Joshua Klopper, MD
April 29, 2024
Afirma GSC’s precision is based upon its two-step process: among Bethesda category 3 and 4 nodules,
Afirma GSC will provide a Benign or Suspicious call that looks beyond the presence or absence of a
variant or fusion. If the result is benign, the risk of malignancy (ROM) is 4% or less; similar to cytology
benign.1
If the result is GSC Suspicious, Xpression Atlas (XA), the gene and fusion panel component of Afirma
GSC, can assess for the presence of 905 variants and 235 fusions.2 A GSC Suspicious result carries a ROM
of 50%, but some variants may further refine this risk of malignancy, such as ETV6/NTRK3 raising the
ROM to >95%, NRAS Q61R raising the ROM to 75%, or TSHR lowering the ROM to 25%.1-4 Additionally,
some variants do not change the risk of malignancy from the original 50% provided by the GSC
Suspicious call, such as BRAF K601E.3
Veracyte’s goal is to ensure that the information provided on our Afirma GSC patient report is as up-
to- date as possible as the science used to determine each ROM is constantly evolving. To ensure the
information provided in this report remains accurate, an internal medical team comprised of
Endocrinologists and PhD scientists conducts periodic, exhaustive reviews of existing literature.
Every six months, this team assesses the data to determine if enough quality information has been
provided to update the report.
If a study meets these qualifications, it must influence the ROM enough to change quartiles (such
as raising the ROM from 50% to 75%, for instance) for this ROM change to be reflected in the
report. Veracyte’s risk of malignancy reporting that includes 25%, 50%, 75%, 90%, >95%, and >99%
for individual variants/fusions on XA. By using this quartile method, Veracyte can capture these
changes without causing unnecessary confusion.
A notable example of a review’s impact can be seen in Fall 2022, when Veracyte updated how
isolated TSHR mutated thyroid nodules are reported due to a recent study. Previously, while
detected, the mutation lacked sufficient evidence to impact the risk of malignancy. However, due to
this review, TSHR reached the necessary threshold for Veracyte to confidently report a ROM of 25%
and update the report.4
This is just one instance of the constant, iterative process that contributes to the accuracy of Afirma
GSC. At Veracyte, we are committed to delivering accurate data and high test utility, and believe that
keeping up with the literature is paramount to achieving that goal. As a result, physicians can trust that
the information provided on their reports is both accurate and up to date.
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