Thus far, we have been considering carcinomas as cancers that pose a threat to life because they are invasive, which means that they have the potential to metastasize to other parts of the body. A pathologist will usually include the term invasive or infiltrating in a pathology report to indicate this important aspect of the cancer. For example, a tumor of the larynx may show invasive squamous cell carcinoma, one from the stomach, invasive adenocarcinoma, or one from the breast, infiltrating ductal carcinoma. The terms invasive or infiltrating will be used when the pathologist sees the cancer cells invading through the first tissue barrier underneath it.
If a tumor biopsy shows invasive carcinoma, then a staging workup will be undertaken to determine if any cancer deposits can be found elsewhere in the body. This evaluation is often performed before surgical removal of the primary tumor but in certain cases may be performed afterward. The results of the staging workup determine the extent of the disease and whether surgery can remove or has removed all visible areas of involvement.
Not all carcinomas, however, are invasive. One class of carcinoma is considered pre-invasive. This type of cancer is called carcinoma insitu (Latin for in site or in place). Under the microscope, carcinoma in-situ (CIS) does not penetrate the tissue barriers beneath it. Although CIS cells are growing in the characteristic disorganized way that identifies the tumor as a cancer, they have not yet acquired the ability to metastasize-to break into surrounding tissues and gain access to the blood or lymph stream to spread to other parts of the body. CIS does not pose an imminent threat to life, but it can develop into invasive carcinoma over time and must be treated. Most cases of CIS are surgically removed if detected, rendering the patient cured of the CIS and eliminating the possibility that invasive cancer will develop from that area of carcinoma in-situ. CIS is not treated with chemotherapy, but radiation and hormonal therapy may play a role in treatment, especially in breast cancer. The cure rate for CIS is almost 100 percent.
In addition to being an early cancer that is highly curable, carcinoma in-situ is also an indicator that the affected person is at an increased risk for the future development of cancer (both in-situ and invasive types). Therefore, after someone is treated for CIS, he or she should undergo regular surveillance testing to detect newly developing cancers at their earliest, most curable stages. In addition, CIS marks an important moment in the health of a patient: it is an ideal time to take advantage of cancer prevention measures or make lifestyle changes that help ward off the disease.
Carcinoma in-situ is most commonly encountered in the breast. The detection of ductal carcinoma in-situ (DCIS) of the breast has dramatically increased since mammography has replaced simple physical examination as the primary way in which breast cancer is detected today. Mammography enables the detection of much smaller cancers than are found by physical examination alone, and an increasing number of these smaller cancers consist of DCIS rather than invasive breast cancer. Many women who develop DCIS are advised to take the drug tamoxifen for five years after DCIS is treated in order to prevent the future development of breast cancer. Tamoxifen blocks the stimulating effects of estrogen on breast cells and reduces the future occurrence of both DCIS and invasive breast cancer. These cancer-reducing effects are experienced by both breasts, not just the one in which the DCIS is found.
Carcinoma in-situ is found in other parts of the body much more often than is widely recognized, in part because patients are usually told that they have, not CIS, but rather a tumor that is the step before [invasive] cancer. For example, CIS can be found in a bladder polyp that may call attention to itself by causing blood in the urine. To screen for cervical cancer, a Pap smear is performed, which may lead to a diagnosis of dysplasia or cervical intraepithelial neoplasia (CIN); the most severe form of dysplasia is CIN III, which is equivalent to carcinoma in situ. Other areas in which CIS can be found include the colon, prostate, thyroid, oral cavity, testicle, anus, and lung. Interestingly, both carcinoma in-situ and invasive cancer are sometimes found in the same tumor, indicating that the invasive cancer grew out of the CIS.
Imagine being told that you have cancer in one or several regions of your body but that the doctors cannot determine where it started. In other words, you have metastatic cancer without a corresponding primary tumor to indicate where the cancer began. The liver, bones, lungs, lymph nodes, or other areas may be affected but in a way that indicates that the cancer spread to them from some other primary location. Investigation of the breast, prostate, lungs, gastrointestinal tract, and other organs, however, fails to reveal the tumor of origin.
People who have this perplexing and frightening condition frequently request that a total body CT scan be performed in an effort to locate the primary tumor. Often, however, a full-body CT scan, an MRI, and even a PET scan cannot locate the primary cancer. Patients may seek numerous opinions and go to the biggest cancer hospitals in the hope that some doctor will be smart enough to figure out where the cancer began. These efforts are natural and thoroughly understandable. In the end, however, neither a sophisticated test nor the most skilled physician will be able to uncover the cancer source. The diagnosis will remain carcinoma of unknown primary site (CUP).
Carcinoma of unknown primary site is not on the list of the most common cancers. I have yet to hear it mentioned in the news, and I have never met a new patient who was familiar with it. One would think it is a rare type of cancer. Yet surprisingly, CUP accounts for approximately 5 percent of cancers, making it a disease that oncologists are quite familiar with. This type of carcinoma has been the subject of many clinical trials and has been studied by cancer researchers for many years. There are standardized ways of treating it in all its manifestations. Patients with CUP must suffer the anguish of battling a cancer they cannot understand and cannot easily describe. Most tell others that they have bone cancer, liver cancer, or another type depending on where the disease is most burdensome; to describe CUP invites questions and doubts about the diagnosis. Some CUP patients I care for ask me at nearly every office visit to explain their cancer again and to review once more where it could possibly have come from. CUP is not only an enormously frustrating cancer but also a lethal one, with average survivals of less than two years.
Most cases of CUP are thought to represent the metastases of a carcinoma that either completely shrank away (involuted) or is too small to be detected by current methods. Pathologists will perform numerous tests on the cancer specimen to try to determine its origin. When such tests fail to identify an organ of origin, the diagnosis is CUP. It is hoped that sophisticated genetic analyses of CUP tumors will yield more accurate ways of classifying them; these tests are undergoing validation in clinical trials.
Cancers of unknown primary site are usually treated with chemotherapy and sometimes also with radiation therapy. Some patients can be cured if the cancer is localized and not disseminated in the body, in which case surgery may play a role. Better treatments are clearly needed for advanced cases of CUP. Researchers are trying to gain a better understanding of how CUP develops so that greater strides can be made against this cancer.
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