Carcinoma of unknown primary (CUP) is a rare disease in which malignant (cancer) cells are found in the body but

the place the cancer began is not known.
Cancer can form in any tissue of the body. The primary cancer (the cancer that first formed) can spread to other parts of the body. This process is called metastasis. Cancer cells usually look like the cells in the type of tissue in which the cancer began. For example, breast cancer cells may spread to the lung. Because the cancer began in the breast, the cancer cells in the lung look like breast cancer cells. Sometimes doctors find where the cancer has spread but cannot find where in the body the cancer first began to grow. This type of cancer is called a cancer of unknown primary (CUP) or occult primary tumor. Tests are done to find where the primary cancer began and to get information about where the cancer has spread. When tests are able to find the primary cancer, the cancer is no longer a CUP and treatment is based on the type of primary cancer.

Sometimes the primary cancer is never found.
The primary cancer (the cancer that first formed) may not be found for one of the following reasons:    The primary cancer is very small and grows slowly. The body’s immune system killed the primary cancer. The primary cancer was removed during surgery for another condition and doctors didn’t know cancer had formed. For example, a uterus with cancer may be removed during a hysterectomy to treat a seriousinfection.

The signs and symptoms of CUP are different, depending on where the cancer has spread in the body.
Signs and symptoms of CUP may include the following:         Lump or thickening in any part of the body. Pain that is in one part of the body and does not go away. A cough that does not go away or hoarseness in the voice. Change in bowel or bladder habits, such as constipation, diarrhea, or frequent urination. Unusual bleeding or discharge. Fever for no known reason that does not go away. Night sweats. Weight loss for no known reason or loss of appetite. Other conditions may cause these same symptoms. Sometimes CUP does not cause any symptoms. Talk to your doctor if you have any of these problems.

Reverse transcription–polymerase chain reaction (RT-PCR) test: A laboratory test in which cells in a sample of tissue are studied using chemicals to look for certain changes in the genes. One of the following types of biopsies may be used:     Excisional biopsy: The removal of an entire lump of tissue. Chest x-ray: An x-ray of the organs and bones inside the chest. white blood cells. one or more of the following laboratory tests may be used to study the tissue samples and find out the type of cancer:  Histologic study: A laboratory test in which stains are added to a sample of cancer cells or tissue and viewed under a microscope to look for certain changes in the cells. A biopsy is the removal of cells or tissues so they can be viewed under a microscope by a pathologist. The amount of hemoglobin (the protein that carries oxygen) in the red blood cells. Small samples of stool are placed on special cards and returned to the doctor or laboratory for testing. such as lumps or anything else that seems unusual. Fine-needle aspiration (FNA) biopsy: The removal tissue or fluid using a thin needle. a biopsy is done. A history of the patient’s health habits and past illnesses and treatments will also be taken. Core biopsy: The removal of tissue using a wide needle. blood. The pathologist views the tissue under a microscope to look for cancer cells and to find out the type of cancer. and platelets. Blood chemistry studies: A procedure in which a blood sample is checked to measure the amounts of certain substances released into the blood by organs and tissues in the body. The following tests and procedures may be used:  Physical exam and history: An exam of the body to check general signs of health. The portion of the sample made up of red blood cells.Different tests are used to detect (find) cancer. such as sugar. Certain changes in the cells are linked to certain types of cancer. blood in the stool may be a sign of cancer in the colon or rectum. An unusual (higher or lower than normal) amount of a substance can be a sign of disease in the organ or tissue that makes it. An x-ray is a type of energy beam that can go through the body and onto film. Because some cancers bleed. Fecal occult blood test: A test to check stool (solid waste) for blood that can only be seen with amicroscope. Urinalysis: A test to check the color of urine and its contents. Complete blood count: A procedure in which a sample of blood is drawn and checked for the following: The number of red blood cells. making pictures of areas inside the body. Immunohistochemistry study: A laboratory test in which dyes or enzymes are added to a sample of cancer cells or tissue to test for certain antigens (proteins that stimulate the body's immune response).    o o o   If tests show there may be cancer. The type of biopsy that is done depends on the part of the body being tested for cancer. Incisional biopsy: The removal of part of a lump or a sample of tissue. protein. If cancer is found.   . including checking for signs of disease. and bacteria.

However. Tests and procedures used to find the primary cancer depend on where the cancer has spread. such as the chest or abdomen. such as the pancreas. a diagnosis of CUP may be made. Anendoscope is inserted through an incision (cut) in the skin or opening in the body. the primary cancer site is likely to be in the lower part of the body. The pictures are made by a computer linked to an x-ray machine. it is likely that the cells have spread to the breast from another part of the body. The PET scanner rotates around the body and makes a picture of where glucose is being used in the body. and a computer to make a series of detailed pictures of areas inside the body. Malignant tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells do. MRI (magnetic resonance imaging): A procedure that uses a magnet. This procedure is also called nuclear magnetic resonance imaging (NMRI). For cancer found in the lymph nodes in the neck. taken from different angles. a sample of cancer tissue taken from the breast is expected to be made up of breast cells. Mammogram: An x-ray of the breast. In some cases. or computerized axial tomography. radio waves. the part of the body where cancer cells are first found helps the doctor decide which diagnostic tests will be most helpful. or other organ in the abdomen. The cells in the body have a certain look that depends on the type of tissue they come from.    When cancer is found above the diaphragm (the thin muscle under the lungs that helps with breathing). such as the mouth. Cytogenetic analysis: A laboratory test in which cells in a sample of tissue are viewed under a microscope to look for certain changes in the chromosomes. In order to plan treatment. For example. Changes in certain chromosomes are linked to certain types of cancer. if the sample of tissue is a different type of cell (not made up of breast cells). the primary cancer site is likely to be in the upper part of the body. Light and electron microscopy: A laboratory test in which cells in a sample of tissue are viewed under regular and high-powered microscopes to look for certain changes in the cells. Endoscopy: A procedure to look at organs and tissues inside the body to check for abnormal areas. The following tests and procedures may be done to find where the cancer first began:  CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body. Some cancers commonly spread to certain areas of the body.  When the type of cancer cells or tissue removed is different from the type of cancer cells expected to be found. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. computerized tomography. This procedure is also called computed tomography. doctors first try to find the primary cancer (the cancer that first formed). A small amount of radioactive glucose (sugar) is injected into a vein.     . the primary cancer site is likely to be in the head or neck. liver. PET scan (positron emission tomography scan): A procedure to find malignant tumor cells in the body. When cancer is found below the diaphragm. because head and neck cancers often spread to the lymph nodes in the neck. such as in the lung or breast.

such as the peritoneum or the cervical (neck). tissues. The results of tests and procedures. urine.  Tumor marker test: A procedure in which a sample of blood. Clinical trials for CUP are taking place in many parts of the country. Whether the patient is male or female. The type of cancer cell. current treatments do not cure the cancer. The extent or spread of cancer is usually described as stages. or tumor cells in the body. or prostate-specific antigen (PSA). The stage of the cancer is usually used to plan treatment. Certain factors affect prognosis (chance of recovery). or tissue is checked to measure the amounts of certain substances made by organs. Whether the cancer is newly diagnosed or has recurred (come back). . In these cases. Patients may want to take part in one of the many clinical trials being done to improve treatment. beta human chorionic gonadotropin (β-hCG). Certain substances are linked to specific types of cancer when found in increased levels in the body. CUP has already spread to other parts of the body when it is found. treatment may be based on what the doctor thinks is the most likely type of cancer. which are checked under a microscope for signs of disease. It may also have a tool to remove tissue or lymph node samples. Doctors use the following types of information to plan treatment:       The place in the body where the cancer is found. Whether the cancer has just been diagnosed or has recurred (come back). The signs and symptoms caused by the cancer. The information that is known about the cancer is used to plan treatment. The way the tumor cells look when viewed under a microscope. axillary(armpit). or inguinal (groin) lymph nodes. The prognosis (chance of recovery) depends on the following:      Where the cancer began in the body and where it has spread. none of the tests can find the primary cancer site. There is no staging system for carcinoma of unknown primary (CUP). such as melanoma. Information about clinical trials is available from the NCI Web site. The blood may be checked for the levels of alpha-fetoprotein (AFP). The number of organs with cancer in them. Whether the cancer cell is poorly differentiated (looks very different from normal cells when viewed under amicroscope). Sometimes. These are called tumor markers. tube-like instrument with a light and a lens for viewing.An endoscope is a thin. However. For most patients with CUP.

The way the radiation therapy is given depends on the type and stage of the cancer being treated. External radiation therapy uses a machine outside the body to send radiation toward the cancer. an organ. the drugs mainly affect cancer cells in those areas (regional chemotherapy). Thin beams of radiation of different intensities (strengths) are aimed at the tumor from many angles. the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). A doctor may remove the cancer and some of the healthy tissuearound it. Treatment given after the surgery. is called adjuvant therapy. and some are being tested in clinical trials. some patients may be given chemotherapy or radiation therapy after surgery to kill any cancer cells that are left. Hormones are substances made by glands in the body and circulated in the bloodstream. or a body cavity such as the abdomen. Some treatments are standard (the currently used treatment). When chemotherapy is placed directly into the cerebrospinal fluid. Some hormones can cause certain cancers to grow. Chemotherapy Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells. Patients may want to think about taking part in a clinical trial. to increase the chances of a cure. Four types of standard treatment are used: Surgery Surgery is a common treatment for CUP. Radiation therapy Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. Even if the doctor removes all the cancer that can be seen at the time of the surgery. Different types of treatment are available for patients with CUP. There are two types of radiation therapy. Hormone therapy Hormone therapy is a cancer treatment that removes hormones or blocks their action and stops cancer cells from growing. and damage to the skin. the new treatment may become the standard treatment. When clinical trials show that a new treatment is better than the standard treatment. When chemotherapy is taken by mouth or injected into a vein or muscle. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. Intensity-modulated radiation therapy (IMRT) is a type of 3-dimensional (3-D) radiation therapy that uses a computer to make pictures of the size and shape of the tumor. Combination chemotherapy is the use of two or more anticancer drugs. drugs. or catheters that are placed directly into or near the cancer.There are different types of treatment for patients with carcinoma of unknown primary (CUP). or radiation therapy are used to reduce the production of hormones or block them from working. trouble swallowing. surgery. . either by killing the cells or by stopping them from dividing. Internal radiation therapy uses a radioactivesubstance sealed in needles. Some clinical trials are open only to patients who have not started treatment. This type of radiation therapy is less likely to cause dry mouth. If tests show that the cancer cells have places where hormones can attach (receptors). seeds. wires.

A subset of patients has lung metastases. and poorly or undifferentiated adenocarcinomas accounting for a further 35%. Lymph nodes. germ cell tumours. and other areas of the body. The fundamental characteristics of CUP are:     Early dissemination Clinical absence of primary site at presentation Generally quite aggressive Unpredictable metastatic pattern HISTOLOGICAL CLASSIFICATION OF CUP The most common histological type of CUP is adenocarcinoma. with well. squamous cells also occur in the lining of thedigestive tract. lungs. These are adenocarcinomas of various levels of differentiation. either solitary or multiple. physical examination and standardised diagnostic work-up fail to identify the site of the cancer’s origin at the time of diagnosis. mouth. Bones. The natural history of cancer of unknown primary site is quite diff-erent to cancers where the primary site is known. or mixed SCC/adenocarcinomas. Another subset of patients has only bone metastases. Lungs.to moderately-differentiated adenocarcinomas accounting for 50% of cases of CUP. and SCC occurs as a form of cancer in diverse tissues. with neuroendocrine features. so is relatively common. with or without psammoma bodies (round collections of calcium). which are usually mucin adenocarcinomas (with or without signet ring cells). These are generally adenocarcinomas. and are adenocarcinomas. natural history. Those with metastases to the axillary nodes may have adenocarcinomas. including neuroendocrine tumours. and looks like ovarian cancer. and those affected in the inguinal nodes could have undifferentiated carcinoma. Peritoneal cavity. Patients with lymph node metastases in a mediastinal to retroperitoneal (midline) distribution may have undifferentiated or poorly differentiated carcinoma. lung. a pancreatic cancer with known primary site has a well-defined metastatic pattern. . Histologically. and cervix. The different histological types can be considered by the organ affected: Liver. However. unfortunately. It accounts for 3%–5% of all malignancies. prostate. Patients with liver metastases often have adenocarcinoma. including the lips. these cancers are papillary or serous adenocarcinomas. CUP with metastases in the peritoneal cavity is termed peritoneal adenocarcinomatosis when found in females. Squamous cell carcinomas account for 10% of CUP cases. urinary bladder. Neuroendocrine tumours. with less than a 5% chance of lung metastasis. squamous cell carcinoma (SCC).Squamous cell carcinoma (SCC or SqCC) is a cancer of a kind of epithelial cell. For example. These are generally poorly differentiated cancers mainly low-grade. Brain metastases can occur either singly or more than one. the SCCs of different body sites can show tremendous differences in their presenting symptoms. which is. esophagus. They sometimes also have metastatic signs in other organs. and this cancer is one of the major forms of skin cancer. melanomas. thesquamous cell. while undifferentiated neoplasms. sarcomas and embryonic malignancies account for 5%. Despite sharing the name squamous cell carcinoma. Brain. Cancer of unknown primary (CUP) represents a heterogeneous group of metastatic tumours for which medical history. and response to treatment. Patients may also have malignant ascites of other unknown origin. However. with either pulmonary metastases or only pleural effusion. with an unpredictable metastatic pattern. These cells are the main part of the epidermis of the skin. vagina. while patients with metastases in the cervical nodes could have squamous cell carcinoma. it might have a 30%–40% chance of metastasis to the lungs. lymphomas. as a hidden pancreatic CUP. CLINICOPATHOLOGICAL ENTITIES OF CUP CUP is not one disease. prognosis. the most common type of CUP. among others.

Melanoma. Patients have undifferentiated neoplasm with melanoma features. Being aware of the subsets of CUP is useful in order to classify patients into appropriate groups for treatment decisions and research purposes. . but with no obvious primary site.