Systemic Diseases Affecting the Salivary Glands Reksten TR
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k Systemic Diseases Affecting the Salivary Glands 161 Reksten TR, Jonsson MV. 2014. Sjogren’s syndrome – An Vairaktaris E, Vassiliou S, Yapijakis C, et al. 2005. Salivary update on epidemiology and current insights on patho- gland manifestations of sarcoidosis: Report of three cases. physiology. Oral Maxillofac Surg Clin N Am 26:1–12. J Oral Maxillofac Surg 63:1016–1021. Talal N, Bunim J. 1964. The development of malignant lym- Werning JT. 1991. Infectious and systemic diseases. In: phoma in the course of Sjogren’s syndrome. Am J Med Ellis GL, Auclair PL, Gnepp DR (eds), Surgical Pathology 36:529–540. of the Salivary Glands. Philadelphia, W.B. Saunders Co., Turner MD. 2014. Salivary gland disease in Sjogren’s syn- pp. 39–59. drome. Sialoadenitis to lymphoma. Oral Maxillofac Surg Clin N Am 26:75–81. k k k k k k k k Chapter 7 Classification, Grading, and Staging of Salivary Gland Tumors John J. Sauk, DDS, MS, FAAAS, FAHNS1 and J. Michael McCoy, DDS 2 1University of Louisville, Louisville, KY, USA 2Departments of Oral and Maxillofacial Surgery, Pathology, and Radiology, University of Tennessee Medical Center, Knoxville, TN, USA Outline Sebaceous Lymphadenocarcinoma Oncocytic Carcinoma Introduction Salivary Duct Carcinoma Classification Systems for Salivary Gland Neoplasms The Cellular Classification Of Salivary Gland Neoplasms Primary Mucinous Adenocarcinoma Benign Salivary Gland Neoplasms Malignant Mixed Tumors Pleomorphic Adenoma (Benign Mixed Tumor) Carcinoma Ex. Pleomorphic Adenoma Salivary Carcinosarcoma Papillary Cystadenoma Lymphomatosum (Warthin Sialoblastoma Tumor) Metastasizing Mixed Tumor Monomorphic Adenomas Rare Carcinomas k Basal Cell Adenoma k Primary Squamous Cell Carcinoma Canalicular Adenoma Epithelial-Myoepithelial Carcinoma Oncocytoma Anaplastic Small Cell Carcinoma Sebaceous Adenoma Undifferentiated Carcinomas Sebaceous Lymphadenoma Small Cell Undifferentiated Carcinoma Myoepithelioma Large Cell Undifferentiated Carcinoma Cystadenoma Lymphoepithelial Carcinoma Ductal Papilloma Myoepithelial Carcinoma Sclerosing Polycystic Adenosis Adenosquamous Carcinoma Malignant Epithelial Neoplasms Mammary Analogue Secretory Carcinoma Mucoepidermoid Carcinoma Non-Epithelial Neoplasms Adenoid Cystic Carcinoma Lymphomas and Benign Lymphoepithelial Lesions Adenocarcinomas Mesenchymal Neoplasms Acinic Cell Carcinoma Benign Mesenchymal Salivary Gland Tumors Polymorphous Low-Grade Adenocarcinoma Malignant Mesenchymal Salivary Gland Tumors Adenocarcinoma not Otherwise Malignant Secondary Neoplasms Specified (NOS) Rare Adenocarcinomas Grading and Staging of Salivary Gland Tumors Molecular Systematics of Salivary Gland Neoplasms Basal Cell Adenocarcinoma Staging of Salivary Gland Tumors Clear Cell Carcinoma Hyalinizing Clear Cell Carcinoma Summary Cystadenocarcinoma References Sebaceous Adenocarcinoma Salivary Gland Pathology: Diagnosis and Management, Second Edition. Edited by Eric R. Carlson and Robert A. Ord. © 2016 John Wiley & Sons, Inc. Published 2016 by John Wiley & Sons, Inc. 163 k k 164 Chapter 7 Introduction demonstrate diagnostic, prognostic, and predictive performance. This can generally be accomplished Scientific classification is a method by which for any data set by training. However, it is well researchers and clinicians categorize species of known that unless training is unsupervised (no organisms. Modern classification has its roots in knowledge of the correct class is involved), the per- the work of Carolus Linnaeus, also known as Carl formance of the system being tested on the training von Linné, the Father of Taxonomy, who grouped dataset is totally uninformative about its true species according to shared physical characteris- operation (Ioannidis 2007). Cross-validation and tics. Accordingly, scientific classification belongs independent validation are two methods to deter- to the science of taxonomy or biological system- mine whether the proposed scheme is an accurate atics. Molecular systematics, which uses genomic classifier (Allison, et al. 2006). Despite the method and proteomic expression data, has driven many employed, different metrics can be used to describe recent revisions in these systems. In a like man- the classifier performance. These may include sta- ner, surgeons, pathologists, and oncologists have tistical testing measures, multiplicative effect endeavored to systematically categorize tumors measures such as likelihood ratios or hazard ratios, on the basis of designated characteristics so as to or absolute effect measures. Although all infor- predict probable biological behavior. This in turn mation has some value, absolute effect measures would help dictate appropriate therapeutic modal- (sensitivity and specificity) are the most meaning- ities to be employed and help forecast a credible ful from a clinical perspective (Buyse, et al. 2006). prognosis. As such, the “designated character- istics” upon which tumors have been classified may be in more contemporary terms considered Classification Systems for Salivary as “biomarkers”. In a like fashion, genomic and Gland Neoplasms proteomic expression profiles of tumors have thrust pathology and oncology into molecular systematics k The classification system for salivary gland neo- k to develop classifications. plasms has evolved with the accumulation of The role of molecular profiling or systematics clinical experience and our understanding of the for clinical decision making and taxonomy has basis of neoplasia. Although a variety of classi- been recently considered and the classification of fications have been advocated, there has been tissue or other specimens for diagnostic, prognos- some geographic variation in terminology and tic, and predictive purposes based on multiple gene classification between European and American expression and proteomics has been noted to hold authors. Historically, the first most notable clas- major promise for optimizing the management of sification was that put forth by Foote and Frazell patients with cancer (Ioannidis 2007). However, (1954). Later systems reflect the recognition and assay development and data analysis have been description of previously unrecognized entities or principally investigative, and there exists a lofty the deletion of some terms that were misnomers or potential for the introduction of bias. Most trou- were considered meaningless. The succeeding clas- bling is that standardization of profiles has been sifications include those by: Thackray and Lucas the exception. Moreover, classifier performance is (1974); Evans and Cruickshank (1970); the World typically over-interpreted by conveying the results Health Organization (WHO; Thackray and Sobin as p-values or multiplicative effects, whereas the 1972); Batsakis (1979); Seifert, et al. (1986b); and absolute sensitivity and specificity of classifica- Auclair and Ellis (1991). The most recent AFIP fas- tion are modest, particularly when tested in large cicle on the subject provides a stepwise evolution validation samples (Ioannidis 2007). Furthermore, of these taxonomies (Ellis and Auclair 2008). validation has frequently been made with less than favorable consideration for methodology and safe- guarding for bias. Most disconcerting is that the THE CELLULAR CLASSIFICATION OF postulated classifier performance can be inflated SALIVARY GLAND NEOPLASMS compared to what these profiles can accomplish. Whether traditional morphological desig- Salivary gland neoplasms are noted for their nated characteristics or molecular systematics histological variability. Reflecting the anatomy are employed, the aim of any classification is to of these glands, benign and malignant salivary k k Classification, Grading, and Staging of Salivary Gland Tumors 165 gland neoplasms may arise either from epithelial, in the determination and correct identification of mesenchymal, or lymphoid origins. The complex- salivary gland lesions. ity of the classification and the rarity of some The following cellular classification system of these tumors, some of which display a wide reiterates that advocated by the National Cancer spectrum of morphological patterns within the Institute of the USPHS (National Cancer Insti- same tumor when added to the existence of hybrid tute, www.cancer.gov), which is derived heavily lesions, challenge the surgical pathologist with a from that published by the Armed Forces Insti- difficult task in differentiating benign from malig- tute of Pathology (AFIP) (Ellis and Auclair 2008) nant tumors (Seifert and Donath 1996; Speight (Table 7.1). Similar to the NCI scheme we also and Barrett 2002). At the present time, the surgical include malignant non-epithelial neoplasms since pathologists often must use every available tool in these lesions embrace a sizable proportion of order to properly diagnose and classify tumors aris- salivary gland neoplasms. Though less common, ing from the major and minor salivary glands. No the inclusion of malignant secondary tumors is longer can histology alone be used for such deter- presented to be inclusive. minations. The pathologist at the moment uses not As noted in the introduction, statistics regard- only routine light microscopy but also immuno- ing the incidence, frequency, and prognosis have histochemistry, specialized imaging, and clinical varied depending on the study. Moreover, a cur- characteristics of each tumor in order to establish sory review of the literature generally reveals that power analyses are rarely performed to access the the exact diagnosis. Time after time, immunohisto- necessary sample size for many of these studies chemistry