Thyroid Cancer

Dr Lusine Harutyunyan
 Thyroid cancer types

Thyroid malignancies are divided

into following:

• papillary carcinomas (80%)

• follicular carcinomas (10%)
• medullary thyroid carcinomas
(5-10%)
• anaplastic carcinomas (1-2%)
• primary thyroid lymphomas
(rare)
• primary thyroid sarcomas (rare)
Hürthle cell carcinoma
• Hürthle cell carcinoma is a rare thyroid
malignancy that is often considered a
variant of follicular carcinoma.
• Hürthle cell carcinomas account for 2-
3% of all thyroid malignancies.
• They occur more commonly in women
than in men and typically manifest in
the fifth decade of life.
A monomorphous cell population of Hürthle cells
• The clinical presentation is similar to arranged in loosely cohesive clusters and single cells.
that of other thyroid malignancies. The cells are polyhedral and have abundant granular
cytoplasm with well-defined cell borders. The nuclei
are enlarged and have a central prominent
macronucleolus.
Epidemiology

• Thyroid cancers represent approximately 1% of new cancer diagnoses each year.

• About 23,500 cases of thyroid cancer are diagnosed annually in the United States.
• The incidence of the disease is three times higher in women than in men; a study by Weir et al,
from the US Centers for Disease Control and Prevention (CDC), predicted that by 2020, the
largest increases in the annual number of cancer cases in women will be for cancers of the
lung, breast, uterus, and thyroid.
• The incidence of thyroid cancer peaks in the third and fourth decades of life.
Etiology
• Thyroid carcinomas arise from the 2 cell types present in the thyroid gland. The endodermally derived follicular
cell gives rise to papillary, follicular, and probably anaplastic carcinomas. The neuroendocrine-derived calcitonin-
producing C cell gives rise to MTCs. Thyroid lymphomas arise from intrathyroid lymphoid tissue, whereas
sarcomas likely arise from connective tissue in the thyroid gland.
• Radiation exposure significantly increases the risk for thyroid malignancies, particularly papillary thyroid
carcinoma. This finding was observed in children exposed to radiation after the nuclear bombings in Hiroshima
and Nagasaki during World War II. Additional evidence was gathered after atomic bombs were tested in the
Marshall Islands, after the accident at the Chernobyl nuclear power plant, and in patients who received low-dose
radiation therapy for benign disorders (eg, acne, adenotonsillar hypertrophy). Low-dose radiation exposure from
imaging studies has not been found to have a tumorigenic effect. Radiation targeting the thyroid gland (eg, iodine-
131 ablation of the thyroid) or high-dose external-beam radiation therapy does not appear to increase the risk of
papillary thyroid carcinoma. This is presumably because cell killing increases with these doses.
• A study by Le et al indicated that among patients in the Veterans Health Administration (VHA) with thyroid
cancer, the percentage of those with self-reported exposure to Agent Orange is significantly higher than in the
general VHA population. The study included 19,592 patients diagnosed with thyroid cancer. [9]
• Low dietary intake of iodine does not increase the incidence of thyroid cancers overall. However, populations with
low dietary iodine intake have a high proportion of follicular and anaplastic carcinomas.
 Clinical Presentation
• Thyroid carcinoma most commonly manifests as a painless, palpable, solitary
thyroid nodule. Patients or clinicians discover most of these nodules during
routine palpation of the neck.
• Signs and symptoms associated with malignancy in thyroid nodules include the
following:
• Solitary nodules: Most likely to be malignant in patients older than 60 years and
in patients younger than 30 years
• Increased rate of malignancy in males
• Nodular growth
• Rapid growth: Ominous sign
• Usually painless (nontender to palpation); sudden onset of pain more strongly
associated with benign disease (eg, hemorrhage into a benign cyst, subacute viral
thyroiditis)
• Hard and fixed nodules
Diagnosis
The key to the workup of the solitary thyroid nodule is to differentiate malignant
from benign disease and, thus, to determine which patients require intervention and
which patients may be monitored serially. History taking, physical examination,
laboratory evaluation, and fine-needle aspiration biopsy (FNAB) are the mainstays
in the evaluation of thyroid nodules. Imaging studies can be adjuncts in select cases.
Examination in patients suspected of thyroid cancer includes the following:
• Thorough head and neck examination, including thyroid gland and cervical soft
tissues
• Indirect laryngoscopy
Firm cervical masses are highly suggestive of regional lymph node metastases. Vocal
fold paralysis implies involvement of the recurrent laryngeal nerve.
Diagnosis: Procedures
FNAB is the most important diagnostic tool in evaluating thyroid nodules and should
be the first intervention. The following are the 4 possible results from this procedure:
• Benign disease
• Malignant disease
• Indeterminate for diagnosis
• Nondiagnostic
Up to 50% of repeated biopsies result in a definitive diagnosis. Patients whose
findings are indeterminate or nondiagnostic despite repeat biopsy can undergo surgery
for lobectomy for tissue diagnosis. Nondiagnostic cases can also be monitored
clinically, and radioiodine scans can be useful for determining the functional status of
the nodule, because most hyperfunctioning nodules are benign.
Diagnosis: Lab Tests
The following laboratory studies may be used to assess patients with
suspected thyroid cancer:
• Serum thyroid-stimulating hormone concentration: Sensitive for
hyperthyroidism/hypothyroidism and for evaluation of solitary thyroid
nodules
• Serum calcitonin/pentagastrin-stimulated calcitonin levels: Elevated
levels highly suggestive of medullary thyroid carcinoma
• Polymerase chain reaction (PCR) assay for germline mutations in the
RET proto-oncogene: For diagnosis of familial medullary thyroid
carcinoma
Diagnosis: Imaging Studies
The following imaging studies may be used to evaluate patients with suspected
thyroid cancer:
• Neck ultrasonography: Most common modality to evaluate thyroid disease;
however, limited usefulness for distinguishing between malignant and benign
nodules
• Thyroid radioiodine imaging: To determine functional status of a nodule but
cannot exclude carcinoma
• Neck computed tomography (CT) scanning or magnetic resonance imaging
(avoid iodinated contrast agents): To evaluate soft-tissue extension of large or
suspicious thyroid masses into the neck, trachea, or esophagus, and to assess
metastases to the cervical lymph nodes; no role in routine management of
solitary thyroid nodules
Guideline Organizations
Organizations that have released guidelines for the diagnosis and/or
management of thyroid cancer include the following:
• American Thyroid Association (ATA)
• National Comprehensive Cancer Network (NCCN)
• American Association of Clinical Endocrinologists/American College
of Endocrinology/Associazione Medici Endocrinologi
(AACE/ACE/AME)

Read the mentioned: https://emedicine.medscape.com/article/851968-

overview#a10
A 2015 consensus statement from the American Thyroid Association
on preoperative imaging for thyroid cancer surgery

• Ultrasonography remains the most important imaging modality in the

evaluation of thyroid cancer and should be used routinely to assess the
primary tumor and all associated cervical lymph node basins
preoperatively
• Ultrasonographically guided fine-needle aspiration of suspicious lymph
nodes may be useful in guiding the extent of surgery
• Cross-sectional imaging (CT scanning with contrast or magnetic
resonance imaging [MRI]) may be considered in select circumstances to
better characterize tumor invasion and bulky, inferiorly located, or
posteriorly located lymph nodes; it may also be used when
ultrasonographic expertise is not available
 Physical Examination
• Physical examination should include thorough head and neck
examination with careful attention to the thyroid gland and cervical soft
tissues, as well as indirect laryngoscopy.
• Solitary thyroid nodules can vary from soft to hard. Hard and fixed
nodules are more suggestive of malignancy than supple mobile nodules
are. Thyroid carcinoma is usually nontender to palpation. Firm cervical
masses are highly suggestive of regional lymph node metastases. Vocal
fold paralysis implies involvement of the recurrent laryngeal nerve.
Treatment
• Malignant diagnoses require surgical intervention.
• Papillary thyroid carcinoma and medullary thyroid carcinoma are
often positively identified on the basis of FNAB results alone.
• Cervical metastases discovered preoperatively or intraoperatively
should be removed by means of en bloc lymphatic dissection of the
respective cervical compartment (selective neck dissection) while
sparing the nonlymphatic structures.
A 2015 consensus statement from the American Thyroid Association
on the management of patients with differentiated thyroid cancer
who have recurrent/persistent nodal disease
• The appropriate management of patients with nodal metastases may
involve compartmental lymph-node dissection, active surveillance,
radioactive iodine ablation therapy, external-beam radiation therapy,
and/or nonsurgical, image-guided, minimally invasive ablative
approaches
• Biologic considerations include aggressive histology, extrathyroidal
extension of primary tumor, and molecular prognosis for aggressive
biology
• Surgical/technical considerations include prior recurrences in the same
or different compartments
Postsurgical Management
• After total thyroidectomy, patients undergo radioiodine scanning to
detect regional or distant metastatic disease, followed by radioablation
of any residual disease found. In addition, patients are given thyroid
replacement therapy with T4 or triiodothyronine (T3).
• In patients with anaplastic thyroid carcinoma, chemotherapy and
radiation therapy are typically administered in combination.
Postoperative external-beam irradiation is effective in improving local
control; this may also be used as primary treatment in unresectable
cases. Chemotherapy (most commonly doxorubicin) is added for
palliation.
Prognosis
The long-term disease-free survival with aggressive treatment and management is nearly 90% overall. A variety of factors, as follow, are
associated with prognosis:
• Age: The patient's age at diagnosis is one of the most important prognostic features of well-differentiated thyroid carcinoma; cancer-
related death is most likely to occur if the patient is >40 years at the time of diagnosis; recurrences are most common in patients
whose disease is diagnosed when they were < 20 years or >60 years
• Sex: Men are twice as likely as women to die from thyroid cancer
• Size: The size of the primary tumor is related to survival; patients with primary tumors >4 cm have increased recurrence and cancer-
related mortality rates (although a study by Nguyen et al indicated that no association exists between increasing tumor size and
survival in patients with thyroid cancer until the tumor reaches dimensions of >2.5 cm [25] )
• Histology: Overall, papillary carcinoma is associated a 30-year cancer-related death rate of 6%; follicular carcinoma has a 30-year
cancer-related death rate of 15%
• Local invasion: Invasion of surrounding tissues outside of thyroid indicates biologic aggressiveness and significantly worsens the
patient's prognosis
• Lymph node metastasis: Lymph node metastasis does not appear to be as important in the outcome of well-differentiated thyroid
carcinomas as in the outcome of most other solid tumors
• Distant metastasis: Distant metastasis at initial examination is associated with a 68.1-fold increase in the rate of disease-specific death
• Socioeconomic factors: A study by Swegal et al indicated that socioeconomic factors affect survival in cases of well-differentiated
thyroid cancer, with lower household income being associated with a higher disease-related death rate; the study included 1317
patients