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The relationship between tumor morphology and the clinical behavior of tumors has been known for more than a century, and the study of such clinicopathologic correlations could be traced to the teachings of Rudolf Virchow and the scientific beginnings of microscopic pathology. From the historical point of view, however, the first attempts to correlate the microscopic features of tumors with their biology and clinical behavior traditionally are attributed to von Hansemann (1–3). In the 1890s, this German pathologist published his observations on anaplasia and abnormal mitotic figures and first suggested that the biologic and clinical behavior of tumors could be predicted from their microscopic characteristics. His pioneering publications on tumor cell atypia, anaplasia, and asymmetrical mitoses were summarized in a 1897 book, which was so popular that it reappeared 5 years later in a second edition (Figure 1-1). This book, based on meticulous microscopic study of tumors, contains drawings illustrating the author’s views of cancer (Figure 1-2).The clarity of these illustrations is fascinating even today.

Tumors of the mouth, pharynx, nose, and paranasal sinuses are commonly encountered in general surgical pathology practice. Some, such as squamous cell carcinoma, resemble homonymous tumors in other parts of the body, whereas others, such as olfactory neuroblastomas, are unique to this anatomic region. This chapter limits the discussion to the tumors that are most often graded by surgical pathologists.

Pathologists generally agree that histologic grading of some malignant salivary gland tumors is predictive of their clinical behavior (1,2). However, the data on the clinical utility of grading all salivary tumors are incomplete (). In addition, subjectivity of grading and interobserver variation appear to limit the impact of tumor grading.

Most neoplastic lesions of the larynx and hypopharynx originate from the squamous epithelium. These tumors include benign lesions such as papillomas, as well as preinvasive intraepithelial neoplasms and invasive squamous cell carcinomas. This chapter reviews only the squamous intraepithelial lesions and invasive squamous cell carcinoma.

Carcinoma of the lung is a common malignant tumor. Histological typing of lung tumors has long been a source of controversy in pathology, in large part due to the marked heterogeneity that these tumors are capable of exhibiting (1–4). Although the bronchi and lungs may give rise to a wide variety of histopathologic types of malignant epithelial neoplasms, lung cancer grading is usually restricted to the 2 most common types of bronchogenic carcinoma included in the latest World Health Organization (WHO) classification: squamous cell carcinoma and adenocarcinoma. Neuroendocrine carcinoma of the lung constitutes a third major group of lung neoplasms for which grading is promising, as the histologic grading of these tumors appears to correlate with their clinical behavior and prognosis (5). The fourth major category of bronchogenic carcinoma in the WHO classification, large cell carcinoma, is not subject to grading, since it is by definition a high-grade neoplasm.

Primary thymic epithelial neoplasms represent the most common type of tumors of the anterior mediastinum. These tumors have been a source of major controversy over the years, due to the difficulty of their histopathologic typing and their often unpredictable biologic behavior. Unlike malignant epithelial neoplasms arising in other organs, for many years it was thought that these tumors were unsuitable for histologic grading. In fact, the latest World Health Organization schema for the classification of thymic epithelial neoplasms does not even mention grading for these tumors.

The tumors of the tubular part of the digestive system, the liver, and the pancreas account for a significant portion of the day-to-day surgical pathology material in most diagnostic pathology laboratories. While many of these gastrointestinal tumors are microscopically identical to the homonymous tumors in other parts of the body, some are unique to the digestive system. This chapter reviews the grading of the most important neoplasms and related preneoplastic conditions of the digestive system.

The grading of endocrine gland tumors has been difficult, inconsistent, and unrewarding. While the reasons for these problems vary from organ to organ, and from one tumor type to another, in general grading has been hampered by the following issues:

Urogenital tumors are among the most common human tumors. Malignant tumors predominate, and the most important malignant neoplasms in this group are renal cell carcinoma, urothelial carcinoma of the urinary bladder, testicular carcinoma, and prostatic carcinoma. Testicular cancer is not generally assigned a microscopic grade, but the other 3 tumors are routinely graded according to well-established principles (; ; ; ).

Tumors of the female genital organs are often biopsied or surgically resected, and thus form a significant part of surgical pathology material in most institutions. Invasive tumors and premalignant or borderline lesions are routinely graded, and in many instances the grade assigned by the pathologist is an important determinant of the treatment for these conditions.