Chapter 5 Neoplasia
Neoplasia means “new growth.” British pathologist Sir Rupert Willis defined it as follows: A neoplasm is an abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of normal tissues and persists in the same excessive manner after cessation of the stimuli that evoke the change.
Dysplasia means abnormal growth and differentiation. The term may have a developmental pathology or oncologic meaning. In developmental pathology, it is used to describe morphogenetic abnormalities (e.g., dysplastic kidneys). In oncology, it is used to describe disorderly growth and maturation of cells that are not normal but that are not obviously malignant. This kind of dysplasia is a premalignant condition, a precursor of invasive neoplasia. Dysplasia can also be considered as a transitional stage linking neoplasia to hyperplasia or metaplasia. Examples include:
Adult somatic cells are differentiated—that is, they express genes in a tissue-specific manner. Anaplasia of tumor cells is defined as lack of differentiation. Anaplastic tumor cells differ from normal cells and pathologists can recognize them as “atypical.” Common features of anaplasia include:
Neoplasms can be classified as benign or malignant on the basis of their clinical behavior. Benign tumors have a good prognosis, whereas malignant tumors have an unfavorable prognosis and are potentially lethal. A third category can be recognized for some tumor types, such as ovarian tumors. These tumors are called borderline malignant or low-grade malignant tumors. If recognized early and surgically resected, such borderline tumors have an excellent prognosis (>95% 5-year survival), but if untreated, they metastasize and will result in death.
Tumors often retain many of the histologic features of their tissue of origin. For example, a squamous cell carcinoma resembles normal squamous epithelium, whereas a transitional cell papilloma of the urinary bladder is lined by transitional epithelium resembling normal transitional epithelium. On the basis of such microscopic data, one can determine the composition of the tumors and in many instances theoretically reconstruct the histogenesis of most tumors (from Greco-Latin words histo, meaning “tissue,” and genesis, meaning “development”). The histologic–histogenetic classification of tumors is widely used to amplify the clinical classification. It serves as a basis for selecting treatment and for formulating the prognosis of the neoplastic disease in each particular case.
Most human organs (except for the nervous system) are composed of epithelial cells, connective tissue cells, or both. Malignant tumors of epithelial origin are called carcinomas. Sarcomas are malignant tumors of connective tissue origin. Epithelial cells of carcinomas form nests surrounded by nonneoplastic connective tissue stroma. In sarcomas, the tumor cells are intermixed with the nonneoplastic stromal cells.
Figure 5-1 Carcinoma and sarcoma. Carcinoma (CA) is composed of epithelial malignant cells surrounded by stroma that contains fibroblasts, collagen, and blood vessels. Because the epithelial cells form glands, this tumor is classified as an adenocarcinoma. Sarcoma (SA) is composed of malignant connective tissue (mesenchymal) cells that merge imperceptibly with other nonneoplastic mesenchymal cells that form the stroma of the tumor. The blood vessels are included in the stroma of this sarcoma but are not as visible as in the loose stroma of the carcinoma.
Yes. The names for benign tumors are formed by adding the suffix -oma to the cell of their origin. Thus a benign tumor originating from fibroblasts is called fibroma, a tumor of fat cells is called lipoma, a tumor of smooth muscle cells is called leiomyoma, a tumor of striated muscles is called rhabdomyoma, a tumor of bone is called osteoma, and so on.
Figure 5-2 Benign epithelial tumors. A, Adenoma is composed of glands. B, Papilloma is a nipplelike protrusion on the surface of the skin or mucosa of an internal organ, such as the urinary bladder. C, Polyp consists of fingerlike protrusions. Such a polyp is called sessile because it has a broad base and does not have a stalk. D, Pedunculated polyp has a stalk.
Mixed tumors are composed of both epithelial and connective tissue tumor cells. Benign mixed tumors composed of epithelial and myoepithelial cells and cells resembling cartilage cells are commonly found in the salivary glands. Malignant mixed tumors are called carcinosarcomas. Carcinosarcomas composed of adenocarcinoma and various sarcoma cells are most often found in the uterus. These uterine tumors are also called malignant mixed Müllerian tumors.
Teratomas are tumors of germ cell origin. They are composed of tissues derived from three germinal layers: ectoderm, endoderm, and mesoderm. Thus in a teratoma one may find ectodermal derivatives such as skin and neural tissue, endodermal derivatives such as intestine-like and bronchial-like structures, and mesodermal tissues such as bone or cartilage all intermixed in a haphazard manner. Malignant teratomas are called teratocarcinomas. These tumors consist of differentiated somatic tissues and malignant stem cells. These stem cells are developmentally equivalent to early embryonic cells and are called embryonal carcinoma cells.
Leiomyomas are tumors composed of smooth muscle cells. Rhabdomyomas are tumors of striated muscle cells (i.e., cells forming the skeletal or heart muscle). Malignant tumors composed of the same cells are called leiomyosarcomas and rhabdomyosarcomas, respectively.
Blastomas are tumors composed of immature cells resembling those that form the fetal anlage or primordia of adult organs. Retinoblastoma is a tumor of the eye, neuroblastoma is a tumor composed of nerve precursors cells (neuroblasts), and a hepatoblastoma is a tumor composed of fetal hepatocytes.
The suffix -oma attached to the cell or tissue of origin of a specific tumor is commonly used to name benign tumors (e.g., osteoma and fibroma). There are, however, some important exceptions to this rule, and seminoma is one of them. Seminoma is a malignant tumor of the seminal epithelium in the testis. The equivalent tumor originating from the female germ cells in the ovary is called dysgerminoma.
Most meningiomas (96%) are biologically benign intracranial tumors of limited growth potential. Because of their intracranial location and the proximity to vital centers, meningiomas must be removed surgically because they can increase the intracranial pressure and compress the vital centers. Although biologically benign, such meningiomas may kill the host (i.e., act in a clinically “malignant” manner).
|Differentiation||Resembles tissue of origin||Anaplastic, does not resemble tissue of origin|
|Nuclei||Normal size and shape||Atypical, pleomorphic|
|Mitoses||Few||Numerous, often abnormal|
During the past 150 years, clinicians and pathologists have been correlating the clinical behavior of various neoplasms with the histologic features of these tumors. Empirical clinicopathologic criteria have been formulated on the basis of such studies and are used to predict whether a tumor is benign or malignant. These criteria include:
Previously, it was thought that carcinomas metastasize through the lymphatics and sarcomas through blood vessels. This rule is only partially correct, and there are many exceptions. Tumors of organs that are rich in lymphatics, such as the breast and the large intestine, metastasize preferentially through the lymphatics. Such tumors may metastasize hematogenously as well, but blood-borne metastases usually occur in later stages of the disease. Tumors originating in organs that are well vascularized but contain few lymphatics, such as bones, tend to metastasize hematogenously. This fact accounts for the high rate of hematogenous metastases of bone sarcomas.
No. Malignant tumors of the brain usually kill the patient before the tumor has the chance to metastasize. The fact that brain tumors do not have metastases does not automatically mean that the cells of these tumors cannot metastasize. Evidence that brain tumors can metastasize includes the following:
Peritoneal seeding is common in patients with ovarian cancer. Malignant tumors originating from the surface epithelium of the ovary tend to detach and float away in the peritoneal fluid. Such floating cells may attach to the serosal surfaces covering the abdominal wall or abdominal organs.
Staging is used to determine the extent of spread of a tumor. It is based on correlating all the available clinical data with the pathologic findings. For example, the size of the tumor is assessed radiologically and on gross examination during surgery and in the pathology laboratory. The lymph nodes are examined to establish whether the tumor has spread to local and distant lymph nodes. Radiologic and radioisotope studies can be used to establish whether there are distant metastases.
Grading of tumors is based on microscopic examination of tumor tissues obtained at the time of operation or by biopsy. Tumors are graded on a scale from I to III, or descriptively as well differentiated, moderately well differentiated, or poorly differentiated. Although grading is important, overall, staging is much more predictive of the tumor behavior and is thus more valuable for prognosis.
The TNM system is used for staging of tumors. T stands for the size of the tumor, which is expressed according to defined criteria for each anatomic site on a scale from 1 to 4. N (from 0 to 3) stands for lymph node involvement, and M (0 negative, 1 positive) stands for distant metastases. Thus a small tumor that has not metastasized is designated as T1, N0, M0. A small tumor that has metastasized to lymph nodes and distant sites is designated as T1, N1, M1.
Yes. TNM is not a perfect system, and many other systems have been developed by cancer societies and even major medical centers. Some tumor staging systems were devised even before the TNM system was proposed and are still used in clinical practice. Probably the best-known staging system is the Dukes system for staging colon cancer.
Cancer epidemiology deals with the occurrence of tumors in human populations. By studying cancer incidence, prevalence, and specific mortality, epidemiologists try to identify environmental and genetic causes of cancer and thus contribute to better diagnosis, treatment, and prevention.
Epidemiologic data may point to a cause-and-effect relationship between a cancer and a potential carcinogen. For example, a high incidence of lung cancer among smokers provided the first indication that lung cancer may be related to tobacco smoking. These initial data were corroborated by showing that there is a dose–response relationship and that the risk of cancer is directly proportional to the number of years and the number of cigarettes smoked (“pack years”). Finally, it was shown that tobacco tar contains carcinogenic polycyclic hydrocarbons. These carcinogens can produce malignant tumors in experimental animals and are the most likely cause of cancer in tobacco smokers.