Multiple Endocrine Neoplasia Syndromes (MEN) and Carney Complex
Skin Cancer (Melanoma, Basal Cell Carcinoma, Squamous Cell Carcinoma)
Chordoma
Cancer of Unknown Primary Site

Other rare childhood cancers include multiple endocrine neoplasia syndrome, skin cancer, chordoma, and cancer of unknown primary site. These other rare childhood cancers are discussed below.

Multiple endocrine neoplasia syndromes or MEN are familial disorders that cause abnormal changes in more than one endocrine organ at the same time (endocrine tissue secretes hormones). These changes may include hyperplasia (overgrowth of tissue) or benign (noncancerous) tumors.

These disorders, called MEN 1, MEN 2A, MEN 2B, and familial medullary carcinoma of the thyroid (FMTC), are caused by abnormal genes. Patients and family members at risk for these syndromes should have both genetic testing and physical examinations.

MEN 1 (Werner syndrome) may involve tumors of the pituitary and parathyroid glands, adrenal, gastric, and pancreatic structures.

MEN 2A (Sipple syndrome) is associated with medullary thyroid carcinoma (cancer that forms in the cells of the thyroid that make the hormone calcitonin) and parathyroid hyperplasia, as well as pheochromocytoma (a usually benign tumor that forms in the center of the adrenal gland, causing it to make too much adrenaline). MEN 2B is associated with medullary thyroid carcinoma, parathyroid hyperplasia, and adenomas as well as pheochromocytoma, mucosal neuromas, and ganglioneuromas.

Patients with the MEN 2A syndrome usually have surgery to remove the thyroid by the age of 5 years or at the time genetic changes are found in order to prevent cancer. Family members of patients with the MEN 2A syndrome should be tested in early childhood, before age 5, for the abnormal gene that leads to this type of cancer. If they are found to have this genetic change, they should have surgery to remove the thyroid and replace it with a transplant of one of their own parathyroid glands by a certain age.

Patients with the MEN 2B syndrome may have a slender body build, long and thin extremities, a high arch palate, and “funnel chest” (sunken chest) or an abnormally high arch in the foot. The lips may appear thickened because of tumors in the mucous membranes. In this syndrome, medullary thyroid cancer may be particularly aggressive; therefore, the thyroid should be removed in infancy to prevent cancer in these affected children.

Familial medullary thyroid carcinoma (FMTC) is an inherited form of medullary thyroid cancer that occurs without pheochromocytoma or parathyroid adenoma/hyperplasia.

Hirschsprung disease (a condition present at birth that causes blockage of the large intestine due to lack of muscle contractions) is also associated with medullary thyroid carcinoma. Patients with Hirschsprung disease should be screened for genetic changes that may be linked to this cancer. If such changes are found, surgery to remove the thyroid in order to prevent cancer may be considered.

The Carney complex is an inherited syndrome that causes myxomas (benign tumors) of the heart and skin, lentigines (brown sun spots on the skin), blue nevi (benign moles), Cushing syndrome, and endocrine and non-endocrine tumors. For patients with the Carney complex, prognosis depends on how often heart, skin, or other tumors recur.

The outcome for patients with the MEN 1 syndrome is generally good, provided adequate treatment can be obtained for parathyroid, pancreatic, and pituitary tumors. The outcome for patients with the MEN 2A syndrome is also generally good, but the possibility exists for recurrence of medullary thyroid carcinoma and pheochromocytoma. Medullary thyroid cancer in children with MEN 2B may be difficult to cure.

Treatment of medullary thyroid carcinoma may include a clinical trial of a tyrosine kinase inhibitor, a drug that interferes with cell communication and growth and may prevent tumor growth, taken by mouth.

Melanoma is the most common skin cancer in children, followed by basal cell and squamous cell carcinomas. The incidence of melanoma in children and adolescents represents approximately 1% of the new cases of melanoma that are diagnosed annually in the United States. Melanoma occurs less often in children younger than 10 years, and occurs more often in older children and adolescents aged 10 to 19 years. The rate of melanoma in children has increased in recent decades. Higher levels of ultraviolet light from the sun increases the risk of this cancer.

Conditions that increase the risk of melanoma in children and adolescents include giant melanocytic nevi (large congenital black spots which may cover the trunk and thigh), xeroderma pigmentosum (a rare genetic condition marked by an extreme sensitivity to sunlight), certain disorders of the immune system, and Werner syndrome. Traits in all age groups that increase the risk of melanoma include being exposed to ultraviolet radiation, having red hair, blue eyes, or freckling, poor tanning, and family history of melanoma. Melanoma in children is similar in many ways to the disease in adults, although the thickness of lesions in children does not seem to predict how likely it is that the melanoma will be cured.

Basal cell carcinoma generally appears as a raised lump or ulcerated lesion, usually in areas with previous sun exposure. Squamous cell carcinomas are usually reddened lesions with varying degrees of scaling or crusting; they have an appearance similar to eczema, infections, trauma, or psoriasis.

Basal and squamous cell carcinomas are generally curable with surgery alone, but the treatment of melanoma requires greater consideration because of its potential for metastasis. Surgery for melanoma depends on the size, site, level of invasion, and metastatic extent or stage of the tumor. If the melanoma has not spread beyond the lymph nodes, adjuvant biologic therapy may be given to increase the chances of a cure. If the melanoma has spread beyond the lymph nodes, treatment may include a combination of chemotherapy and biologic therapy. Information about ongoing clinical trials for melanoma in children aged 10 years or older is available from the NCI Web site ¹.

Chordoma is a very rare type of bone tumor that may develop along the spine at any point from the base of the skull to the tailbone. Chordomas start in clusters of cells leftover from spinal column development in the embryo. These cells normally disappear, but very rarely they remain and grow into tumors. In children and adolescents, chordomas develop more often in the base of the skull, making them difficult to completely remove with surgery. Symptoms vary and may include pain and nerve trouble. When chordoma recurs, it usually comes back in the same area, but may appear in the lungs or other areas of bone.

Standard treatment includes surgery and radiation therapy. The best results are seen with proton beam therapy, a special kind of high-energy radiation that is different from an x-ray.

Cancer can form in any tissue of the body and can spread from the primary site (the place where the cancer first began to grow) to other parts of the body. Cancer that has spread from the place in which it started to other parts of the body is called metastatic cancer. Metastatic cancer cells usually look like cells in the type of tissue where the cancer began. For example, breast cancer cells that spread to the lung look like breast cancer cells, not lung cancer cells. Sometimes metastatic cancer cells are found in the body, but tests do not find a primary tumor. If cancer cells are found in the body but the place where the cancer started cannot be identified, the disease is called cancer of unknown primary site. Treatment is based on what the cancer cells look like under a microscope, the patient's age and symptoms, and the extent of the cancer in the body. Treatment is usually chemotherapy or radiation therapy.

Glossary Terms

Not normal. An abnormal lesion or growth may be cancer, premalignant (likely to become cancer), or benign (not cancer).

Additional cancer treatment given after the primary treatment to lower the risk that the cancer will come back. Adjuvant therapy may include chemotherapy, radiation therapy, hormone therapy, targeted therapy, or biological therapy.

A small gland that makes steroid hormones, adrenaline, and noradrenaline. These hormones help control heart rate, blood pressure, and other important body functions. There are two adrenal glands, one on top of each kidney. Also called suprarenal gland.

A hormone and neurotransmitter. Also called epinephrine.

A quickly growing cancer.

A small, round cell found in the lower part (or base) of the epidermis, the outer layer of the skin.

A type of skin cancer that arises from the basal cells, small round cells found in the lower part (or base) of the epidermis, the outer layer of the skin.

Not cancerous. Benign tumors may grow larger but do not spread to other parts of the body. Also called nonmalignant.

A substance that is made from a living organism or its products and is used in the prevention, diagnosis, or treatment of cancer and other diseases. Biologic agents include antibodies, interleukins, and vaccines. Also called biological agent and biological drug.

Cancer that forms in tissues of the breast, usually the ducts (tubes that carry milk to the nipple) and lobules (glands that make milk). It occurs in both men and women, although male breast cancer is rare.

A hormone formed by the C cells of the thyroid gland. It helps maintain a healthy level of calcium in the blood. When the calcium level is too high, calcitonin lowers it.

A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is a cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is a cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is a cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord. Also called malignancy.

A case in which cancer cells are found in the body, but the place where the cells first started growing (the origin or primary site) cannot be determined. Also called carcinoma of unknown primary and CUP.

A rare, inherited disorder marked by dark spots on the skin and tumors in the heart, endocrine glands, skin, and nerves. There are two types of Carney complex, which are caused by mutations (changes) in different genes. Also called Carney syndrome.

The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.

Treatment with drugs that kill cancer cells.

A type of bone cancer that usually starts in the lower spinal cord.

A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called clinical study.

A condition or trait present at birth. It may be the result of genetic or non-genetic factors.

To heal or restore health; a treatment to restore health.

A condition in which there is too much cortisol (a hormone made by the outer layer of the adrenal gland) in the body. Cushing syndrome may be caused by taking too many steroid drugs or by certain types of tumors. Tumors that make adrenocorticotropic hormone (ACTH) cause the adrenal gland to make too much cortisol. Symptoms of Cushing syndrome include a round face, thin arms and legs, severe fatigue and muscle weakness, high blood pressure, high blood sugar, purple or pink stretch marks on the skin, and weight gain, especially in the abdomen.

The process of identifying a disease, such as cancer, from its signs and symptoms.

In medicine, a disturbance of normal functioning of the mind or body. Disorders may be caused by genetic factors, disease, or trauma.

Any substance, other than food, that is used to prevent, diagnose, treat or relieve symptoms of a disease or abnormal condition. Also refers to a substance that alters mood or body function, or that can be habit-forming or addictive, especially a narcotic.

Early stage in the development of a plant or an animal. In vertebrate animals (have a backbone or spinal column), this stage lasts from shortly after fertilization until all major body parts appear. In particular, in humans, this stage lasts from about 2 weeks after fertilization until the end of the seventh or eighth week of pregnancy.

An inherited form of medullary thyroid cancer (cancer that forms in the cells of the thyroid that make the hormone calcitonin).

A record of the relationships among family members along with their medical histories. This includes current and past illnesses. A family history may show a pattern of certain diseases in a family. Also called family medical history.

Having to do with the stomach.

The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein.

Inherited; having to do with information that is passed from parents to offspring through genes in sperm and egg cells.

Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder.

One of many chemicals made by glands in the body. Hormones circulate in the bloodstream and control the actions of certain cells or organs. Some hormones can also be made in the laboratory.

An abnormal increase in the number of normal cells in an organ or tissue.

The complex group of organs and cells that defends the body against infections and other diseases.

The number of new cases of a disease diagnosed each year.

Invasion and multiplication of germs in the body. Infections can occur in any part of the body and can spread throughout the body. The germs may be bacteria, viruses, yeast, or fungi. They can cause a fever and other problems, depending on where the infection occurs. When the body’s natural defense system is strong, it can often fight the germs and prevent infection. Some cancer treatments can weaken the natural defense system.

Transmitted through genes that have been passed from parents to their offspring (children).

The long, tube-like organ that is connected to the small intestine at one end and the anus at the other. The large intestine has four parts: cecum, colon, rectum, and anal canal. Partly digested food moves through the cecum into the colon, where water and some nutrients and electrolytes are removed. The remaining material, solid waste called stool, moves through the colon, is stored in the rectum, and leaves the body through the anal canal and anus.

An area of abnormal tissue. A lesion may be benign (not cancer) or malignant (cancer).

One of a pair of organs in the chest that supplies the body with oxygen, and removes carbon dioxide from the body.

Cancer that forms in tissues of the lung, usually in the cells lining air passages. The two main types are small cell lung cancer and non-small cell lung cancer. These types are diagnosed based on how the cells look under a microscope.

Cancer that develops in C cells of the thyroid. The C cells make a hormone (calcitonin) that helps maintain a healthy level of calcium in the blood.

A form of cancer that begins in melanocytes (cells that make the pigment melanin). It may begin in a mole (skin melanoma), but can also begin in other pigmented tissues, such as in the eye or in the intestines.

A rare, inherited disorder that affects the endocrine glands and can cause tumors in the parathyroid and pituitary glands and the pancreas. These tumors are usually benign (not cancer). They cause the glands to secrete high levels of hormones, which can lead to other medical problems, such as kidney stones, fertility problems, and severe ulcers. In some cases, tumors inside the pancreas can become malignant (cancer). Also called multiple endocrine adenomatosis, multiple endocrine neoplasia type 1 syndrome, and Wermer syndrome.

The spread of cancer from one part of the body to another. A tumor formed by cells that have spread is called a “metastatic tumor” or a “metastasis.” The metastatic tumor contains cells that are like those in the original (primary) tumor. The plural form of metastasis is metastases (meh-TAS-tuh-SEEZ).

Having to do with metastasis, which is the spread of cancer from the primary site (place where it started) to other places in the body.

The moist, inner lining of some organs and body cavities (such as the nose, mouth, lungs, and stomach). Glands in the mucosa make mucus (a thick, slippery fluid). Also called mucous membrane.

The moist, inner lining of some organs and body cavities (such as the nose, mouth, lungs, and stomach). Glands in the mucous membrane make mucus (a thick, slippery fluid). Also called mucosa.

An inherited condition that may result in the development of cancers of the endocrine system. There are several types of multiple endocrine neoplasia syndrome, and patients with each type may develop different types of cancer. The altered genes that cause each type can be detected with a blood test. Also called MEN syndrome.

A bundle of fibers that receives and sends messages between the body and the brain. The messages are sent by chemical and electrical changes in the cells that make up the nerves.

A tumor that arises in nerve cells.

A benign (not cancer) growth on the skin that is formed by a cluster of melanocytes (cells that make a substance called melanin, which gives color to skin and eyes). A nevus is usually dark and may be raised from the skin. Also called mole.

A part of the body that performs a specific function. For example, the heart is an organ.

The roof of the mouth. The front portion is bony (hard palate), and the back portion is muscular (soft palate).

Having to do with the pancreas.

One of four pea-sized glands found on the surface of the thyroid. The parathyroid hormone made by these glands increases the calcium level in the blood.

Tumor that forms in the center of the adrenal gland (gland located above the kidney) that causes it to make too much adrenaline. Pheochromocytomas are usually benign (not cancer) but can cause high blood pressure, pounding headaches, heart palpitations, flushing of the face, nausea, and vomiting.

An exam of the body to check for general signs of disease.

The main endocrine gland. It produces hormones that control other glands and many body functions, especially growth.

The original tumor.

The likely outcome or course of a disease; the chance of recovery or recurrence.

A type of high-energy, external radiation therapy that uses streams of protons (small, positively charged particles) that come from a special machine. Proton beam radiation is different from x-ray radiation.

A chronic disease of the skin marked by red patches covered with white scales.

The use of high-energy radiation from x-rays, gamma rays, neutrons, protons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body near cancer cells (internal radiation therapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that travels in the blood to tissues throughout the body. Also called irradiation and radiotherapy.

To come back or to return.

Cancer that has recurred (come back), usually after a period of time during which the cancer could not be detected. The cancer may come back to the same place as the original (primary) tumor or to another place in the body. Also called recurrent cancer.

Checking for disease when there are no symptoms. Since screening may find diseases at an early stage, there may be a better chance of curing the disease. Examples of cancer screening tests are the mammogram (breast), colonoscopy (colon), Pap smear (cervix), and PSA blood level and digital rectal exam (prostate). Screening can also include checking for a person’s risk of developing an inherited disease by doing a genetic test.

Cancer that forms in tissues of the skin. There are several types of skin cancer. Skin cancer that forms in melanocytes (skin cells that make pigment) is called melanoma. Skin cancer that forms in basal cells (small, round cells in the base of the outer layer of skin) is called basal cell carcinoma. Skin cancer that forms in squamous cells (flat cells that form the surface of the skin) is called squamous cell carcinoma. Skin cancer that forms in neuroendocrine cells (cells that release hormones in response to signals from the nervous system) is called neuroendocrine carcinoma of the skin. Most skin cancers form in older people on parts of the body exposed to the sun or in people who have weakened immune systems.

The bones, muscles, tendons, and other tissues that reach from the base of the skull to the tailbone. The spinal column encloses the spinal cord and the fluid surrounding the spinal cord. Also called backbone, spine, and vertebral column.

The bones, muscles, tendons, and other tissues that reach from the base of the skull to the tailbone. The spine encloses the spinal cord and the fluid surrounding the spinal cord. Also called backbone, spinal column, and vertebral column.

Cancer that begins in squamous cells, which are thin, flat cells that look like fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma.

In medicine, treatment that experts agree is appropriate, accepted, and widely used. Health care providers are obligated to provide patients with standard therapy. Also called best practice and standard of care.

A procedure to remove or repair a part of the body or to find out whether disease is present. An operation.

An indication that a person has a condition or disease. Some examples of symptoms are headache, fever, fatigue, nausea, vomiting, and pain.

A set of symptoms or conditions that occur together and suggest the presence of a certain disease or an increased chance of developing the disease.

A gland located beneath the larynx (voice box) that makes thyroid hormone and calcitonin. The thyroid helps regulate growth and metabolism. Also called thyroid gland.

A group or layer of cells that work together to perform a specific function.

A surgical procedure in which tissue or an organ is transferred from one area of a person’s body to another area, or from one person (the donor) to another person (the recipient).

An abnormal mass of tissue that results when cells divide more than they should or do not die when they should. Tumors may be benign (not cancer), or malignant (cancer). Also called neoplasm.

A drug that interferes with cell communication and growth and may prevent tumor growth. Some tyrosine kinase inhibitors are used to treat cancer.

The formation of a break on the skin or on the surface of an organ. An ulcer forms when the surface cells die and are cast off. Ulcers may be associated with cancer and other diseases.

Invisible rays that are part of the energy that comes from the sun. Ultraviolet radiation also comes from sun lamps and tanning beds. It can damage the skin and cause melanoma and other types of skin cancer. Ultraviolet radiation that reaches the Earth's surface is made up of two types of rays, called UVA and UVB rays. UVB rays are more likely than UVA rays to cause sunburn, but UVA rays pass deeper into the skin. Scientists have long thought that UVB radiation can cause melanoma and other types of skin cancer. They now think that UVA radiation also may add to skin damage that can lead to skin cancer and cause premature aging. For this reason, skin specialists recommend that people use sunscreens that reflect, absorb, or scatter both kinds of ultraviolet radiation. Also called UV radiation.

A type of high-energy radiation. In low doses, x-rays are used to diagnose diseases by making pictures of the inside of the body. In high doses, x-rays are used to treat cancer.

A genetic condition marked by an extreme sensitivity to ultraviolet radiation, including sunlight. People with xeroderma pigmentosum are not able to repair skin damage from the sun and other sources of ultraviolet radiation, and have a very high risk of skin cancer.