Unknown Primary: Subtypes

Approved by the Cancer.Net Editorial Board, 10/2022

ON THIS PAGE: You will find descriptions of the most common types of cancer of unknown primary (CUP) tumors. Use the menu to see other pages.

The subtypes of CUP describe the type of tumor found in the body. These subtypes are identified by the pathologist when the tumor biopsy is examined under the microscope. Knowing the subtype can help the doctor recommend what kind of treatment is best, and it can help predict a patient's prognosis, which is the chance of recovery.

Most people with CUP have 1 of these 4 types of tumors:

Adenocarcinoma. Nearly 70% of people with CUP have adenocarcinoma. Adenocarcinoma can develop in the glandular tissue of most internal organs, including the lungs, stomach, pancreas, colon, ovary, and breast. Adenocarcinomas arising in different organs look similar under the microscope, so it is extremely difficult for a pathologist to tell where an adenocarcinoma began when it is found at a metastatic site.

Additional diagnostic tests on biopsy samples, called IHC stains, can predict the primary site about 30% to 40% of the time. A molecular cancer classifier assay of the biopsy specimen can accurately predict the primary site for most other patients. Learn more about gene expression profiling in the Types of Treatment and Latest Research sections.

Poorly differentiated carcinoma. About 20% to 25% of people with CUP have poorly differentiated carcinoma. Pathologists do extra testing on biopsy samples of these tumors because some very treatable cancers may be first diagnosed as poorly differentiated carcinoma. Similar to patients with adenocarcinoma, a molecular cancer classifier assay can usually predict the tumor type of the primary site and is useful in helping choose treatment options. If this testing shows the cancer is lymphoma, germ cell carcinoma, or neuroendocrine carcinoma, effective treatments are often available.

Squamous cell carcinoma. About 5% of people with CUP have squamous cell carcinoma. If squamous cell carcinoma is found in the cervical lymph nodes in the neck, the primary site is often in the head and neck area. If it is found in the inguinal lymph nodes in the groin, the primary site may be in the vulva, vagina, cervix, anus, or bladder. A careful search is important because these cancers can often be successfully treated. Read more about squamous cell carcinoma of unknown primary in the head and neck.

Neuroendocrine carcinoma. About 1% to 5% of people with CUP have neuroendocrine carcinoma. The diagnosis of neuroendocrine cancer is often dependent on the results of IHC stains performed by the pathologist. Some of these tumors are aggressive and fast growing, but combination chemotherapy (see the Types of Treatment section) may be effective. Others are very slow growing, and people sometimes live for several years, even without treatment.

Information about the tumor’s subtype will help the doctor recommend a specific treatment plan. The next section in this guide is Types of Treatment. Use the menu to choose another section to continue reading this guide.