Etiology | Unknown. The precise cellular derangements that lead to the abnormal accumulation of mitochondria in oncocytes and tumor development are obscure. Alterations of nuclear genetic material (marked aneuploidy) and of mitochondrial DNA are a feature of thyroid oncocytic tumors. |
Epidemiology | The mean age at diagnosis was 43 years for adenomas and 52 for oncocytic carcinomas in a recent series. There is a female preponderance in both subgroups, with a female-to-male ratio of 8:1 in adenomas and 2:1 in carcinomas. Thyroid oncocytic tumors represent approximately 5-10% of thyroid neoplasms. |
Clinics | Most patients with oncocytic neoplasms are euthyroid and present with a thyroid nodule. Secondary syntoms due to compression of the adjacent structures in the neck (e.g. dysphonia, dysphagia) may be present, particularly in patients with malignant tumors. |
Pathology | Grossly, oncocytic adenomas are encapsulated, solid nodules with a characteristic brown cut surface. Secondary changes, including infarction and hemorrhage are common (particularly after fine needle aspiration), possibly as a result of the low tolerance to ischemia displayed by the oncocytes. Histologically, the follicular growth pattern is most common but cells may also be arranged in trabeculae, solid sheets or papillary formations. The colloid is typically purple (amphophilic) rather than pink on conventional histology sections stained with hematoxylin and eosin. Oncocytes have round uniform nuclei with prominent nucleoli but may display scattered areas of marked nuclear atypia and anisonucleosis. The gross appearance of a minimally invasive oncocytic carcinoma is indistinguishable to that of an adenoma, while widely invasive oncocytic carcinomas are obviously invasive macroscopically and display pervasive vascular invasion with multifocal involvement of the thyroid gland. There are no reliable cytologic features which distinguish oncocytic adenomas from carcinomas and the only criteria for a diagnosis of malignancy is the identification of transcapsular and/or vascular invasion. |
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| Fig 1 : Oncocytic cells showing abundant granular cytoplasm and prominent nucleoli (arrowheads) Fig 2 : Mitochondria accumulation in oncocytic cells. Some mitochondria have abnormal architecture with electrondense deposits (inset) |
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Treatment | Oncocytic adenomas are treated with a simple lobectomy or nodulectomy, which is curative but should not be enucleated, as an evaluation of their capsule is essential for the pathologist to determine whether the tumor is benign or malignant. Carcinomas are treated with total/subtotal thyroidectomy followed by radioactive iodine therapy. Oncocytic carcinomas tend to have lower iodide uptake compared with non-oncocytic cancers and are often therefore less responsive to radioactive iodide administration. |
Prognosis | The extent of tumor invasion determines the prognosis in oncocytic carcinomas. Patients with widely invasive tumors (defined as having 2 or more foci of capsular and/or vascular invasion) have a mortality of approximately 50% with median disease specific survival of 7 years. Patients with minimally invasive carcinoma have excellent prognosis with no tumor recurrences or disease related deaths reported in a recent series. Extrathyroidal extension and nodal metastases are adverse predictors of survival after multivariate analysis in widely invasive oncocytic carcinoma. |
Cytogenetics Morphological | Relatively few cases of oncocytic thyroid tumors have been studied by convential cytogenetic analysis, usually in general reports dealing with chromosomal alterations of thyroid neoplasia. 42-47 chromosomes with structural and numerical changes have been demonstrated in one oncocytic carcinoma. |
Cytogenetics Molecular | CGH: Chromosomal DNA unbalance and aneuploidy are present in 70-80% of oncocytic thyroid neoplasms. Chromosomal DNA gains (+5, +7, +12, +17 , +19, +20) are more common than losses (-2, -9). Although aneuploidy is a feature of both oncocytic adenomas and carcinomas, sequential acquisition of numerical chromosomal changes (possibly beginning with trisomy 7) appears associated with tumor progression. Carcinomas tend to have more chromosomal gains and losses then adenomas and a statistical association has been demonstrated between the degree of aneuploidy and loss of differentiation, extent of tumor invasion, and recurrence. |
Follicular Hurthle cell tumors of the thyroid gland. |
Carcangiu ML, Bianchi S, Savino D, Voynick IM, Rosai J |
Cancer. 1991 ; 68 (9) : 1944-1953. |
PMID 1913544 |
|
Frequent occurrence of cytogenetic abnormalities in sporadic nonmedullary thyroid carcinoma. |
Jenkins RB, Hay ID, Herath JF, Schultz CG, Spurbeck JL, Grant CS, Goellner JR, Dewald GW |
Cancer. 1990 ; 66 (6) : 1213-1220. |
PMID 2400971 |
|
Prognostic factors in patients with Hürthle cell neoplasms of the thyroid. |
Lopez-Penabad L, Chiu AC, Hoff AO, Schultz P, Gaztambide S, Ordoñez NG, Sherman SI |
Cancer. 2003 ; 97 (5) : 1186-1194. |
PMID 12599224 |
|
Mitochondrial DNA somatic mutations (point mutations and large deletions) and mitochondrial DNA variants in human thyroid pathology: a study with emphasis on Hürthle cell tumors. |
Máximo V, Soares P, Lima J, Cameselle-Teijeiro J, Sobrinho-Simá M |
The American journal of pathology. 2002 ; 160 (5) : 1857-1865. |
PMID 12000737 |
|
RAS point mutations and PAX8-PPAR gamma rearrangement in thyroid tumors: evidence for distinct molecular pathways in thyroid follicular carcinoma. |
Nikiforova MN, Lynch RA, Biddinger PW, Alexander EK, Dorn GW 2nd, Tallini G, Kroll TG, Nikiforov YE |
The Journal of clinical endocrinology and metabolism. 2003 ; 88 (5) : 2318-2326. |
PMID 12727991 |
|
Hürthle cell carcinoma: a critical histopathologic appraisal. |
Stojadinovic A, Ghossein RA, Hoos A, Urist MJ, Spiro RH, Shah JP, Brennan MF, Shaha AR, Singh B |
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2001 ; 19 (10) : 2616-2625. |
PMID 11352953 |
|
Frequent chromosomal DNA unbalance in thyroid oncocytic (Hürthle cell) neoplasms detected by comparative genomic hybridization. |
Tallini G, Hsueh A, Liu S, Garcia-Rostan G, Speicher MR, Ward DC |
Laboratory investigation; a journal of technical methods and pathology. 1999 ; 79 (5) : 547-555. |
PMID 10334566 |
|
Chromosomal aberrations by comparative genomic hybridization in hürthle cell thyroid carcinomas are associated with tumor recurrence. |
Wada N, Duh QY, Miura D, Brunaud L, Wong MG, Clark OH |
The Journal of clinical endocrinology and metabolism. 2002 ; 87 (10) : 4595-4601. |
PMID 12364440 |
|