An Inconclusive Biopsy: Why Another Procedure May Be Needed

Start with an honest limit. The National Cancer Institute does not publish a patient page about biopsy samples that give no answer, or about repeating a biopsy. Its diagnosis pages describe how biopsies are done and what a pathology report contains. They do not explain why one sample fails to give an answer, or when a second procedure is needed.

So this article sticks to what NCI does document. Everything specific to your own case has to come from the team that took the sample. Be careful with any source that gives you confident general rules about repeat biopsies. That guidance is not coming from NCI.

NCI is direct about this: "There is no single test that can diagnose cancer." A doctor may start by asking about your own and your family's medical history, and by doing a physical exam. Then they use some mix of lab tests, imaging tests, and a biopsy.

Lab tests can include several things. A blood chemistry test measures substances released into the blood by organs and tissues. A complete blood count counts your blood cells. Cytogenetic analysis looks at chromosome changes in tissue and blood samples. Immunophenotyping uses antibodies to identify cells by the types of antigens, or markers, they carry. A liquid biopsy is done on a blood sample, to look for cancer cells. Tumor marker tests measure substances made by cancer cells. Imaging tests include CT, MRI, nuclear scans, bone scans, PET, ultrasound, and x-rays.

Each of these answers a different piece of the question. So a result that does not settle things is not automatically a failed test.

NCI describes several ways to get a biopsy sample: with a needle, through an endoscope (a thin tube with a camera), or by surgery. Surgical biopsies come in two kinds. An excisional biopsy removes a whole lump or area. An incisional biopsy removes only part of it. Once the sample is out, a pathologist looks at the tissue under a microscope and runs other tests on the cells.

Ask which method was used. It decides how much tissue the pathologist had to work with.

There are two ways to prepare tissue. They are not interchangeable.

For fixed, or paraffin, sections, the tissue is treated with formalin. A machine then removes the water and replaces it with paraffin wax. The block is sliced very thin, placed on slides, and stained. NCI notes that this normally takes several days. Results are usually available in about 10 days.

For frozen sections, tissue is frozen quickly and cut with a cryostat, then stained and examined. This takes about 15 to 20 minutes. That is why it is used to get an answer while surgery is still going on. But NCI adds an important point. Fixed sections show finer detail, and are used more often to make a diagnosis. A quick answer during surgery is not the same as the final answer.

A pathology report, sometimes called a surgical pathology report, describes the features of a tissue specimen. It includes information identifying you and where the specimen came from. It gives a gross description, which is what the tissue looked like to the naked eye. It gives the microscopic findings. And it gives a final diagnosis. It may also include comments from the pathologist and the results of molecular tests.

Read the final diagnosis line first. Then ask your team to walk you through the microscopic description, and any comment attached to it.

You or your doctor can ask another pathologist for a second opinion on the report. That means getting the slides, and sometimes the paraffin blocks, from the original facility. Many NCI-designated cancer centers and academic institutions offer this service.

• What did the pathology report say in its final diagnosis line, and is there a comment section?
• Which biopsy method was used, and how much tissue did the pathologist receive?
• Was this a frozen section or a fixed section?
• Are any stains or molecular tests still running, and when are they due?
• Would a second pathology opinion change anything, and who would send the slides?
• If another procedure is being proposed, what exactly would it answer that the first one did not?

That last question is the one to insist on. Ask it plainly, and ask for the answer in writing.

• National Cancer Institute — Tests and Procedures Used to Diagnose Cancer
• National Cancer Institute — Surgical Pathology Reports
• StatPearls (NCBI Bookshelf) — Thyroid Nodule: nondiagnostic (Bethesda I) cytology and repeat aspiration