Endocrine Tumors—Part 1

Abstract

FigureFigureSince the third volume of the World Health Organization (WHO) Classification of Tumours of Endocrine Organs was published in 2004, more than a decade ago, the following remarkable accomplishments have been achieved and included in the new fourth volume released in June of 2017. biologic behavior and prognosis new therapies and corresponding surrogate biomarkers immunophenotypes and molecular pathology genetic background of the tumors The new WHO volumes contain the following chapters: Tumors of the Pituitary Tumors of the Thyroid Gland Tumors of the Parathyroid Gland Tumors of the Adrenal Cortex Tumors of the Adrenal Medulla and Extra-adrenal Paraganglia Neoplasms of the Neuroendocrine Pancreas Inherited Tumor Syndromes In order to make new fourth WHO classification practically familiar among surgical pathologists and other professionals dealing with endocrine tumors, AJSP-RR is publishing 2 issues devoted to the fourth WHO classification of the endocrine tumors. Each chapter in WHO blue book has the structure with the items in order: Definition, Synonyms, Epidemiology, Etiology, Localization, Clinical Features (including diagnostic tests, Imaging), Macroscopy, Microscopy, Genetic Profile, Genetic Susceptibility, Prognosis, and Predictive Factors. This first AJSP-RR issue includes reviews on the following topics: (1) pituitary (Osamura), (2) medullary thyroid carcinoma (DeLellis), (3) nonmedullary thyroid cancers (Lam), and (4) adrenal cortex (Sasano). We have also included a case report devoted to cytopathology of paragangliomas. PITUITARY GLAND The fourth edition devotes attention to the transcription factors, which are involved in the differentiation pathways linked to particular hormone production; it has been shown that pituitary adenomas are derived from the differentiated anterior pituitary cells: somatotroph, lactotroph, thyrotroph, and so on. Therefore, the nomenclature of adenomas has been changed to somatotroph adenoma, lactotroph adenoma, thyrotroph adenoma, and others. The atypical adenoma category proposed in 2004 (Ki-67 >3% and p53 positive) is no longer included in the new WHO classification because its incidence is low and its significance for prognosis is not evident. Instead, the fourth edition proposes to use morphologic features that portend aggressive behavior, for example, sparsely granulated somatotroph adenoma with fibrous bodies, Crooke’s adenoma, and others. SSTR2, SSTR5, MGMT, and MSH6 are the predictive biomarkers that can be detected by immunohistochemistry. Familial tumor syndromes include 10 genetic alterations, and growth hormone (GH), prolactin (PRL) production in these conditions has been emphasized. THYROID Epithelial tumors: The most important achievement in the area of thyroid pathology is molecular genetics characterization of well-differentiated, follicular-patterned thyroid tumors composed of follicular cells with a differential diagnosis of papillary versus follicular and benign versus malignant. Several new categories have been introduced for papillary thyroid carcinoma. Several categories remained in the intermediate group between follicular adenoma versus follicular carcinoma/follicular variant of papillary carcinoma. These tumors sometimes are designated as “tumors of uncertain malignancy” and are still under discussion. “Noninvasive follicular thyroid neoplasm with papillary-like nuclear features” was adopted as a new terminology for the indolent tumors with particular nuclear appearance. Poorly differentiated carcinoma and oncocytoma were recognized as distinct entities. Medullary thyroid carcinoma is a unique tumor that produces calcitonin and carcinoembryonic antigen and is a part of multiple endocrine neoplasia type 2 syndrome. In the fourth edition, morphologic appearance is emphasized along with notable variants. Genetic molecular aberrations including RET and RAS are included in the discussion. ADRENAL CORTEX This review includes the Weiss criteria for malignancy in adrenal cortical tumors and Weiss and Lin-Weiss-Bisceglia criteria of malignancy in oncocytic adrenal cortical neoplasms. It is noteworthy to mention that various molecular parameters can distinguish adenomas from carcinomas. Carcinomas can be further divided into good and poor prognostic groups. Various hereditary syndromes are also included in this review. IN THE SECOND INSTALLMENT OF THIS ISSUE The second installment of the endocrine topics will contain review articles reflecting the WHO 2017 positions on the following: tumors of the adrenal medulla and extra-adrenal paraganglia, neuroendocrine tumors of the pancreas and inherited endocrine tumor syndromes.