Transcript Thyroid cancer : a morphological and molecular entity

Thyroid cancer :
a morphological and molecular entity
cytologically detectable
Sessione
Anatomia Patologica e Ricerca Molecolare
Molecular Cytology
Chairman
Gianni Simone and Leonardo Resta
[email protected]
History of the
thyroid FNAs
Lipton RF, Abel MS:
aspiration biopsy of the
thyroid in the evaluation
of thyroid dysfunction Am
J Med Sci 1944
Löwhagen T
(Sweden)1970th
1980-1990th:
Kini SR, Koss LG; Frable WJ
(USA)
Akerman M (Sweden)
Orell S (Australia)
France: Institut Curie
(Zajicek J)
Clinicians asked for:
Series
Loewhagen,
1979
Gharib, 1985
Sensitivity
91
90
Specificity
69
70
Akerman, 1985
57
98
Baloch, 1998
92
84
Ramzy, 2001
93
76
Cheung, 2006
54
100
Sangalli, 2006
93
74
More specific diagnoses
Assessment for risk
cancer
Helpful diagnosis linked
with the
patients’management



Benign
Malignant
« Indeterminate »
Terminologies
Follicular lesion without
nuclear atypia: 6.8 % K
Follicular lesion with
nuclear atypia : 44.4 % K
Nuclear atypia: 20 % K
(PTC exclusively)
R. Goldstein Ann Surg 2002;
235 : 656-62
B. Miller, Am J Surg 2004; 188 : 459-62
Terminologies:
The professionnal Societies Recommandations
PSC 1997
ATA 2006
AACE 2006
Working
group 2006
Inadequate
Inadequate
Benign
Benign
Benign
Malignant
Malignant
or suspicious
US Lesion
Presence of
atypical cells
Indeterminate/
suspicious for
neoplasia
Follicular
neoplasia
Follicular
neoplasia
Suspicious for
malignancy
Indeterminate/
Suspicious for
carcinoma
Non Diagnostic
or
Suspicious US
Suspicious
Malignant
Benign
Malignant
Unsatisfactory
PSC : Papanicolaou Society of Cytology; Working group : Thyroid 2006;16
BTA 2009
Thy1Insufficient
for dg
Thy 1c-Cyst fluid
with macs only
SIAPEC 2014
Tir 1
Non diagnostic
Thy 2 Non
neoplastic Thy 2ccyst fluid with
colloid
Tir 2 Negative for
malignant cells
Thy 3a-atypia
Neoplasm possible
Thy3f- follicular
neoplasm
Tir3 atypical
Thy4 Suspicious of
malignancy
Thy 5 Malignant
Tir 3 follicular
proliferation
Terminology
2009
Malignancy
Risk (%)
Usual
Management
Non Diagnostic
or
Unsatisfactory
**
Repeat FNA
with US
Benign
0-3
Clinical Followup
6-18 months
AUS or FLUS
5-15
Repeat FNA
Foll Neoplasm
or
Suspicious for
a foll neoplasm
(specify if
Hürthle cell
(oncocytic) type)
15-30
Surgical
lobectomy
Suspicious for
malignancy
60-75
Near-total
Thyroidectomy
or
Surgical
lobectomy
Malignant
97-99
Near-total
thyroidectomy
Tir 4 suspicious for
malignancy
Tir 5 diagnostic for
malignancy
The current terminologies
essential :
Criteria well described
 Key for diagnostic
reproducibility
 National/
International correlation

Blue book
TIRADS 0
TIRADS 1
Normal
Nothing else to do
TIRADS 2
Benign
US control
TIRADS 3
Likely benign
FNA depending on
the context
TIRADS 4
Suspicious
FNA recommended
TIRADS 5
Likely malignant
FNA recommended
TIRADS 6
Malignant on histology
sens = 95.7%, spec = 61%, NPV= 99.7%
Russ, J Radiol, 2011
Russ, Eur J Endocrinol, 2013
Selection of the patients
Selection of the patients
Olson MT Acta Cytol 2014

Meta-analysis SM

50 192 cas/12 articles post BSRTC

51 863 cas/13 articles pre BSRTC
-Percentage of cancers is now higher in the thyroid with surgical control
(14% →50%)
-Specificity 50% higher for cat V; 100% cat VI
Kocjan G Acta Cytol 2011
-Cat V BSRTC combined with score TI-RADS 4B and 5 : Malignancy risk> 75%
Maia FF Clin Endocrinol 2014
The indeterminate cases still represent
20-25% of all FNAs
How can we still improve these results ?
•
To analyze our own cytological results
•
To optimize the FNA quality
•
To apply ancillary techniques
Analysis of our own results
Number of cases
Non
diagn
Benign
FLUS
Or
AUS
FN/
FNHC
SM
Malignant
2277
2009/10
14.1%
64.9%
9.2%
5.6%
4.2%
2%
2210
2011/12
14.3%
65.5%
11%
4.9%
2.3%
2%
NA
NA
25.9%
15.1%
58.7%
100%
<15%
60%
<7%
6-11%
2-8%
3-7%
?
0-3%
5-15%
15-30%
60 -75%
97 -99 %
Cancer
Bethesda
FLUS and risk of malignancy
CYTOLOGICAL CRITERIA and Risk of
malignancy
Microfollicular architecture but sparse
cellularity
AA Renshaw
Cancer Cytopathol
2011
MH Luu
Acta Cytol
2011
21-34%
MT Olson
Acta Cytol
2011
27%
S Onder
Cytopathol
2013
6.9%
Predominant oncocytic cells and low
cellularity
0%
Predominant oncocytic cells and goiter or
Hashimoto
Cytological atypias suggesting papillary
carcinoma
39%
32.3%
48%
28%
Atypical « cyst lining cells »
Cytological atypias
50%
22%
Cytological atypias due to technical
artifact
Abnormal lymphocytic population
% FLUS/AUS/% malignant (BCP)
% FLUS/AUS/% malignant
9-11%/25.9%
8%/25%
3.2%/26%
3.3%/32%
6.7%/18.9%
2011-2012
9970 thyroid ultrasound-guided FNAs
Russ G and Royer B
BRSTC Category
Number
%
408
4
Benign
7389
74
Atypia of undetermined
significance
1054
10.5
Follicular neoplasm (FN)
598 (170 Oncocytic type)
6
Suspicious for malignancy
288
3
Malignant
233
2.5
Non diagnostic
Litterature Results
Authors
Cases
Number
Non
diagn
Benign
FLUS or
AUS
FN/
FNHC
SM
Malignant
Cochand-Priollet B
et al 2012
2210
14.3%
65.5%
11%
(23.6%)
4.9%
(15.2%)
2.3%
(58.7%)
2%
(100%)
Lacoste-Collin L
et al 2012
1317
31.6%
48%
7.8%
(18.5%)
7%
(22.2%)
3%
(55.6%)
2.6%
(100%)
Bongiovanni
et al 2012
7686
2%
54.7%
6.3%
25.3%
6.3%
4%
(14.4%)
32.1%
(74.9%)
99.4%
6.7%
1.7%
2%
2.9%
(18.9%)
(45.7%)
(71%)
(98.3%)
<7%
6-11%
2-8%
3-7%
5 -15%
15 - 30%
Önder S
et al 2013
Bethesda
655
(6310)
25.6%
<15%
61.1%
60%
Litterature Results
?
0 - 3%
60 -75%
97 - 99 %
Litterature Results
Authors
Cases
Number
Non
diagn
Benign
FLUS or
AUS
FN/
FNHC
SM
Malignant
500
NA
49%
9.4%
(23.4%)
1.2%
10.6%
(96%)
26.8%
(100%)
500
NA
72.2%
5%
(8%)
2.2%
3.2%
(87.5%)
12.2%
(100%)
Elsheikh et al 2012
1382
20.1%
39%
(3%)
27.2%
(6%)
8.4%
(22%)
2.6%
(56%)
2.7%
(100%)
Firat P et al 2012
764
11.7%
64.1%
9.8%
(36%)
3.7%
(45%)
3.5%
(100%)
7.2%
(100%)
Mondal SK et al
2013
1020
1.2%
(0%)
87.5%
(4.5%)
1%
(20% )
4.2%
(30.6%)
1.4%
(75%)
10%
(97.8%)
Park JH et al 2014
1730
13.3%
(35.3%)
40.6%
(5.6%)
9.1%
(69%)
0.4%
(50%)
19.3%
(98.7%)
17.3%
(98.9%)
<15%
60%
<7%
6-11%
2-8%
3-7%
?
0 - 3%
5 -15%
15 - 30%
60 -75%
97 - 99 %
Mastorakis et al
Cytopathology
2012
Bethesda
Conventional slides
 Liquid-based cytology
 Ancillary techniques


Quantity of cytological material
Techniques to improve the FNAs
quality
Conventional slides
Liquid-based cytology
Ancillary techniques
ICC
Thyroid. 2011 Oct;21(10):1067-7
Terminology
Bethesda 2009
Risk of cancer
Alternatives for the
Management
?
Non Diagnostic or
Unsatisfactory
Repeat FNA
with US
0-3%
Benign
AUS or FLUS
Foll Neoplasm or
Suspicious for
a foll neoplasm
(specify if
Hürthle cell
(oncocytic) type)
5-15%
Repeat FNA
Or
Clinical and US follow-up
15-30 %
Surgical
Lobectomy
Or
Clinical and US follow-up
60-75%
Suspicious for
malignancy
Malignant
Clinical Follow-up
6-18 months
97-99%
Near-total
Thyroidectomy
or
Surgical
lobectomy
Near-total
thyroidectomy
Rossi ED et al Cancer Cytopathology 2005:
RET/HBME1/Galectine 3
Fadda G et al Eur J Endocrinol 2011: HBME1/Galectine 3
Lacoste Collin L et al Cytopathology 2014:
CK19/HBME1/Ki67
Pustaszeri MF et al Cancer Cytopathology CD117
Thyroglobulin, TCT, PTH etc………
TROP-2
Simone G, Cytopathology 2014
Molecular
markers/BRAF
V600E mutation-MAPKinase
Highly specific for PTC
80% PTC Tall cells
60% PTC classic variant
10% PTCFV
Molecular
markers/BRAF
Poller D et al Cytopathology 2014
Johnson SJ et al Cytopathology 2014
Rossi ED et al Cancer Cytopathology 2014
Zimmerman AK et al Cancer Cytopathol 2014



40-50% FC
10-20% PTCFV
20-40% PDC/Anapl K

20-40% FA
Molecular
markers/
RAS
Cancer cytopathology 2014
New algorithms
Rossi ED et al Cancer Cytopathology 2014
Tests
•
Afirma test
(RNA based
test)
•
miRInform
test (DNA and
RNA based
test)
•
ThyroSeq test
(DNA based
test/12
genes)
•
The Afirma GEC demonstrates a lower than expected rate of benign reports in FN/HCN, and a lower
than anticipated malignancy rate within GEC-suspicious nodules. These data suggest that the
PPV of the GEC is lower than previously reported, and call into question the performance of the
test when applied in the context of specialized Academic cytopathology.
Mc Iver et al
JCEM 2014
Aragon P
Ann Surg Oncol 2014
MicroRNA
Dettmer et al, Thyroid 2013
TAKE HOME
MESSAGES
Cytology is still relevant
ICC is helpful but resolves
only about 50% of the
« indeterminate »
Sensitivity and specificity of
the Molecular testings are
not sufficient to recommend
these techniques in a routine
practice
But all these techniques are
promising and feasible on
cytology
A rigourous technique is
required
Targeted therapies will
change our approach