The Biopsy was NEGATIVE! Desired Result or False Hope? 

The words “the biopsy is negative” are music to the ears of anyone who had a biopsy of a suspicious lung nodule. But sadly a “negative biopsy” does not always prove the nodule is not cancer. This is a critical concept to understand because I have diagnosed lung cancer in patients years after their first biopsy was “negative.”

Biopsy types:

There are two types of biopsies. The first is called excisional because a surgeon removes the entire nodule. If they don’t find cancer in the removed nodule, then you can be certain its not cancer because they pathologists examine the entire nodule.

 

The second biopsy type is a sampling biopsy. The biopsy removes a small portion of the nodule for examination. These biopsies are typically preferred over an excisional biopsy because they are less invasive with less complications. For lung biopsies, you also lose far less lung in the sampling biopsy versus the excisional biopsy. However, a cancerous nodule is also typically only 30-50% cancer. The rest is made up of non cancerous tissue. So based on where the biopsy is performed, there is the possibility of missing the cancer. This is called sampling error.  Its no one’s fault, its just the fact that its impossible to know what part of the nodule to biopsy by imaging.

What to do:

If the biopsy is “negative,” the next steps depend on how likely the nodule is to be cancer and how big the nodule is. Nodules that have a high chance of being a cancer should receive an additional biopsy via a different mechanism. If the initial biopsy was done via bronchoscopy by a pulmonologist, then getting a second biopsy by interventional radiology makes sense. And vice versa. Alternatively, if the chance of cancer is so high (i.e. the nodule is growing), then it may make sense to have it surgically removed.

 

Nodules that are smaller or have a lower chance of being a cancer, could be followed with another chest CT at a later date. The timing of the next scan should depend on the size of the nodule. Since we usually only attempt biopsies of nodules at least 8mm in size, the next scan should be in 3 to 4 months. If a biopsy was performed on a nodule below 8mm, then a follow up scan at 6 months makes most sense. The timing of these follow up scans is based on the current sensitivity of Chest CTs and the biology of tumor growth. Remember, these are suggestions and individual cases could differ for legitimate reasons.

 

When is it really negative?:

This is the question everyone wants answered. When can I stop worrying about the nodule. All solid nodules that do not change in size over two years are considered benign and do not need additional follow up. Nodules that are not solid tend to be called benign when they do not change for 5 years. This is due to the fact solid nodules tend to grow faster than not solid nodules. The nodule disappears infrequently but when this happens, we rejoice. Occasionally, they decrease in size and although this increases the chance the nodule is not cancer, consultation with a pulmonary doctor skilled in nodule management is still warranted.

 

Better Term:

I prefer the term “non-diagnostic” for biopsies that are otherwise called “negative.” Its hard to prove a negative, so a negative biopsy may not means what we want it to mean. So its important to realize biopsies are not perfect and appropriate follow up after a non-diagnostic biopsy is very important.

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