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oncocytic cells

Wednesday 3 May 2017

oncocytic cell: Hürthle cell

See also : oncocytic metaplasia

In some circumstances, oncocytic change is a feature of tumours that have a benign behaviour, such as oncocytic renal cell tumors.

Parathyroid gland

Parathyroid tumours with oncocytic change were thought to have reduced functional capacity for hormone production. This has not been substantiated because there are cases of hormone hypersecretion in patients with these lesions, and immunohistochemical studies show that these lesions express PTH. In general, however, oncocytic parathyroid tumours tend to be larger than non-oncocytic tumours with similar concentrations of circulating PTH.

Thyroid gland

See also : thyroid oncocytic anomalies / thyroid oncocytic tumors

In the thyroid, Hürthle cells are found in a variety of conditions and, therefore, are not specific for a particular disease. Individual cells, follicles, or groups of follicles may show Hürthle cell features in irradiated thyroids, in aging thyroids, in nodular goitre, and in chronic lymphocytic thyroiditis, in addition to that seen in long standing autoimmune hyperthyroidism (Graves’ disease). In some of these situations, one can often find an entire nodule composed of oncocytes, and the distinction of hyperplasia from neoplasia can be problematic.

In chronic lymphocytic thyroiditis, follicular cells can show extensive oncocytic change, which is most pronounced in areas of inflammation. The nuclei can exhibit crowding, clearing, irregular contours, and grooves, mimicking papillary carcinoma.

Nodules of oncocytes in the setting of chronic lymphocytic thyroiditis or in nodular hyperplasia may be hyperplastic or neoplastic. The distinction can be extremely difficult or impossible.

The identification of oncocytic change in thyroid tumours has led to major controversies. Because some lesions that were called benign developed metastases, there were proponents of the view that all oncocytic tumours of the thyroid should be treated as malignancies.

Numerous studies indicated that the criteria that apply to follicular tumours of the thyroid also distinguish malignant from benign Hürthle cell lesions.

These included capsular and vascular invasion. Moreover, studies showed that the larger the Hürthle cell lesion, the more likely it is to show invasive characteristics; a Hürthle cell tumour that is 4 cm or greater has an 80% chance of showing histological evidence of malignancy.

Nuclear atypia, which is the hallmark of the Hürthle cell, multinucleation, and mitotic activity were not considered useful for predicting prognosis.

However, there remained a group of Hürthle cell lesions that were not invasive and were considered to be Hürthle cell adenomas, yet they gave rise to lymph node metastases. These lesions can be a reflection of the failure to recognise oncocytic follicular variant papillary carcinomas.


Hürthle cells have been studied by enzyme histochemistry and have been shown to contain high concentrations of oxidative enzymes.

The pathogenetic basis of oncocytic change is fascinating because mitochondria contain their own separate and parallel DNA. There is a large body of literature that has described and characterised the human mitochondrial genome. Mitochondrial mutations have been identified as the cause of several inherited degenerative disorders.

Recently, mitochondrial DNA polymorphisms and mutations have been associated with neoplastic disorders.

In much of the literature, the focus has been on mitochondrial DNA alterations that result in preferential survival in hypoxic conditions.

This work provides an explanation for the malignant behaviour of some tumours that are able to grow in hypoxic conditions and are resistant to conventional treatments.

However, much of this work deals with gliomas and cervical carcinomas, where oncocytosis is not a prominent feature, suggesting that the mitochondrial mutations do not result in proliferation.

Mitochondrial mutations have been identified in oncocytic tumours of the thyroid.

These are found in benign and malignant tumours and, therefore, unlike mutations that result in hypoxic survival, do not appear to have prognostic significance.

Moreover, similar changes have been found in the non-tumorous thyroid tissue of patients with oncocytic tumours, suggesting that certain polymorphisms predispose to this cytological alteration, rather than predisposing to neoplastic alteration.

“Hürthle cells have been studied by enzyme histochemistry and have been shown to contain high concentrations of oxidative enzymes”

Apart from these mitochondrial DNA characteristics, the somatic genetic events underlying oncocytic neoplasms of the thyroid tend to be similar to those in non-oncocytic tumours.

Activating ras mutations are infrequent in oncocytic tumours, as they are in non-oncocytic differentiated thyroid follicular and papillary carcinomas.

Oncocytic papillary carcinomas harbour ret/PTC gene rearrangements similar to those of non-oncocytic papillary carcinomas.

The only difference identified to date is frequent chromosomal DNA imbalance, with numerical chromosomal alterations being the dominant feature.

The importance of these alterations is not known.

Flow cytometric analyses document aneuploid cell populations in 10–25% of Hürthle cell tumours that are clinically and histologically classified as adenomas.

However, once a histological diagnosis of carcinoma is made, aneuploidy on flow cytometry may predict a more aggressive clinical behaviour for that carcinoma.

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