The issue of “how much tissue is enough” for various ancillary testing often comes up, especially in the realm of cancer diagnostics. The amount of tissue a pathologist needs to make a diagnosis varies, but quite a bit more tissue is necessary for molecular testing. As we continue to move into the era of targeted therapeutics (that is, medicines that are active against tumors which express certain genes or proteins, but not active against tumors which don’t express those genes or proteins), pathologists find ourselves asking our clinical colleagues for more and more tissue.
In general, core needle biopsies are superior to fine needle aspirations for the purpose of obtaining sufficient tissue for molecular studies (Am J Clin Pathol. 2015 Feb;143(2):193-200), and larger bore FNA needles are also superior to smaller FNA needles (J Bronchology Interv Pulmonol. 2018 Dec 14.), although much depends on the skill of the proceduralist. Adequacy assessment at the time of biopsy by a trained cytotechnologist or pathologist improves yield (Archives of Pathology & Laboratory Medicine 2016 140:11,1191-1199) by giving the proceduralist the opportunity to collect more tumor immediately.
However, even when enough tissue has been obtained initially, sometimes making the diagnosis of cancer requires the use of some of that tissue. If the diagnostic workup is extensive, little tissue may be left over for molecular studies.
How much tissue is “enough”? Well, for IHC or FISH studies (like PDL-1 or ALK, respectively), as little as a square millimeter of tissue is usually necessary. However, for PCR-based molecular tests, tumor must be dissected out of paraffin blocks, requiring much more tissue – technically, at least 5 ng of tumor DNA or 1000 cells (Arch Pathol Lab Med. 2016;140(11):1191–1199). However, the tumor needs to be as free of normal tissue as possible to ensure that only the cancer is tested (testing normal tissue will potentially result in false-negatives). In addition, various other factors can interfere with the analysis (like necrosis). Combined with the necessity of having enough tissue for diagnostic purposes, these factors have led some to recommend up to four separate cores and 2 cm of tissue.
Please contact us if you have any questions about tissue adequacy before or after procedures.