Oncocytes, Oxyphils, Hürthle, and Askanazy Cells: Morphological and Molecular Features Of Oncocytic Thyroid Nodules Ozgur Mete & Sylvia L. Asa Published online: 16 December 2009 # Springer Science+Business Media, LLC 2009 Abstract Our understanding of oncocytic change in thyroid nodules is evaluated in light of the recent progress in understanding the mitochondrial DNA, its mutations, and somatic mutations that affect mitochondrial function. These changes are largely unrelated to the genetic events that result in proliferation and neoplastic transformation of thyroid follicular epithelial cells. The criteria for diagnosing lesions that are composed predominantly of oncocytic cells are the same as those applied to follicular lesions that do not contain oncocytic cells, including follicular variant papillary carcinomas, based on nuclear morphology, immunohistochemical profiles, and molecular markers. Keywords Oncocytes . Oxyphils . Hürthle cells . Thyroid nodules . Oncocytic thyroid carcinoma What are Oncocytes, Oxyphils, Hürthle, and Askanazy Cells? Oncocytes (from the Greek word “onkos” meaning “swelling”) are enlarged polygonal to square-shaped epithelial cells with distinct cell borders and voluminous granular, eosinophilic cytoplasm due to the accumulation of mitochondria. The staining characteristics of these cells have given them another name, oxyphils. In the thyroid, these cells are also known as Hürthle cells or Askanazy cells. In fact, the cells originally described in 1894 by Hürthle [1] were actually the ultimobranchial body-derived parafollicular calcitonin- producing C cells, and oncocytic cells derived from follicular epithelium were actually described in 1898 by Askanazy [2]. Nevertheless, the terminology “Hürthle cells” has been established in most parts of the world with the exception of Germany where the term ‘‘Askanazy cells’’ has persisted. Cytoplasmic Eosinophilia vs Oncocytic Change The eosinophilic appearance of cellular cytoplasm in hematoxylin and eosin stain (H&E)-stained sections is due to the presence of cationic (basic) structures in the cytoplasm because of the anionic (acidic) nature of eosin [3]. The majority of cytoplasmic organelles other than ribosomes are cationic, including mitochondria, lysosomes, smooth endoplasmic reticulum, cytofilaments, and some neuroendocrine and exocrine granules [3–5]. The form of cytoplasmic eosinophilia defined as “oncocytic change” is unique, characterized by abundant eosinophilic granularity as a result of the accumulation of numerous altered mitochondria [3–7]. It is often associated with nuclear enlargement and hyperchromasia and a prominent ‘‘cherry pink’’ macronucleolus [6, 8]. With the Papanicolau stain, oncocytic cytoplasm may be orange, green, or blue. By electron microscopy, the cytoplasmic granularity is composed of large, often vacuolated and dilated mitochondria [5, 6, 8]. The swelling of mitochondria can result in some oncocytic cells having variably clear rather than eosinophilic cytoplasm [5, 6, 8]. Although oncocytic transformation is easily recognized because of its distinctive histologic O. Mete (*) : S. L. Asa Department of Pathology, University Health Network, 200 Elizabeth Street, 11th floor, Toronto, ON M5G 2C4, Canada e-mail: ozgurmete77@gmail.com O. Mete Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey Endocr Pathol (2010) 21:16–24 DOI 10.1007/s12022-009-9102-2