malignant tumors

The nomenclature of malignant tumors essentially follows the same schema used for benign neoplasms, with certain additions.

Malignant tumors arising in mesenchymal tissue are usually called sarcomas (Greek sar = fleshy) because they have little connective tissue stroma and so are fleshy (e.g., fibrosarcoma, liposarcoma, leiomyosarcoma for smooth muscle cancer, and rhabdomyosarcoma for a cancer that differentiates toward striated muscle).

Malignant neoplasms of epithelial cell origin, derived from any of the three germ layers, are called carcinomas. Thus, cancer arising in the epidermis of ectodermal origin is a carcinoma, as is a cancer arising in the mesodermally derived cells of the renal tubules and the endodermally derived cells of the lining of the gastrointestinal tract.

Carcinomas may be further qualified. One with a glandular growth pattern microscopically is termed an adenocarcinoma, and one producing recognizable squamous cells arising in any epithelium of the body is termed a squamous cell carcinoma.

It is common practice to specify, when possible, the organ of origin (e.g., a renal cell adenocarcinoma or bronchogenic squamous cell carcinoma).

Not infrequently, however, a cancer is composed of undifferentiated cells of unknown tissue origin, and must be designated merely as a poorly differentiated or undifferentiated malignant tumor (see anaplasia).

The natural history of most malignant tumors can be divided into four phases:
 (1) malignant change in the target cell, referred to as transformation;
 (2) growth of the transformed cells;
 (3) local invasion;
 (4) distant metastases.

The differences between benign and malignant tumors correspond to these characteristics and are discussed under the headings of differentiation and anaplasia, rate of growth, local invasion, and metastasis.

In the great majority of instances, a benign tumor may be distinguished from a malignant tumor with considerable confidence based on morphology; sometimes, however, a neoplasm defies categorization.

Certain anatomic features may suggest innocence, whereas others point toward cancerous potential. Ultimately, morphologic diagnosis cannot predict the biologic behavior or clinical course of a neoplasm with absolute certainty.

Occasionally, this prediction is confounded by a marked discrepancy between the morphologic appearance of a tumor and its behavior: An innocent face may mask an ugly nature.

Such deception or ambiguity, however, is not the rule; in general, there are morphologic criteria by which benign and malignant tumors can be differentiated, and the behavior of the tumors can be predicted by these criteria.

See also

 tumoral differentiation
 dysplasia

Cellular characteristics

 Pleomorphism. Both the cells and the nuclei characteristically display pleomorphism-variation in size and shape. Cells may be found that are many times larger than their neighbors, and other cells may be extremely small and primitive appearing.

 Abnormal nuclear morphology. Characteristically the nuclei contain an abundance of DNA and are extremely dark staining (hyperchromatic). The nuclei are disproportionately large for the cell, and the nucleus-to-cytoplasm ratio may approach 1:1 instead of the normal 1:4 or 1:6. The nuclear shape is very variable, and the chromatin is often coarsely clumped and distributed along the nuclear membrane. Large nucleoli are usually present in these nuclei.

 Mitoses. As compared with benign tumors and some well-differentiated malignant neoplasms, undifferentiated tumors usually possess large numbers of mitoses, reflecting the higher proliferative activity of the parenchymal cells. The presence of mitoses, however, does not necessarily indicate that a tumor is malignant or that the tissue is neoplastic. Many normal tissues exhibiting rapid turnover, such as bone marrow, have numerous mitoses, and non-neoplastic proliferations such as hyperplasias contain many cells in mitosis. More important as a morphologic feature of malignant neoplasia are atypical, bizarre mitotic figures, sometimes producing tripolar, quadripolar, or multipolar spindles.

 Loss of polarity. In addition to the cytologic abnormalities, the orientation of anaplastic cells is markedly disturbed (i.e., they lose normal polarity). Sheets or large masses of tumor cells grow in an anarchic, disorganized fashion.

 Anaplasia. Another feature of anaplasia is the formation of tumor giant cells, some possessing only a single huge polymorphic nucleus and others having two or more nuclei. These giant cells are not to be confused with inflammatory Langhans or foreign body giant cells, which are derived from macrophages and contain many small, normal-appearing nuclei. In the cancer giant cell, the nuclei are hyperchromatic and large in relation to the cell. Although growing tumor cells obviously require a blood supply, often the vascular stroma is scant, and in many anaplastic tumors, large central areas undergo ischemic necrosis.

As mentioned, malignant tumors differ widely in the extent to which their morphologic appearance deviates from the norm. On one end of the spectrum are the extremely undifferentiated, anaplastic, tumors and at the other end are cancers that bear striking resemblance to their tissues of origin.

Certain well-differentiated adenocarcinomas of the thyroid, for example, may form normal-appearing follicles, and some squamous cell carcinomas contain cells that do not differ cytologically from normal squamous epithelial cells.

Thus, the morphologic diagnosis of malignancy in well-differentiated tumors may sometimes be quite difficult. In between the two extremes lie tumors that are loosely referred to as moderately well differentiated.