MALIGNANT THYROID
Schwartzs
Choose the letter of the best answer (July 12, 2012); Just copied
A. Papillary Thyroid Cancer
B. Follicular Thyroid Cancer
C. Anaplastic Thyroid Cancer
D. A and B only
E. A, B, and C
A 1. Characterized by Orphan Annie Nuclei and Psammoma Bodies
C 2. Whatever the size of the tumor, px is automatically stage IV
D 3. Radioactive iodine ablation therapy plays a role in improving outcome
B 4. May present as a thyroid mass w/ bone metastasis at initial presentation
B 5. Diagnosis is difficult to establish by FNAB
C 6. Survival rate is very low and usually has 6 months survival period
A 7. Thyroid cancer w/ propensity to metastasize to cervical lymph node
E 8. Origin is from the follicle cells of the thyroid glands
E 9. Surgery can be done for cure or palliation of symptoms
D 10. Serum thyroglobulin is a useful marker to detect recurrence
Papillary Carcinoma
80% of all thyroid malignancies in iodine-sufficient areas
predominant thyroid cancer in children and individuals exposed to
external radiation
often in women, with a 2:1 female-to-male ratio
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 usually are associated with
locally advanced invasive disease
Lymph node metastases are common, especially in children and
young adults, and may be the presenting complaint
"Lateral aberrant thyroid" almost always denotes a cervical lymph
node that has been invaded by metastatic cancer
Diagnosis = FNAB of the thyroid mass or lymph node
Once diagnosed on FNAB, a complete neck ultrasound is strongly
recommended to evaluate the contralateral lobe and for lymph node
metastases in the central and lateral neck compartments
Distant metastases are uncommon at initial presentation, but may
ultimately develop in up to 20% of patients
The most common sites are lungs, followed by bone, liver, and
brain.
Pathology
On gross examination, 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
apparent
Histologically, papillary carcinomas 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 nuclear cellular features:
Cells are cuboidal with pale, abundant cytoplasm, crowded nuclei that may
demonstrate "grooving," and intranuclear cytoplasmic inclusions [leading to
the designation of Orphan Annie nuclei which allow diagnosis by FNAB
Psammoma bodies, which are microscopic, calcified deposits representing
clumps of sloughed cells, also may be present
Multifocality is common in papillary carcinoma and may be present
in up to 85% of cases on microscopic examination
Multifocality is associated with an increased risk of cervical nodal
metastases, and these tumors may rarely invade adjacent structures
such as the trachea, esophagus, and RLNs
Other variants of papillary carcinoma include tall cell, insular, columnar,
diffuse sclerosing, clear cell, trabecular, and poorly differentiated types; these
variants account for about 1% of all papillary carcinomas and are generally
associated with a worse prognosis
Minimal or occult/microcarcinoma refers to tumors of 1 cm or less in size
with no evidence of local invasiveness through the thyroid capsule or
angioinvasion, and that are not associated with lymph node metastases.
They are nonpalpable and usually are incidental findings
Studies have demonstrated occult PTC to be present in 2 to 36% of
thyroid glands removed at autopsy
These tumors are also being identified more frequently due to the
widespread use of ultrasound
These occult tumors are generally associated with a better
prognosis than larger tumors, but they may be more aggressive than
previously appreciated
TNM see last page
Prognostic Indicators
Excellent prognosis with a >95% 10-year survival rate
System
AGES Age, histologic Grade, Extrathyroidal invasion, and metastases and
tumor Size
predict the risk of dying from papillary cancer
Low-risk patients are young, with well-differentiated tumors,
no metastases, and small primary lesions
high-risk patients are older, with poorly differentiated tumors,
local invasion, distant metastases, and large primary lesions
MACIS Postoperative system modified from the AGES scale
Distant Metastases, Age at presentation (<40 or >40 years old),
Completeness of original surgical resection, extrathyroidal Invasion, and
Size of original lesion (in cm)] classifies patients into four risk groups
based on their scores
AMES classify differentiated thyroid tumors into low- and high-risk groups [Age
(men <40 years old, women <50 years old), Metastases, Extrathyroidal
spread, and Size of tumors (less than or >5 cm)]
TNM Tumor, Nodal status, Metastases
DeGroot class I (intrathyroidal), class II (cervical nodal metastases), class III
and (extrathyroidal invasion), and class IV (distant metastases)
associates
Several molecular and genetic markers such as tumor DNA aneuploidy, decreased
cyclic adenosine monophosphate response to TSH, increased epidermal growth factor
binding, presence of N-ras and gsp mutations, overexpression of c-myc, and presence
of p53 mutations also have been associated with a worse prognosis. The presence of
BRAF mutations also has been demonstrated to be associated with lymph node
metastasis and higher stage (III and IV) papillary tumors.
Surgical Treatment
High-risk tumors or bilateral tumors should undergo total or near-
total thyroidectomy
When patients have a minimal papillary thyroid carcinoma in a
thyroid specimen removed for other reasons, unilateral thyroid
lobectomy and isthmusectomy is usually considered to be
adequate treatment, unless the tumor has evidence of
angioinvasion, multifocality, or positive margins
The optimal surgical strategy in the majority of patients with low-risk (small,
unilateral) cancers remains controversial
Total thyroidectomy Lobectomy
(a) enables the use of RAI to effectively detect (a) total thyroidectomy is associated with a
and treat residual thyroid tissue or metastatic higher complication rate than lobectomy
disease (b) recurrence in the remaining thyroid tissue is
(b) makes serum Tg level a more sensitive unusual (5%) and most are curable by surgery
marker of recurrent or persistent disease (c) tumor multicentricity seems to have little
(c) eliminates contralateral occult cancers as prognostic significance
sites of recurrence (because up to 85% of (d) patients who have undergone lesser
tumors are bilateral) procedures such as lobectomy still have an
(d) reduces the risk of recurrence and improves excellent prognosis
survival
(e) decreases the 1% risk of progression to
undifferentiated or anaplastic thyroid cancer
(f) reduces the need for reoperative surgery with
its attendant risk of increased complication rates
However,
it is known that a significant proportion (33 to 50%) of patients who
develop a recurrence die from their disease
recurrence rates are lowered and survival is improved in patients
undergoing near-total or total thyroidectomy
diminished survival is noted in patients with low-risk disease
(mortality rates of 5% at 10 to 20 years), and it is not possible to
accurately risk stratify patients preoperatively
it is recommended that even patients with low-risk tumors
undergo total or near-total thyroidectomy, provided
complication rates are low (<2%)
Thus, when PTC is diagnosed by FNAB, the definitive operation can be
done without confirming the diagnosis by frozen section during the
operation
Patients with a nodule that may be papillary cancer should be
treated by thyroid lobectomy, isthmusectomy, and removal of any
pyramidal lobe or adjacent lymph nodes
If intraoperative frozen-section examination of a lymph node or
primary tumor confirms carcinoma, completion total or near-total
thyroidectomy is performed
If a definitive diagnosis cannot be made or the surgeon is concerned
about the viability of the parathyroid glands or the status of the RLN,
the operation is terminated
When final histology confirms carcinoma, completion thyroidectomy
is performed
For patients who have minimal PTCs (<1 cm) without angioinvasion,
no further operative treatment is recommended
During thyroidectomy, enlarged central neck nodes should be
removed
Some investigators recommend routine bilateral central neck dissection due
to the high incidence of microscopic metastases and improved rates of
recurrence and survival
However, increased risk of hypoparathyroidism with routine
central neck dissection
Biopsy-proven lymph node metastases detected clinically or by
imaging in the lateral neck in patients with papillary carcinoma are
managed with modified radical or functional neck dissection
Dissection of the posterior triangle and suprahyoid dissection usually are not
necessary unless there is extensive metastatic disease in levels 2, 3, and 4,
but should be performed when appropriate
Prophylactic lateral neck node dissection is not necessary in patients with
PTC, because these cancers do not appear to metastasize systemically from
lymph nodes, and micrometastases often can be ablated with RAI therapy
Follicular Carcinoma
10% of thyroid cancers
more commonly in iodine-deficient areas (vs Papillary: Iodine-Sufficient)
Women, with a female-to-male ratio of 3:1
mean age at presentation of 50 years old
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 (about 5%), although distant
metastases may be present
 In <1% of cases, follicular cancers may be hyperfunctioning, leading
patients to present with signs and symptoms of thyrotoxicosis
FNAB is unable to distinguish benign follicular from follicular carcinomas
Therefore, preoperative clinical diagnosis of cancer is difficult
unless distant metastases are present
Large follicular tumors (>4 cm) in older men are more likely to be
malignant
Due to limitations of FNAB, studies have focused on molecular markers to
distinguish benign from malignant follicular lesions
Loss of heterozygosity (LOH) analysis compares normal and tumor tissue
DNA at specific chromosomal loci for loss of one copy of a gene pair
LOH near the von Hippel-Lindau (VHL) locus of chromosome 3p25-26
has been reported to be a strong discriminant of benign from malignant
follicular lesions
Other studies used complementary DNA microarrays to compare
Expression arrays also have been used to investigate the role of microRNAs,
which are a new class of small, noncoding RNA that have been implicated in
carcinogenesis; the specific microRNAs miR-197 and miR-364 are
upregulated in follicular thyroid cancers
Many of these genetic changes can be identified using tissue obtained during
FNAB and have the potential to be used as diagnostic and possibly prognostic
markers
Pathology
Usually are solitary lesions, majority surrounded by a capsule
Histologically, follicles are present, but the lumen may be devoid of
colloid Architectural patterns depend on the degree of differentiation
demonstrated by the tumor
Malignancy is defined by the presence of capsular and vascular
invasion
appear grossly encapsulated
Minimally have microscopic invasion through the tumor capsule without
invasive extension into the parenchyma and/or invasion into small- to
tumors medium-sized vessels (venous caliber) in or immediately outside
the capsule, but not within the tumor
Widely evidence of large vessel invasion and/or broad areas of tumor
invasive invasion through the capsule. They may, in fact, be unencapsulated
tumors
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 FNAB as having a follicular lesion should undergo
thyroid lobectomy because at least 80% of these patients will have benign
adenomas
Some recommend total thyroidectomy in older patients with follicular
lesions >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
There is debate whether patients with minimally invasive follicular
cancers should undergo completion thyroidectomy because the
prognosis is so good in these patients
A frankly invasive carcinoma or follicular carcinoma with
angioinvasion, with or without capsular invasion, necessitates
completion of total thyroidectomy primarily so that 131I can be used
to detect and ablate metastatic disease
Prophylactic nodal dissection is unwarranted because nodal
involvement is infrequent, but in the unusual patient with nodal
metastases, therapeutic neck dissection is recommended
The cumulative mortality is approximately 15% at 10 years and
30% at 20 years
Poor long-term prognosis
age over 50 years old at marked vascular invasion
presentation extrathyroidal invasion
tumor size >4 cm distant metastases at the time of
higher tumor grade diagnosis
Hrthle Cell Carcinoma
3% of all thyroid malignancies
WHO classification: considered to be a subtype of follicular thyroid cancer
Also characterized by vascular or capsular invasion and can, therefore, not be
diagnosed by FNAB
Tumors contain sheets of eosinophilic cells packed with mitochondria, which are
derived from the oxyphilic cells of the thyroid gland
Hrthle cell tumors differ from follicular carcinomas in that
they are more often multifocal and bilateral (about 30%)
usually do not take up RAI (about 5%)
more likely to metastasize to local nodes (25%) and distant sites
associated with a higher mortality rate (about 20% at 10 years)
Hence, they are considered to be a separate class of tumors by some
groups
Management is similar to that of follicular neoplasms, with lobectomy and
isthmusectomy being sufficient surgical treatment for unilateral Hrthle cell
adenomas
When found to be invasive on definitive paraffin-section histology,
then total thyroidectomy should be performed
These patients should also undergo routine central neck node
removal, similar to patients with MTC, and modified radical neck
dissection when lateral neck nodes are palpable
Although RAI scanning and ablation usually are ineffective, they probably should be
considered to ablate any residual normal thyroid tissue and occasionally ablate tumors
because there is no other good therapy
Redifferentiating therapies such as retinoic acid, PPAR agonists have shown some utility
in treating these tumors in vitro; however, the results of phase II clinical trials have been
mixed
Postoperative Management of Differentiated Thyroid Cancer
Radioiodine Therapy
Long-term cohort demonstrate that postoperative RAI therapy reduces
recurrence and provides a small improvement in survival, even in low-risk
patients
Screening with RAI is more sensitive than chest x-ray or CT scanning for
detecting metastases
however, it is less sensitive than Tg measurements for detecting metastatic
disease in most differentiated thyroid cancers except Hrthle cell tumors
Screening and treatment are facilitated by the removal of all normal thyroid
tissue, which effectively competes for iodine uptake
Metastatic differentiated thyroid carcinoma can be detected and treated by
131
I in about 75% of patients
Studies show that RAI effectively treats >70% of lung micrometastases that
are detected by RAI scan in the presence of a normal chest x-ray, whereas
the success rates drop to <10% with pulmonary macrometastases
Early detection therefore appears to be very important to improve prognosis
RAI ablation currently is recommended for:
a. all patients with stage III or IV disease
b. all patients with stage II disease younger than 45 years old
c. most patients 45 years or older with stage II disease
d. patients with stage I disease who have aggressive histologies, nodal
metastases, multifocal disease, and extrathyroid or vascular invasion
Generally, T4 therapy should be discontinued for approximately 6 weeks
before scanning with 131I
Patients should receive T3 during this time period to decrease the period
f hypothyroidism
T3 has a shorter half-life than T4 (1 day vs. 1 week) and needs to be
discontinued for 2 weeks to allow TSH levels to rise before treatment
Levels >30 mU/L are considered optimal
A low-iodine diet also is recommended during this 2-week period
The usual protocol involves administering a screening dose of 1 to 3 mCi of
123
I and measuring uptake 24 hours later
After a total thyroidectomy, this value should be <1%
A "hot" spot in the neck after initial screening usually represents
residual normal tissue in the thyroid bed
If there is significant uptake, then a therapeutic dose of 131I should
be administered,
30 to 100 mCi to low-risk patients
100 to 200 mCi in high-risk patients
If patients have an elevated Tg level, but negative RAI scan, some
physicians recommend treating once with 100 mCi of 131I and
repeating the imaging 1 to 2 weeks later
Approximately one third of these patients demonstrate uptake on
posttreatment imaging, and Tg levels usually decrease in these
patients, documenting therapeutic benefit
Patients with previously positive scans and patients with serum Tg
levels >2 ng/mL usually need another 131I treatment after 6 to 12
months until one or two negative scans are obtained
The follow-up scan can be done after hormone withdrawal or after
recombinant TSH
The maximum dose of radioiodine that can be administered at one time
without performing dosimetry is approximately 200 mCi with a cumulative
dose of 1000 to 1500 mCi
Up to 500 mCi can be given with proper pretreatment dosimetry
131
Table 38-7 Complications of Radioactive Iodine Therapy ( I) and Doses at
Which They Are Observed
Long-Term
Acute
Neck pain, swelling, and tenderness Hematologic
Thyroiditis (if remnant present) Bone marrow suppression (>500 mCi)
Sialadenitis (50450 mCi), taste dysfunction Leukemia ( >1000 mCi)
Hemorrhage (brain metastases) Fertility
Cerebral edema (brain metastases, 200 mCi) Ovarian/testicular damage, infertility
Vocal cord paralysis Increased spontaneous abortion rate
Nausea and vomiting (50450 mCi) Pulmonary fibrosis
Chronic sialadenitis, nodules, taste dysfunction
Bone marrow suppression (200 mCi)
Increased risk of cancer
Anaplastic thyroid cancer
Gastric cancer
Hepatocellular cancer
Lung cancer
Breast cancer (>1000 mCi)
Bladder cancer
Hypoparathyroidism
External Beam Radiotherapy and Chemotherapy
occasionally required to control unresectable, locally invasive or recurrent
disease and to treat metastases in support bones to decrease the risk of
fracture
It also is of value for the treatment and control of pain from bony metastases
when there is minimal or no RAIU
Single and multidrug chemotherapy has been used with little success in
disseminated thyroid cancer, and there is no role for routine chemotherapy
Doxorubicin (Adriamycin) and paclitaxel (Taxol) are the most frequently
used agents
Doxorubicin acts as a radiation sensitizer and should be considered in
patients undergoing external beam radiation
Thyroid Hormone
T4 is necessary not only as replacement therapy in patients after total or
near-total thyroidectomy, but has the additional effect of suppressing TSH
and reducing the growth stimulus for any possible residual thyroid cancer
cells
TSH suppression reduces tumor recurrence rates
T4 should be administered to ensure that the patient remains
euthyroid, with circulating TSH levels at about 0.1 U/L in low-risk
patients, or <0.1 U/mL in high-risk patients
The risk of tumor recurrence must be balanced with the side effects
associated with prolonged TSH suppression, including osteopenia
and cardiac problems, particularly in older patients
Follow-Up of Patients with Differentiated Thyroid Cancer
Thyroglobulin Measurement
Tg levels in patients who have undergone total thyroidectomy should be <2
ng/mL when the patient is taking T4 , and <5 ng/mL when the patient is
hypothyroid
A Tg level >2 ng/mL is highly suggestive of metastatic disease or
persistent normal thyroid tissue, especially if it increases when
TSH levels increase when hypothyroid during preparation for RAI
scanning or after recombinant TSH
Approximately 95% of patients with persistent or recurrent thyroid
cancer of follicular cell origin will have Tg levels >2 ng/mL
Tg and anti-Tg antibody levels should be measured initially at 6-
month intervals and then annually if the patient is clinically
disease free
More recently, Tg measurements in FNAB aspirates have been
shown to be useful in the detection of nodal metastatic disease
Imaging
After the first posttreatment scan, low-risk patients with negative TSH-
stimulated Tg and cervical ultrasound do not require routine diagnostic
whole body radioiodine scans
diagnostic whole body scans 6 to 12 months after remnant ablation
may be of value in the follow-up of high or intermediate risk of
persistent disease
also recommended that cervical ultrasound to evaluate the thyroid
bed and central and lateral cervical nodal compartments should be
performed at 6 and 12 months postthyroidectomy and then
annually for at least 3 to 5 years, depending on the patients' risk
for recurrent disease and Tg status
If RAI and ultrasound scans are negative but Tg levels remain
elevated, FDG PET scans can help to localize the disease
Medullary Carcinoma
5% of thyroid malignancies
arises from the parafollicular or C cells of the thyroid, which, in turn, are
derived from the ultimobranchial bodies (these cells are concentrated
superolaterally in the thyroid lobes, and this is where MTC usually
develops)
C cells secrete calcitonin, a 32-amino-acid polypeptide that functions to lower serum
calcium levels, although its effects in humans are minimal
Female-to-male ratio is 1.5:1
Most patients present between 50 and 60 years old, although patients with
familial disease present at a younger age
Most occur sporadically
However, approximately 25% occur within the spectrum of several inherited
syndromes such as familial MTC, MEN2A, and MEN2B
All these variants are known to result secondary to germline
mutations in the RET proto-oncogene
genotype-phenotype correlations with specific mutations leading to
particular clinical manifestations
Patients with MTC often present with a neck mass that may be associated
with palpable cervical lymphadenopathy (15 to 20%)
Pain or aching is more common
Local invasion may produce dysphagia, dyspnea, or dysphonia
Distant blood-borne metastases to the liver, bone (frequently
osteoblastic), and lung occur later in the disease
Medullary thyroid tumors secrete not only calcitonin and
carcinoembryonic antigen (CEA), but also other peptides such as
calcitonin generelated peptide, histaminadases, prostaglandins E2
and F2, and serotonin
Patients with extensive metastatic disease frequently develop
diarrhea, which may result from increased intestinal motility and
impaired intestinal water and electrolyte flux
About 2 to 4% of patients develop Cushing's syndrome as a result of
ectopic production of adrenocorticotropic hormone (ACTH)
Pathology
Unilateral (80%) in patients with sporadic disease and multicentric in familial
cases, with bilateral tumors occurring in up to 90% of familial patients
Familial cases also are associated with C-cell hyperplasia, which
is considered a premalignant lesion
Microscopically, tumors are composed of sheets of infiltrating
neoplastic cells separated by collagen and amyloid
Marked heterogeneity is present; cells may be polygonal or spindle
shaped
The presence of amyloid is a diagnostic finding, but
immunohistochemistry for calcitonin is more commonly used as
a diagnostic tumor marker
These tumors also stain positively for CEA and calcitonin gene
related peptide
Diagnosis
Established by history, physical examination, raised serum calcitonin, or
CEA levels, and FNAB cytology of the thyroid mass
Attention to family history is important because about 25% of
patients with MTC have familial disease
Because it is not possible to distinguish sporadic from familial
disease at initial presentation, all new patients with MTC should be
screened for RET point mutations, pheochromocytoma, and
HPT
Calcitonin and CEA are used to identify patients with persistent or
recurrent MTC [Calcitonin is a more sensitive tumor marker, but CEA is
a better predictor of prognosis]
Treatment
If patients are found to have a pheochromocytoma, this must be operated
on first
These are generally (>50%) bilateral
Total thyroidectomy is the treatment of choice for patients with
MTC because of the high incidence of multicentricity, the more
aggressive course, and the fact that 131I therapy usually is not
effective
Central compartment nodes frequently are involved early in the
disease process, so that a bilateral central neck node dissection
should be routinely performed
In patients with palpable cervical nodes or involved central neck
nodes, ipsilateral or bilateral, modified radical neck dissection is
recommended
The role of prophylactic lateral neck dissection is controversial. However, in
patients with tumors >1 cm, ipsilateral prophylactic modified radical
neck dissection is recommended because >60% of these patients have
nodal metastases
If ipsilateral nodes are positive, a contralateral node dissection
should be performed
In the case of locally recurrent or metastatic disease, tumor
debulking is advised not only to ameliorate symptoms of flushing
and diarrhea, but also to decrease risk of death from recurrent
central neck or mediastinal disease
External beam radiotherapy is controversial, but is recommended for
patients with unresectable residual or recurrent tumor
There is no effective chemotherapy regimen
Radiofrequency ablation done laparoscopically appears promising in
the palliative treatment of liver metastases >1.5 cm.
In patients who have hypercalcemia at the time of thyroidectomy, only
obviously enlarged parathyroid glands should be removed
The other parathyroid glands should be preserved and marked in
patients with normocalcemia, as only about 20% of patients with
MEN2A develop HPT
When a normal parathyroid cannot be maintained on a vascular
pedicle, it should be removed, biopsied to confirm that it is a
parathyroid, and then autotransplanted to the forearm of the
nondominant arm
Total thyroidectomy is indicated in RET mutation carriers once the
mutation is confirmed
The procedure should be performed
before age 6 in MEN2A patients
before age 1 in MEN2B patients
When the calcitonin is increased or the ultrasound suggests a
thyroid cancer, a prophylactic central neck dissection is indicated
Postoperative Follow-Up and Prognosis
Annual measurements of calcitonin and CEA levels, in addition to
history and physical examination
Other modalities include ultrasound, CT, MRI, and more recently,
FDG PET scans (reported to be superior to other radionuclide-
based and routine morphologic imaging)
Prognosis is related to disease stage
The 10-year survival rate is approximately 80% but decreases to
45% in patients with lymph node involvement
Survival also is significantly influenced by disease type
It is best in patients with non-MEN familial MTC, followed by those
with MEN2A, and then those with sporadic disease
Prognosis is the worst (survival 35% at 10 years) in patients
with MEN2B
Performing prophylactic surgery in RET oncogene mutation carriers
not only improves survival rates but also renders most patients
calcitonin free
Anaplastic Carcinoma
approximately 1% of all thyroid malignancies in the United States
declining in incidence
Women are more commonly affected
majority of tumors present in the seventh and eighth decade 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 with areas of necrosis
Lymph nodes usually are palpable at presentation
 Evidence of metastatic spread also may be present From page 1
Table 38-6 TNM Classification of Thyroid Tumors
Diagnosis is confirmed by FNAB revealing characteristic giant and
multinucleated cells Papillary or Follicular Tumors
Incisional biopsy occasionally is needed to confirm the diagnosis, and Stage TNM
isthmusectomy with or without a tracheostomy may be needed to alleviate
tracheal obstruction <45 y
I Any T, any N, M0
Pathology
Gross: anaplastic tumors are firm and whitish in appearance II Any T, any N, M1
Microscopic: sheets of cells with marked heterogeneity are seen 45 y
Cells may be spindle shaped, polygonal, or large, multinucleated cells. Foci
of more differentiated thyroid tumors, either follicular or papillary, may be I T1, N0, M0
seen, suggesting that anaplastic tumors arise from more well-differentiated II T2, N0, M0
tumors
One should confirm that the tumor is not a MTC or a small cell lymphoma III T3, N0, M0; T13, N1a, M0
because the prognosis varies considerably IVA T4a, N01a, M0; T14a, N1b, M0

Treatment and Prognosis IVB T4b, any N, M0

One of the most aggressive thyroid malignancies, with few patients IVC Any T, any N, M1
surviving 6 months beyond diagnosis
All forms of treatment have been disappointing Medullary Thyroid Cancer
If anaplastic carcinoma presents as a resectable mass, Stage TNM
thyroidectomy may lead to a small improvement in survival,
I T1, N0, M0
especially in younger individuals
Combined radiation and chemotherapy in an adjuvant setting in II T23, N0, M0
patients with resectable disease has been associated with
III T13, N1a, M0
prolonged survival, although these agents are also being used in a
neoadjuvant fashion IVA T4a, N01a, M0; T14a, N1b, M0
Tracheostomy may be needed to alleviate airway obstruction IVB T4b, any N, M0

Lymphoma IVC Any T, any N, M1

<1% of thyroid malignancies Anaplastic Cancer
most are non-Hodgkin's B-cell type Stage TNM
Although the disease can arise as part of a generalized lymphomatous
condition, most thyroid lymphomas develop in patients with chronic IVA T4a, Any N, M0
lymphocytic thyroiditis IVB T4b, Any N, M0
Chronic antigenic lymphocyte stimulation has been suggested to
result in lymphocyte transformation IVC Any T, Any M, M1
Patients usually present with symptoms similar to those of patients
with anaplastic carcinoma, although the rapidly enlarging neck mass Definitions:
often is painless Primary tumor (T)
TX = Primary tumor cannot be assessed
Patients may present with acute respiratory distress T0 = No evidence of primary tumor
The diagnosis usually is suggested by FNAB, although needle-core T1 = Tumor 2 cm in diameter, limited to thyroid
or open biopsy may be necessary for definitive diagnosis T2 = Tumor >2 cm but <4 cm in diameter, limited to thyroid
Staging studies should be obtained expeditiously to assess the T3 = Tumor >4 cm in diameter, limited to thyroid, or any tumor with minimal
extent of extrathyroidal spread extrathyroidal invasion
T4a = Any size tumor extending beyond capsule to invade subcutaneous soft tissue,
Treatment and Prognosis larynx, trachea, esophagus, or recurrent laryngeal nerve, or intrathyroidal anaplastic
cancer
Respond rapidly to chemotherapy (CHOPcyclophosphamide, doxorubicin, T4b = Tumor invading prevertebral fascia, or encasing carotid artery or mediastinal
vincristine, and prednisone), which also has been associated with improved vessels; or extrathyroidal anaplastic cancer
survival Regional lymph nodes (N)include central, lateral cervical, and upper mediastinal
Combined treatment with radiotherapy and chemotherapy often is nodes
recommended NX = Regional lymph nodes cannot be assessed
Thyroidectomy and nodal resection are used to alleviate symptoms N0 = No regional lymph node metastasis
of airway obstruction in patients who do not respond quickly to the N1 = Regional lymph node metastasis
N1a = Metastases to level VI (pretracheal, paratracheal, and prelaryngeal/Delphian
above regimens or who have completed the regimen before lymph nodes)
diagnosis N1b = Metastases to unilateral, bilateral, or contralateral cervical or superior
Prognosis depends on the histologic grade of the tumor and whether the mediastinal lymph nodes
lymphoma is confined to the thyroid gland or is disseminated Distant metastasis (M)
The overall 5-year survival rate is about 50%; patients with MX = Distant metastases cannot be assessed
extrathyroidal disease have markedly lower survival rates M1 = No distant metastasis

Metastatic Carcinoma
The thyroid gland is a rare site of metastases from other cancers, including SOURCE:
th
kidney, breast, lung, and melanoma. Clinical examination and a review of Schwartzs Principles of Surgery, 9 edition
the patient's history often suggest the source of the metastatic disease, and
FNAB usually provides definitive diagnosis. Resection of the thyroid, usually
lobectomy, may be helpful in many patients, depending on the status of
their primary tumor.

end