The majority of thyroid nodules are benign and do
not require removal.
Therefore, it is of utmost importance to determine
which patients with solitary thyroid nodule would
benefit from surgery.
Solitary Thyroid Nodule
Details regarding the nodule, such as
time of onset, change in size,
Associated symptoms, such as
pain, dysphagia, dyspnea, or choking, should be elicited.
Pain is an unusual symptom and when present, should
raise suspicion for
intrathyroidal hemorrhage in a benign nodule, thyroiditis,
Patients with medullary thyroid cancer may complain of
a dull, aching sensation.
A hx of hoarseness is worrisome because it may be
secondary to malignant involvement of the recurrent
Most importantly, patients should be questioned
regarding risk factors for malignancy,
such as exposure to ionizing radiation and family
history of thyroid and other malignancies associated
with thyroid cancer.
External Beam Radiation- The risk is maximum 20 to
30 years after exposure
is a risk factor for the development of both medullary and
nonmedullary thyroid cancer
Familial medullary thyroid cancers occur in isolation or in
association with other tumors as part of multiple endocrine
neoplasia type 2 (MEN2) syndromes.
Nonmedullary thyroid cancers can occur in association with
other known familial cancer syndromes such as
Cowden's syndrome, Werner's (adult progeroid) syndrome,
and familial adenomatous polyposis.
Nonmedullary thyroid cancers also can occur
independently of these syndromes.
Thyroid masses move with swallowing and failure to observe
the patient swallowing may lead one to miss a large
The thyroid gland is best palpated from behind the patient
and with the neck in mild extension.
The cricoid cartilage is an important landmark
because the isthmus is situated just below it.
Nodules that are hard, gritty, or fixed to surrounding
structures, such as to the trachea or strap muscles
more likely to be malignant.
The cervical chain of lymph nodes should be assessed as well
as the nodes in the posterior triangle.
One should examine the patient for a Delphian node and
pyramidal lobe situated just above the thyroid isthmus and
Fine-Needle Aspiration Biopsy
single most important test in the evaluation of patients with
can be performed with or without ultrasound guidance.
Ultrasound guidance is recommended for
nodules that are difficult to palpate and
for complex, solid cystic nodules that recur after the initial
After FNA biopsy, the majority of nodules can be
categorized into the following groups:
benign (65%), suspicious (20%), malignant (5%), and
The incidence of false-positive results is approximately
1% and false-negative results occur in approximately 3%
Nondiagnostic, it should usually be repeated.
Bloody FNA biopsy may also be reported as nondiagnostic
and often indicates a follicular neoplasm.
Benign lesions include cysts and colloid nodules. The risk
of malignancy in this setting is less than 3%.
Suspicious cytology- The risk of malignancy is 10 to 20%.
Most are follicular or Hürthle cell neoplasms.
Diagnosis of malignancy in this situation relies on
demonstrating capsular or vascular invasion,
features that cannot be determined via FNA biopsy.
FNA biopsy is also less reliable in patients who have
a history of head and neck irradiation or a family
history of thyroid cancer,
because of a higher likelihood of multifocal lesions.
There is little or no value in repeating an FNA biopsy
for a follicular or Hürthle cell lesion,
Repeat FNA biopsy can be useful for patients when
the cytology has some abnormalities that suggest a
papillary thyroid cancer, but not enough to make
Serum TSH- Most patients with thyroid nodules are
If a patient with a nodule is found to be hyperthyroid, the
risk of malignancy is approximately 1%.
Serum Tg levels cannot differentiate benign from
malignant thyroid nodules unless the levels are extremely
in which case metastatic thyroid cancer should be
Useful in following patients who have undergone total
thyroidectomy for thyroid cancer
For serial evaluation of patients undergoing nonoperative
management of thyroid nodules.
Serum calcitonin levels should be obtained in patients
with medullary thyroid cancer or a family history of
medullary thyroid cancer (MTC) or MEN2.
Ultrasound is helpful for detecting nonpalpable thyroid
for differentiating solid from cystic nodules, and
for identifying adjacent lymphadenopathy.
It also provides a noninvasive and inexpensive method of
following the size of suspected benign nodules diagnosed by
CT and MRI are unnecessary in the routine evaluation of
thyroid tumors, except for large, fixed, or substernal lesions.
Scanning the thyroid with 123I or 99mTc is rarely necessary,
unless evaluating patients for "hot" or autonomous thyroid
currently recommended in the assessment of thyroid nodules
only in patients
who have follicular thyroid nodules on FNA biopsy and a
Malignant tumors are treated by thyroidectomy
Simple thyroid cysts resolve with aspiration in
approximately 75% of cases, although some require a
second or third aspiration.
Unilateral thyroid lobectomy is recommended
If the cyst persists after three attempts at aspiration.
for cysts >4 cm in diameter
for complex cysts with solid and cystic components,
because of higher incidence of malignancy (15%).
When FNA biopsy is used in complex nodules, the solid
portion should be sampled.
If a colloid nodule is diagnosed by FNA biopsy, patients
should still be observed with serial ultrasound and Tg
If the nodule enlarges, repeat FNA biopsy is often
l-thyroxine in doses sufficient to maintain a serum TSH
level between 0.1 and 1.0 µU/ mL may also be
Most effective for nodules smaller than 3 cm.
Previous irradiation of the thyroid gland or who has a
family history of thyroid cancer-
total or near-total thyroidectomy
High incidence of thyroid cancer (40%)
and decreased reliability of FNA biopsy in this setting.
80% of all thyroid malignancies in iodine-sufficient areas
The predominant thyroid cancer in children and individuals
exposed to external radiation.
Occurs more often in women, with a 2:1 female: male ratio;
The mean age at presentation is 30 to 40 years.
Most patients are euthyroid and present with a slow-growing
painless mass in the neck.
Dysphagia, dyspnea, and dysphonia are usually associated
with locally advanced invasive disease.
Lymph node metastases are common, especially in children
and young adults, and may be the presenting complaint.
The so-called "lateral aberrant thyroid" almost always
denotes a cervical lymph node that has been invaded by
Suspicion of thyroid cancer often originates through
physical examination of the patient and a review of the
Diagnosis is established by FNA biopsy of the thyroid
mass or lymph node.
Distant metastases are uncommon at initial
presentation, but may ultimately develop in up to 20%
The most common sites are the lungs, followed by bone,
liver, and brain.
Gross - hard and whitish and remain flat on sectioning with
a blade, in contrast to normal tissue or benign nodular lesions
that tend to bulge.
Macroscopic calcification, necrosis, or cystic change may be
Histologically- may exhibit papillary projections, a mixed
pattern of papillary and follicular structures, or a pure
follicular pattern (follicular variant).
The diagnosis is established by characteristic cellular features.
Cells are cuboidal with pale, abundant cytoplasm,
"grooving," crowded nuclei, and intranuclear cytoplasmic
inclusions, leading to the designation of Orphan Annie nuclei,
which allows diagnosis by FNA biopsy.
Psammoma bodies, which are microscopic, calcified deposits
representing clumps of sloughed cells, may be present.
Mixed papillary–follicular tumors and follicular variant of
papillary carcinoma are classified as papillary carcinomas
because they act biologically as papillary carcinomas.
Multifocality - in up to 85% of cases. It is associated with
an increased risk of cervical nodal metastases
Rarely invade adjacent structures such as the trachea,
esophagus, and recurrent laryngeal nerves.
Other variants of papillary carcinoma (approximately 1%
of all papillary carcinomas) include
tall cell, insular, columnar, diffuse sclerosing, clear cell,
trabecular, and poorly differentiated types.
They are generally associated with a worse prognosis
In general, patients with PTC have an excellent
prognosis with a >95% 10-year survival rate.
AGES scoring system, which incorporates Age,
histologic Grade, Extrathyroidal invasion and
metastases, and tumor Size to predict the risk of
dying from papillary cancer.
The MACIS scale- Metastases, Age at presentation,
Completeness of original surgical resection,
extrathyroidal Invasion, and Size of original lesion
Papillary or Follicular Tumors
Younger than age 45 Years
I Any T, Any N, M0
II Any T, Any N, M1
Age 45 Years and older
I T1, N0, M0
II T2, N0, M0
III T3, N0, M0; T1-3, N1a, M0
IVA T4a, N0-1a, M0; T1-4a, N1b, M0
IVB T4b, Any N, M0
IVC Any T, any N, M1
Medullary Thyroid Cancer
I T1, N0, M0
II T2-3, N0, M0
III T1-3, N1a, M0
IVA T4a, N0-1a, M0; T1-4a, N1b, M0
IVB T4b, any N, M0
IVC Any T, Any N, M1
IVA T4a, Any N, M0
IVB T4b, Any N, M0
IVC Any T, Any M, M1
Primary tumor (T)
TX = Primary tumor cannot be assessed
T0 = No evidence of primary tumor
T1 = Tumor ≤2 cm in diameter, limited to thyroid
T2 = Tumor >2 cm but <4 cm in diameter, limited to thyroid
T3 = Tumor >4 cm in diameter, limited to thyroid, or any
tumor with minimal extrathyroidal invasion
T4a = Any size tumor extending beyond capsule to invade
subcutaneous soft tissue, larynx, trachea, esophagus, or
recurrent laryngeal nerve, or intrathyroidal anaplastic cancer
T4b = Tumor invading prevertebral fascia, or encasing carotid
artery or mediastinal vessels; or extrathyroidal anaplastic
Regional lymph nodes (N)—include central, lateral
cervical, and upper mediastinal nodes
NX = Regional lymph nodes cannot be assessed
N0 = No regional lymph node metastasis
N1 = Regional lymph node metastasis
N1a = Metastases to level VI (pretracheal,
paratracheal, and prelaryngeal/Delphian lymph
N1b = Metastases to unilateral, bilateral, or
contralateral cervical or superior mediastinal LNs
Total or near-total thyroidectomy
Follicular carcinomas account for 10% of thyroid
Occur more commonly in iodine-deficient areas.
The overall incidence of this tumor is, probably as a
result of iodine supplementation and improved
female: male ratio of 3:1,
a mean age at presentation of 50 years.
Usually present as solitary thyroid nodules,
Occasionally with a history of rapid size increase, and
Pain is uncommon, unless hemorrhage into the
nodule has occurred.
Unlike papillary cancers, cervical lymphadenopathy
is uncommon at initial presentation (approximately
Although distant metastases may be present.
may be hyperfunctioning in <1% of cases,
leading patients to present with signs and symptoms
FNA biopsy is unable to distinguish benign follicular
lesions from follicular carcinomas.
Therefore, preoperative diagnosis of cancer is
difficult unless distant metastases are present.
Large follicular tumors (>4 cm) in older men are
more likely to be malignant.
Usually solitary lesions, the majority of which are
surrounded by a capsule.
Histologically, follicles are present, but the lumen may
be devoid of colloid.
Malignancy is defined by the presence of capsular and
appear grossly encapsulated
but have evidence of microscopic invasion through the
tumor capsule and/or
invasion into small- to medium-size vessels (venous
caliber) in or immediately outside the capsule, but not
within the tumor.
Widely invasive tumors demonstrate evidence of
large-vessel invasion and/or broad areas of tumor
invasion through the capsule.
They may, in fact, be unencapsulated.
Tumor infiltration and invasion, as well as tumor
thrombus within the middle thyroid or jugular veins,
may be apparent at operation.
Patients diagnosed by FNA biopsy as having a follicular lesion
should undergo thyroid lobectomy because at least 80% of
these patients will have benign adenomas.
Some surgeons recommend total thyroidectomy in older
patients with follicular lesions larger than 4 cm because of the
higher risk of cancer in this setting (50%).
Intraoperative frozen-section examination
usually is not helpful,
but should be performed
when there is evidence of capsular or vascular invasion, or
when adjacent lymphadenopathy is present.
Total thyroidectomy should be performed when thyroid cancer
Surgical Treatment and
3% of all thyroid malignancies
Subtype of follicular thyroid cancer.
Like follicular cancers, Hürthle cell cancers are characterized
by vascular or capsular invasion, and therefore can’t be
diagnosed by FNA biopsy.
Tumors contain sheets of eosinophilic cells packed with
mitochondria, which are derived from the oxyphilic cells of
the thyroid gland.
differ from follicular carcinomas in that they are more often
multifocal and bilateral (approximately 30%),
usually don’t take up RAI (approximately 5%),
more likely to metastasize to local nodes (25%) and distant sites
associated with a higher mortality rate (20% at 10 yrs).
Hürthle Cell Carcinoma
Hence, they are considered to be a separate class of
tumors by some surgeons.
Management is similar to that of follicular neoplasms,
with lobectomy and isthmusectomy being sufficient surgical
treatment for unilateral Hürthle cell adenomas.
When Hürthle cell neoplasms are found to be invasive on
intraoperative, frozen-section, or definitive paraffin-
then total thyroidectomy should be performed.
Radioiodine Therapy- benefit to patients with
differentiated thyroid cancer
External Beam Radiotherapy and Chemotherapy
External beam radiotherapy is occasionally required to
control unresectable, locally invasive or recurrent disease
and to treat metastases in support bones to decrease the risk
Single and multidrug chemotherapy has been used with
little success in disseminated thyroid cancer.
Adriamycin and Taxol are the most frequently used agents.
MTCs account for about 5% of thyroid malignancies
arise from the para-follicular or C cells of the thyroid, which,
in turn, are derived from the ultimobranchial bodies.
These cells are concentrated superolaterally in the thyroid
lobes, which is where MTC usually develops.
C cells secrete calcitonin, a 32-amino-acid polypeptide that
functions to lower serum calcium levels. (regulator of
Most MTCs occur sporadically.
However, approximately 25% occur within the spectrum of
several inherited syndromes such as familial medullary
thyroid cancer, MEN2A, and MEN2B.
All these variants are known to result secondary to germline
mutations in the RET proto-oncogene.
Patients with MTC often present with a neck mass that may be
associated with palpable cervical lymphadenopathy (15 to
Local pain or aching is more common in patients with these
tumors, and local invasion may produce symptoms of
dysphagia, dyspnea, or dysphonia.
Distant blood-borne metastases to the liver, bone (frequently
osteoblastic), and lung occur later in the disease.
The female:male ratio is 1.5:1.
Most patients present between 50 and 60 years of age, although
patients with familial disease present at a younger age.
Medullary thyroid tumors secrete
not only calcitonin and carcinoembryonic antigen (CEA),
but also other peptides such as calcitonin gene-related peptide
(CGRP), histaminadases, prostaglandins E2 and F2, and
MTCs are typically unilateral (80%) in patients with
and multicentric in familial cases, with bilateral
tumors occurring in up to 90% of familial patients.
Familial cases are also associated with C-cell
hyperplasia, which is considered a premalignant
The diagnosis of MTC is established
by history, physical examination,
raised serum calcitonin or CEA levels,
FNA cytology of the thyroid mass.
Attention to family history is important
because approximately 25% of patients with MTC
have familial disease.
Total thyroidectomy is the treatment of choice for
patients with MTC because of
the high incidence of multicentricity,
the more aggressive course,
131I therapy is not usually effective.
External beam radiotherapy is controversial, but is
recommended for patients with unresectable
residual or recurrent tumor.
There is no effective chemotherapy regimen.
approximately 1% of all thyroid malignancies
Women are more commonly affected, and the
majority of tumors present in the 7th and 8th
decades of life.
The typical patient has a long-standing neck mass,
which rapidly enlarges and may be painful.
Associated symptoms, such as dysphonia,
dysphagia, and dyspnea, are common.
The tumor is large and may be fixed to surrounding
structures or may be ulcerated
Lymph nodes usually are palpable at presentation.
Evidence of metastatic spread also may be present.
Diagnosis is confirmed by FNA biopsy revealing
characteristic giant and multinucleated cells.
Incisional biopsy is occasionally needed to confirm
the diagnosis and isthmusectomy is performed to
alleviate tracheal compression.
Gross - firm and whitish in appearance.
Microscopically, sheets of cells with marked
heterogeneity are seen.
Treatment and Prognosis
This tumor is one of the most aggressive thyroid
malignancies, with few patients surviving 6 months
All forms of treatment have been disappointing.
A ccount for less than 1% of thyroid malignancies
most are of the non-Hodgkin's B-cell type.
Although the disease can arise as part of a generalized
lymphomatous condition, most thyroid lymphomas develop
in patients with chronic lymphocytic thyroiditis.
Patients usually present with symptoms similar to those of
patients with anaplastic carcinoma, although the rapidly
enlarging neck mass often is painless.
Patients may present with acute respiratory distress.
The diagnosis usually is suggested by FNA biopsy, although
needle-core or open biopsy may be necessary for definitive
Staging studies should be obtained to assess the extent of
Respond rapidly to chemotherapy (CHOP—
cyclophosphamide, doxorubicin, vincristine, and prednisone),
which is also associated with improved survival.
Combined treatment with radiotherapy and chemotherapy is
Thyroidectomy and nodal resection are used to alleviate
symptoms of airway obstruction in patients who do not
respond quickly to the above regimens, or in patients who
have completed the regimen prior to diagnosis.
Prognosis depends on
the histologic grade of the tumor and
whether the lymphoma is confined to the thyroid gland or is
The overall 5-year survival rate is about 50%;
patients with extrathyroidal disease have markedly lower
Treatment and Prognosis
The thyroid gland is a rare site of metastases from
other cancers, including kidney, breast, lung, and
Clinical examination and a review of the patient's
history often suggest the source of the metastatic
disease, and FNA biopsy usually provides definitive
Resection of the thyroid, usually lobectomy, may be
helpful in many patients, depending on the status of
their primary tumor