Absence of HinfI restriction abnormalities in renal oncocytoma mitochondrial DNA. Mol Urol. 1999;3:1-3.
Google Scholar | Medline
21. Gasparre, G, Hervouet, E, de Laplanche, E. Clonal expansion of mutated mitochondrial DNA is associated with tumor formation and complex I deficiency in the benign renal oncocytoma. Hum Mol Genet. 2008;17:986-995.
Google Scholar | Crossref | Medline | ISI
22. Mayr, JA, Meierhofer, D, Zimmermann, F. Loss of complex I due to mitochondrial DNA mutations in renal oncocytoma. Clin Cancer Res. 2008;14:2270-2275.
Google Scholar | Crossref | Medline | ISI
23. Henderson, A, Douglas, F, Perros, P, Morgan, C, Maher, ER. SDHB-associated renal oncocytoma suggests a broadening of the renal phenotype in hereditary paragangliomatosis. Fam Cancer. 2009;8:257-260.
Google Scholar | Crossref | Medline | ISI
24. Lewis, PD, Baxter, P, Paul, GA, Parry, JM, Skibinski, DO. Detection of damage to the mitochondrial genome in the oncocytic cells of Warthin’s tumour. J Pathol. 2000;191:274-281.
Google Scholar | Crossref | Medline | ISI
25. Lewis, PD, Fradley, SR, Griffiths, AP, Baxter, PW, Parry, JM. Mitochondrial DNA mutations in the parotid gland of cigarette smokers and non-smokers. Mutat Res. 2002;518:47-54.
Google Scholar | Crossref | Medline | ISI
26. Capone, RB, Ha, PK, Westra, WH. Oncocytic neoplasms of the parotid gland: a 16-year institutional review. Otolaryngol Head Neck Surg. 2002;126:657-662.
Google Scholar | SAGE Journals | ISI
27. Duregon, E, Volante, M, Cappia, S. Oncocytic adrenocortical tumors: diagnostic algorithm and mitochondrial DNA profile in 27 cases. Am J Surg Pathol. 2011;35:1882-1893.
Google Scholar | Crossref | Medline | ISI
28. Costa-Guda, J, Tokura, T, Roth, SI, Arnold, A. Mitochondrial DNA mutations in oxyphilic and chief cell parathyroid adenomas. BMC Endocr Disord. 2007;7:8.
Google Scholar | Crossref | Medline
29. Volante, M, Papotti, M, Gugliotta, P, Migheli, A, Bussolati, G. Extensive DNA fragmentation in oxyphilic cell lesions of the thyroid. J Histochem Cytochem. 2001;49:1003-1011.
Google Scholar | SAGE Journals | ISI
30. Vander Heiden, MG, Cantley, LC, Thompson, CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009;324:1029-1033.
Google Scholar | Crossref | Medline | ISI
31. Petersson, F, Gatalica, Z, Grossmann, P. Sporadic hybrid oncocytic/chromophobe tumor of the kidney: a clinicopathologic, histomorphologic, immunohistochemical, ultrastructural, and molecular cytogenetic study of 14 cases. Virchows Arch. 2010;456:355-365.
Google Scholar | Crossref | Medline | ISI
32. Chakrabarti, I, Basu, A, Ghosh, N. Oncocytic lesion of parotid gland: a dilemma for cytopathologists. J Cytol. 2012;29:80-82.
Google Scholar | Crossref | Medline | ISI
33. DeLellis, RA LR, Heitz, PU, Eng, C, eds. World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Endocrine Glands. Lyon, France: IARC Press; 2004.
Google Scholar
34. Abrahams, NA, Tamboli, P. Oncocytic renal neoplasms: diagnostic considerations. Clin Lab Med. 2005;25:317-339.
Google Scholar | Crossref | Medline | ISI
35. Zhou, CX, Shi, DY, Ma, DQ, Zhang, JG, Yu, GY, Gao, Y. Primary oncocytic carcinoma of the salivary glands: a clinicopathologic and immunohistochemical study of 12 cases. Oral Oncol. 2010;46:773-778.
Google Scholar | Crossref | Medline | ISI
36. Wong, DD, Spagnolo, DV, Bisceglia, M, Havlat, M, McCallum, D, Platten, MA. Oncocytic adrenocortical neoplasms—a clinicopathologic study of 13 new cases emphasizing the importance of their recognition. Hum Pathol. 2011;42:489-499.
Google Scholar | Crossref | Medline | ISI
37. Mearini, L, Del Sordo, R, Costantini, E, Nunzi, E, Porena, M. Adrenal oncocytic neoplasm: a systematic review. Urol Int. 2013;91:125-133.
Google Scholar | Crossref | Medline | ISI
38. Erickson, LA, Jin, L, Papotti, M, Lloyd, RV. Oxyphil parathyroid carcinomas: a clinicopathologic and immunohistochemical study of 10 cases. Am J Surg Pathol. 2002;26:344-349.
Google Scholar | Crossref | Medline | ISI
39. Dytz, MG, Souza, RG, Lazaro, AP. Parathyroid carcinoma and oxyphil parathyroid adenoma: an uncommon case of misinterpretation in clinical practice. Endocr J. 2013;60:423-429.
Google Scholar | Medline | ISI
40. Zhao, Y, Butler, EB, Tan, M. Targeting cellular metabolism to improve cancer therapeutics. Cell Death Dis. 2013;4:e532.
Google Scholar | Crossref | Medline | ISI

Access content

To read the fulltext, please use one of the options below to sign in or purchase access.
  • Access Options

    My Account

    Welcome
    You do not have access to this content.

    Chinese Institutions / 中国用户

    Click the button below for the full-text content

    请点击以下获取该全文

    Institutional Access

    does not have access to this content.

    Purchase Content

    24 hours online access to download content

    Added to Cart

    Cart is full

    There is currently no price available for this item in your region.

    Research off-campus without worrying about access issues. Find out about Lean Library here


Purchase

IJS-article-ppv for GBP32.00
IJS-article-ppv for $41.50
Single Issue 24 hour E-access for GBP265.82
Single Issue 24 hour E-access for $318.50

Cookies Notification

This site uses cookies. By continuing to browse the site you are agreeing to our use of cookies. Find out more.
Top