By Amy L. Friedman, MD, FACS & Thomas G. Peters, MD, FACS, FASN

Since the early years of kidney transplantation, the risk of certain types of cancer in transplant recipients has been widely known. Common cancers, such as breast, colon and prostate cancer, do not occur much more often in transplant patients. Other tumors such as certain leukemia and lymphomas, skin cancers and Kaposi’s sarcoma do occur far more often in transplant patients than in the general population. In order to best describe the cancers which are most often seen following transplantation, we will review tumors of the skin, other related (squamous) cancers, blood or white cell malignancies (lymphoma), and the soft tissue tumors which occur in transplant patients and other persons who are immunosuppressed. The reasons for development of tumors and the general treatment plans will also be mentioned as well as the likelihood that cancer would develop in a kidney transplant recipient.

 Skin Cancers

Cancers of the skin, especially skin which is exposed to sun, are the most common cancers that occur in transplant recipients. There are three broad categories of skin cancer: squamous cell, basal cell and melanoma. The most common type of skin cancer is squamous cell cancer. The risk for development of squamous cell skin cancer may be twenty-times greater in transplant recipients than in the general population. Basal cell cancers also are estimated to occur at rates tentimes higher than the general population, while malignant melanoma is estimated to occur at about five-times the rate experienced by those who have not had a transplant and are not immunosuppressed. While both squamous cell and basal cell cancers are usually considered "curable", these tumors can spread to other areas of the body and can be very dangerous in certain patients, especially those taking immunosuppressive medications. Malignant melanoma is one of the most dangerous of all known cancers and these tumors may spread rapidly and take the life of the patient.

The removal and care for melanoma is different from squamous cell or basal cell cancer. Because melanoma poses a very high risk, patients may need rather extensive surgery to remove lymph nodes or even other major procedures. While alterations in immunosuppressive drugs, usually by lowering the dose or placing the patient on less potent medicines, is common with squamous cell and basal cell cancer, withdrawal of immunosuppression may be indicated if the patient develops melanoma. This may mean the patient would reject the kidney, but ongoing immunosuppression in the face of melanoma may prove fatal for the patient. It may be far better to withdraw immunosuppression, allow rejection to occur, return to dialysis treatment and hope that a competent immune system would combat the melanoma.

A very rare skin cancer is called Merkel’s cell tumor.This type of cancer can also be quite aggressive, and usually requires surgery on the tumor and the local lymph nodes. Just as with melanoma, treatment of Merkel’s cell tumor may require stopping immunosuppressive medications. Merkel’s cell tumor can spread to other areas of the skin, deeper tissues and internal organs. In its most aggressive form, this cancer also can be fatal.

Kaposi’s Sarcoma

The tumor called Kaposi’s sarcoma is often associated with acquired immune deficiency syndrome (AIDS). The reason for this is that patients who have AIDS are immunosuppressed by the nature of the disease. Kidney transplant patients take medications which cause them to be immunosuppressed so rejection of the kidney does not occur. Generally speaking, immunosuppression in AIDS is more profound than for patients who have a transplanted organ. Therefore, Kaposi’s sarcoma occurs much less often in transplant patients than in those patients affected with AIDS. Furthermore, the presence of Kaposi’s sarcoma in a transplant patient does not mean the patient either has AIDS or is more susceptible to AIDS. Testing for the virus which causes AIDS is done in all transplant recipients, and if a transplant recipient contracts Kaposi’s sarcoma, it is much more easily treated than in a patient who has AIDS.

Kaposi’s sarcoma occurs rarely in the general population. For patients having had an organ transplant, the risk of Kaposi’s sarcoma is higher than the general population, but still very low in terms of number of cases since this tumor is so rare. In a very good study done in Australia, over 10,000 patients who had received a transplant were studied, and only 14 of those patients developed Kaposi’s sarcoma.

The treatment for Kaposi’s sarcoma in the transplant patient is stopping of all immunosuppressional drugs. About half of the patients who have immunosuppressive drugs stopped reject the kidney but also are able to expect significant improvement or cure from the cancer. The other half of patients also may expect improvement in the tumor, and may go on to retain function of the transplant.

Other Squamous Cancers

There are other types of squamous cancers that can affect transplant patients. The word squamous comes from Latin and French words which mean scale, as in the skin of a lizard or snake. So the cells which are designated as squamous cells in our body are cells which cover surfaces. These surfaces may be outside surfaces such as our skin, or the inside lining of certain organs such as the esophagus, anal canal, or areas of the reproductive tract including the vagina. All of these areas are susceptible to squamous cell cancers in the normal population as well as in those patients having received an organ transplant. Further, cancer of the esophagus, anal canal and the female reproductive tract may occur two to five times more often in transplant patients than in the general population. It is important, therefore, for all transplant patients to have a routine health assessment and physical examination to address these increased risks. This is especially so for women who should have a pelvic examination and Pap smear once annually after a kidney transplant.

The treatment for non-skin squamous cell cancers in transplant patients is the same as for the general population. Often times, surgical removal and radiation or chemotherapy are needed in order to address these tumors, which can be dangerous in some cases. Reduction of immunosuppressive medication may also be recommended. In all cases of squamous cell cancer, patients need to be followed by the transplant center physicians as well as specialists who deal with these tumors on a regular basis.

Lymphoma

Lymphoma is the least predictable of cancers in transplant recipients and occurs in approximately two percent of patients. This tumor is caused by an uncontrolled growth of lymphocytes, one of the types of white blood cells. It is usually linked to infection with the Epstein Barr virus, the same virus that causes infectious mononucleosis. Since lymphocytes circulate in the blood stream, they may cause a concentrated growth, or tumor, in virtually any location in the body. For this reason, detection of such a tumor depends on where it grows. In most instances, the growth is found because it becomes large enough to cause pressure on or within a structure in the body. Typically, the growth is identified when an imaging study such as a CAT scan is performed to explain the symptoms caused by the pressure. As with any type of cancer, a biopsy is required to confirm the diagnosis. In addition, blood tests may confirm the presence of the Epstein Barr virus.

It is thought that lymphoma results from suppressing the immune system too far, making viral infection and the cancer it causes more likely. Thus, an important part of treatment is stopping or lowering the amount of immunosuppressive medications. In addition, chemotherapy and, occasionally, radiation therapy may be advised. Finally, an anti-viral medication may be added to the regimen. Although lymphoma is a very serious cancer, it often responds remarkably well to the approaches described above. With successful treatment, a new balance with the immune system must be achieved, usually requiring less of the anti-rejection medications than were used before the lymphoma was identified.

General Considerations

Transplant recipients are also susceptible to the standard types of tumors that are not specifically linked to the use of immunosuppression, such as breast, colon and prostate cancer. For this reason it is important screening and preventive care measures advised for the general population are followed, in addition to post-transplant care, including colonoscopy and mammograms. In most cases, these considerations are managed by the primary care physician. Yet, if a cancer is identified, it often becomes important to seek the transplant team’s involvement in the way it is managed. In order to achieve the best possible outcome of the cancer, it may be appropriate to consider lowering the total amount of immunosuppression, although the risk of rejection may be increased by doing so. This judgment should be discussed directly between the patient and the treating physician. If chemotherapy is required, the presence of a transplanted organ and the ongoing use of immunosuppression may prompt selection of the specific drugs used for treatment, or may alter the amount that is used. If surgery is required, the slower healing process caused by the use of immunosuppression will also be considered.

Conclusions

The diagnosis and treatment of cancer in a transplant recipient requires thoughtful judgment by both the patient and the healthcare provider. A key issue to consider is whether treatment of the cancer, or protection of the kidney is the priority. This should be discussed openly by the patient and treating team. Collaboration between the cancer experts and the transplant team is important both to reassure the patient and to select the approach that is best suited to the specific tumor. As the outcomes of transplants continue to improve, and recipients age, cancer is more likely to become a relevant health issue. Many transplant recipients are also cancer survivors, and can bear witness to the importance of aggressive and knowledgeable treatment. When complete cure is unlikely, surviving with the cancer that, though present, is relatively quiet, may still be a real possibility.

Amy L. Friedman, MD, FACS, is Director of Transplantation at SUNY Upstate Medical University in Syracuse, New York, and serves on the AAKP National Board of Directors and the AAKP Medical Advisory Board.

Thomas Peters, MD, FACS, FASN, is a transplant surgeon at Jacksonville Transplant Center at Shands Jacksonville Medical Center in Jacksonville, Fla. Dr. Peters serves on the AAKP National Board of Directors and AAKP Medical Advisory Board. Dr. Peters is also Co-Editor of aakpRENALIFE.