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Dr. Sadow is the Associate Program Director responsible for resident training in Anatomic Pathology at Massachusetts General Hospital.
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Dr. Sadow is Associate Director of the MGH Head and Neck Pathology Service. He is also Associate Director of ENT Pathology in the Department of Otolaryngology at the Massachusetts Eye and Ear Infirmary. His clinical and research interests involve endocrine pathology, studying the mechanisms of endocrine carcinogenesis through translational studies involving the proteomics and genomics of endocrine neoplasms, primarily of the thyroid and adrenal glands.
Endocrine tumors present a particularly difficult challenge for both pathologists and clinicians in that they are often remarkably benign-appearing under the microscope. Clearly, when they are horrifically malignant, they are horrifically malignant, but often, in the worlds of endocrine pathology and clinical medicine, the biggest tip-off to the level of malignancy is metastasis. Thus, classifying these tumors at an earlier stage in order to both risk stratify patients as well as to develop markers with a better molecular understanding of these neoplasms is the current focus of the field.
We have a very nice working knowledge of some of the molecular defects involved in the biology of thyroid neoplasms, such as mutations in BRAF, RET, beta catenin, PTEN and p53. We also have some functional understanding of these tumors through translocations, such as RET-PTC and PAX8-PPARgamma, the types of functional abnormalities first seen in hematopoietic malignancies. In tumors of the adrenal medulla and paraganglia, we have seen these arise in high probability in association with cancer syndromes, such as MEN (multiple endocrine neoplasia), VHL (Von Hippel Lindau), and Familial Paragangliomatosis (FP). These syndromes are also associated with known mutations in RET (MEN), VHL (VHL) and SDH (FP) genes.
However, for as much as we know, we still are stymied in our ability to predict which of these tumors will become malignant, which will metastasize, and which will ultimately kill the patient, or even more puzzling, which will do absolutely nothing whatsoever if left alone. So, in this, we have a conundrum. It's a classification problem, it's a treatment problem, and it's a challenge for those with an interest to forward the field diagnostically and in the basic understanding of the pathophysiology of endocrine neoplasia.
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