Transcript Document

SHAHZAD AHMAD M.D
F.A.C.E
DIPLOMATE AMERICAN BOARD OF
INTERNAL MEDICINE
DIPLOMATE AMERICAN BOARD OF
ENDOCRINOLOGY/DIABETES AND
METABOLISM
THYROID INSTITUTE OF UTAH
Thyroid nodule
• discrete lesion in the thyroid gland
radiologically distinct from the surrounding
Thyroid
Nonpalpable nodules are called
“incidentilomas”
How Common are nodules?
• 19-67 % if ultrasound is done
How common is Thyroid Cancer
• 5-15% depending on risk factors
• Incidence of thyroid cancer has increased
more than threefold.
• nearly 50% of the increased incidence is
from tumors >2 cm, suggesting that a
significant number of patients have
clinically important tumors.
So you feel a nodule, now what
• Nonpalpable nodules have the same risk
of
malignancy as palpable nodules with the
same size
Who should you send for an
ultrasound ?
• All patients with a suspected thyroid
nodule, nodular goiter,
a nodule found incidentally
• On (CT) or MRI
or on PET scan.
Anyone with a first degree relative with
thyroid cancer
• Generally, only nodules >1 cm should be
evaluated
• Any thyroid lesion seen on PET scan
should be evaluated by an Endocrinologist
appropriate evaluation of clinically
or incidentally discovered thyroid
nodule(s)
• Measure TSH
• If serum TSH is subnormal,
radionuclide thyroid I-123 scan
Right
Left
TOXIC MNG
Normal TSH with Irregular gland
What will the u/s tell us ?
Hyperthyroidism
Diffuse Goiter,
thyroid stimualting immunoglobulin
negative
• Routine FNA is not recommended for
subcentimeter nodules
unless
• Family history of PTC
• history of external beam radiation
• 18FDGPET–positive thyroid nodules.
• Suspicious imaging charecteristics
long-term
follow-up of patients with thyroid
nodules?
• benign nodules require follow-up
As there is a 5 % fasle negative rate
its actually only 0.6% for u/s guided !
• which may be even higher with
• nodules >4 cm
• reasonable definition of growth is a 20%
increase in nodule diameter
• serial US examinations 6–18 months
after the initial FNA.
Cytology interpretation
• 6 follicular cell groups ,10-15 cells each
• 7% of biopsies can be non diagnostic
Follicular neoplam
• Can be seen in 15-30% of biopsies
• If the cytology reading reports a follicular
neoplasm, a 123I
• thyroid scan may be considered, if not
already done, especially
• if the serum TSH is in the low-normal
range
Indeterminate
cytology/neoplasm
• Indeterminate cytology, reported as
‘‘follicular neoplasm’’ or ‘Hurthle cell
neoplasm’’ can be found in 15–30% FNA’s
• carries a 10–30% risk of malignancy
• If the cytology reading reports a follicular
neoplasm,
• a 123I thyroid scan may be considered
• The use of molecular markers (e.g., BRAF,
RAS,RET=PTC, or galectin-3)
may be considered
for patients with indeterminate cytology
Recommendation rating: C
Brief Discussion Of molecular
markers
• BRAF V-600 E, associated with PTC,
predicts aggressive course and lymph
node mets
• Not associated with Radiation!
Enviromental toxins?
FOLLICULAR CANCERS
• RAS MUTATION seen in approximately 40
percent of follicular cancers
• PAX8-PPAR gamma 1, seen in 10 percent
of Follicular cancers
MOLECULAR ANALYSIS
OF INDETERMINATE
CYTOLOGY
•
1056 indeterminate FNA samples
•
Assessed for- BRAF V600E,
RAS,RET/PTC,
PAX/PPAR
False negative rate at surgery was 5.9%
Finding of RAS mutation increased risk of Thyroid cancer to 80%
•
J
Clin Endocrinol Metab 2011;96:3390-7.
Cystic nodules
Recurrent cystic thyroid nodules with
benign cytology
should be considered for surgical
removal or PEI
Recommendation B
What is the role of medical therapy for
benign thyroid nodules?
• Old time Endocrinologists are still using
Thyroid hormone to “shrink” thyroid
nodules
• 30 YEAR OLD FEMALE WITH MULTI
NODULAR GOITER
DISCOVERED SEPT 2006
ANTI-TPO 154, ANTI TG AB-368
TSH 7.36
• FNA CONSISTENT WITH WELL
DIFFERENTIATED PAPILARY THYROID
CANCER ON THE RIGHT
• LEFT INDETERMINATE
Next step(s) ?
Preoperative Ultrasound ?
• Preoperative neck ultrasound for cervical lymph nodes is
recommended for all patients undergoing
thyroidectomy
• Use of CT/MRI/PET not recommended by the American
Thyroid Association
•
Cooper ,D.S thyroid 16(2) 109-141 2006
Ultrasonographic lymph node "map"
WHY TOTAL THYROIDECTOMY?
• Multiple Foci of PTC are found in thyroid
lobes in up to 80 percent of patients
•
Upto 40 % can be bilateral
The only predictor of contra lateral cancer is
multifocality in ipsilateral lobe
Katoh R, sasaki , cancer 1992 15;70
What does the A.T.A recommend?
•
•
•
•
NTT for bilateral nodules
NTT if metastatic lymph nodes seen
Age more than 45
Nodule more than 1 cm
• Cervical recurrence occurs in up to 25% of
patients with papillary thyroid carcinoma
(PTC)
• The use of total thyroidectomy for most
patients with thyroid carcinoma is
supported by the following arguments:
NODE DISSECTION
• should be performed if there is clinical
evidence of cervical or mediastinal node
metastases due to the increased risk of
neck recurrence and mortality
Am J Med 1994 Nov;97(5):418-28 MAZAFFERI
Extent of surgery improves survival
• 50000 patients with NTT,
• Survival improved in tumours >1 cm
• Patients undergoing lobectomy had a 49%
higher mortality rate
• 2007 Ann of surgery 246:375-
Threshold size for lymph node
metastases
• 5mm for Pappilary thyroid cancer
• 20 mm for Follicular thyroid cancer
•
Machens et al Cancer 103(11) 2269-2273
Radioactive iodine
•
•
•
•
Indications
Benefits
Risks
Dose?
NEAR TOTAL THYROIDECTOMY
• OCTOBER 2006
PATHOLOGY
WELL DIFFERENTIATED
MULTICENTRIC
( 4) TUMOUR FOCI WITHIN THYROID
0.8 CM AND 0.4 CM WERE THE LARGEST FOCI
ONE LYMPH NODE DISSECTED, NEGATIVE FOR
TUMOUR
POST – OP
• WHOLE BODY SCAN ON 12/21/26 SOLITARY TRACER
OF INTENSE UPTAKE IN UPPER OUTER QUADRENT
OF NECK RIGHT OF MIDLINE
•
TSH WAS 150, ANTI TG ANTIBODY 292
REMNANT ABLATION
• 12/29/06 WITH 49.8 MILLICURIE
• POST TREATMENT SCAN 1/9/07
• RIGHT NECK UPTAKE WORRISOME
FOR METASTATIC FOCUS !!
• HOW DO WE LOOK FOR
RESIDUAL/RECURRENT
DISEASE ?
• C.T scan neck looking for recurrence/
persistent mass
• NEGATIVE !
SEARCH FOR
RECURRENT/RESIDUAL DISEASE
• HYPOECHOIC MASS, LIKELY LYMPH NODE
• AP/T 0.7 CM !!
Now to evaluate this lymph node!
• What are my options?
a) should we have this resected ?
b) check a whole body scan at 6 months
c) Biopsy it
Ultrasound characteristics of a
benign lymph node
Flattened or oval ( AP/T < 0.5
Echogenic Hilus
Hilar Flow on Doppler
Best ultrasound criteria for
malignancy
• Short to long axis diameter ratio of more
than 0.5
• It has 75 % sensitivity, 81 % specificity
• 79 % accuracy
Does size help predict a malignant
lymph node?
• NO !
• Size doesn’t matter,
• Border doesn’t help either
What's the Best Way to Detect
Cancer Recurrence After a
Thyroidectomy?
• Cervical ultrasonography is the best way
to detect early recurrent disease
• Albert B. Lowenfels, MD, Professor of Surgery Medscape General
Surgery. 2007;
How sensitive is ultrasonography?
• Operator dependent
• Frasoldati et al reported cytology to be
84% sensitive and if combined with TG
washout 95.6 % sensitive
Cervical Ultrasonography,
A.T.A recommends cervical
ultrasound at 6 and 12 months
after surgery and then annually
Thyroglobulin measurement in washout
fluid from F.N.A of neck lymph nodes
• Tg-FNAB more than 36 ng/ml in the
presence of thyroid gland,
• Tg-FNAB of more than 1.7 ng/ml in the
absence of thyroid gland
INDICATIVE OF METASTASIS
J Clin Endocrinol Metab. 2006 Apr;91(4):1364-9. Epub 2006 Jan 24
Boi F,
Baghino G,
• Clinical performance of Tg-FNAB appears
to be not substantially affected by TgAb
J Clin Endocrinol Metab. 2006 Apr;91(4):1364-9. Epub 2006 Jan 24
Boi F,
Baghino G,
ULTRASOUND+TG vs.
DxWBS
rhTSH -TG Diagnostic
(%)
WBS
(%)
rhTSH-TG
+ US
LOW RISK 85.7
4.7
100
HIGH RISK 84.6
33.3
92.3
rhTSH TG with neck
ultrasonography has the highest
sensitivity in monitoring
differentiated thyroid cancer !
• Pacini, F J clin Endocrinol, Met 2003
Comparison of cytology and TG
washout
European Journal Of Endocrinology 2007, Cunha et al
“The data will be tortured untill
they confess”
WHAT DOES THE DATA REALLY
SAY
• Both Central and ipsilateral Lymph Nodes
are affected commonly even with small
PTCs
• Skip lesions ( involvement of lateral lymph
nodes without central involvement)
is RARE
• PATIENTS WITH MULTIFOCAL
TUMOURS MUCH MORE LIKELY TO
HAVE LYMPH NODE METASTASIS
• MORTALITY HIGHER IN PATIENTS WITH
MULTIFOCAL INTRATHYROIDAL
TUMOUR
• AMERICAN JOURNAL OF MEDICINE 1997 VOL 97
MAZZAFERI ET AL
CONCLUSIONS
(OPINION)
• PRE-OP NECK ULTRASOUND TO EVAULATE
COTRALATERAL LOBE AND LYMPH NODES
(AACE RECOMMENDATION LEVEL B)
• BIOPSY SUSPICIOUS LYMPH NODES
(CYTOLOGY AND TG-WASHOUT) BASED ON
MORPHOLOGY TO HELP SURGEONS
DECIDE ABOUT NECK DISSECTION
• MULTIFOCAL MICRO PTC MORE
LIKELY TO HAVE LYMPH NODE METS
• PROBABLY SHOULD HAVE CENTRAL
COMPARTMENT DISSECTION
• THIS WILL IMPACT RECURRENCE
• NO LONG TERM OUTCOMES DATA
AVAILABLE
• We should concentrate on mid-lower
central compartment to avoid recurrence
IN HIGHER RISK PATIENTS
DID ALL THIS SURGERY AFFECT
LONG TERM OUTCOME?
• Recurrence was followed for 53 months in a
japanese study
• One group of patients had prophylactic lymph
node resection, the other only therapeutic
• Recurrence rate was 16.7 % lower in the group
with therapeutic lymp node resection
• Patients with no palpable lymph nodes who had
prophylactic dissection had a much lower
recurrence rate- 0.4 %
Case 2
32 y/o male with Papillary thyroid cancer 1999
NTT pathology showed 4.5 x2.6 x 2.0 cm mass
Multi focal
Multiple lymph nodes positive, bilaterally
T3 N1B MX
Remnant Ablation
• 152 mCi dose of I-131 given 12/1999
• Lost to follow up until 2006
• Repeat WBS and PET negative
2007
• On synthroid 225 mcg
• TSH 0.30
•
Thyroglobulin AB 0.7 IU/ML (range 0 to 14.4)
• Thyroglobulin 5.4 ng/ml
Looking for disease
• Repeat Surveillance WBS scan negative
NOW WHAT ?
• Role of ultrasound
WHERE AND WHEN DOES RECURRECE
OCCUR
• 79 % RECURRENCE OCCURS IN THE NECK
• 74 % OF RECURRENCE IS IN THE LYMPH
NODES
• TIME TO RECURRENCE USUALLY VARIES,
SOME CASES RECUR AT 7-10 YEARS
AMERICAN JOURNAL OF MEDICINE 1997 VOL 97
MAZZAFERI ET AL
HIGH SERUM THYROGLOBULIN
NEGATIVE IMAGING !
LIKELY DUE TO
A) CERVICAL LYMPH NODE METASTASIS
B) METASTASIS TOO SMALL TO BE SEEN
ON DxWBS OR RxWBS
• Higher Thyroglobulin level means a higher
chance of detection of mets/mass
• In patients with TG > 5 after rhTSH
ultrasound picked up neck masses/mets in
67 % patients
Cystic metastatic lymph nodes
• 20 % of patients with Thyroid Cancer
present with the sole finding of an
abnormal lymph node
• Cystic metastasis cause most of the nondiagnostic lymph node biopsies
• Use a THYROGLUBULIN washout to
prevent this from happening !
POST THYROIDECTOMY NECK
MEDIAL MOVEMENT OF CAROTID AND
JUGULAR
Thyroid bed is filled with HYPER echoic
connective tissue
This demarcates it from recurrence or
metastatic lymph nodes which will be
HYPO echoic
AP/T 0.79/1.45= 0.54 !
PET/CT IN TG +ve, SCAN
NEGATIVE PATIENTS
• which is better, PET scan OR PET/CT
Palmedo et al Journal of Nuclear Medicine Vol. 47 No. 4 616-624
PET/CT IMPACT ON
MANAGMENT
•
•
•
•
•
PET
Sensitivity (%) 79
Specificity (%) 76
PPV (%)
75
NPV (%)
80
Accuracy (%) 78
PET/CT
95
91
86
95
93
•
Palmedo ET AL 2006 Journal of Nuclear Medicine Vol. 47 No. 4 616-624
Limitations
• PET/C.T will miss small lymph nodes
which might be malignant
PET/CT with a suppressed TSH
vs. rhTSH stimulated PET/CT
• Which is better?
• Higher Thyroglobulin level means a higher
chance of detection of mets/mass
• In patients with TG > 5 after rhTSH
ultrasound picked up neck masses/mets in
67 % patients
Elastography !
• Imaging Modality to map elastic properties
of tissue
• Compression is done and strain distributed
is checked on ultrasound
• Results are displayed on an elastogram
Lyschick et al, Radiology april 2007
• Stiff objects appear dark and flexible
objects are bright !
Neck lymph nodes are in a great position for
this technique to be applied
Lyschick et al, Radiology april 2007
How accurate is it ?
Elastography
• 98 % specificity 92% accuracy
Other ultrasound criteria
• AP/ T ratio, vascularity,calcification
81 % specific 79%
Lyschick et al, Radiology April 2007
Metastatic lymph nodes
why they matter
PYTHIAN LYMPH NODES
• Pythia was the priestess of Delphi , whose
utterence was ambiguous and interpretable in
different ways
what happens to these lymph nodes
• some may grow and become significant
• Some may metastasize
• Some may remain dormant and surgery not
needed
AFTER thyroidectomy and RAI
ablation how often do patients have
residual disease?
• 20- 25 % have disease 1 or more years
after thyroidectomy and RAI !
• Rate of clinical lymph node recurrence is
13 %
• Given a 20-25 % rate of PERSISTENT
DISEASE
And a 13 % risk of gross lymph node
recurrence,
THIS IMPLIES that one out of every 2
patients with Pythian Lymph nodes will
eventually have a gross clinical recurrence
• CUMULTATIVE RISK OF death due to
papillary thyroid cancer after diagnosis of
neck nodal metastasis was 10 %
Can adverse outcomes from
Malignant lymph nodes be
prevented?
• Because of a high rate of recurrent LN
mets despite initial surgery and RAI its
thought that pre op u/s might detect lymph
node mets that wouldn’t be addressed
otherwise
• ATA recommends pre op u/s for all thyroid
cancer patients
How often can patients with neck
lymph node mets be rendered
disease free ?
• It ranges between 19 to 46 %
• Probably around 20% of patients can be
rendered disease free with re-operation for
PYTHIAN LYMPH NODES with a low but
possible risks of operative complications
• NOT CLEAR HOW MANY CLINICAL
RECURRENCES THIS APPROACH OF
RESECTING CANCEROUS LYMPH
NODES PREVENTS
• SURVIVAL BENEFIT ALSO ISNT CLEAR
TAKE HOME POINTS
• Pre-operative ultrasound is essential
because it guides surgery and decision to
use remnant ablation even in “low risk”
patients
• We don’t need a WBS for low risk patients
if stimulated TG is negative and ultrasound
is normal
• TG positive scan negative patients should
be evaluated with an ultrasound
• Ultrasound and needle biopsy TG washout
is the most sensitive modality to evaluate
recurrence
QUESTIONS/COMMENTS?