Macroscopic And Microscopic Features Of Neoplasms

The pathologist can gain valuable insights about the nature of a neoplasm by careful examination of the overall appearance of a surgical specimen. Often, by integrating the clinical findings with macroscopic characteristics of a tumor, a tentative differential diagnosis can be reached. Also, notation of whether the tumor is encapsulated, has extended through tissue borders, or reached to the margins of the excision provides important diagnostic information.

The location of the anatomic site of the neoplasm is important for several reasons. The site of the tumor dictates several things about the clinical course of the tumor, including (1) the likelihood and route of metastatic spread, (2) the effects of the tumor on body functions, and (3) the type of treatment that can be employed. It is also important to determine whether the observed tumor mass is the primary site (i.e., tissue of origin) of the tumor or a metastasis. A primary epidermoid carcinoma of the lung, for example, would be treated differently and have a different prognosis than an embryonal carcinoma of the testis metastatic to the lung. It is not always easy to determine the primary site of a neoplasm, particularly if the tumor cells are undifferentiated. The first signs of a metastatic tumor may be a mass in the lung noted on CT scan or a spontaneous fracture of a vertebra that had been invaded by cancer cells. Because the lungs and bones are frequent sites of metastases for a variety of tumors, the origin of the primary tumor may not be readily evident. This is a very difficult clinical situation, because to cure the patient or to produce long-term remission, the oncologist must be able to find and remove or destroy the primary tumor to prevent its continued growth and metastasis. If histologic examination does not reveal the source of the primary tumor, or if other diagnostic techniques fail to reveal other tumor masses, the clinician has to treat blindly, and thus might not choose the best mode of therapy.

Another consideration is the accessibility of a tumor. If a tumor is surgically inaccessible or too close to vital organs to allow complete resection, surgical removal is impossible. For example, a cancer of the common bile duct or head of the pancreas is often inoperable by the time it is diagnosed because these tumors invade and attach themselves to vital structures early, thus preventing curative resection. Similarly, if administered anticancer drugs cannot easily reach the tumor site, as is the case with tumors growing in the pleural cavity or in the brain, these agents might not be able to penetrate in sufficient quantities to kill the tumor cells.

The site of the primary tumor also frequently determines the mode of, and target organs for, metastatic spread. In addition to local spread, cancers metastasize via lymphatic channels or blood vessels. For example, carcinomas of the lung most frequently metastasize to regional lymph nodes, pleura, diaphragm, liver, bone, kidneys, adrenals, brain, thyroid, and spleen. Carcinomas of the colon metastasize to regional lymph nodes, and by local extension, they ulcerate and obstruct the gastrointestinal tract. The most common site of distant metastasis of colon carcinomas is the liver, via the portal vein, which receives much of the venous return from the colon and flows to the liver. Breast carcinomas most frequently spread to axillary lymph nodes, the opposite breast through lymphatic channels,lungs,pleura,liver,bone,adrenals,brain, and spleen.

Some tissues are more common sites of metastasis than others. Because of their abundant blood and lymphatic supply, as well as their function as "filters" in the circulatory system, the lungs and the liver are the most common sites of metastasis from tumors occurring in visceral organs. Metastasis is usually the single most important criterion determining the patient's prognosis. In breast carcinoma, for example, the 5-year survival rate for patients with localized disease and no evidence of axillary lymph node involvement is about 85%; but when more than four axillary nodes are involved, the 5-year survival is about 30%, on average.3

The anatomic site of a tumor will also determine its effect on vital functions. A lymphoma growing in the mediastinum may press on major blood vessels to produce the superior vena caval syndrome, manifested by edema of the neck and face, distention of veins of the neck, chest, and upper extremities, headache, dizziness, and fainting spells. Even a small tumor growing in the brain can produce such dramatic central nervous system effects as localized weakness, sensory loss, aphasia, or epileptic-like seizures. A lung tumor growing close to a major bronchus will produce airway obstruction earlier than one growing in the periphery of the lung. A colon carcinoma may invade surrounding muscle layers of the colon and constrict the lumen, causing intestinal obstruction. One of the frequent symptoms of prostatic cancer is inability to urinate normally.

The cytologic criteria that enable the pathologist to confirm the diagnosis, or at least to suspect that cancer is present (thus indicating the need for further diagnostic tests), are as follows:

1. The morphology of cancer cells is usually different from and more variable than that of their counterpart normal cells from the same tissue. Cancer cells are more variable in size and shape.

2. The nucleus of cancer cells is often larger and the chromatin more apparent ("hy-perchromatic'') than the nucleus in normal cells; the nuclear-to-cytoplasmic ratio is often higher; and the cancer cell nuclei contain prominent, large nucleoli.

3. The number of cells undergoing mitosis is usually greater in a population of cancer cells than in a normal tissue population. Twenty or more mitotic figures per 1000 cells would not be an uncommon finding in cancerous tissue, whereas less than 1 per 1000 is usual for benign tumors or normal tissue.4 This number, of course, would be higher in normal tissues that have a high growth rate, such as bone marrow and crypt cells of the gastrointestinal mucosa.

4. Abnormal mitosis and ''giant cells,'' with large, pleomorphic (variable size and shape) or multiple nuclei, are much more common in malignant tissue than in normal tissue.

5. Obvious evidence of invasion of normal tissue by a neoplasm may be seen, indicating that the tumor has already become invasive and may have metastasized.

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