Pathologist David Klimstra

Pathologist David Klimstra has a high level of expertise in distinguishing one type of cancer from another. Getting the most accurate diagnosis is an essential step in planning treatment.

Because cancer of unknown primary origin is a metastatic cancer (cancer that has spread from one part of the body to another), it is already considered advanced. Doctors may first try to find the primary site, but for many patients, it will never be found. If the primary site cannot be found, diagnosis will focus on identifying the location(s) of the cancer and the type of cells that make up the tumor to develop a treatment plan.

Sometimes, doctors can identify the primary site with near certainty based on a specific combination of factors:

  • In women, an adenocarcinoma found in a lymph node under the arm often indicates breast cancer. A mammogram and breast examination can help to make a diagnosis.
  • In young men, a tumor in the abdomen may suggest testicular cancer.
  • Head and neck cancer is usually the primary source for squamous cell carcinomas in the upper body or in lymph nodes in the neck.
  • Cholangiocarcinoma (cancer of the bile ducts in the liver) may be the primary source of a single liver tumor.
  • Prostate, penile, or anal cancer may be the primary site for men with cancer in the lymph nodes of the groin. For women, enlarged lymph nodes in the groin may indicate cervical or vaginal cancer.
  • In women, the ovaries may be the primary site for an adenocarcinoma in the abdomen.

For most patients, doctors rely on information from blood tests, imaging studies, and pathology tests to learn more about a tumor. Many patients who arrive at Memorial Sloan Kettering with a tumor designated as cancer of unknown primary origin have already had some of these tests. Our doctors may perform more sophisticated laboratory and imaging tests to narrow down the possible organs or regions of the body where the cancer began, characterize the cells contained in the tumor(s), and select the most effective treatment possible.

Blood and Urine Tests

Blood and urine tests can reveal the presence of tumor markers (substances such as enzymes, hormones, and proteins that are produced by some tumors). When tests reveal high levels of tumor markers, medical imaging and other tests can help to confirm a diagnosis.


Our doctors use state-of-the-art imaging tests to create high-quality pictures of tumors, pinpointing their location and possible distribution throughout the body. Diagnostic imaging reveals information such as the size and density of a tumor, helping our doctors determine the most effective treatment plan. Your doctor may use one or more of the following imaging techniques:

CT uses x-rays to produce an image that reveals the location, size, and extent of tumor growth, and whether the cancer has spread into the lymph nodes or other areas.

High-frequency sound waves may be used to help map the location and number of tumors in the body. Ultrasound can also help distinguish a cancerous tumor from a benign growth.

Before imaging with PET, a small amount of radioactive sugar is injected into a vein. Cancer cells absorb sugar more rapidly than normal cells and are highlighted on the PET scan. PET is often combined with CT scans to identify areas of the body where a cancer of unknown primary origin has spread, even when the primary site cannot be found.


A biopsy (removal of tumor tissue or fluid for examination under a microscope) is commonly performed to confirm a diagnosis of cancer of unknown primary origin and to obtain cells for further study under a microscope. A pathologist examines the sample to determine the type of cells involved. Depending on the location of the tumor, doctors may perform one or more of the following types of biopsy:

A large needle is inserted into the tumor to obtain tissue for sophisticated pathology tests. Imaging tests may help guide placement of the needle. Core needle biopsy is usually performed using a local anesthetic.

A smaller needle is inserted during a core needle biopsy to extract a sample of cells and/or fluid for immediate microscopic examination in the procedure room. The biopsy can also be used for additional studies in the laboratory.

In this type of biopsy, a surgeon removes some or all of the tumor or affected lymph node. General anesthesia is required if the tumor or lymph node is located in the chest or abdomen.

Pathology Tests

In many cases, routine laboratory tests do not provide enough information about a cancer of unknown primary origin to identify or narrow down the possible primary site. Memorial Sloan Kettering’s innovative pathology program uses sophisticated laboratory tests to study the molecular characteristics of cancers of unknown primary origin, which can yield important information about the tumor type and how it will respond to treatment. Our pathologists perform a variety of sensitive microscopic tests that use antibodies to screen for proteins produced by certain tumors, and are highly experienced in identifying subtle cell patterns that may indicate certain types of cancer.

In conjunction with Memorial Sloan Kettering’s Human Oncology and Pathogenesis Program, our pathologists are leading a promising new area of research to identify therapeutic biomarkers — genetic mutations or other characteristics of a cell that promote tumor growth and may predict its response to treatment. Researchers believe that in the future, this approach could make it possible to select an effective treatment without needing to identify the primary tumor site.

Doctors at Memorial Sloan Kettering are also evaluating new diagnostic tests that screen for large amounts of messenger RNA — a substance that contains the chemical blueprint for protein production and is found in abnormally high levels in some tumors. This approach may have some value in helping to identify the primary site.