Transcript Imaging of differentiated thyroid cancer: Pre-surgical

eEdE–153
Control #: 1785
Imaging of Differentiated Thyroid Cancer:
Pre-surgical Planning, Evaluation of Locally
Aggressive Disease and Intra-operative Ultrasound
1Salmaan
Ahmed MD, 3Michael Ghazarian MD, 3Nakul Gupta MD, 1James
Debnam MD, 1Thinh Vu MD, 2Gary Clayman MD
UT MD Anderson Cancer Center
1Department
of Radiology
2Department of Head and Neck Surgery
University of Texas Medical School Houston
3Department
of Radiology
Disclosure: None
Background/Purpose

The incidence of thyroid cancer in the U.S. is increasing
at a rate of more than any other cancer

This is in part due to increased workup of incidental
thyroid nodules discovered on routine physical exam or
imaging (ultrasound, CT or MRI)

Estimated incidence (2015) = 62,450 cases
 47,230 in women and 15,220 in men
 10th most among solid organ malignancies (2013)

The purpose of this exhibit is to discuss the imaging
workup of differentiated thyroid cancer, with a focus of
locally aggressive tumors.
American Cancer Society. Thyroid Cancer Overview. 2015. Available at:
http://www.cancer.org/acs/groups/cid/documents/webcontent/acspc-030369-pdf.pdf
Prevalence (%)
Poorly differentiated
carcinoma (<2)
Medullary (3-5)
Anaplastic (1-2)
Follicular (10-15)
Papillary
Thyroid
Carcinoma
(80-85)
Patel K. Genetic mutations, molecular markers and future directions in research. Oral Oncology. 2013;49(7):711-721. doi:10.1016/j.oraloncology.2013.03.437.
Papillary thyroid cancer
 Often with indolent clinical course, low mortality and high






likelihood of cure
Variants: follicular, tall cell, insular carcinoma
Local lymph node metastasis to the central neck (level VI)
and lateral neck (level II-V) is the typical spread of disease
Regional metastatic disease is very common, with rates
as high as 80%
Impact of nodal disease on outcome depends on age
(older = worse), number of nodes, location, size, and
presence of extra capsular extension
Micrometastases and intraoperatively discovered low
volume metastases – no impact on outcome
10-15% of cases are aggressive with early metastasis,
disease recurrence and increased morbidity/mortality
Saindane A. Pitfalls in the Staging of Cancer of Thyroid. Neuroimaging Clinics of North America. 2013;23(1):123-145.
doi:10.1016/j.nic.2012.08.010.
Patel K. Genetic mutations, molecular markers and future directions in research. Oral Oncology. 2013;49(7):711-721.
doi:10.1016/j.oraloncology.2013.03.437
Follicular thyroid cancer
 10-15% of all thyroid cancer cases
 Often difficult to distinguish from benign follicular
neoplasms on FNA
 Lymph node spread is uncommon (8-13% of cases)
 Typical spread hematogenously with distant metastases
(typically lung and bones) in 10-15% of cases
 Variant: Hurthle cell carcinoma
○ Higher rate of lymph node metastasis than classic FTC
○ Rarely presents with distant metastasis
○ However, highest incidence of late distance metastasis
Saindane A. Pitfalls in the Staging of Cancer of Thyroid. Neuroimaging Clinics of North America. 2013;23(1):123-145.
doi:10.1016/j.nic.2012.08.010.
Medullary thyroid cancer
 Up to 5% of all thyroid cancer cases
 Arises from the neuroendocrine parafollicular (C cells)
responsible for the production of calcitonin
 ~20% of cases occur in those with multiple endocrine
neoplasia (MEN) syndrome type 2A and 2B or familial
MTC
 Typical spread of disease is to lymph nodes and
hematogenously
Sherman S. Lessons learned and questions unanswered from use of multitargeted kinase inhibitors in medullary thyroid cancer.
Oral Oncology. 2013;49(7):707-710. doi:10.1016/j.oraloncology.2013.03.442.
Anaplastic thyroid cancer
 Accounts for approximately 1.7% of thyroid cancer cases
 Can arise de novo or in the setting of multinodular goiter




(up to 80%) or within longstanding differentiated thyroid
cancer (DTC)
Marked degree of invasiveness and necrosis
All tumors are considered T4
Stage IVA (intrathyroidal tumor), IVB (gross extrathyroidal
extension), IVC (distant mets)
Rapidly progressive clinical course with overall poor
prognosis
O’Neill J, Shaha A. Anaplastic thyroid cancer. Oral Oncology. 2013;49(7):702-706.
doi:10.1016/j.oraloncology.2013.03.440.
Staging

Generally, the most predictive factors in outcome include age,
presence of distant metastases, and extent of the tumor

Given the favorable prognosis of DTC, many of the staging
schemes stratify based on risk of recurrence rather than overall
survival

However, due to the utility in predicting disease mortality and
requirement for cancer registries, the American Thyroid Association
continues to recommend AJCC/UICC staging for all patients with
DTC
ANATOMIC STAGE/ PROGNOSTIC GROUPS FOR
DIFFERENTIATED THYROID CANCER
UNDER 45 YEARS
Stage I
Any T
Any N
M0
Stage II
Any T
Any N
M1
45 YEARS AND
OLDER
Stage I
T1
N0
M0
Stage II
T2
N0
M0
Stage III
T3
N0
M0
T1, T2, T3
N1a
M0
T4a
N0, N1a
M0
T1, T2, T3, T4
N1b
M0
Stage IVB
T4b
Any N
M0
Stage IVC
Any T
Any N
M1
Stage IVA
From Greene FL, Trotti A, Fritz AG, et al, editors. AJCC Cancer staging handbook. 7th edition. Chicago: American Joint Committee on Cancer; 2010.
Chapter 8: Thyroid.
THYROID CANCER SURVIVAL
Papillary
carcinoma
Follicular
carcinoma
Poorly
differentiated
carcinoma
Anaplastic
(undifferentiated)
carcinoma
Medullary
carcinoma
95-98
90-95
~50
<10
60-80
10 Year
Survival (%)
Stage
5 year Relative Survival Rate (%)
Papillary carcinoma
Follicular carcinoma
I
~100
~100
II
~100
~100
III
93
71
IV
51
50
American Cancer Society. Thyroid Cancer Overview. 2015. Available at:
http://www.cancer.org/acs/groups/cid/documents/webcontent/acspc-030369-pdf.pdf.
Patel K. Genetic mutations, molecular markers and future directions in research. Oral Oncology. 2013;49(7):711-721.
doi:10.1016/j.oraloncology.2013.03.437.
Discussion: Imaging Workup in Papillary
Carcinoma

Real time, 2-D high resolution ultrasound (HRUS) is the
preferred modality for evaluation of:
 Primary tumor
 Extrathyroidal extension
 Contralateral/multifocal disease
 Lymph node metastasis, particularly to the lateral compartment

US guides fine needle aspiration of suspicious nodes (UGFNA) in the central and lateral compartments

Disadvantages of US
 Low sensitivity/specificity for central compartment nodes
 Lateral retropharyngeal and mediastinal nodes not evaluated
Imaging Workup in Papillary Carcinoma:
Lymph Node Metastasis

Metastasis to regional nodes is extremely common, typically
ipsilateral

Orderly progression from level VI to level III, IV or VII
(superior mediastinum)

US features of metastatic lymph nodes:
 Hypoechoic or heterogeneous echotexture with loss of fatty





hilum
Internal calcification
Rounded configuration
Irregular vascular pattern
Cystic appearance (cystic change is highly suggestive of PTC)
US has variable sensitivity (37-84%), but high sensitivity (8998%) for nodal metastasis
Jun H, Kim S, Kim B, Lee Y, Chang H, Park C. Overcoming the Limitations of Fine Needle Aspiration Biopsy:
Detection of Lateral Neck Node Metastasis in Papillary Thyroid Carcinoma. Yonsei Medical Journal.
2015;56(1):182. doi:10.3349/ymj.2015.56.1.182.
Imaging Workup in Papillary Carcinoma:
Cross-Sectional Imaging

The ATA does not recommend routine use of CT, MRI, or
PET pre-operatively

However, these alternative imaging modalities may be useful
in certain clinical settings to assess for involvement of
extrathyroidal tissue:
 Large, rapidly growing tumors
 Locally invasive tumors
 Mediastinal extension

CT is useful for the evaluation of mediastinal and lateral
retropharyngeal lymph nodes
Imaging Workup in Papillary Carcinoma: CT
Iodinated Contrast Agents

The iodine load from contrast enhanced CT may alter the
radioactive iodine uptake within the thyroid for up to 6 weeks.

Some institutions inappropriately withhold contrast.

Sohn and Choi, et al. demonstrated no significant difference
in UIE at 1 month versus 6 months after preoperative CT
scan with ICA

Padovani and Kasamatsu, et al. demonstrated 1 month is
sufficient for UIE to return to baseline following ICA
administration in post-thyroidectomy patients

Some institutions delay RAI for 2 months post-thyroidectomy
and checking UIE, with others delaying ~3 months
Case 1: Typical sonographic appearance of PTC
27 y.o. female with 1.6 cm right lobe papillary thyroid carcinoma. Gray
scale sonographic images with color doppler demonstrate a hypoechoic
solid nodule in the right lobe with microcalcification and vascular flow.
Case 1 (cont’d)
US images inferior to the right lobe of the thyroid (star) demonstrates
prominent, hypoechoic, rounded nodes in the central compartment. There
is loss of normal hilum and increased flow. Right central compartment
dissection was performed confirming metastasis in 3 lymph nodes, with the
largest measuring 7 mm.
Case 2: Diffuse infiltrative PTC
Right thyroid lobe
13 y.o. female with neck mass that
has been present since two years of
age and gradually increasing in size.
CECT demonstrates diffuse
heterogenous attenuation of both
thyroid lobes with slight mass effect.
There is a tiny calcification on the
left.
Sonographic images demonstrate diffusely infiltrative
hypoechoic heterogenous echotexture with foci of
hyper echogenicity. Surgical pathology showed
diffuse sclerosing variant of papillary thyroid
carcinoma involving both lobes with extrathyroidal
extension in a background of chronic lymphocytic
thyroiditis.
There were nodal metastasis to the bilateral central
and lateral compartments.
Case 2 (cont’d)
Imaging of the neck in the same patient
demonstrates bilateral level II adenopathy
and some of the nodes have calcification,
characteristic of PTC metastasis. On
ultrasound, there is abnormal hypoechoic
echotexture, loss of the hilum, disorganized
flow, and calcification is redemonstrated.
Patient underwent total thyroidectomy with
bilateral central and lateral compartment
neck dissections, confirming the nodal
metastasis.
Case 3: Imaging of recurrent PTC
CECT demonstrate pathologic nodes in the
right lower neck with total thyroidectomy
changes.
Metastasis at the right tracheoesophageal
groove (yellow arrow) which require central
compartment dissection. The pathologic
node located lateral to this and posterior to
the right internal jugular vein (red arrow) will
require right lateral neck dissection.
Preoperative cytologic confirmation of
metastasis in both, the central and lateral
compartments, should be obtained by the
radiologist, so the appropriate surgery can
be planned.
In case of bilateral recurrence, FNA
confirmation of metastasis in bilateral
central and lateral compartments should be
performed.
Imaging Workup in Papillary Carcinoma:
Fine needle aspiration

UG-FNA is used to biopsy the thyroid nodule and suspicious
nodes in the lateral compartment

Suspected central compartment metastasis should be
biopsied in the absence of lateral compartment metastasis to
guide extent of surgical resection.

Most significant complication – neck hematoma, however
exceedingly rare

Routine lab screening for coagulation not required
 The patient should be questioned regarding recent
anticoagulation therapy, which should be withheld for 4-7 day
prior to procedure
Imaging Workup in
Papillary Carcinoma: FNA

Thyroglobulin (Tg) measurement in washout from lymph node FNA (TgFNA) can be used when cystic lymph node FNA biopsy is
nondiagnostic

Tg is only produced by follicular cells and thus allows diagnosis of
persistence, recurrence, or metastasis of DTC.


False-positives have been described in the literature, predominantly
relating to aspiration of level VI nodes


Overall sensitivity 95.0% and overall specificity 94.5%
Traversal of residual thyroid tissue post-thyroidectomy or normal thyroid tissue
False-negatives have been reported in cases of undifferentiated/poorly
differentiated DTC
Grani G, Fumarola A. Thyroglobulin in Lymph Node Fine-Needle Aspiration Washout: A Systematic Review and
Meta-analysis of Diagnostic Accuracy. The Journal of Clinical Endocrinology & Metabolism. 2014;99(6):1970-1982.
doi:10.1210/jc.2014-1098
Case 4: Cystic nodal metastasis from PTC
64 y.o. female with past history of PTC, diagnosed over 25 years ago. CECT
demonstrates cystic right level IIA and IIb nodes (white arrows). Cystic node is also
seen in the right inferior neck involving the central and lateral compartment (yellow
arrow).
Case 5: Cystic nodal metastasis
46 y.o. female with a 1 cm hypoechoic right lobe
nodue with microcalcification biopsied as PTC.
Imaging of the right lower neck demonstrates a
predominantly cystic, septated lymph node in
lateral compartment. US guided FNA of this lymph
node revealed a non-diagnostic, acellular sample.
Repeat aspiration was performed for thyroglubulin
assay, with Tg=141,840, confirming metastatic
PTC to the lateral compartment.
Aspirate from cystic nodal metastasis
in a different patient with PTC
demonstrates yellowish clear, nonbloody fluid.
Lateral Retropharyngeal Nodal
Metastasis in PTC

Some recent literature suggests a higher incidence of RPN
metastasis than previously reported

RPN metastases are only evaluated by CT
 Mean maximum node size – 23 mm (Togashi et al.)
 All patients had metastases in the upper jugular chain
nodes

Preoperative transoral FNA is useful to confirm cytology for
presurgical planning.
Togashi T, Sugitani I, Toda K, Kawabata K, Takahashi S. Surgical Management of Retropharyngeal Nodes Metastases from
Papillary Thyroid Carcinoma. World Journal of Surgery. 2014;38(11):2831-2837. doi:10.1007/s00268-014-2707-8.
Case 5: Lateral retropharyngeal metastasis
71 y.o. male with metastatic PTC. Right lateral retropharyngeal metastasis is obscured by
dental artifact. Angled images are useful in accurately diagnosing lateral retropharyngeal
metastasis and also in evaluating the parotid regions.
Locally Invasive PTC

6-13% of patients with DTC have extrathyroidal extension
(ETE)

Increased incidence of local recurrence, regional and distant
metastases, and decreased survival

Most commonly involved structures:
 Strap muscles (53%)
○ Isolated involvement does not correlate with decreased




survival
Recurrent laryngeal nerve (RLN) (47%)
Trachea (43%)
Esophagus (21%)
Larynx (12%)
Saindane A. Pitfalls in the Staging of Cancer of Thyroid. Neuroimaging Clinics of North America.
2013;23(1):123-145. doi:10.1016/j.nic.2012.08.010.
Locally Invasive PTC: Recurrent
laryngeal nerve paralysis

RLN paralysis can be demonstrated on CT or MR
 Ipsilateral laryngeal ventricular enlargement, Internal rotation of
the arytenoid
 Lack of medial conversion of the vocal cord

RLN paralysis is related to tumor invasion, but also mass
effect/pressure on the nerve without invasion

Resection of the RLN recommended with tumor invasion
 Must confirm that the contralateral RLN is not involved
 If RLN is functional pre-operatively, most recommend surgical
preservation – no difference in outcome with RLN sacrifice vs.
preservation with RAI ablation
Case 6: Tracheal invasion

Significantly decreased survival
 Independent prognostic factor for
survival in thyroid cancer
(whereas RLN or
pharynoesophageal invasion is
not)

No difference in survival between
radial resection and shave
procedures in which all gross
disease is resected
56 y.o. male with aggressive PTC. CECT shows left lobe and isthmus mass directly invading the trachea
on the left with endoluminal enhancing soft tissue (red arrow). He underwent thyroidectomy with tracheal
resection, manubriectomy, first rib resection, clavicular head resection, free anterolateral thigh flap
reconstruction of sternotomy defect, and placement of pedicled vastus lateralis flap.
Saindane A. Pitfalls in the Staging of Cancer of Thyroid. Neuroimaging Clinics of North America. 2013;23(1):123-145.
doi:10.1016/j.nic.2012.08.010.
Case 7: Tracheal and esophageal invasion

Esophgeal involvement is
variable
 5-21% of cases of invasive
disease

MR is the preferred imaging
modality for evaluation, and
involvement on CT can be
suggested when fat planes
are entirely effaced.
94 y.o. woman with invasive papillary thyroid cancer, presenting with right TVC paralysis and
clinical suggestion of esophageal and tracheal invasion. CECT shows a large right thyroid mass
displacing midline structures towards the left. There is extenive tumor infiltrating the right
tracheoesophageal groove and fat planes with the trachea, esophagus, and prevertebral soft
tissues are effaced. Surgical resection included esophageal muscularis excision for diffuse
involvement and tracheal resection with primary anatamosis. The right recurrent laryngeal
nerve was sacrificed.
Saindane A. Pitfalls in the Staging of Cancer of Thyroid. Neuroimaging Clinics of North America. 2013;23(1):123-145.
doi:10.1016/j.nic.2012.08.010.
Case 7: Esophageal invasion (cont’d)
94 y.o. woman with invasive papillary thyroid cancer, presenting with right TVC paralysis and clinical
suggestion of esophageal and tracheal invasion. CECT shows a large right thyroid mass displacing midline
structures towards the left. There is extenive tumor infiltrating the right tracheoesophageal groove and fat
planes with the trachea, esophagus, and prevertebral soft tissues are effaced. Surgical resection included
esophageal muscularis excision for diffuse involvement and tracheal resection with primary anatamosis. The
right recurrent laryngeal nerve was sacrificed.
Case 8: Prevertebral and Carotid Invasion

Involvement of prevertebral
muscles and encasement of the
carotid or brachiocephalic
arteries upstages to T4b
63 y.o. male with advanced papillary thyroid
carcinoma. CECT demonstrates
circumferential encasement of the right
common carotid artery (red arrow).
Enhancing tumor extends posteriorly to
involve the prevertebral soft tissues on the
right. Imaging higher up demonstrated
invasion of the supraglottic larynx and
hypopharynx.
Patient was treated with vemurafenib and
subsequently with dabrafenib, and then
taken to the OR for extensive complicated
right neck dissection, flap rescontruction
and radiation therapy.
Case 9: Jugular vein invasion
46 y.o. woman with papillary thyroid carcinoma metastatic to the right neck and
mediastinum. Right level II adenopathy surrounds the internal carotid artery and
the internal jugular vein is partially effaced. Sagittal image suggests there is
compression of the vein without frank invasion.
Case 9: Jugular vein invasion
(cont’d)
US evaluation of the right upper neck demonstrates
tumor thrombus (white arrow) within the internal
jugular vein, rather than extrinsic compression.
CT Imaging of the mediastinum demonstrates
extensive tumor thrombus filling the bracheocephalic
vein (red arrow).
Summary

The incidence of thyroid cancer in the U.S. is increasing at a rate of more than
any other cancer, in part due to increased workup of incidental thyroid nodules.

Majority of patients with PTC will have an indolent clinical course. 10-15% of
cases are aggressive with early metastasis, disease recurrence and increased
morbidity/mortality.

2-D high resolution ultrasound with color doppler and ultrasound guided FNA
are the preferred modalities for evaluating patients with PTC

Thyroglobulin (Tg) measurement in washout from lymph node FNA (Tg-FNA)
can be used when cystic lymph node FNA biopsy is nondiagnostic.

High resolution contrast enhanced CT is useful in evaluating locally invasive
tumors, mediastinal extension/adenopathy, and lateral retropharyngeal
adenopathy.
References








Jun H, Kim S, Kim B, Lee Y, Chang H, Park C. Overcoming the Limitations of Fine Needle
Aspiration Biopsy: Detection of Lateral Neck Node Metastasis in Papillary Thyroid Carcinoma.
Yonsei Medical Journal. 2015;56(1):182. doi:10.3349/ymj.2015.56.1.182.
Kim M, Kim E, Park S et al. US-guided Fine-Needle Aspiration of Thyroid Nodules:
Indications, Techniques, Results1. RadioGraphics. 2008;28(7):1869-1886.
doi:10.1148/rg.287085033.
Grani G, Fumarola A. Thyroglobulin in Lymph Node Fine-Needle Aspiration Washout: A
Systematic Review and Meta-analysis of Diagnostic Accuracy. The Journal of Clinical
Endocrinology & Metabolism. 2014;99(6):1970-1982. doi:10.1210/jc.2014-1098.
Sohn S, Choi J, Kim N et al. The Impact of Iodinated Contrast Agent Administered During
Preoperative Computed Tomography Scan on Body Iodine Pool in Patients with Differentiated
Thyroid Cancer Preparing for Radioactive Iodine Treatment. Thyroid. 2014;24(5):872-877.
doi:10.1089/thy.2013.0238.
Nimmons G, Funk G, Graham M, Pagedar N. Urinary Iodine Excretion After Contrast
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Padovani R, Kasamatsu T, Nakabashi C et al. One Month Is Sufficient for Urinary Iodine to
Return to Its Baseline Value After the Use of Water-Soluble Iodinated Contrast Agents in
Post-Thyroidectomy Patients Requiring Radioiodine Therapy. Thyroid. 2012;22(9):926-930.
doi:10.1089/thy.2012.0099.
Shellenberger T, Fornage B, Ginsberg L, Clayman G. Transoral resection of thyroid cancer
metastasis to lateral retropharyngeal nodes. Head & Neck. 2007;29(3):258-266.
doi:10.1002/hed.20513.
Togashi T, Sugitani I, Toda K, Kawabata K, Takahashi S. Surgical Management of
Retropharyngeal Nodes Metastases from Papillary Thyroid Carcinoma. World Journal of
Surgery. 2014;38(11):2831-2837. doi:10.1007/s00268-014-2707-8.
References

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








Saindane A. Pitfalls in the Staging of Cancer of Thyroid. Neuroimaging Clinics of North
America. 2013;23(1):123-145. doi:10.1016/j.nic.2012.08.010.
McIver B. Evaluation of the thyroid nodule. Oral Oncology. 2013;49(7):645-653.
doi:10.1016/j.oraloncology.2013.03.435.
Nixon I, Shaha A. Management of regional nodes in Thyroid Cancer. Oral Oncology.
2013;49(7):671-675. doi:10.1016/j.oraloncology.2013.03.441.
Tuttle R, Ganly I. Risk stratification in medullary thyroid cancer: Moving beyond static
anatomic staging. Oral Oncology. 2013;49(7):695-701.
doi:10.1016/j.oraloncology.2013.03.443.
Nixon I, Ganly I, Shah J. Thyroid cancer: Surgery for the primary tumor. Oral Oncology.
2013;49(7):654-658. doi:10.1016/j.oraloncology.2013.03.439.
O’Neill J, Shaha A. Anaplastic thyroid cancer. Oral Oncology. 2013;49(7):702-706.
doi:10.1016/j.oraloncology.2013.03.440.
Patel K. Genetic mutations, molecular markers and future directions in research. Oral
Oncology. 2013;49(7):711-721. doi:10.1016/j.oraloncology.2013.03.437.
Darr E, Randolph G. Management of laryngeal nerves and parathyroid glands at
thyroidectomy. Oral Oncology. 2013;49(7):665-670. doi:10.1016/j.oraloncology.2013.03.438.
Sherman S. Lessons learned and questions unanswered from use of multitargeted kinase
inhibitors in medullary thyroid cancer. Oral Oncology. 2013;49(7):707-710.
doi:10.1016/j.oraloncology.2013.03.442.
American Cancer Society. Thyroid Cancer Overview. 2015. Available at:
http://www.cancer.org/acs/groups/cid/documents/webcontent/acspc-030369-pdf.pdf.
Accessed April 3, 2015.
Greene FL, Trotti A, Fritz AG, et al, editors. AJCC Cancer staging handbook. 7th edition.
Chicago: American Joint Committee on Cancer; 2010. Chapter 8: Thyroid.