Solitary Thyroid Nodule
• 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.
• Details regarding the nodule, such as
– time of onset, change in size,
• Associated symptoms, such as
– pain, dysphagia, dyspnea, or choking, should be
• Pain is an unusual symptom and when
present, should raise suspicion for
– intrathyroidal hemorrhage in a benign
nodule, thyroiditis, or malignancy.
• 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 laryngeal nerves.
• 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
• Family History
– 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 substernal goiter.
• 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 aspiration.
• After FNA biopsy, the majority of nodules can be
categorized into the following groups: benign (65%),
suspicious (20%), malignant (5%), and nondiagnostic (10%).
• The incidence of false-positive results is approximately 1%
and false-negative results occur in approximately 3% of
• 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
– 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 this diagnosis.
• 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 high,
– in which case metastatic thyroid cancer should be suspected.
– 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
• Scanning the thyroid with 123I or 99mTc is rarely
necessary, unless evaluating patients for "hot" or
autonomous thyroid nodules.
– 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 greater than 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 measurements.
– 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 slowgrowing 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 metastatic cancer.
• 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
– 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 greater than 95% 10-year survival
• 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
• AMES system
Papillary or Follicular Tumors
Younger than age 45 Years
Age 45 Years and older
Medullary Thyroid Cancer
Any T, Any N, M0
Any T, Any N, M1
T1, N0, M0
T2, N0, M0
T3, N0, M0; T1-3, N1a, M0
T4a, N0-1a, M0; T1-4a, N1b, M0
T4b, Any N, M0
Any T, any N, M1
T1, N0, M0
T2-3, N0, M0
T1-3, N1a, M0
T4a, N0-1a, M0; T1-4a, N1b, M0
T4b, any N, M0
Any T, Any N, M1
T4a, Any N, M0
T4b, Any N, M0
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
• T4b = Tumor invading prevertebral fascia, or encasing
carotid artery or mediastinal vessels; or extrathyroidal
• 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
• Occur more commonly in iodine-deficient
• The overall incidence of this tumor is,
probably as a result of iodine supplementation
and improved histologic classification.
• 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 long-standing goiter.
• Pain is uncommon, unless hemorrhage into
the nodule has occurred.
• Unlike papillary cancers, cervical
lymphadenopathy is uncommon at initial
presentation (approximately 5%)
• Although distant metastases may be present.
• may be hyperfunctioning in less than 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 vascular invasion.
• Minimally-invasive tumors
– 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.
Surgical Treatment and Prognosis
• 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 is diagnosed.
Hürthle Cell Carcinoma
• 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 cannot 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 do not take up RAI (approximately 5%),
– are more likely to metastasize to local nodes (25%) and distant
– are associated with a higher mortality rate (20% at 10 yrs).
• Hence, they are considered to be a separate class
of tumors by some surgeons.
• Management is similar to that of follicular
– with lobectomy and isthmusectomy being sufficient
surgical treatment for unilateral Hürthle cell
• When Hürthle cell neoplasms are found to be
invasive on intraoperative, frozen-section, or
definitive paraffin-section histology,
– 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 of fractures.
• 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 parafollicular or C cells of the
thyroid, which, in turn, are derived from the
• 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 calcium metabolism)
• 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 20%).
• Local pain or aching is more common in patients with these tumors,
and local invasion may produce symptoms of dysphagia, dyspnea,
• 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 serotonin.
• MTCs are typically unilateral (80%) in patients
with sporadic disease,
• and multicentric in familial cases, with
bilateral tumors occurring in up to 90% of
• Familial cases are also associated with C-cell
hyperplasia, which is considered a
• 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 seventh and
eighth 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
• Evidence of metastatic spread also may be
• 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 beyond diagnosis.
– 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
Treatment and Prognosis
• Respond rapidly to chemotherapy (CHOP—cyclophosphamide,
doxorubicin, vincristine, and prednisone), which is also associated
with improved survival.
• Combined treatment with radiotherapy and chemotherapy is often
• 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 survival
• 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
• Resection of the thyroid, usually lobectomy, may
be helpful in many patients, depending on the
status of their primary tumor
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