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About four of every five cases that are first diagnosed as cancer of unknown primary eventually are confirmed to be specific types of cancer. CUP most often is found in the lymph nodes, liver, lung, peritoneum (lining of the bowel) or bone.
Cancer of unknown primary often is challenging because it tends to be aggressive and has often spread to many parts of the body before it is found. In addition, because origin of cancer is unknown, it may be more challenging to choose the best treatment.
Cancer of Unknown Primary Types
Although doctors are at first unable to determine where CUP began, they study the cancer to find out as much as possible about them. After looking at the cancer cells under a microscope, they usually decide the cancer belongs in one of the following categories:
Adenocarcinomas: About six of every 10 cancer of unknown primary cases are adenocarcinomas, meaning they began in gland cells. Most frequently, the primary sites are the lung, pancreas, breast, prostate, stomach, liver or colon.
Poorly differentiated carcinoma: Cancer cells are present, but they do not have enough detail for doctors to decide the type of cancer. Around 10% of these CUP cases are found to be lymphoma, melanoma or sarcoma.
Squamous cell cancer: The cells are flat, similar to cells on the skin or linings of some organs.
Poorly differentiated malignant neoplasm: Cells are definitely cancer, but they are so abnormal it cannot be determined what type of cell or part of the body they began in. Sometimes they are lymphomas, sarcomas or melanomas.
Neuroendocrine carcinoma: This type of CUP begins in the neuroendocrine system, making the cells like nerve cells and hormone-making cells. They are scattered in organs including the esophagus, stomach, pancreas, intestines and lungs.
CUP Risk Factors
Because the primary site of many cancer of unknown primary cases is never found, it is difficult to say what causes them. In the cases in which the primary site is determined, possible risk factors are based on that type of cancer.
- Smoking tobacco is a risk factor in cancers of the pancreas, lungs, kidney, throat, larynx and esophagus. More than half of people with CUP have used tobacco.
- Diet and being overweight are linked to cancers that begin in the stomach, colon or rectum.
- Too much sun exposure causes some melanomas.
However, it has not been proven that any of these factors make a person more likely to develop cancer of unknown primary.
Symptoms of cancer of unknown primary (CUP) vary from person to person and depend on where the cancer has spread. They may include:
- Swollen lymph nodes that are firm and not painful
- Mass in the abdomen that can be felt from the outside or causes a feeling of fullness after a small meal
- Shortness of breath
- Pain in the chest or abdomen
- Pain in the bones
- Skin tumors
- Fatigue or weakness
- Lack of appetite or unexplained weight loss
These symptoms do not always mean you have CUP. However, it is important to discuss any symptoms with your doctor, since they may signal other health problems.
With new scientific advances, doctors increasingly are able to find where cancer of unknown primary (CUP) began. In fact, now the primary site can be found in about four of five cases that originally were diagnosed as CUP.
Clues to where CUP began may include where cancer cells are found first, the pattern in which the cells are spreading and the type of cell in the remote cancer.
CUP Diagnostic Tests
The first step in diagnosing CUP is a thorough history and physical examination. The doctor will ask you questions about your current and past health and risk factors, such as smoking or family history.
If your doctor suspects cancer of unknown primary, one or more of the following tests may be done:
Different methods are used to perform biopsies for CUP, depending on where the cancer is and the type of cancer. These include:
Fine needle aspiration (FNA): A thin needle is inserted into the body and cells are drawn out and looked at under a microscope.
Core needle biopsy: Although a slightly larger needle is used, this test is similar to FNA biopsy. It is more common than FNA because it removes a larger piece of tissue, which may give doctors more information.
Excisional biopsy: The entire tumor or swollen lymph node is removed surgically. If the tumor or node is close to the surface of the skin, this procedure can be done in the doctor’s office after the skin has been numbed.
Incisional biopsy: This type of biopsy is similar to an excisional biopsy, but only part of the tumor or lymph node is removed.
Fluid removal: A long, hollow needle is used to remove a small amount of fluid. This is most commonly used if there is a large amount of fluid in the abdomen or lungs.
Bone marrow aspiration and biopsy: A small amount of bone marrow (liquid in the middle of large bones) is withdrawn with a needle that is inserted into the hip bone.
Blood and urine tests
Imaging tests, which may include:
- CT or CAT computed axial tomography) scans
- MRI (magnetic resonance imaging) scans
- PET (positron emission tomography) scans
- Endoscopy: An endoscope is inserted into your mouth, nose or anus, depending on where the cancer is. Sometimes the tube is inserted through a small incision (cut) in the skin.
Staging is a way of determining how much disease is in the body and where it has spread. This information is important because it determines the type of treatment you will receive and the outlook for your recovery (prognosis).
Cancer of unknown primary cannot be staged the way other cancers are because the origin of the primary cancer is not known. But doctors can make some predictions based on:
- Where the cancer has spread
- How the cancer cells look under a microscope
- How well the cancer responds to treatment
- Your general health
Your treatment at MD Anderson for a cancer of unknown primary (CUP) is individualized to provide the best options with the least impact on your body. As one of the nation’s largest cancer centers, MD Anderson sees a higher level of CUP patients than many other centers, giving us experience that can be vital in achieving a successful outcome.
Because each patient – and each cancer of unknown primary – is one of a kind, we tailor your treatment to match your needs. Our team approach ensures that some of the best and brightest minds work together to provide optimal care.
Cancer of Unknown Primary Treatments
If you are diagnosed with CUP, your doctor will discuss the best options to treat it. Several factors are taken into consideration, including:
- Extent: the number of areas of the body affected by a CUP tumor and the size of these cancerous areas
- Site: Which organs are affected - lymph nodes, liver, lungs, bones, etc.
- Your general health
Your treatment for cancer of unknown primary will be customized to your particular needs. One or more of the following therapies may be recommended to treat the cancer or help relieve symptoms.
Surgery may be used if the cancer is in only one area, such as the lymph nodes or one organ. The type of surgery depends on where the CUP is located. Surgery may be combined with chemotherapy or radiation therapy.
Chemotherapy: MD Anderson offers the most up-to-date and advanced chemotherapy options for CUP.
Radiation therapy: MD Anderson provides the very latest radiation treatments, including:
- Brachytherapy: Tiny radioactive seeds are placed in the body close to the tumor
- 3D-conformal radiation therapy: Several radiation beams are given in the exact shape of the tumor
- Intensity-modulated radiotherapy (IMRT): Treatment is tailored to the specific shape of the tumor
Proton therapy: The Proton Therapy Center at MD Anderson is one of the world’s largest and most advanced centers. Proton therapy delivers high radiation doses directly into the tumor, sparing nearby healthy tissue and vital organs.
Targeted therapies: MD Anderson is among just a few cancer centers in the nation that are able to offer targeted therapies for some types of cancer of unknown primary. These innovative new drugs stop the growth of cancer cells by interfering with certain proteins and receptors or blood vessels that supply the tumor with what it needs to grow.
Why choose MD Anderson for cancer of unknown primary care?
At MD Anderson’s Gastrointestinal Center, we have the depth of expertise to provide customized treatment for each patient with cancer of unknown primary (CUP). Our pathology experts have significant experience in evaluating cancer of unknown primary. We use advanced diagnostic methods to pinpoint the origin of CUP tumors, which are then treated by a team of renowned specialists.
Our experts work together in specialized teams that focus an incredible level of knowledge on you. Using the latest, most advanced technology, MD Anderson’s pathologists have extraordinary skill in diagnosing the origin of cancer of unknown primary.
Advanced Treatment, Range of Support
If the site of origin of cancer of unknown primary is found, MD Anderson offers a full range of the most advanced treatments for every diagnosis. Depending on the type of cancer, these may include proton therapy, targeted therapies, surgery and others.
As one of the world’s leading cancer centers, we offer a range of clinical trials of new therapies. And because we know CUP can take a toll on you and your family’s quality of life, we provide a range of support and wellness services to help you live your life to the fullest. This includes specially trained psychologists and a supportive care team who know what you are going through and can help.