L26 Characters of Benign and Malignant Tumors PDF

L26 CHARACTERS OF BENIGN VERSUS MALIGNANT TUMORS ILOs By the end of this lecture, students will be able to 1. Relate nomenclature of tumors to their tissue of origin. 2. Explain the relation between Metaplasia, Dysplasia, and Carcinoma in Situ to malignancy. 3. Differentiate betw...

L26 CHARACTERS OF BENIGN VERSUS MALIGNANT TUMORS ILOs By the end of this lecture, students will be able to 1. Relate nomenclature of tumors to their tissue of origin. 2. Explain the relation between Metaplasia, Dysplasia, and Carcinoma in Situ to malignancy. 3. Differentiate between benign and malignant tumors as regards rate of growth, anaplasia, differentiation, invasion and metastasis. Nomenclature The terms neoplasm, “new growth” or “tumor” refer to abnormal masses of tissue. Definition; In contrast to non-neoplastic proliferations, Tumor is a new growth, that is autonomous, exceeds growth of normal tissues and persists after cessation of the initiating stimulus. A more modern definition; Neoplasm is a genetic disorder of cell growth that is triggered by acquired or ‘less commonly’ inherited mutations affecting a single cell and its clonal progeny. All tumors have two basic components: 1- Tumor parenchyma composed of clonal expansions of neoplastic cells. The classification of tumors and their biologic behavior are based primarily on the parenchymal component. 2- Supporting stroma composed of non-neoplastic connective tissue and blood vessels; abundant collagenous stroma is called desmoplasia. Tumor growth and spread are critically dependent on their stroma. Tumors are broadly classified based on clinical behaviors: Benign—with an “innocent” behavior characterized by a localized lesion without spread to other sites and amenable to surgical resection; the patient typically survives—although there are exceptions. Malignant—called cancers, with aggressive behavior including invasion and destruction of adjacent tissues, and capacity for spread to other sites (metastasis). Benign tumors typically end with the suffix -oma; o Benign mesenchymal tumors include lipoma, fibroma, angioma, osteoma, and leiomyoma. o Benign epithelial tumors also typically use the -oma suffix but in addition incorporates elements of histogenesis, macroscopic appearance, and microscopic architecture: Adenomas: Epithelial tumors arising in glands or forming glandular patterns. Examples; adenoma of solid organs as kidney and liver, and endocrine organ adenoma, as thyroid, pituitary gland, ect… Page 1 of 4  Cystadenomas: Adenomas producing large cystic masses, common in ovary. Papillomas: Surface Epithelial tumors forming gross or microscopic finger like projections, as skin papilloma and breast duct papilloma. Polyp: A neoplasm-benign or malignant-produces a grossly visible projection above a mucosal surface, for example, into the gastric or colonic lumen. If the polyp has glandular tissue, it is called an adenomatous polyp (e.g., a colon polyp) It is worth emphasizing that some tumors do not follow the -oma rule; for example, melanoma, lymphoma, and mesothelioma are all malignant. Malignant tumors are categorized as the following: Carcinomas derived from epithelium cells whether ectodermal or endodermal in origin. Sarcomas of mesenchymal cell origin. Mesenchymal tumors of blood-forming cells are called leukemias, and tumors of lymphocytes or their precursors are called lymphomas. The nomenclature for specific malignant tumors is based on their appearance and/or presumed cell of origin. Malignant epithelial tumors; Squamous Cell Carcinoma originates from Stratified squamous epithelial. Commonly found on the skin, mouth, esophagus, or vagina. Transitional cell carcinoma originates from transitional epithelium of urinary bladder. Adenocarcinomas, tumors with glandular epithelial origin. Malignant mesenchymal tumors; Sarcomas are designated by the appropriate cell prefix (e.g., smooth muscle malignancies are leiomyosarcomas). Neoplasms composed of poorly differentiated unrecognizable cells can only be designated as undifferentiated malignant tumors. Special tumor forms: Some tumors appear to have more than one parenchymal cell type: Mixed tumors derive from a neoplastic clone of a single germ cell layer that differentiates into more than one cell type (e.g., pleomorphic adenoma \ mixed salivary gland tumors containing epithelial cells mixed with myxoid and chondroid stroma). Teratomas; tumors that arise from totipotential cells capable of forming endodermal, ectodermal, and mesenchymal tissues. They are composed of various parenchymal cell types representative of more than one germ cell layer, and can have both benign and malignant forms. Such tumors typically occur in testis or ovary or rarely midline embryonic rests. Characteristics of Benign and Malignant Neoplasms Classification of a tumor as benign or malignant ultimately depends on its clinical behavior; however, morphologic and molecular evaluation allows categorization based on degree of differentiation, local invasion, and metastasis. Page 2 of 4 The above characteristics are only broad generalizations, and there are always exceptions. Metastasis is the only solid criteria of malignancy. 1- Differentiation and Anaplasia Differentiation refers to how closely tumor cells histologically (and functionally) resemble their normal cell counterparts Anaplasia refers to lack of differentiation. In general, neoplastic cells in benign lesions are well differentiated; cells in malignant neoplasms can range from well differentiated to completely undifferentiated. Well-differentiated tumors, whether benign or malignant, tend to retain the functional characteristics of their normal counterparts (e.g., hormone production by endocrine tumors or keratin production by squamous epithelial tumors). Malignant cells can revert to embryologic phenotypes or express proteins\ functional hormones not elaborated by the original cell of origin. Histologic changes in tumors (cytological features of malignancy) include the following: Pleomorphism: Variation in the shape and size of cells and/or nuclei Abnormal nuclear morphology: Darkly stained (hyperchromatic) nuclei with irregularly clumped chromatin, prominent nucleoli, and increased nuclear-to-cytoplasmic ratios (approaching 1:1 versus normal ratios of 1:4 or 1:6) Abundant and/or atypical mitoses reflecting increased proliferative activity and abnormal cell division (e.g., tripolar mitoses, so called Mercedes-Benz sign) Loss of polarity: Disturbed orientation and tendency for forming anarchic, disorganized masses Tumor giant cells with single polyploid nuclei or multiple nuclei Ischemic necrosis due to insufficient vascular supply. 2- Local Invasion Most benign tumors grow by expansion as cohesive, expansile masses that develop a surrounding rim of condensed connective tissue, or capsule. These tumors do not penetrate the capsule or the surrounding normal tissues, and the plane of cleavage between the capsule and the surrounding tissues facilitates surgical enucleation. Malignant neoplasms are typically invasive and infiltrative, destroying surrounding normal tissues. They commonly lack a well-defined capsule and cleavage plane, making simple excision impossible. Consequently, surgery requires removal of a considerable margin of healthy and apparently uninvolved tissue. 3- Metastasis Metastasis involves invasion of lymphatics, blood vessels, or body cavities by tumor, followed by transport and growth of secondary tumor cell masses discontinuous from the primary tumor. This is the single most important feature distinguishing benign from malignant. Page 3 of 4  Metastatic spread increases with lack of differentiation, local invasion, rapid growth, and large size. Almost all malignant tumors can metastasize; except for central nervous system (CNS) tumors and cutaneous basal cell carcinomas that rarely metastasize. Special forms of malignant tumors Occult carcinoma: it is the term given to carcinoma which manifests itself primarily as metastases because the original tumor is not sufficiently large to produce symptoms, e.g.: carcinoma of prostate, nasopharynx, maxillary antrum, and thyroid gland. Locally malignant tumors: they are malignant tumors which are locally invasive and destructive, but they do not give rise to distant metastases, e.g Basal cell carcinoma, Giant cell tumor of bone (osteoclastoma), carcinoid tumor of the appendix, and adamantinoma of the jaw. References: 1. Kumar, Abbas, Aster. Robbins Basic Pathology, 10th ed. Elsevier. 2. Mitchell, Kumar, Abbas, Aster. Pocket Companion to Robbins and Cotran Pathologic Basis of Disease, 9 th ed. Elsevier. Page 4 of 4