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Fig. 12.10 Computed tomography (CT) scan showing
secondary retrosternal goiter (RSG) extending from the
left thyroid lobe into the mediastinum
M. Sakr
is not possible for several weeks after this iodine
load. Iodinated contrast can reduce the efcacy
of RAI for up to 6months. Currently, CT scan is
the best proven diagnostic modality of
RSG.Michel and Bradpiece [109] reported 100%
sensitivity with CT scanning, 77% with thyroid
scanning, and 59% with chest radiography.
12.3.6.5 Barium Esophagraphy
Barium esophagraphy is often obtained in the
evaluation of “dysphagia” because it may demonstrate extrinsic compression (indentation) or deviation, suggesting a certain length of RSG causing
mass effect. However, its usefulness is limited
given its inability to accurately conrm a thyroid
mass because of poor anatomic detail. Thus, barium esophagraphy is often not particularly helpful
in the preoperative assessment of a known RSG.
12.3.6.6 Nuclear Thyroid Imaging
(Scintigraphy)
A radionuclide thyroid scan may be useful in differentiating goiter from other mediastinal masses
(Fig. 12.12). Nevertheless, a solitary, large cyst
may appear as a “cold” nodule on thyroid scan
and thus provide a false negative result. Thus, the
absence of uptake in the mediastinum does not
exclude a diagnosis of RSG.
Fig. 12.11 Magnetic resonance imaging (MRI) of the
neck showing extension of the goiter into the upper part of
the mediastinum with narrowing and displacement of the
trachea (arrow)
CT scan with iodinated contrast media should
generally be avoided to preclude triggering of
thyrotoxicity. However, if performed, it should
follow thyroid scanning because nuclear imaging
t.me/Dr_Mouayyad_AlbtousH
12.3.6.7 Ultrasonography (US)
Ultrasonography (US) is generally not necessary
but can be helpful in selected patients. It may
demonstrate a mediastinal mass (Fig.12.13), but
it is not as helpful as CXR or CT scan because the
bones of the chest block the transmission of
acoustic information.
12.3.6.8 Fine Needle Aspiration
Cytology (FNAC)
Fine-needle aspiration cytology (FNAC) of RSGs
may be helpful when a signicant cervical component exists. In most patients, thyroid nodules
readily available in the cervical part will be cytologically representative of the whole gland.
However, FNAC often is not recommended for
the retrosternal part or in primary RSGs because
it may be dangerous causing unnecessary bleeding, pneumothorax, airway obstruction, or respiratory distress [110]. Moreover, it may difcult or
12 Benign Thyroid Disease
Fig. 12.12 Radionuclide thyroid scan using Technetium
99m
(
Tc) showing intra-thoracic (primary) retrosternal goi-
ter (RSG) (black arrow)
297
“anterior- superior” mediastinal masses can be
grouped mainly into thymic lesions, teratoid
lesions, thyroid, LNs, lesions of the cardiovascular system, and cysts. Thus, RSG should be differentiated from aortic aneurysm, dissecting
aorta, high aortic arch, angiomatous tumor, goiter, lipoma, lymphoma, Morgagni hernia, parathyroid tumor, pericardial cyst, epicardiac pad of
fat, pleural cyst, teratoma and teratoid lesions,
thymoma, secondary carcinoma, and lymphadenopathy [105, 111].
According to pathological causes, “posterior”
mediastinal masses can be grouped mainly into
neoplasms, inammation, vascular lesions, trauma,
developmental lesions, and abdominal disease
[112, 113]. Thus, a RSG in the posterior mediastinum should be differentiated from neurogenic
lesions, neoplasms, lymphadenopathy, aortic aneurysm, adjacent pleural or lung mass, neuroenteric
cyst or lateral meningocele, esophageal diverticulum, esophageal tumor, and extra- medullary hematopoiesis [106, 114]. Anterior–superior and
posterior mediastinal masses according to their tissue of origin and constituents (uid, fat, and vascular) are summarized in Table12.8.
Fig. 12.13 Spot image of ultrasound of the sternal notch.
Retrosternal thyroid tissue with mixed solid and cystic
nodule measuring 2.1 × 1.3 cm (red arrows). No sonographic suspicious features were seen and the nodule is
classied as U2 (benign)
even impossible to obtain due to difcult
accessibility.
In general, neither nuclear imaging nor sonography is necessary in the preoperative assessment
of a known RSG.
12.3.7 Dierential Diagnosis
The substernal or RSG should be differentiated
from antero-superior and posterior mediastinal
masses. According to the tissue of origin,
12.3.8 Treatment
12.3.8.1 Pharmacotherapy
A patient with an elevation of TSH or defects in
thyroxin synthesis is a candidate for suppressive
thyroxin (L-T4) therapy. However, RSGs, especially those that have cystic change and hemorrhage, do not respond to L-T4 therapy. Overall,
only about 20–30% of patients respond to such
treatment after 1year, and cessation of therapy is
often followed by recurrence. The presence of
cardiac disease and osteoporosis in elderly
patients poses an additional hazard to suppressive
thyroxin therapy. Failure of suppressive therapy
is probably based on autonomicity. Once stimulated for a long time, autonomous growth occurs,
and the hyperplasia is no longer a fully reversible
process. In large goiters, suppressive L-T4 therapy does not provide a signicant reduction of
thyroid volume [115]. In general, most patients
with large nodular goiters are “ineligible” for L–
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298
M. Sakr
Table 12.8
Compartment Lesions Fluid Fat Vascular
Anterior
Posterior – Neurogenic
More than one
compartment
T4 therapy [81, 116, 117]. Although suppressive
therapy generally is ineffective in the management of RSGs, it may be considered when a con-
Anterior–superior and posterior mediastinal masses according to tissue of origin
– Thymic
– Lymphoma
– Germ cell
– Goiter
(Schwannoma)
– Bone
– Bone marrow
– Infection
– Hemorrhage
– Lung cancer
– Thymic cyst
– Thymoma
– Pericardial cyst
– Germ cell
– Lymphoma
– Neuroenteric cyst
– Meningocele
– Mediastinitis
– Lymphangioma
– Germ cell tumor
– Thymolipoma
– Fat pad
– Extra- medullary
– Hematopoiesis
– Liposarcoma – Hemangioma
may be useful in the treatment of hyperthyroidism associated with RSGs but usually is unhelpful in relieving obstructive symptoms.
– Thyroid
– Cardiac
– Coronary
– Descending aorta
traindication for surgical intervention exists [79,
80, 118, 119].
12.3.8.3 Surgical Treatment
Surgical treatment is the most effective treatment
12.3.8.2 Radioactive Iodine (RAI)
Therapy
The use of radioactive iodine (RAI) for the treatment of non-toxic goiter was rst reported by
Keiderling in 1964, but it was not until 1994 that
its use in RSGs was evaluated by Huysmans etal.
[120]. In their prospective study of 19 patients
with large compressive goiters, 11 had intrathoracic extensions for >2cm. They reported a
of RSG, and the presence of RSG is itself an indication for surgery [79–81, 83, 87, 89, 121–123].
It is currently believed that TT is the procedure of
choice particularly that about 95% of cases can
be performed via a cervical incision. Ligation of
the ITA branches close to the thyroid capsule,
preserving the blood supply to the PTG, and minimal dissection of the RLN are the hallmarks of a
safe operation.
40% reduction in the volume of the goiter using
MRI and a 10% decrease in tracheal narrowing
and deviation in 75% of their patients. However,
one-third of their patients did not have any
improvement in dyspnea. Complications of RAI
may include radiation-induced thyroiditis, stridor
from a transient increase in volume, neck pain,
occasional hyperthyroidism, sore throat, mild
dysphagia, and dryness of the mouth.
Contraindications ofSurgery
Thyroidectomy for RSG is contraindicated in (1)
patients who are inappropriate candidates for sur-
gery in general, (2) the known presence of ana-
plastic carcinoma because treatment of this
condition often is futile, and the likelihood of
malignant invasion of critical structures includ-
ing the great vessels may be high.
The main problems with RAI therapy are (1)
the limited and slow onset, (2) risk of initial thyroid growth of up to 25%, (3) risk of radiation
thyroiditis (3%), (4) risk of developing Graves’
disease (5%), (5) attenuated effect with increasing thyroid size, and (6) the need of very high
activities in patients with low RAI uptake, which
may necessitate in-patient therapy. On top of this,
the efcacy is unpredictable in the individual
patient and fails in up to 20% [119]. RAI therapy
Preoperative Planning
Preoperative management of RSG focuses on (1)
avoidance of thyroid storm, (2) detailed comprehension of the patient’s anatomic considerations,
131
and (3) preparation for airway difculties during
I
anesthesia (may necessitate expertise in beroptic intubation).
Computed tomography scan currently is the
most useful tool in preoperative assessment of
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12 Benign Thyroid Disease
299
patient anatomy, which may necessitate the assistance of a surgeon experienced in sternotomy or
thoracotomy [124, 125]. The measurement of
thyroid functions and assessment of the vocal
cords using exible beroptic laryngoscopy are
essential before surgery.
Approaches toRetro-sternal Goiter
1. Trans-cervical approach
Most RSGs can be resected through the
standard cervical Kocher’s incision [64, 126,
127] (Fig.12.14). The head is reclined and the
patient is positioned in an anti-Trendelenburg
of about 15–20° to reduce the venous pressure.
In order to gain good access, the incision
should be placed 1–2 cm higher than usual
[126]. The skin/platysma ap is elevated, the
cervical fascia is separated at the midline, and
the muscles are held aside or incised laterally
in the case of very large goiters.
First, the upper pole is mobilized under
ligation of the superior thyroid vessels with
preservation of the external branch of the
ELN. This is important in the subsequent
upward movement of the thyroid gland from
the retro-sternal to a cervical position. The
RLN and superior PTGs are routinely identied particularly that the inferior PTGs may
be more difcult to locate in RSG.The next
step is the delivery of the thyroid gland by
blunt dissection with the nger inferiorly,
completed by sharp dissection under vision.
The inferior vascular structures are then
ligated as near as possible to the gland, selectively ligating the branches of the ITA to the
level of the thyroid capsule [64]. The ITA
should not be ligated at the main stem [57,
71]. If the thyroid lobe cannot be brought to
the neck, more room is provided by removing
the opposite thyroid lobe in its cervical
position.
2. Mediastinal approach (Midline sternotomy—
Manubriotomy—Thoracotomy)
In cases of very large intra-thoracic goiters, invasive tumors, dense adhesions in
recurrent cases, uncontrollable hemorrhage,
or truly ectopic intra-thoracic gland with its
major blood supply from intra-thoracic vessels, a “mediastinal” approach using midline
“sternotomy” is required [64, 126]. Sand etal.
[90] have proposed indications for sternotomy, which is listed in Table12.9.
Fig. 12.14 Total thyroidectomy of a huge retro-sternal
goiter through the trans-cervical approach is 54-year-old
lady
t.me/Dr_Mouayyad_AlbtousH
Table 12.9
ter (RSG)
– Goiter size larger than the thoracic inlet or a mass
– Primary intra-thoracic goiter with intra-thoracic
– Goiters in the posterior mediastinum displacing or
– RSGs reaching the level of the aortic arch
– Large RSG extending towards the tracheal
– If the lowermost extent of the tumor cannot be
– Potential for acute airway problems
– Goiters associated with SVC syndrome, pressure
– Recurrent (postoperative) RSG
– Malignant RSG with LN metastasis or suspicious
SVC superior vena cava; RSG retro-sternal goiter; LN
lymph node
Indications of sternotomy in retrosternal goi-
not accessible from the neck
blood supply
compressing the aortic arch
bifurcation
palpated
effects, or severe venous obstruction
involvement of neighboring structures
300
M. Sakr
As an alternative to complete sternotomy, a
partial upper sternal split (manubriotomy) is possible in most cases [127]. Division of the manubrium to below the manubrio-sternal junction is
performed. The innominate vein and the pleura
are freed from the back of the manubrium. The
manubrium and the upper sternum are divided in
the middle and gently spread with a right-angled
retractor. Sternotomy is closed using sternal
wires. If complete sternotomy is performed, the
skin incision is extended to just above the xiphoid
process, and the pericardial and diaphragmatic
attachments are freed from the back of the sternum before its division.
In 2008, Huins etal. proposed a new classication system for the approach to RSG, reported
as grades or levels 1, 2, and 3 (Table 12.10).
Accordingly, it would seem inappropriate to perform a full sternotomy for RSGs that do not reach
the level of the aortic arch. On the other hand, any
gland below the level of the right atrium would
require a full sternotomy for adequate exposure.
This classication system correlates with the
results of Grainger etal. [80] with regard to ndings on CT scanning and, more importantly,
reects to a signicant degree the practice of the
majority of surgeons.
For resection of a “crossed” RSG with extension from a left-side gland to the right mediastinum, right anterolateral “thoracotomy” can be
helpful [128]. Thoracotomy is also advised for
the removal of posterior mediastinal goiters. Van
Schil et al., in 1989, proposed thoracotomy for
the removal of RSGs to avoid troublesome bleeding [100]. It is noteworthy that maneuvers involving “blind” dislocation of the gland from the
mediastinum towards the neck (Foley catheter
applied through the cervical incision, morcellation, and use of heavy silk structures into the cer-
Table 12.10 Classication and approach for retrosternal
goiters
Grade Anatomical location Approach
1 Above aortic arch (above T4) Cervical
2 Aortic arch to the
pericardium
3 Below right atrium Full
Manubriotomy
sternotomy
vical component to apply traction) are
discouraged due to high risk of hemorrhage or
damage of adjacent structures located in the thoracic inlet.
Minimally Invasive Techniques
(Approaches)
Minimally invasive approaches are associated
with faster recovery, reduced morbidity and pain,
shorter hospital stays, and better cosmetic results
compared to open surgery.
1. Video-Assisted Thoracoscopic Surgery (VATS)
There has been accumulating evidence that
VATS may provide a reliable alternative to
thoracotomy. Shigemura et al. [129],
employed VATS along with a supra-clavicular
window in 5, high-risk patients with huge
anterior mediastinal RSGs resulting in uncomplicated postoperative course and favorable
outcomes in all cases. Gupta et al. [130]
described the use of VATS in seven cases of
RSGs highlighting its potential benets over
sternotomy and thoracotomy. Additionally,
Bhargav etal. [130] treated 11 posterior mediastinal RSGs through the thoracoscopic
approach and reported no major morbidity
except for one case of RLN injury.
Despite encouraging preliminary results,
there are still some limitations with thoracoscopy, which may discourage some surgeons to
proceed with this approach. These include the
2D visualization provided by the system and
the difcult access to the upper mediastinum
due to the rigidity and length of the VATS
instruments.
2. Robotic-assisted Trans-thoracic Surgery
Compared to the VATS approach, the
robotic da Vinci system, according to Podgaetz
et al. [131], offers superior maneuverability
and 3D visualization, which permits a precise
dissection of the delicate vessels surrounding
the thyroid gland and its mediastinal extension. Rea etal. [132] described 108 roboticassisted thoracoscopic operations for RSGs
with no reported surgical mortality.
Furthermore, Wang etal. [133] described the
use of robot-assisted approach in the treat-
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12 Benign Thyroid Disease
301
Table 12.11
Retro-sternal thyroidectomy Midline sternotomy
– Bleeding
– Hematoma/seroma
– Infection
– Hypoparathyroidism/hypocalcemia
– Injury to the external branch of the SLN and/or
– Injury of the pharynx, trachea, or sympathetic
– Unsightly scar
ment of a huge RSG.It has to be noted that the
aforementioned studies reported on a combined cervico-mediastinal approach for posterior masses; mediastinal approach was crucial
for the dissection and mobilization, whereas
neck incision aided in the removal of the goiters [131, 133]. Two main drawbacks of
robotic-assisted surgery pose dilemmas for its
establishment in clinical practice, high cost,
and the slow learning curve.
Complications of retro-sternal thyroidectomy and midline sternotomy
– Mediastinal bleeding
– Hematoma/seroma.
– Infection (mediastinitis/abscess/osteomyelitis).
– Chest bone fracture, sternum shift/disgurement, or
dehiscence.
RLN
chain
– Injury of Pleura (pneumo-thorax/pneumo-mediastinum).
– Unsightly scar
an infected hematoma) [137, 138], and injury of
the pharynx, trachea, or sympathetic chain with
resultant Horner’s syndrome. Sternal infection
may manifest late and is treated with a surgical
debridement and appropriate antibiotics. Other
complications related to sternotomy include sternum disgurement, chest bone fracture, sternum
dehiscence, and unsightly scar.
Postoperative complications after RSG thyroidectomy including complications of midline
sternotomy are summarized in Table12.11.
Complications ofRSG Surgery
Many authors reported overall incidence of complications in RSG thyroidectomy as similar to
that for standard thyroidectomy (<5%). As with
12.4 Benign Solitary Thyroid
Nodule (STN)
cervical goiter, the main complications of RSG
surgery are hemorrhage, RLN injury, hypopara-
12.4.1 Overview
thyroidism, hemorrhage, and hematoma or
seroma formation [82, 134, 135]. An intrathoracic goiter was found to be an independent
risk factor for postoperative complications [62].
In a prospective study of 2235 thyroid resections, 312 were performed for RSG in which the
complication rate was signicantly elevated,
including hemorrhage, wound infections, transient hypocalcemia, and transient RLN paresis
[136]. However, Raffaelli et al. found no
increased rate of complications with substernal
thyroidectomy compared to non-substernal thyroidectomy [83].
In addition, mediastinal injuries may occur
during RSG surgery. If mediastinal hemorrhage
occurs, immediate surgical revision via a complete sternotomy is indicated for adequate control. Pneumo-thorax after pleural injury is treated
with the insertion of a chest tube [86, 101]. More
rare complications are infections (mostly due to
A solitary thyroid nodule (STN) is a “discrete
lesion within the thyroid gland that is radiologically distinct from the surrounding thyroid parenchyma” [139]. A non-palpable nodule detected in
imaging studies is termed “incidentaloma.” Nonpalpable nodules have the same risk of malignancy as do sonographically conrmed palpable
nodules of the same size [140]. Generally, only
nodules >1 cm should be evaluated since they
have a greater potential to be clinically signicant cancers. Occasionally, there may be a nodule
<1cm that requires further evaluation because of
clinical symptoms or associated
lymphadenopathy.
Most STNs are benign hyperplastic lesions,
but 5–20% of thyroid nodules are true neoplasms.
A retrospective study by Keh etal. of 61 patients
found 75.4% of STNs to have a neoplastic pathology and 34.4% to be malignant [141].
t.me/Dr_Mouayyad_AlbtousH
302
M. Sakr
One of the major goals in the evaluation of the
STNs is to differentiate hyperplasia from true
neoplasms. Evaluation of STNs requires the collaboration of the primary care physician, endocrinologist, pathologist, radiologist, and head and
neck surgeon to provide comprehensive and
appropriate management of this clinical entity.
Medical history and physical examination of
the patient add signicantly to the determination
of the nature of the STN.Currently, a variety of
serological and cytogenetic tests, diagnostic
imaging studies, and histopathological techniques exist for the evaluation of STN.Of these
methods, ne- needle aspiration biopsy (FNAB)
has become the most important assessment tool;
it inuences the management strategy of the
patient.
12.4.2 Prevalence
The prevalence of thyroid nodules depends on
age, gender, diet, iodine deciency, and radiation
exposure. Thyroid nodules are found in approximately 1.5% of children and adolescents. They
are more common in females, and this predisposition exists throughout all age groups. In fact,
palpable nodular disease is six times more common in adolescent females compared with males
of the same age group [142].
Exposure of the head and neck to ionizing
radiation increases the incidence of thyroid nodules. Radiation treatments were not uncommon
in the rst half of the twentieth century for benign
conditions such as acne, adeno-tonsillar hypertrophy, and enlarged thymus glands. The prevalence rate of thyroid nodules in radiation-exposed
patients increases signicantly (16%–31% relative to the general population).
12.4.3 Pathology ofBenign STN
The most important distinction in the work-up of
a STN is whether or not it represents a malignant
lesion. Thus, the primary goal is to distinguish
those nodules that require surgical excision from
those that can be safely observed. Many thyroid
diseases can present clinically as a benign STN
such as adenomatous nodules or colloid nodules,
follicular adenoma, hurthle cell adenoma, thyroid
cysts, inammatory lesions (thyroiditis), and
developmental abnormalities (cystic hygroma,
dermoid, teratoma).
The differential diagnosis of STN can be broadly
classied into “benign” and “malignant.” Parameters
for cytological assessment of solitary nodules
should include the following parameters: (1) cellularity, (2) colloid content, (3) acinar formation, (4)
papillary formation, (5) intra-nuclear cytoplasmic
inclusions, (6) nuclear grooves, (7) marginal vacuoles, (8) Hürthle cells, (9) the presence of various
inammatory cells, and (10) cellular atypia.
12.4.3.1 Thyroid Adenomas
Thyroid adenomas are benign neoplasms, which
are usually classied as follicular or papillary.
Follicular Adenoma
Follicular adenomas are the most common type
of adenomas and arise from the follicular epithelium within the thyroid gland. It usually occurs in
adults, usually between 20 and 50years, with a
female preponderance (M:F=1:6).
Denition
A follicular adenoma is a benign tumor that
shows evidence of follicular differentiation but
lacks evidence of capsular and vascular invasion
and lacks the nuclear features of PTC.In “atypical adenoma,” there may be pleomorphism, cellularity, mitotic gures, or necrosis, but still
without capsular or vascular invasion. It is typically considered to have a benign behavior but
may be the precursor of anaplastic thyroid carcinoma (ATC).
Gross Appearance
A follicular adenoma is seen as a solitary, encapsulated, tumor of variable size (1–10cm); typically homogeneous, solid, eshy, tan to light
brown. It has a thin capsule and compresses adjacent thyroid tissue (Fig.12.15). It may resemble
multinodular goiter (MNG) due to secondary
changes of hemorrhage and cystic degeneration
(Fig.12.16)
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Fig. 12.15 Follicular adenoma. Typically, solitary,
encapsulated, homogenous, solid, and tan to brown in
color. It has a thin capsule and compresses the surrounding thyroid tissue (distinct from it)
Fig. 12.16 Follicular adenoma showing necrosis and
marked cystic changes (resembling multinodular goiter)
Histological (Microscopical) Picture
Typically, a follicular adenoma shows the following microscopical features: (1) completely enveloped by a thin brous capsule, (2) architecturally
and cytologically different from the surrounding
thyroid tissue, which shows signs of compression, and (3) closely packed follicles, trabeculae,
or solid sheets.
Fig. 12.17 Normo-follicular (simple) adenoma with
regular cells and no capsular or vascular invasion
Fig. 12.18 Macro-follicular adenoma. Normal thyroid
follicles appear at the lower right. Follicles of the adenoma (upper left) contain colloid, but there is greater variability in size than normal
Follicular adenomas are further classied
according to their cellular architecture and relative amounts of cellularity and colloid into the
following four patterns (varieties): (1) normofollicular (simple) (Fig. 12.17), (2) macrofollicular (colloid) with large colloid lled
follicles with attened epithelium (Fig. 12.18),
(3) micro-follicular (fetal) with small follicles
(Fig. 12.19), and (4) trabecular/solid (embryonal—atypical) with cords/trabeculae and few follicles (Fig.12.20).
Colloid adenomas do not have any potential
for micro-invasion, while fetal and embryonal
adenomas all have the potential for microinvasion. Secondary changes of hemorrhage,
hemosiderin deposition, sclerosis, edema, necrosis, and cystic changes may be seen. Characteristic
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304
Fig. 12.19 Micro-follicular adenoma with sharp circumscription by delicate brous capsule
M. Sakr
Fig. 12.21 Hyperplastic nodule composed of follicles of
variable sizes and age, colloid, and macrophages (yellow
arrow). Normal thyroid follicles are seen at the bottom
right side (white arrow)
cinomas, and tend to be polarized at the basal or
central part of the cell. Papillary adenoma does
not actually exist and any papillary architecture
should be diagnosed as PTC and treated as such.
Fig. 12.20 Trabecular/solid adenoma (atypical adenoma/
embryonal) with few follicles
benign features include (1) no capsular or vascular invasion after thorough sampling of at least 10
blocks, (2) no or rare mitotic gures, and (3) no
papillary nuclear features (characteristic of PTC).
Papillary Adenoma
Papillary adenomas are the least common type of
thyroid adenoma. “Papillary hyperplasia” is the
term that is preferred to “papillary adenoma.”
The basic lesion is a follicular adenoma or adenomatous nodule in which hyperplastic changes
occur. This lesion tends to occur, most often in
children and adolescents, as a STN that develops
approximately at the age of puberty. Pathologic
examination reveals that the nodule is always
well circumscribed, often even encapsulated, and
may show cystic change centrally. The papillae,
which are directed to the center of the nodule,
contain extremely edematous stalks with follicles
in them. The nuclei are round, not clear as in car-
12.4.3.2 Hyperplastic Nodules
Hyperplastic nodules are areas of the thyroid that
are stimulated to undergo follicular hyperplasia
and accumulation of colloid. They can be differentiated from colloid goiters by the presence of
excessive cellularity, acinar formation, marginal
vacuoles, papillary formation, and the amount of
colloid present in the specimen (Fig. 12.21).
Neoplasms have a higher degree of papillary formation, intra-nuclear inclusions and nuclear
grooves, and fewer marginal vacuoles.
12.4.3.3 Solitary Toxic Nodule
A solitary toxic nodule is a “discrete, autonomous, hyperfunctioning nodule that occurs in an
otherwise normal thyroid gland and causes
hyperthyroidism.” Only 25% of all hyperfunctioning nodules are toxic nodules. The term
“autonomous” means it functions independently
of the hypothalamic–pituitary–thyroid feedback
mechanism and secretes thyroid hormone despite
suppressed TSH levels.
The clinical thyrotoxic manifestations of a
solitary toxic nodule are generally milder than in
patients with Graves’ disease. It usually occurs
more commonly in women and patients <50years
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12 Benign Thyroid Disease
305
of age. A thyroid scan using
131
I conrms the
presence of a hyperfunctioning nodule. The
pathology of a toxic STN is almost uniform either
a follicular adenoma or an adenomatous nodule.
Carcinoma occurs in only about 1% of cases
[143].
12.4.3.4 Congenital Thyroid Nodules
Congenital thyroid nodules include congenital
hemangioma, thyroglossal duct anomalies, and
familial disorders, such as multiple endocrine
neoplasia (MEN) syndromes and congenital goi-
trous hypothyroidism. A residual thyroglossal
duct cyst is a benign condition that may be found
on biopsy of a midline neck mass, especially in
children. This structure retains the thyroid acinar
epithelium and may be surrounded by lymphocytic inltrate. It may also become infected and
progress to abscess formation.
12.4.3.5 Thyroid Cyst
Thyroid cysts represent 15–25% of all thyroid
nodules and are usually diagnosed by the aspiration of uid from a STN.These entities are often
caused by cystic degeneration of normal thyroid
tissue, hemorrhage or trauma, occult follicular
adenoma or carcinoma, multinodular goiter
(MNG), or branchial anomalies that involve the
thyroid gland. Simple epithelium-lined cysts,
hemorrhagic colloid nodules, or necrotic PTCs
can be found in resection specimens.
12.4.3.6 Thyroiditis
“Hashimoto’s (lymphocytic) thyroiditis” is an
autoimmune disease, the principal manifestations
of which are goiter and hypothyroidism. It may
accompany malignancy in as many as 50% of
children with cancer. Microscopically, there is
diffuse epithelial cell destruction, lymphoid cellular inltration, and brosis (Fig. 12.22). The
follicular spaces shrink, and the colloid is absent
or sparse. Foreign body giant cells and granulomas are not features of Hashimoto’s thyroiditis,
in contrast to subacute thyroiditis.
“Subacute granulomatous thyroiditis” is probably viral in origin, and patients usually present
with a tender goiter. “Acute suppurative thyroiditis” results from bacterial or fungal infection
Fig. 12.22 Microscopic picture of Hashimoto’s thyroiditis. The dominant feature is a profuse mononuclear lymphocytic inltrate accompanied by actual follicles and
germinal centers
causing abscess. The presence of clinical or metabolic hyperthyroidism with painful nodular thyroid disease strongly suggests thyroiditis. Local
abscess is usually infectious, but it may develop
from necrotic undifferentiated thyroid carcinoma.
12.4.4 Clinical Considerations
12.4.4.1 History-Taking (Risk Factors)
Any nodule developing prior to puberty should
be viewed with suspicion. It has been reported
that >50%f of all thyroid nodules in children are
malignant [144]. The incidence of malignancy is
also higher in nodules that develop after the age
of 65 years. Benign nodules are more common
than malignant nodules in both males and
females; however, the proportion of malignant
nodules in males is twice that of females.
Prevalence of cancer is 30–50% in a patient
with a STN and a history of head or neck irradiation in childhood [78]. Other factors to consider
include symptoms of pheochromocytoma or
HPT, long-standing constipation and/or diarrhea,
hypertension, and/or episodes of nervousness.
These should alert the clinician to the possibility
of medullary thyroid carcinoma (MTC) in association with familial MEN syndrome.
A nodule that has been stable in size for years
is almost always benign. Thyroid malignancies
usually develop over weeks or months.
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