Oncocytic versus mitochondrion‐rich follicular thyroid tumours: should we make a difference?

Aims:  To separate true oncocytic neoplasms from mitochondrion‐rich non‐oncocytic lesions based on the intracellular relationship between major cell organelles, and to establish the diagnostic and clinical relevance of this distinction. Methods and results:  Tissue samples from 276 follicular adenomas, 194 follicular carcinomas, 162 normal thyroids and 296 non‐neoplastic lesions were classified as conventional, mitochondrion‐rich or oncocytic based on the immunohistochemically assessed quantity and intracellular distribution of mitochondria and endoplasmic reticulum (ER) and nuclear position. Pathological and clinical features were compared among the groups. In oncocytes, densely packed mitochondria resulted in homogeneous immunolabelling of basal cytoplasmic regions, whereas ER and the nuclei were typically displaced to the apical position. This aberrant organelle distribution was not observed in non‐oncocytes, which allowed reliable distinction between oncocytic and mitochondrion‐rich lesions. Clinically, mitochondrial increase in non‐oncocytic lesions was associated with neoplasia, malignancy and higher cancer recurrence rates. Similar correlation, albeit less pronounced, was observed within the oncocytic tumour group. By contrast, oncocytic change per se was not associated with neoplasia, malignancy or cancer aggressiveness. Conclusions:  True oncocytic neoplasms can be distinguished from mitochondrion‐rich non‐oncocytic tumours based on aberrant distribution of all major cell organelles. This distinction has immediate clinical relevance and should be implemented in practice.