Structure, Function, and Morphology in the Classification of Pituitary Neuroendocrine Tumors: the Importance of Routine
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Structure, Function, and Morphology in the Classification of Pituitary Neuroendocrine Tumors: the Importance of Routine Analysis of Pituitary Transcription Factors Ozgur Mete 1,2
&
Sylvia L. Asa 3,4
Accepted: 10 August 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract The traditional approach to the diagnosis of primary adenohypophyseal cell proliferations uses hormone immunohistochemistry to classify pituitary neuroendocrine tumors (PitNETs). The routine application of immunolocalization of pituitary transcription factors (SF1, PIT1, TPIT, ERα, and recently GATA3) along with adenohypophyseal hormones has taught us critical lessons that are discussed in this communication. We point out that appropriate patient care requires accurate diagnosis and is critical in the era of precision medicine. A misdiagnosis can result in far greater health care costs than the cost of accurate tumor classification and may have other unintended consequences. We provide additional insights about confusing findings in genomic studies, emphasizing that high-quality pathology is essential for strong science and translational research. Keywords Pituitary adenoma . Pituitary carcinoma . Pituitary neuroendocrine tumor . TPIT1 . SF1 . PIT1 . Hormones . Immunohistochemistry . Biomarkers
The advent of new technologies allows tremendous advances in our understanding of disease. While histopathology has been a foundational science for over 400 years and remains the mainstay of diagnosis, the exponential increase in our understanding of pathology has been achieved by the addition of technological developments including electron microscopy in the 1970s, followed by immunohistochemistry, molecular genetics, and proteomics [1, 2]. In the pituitary, a gland composed of multiple hormonesecreting epithelial neuroendocrine cell types, stromal cells, and hypothalamic neurons and modified glia, these advances have provided the basis for a complex classification of tumors * Ozgur Mete [email protected] * Sylvia L. Asa [email protected] 1
Department of Pathology, University Health Network, 200 Elizabeth Street, 11th floor, Toronto, ON M5G 2C4, Canada
2
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
3
Department of Pathology, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA
4
Department of Pathology, Case Western Reserve University, Cleveland, OH, USA
[2, 3]. Evolving from acidophilic tumors [4] and basophilic tumors [5], we have come to classify adenohypophyseal tumors as a complex family of epithelial neuroendocrine neoplasms with specific cell lineages and subtypes [3, 6]. Cell lineages are now known to be dependent on the expression of pituitary transcription factors, PIT1, TPIT, and SF1 that, in concert with ERα and GATA2/3, regulate cellular differentiation and hormone secretion [7, 8]. Posterior pituitary lobe tumors have a unique signature of TTF1 expression that allows the distinction of a group of pituicyte-derived tumors, includi
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