Carcinoma of unknown primary origin (CUP)
Carcinoma of unknown primary origin (CUP) is a type of cancer characterized by malignant growths that have metastasized without an identifiable source. It accounts for approximately 2 to 5 percent of all diagnosed carcinomas, which are the most common cancer type, including well-known forms like skin, breast, and lung cancers. Risk factors for CUP include exposure to carcinogens (such as tobacco smoke and radiation), certain viral infections, and genetic predispositions. The cancer typically originates in epithelial cells and can lead to various local, metastatic, and systemic symptoms, including unusual lumps, pain, weight loss, and hormonal changes.
Diagnosis is challenging; doctors rely on a series of tests, including biopsies, to determine the presence and characteristics of cancerous cells. Treatment strategies for CUP vary based on suspected origins and often include surgery, chemotherapy, and radiation. The prognosis for CUP is generally poor, with a significant number of patients experiencing limited survival times. However, advancements in immunotherapy are being explored as promising treatment options, potentially allowing for more targeted approaches that minimize damage to healthy tissues. Understanding CUP is critical for early detection and management, as timely intervention may improve outcomes.
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Carcinoma of unknown primary origin (CUP)
RELATED CONDITIONS: Skin cancer, lung cancer, prostate cancer, breast cancer, lung cancer, recurrent carcinoma
DEFINITION: Carcinoma of unknown primary origin (CUP) is an abnormal growth of cells resulting in malignant (metastasized) cancer with no known origin. Carcinoma represents the most common cancers, including the common forms of skin, breast, prostate, lung, and colon cancer.
Risk factors: Malignant transformation can be caused by exposure to toxic carcinogens such as such as radiation, tobacco smoke, and certain chemicals. Some viruses have been linked to cancer: Epstein-Barr virus and lymphoma, human papillomavirus and cervical cancer, hepatitis B virus and liver cancer, and Kaposi sarcoma-associated virus and Kaposi sarcoma. Additionally, many carcinomas are the result of a random genetic mutation, resulting in abnormally formed cells that can be cancerous. There are strong hereditary factors involved in carcinoma, so having a family history of cancer can mean being predisposed to developing cancer.
Etiology and the disease process: The origin of carcinoma is in the cells of the epithelium, which lines both the outside (skin) and the inside cavities and lumen of tissues and organs. In normal tissue, cells multiply to form new cells, and the old or damaged cells self-destruct by apoptosis (cell suicide). However, when cells undergo malignant transformation (genetic mutations that lead to cancer), they divide and grow rapidly, and tumors form and grow. Tumors can proliferate if the cells divide rapidly, while slow-growing tumors result from slowly dividing cells. As more and more of these dividing cells accumulate, the normal tissue becomes diseased. The cancer can spread to other regions of the body.
Incidence: Over 90 percent of all diagnosed cancers are a result of carcinoma. Of those, from 2 to 5 percent are carcinomas of unknown origin, which have metastasized from an unknown location.
Symptoms: Symptoms of carcinoma of unknown primary origin include local, metastasis, and systemic symptoms. Local symptoms include:
- Unusual bumps, nodes, cysts, or swelling.
- Bleeding (usually found internally or in urine tests).
- Pain from compression of the tissues surrounding the area of tumor growth.
Metastasis symptoms include enlarged lymph nodes, neurological symptoms, an enlarged liver, and occasionally coughing or broken bones. Systemic symptoms refer to symptoms that affect the entire body, such as weight loss, excessive sweating, hormonal changes, or lack of iron in the bloodstream.
Screening and diagnosis: Cancer is usually classified according to the tissue from which the cancerous cells originate and the normal cell type they most resemble. Sometimes, however, although cancerous cells are present, their origin is unknown.
Depending on the symptoms present, a patient may undergo several tests, including blood, urine, stool tests, and X-rays. If carcinoma is suspected, the physician usually orders a biopsy to examine a small piece of the cancerous tissue under a microscope. Cancer is determined to be carcinoma of unknown primary origin when there is no evidence to determine the origin of the cancerous cells.
By examining the cancer's spreading pattern, the physician may derive more information about where it originated. In cancers that appear above the diaphragm, lung cancer is usually the cause. Research has shown that over half of patients with carcinoma of unknown primary origin have cancer that originated in the lung or pancreas.
According to the National Cancer Institute, physicians classify carcinoma of unknown primary origin into one of the following categories:
- Poorly differentiated carcinomas: The cancer cells look very different from normal cells.
- Metastatic melanoma to a single nodal site: Cancer of the cells that color the skin (melanocytes) has spread to lymph nodes in only one part of the body.
- Cancer in the cervical lymph nodes: Cancer is in the small, bean-shaped organs that make and store infection-fighting cells (lymph nodes) in the neck area.
- Isolated axillary metastasis: Cancer has spread only to lymph nodes in the area of the armpits.
- Inguinal node metastasis: Cancer has spread to lymph nodes in the groin area.
- Multiple involvement: Cancer has spread to several different areas of the body.
Treatment and therapy: Treatment of carcinoma of unknown primary origin depends on the suspected origin of the cancer, the microscopic analysis of the cancer cells, and other factors.
Surgery is a standard treatment for carcinoma of unknown primary origin; the cancer and a small portion of the healthy tissue surrounding it are removed. Various surgical procedures are used, depending on the location of the tumor.
Radiation therapy is often used before surgery to shrink tumors or after surgery to kill remaining cancer cells; it can also be used as a therapy without surgery.
Chemotherapy is a systemic treatment that uses drugs to kill cancerous cells. Once the drugs enter the body and travel through the bloodstream, they kill cancerous cells throughout the body. Drugs can be administered orally or by injection into the veins or muscles. Occasionally, chemotherapy is administered after surgery has removed all cancer cells as a preventive measure to ensure that new cancer cells do not develop (adjuvant therapy).
Hormone therapy has shown success in halting the production of hormones that assist in the growth of cancerous cells. Synthetic hormones or other drugs block the body's natural hormones, or hormone-producing glands are removed by surgery.
If carcinoma of unknown primary origin has been categorized, the treatment is more specific. If the cancer is classified as poorly differentiated cells or discovered within the abdomen, the most common treatment is chemotherapy. If the cancer is found in the neck area, treatment may include removal of the lymph nodes and tonsils, radiation therapy, or neck surgery. A lymph node dissection may be performed if the cancer has spread to the lymph nodes. When cancer is found in lymph nodes near the armpit, surgery is performed to remove the nodes and often the breast tissue, along with radiation and chemotherapy. If the cancer is found in the lymph nodes near the groin area, surgery is performed to remove the lymph nodes and some groin tissue. If the cancer is found in several areas of the body, usually a systemic therapy such as chemotherapy or hormone therapy will be used to deliver treatment to the entire body.
Prognosis, prevention, and outcomes: The prognosis for patients with carcinoma of unknown primary origin is poor. Eighty percent of those afflicted will experience an average time of survival of approximately three to six months; 25 percent of patients survive one year, and only 10 percent of patients survive five years. Studies have shown that cancer found in the lymph nodes has a longer survival rate. Colonoscopies, mammograms, and prostate cancer screenings can lead to early detection and possibly longer survival times.
In the 2020s, immunotherapies are showing great promise to include in treatments for carcinomas of unknown origins. In addition to the potential as a more effective treatment, immunotherapies can be targeted to eliminate only the cancerous tissue. This contrasts with chemotherapy, in which non-cancerous tissue can be destroyed as well.
Bibliography
"Carcinoma of Unknown Primary." Mayo Clinic, 6 Oct. 2022, www.mayoclinic.org/diseases-conditions/carcinoma-unknown-primary/symptoms-causes/syc-20370683. Accessed 27 June 2024.
"Carcinoma of Unknown Primary Treatment." National Cancer Institute, 17 Dec. 2021, www.cancer.gov/types/unknown-primary/patient/unknown-primary-treatment-pdq. Accessed 27 June 2024.
Dabbs, David J. Diagnostic Immunohistochemistry: Theranostic and Genomic Applications. 4th ed., Philadelphia, Elsevier, 2014.
Fizazi, Karim. Carcinoma of an Unknown Primary Site. New York, Taylor, 2006.
Jie, Mei, et. al. "Case Report: Successful Immunotherapy Improved the Prognosis of the Unfavorable Subset of Cancer of Unknown Primary." Frontiers in Immunology, 22 Jun. 2022, www.ncbi.nlm.nih.gov/pmc/articles/PMC9256999. Accessed 27 June 2024.
Rassy, Pavlidis, "Progress in Refining the Clinical Management of Cancer of Unknown Primary in the Molecular Era." National Review of Clinical Oncology, 29 Apr. 2020, doi.org/10.1038/s41571-020-0359-1. Accessed 27 June 2024.
"Survival Rates for Cancer of Unknown Primary." American Cancer Society, 9 Mar. 2018, www.cancer.org/cancer/types/cancer-unknown-primary/detection-diagnosis-staging/survival-statistics.html. Accessed 27 June 2024.
The Official Patient’s Sourcebook on Carcinoma of Unknown Primary: A Revised and Updated Directory for the Internet Age. San Diego, Icon Health, 2002.
Tan, Winston W. "Metastatic Cancer with Unknown Primary Site." Medscape, 25 Sept. 2023, emedicine.medscape.com/article/280505-overview. Accessed 27 June 2024.