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346
M. Sakr
Postoperative
131
I Ablation
Patients >45years with tumors >1.5cm should
receive
131
I ablation to reduce local and distant
recurrence and cancer mortality [37, 38]. The
benet of
131
I ablation for low-risk patients may
however be questionable. Other factors such as
invasion, metastases, completeness of excision,
and associated disease should be considered.
Benets of
131
I ablation include
1. Eradication of all thyroid cells including
residual postoperative microscopic disease
and thus possible reduction of risk of local
and distant tumor recurrence.
2. Reassurance to patients imparted by the
knowledge that serum Tg is undetectable and
iodine scan negative, implying that all thyroid
tissue has been destroyed.
3. Possible prolonged survival [39].
4. Increased sensitivity of monitoring by serum
Tg measurements and possibly earlier detection of recurrent or metastatic disease [40].
Indications ofRemnant Ablation with
No Indication for(Low Risk ofRecurrence or
Cancer-Specic Mortality) [41, 42]
131
I
Patients should satisfy all the following criteria
131
for
I ablation to be omitted; complete surgery,
favorable histology, tumor unifocal, ≤1cm, N0,
M0, or minimally invasive FTCs, without vascular invasion, <2cm [43], and no extension beyond
the thyroid capsule.
Denite Indications
The presence of any of the following is a denite
indication for
131
I ablation; distant metastases,
incomplete tumor resection, or complete tumor
resection but high risk of recurrence or mortality
(tumor extension beyond the thyroid capsule,
or >10 involved LNs and >3 LNs with extracapsular spread) [44].
able histology (tall-cell, columnar-cell or diffuse
sclerosing papillary cancers, widely invasive or
poorly differentiated follicular cancers), and multifocal tumors <1cm [44].
Short-Term andLong-Term Side Eects
131
of
I Ablation Treatment
The main side effect is transient hypothyroidism,
unless rh TSH is used [45–49]. The possible
“early” effects include abnormality of taste and
sialadenitis (can be minimized by good hydration), nausea (can be minimized by anti-emetics),
neck discomfort, and swelling within a few days
of RAI (rare, simple analgesics should be tried
initially, but a short course of steroids may be
necessary), radiation cystitis, radiation gastritis,
bleeding into secondary deposits, and edema in
cerebral secondary deposits (extremely rare)
[44].
The possible “late” effects include dry mouth,
abnormal taste, sialadenitis, lacrymal gland dysfunction, life-time risk of leukemia and secondary cancers (0.5%) [50], radiation brosis [51],
increased risk of miscarriage (may persist for one
year after
131
I therapy) [52], and infertility in men
[36].
13.2.3.3 External Beam Radiotherapy
(EBRT) ofWDTC
External beam radiotherapy (EBRT) is only
occasionally used in the treatment of
WDTC. Postoperative adjuvant EBRT may be
indicated to reduce local recurrence in patients at
high risk due to residual disease where further
surgery is not appropriate [25, 53]. High-dose
EBRT as part of primary treatment is indicated
for unresectable tumors that do not concentrate
RAI, and unresectable bulky tumors in addition
to RAI treatment.
13.2.4 Follow-Up ofWDTC
Probable Indications
Any one of the following categories is a “probable” indication for
131
I ablation: Less than TT,
status of LNs not assessed at surgery, tumor size
>1cm and<4 cm, tumors <1 cm with unfavor-
t.me/Dr_Mouayyad_AlbtousH
Follow-up should be lifelong because (1) the disease has a long natural history, (2) late recurrences are not rare and can be treated successfully,
(3) regular follow-up is also necessary for monitoring of treatment (TSH suppression, the
13 Malignant Thyroid Disease
347
consequences of supra-physiological L-thyroxin
replacement, treatment of hypocalcaemia), (4)
Lifelong suppression of serum TSH level below
normal (<0.1 mIU/L) is one of the main components of treatment in high-risk cases, and (5)
patients should be monitored for late side effects
131
of
I treatment.
Surveillance for recurrence is based on (1)
annual clinical examination, (2) annual measurement of serum Tg and TSH, and (3) diagnostic
imaging and FNAC when indicated.
13.2.4.1 Voice Dysfunction
Voice dysfunction may result if there is ELN and/
or RLN injury. It must be investigated if symptoms persist beyond 2weeks after surgery. The
patient should be referred to a specialist for direct
and/or indirect laryngoscopy.
13.2.4.2 Management
ofHypocalcaemia
Serum Calcium (Ca) should be checked on the
day after surgery and daily until the hypocalcaemia improves [54]. A decline in serum Ca in the
rst 24h after surgery indicates the need for Ca
supplementation [55]. If hypocalcaemia develops, Ca supplement should be started at an initial
dose of 500mg elemental Ca three times daily.
The dose is adjusted as indicated by the response.
Occasionally, IV Ca gluconate may be required.
Mild asymptomatic hypocalcaemia usually does
not require treatment, although monitoring is
indicated. If hypocalcaemia does not improve or
worsens, alfa-calcidol should be added.
Hypoparathyroidism is often transient and a
predictor of this is increase in serum PTH at the
time of occurrence of hypo-calcemia [56]. Thus,
most patients on calcitriol/alfacalcidol/Ca supplements can have this treatment withdrawn during “euthyroidism.” Supplements should be
slowly and gradually reduced and serum Ca monitored every few months until withdrawn and
eucalcemia restored.
If hypoparathyroidism is permanent, the lowest dose of supplements should be given to maintain the serum Ca at the lower end of the normal
range, while avoiding hypercalciuria. In stable
cases, annual measurement of serum Ca is rec-
ommended. Close monitoring of serum Ca is
needed to prevent hypercalcemia. After TT, 30%
of patients will need Ca supplement ± alfacalcidol. By 3 months, <10% of patients will still
need Ca [56].
13.2.4.3 Long-Term Suppression
ofSerum Thyrotrophin
L-T4 should be used in preference to T3 for longterm suppression. The dose should suppress the
TSH to <0.1 mIU/L [57] and should be adjusted
by 25μg (every 6weeks) until serum TSH is <0.1
mIU/L). To achieve this, most patients may
require 175–200μg daily.
13.2.4.4 Measurement ofSerum
Thyroglobulin (Tg) inLongTerm Follow-Up
Thyroglobulin (Tg) is secreted by both normal
and cancerous thyroid cells. In patients who have
not had a TT and
131
I ablation, the interpretation
of serum Tg measurements is limited by the
inability to differentiate between tumor and thyroid remnant [58]. Detectable serum Tg is highly
suggestive of thyroid remnant, residual, or recurrent tumor. A serum Tg rising with time while on
suppressive L-T4 treatment highly suggests
tumor recurrence or progression.
The diagnostic sensitivity of serum Tg measurements increases by elevated TSH concentration [59]. Tumor recurrence or progression can
be diagnosed earlier by detecting increased Tg
after TSH stimulation than by measuring Tg on
suppressive thyroxin therapy; Tg should be measured when serum TSH is >30 mIU/L.
13.2.4.5 Role ofUS andWhole-Body
131
I Scan (WBS) inRoutine
Follow-Up
After TT and postoperative
131
I ablation, diagnostic WBSs have relatively low sensitivity in detecting residual or recurrent disease compared with
measurement of serum Tg [60]. US is sensitive
for detection of residual disease in the thyroid
bed and metastatic disease in LNs. It may also
have a particular role when serum Tg measurements are unreliable because of the presence of
assay interference.
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348
M. Sakr
Fig. 13.1 A 47-year-old lady with recurrent thyroid cancer. Note swelling on the right side (arrow) and the scar of
previous surgery
13.2.5 Recurrent/Persistent DTC
Early detection of recurrent disease can lead to
cure or long-term survival, particularly if disease
is operable or takes up RAI [39, 44]. Distant
metastases develop in 5–23% of patients with
WDTC, mainly in the lungs and bones.
13.2.5.1 Recurrence intheThyroid Bed
or Cervical Lymph Nodess
For tumor recurrence in the thyroid bed
(Fig.13.1) or cervical LNs (Fig.13.2), surgical
re-exploration is the preferred method of treatment, usually followed by
131
I therapy [60].
Recurrent neck disease uncontrolled by surgery
131
and
I treatment is best treated by high-dose palliative EBRT.As patients are likely to survive for
a signicant period, radical EBRT (doses
50–66 Gy) is often necessary with a daily
fractionation.
13.2.5.2 Metastases intheLungs
andOther Soft Tissue Areas
These sites are usually not amenable to surgery
and should be treated with
131
I therapy [51]. If the
tumor takes up RAI, long-term survival is possible in such cases [61]. There is no maximum
limit to the cumulative
131
I dose that can be given
Fig. 13.2 A 52-year-old lady with recurrent thyroid cancer (lymph nodes). Note swelling on the surgical site
(arrow) and scar of previous neck dissection
to patients with persistent disease. A normal CBC
must be conrmed prior to each
131
I treatment and
impairment of renal function demands a lower
dose [62].
13.2.5.3 Cerebral Metastases
EBRT has a palliative role in cerebral metastases
along with surgery if appropriate.
13.2.5.4 Bone Metastases
Extensive bony metastases are generally not curable by
131
I treatment alone. For solitary or lim-
ited number of bony metastases that are not cured
131
by
I therapy, EBRT ± resection and/or embolization should be considered. EBRT also has a
very important role in the treatment of spinal
cord compression for vertebral metastases [63].
13.2.5.5 Other Metastatic Sites
Metastasectomy or radiofrequency ablation may
be helpful in cases with a limited number of
metastases.
13.2.5.6 Palliative Care
Palliative care is not necessary in most patients
with WDTC because they are cured. High-dose
palliative EBRT may be appropriate in good performance status patients with anticipated survival
t.me/Dr_Mouayyad_AlbtousH
13 Malignant Thyroid Disease
349
of >6months. It also has a role in palliation of
symptoms from fungating LNs, bleeding tumor,
stridor, SVC obstruction, and dysphagia [64].
Stridor can also be alleviated by palliative surgery. Palliative chemotherapy may have a role in
end-stage disease uncontrolled by surgery,
therapy or EBRT.
131
13.3 Papillary Thyroid Cancer
(PTC)
13.3.1 Introduction
Papillary thyroid carcinoma (PTC), which is a
differentiated type of thyroid cancer derived from
follicular epithelial cells, is the most common
histological type, constituting 80% of all thyroid
carcinomas [65]. Women are more affected than
men in ratios of 2:1–4:1. It has become the sixth
most common cancer in women. It can present in
any age group with the mean age at the time of
initial diagnosis being approximately 40years. In
children, PTC accounts for more than 90% of
thyroid malignancies [66].
cause exists for exposure to “ionizing radiation.”
In 5–10% of the cases, there is a history of irradiation exposure to the neck, and the nonneoplastic gland may show nuclear aberrations as a
result. These data are derived from studies of
I
children who were exposed to the nuclear fallout
from Chernobyl, adult survivors of the atomic
bombings of Hiroshima and Nagasaki, and
patients who received head and neck radiotherapy (RT) in childhood for the treatment of a variety of benign conditions [71]. Other factors
include hormonal factors, iodine (I2) intake, and
the presence of Hashimoto’s thyroiditis (HT).
Even though the majority of patients with PTC
are women, no convincing hormonal associations
have been elucidated [72]. Studies examining the
inuence of I2 intake on the risk of thyroid cancer
have shown conicting results, and at the present
time, I2 intake is generally not considered a risk
factor [73]. The inuence of HT on thyroid cancer risk is controversial, but large studies have
shown an increased prevalence of HT in patients
with PTC [74, 75]. Whether the frequency of
PTC is increased in Graves’ disease remains controversial [76].
13.3.2 Risk Factors
Both genetic and environmental factors have
been reported to increase the risk of developing
PTC.
Genetic Factors: About 3% of cases of PTC
are “familial” [67]. Some familial syndromes
known to be associated with PTC include familial adenomatous polyposis (FAP), Gardner syndrome (both caused by a mutation in the APC
gene), Cowden syndrome (caused by a mutation
in PTEN gene), and Carney complex (caused by
a mutation in the PRKAR1A gene) [68, 69]. A
family history of PTC in two rst-degree relatives increases the risk of PTC three- to nine-fold,
and these families are likely part of familial nonmedullary thyroid cancer (FNMTC) kindred,
whose specic genetic defect has not yet been
determined [70].
Environmental Factors: The strongest evidence linking thyroid cancer to an environmental
13.3.3 Gross Features
The size of the primary tumor ranges from microscopic to huge. A very high proportion of thyroid
cancers measuring <1 cm in diameter is PTCs.
Grossly, most cases are solid, whitish, rm, and
clearly invasive; fewer than 10% are surrounded
by a complete capsule. Marked cystic changes
are seen in 10% of cases. Papillary formations
may be evident to the naked eye [77].
13.3.4 Microscopic Features
13.3.4.1 Classical or Non-Otherwise
Specied (NOS) PTC
Classical or non-otherwise specied (NOS) PTC
is characterized by the formation of “papillae”
and a set of distinctive “nuclear features”
(Fig. 13.3) [78–81]. These papillae are nearly
always associated with the formation of follicles
t.me/Dr_Mouayyad_AlbtousH
350
M. Sakr
a b
Fig. 13.3 (a) PTC metastatic to a LN: typical appearance of PTC with complex and branching papillae. (b) Higher
magnication showing optical clear, overlapping, and grooved (arrow) nuclei
Table 13.7 Variants of papillary thyroid carcinoma (PTC) and their prognosis
Good prognosis Variable prognosis Guarded prognosis
– Micro- carcinoma – Oxyphilic cell – Diffuse sclerosing
– Encapsulated – Follicular – Tall/columnar cell
– Macrofollicular – Solid sclerosing – Diffuse follicular
– Solid/trabecular
– With nodular fasciitis-like
stroma
with great variation of the ratio between the two
components. Follicles tend to be irregularly
shaped, often tubular and branching. Tumors
with a combination of papillary and follicular
structures have the biological behavior of PTC
and should thus be classied as such instead of as
“mixed carcinomas” [78–81].
Diagnosis of PTC depends on the characteristic nuclear features rather than a papillary architecture, which may be minor or absent. These
nuclear features consist of (1) ground glass nuclei
[82], (2) nuclear pseudo-inclusions (cytoplasmic
invaginations that appear as sharply outlined acidophilic formations) [83], and (3) nuclear grooves
(infoldings of a redundant nuclear membrane)
[68, 79].
Mitosis is very scanty or absent [84], and over
half of the cases show extensive brosis.
Psammoma bodies are seen in nearly half of the
cases. Their presence strongly suggests the diagnosis of PTC, as their occurrence in other thyroid
lesions is exceptional [85]. These laminated
basophilic structures stain for mucin, Ca, and
iron and appear to arise from necrosis of individual tumor cells, which occasionally may be seen
at their very center [86, 87]. Lymphocytic inl-
tration of the stroma is seen in 25% of cases, and
it is not clear whether it represents a reaction to
the tumor or preexisting thyroiditis [88].
Multiple microscopic foci of tumor are found
in about 20% of cases [89, 90]. Controversy still
exists as to whether this represents multicentricity or intra-thyroidal lymphatic permeation.
Blood vessel invasion is found in only 5% of
cases. The mode of spread of PTC is most commonly via lymphatics within the thyroid leading
to “multifocal” disease and to cervical LN metastases [78, 90]. About 50% of PTCs have nodal
metastases at initial diagnosis [91].
13.3.4.2 Histological Variants ofPTC
There are several histological variants of PTC,
some of which are associated with a more
guarded prognosis than others (Table13.7) [77].
Papillary Micro-carcinoma
The term refers to PTC measuring <1 cm in
diameter and replaces the older designation of
“occult” PTC [78]. It may be incidentally found
in autopsy (4–35% of cases) [92–94], or in surgical specimens. Prognosis is excellent despite
occasional regional LN metastases.
t.me/Dr_Mouayyad_AlbtousH
13 Malignant Thyroid Disease
351
Encapsulated Variant
The tumor is totally surrounded by a brous capsule, which may be intact or focally inltrated by
the tumor. These tumors have good prognosis
and, although some lesions show LN involvement, distant metastases or death due to tumor is
practically nonexistent [95].
Follicular Variant
Follicular variant of PTC has the characteristic
nuclear features of PTC and an almost totally follicular architecture [96]. It can be either encapsulated or poorly circumscribed and inltrative.
The encapsulated follicular variant has a generally favorable prognosis, while the other two
types need to be treated more aggressively. The
biological behavior of this variant is analogous to
that of conventional PTC.However, when considered in conjunction with their higher propensity for angio-invasion and lower incidence of
LN metastases [20], it has become evident that at
least a subset of the encapsulated follicular variant display biological features that are more comparable to minimally invasive follicular
carcinoma than conventional PTC [97, 98].
Tall Cell andColumnar Cell Variants
The main histological feature of the tall cell variant of PTC is the presence of “tall” cells (the
height being twice the width), with an intense
eosinophilic cytoplasm, lining well-developed
papillae (Fig.13.4). In the columnar cell variant,
there is a marked nuclear stratication and the
cytoplasm is clear, sometimes with subnuclear
vacuolization [78, 90]. Both the tall cell and
columnar cell variants are more aggressive than
classical PTC [99, 100]. However, recent studies
suggest that the clinical behavior of these rare
variants depends on tumor size, extra-thyroidal
invasion, and distant metastases [101, 102]. The
tall-cell variant PTCs harbor BRAF mutations in
most cases (50–100%) and often have RET/PTC
translocations as well. The occurrence of these
two aberrations together may synergistically
enhance MAPK signaling, contributing to the
aggressive behavior of this variant [103].
Diuse Sclerosing Variant
The diffuse sclerosing variant is an unusual form
of PTC more frequently affects children and is
associated with a poor prognosis. It is characterized by diffuse involvement of one or two lobes
and clinically may be misdiagnosed as HT [78].
Its hallmark, microscopically, is the presence of
widespread intra-thyroid lymphatic permeation
by numerous neoplastic micro-papillae. LN
metastases are present in almost all cases [104,
105]. This variant lacks BRAF mutations, but
RET/PTC translocations are found in approximately half the cases.
Other Variants ofPTC
Variants such as solid variant, spindle cell variant, clear cell (Fig.13.5), and oxyphilic (Hurthle)
cell variant, PTC with lipomatous stroma,
Warthin’s-like tumor or with nodular fasciitislike stroma, and cribriform PTC have been
reported, but they are too few in number for an
Fig. 13.4 Tall cell variant papillary carcinoma, lined by
tall cells (arrow)
t.me/Dr_Mouayyad_AlbtousH
Fig. 13.5 Papillary thyroid carcinoma with clear cell
changes: typical intra-nuclear inclusion (inset)
352
M. Sakr
adequate assessment of their prognostic implication [106, 107].
13.3.5 Clinical Aspects
The most likely thyroid tumor type to manifest
cervical LN metastasis is PTCs [108]. Patients
with PTC are usually asymptomatic and present
with a STN or multiple nodules. Some patients
present with a palpable cervical LN (occult
PTC) (Fig.13.6). Occasionally, a patient presents with symptoms worrisome for an aggressive or invasive thyroid cancer such as
hoarseness, dysphagia, or hemoptysis [109].
Distant metastases are uncommon, occurring in
fewer than 4% of patients at the time of initial
diagnosis [110].
Clinically, the behavior of follicular variant of
PTC (FVPTC) is generally regarded as being
similar to the pure PTC.Some reports have suggested differences in the frequency of LN
involvement, distant metastases, and prognosis
[111]. Another variant is the papillary thyroid
micro-carcinoma (PTMC), which are rather common and rarely behave as cancers (with metastasis and invasion) [111–116]. A subset of patients
with PTMC, however, presents with palpable
neck LN metastasis, which then leads to the diagnosis of PTCs that were initially not apparent
[117].
Fig. 13.6 A 58-year-old gentleman with right cervical
lymphadenopathy and a non-palpable thyroid gland;
occult papillary thyroid carcinoma
13.3.6 Lymphatic Spread
The thyroid gland has an extensive network of
draining lymphatics, both intra- and extraglandular [118, 119]. The extra-glandular lymphatic network comprises four main groups of
collection channels (1) the infero-medial route
draining to the pre- and paratracheal LNs (main
route for metastases), (2) the super-omedial
route, which terminates in the Delphian LNs situated at the level of crico-thyroid membrane, (3)
the supero-lateral route extending up to the supe-
rior jugular LN chain, and (4) the infero-lateral
route draining the supra-clavicular and jugulosubclavian LN chains. The thyroid lymphatic
network is hence rich in anastomoses between
the numerous lymphatic channels. This explains
the multiple patterns of LN metastases from PTC.
In large studies, thyroid cancer was localized
to the thyroid gland in 67% of cases, thyroid and
LNs in 13%, and LNs alone in 20% [120–127].
In another series, 35% of patients with PTC presented with loco-regional LN metastases [128].
The incidence of cervical metastasis in children
with PTC was reported to be as high as 90%
[129]. Cervical metastases from PTC usually
occur in predictable patterns with the disease
commonly presenting at levels II-V, with level III
being the most commonly involved area and level
I the least [130–133]. Level VI represents the
central compartment and is mentioned in many
other series as the rst station of nodal spread
from PTC. Classication of the levels of neck
nodes [134, 135] is demonstrated in Fig.13.7.
Despite the recognized sequence of lymphatic
dissemination, discontinuous lymphatic spread
or “skip metastasis” varies between 11.1% and
37.5% in node-positive PTC [136–138]. Thus,
clearing the central LN compartment should be
considered when lateral or mediastinal LN compartments are involved [139].
The prognostic signicance of cervical LN
metastases is still controversial. Some authors nd
it to be a signicant predictor of recurrence and
survival [140–144] and that a neck dissection
improves prognosis [145–147], whilst other
believe that LN involvement in PTC does not have
a negative impact on cure rates or survival
t.me/Dr_Mouayyad_AlbtousH
13 Malignant Thyroid Disease
353
Fig. 13.7 Regional
nomenclature of cervical
lymph
nodes (Levels I–VI)
Anterior belly of digastric
IA
Superior
omohyoid
Posterior belly of digastric
IIAIB
III
VI
IV VB
IIB
Inferior
omohyoid
VA
[148–151]. A matched-pair analysis from
Memorial Sloan-Kettering Cancer Center,
New York, suggested that the presence of neck
node metastases had a signicant impact on recurrence in patients older than 45years only [31]. In
spite of this debate in the literature concerning the
clinical signicance of this lymphatic spread, it
becomes more worrisome when the disease has
extended to contralateral or bilateral neck nodes or
to mediastinal LNs [140]. The spread of metastatic
tumor beyond the LN capsule is an especially worrisome nding, as is extension of the primary
tumor to tissues outside of the thyroid gland [152].
13.3.7 Distant Metastases
Blood-borne metastases are less frequent in PTC
than with other thyroid carcinomas. The most
common site is the lung [77, 153]. Pulmonary
metastases can have a miliary micro-nodular pattern that may be detectable only by
scan, or they can be rounded and macro-nodular
131
I scinti-
[154]. Usually, lung metastases are detected by
chest X-ray (Fig.13.8) or CT scan (Fig.13.9).
One large-scale review of 13 series comprising
1231 patients showed that 5% of PTCs have
extended beyond the neck at diagnosis [155]. This
distant spread was most common within the lung
(49%), followed by bone (25%), lung and bone
(15%), and CNS or other tissues (10%). The incidence of overall distant metastases in PTC reaches
10% [156], and nearly 50% of these patients die
of their disease within 5years [155]. About half of
patients receiving RAI for lung deposits alone
will survive for 10–15years. Prognosis is, however, much worse for those with bone disease, and
when tumors fail to concentrate RAI [157].
13.3.8 Evaluation oftheNeck inPTC
(Primary Tumor andLNs)
13.3.8.1 Physical Examination
Careful palpation of the neck is a must, with specic attention to location, size, consistency, and
t.me/Dr_Mouayyad_AlbtousH
354
Fig. 13.8 X-ray chest showing PTC with miliary lung
metastases
M. Sakr
Fig. 13.10 US neck showing hypoechoic nodule in left
thyroid lobe (proved to be PTC)
Fig. 13.9 CT chest showing lung metastases caused by
papillary thyroid carcinoma (PTC)
mobility of each node. Direct attention to nodes
that appear xed or demonstrate skin inltration
should be paid [158, 159]. Although inexpensive
to perform and repeat, palpation ndings are generally accepted as inaccurate [159, 160].
13.3.8.2 Ultrasound (US)
Ultrasonography (US) provides valuable information regarding echogenicity (Fig.13.10), nodular composition (solid nodules versus simple or
t.me/Dr_Mouayyad_AlbtousH
Fig. 13.11 US neck showing heterogeneous solid and
partly cystic thyroid mass (extensive PTC)
complex cysts) (Fig.13.11), presence of calci-
cations (micro i.e., 1 mm or less, or macro)
(Fig. 13.12), as well as shape and margins.
Moreover, US may differentiate extra-thyroidal
structures from the thyroid gland and may give
information on regional lymphadenopathy
(Fig.13.13) [161]. There is certainly some subjectivity to sonographic features, and characteristics vary depending on the histology such that US
alone cannot reliably distinguish malignant from
benign lesions. Although these features do not
obviate the need for biopsy, they are extremely
useful in selecting the site within a nodule for
FNA in order to improve diagnostic yield or to
select appropriate nodules to aspirate within a
MNG [162, 163].
13 Malignant Thyroid Disease
Fig. 13.12 US neck showing PTC with a hypoechoic
mass and punctate calcications
355
vascularity but are usually hypovascular [166].
Malignant inltration alters US features of LNs,
resulting in enlarged LNs that are usually rounded
and show peripheral or mixed vascularity [167].
The accuracy of US in differentiating malignant
from benign cervical LNs is 89–94% [168, 169].
13.3.8.3 Ultrasound-Elastography
(Elasto-Sonography)
The addition of US-elastography (elastosonography) to high-resolution US has signicantly improved the diagnostic accuracy of US.A
thyroid nodule with rm or hard consistency is
associated with an increased risk of malignancy.
The predictive value of elasto-sonography is
independent of nodule size [170, 171] and is
maintained for indeterminate lesions on FNAB
[172]. Cystic nodules and nodules with a calcied shell are not suitable for elasto-sonography.
MNGs with coalescent nodules are also not suitable because the nodule to be examined must be
distinguishable from other nodules [171].
Fig. 13.13 US neck showing PTC with LN metastasis
with punctate calcications (arrow)
Color-ow Doppler US gives further information on vascular ow and velocity. They are categorized as (a) Type 1: no blood ow, (b) Type 2:
peri-nodular ow, and (c) Type 3: intra-nodular
blood ow (peri-nodular vessels may or may not
be present). Although nonspecic, thyroid cancers may have internal hyper-vascularity, whereas
benign nodules may have peripheral vascularization. However, type 3 vascularization can be
found in both benign and malignant nodules
[164]. Completely avascular nodules are more
likely to be benign.
Normal cervical LNs appear sonographically
as attened hypoechoic structures with varying
amounts of hilar fat [165]. They may show hilar
13.3.8.4 Cross-Sectional Imaging (CT
andMRI)
Cross-sectional imaging such as CT scan and
MRI are noninvasive, have high patient acceptance, and require a short examination time.
Indications
Indications for these imaging techniques include
(1) suspected involvement, either by invasion or
compression of the larynx, pharynx, trachea,
esophagus, major blood vessels, retro-pharyngeal
region, or para-vertebral muscles (Fig.13.14), (2)
extension into the mediastinum, (3) recurrent disease, (4) the presence of cervical LNs providing
information on their characteristics and level
(Figs. 13.15, 13.16, 13.17 and 13.18), and (5)
hemoptysis indicating pulmonary metastasis.
On cross-sectional imaging, a “normal” LN
usually measures <1cm in size, has a smooth and
well-dened border, a central fatty hilum, has an
oval shape, and shows uniform, homogenous
density or signal intensity. The primary yardstick
for nodal staging by CT and MRI is LN size, with
the additional ability to assess for nodal morphology and signal intensity changes [173–178].
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