This presentation outlines a comprehensive clinical approach to managing thyroid nodules, emphasizing the importance of initial evaluation, diagnostic tools like ultrasound and fine-needle aspiration biopsy (FNA), and the emerging role of molecular testing in refining treatment decisions.
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uh good afternoon everyone I'm Lila
shobab and today's talk is rather really
clinical and I I chose to focus on an
area that is quite common and endocrine
that you probably have seen and we'll
see quite a bit and hopefully will be
also some learning uh uh experience for
our trainees and the faculty so I'm
talking about General approach and
hopefully provide you with a
basic approach in clinical management of
thyroid nodule with the
objective to provide you with a review
of ultrasound characteristic of thyroid
nodule and their significance in
clinical management of nodules
and I hoping also to help you understand
the role of fine needle aspiration
biopsy and cytology interpretation of
thyroid nodule and provide you with some
appreciation of the role of molecular
testing which is a rather a new field in
management nodule so over the next 40 to
45 minutes hopefully we'll I'll give you
a brief snapshot of epidemiology of
thyroid nodule we'll go over initial
clinical evaluation mainly focusing on
History taking and physical examination ultrasound
ultrasound
characteristic and financial aspiration
biopsy and we review a couple of
platform of molecular testing for
thyroid nodule and if time allows I will
introduce some of our ongoing studies
and of course there will be time for questions
questions
so the incidence of thyroid nodule had
increased over the past two to three
decades but is now plateauing uh as you
can see there's quite a big rise in the
instant of thyroid nodule uh that brings
the question about why do we see so many
thyroid nodule now uh one theory is that
with the increasing access to different
Imaging modalities including ultrasound
of head and neck MRI CT scan Etc we
discover incidentally a large number of
thyroid nodules which we probably would
have never known about before which
could be true however the entire nodules
are also found by palpation regardless
of the Imaging in the prevalence of
thyroid nodules that are discovered in
palpations are also significantly high
so approximately eight to sixteen
percent of population will have some
nodule that can be pulpated clinically
on physical examination however if I use
ultrasound let's see on a random sample
of a hundred people I probably will find
thyroid nodule in approximately half of
the sample anywhere between 19 to 67
percent of individuals will have some
detectable nodule on ultrasound so it's
a very common phenomena and now that we
see more we have to come with a approach
with an organized approach to deal with
this large volume of thyroid nodules the
good news is that the majority of these
nodules are benign so generally they
just sit there really don't do anything
but for two reasons that we get
concerned one is the share size that
they can grow and obviously neck is a
quite a quite a crowded place with vital
structures and if something grows that
becomes a problem and the second issue
is that they can Harbor risk of cancer
so approximately eight to sixteen
percent of these nodule can Harbor
cancer are in them
so to show you also the incident rate of
thyroid cancer this one is papillary
thyroid cancer which is the most common
type of thyroid cancer that has been
also a rise in the incidence of thyroid
cancer which may just mimic and mirror
the um you know incidence of thyroid
nodule obviously when you have more
thyroid nodule you also discover more
thyroid cancer I use the slides because
I would like to make a point that if you
look a little bit closely you see that
not only small nodules are on the rise
in terms of instance but we have all
these large nodules in this case two to
five centimeter These Are nodules that
you don't necessarily you know identify
incidentally on Imaging often they
present with some sort of a clinical
presentation whether that could be a
palpable Mass it could be some clinical
compressive neck symptom Etc so maybe
there is the rise in the thyroid nodule
is really related to increased use of
Imaging but probably there's some
contribution to to uh you know increase
there's a true rise in the instance of
thyroid cancer especially the larger
nodules as we can see have risen in
terms of the incidence so probably
there's a combination of true increase
in the incident as well as just
incidental finding uh as well so the
question is why do we see we don't
really know maybe some environmental
factor that is contributing to higher uh
risk of developing thyroid nodules
so now you have a patient in your office
with thyroid nodule and you wonder okay
what should I do next before I um I get
an appointment with an endocrinologist
to see them so again a same basic
approach of taking a good focused
history and physical examination always
is um you know it it's a good first
start in terms of uh history there are
certain clinical findings that are
associated with increased risk of
thyroid cancer and thyroid nodules and
those include history of differentiated
thyroid cancer at least in one of the
first degree relatives will increase the
risk of nodule Harbor cancer also
history of external beam radiation or
exposure to ionizing radiation as a
child or other lessons this can include
a prior treatment uh you know for
childhood cancers for example I believe
at some point a certain skin condition
were treated with some form of radiation
so those less obvious you know
circumstances that you know you you have
to sort of evaluate and ask these
questions the patient interestingly are
also male sex this is an area of my my
research so there is an increased risk
among nail in particular more aggressive
thyroid cancer so the male sex does
increase the risk of a nodule being malignant
malignant
and then if the patient had a pet scan
with positive uptake maybe for other
reasons in this incidentally found a
thyroid nodule that increases the risk
of that nozzle being malignant in general
general
and any personal and family history of
multiple endocrine neoplesia type 2 or
familial majority thyroid cancer
obviously will increase the risk and if
you were suspecting a majority thyroid
cancer and measuring calcitonin a
calcitonin level more than 50 in 100
that certainly increased the risk of
nodule uh being malignant in particular
medullary thyroid cancer in another
pretty obvious but something that
actually we get always surprised that we
do see patients still any exposure in
the Resident near the nuclear reactor
accident in particular Chernobyl is one example
um other question that I also try to uh
remember in this sort of part of my
template and and seeing any thyroid uh
patient is uh you have to ask them about
um symptoms of hyper and hypothyroidism
I I suppose there are some residents or
some trainees in our audience so what
are symptoms of hypothyroidism anything
such as heat cold intolerance
constipation weight gain fatigue a bit
you know kind of nebulous symptoms but
still important to ask because sometimes
it gives you a bit more information uh
symptoms of high thyroid State such as
you know palpitation heat intolerance
weight loss and anxiety
and Tremor will be symptoms of elevated
thyroid level and and that can be
helpful because that may it it may give
you some clue about this nodule being a um
um
toxic nodule which may have a little bit
different leans you toward a bit
different decision making so those are
important questions to ask another
question is also another category of
question is compressive neck symptoms
really important to ask about things
such as dysphagia or dinophagia
dysphonia a recent onset of hoarseness
is really important because it may give
you some clue about a tumor that may be
invading the recurrent laryngeal nerve
so so that that can be quite important
uh and then uh another aspect is
important which may uh we may take it
for granted that the patient hasn't told
me anything about it but sometimes they
actually may have already known thyroid
disease hypothyroidism Hashimoto
stereotypes Etc so ask about whether
they have any known thyroid disease are
they taking any medicine
um there is this long debate about the
you know correlation of uh increased
risk of autoimmune disease chronic
inflammation and thyroid gland and risk
of thyroid cancer so Hashimoto's has
been considered to be a risk for forming
nodule but also uh for developing
thyroid cancer based on chronic
inflammation in the gland
on physical examination there is you
know a different approach there's the
anterior approach in examining thyroid
and the posterior approach uh whatever
you choose there is no right answer to
this you just develop your own approach
I I started examining tariffs from the
anterior aspect but now I changed my
Approach I find that I have a bit more
control I can palpate at the neck a
better from the posterior often I ask if
they have water with them and their
covet time is a little bit difficult but
having patients take a sip of water
while I'm very gently putting my hands
I'm not pressing on any structure I'm
just gently putting my hand where I
anticipate that the thyroid gland to be
and when they take a sip of water that
brings the thyroid up and makes it
easier to palpate and then obviously
it's important to inform the patient
that you are gently going to palpate
their neck so that they're not surprised
by you know two hands are approaching
your neck from behind so that's always a
good idea to tell the patient an
important to also check for cervical
supraclavicular mandibular adenopathy
can be very informative in general a
firm a mobile nodule in the neck is a
high risk nodule in in harboring cancer
and for the lymph node also a firm lymph
node immobile especially on the
ipsilateral side of the neck where the
thyroid nodule is can be uh you know an
indication of local Regional metastasis
to the lymph node
and other findings you know General
finding I'm sure that's just look for
the general signs of hypo hypothyroidism
but in particular some of the familial
disease related to thyroid cancer things
you can look for skin tongue because of
small nodules hematomas in the context
uh so now uh the question is you've got
a history uh you took a physical
examination you've got a let's say two
centimeter nodule what do you do next
uh the next step is to order investigations
investigations
um you know lab and imaging lab is
pretty simple so a TSH would suffice
initially as the first Next Step uh it
would it could be very informative in
general low TSH will be uh you know
leaning toward more hyper functioning
nodule a toxic nodule and in that case
you order further uh lab investigation I
usually order as a next step in terms of
having a comprehensive thyroid profile
uh I get free T4
vt3 total T3 and then I get the antibody
levels since TSI thyroid stimulating
immunoglobulin TSH receptor antibody and
I also add the thyroid peroxide so those
three antibodies in the setting of when
I'm uh suspecting hyper functioning
gland as well as the fee hormones and
then depending on the clinical context
you may also order a uptake and scan
because I've taken scan will be give you
a bit more information where does the
uptake where does the functioning come
from is it the local areas the toxic
nodule versus diffuse uptake which is
associated with uh Graves disease a
normal TSH don't need to do anything
further High T stage you may order again
uh you know further uh
component of the
thyroid hormone to get a better sense
and then and then the next step also
important is the thyroid ultrasound
which we're going to spend a little bit
more time on
so this probably you have seen and if
not this is a kind of summarizing some
of the ultra sound characteristic that
has been associated with the risk either
low or high risk of thyroid nodule being
malignant and then based on these
characteristics you can actually
estimate the risk so let's go over some
of those
ultrasound characteristics that are
associated let's say with high risk of
nodule uh being malignant they include
calcium deposits so micro macro calcification
calcification
hypoechoic meaning we have darker than
the surrounding tissue if they are
taller than than wider here irregular
borders so if there is some Interruption
of the calcium rims for example that
suggests extension beyond the uh
capsular extension in the surrounding
tissue so that's always not a good sign
for malignancy uh and then uh and then
it goes you know to the range of being
high risk to low risk we have uh here
hyper echoic which is associated with
lower risk meaning is is more dense
equidense compared to the surrounding
tissue isoechoic is sort of intermediate
with Loris characteristic could be
spongiform which is a sort of
combination of cystic and solid and then
you also have the cystic nodule which
really is associated with low risk of
malignancy and then based on these
ultrasound characteristic
um you sort of categorize the nodule
into different risk categories as you
you appreciate in the previous slide
from benign to very low low intermediate
and high suspicion and this is a a table
from the American entire Association the latest
latest
guideline from 2016 and let's say if you
have a high risk nodule which is
associated with it's a solid nodule a
hypoechoic irregular margin
microcalcification extratory extension
would bear about 70 to 90 percent risk
of malignancy and in this case we move
forward in arranging finite El
aspiration biopsy to further
characterize the nodule notice that one
centimeter is a a
cut off size cut off
usually considered to be a smaller big
nodule the definition is is not not
written anywhere but understanding when
we're talking about small nodule
generally is one less than one
centimeter and anything then considered
to be non-smallow or big nodules but any
anyway so then even if your nodule is
one centimeter you go ahead and and
arrange to finally last patient biopsy
and note that for Laura for benign
nodules or another who That You Don't
See really high characteristic of uh you
know being suspicious for cancer
spongiform and cystic uh you don't
biopsy even the size could be four or
five centimeter let's say for Cystic
nodule you just leave it alone
uh and then uh sort of it's like
intermediate range between benign and
high suspicion and sometimes in the
intermediate range may be a little bit
difficult but then you consider the
clinical context history
Etc in order to make a decision about
finding the last patient biopsy having
uh said that I have patients that have a
very small nodule in the thyroid gland
0.6 0.7 and initially they presented
with metastatic thyroid cancer in their
bone with a bone fractures how they
present so I take this with a little bit
grain of salt and you know the nodules
at this point it's although we have
better tool and predicting but you know
there is still a good chance of some
chance of a nodular small malignant okay
okay
so I then I want to also point out
the other system that you may be more
familiar and you may have seen and uh in
your patient record is the thyroid
system of recording the ultrasound
characteristic and giving you a report
of the risk stratification this is the
thyroid Imaging reporting and data
system of the American College of
radiology so it's a very similar
approach so they use the composition
echogenicity shape margin presence of
echogenic Foci to come up with a you
know a risk number or I give a point and
then points are all uh you know added to
generate a tie rod risk level generally
goes from zero to seven so if we look
maybe in composition a cystic nodule
will not get a point a spongy form also
that they will not get a point and
notice the spongy form was associated
with a little bit higher risk in the ATA
guidelines so there's a little different
here mixer second solid will get one
point in solid uh nodule would get two
points so then you add these points and
if your total point is zero you don't
get any final last Brain position biopsy
because it's considered to be benign and
so on uh and then then
based on this uh sometimes you actually
see in the report Radiology report is
giving you a recommendation about biopsy
went to biopsy went to not
Etc so those are very useful I have to
say useful but um to make a decision
about biopsy I have to really as a
clinician I I need to put in the context
of other clinical
parameter including the history and
physical examination my degree of
Suspicion so and and not just what I see
um don't forget about the lymph nodes
they can also be detected in an
ultrasound and can be very useful in
using the ultrasound characteristic to
predict the risk of malignancy some
features associated with risk of
malignancy include microcalcification uh cystic
cystic
aspect peripheral vascularity
hyper-ecogenicity in round shape and the
round shape is sort of associated with
the same concept of loss of fatty hyalur
and I find comments of Radiologists in
regard to you know fatty hyalum whether
they are present they clearly can see
the fatty hyaluma there's some loss or
it's unclear with a fatty Highland can
be identified clearly you find it
helpful uh so the
philosophatty hilum in the center of
lymph node is associated with increased
so the ultrasound
and then fine little aspiration biopsies
the next
step and uh evaluating the nodule so
it's these days is perform ultrasound
guided uh as opposed to Blind fine
utilization biopsy and they finally the
last patient biopsy is really the most
sensitive and cost effective method in
evaluating nodules for risk of
malignancy in general
we run about two to five passes through
the nodule most of the time just only a
couple of passes through the nodule uh
and then it is very important to uh
ensure sample adequacy that can be
sometimes a problem uh in in several
institutions and therefore it is ideal
if you have a pathologist that you know
experiences Pathologists in your
institution who can uh uh inform that
this is a sufficient uh sample uh
because then the patient I have patients
that performed in different institutions
coming back very anxious about the
results and the results come back
insufficient after days and weeks
potentially and then the patient has to
go again through the same uh so that can
be avoided and then the other thing is
which I'll be talking about later you
can perform a final aspiration biopsy
right after a first attempt because
um you know you want to avoid a
potentially false positive because there
will be a bit of inflammation and
scarring and if you go back right away
um there is an increased risk of having
false positive biopsy so you've got to
wait up at least two three months to
repeat your uh biopsy so we have a quite
experienced pathologist in Washington
Hospital Center who routinely make sure
that we have sufficient sample which has
decreased the you know incidence of
inadequate samples significantly we
hardly have any
and then usually if I have any suspicion
on lymph node I order the biopsy at the
same time which saves a Time
uh and um I I I want to just briefly
talk about the non-diagnostic or
unsatisfactory uh samples actually they
can Harbor risk of malignancy despite
the fact you haven't obtained any tissue
um I will show you uh shortly that uh
the actual risk of malignancy in these
nodules are uh considerable so you can't really
really
um forget about these not just let's say
you were not able to obtain adequate
sample and you just said well fine I'll
just follow and see what happens but you
know actually the recommendation is that
a second attempt should be tried and if
you uh and the second attempt if no
tissue is obtained successfully then a
excisional biopsy is recommended to make
sure that there is no malignancy in
these nodules sometimes it may be that
the nodule is pretty hard and harbors
cancer and it's very difficult to get to
that that's a potential explanation of
why you can get a sufficient sample I I
did mention this but for the benign nodules
nodules
um so generally if it's a low malignancy
uh they have low malignancy rate in
general and they repeat biopsy FNA is
not recommended especially in the
setting of no features of ultrasound
that suggests malignancy large and
lodges can become problematic so if you
have a large nodule with benign
FNA and with large generally the cutoff
is considered to be four centimeter they
can have a higher risk of false negative
and that's substantial about five to ten
percent so if you have a large nodule in
our in your patient with benign biopsy
final aspirin biosity you can't um you
know just you know stop following this
nodule they require a bit more
surveillance maybe repeat
ultrasound to make sure the
characteristic haven't changed the size
haven't changed
um I I drew that just to give you a bit
of a sense of what I'm trying to say
let's say you have a nodule
um one centimeter small nodule and a
five centimeter large nodule they both
Harbor the same let's say tissue
transformation of same area same amount
of tissue that has transformed to a
malignant character a malignancy and
you're passing two runs to get a final
expression biopsy in a smaller nodule it
is more likely that you're going to hit
the transform tissue and have a positive
biopsy whereas in large nodule there is
a higher potential of you missing that
area of transformed tissue so therefore
it although with the setting of large
nodule the result of final aspiration
biopsy even benign you have to take it a
little bit into consideration
so after you get your result of fine
needle aspiration biopsy we generally
use the Bethesda system risk of
malignancy category as a stratification
which categorize the aspirate in six
different categories based on the risk
stratification it goes from
non-diagnostic I mentioned to you the
ones that we can get satisfactory
sampled to malignant so the if you
notice so here is the estimated risk
based on clinical and
historical characteristic and this is
the actual risk of malignancy based on
these nodule actually some of the
nodules are studies that have performed
thyroidectomy and looked at these nodule
uh individually so actual risk of
malignancy is pretty accurate estimation
of malignancy risk in the nodule the
non-diagnosticone unsatisfactory has a
significant high risk of being malignant
and I have to say that's also really
dependent on the institution you know as
I mentioned all the characteristic that
of Institutions
availability of the Pathologists being
on site performing satisfactory sample
collection Etc
um I would say in our institution this
is much lower
benign nodules are generally uh you know
they don't have a low risk of malignancy
generally reassuring doesn't require any
further investigation in terms of you
know uh surgery surgery or excisional
biopsy Etc and the same goes if if some
nodule is malignant or suspicion with
malignancy you've got pretty high risk
of it being malignant and often surgical
consult is appropriate but in the middle
category basically the category three
and four is sort of intermediate
sometimes it's not very clear in terms
of what is our next step in managing
these nodules in particular the category
of Ethiopia of Uncertain significance or
clinical significant follicular lesion
of undetermined significant that's
category three and the category for
follicular neoplasm of Suspicion for
follicular neoplasm the risk of
malignancy is very similar between
estimated and actual so somewhere around
five to fifteen percent of 15 to 30
percent risk of malignancy which not is
not obvious always about what to do next
although that really depends on patients
uh you know uh uh preference
um sometimes maybe a clinical context
will help you to make a decision but
it's not uncommon where we we don't know
really what to do with these nodules for
the for the next step and therefore
um strategies have been developed and
one of them is to develop the use of
molecular testing platforms to
understand what is the underlying
mutation on molecular changes which may
be helpful in predicting the behavior of
these nodules and um
so the general uh you know principle
uses as I mentioned in indeterminate
nodule you want to rule out the presence
of malignancy I already mentioned this
but um it is really important to
although these platforms are becoming
more and more available it is really
important to still
consider other important uh aspects of
decision making and they are not here to
replace uh you know ultrasound finding
uh that are important also to making
decision feasibility of surgery is uh
you know at the surgery or surgeons are
accessible for this patient for that
situation what is patient preference Etc
so you use these Platforms in molecular
testing together with all the other
clinical information that you obtain from
from
your patient I don't want to go too much
over this but I want to mention this
just because so that you have a context
and background in understanding why the
molecular testing are useful uh with the
Advent of uh cancer genome Atlas in 2014
we know much more about the genetic
transformation of mutation that is uh
underlying thyroid cancer
we know that there are an approximately
80 to 90 percent of patient with thyroid
cancer you can actually isolate or
identify mutation that could be a point
mutation or a fusion a copy number
alteration but these information makes
it much more
um you know they're very helpful in
order to predict the behavior of cancer
as well as a thyroid nodule for the
potential risk of malignancy of
transforming to malignancy in general
most of the thyroid cancer patients with
identified mutation can act like b-raph
like or vast like or some others I
mentioned copy number alteration of
fusion and there is a genotype phenotype
characteristic as I mentioned there are
certain behavior of cancer that you can
predict and this is based on us knowing
a little bit more about the driving
pathway important for the pathogens the
thyroid cancer in particular the map
kinase or mitrogen activated protein
kinase cascade has been identified as an
important driver pathway leading to to
increase Pro if mutation involved in
this pathway is driving the cancer and
leading to proliferation Invasion
metastasis you can see that there are certain
certain
driver of this pathway that has been
associated with you know mutation that
has been identified and to give you a
bit of a sense in approximately 70
percent of patients that we can identify
mutation you can find point mutation in
the 27 it could be a copy number
alteration in particular b-raph is
present in approximately 50 to 60
percent of thyroid cancer patients so
pretty common mutation uh in thyroid
cancer followed by rust different type
of in particular ahrefs and enrass is
common and thyroid cancer in different
type of Gene fusion important uh in
thyroid cancer pathogenesis and this is
nice because now you can actually see if
you identify B ref so where does that
come from the pathway this is where the
b-raph is important and and mutation
actually leads to more
um a
hyperphosphorylation and increased
activity of downput output in the in
this uh in the downstream Pathways in
the ultimately to more proliferation
Invasion metastasis so this is not only
very useful in predicting the behavior
a thyroid nodule and thyroid cancer but
now we also have as you may be very
aware from other fields of oncology we
have actually targeted treatment for
specific mutation and entire cancer in
particular we have for braf mutated
Cancers and rat mutated cancer medullary
cancer now we have a targeted treatment
that addresses the
cancer that bear this mutation although
we still have quite a bit work to do
because they haven't they have improved
you know the
management our ability to manage
aggressive thyroid cancer but they
haven't led to a really clear survival
benefit and the use is associated with
significant toxicity but that's a huge
step forward especially for a patient
who no longer respond to radioactive iodine
iodine
and surgery
so I just want to introduce this so that
you understand the purpose of these
molecular testing an ideal word we want
the molecular test to have a you know a
high positive predictive value uh so to
rule in the presence of malignancy or to
rule out with the higher negative
predictive value and I want to just show
you and remind you again that when we're
calculating the positive predictive
value or negative predictive value it is
really important to be mindful of the
prevalence or institutional prevalence
because that will really impact uh our
uh ability to you know predict the or to
to a positive critical value or negative
predictive value so that we have to take
this in the context of the prevalence of
um so with this let's just move on to
just uh take a look in a couple of these
testing platform affirmas probably you
have heard uh before a from a gene
expression classifier is one of the uh
platform is used quite frequently it's
based on microarray technology for
measuring a messenger RNA in the measure
167 genes and only used for category
three and four of uh beta cytology which
is what we need for and they generate
two possible results something is either
benign or suspicious
and uh the great thing is this test has
a really high negative predictive value
so if it comes back as benign very
likely that is going to be benign
however the problem is a very poor
positive predictive value so if it comes
back as cancer is we still are a little
bit in the unknown territory in terms of
what to do next so then
um you know you have to consider all the
clinical information that you get from
the history and ultrasound Etc but it's
a great test for a ruling out cancer
um so there are some other limitation
one would be that it's really false the
high rate of benign hurdle cell neoplasm
that are reported as suspicious so using
for a hurdle cell it's it's a little bit
tough and then there's a newer version
of affirma that has a high specificity
which is improved from the initial
version so it's a little bit better foreign
foreign
so has that improved our clinical care I
would say yes it has one of the study
has shown that there has been a
significant decrease in surgical
resection of these um indeterminate
nodule from 74 down to 7.6 so I would
say there's a huge impact on decision
making and indetermined nodule
uh there is the other platform Thai Gen
X which uses a panel of genetic mutation
and thyroid cancer also has undergone a
lot of development since the initial
Inception but it uses more than 100
genetic mutation across eight genes uh
listed here
for the two categories we mentioned uh
and now they have included another
tested incorporates micro rnas 10
different micro rnas which has led to a
bit improved sensitivity and specificity
of the test so a negative predictive
value pretty good 94 and positive
predictive value which is much greater
74 actually this is the best we have in
predicting cancer
another platform that is frequently used
is thyro seek which we use pretty frequently
frequently
it uses Next Generation sequencing uh
strategy to um uses a mutation and
infusion panel uh it it has undergone
quite a lot of uh development since its first
first
version which was tyrosy version zero it
had only seven cancer Gene and now the
latest one is thyroxide version 3 which
has over uh 12 000 mutation hotspot and
over 120 Fusion types quite sensitive 98
94 and specificity is also much improved
with a negative predictive value of 97
and positive predictive value 66
although it seems low but that's
actually much improved from what we were
able to do before
uh and to just put it in in context in
comparison probably you have seen or you
will see these two platforms and they've
been coming head to head in comparison
with each other uh a lot so they're very
similar uh the only difference I would
say is the positive predictive value a
little higher entire C compared to the
latest version of affirma so if you
really want to know uh and you have a
high suspicion of cancer and you know
that probably uh the styrocip version 3
would be a better one to take
of note we in Washington Hospital Center
uh we have a reflex system which is
great everything has its benefits and
you know cost uh associated with it but
we do have a reflex system in place that
when we have Financial aspiration biopsy
of Bethesda 3 and 4 it goes to uh
molecular testing in general we use all
the three platforms depending on the
physician's preference but they have
kind of similar performance within our Institution
so do molecular testing change my
practice the first diagnostic utility
we know that a Firma if it's negative
it's very useful and we we saw that it
does it may obviate surgery we saw and
there are studies that prove that there
are still variability in test
performance and maybe this is related to
specific institutional prevalence
um and then sometimes there is lack of
correlation between a specific
biomarkers such as if you have certain
Ras mutation it's not always clear how
this Ras mutation is going to behave in
thyroid cancer so although you have a
Ras mutation sure increased risk of
malignancy but it may just be benign or maybe
maybe
malignant and aggressive so it's not
always very clear in terms of you know
this genotype phenotype correlation in
every mutation
uh and it can be still there is some
issues with certain uh histopathological
uh subtypes uh I mentioned uh hurdle
cell and
cytology is still a little bit of a problem
problem
what about impact on surgical decision
making we saw that it did certainly
impact uh especially useful if you have
really high risk mutation especially if
they come in two like if you have a
combination of b-raph mutation and third
mutation which are both very high risk
in particular a third mutation has been
correlated with really high risk
Advanced thyroid cancer so if you have
those in a nodule you can you can be
sure that this is going to lead to
malignancy and it will be an aggressive
cancer so it's helpful for making a
clinical decision about surgery and more
closer so their surveillance afterward
um uh what about the impact of extent
extent of surgery such as lobectomy
versus told thyroidectomy it can be
helpful but not so because the
guidelines surgical guideline keeps
changing and they have other character
other uh uh you know priorities
especially recently there is more
um sort of conservative approach in
avoiding low back to me in general and
surveillance is more emphasized so
guidelines change and it's not always
very clear what to do when you get the
result of molecular testing based on the
you know local National guidelines
cost Effectiveness are they cost
effective that's a difficult question so
I'm going to put just give you a bit of
a comparison about the cost of different
assays so affirma gene expression a
classifier you can see about close to
five thousand uh the more sophisticated
version is 6500 pretty expensive
thyroseq is relatively cheap and then
the lobectomy itself nine thousand to
twelve thousand so that gives you a bit
of a perspective in terms of cost not
always very clear uh if we
save cost by performing these molecular
tests I think it really depends on the specific
specific
clinical context sometimes sure maybe we
are preventing the
um ex very extensive surgery if you have
a benign nodule and you know we just
monitor but what if we have a mutation
that is unclear genotype phenotype and
we have now found a mutation and now
there will be increased use of surveillance
surveillance
um you know methods use of ultrasound
clinical evaluation Labs Etc so it can
actually lead to additional cost for a
nodule that may actually clinically will
end up being quite benign so it that is
not very clear so something that I think
we need a bit more studies and I ideally
if we can find a way to decrease the
cost of these uh testing platforms uh if
it's a thousand dollar approximately it
may break even so that that hopefully
will be the goal
so how long should I follow up these
nodule um you know if you have a high
suspicious Ultrasound with benign FNA
and you look at the final aspiration
biopsy again and you think okay I'm not
sure I actually was expecting look at
the hypo apoism uh microclassification
very you know um irregular board Etc and
I I usually then follow them up again
with ultrasound within six months even
or sometimes even earlier than that if I
have really high suspicion I may repeat
the fine needle aspiration biopsy within
12 months as also endorsed by the ATA guideline
um in law to intermediate suspicious
ultrasound and benign FNA you may also
want to repeat the ultrasound don't have
to repeat the FNA but ultrasound and
look for any changes in size or in in
characteristic of nodule if there is
significant growth and significant is
considered to be anything more than 50
volume so you have to make sure that uh
um you know in your institution usually
most of the institutions do report it in
three dimensions and therefore you see
three centimeter by two by
five Etc so that that's the purpose is
to make sure be able to calculate the
volume and understand whether that has
been a significant growth and volume or
over 20 increase in at least two
Dimension and it has to be more than two
millimeter uh then you will repeat the
FNA if there has been a change uh in the
characteristic or size of the nodule for
low risk ultrasound and benign FNA you
can just follow it one to two years
sometimes it's debated it's not clear
how long but within the clinical context
and patient's preference you can decide
when to repeat and a very low ultrasound
risk and benign FNA really limited
evidence whether you should actually
repeat or not but generally I don't uh
repeat the ultrasound earlier than 18 to
24 months foreign
foreign
but if you have a really low uh risk
Ultrasound with
um benign FNA then generally really you
don't really need to do anything else
except just um
nothing easy don't really even there's
no evidence in showing that you need to
it's beneficial to to repeat any of it
so in conclusion thyroid nodules are
common majority of them are benign
however about six to fifteen percent
with a Dubey or malignancy uh clinical
evaluation is very important next step
it will be TSH evaluation and then ultrasound
ultrasound
are the initial approach in managing
thyroid nodule and FNA is really the
most sensitive and cost effective too
uh and then molecular testing in
indetermined cytology has helped in
making clinical decision however we need
to really interpret it within the
institutional prevalence and
um you know consider the cost as well as
you know incorporate other important
clinical uh aspect of care including
history and physical exam Etc
um so with this
um I'm not sure uh what time it is maybe
I'm just going to introduce or mention
some of our ongoing studies
we have some studies
mainly medsar Washington Hospital Center
with in collaboration also with
Georgetown University NIH
in the uniform services we've got a
number of basic science in clinical
research studies going on one important
emphasis of our program is understanding
the sex difference in thyroid cancer one
of our study looks into sex specific
immune landscape of differentiated
thyroid cancer
I can tell you a little bit more about
it but I also want to make sure you have
enough time for uh questions but uh this
we have some really
um interesting preliminary
finding or
um that that is actually suggestive that
male having a suppressed immune response
compared to female which may be the
basis of seeing more aggressive cancer
in males compared to female despite the
fact that females have a higher
prevalence of thyroid cancer so I'm just
going to put that up because if there is
any um of our trainees or interested in
getting involved we have both basic
science and clinical studies and you're
more than welcome to join our program
just get in touch with me and I'll be
happy to find something that you know
targets your interest and with this I'm
more than happy to answer any questions
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