MALIGNANT THYROID (men <40 years old, women <50 years old), Metastases, Extrathyroidal

Schwartzs spread, and Size of tumors (less than or >5 cm)]

TNM Tumor, Nodal status, Metastases
Choose the letter of the best answer (July 12, 2012); Just copied DeGroot class I (intrathyroidal), class II (cervical nodal metastases), class III
A. Papillary Thyroid Cancer and (extrathyroidal invasion), and class IV (distant metastases)
B. Follicular Thyroid Cancer associates
C. Anaplastic Thyroid Cancer
D. A and B only Several molecular and genetic markers such as tumor DNA aneuploidy, decreased
E. A, B, and C cyclic adenosine monophosphate response to TSH, increased epidermal growth factor
A 1. Characterized by Orphan Annie Nuclei and Psammoma Bodies binding, presence of N-ras and gsp mutations, overexpression of c-myc, and presence
C 2. Whatever the size of the tumor, px is automatically stage IV of p53 mutations also have been associated with a worse prognosis. The presence of
D 3. Radioactive iodine ablation therapy plays a role in improving outcome BRAF mutations also has been demonstrated to be associated with lymph node
B 4. May present as a thyroid mass w/ bone metastasis at initial presentation metastasis and higher stage (III and IV) papillary tumors.
B 5. Diagnosis is difficult to establish by FNAB
C 6. Survival rate is very low and usually has 6 months survival period Surgical Treatment
A 7. Thyroid cancer w/ propensity to metastasize to cervical lymph node High-risk tumors or bilateral tumors should undergo total or near-
E 8. Origin is from the follicle cells of the thyroid glands total thyroidectomy
E 9. Surgery can be done for cure or palliation of symptoms
When patients have a minimal papillary thyroid carcinoma in a
D 10. Serum thyroglobulin is a useful marker to detect recurrence
thyroid specimen removed for other reasons, unilateral thyroid
lobectomy and isthmusectomy is usually considered to be
Papillary Carcinoma
adequate treatment, unless the tumor has evidence of
80% of all thyroid malignancies in iodine-sufficient areas angioinvasion, multifocality, or positive margins
predominant thyroid cancer in children and individuals exposed to
external radiation The optimal surgical strategy in the majority of patients with low-risk (small,
often in women, with a 2:1 female-to-male ratio unilateral) cancers remains controversial
mean age at presentation is 30 to 40 years
Total thyroidectomy Lobectomy
(a) enables the use of RAI to effectively detect (a) total thyroidectomy is associated with a
Most patients are euthyroid and present with a slow-growing painless and treat residual thyroid tissue or metastatic higher complication rate than lobectomy
mass in the neck 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
Dysphagia, dyspnea, and dysphonia usually are associated with marker of recurrent or persistent disease (c) tumor multicentricity seems to have little
locally advanced invasive disease (c) eliminates contralateral occult cancers as prognostic significance
Lymph node metastases are common, especially in children and sites of recurrence (because up to 85% of (d) patients who have undergone lesser
tumors are bilateral) procedures such as lobectomy still have an
young adults, and may be the presenting complaint (d) reduces the risk of recurrence and improves excellent prognosis
"Lateral aberrant thyroid" almost always denotes a cervical lymph survival
node that has been invaded by metastatic cancer (e) decreases the 1% risk of progression to
undifferentiated or anaplastic thyroid cancer
Diagnosis = FNAB of the thyroid mass or lymph node (f) reduces the need for reoperative surgery with
Once diagnosed on FNAB, a complete neck ultrasound is strongly its attendant risk of increased complication rates
recommended to evaluate the contralateral lobe and for lymph node
metastases in the central and lateral neck compartments However,
Distant metastases are uncommon at initial presentation, but may it is known that a significant proportion (33 to 50%) of patients who
ultimately develop in up to 20% of patients develop a recurrence die from their disease
The most common sites are lungs, followed by bone, liver, and
recurrence rates are lowered and survival is improved in patients
brain. undergoing near-total or total thyroidectomy
diminished survival is noted in patients with low-risk disease
Pathology (mortality rates of 5% at 10 to 20 years), and it is not possible to
On gross examination, hard and whitish and remain flat on accurately risk stratify patients preoperatively
sectioning with a blade, in contrast to normal tissue or benign it is recommended that even patients with low-risk tumors
nodular lesions that tend to bulge undergo total or near-total thyroidectomy, provided
Macroscopic calcification, necrosis, or cystic change may be complication rates are low (<2%)
apparent
Histologically, papillary carcinomas may exhibit papillary Thus, when PTC is diagnosed by FNAB, the definitive operation can be
projections, a mixed pattern of papillary and follicular structures, or done without confirming the diagnosis by frozen section during the
a pure follicular pattern (follicular variant) operation
Patients with a nodule that may be papillary cancer should be
The diagnosis is established by characteristic nuclear cellular features: treated by thyroid lobectomy, isthmusectomy, and removal of any
Cells are cuboidal with pale, abundant cytoplasm, crowded nuclei that may pyramidal lobe or adjacent lymph nodes
demonstrate "grooving," and intranuclear cytoplasmic inclusions [leading to If intraoperative frozen-section examination of a lymph node or
the designation of Orphan Annie nuclei which allow diagnosis by FNAB
primary tumor confirms carcinoma, completion total or near-total
Psammoma bodies, which are microscopic, calcified deposits representing
clumps of sloughed cells, also may be present thyroidectomy is performed
Multifocality is common in papillary carcinoma and may be present If a definitive diagnosis cannot be made or the surgeon is concerned
in up to 85% of cases on microscopic examination about the viability of the parathyroid glands or the status of the RLN,
Multifocality is associated with an increased risk of cervical nodal the operation is terminated
metastases, and these tumors may rarely invade adjacent structures When final histology confirms carcinoma, completion thyroidectomy
such as the trachea, esophagus, and RLNs is performed
Other variants of papillary carcinoma include tall cell, insular, columnar, For patients who have minimal PTCs (<1 cm) without angioinvasion,
diffuse sclerosing, clear cell, trabecular, and poorly differentiated types; these no further operative treatment is recommended
variants account for about 1% of all papillary carcinomas and are generally During thyroidectomy, enlarged central neck nodes should be
associated with a worse prognosis removed

Minimal or occult/microcarcinoma refers to tumors of 1 cm or less in size Some investigators recommend routine bilateral central neck dissection due
with no evidence of local invasiveness through the thyroid capsule or to the high incidence of microscopic metastases and improved rates of
angioinvasion, and that are not associated with lymph node metastases. recurrence and survival
They are nonpalpable and usually are incidental findings However, increased risk of hypoparathyroidism with routine
Studies have demonstrated occult PTC to be present in 2 to 36% of central neck dissection
thyroid glands removed at autopsy Biopsy-proven lymph node metastases detected clinically or by
These tumors are also being identified more frequently due to the imaging in the lateral neck in patients with papillary carcinoma are
widespread use of ultrasound managed with modified radical or functional neck dissection
These occult tumors are generally associated with a better Dissection of the posterior triangle and suprahyoid dissection usually are not
prognosis than larger tumors, but they may be more aggressive than necessary unless there is extensive metastatic disease in levels 2, 3, and 4,
previously appreciated but should be performed when appropriate
Prophylactic lateral neck node dissection is not necessary in patients with
TNM see last page
PTC, because these cancers do not appear to metastasize systemically from
lymph nodes, and micrometastases often can be ablated with RAI therapy
Prognostic Indicators
Excellent prognosis with a >95% 10-year survival rate
System
Follicular Carcinoma
AGES Age, histologic Grade, Extrathyroidal invasion, and metastases and
tumor Size 10% of thyroid cancers
predict the risk of dying from papillary cancer more commonly in iodine-deficient areas (vs Papillary: Iodine-Sufficient)
Low-risk patients are young, with well-differentiated tumors, Women, with a female-to-male ratio of 3:1
no metastases, and small primary lesions mean age at presentation of 50 years old
high-risk patients are older, with poorly differentiated tumors, usually present as solitary thyroid nodules, occasionally with a history of
local invasion, distant metastases, and large primary lesions
rapid size increase, and long-standing goiter
MACIS Postoperative system modified from the AGES scale
Distant Metastases, Age at presentation (<40 or >40 years old),
Pain is uncommon, unless hemorrhage into the nodule has occurred
Completeness of original surgical resection, extrathyroidal Invasion, and Unlike papillary cancers, cervical lymphadenopathy is
Size of original lesion (in cm)] classifies patients into four risk groups uncommon at initial presentation (about 5%), although distant
based on their scores metastases may be present
AMES classify differentiated thyroid tumors into low- and high-risk groups [Age
 In <1% of cases, follicular cancers may be hyperfunctioning, leading Although RAI scanning and ablation usually are ineffective, they probably should be
considered to ablate any residual normal thyroid tissue and occasionally ablate tumors
patients to present with signs and symptoms of thyrotoxicosis because there is no other good therapy
Redifferentiating therapies such as retinoic acid, PPAR agonists have shown some utility
FNAB is unable to distinguish benign follicular from follicular carcinomas in treating these tumors in vitro; however, the results of phase II clinical trials have been
mixed
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 Postoperative Management of Differentiated Thyroid Cancer
malignant Radioiodine Therapy
Long-term cohort demonstrate that postoperative RAI therapy reduces
Due to limitations of FNAB, studies have focused on molecular markers to recurrence and provides a small improvement in survival, even in low-risk
distinguish benign from malignant follicular lesions patients
Loss of heterozygosity (LOH) analysis compares normal and tumor tissue Screening with RAI is more sensitive than chest x-ray or CT scanning for
DNA at specific chromosomal loci for loss of one copy of a gene pair detecting metastases
LOH near the von Hippel-Lindau (VHL) locus of chromosome 3p25-26 however, it is less sensitive than Tg measurements for detecting metastatic
has been reported to be a strong discriminant of benign from malignant disease in most differentiated thyroid cancers except Hrthle cell tumors
follicular lesions Screening and treatment are facilitated by the removal of all normal thyroid
Other studies used complementary DNA microarrays to compare tissue, which effectively competes for iodine uptake
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 Metastatic differentiated thyroid carcinoma can be detected and treated by
131
carcinogenesis; the specific microRNAs miR-197 and miR-364 are I in about 75% of patients
upregulated in follicular thyroid cancers Studies show that RAI effectively treats >70% of lung micrometastases that
Many of these genetic changes can be identified using tissue obtained during are detected by RAI scan in the presence of a normal chest x-ray, whereas
FNAB and have the potential to be used as diagnostic and possibly prognostic the success rates drop to <10% with pulmonary macrometastases
markers Early detection therefore appears to be very important to improve prognosis

Pathology RAI ablation currently is recommended for:

Usually are solitary lesions, majority surrounded by a capsule a. all patients with stage III or IV disease
Histologically, follicles are present, but the lumen may be devoid of b. all patients with stage II disease younger than 45 years old
colloid Architectural patterns depend on the degree of differentiation c. most patients 45 years or older with stage II disease
demonstrated by the tumor d. patients with stage I disease who have aggressive histologies, nodal
Malignancy is defined by the presence of capsular and vascular metastases, multifocal disease, and extrathyroid or vascular invasion
invasion
appear grossly encapsulated Generally, T4 therapy should be discontinued for approximately 6 weeks
Minimally have microscopic invasion through the tumor capsule without before scanning with 131I
invasive extension into the parenchyma and/or invasion into small- to Patients should receive T3 during this time period to decrease the period
tumors medium-sized vessels (venous caliber) in or immediately outside f hypothyroidism
the capsule, but not within the tumor T3 has a shorter half-life than T4 (1 day vs. 1 week) and needs to be
Widely evidence of large vessel invasion and/or broad areas of tumor discontinued for 2 weeks to allow TSH levels to rise before treatment
invasive invasion through the capsule. They may, in fact, be unencapsulated Levels >30 mU/L are considered optimal
tumors A low-iodine diet also is recommended during this 2-week period
Tumor infiltration and invasion, as well as tumor thrombus within the middle thyroid or
jugular veins, may be apparent at operation.
The usual protocol involves administering a screening dose of 1 to 3 mCi of
123
I and measuring uptake 24 hours later
Surgical Treatment and Prognosis
After a total thyroidectomy, this value should be <1%
Patients diagnosed by FNAB as having a follicular lesion should undergo
A "hot" spot in the neck after initial screening usually represents
thyroid lobectomy because at least 80% of these patients will have benign
residual normal tissue in the thyroid bed
adenomas
If there is significant uptake, then a therapeutic dose of 131I should
Some recommend total thyroidectomy in older patients with follicular
be administered,
lesions >4 cm because of the higher risk of cancer in this setting
30 to 100 mCi to low-risk patients
(50%)
100 to 200 mCi in high-risk patients
Intraoperative frozen-section examination usually is not helpful, but
If patients have an elevated Tg level, but negative RAI scan, some
should be performed when there is evidence of capsular or vascular
physicians recommend treating once with 100 mCi of 131I and
invasion, or when adjacent lymphadenopathy is present
repeating the imaging 1 to 2 weeks later
Approximately one third of these patients demonstrate uptake on
Total thyroidectomy should be performed when thyroid cancer is diagnosed
posttreatment imaging, and Tg levels usually decrease in these
There is debate whether patients with minimally invasive follicular
patients, documenting therapeutic benefit
cancers should undergo completion thyroidectomy because the
prognosis is so good in these patients
Patients with previously positive scans and patients with serum Tg
A frankly invasive carcinoma or follicular carcinoma with
levels >2 ng/mL usually need another 131I treatment after 6 to 12
angioinvasion, with or without capsular invasion, necessitates
months until one or two negative scans are obtained
completion of total thyroidectomy primarily so that 131I can be used
The follow-up scan can be done after hormone withdrawal or after
to detect and ablate metastatic disease
recombinant TSH
Prophylactic nodal dissection is unwarranted because nodal
involvement is infrequent, but in the unusual patient with nodal
The maximum dose of radioiodine that can be administered at one time
metastases, therapeutic neck dissection is recommended
without performing dosimetry is approximately 200 mCi with a cumulative
The cumulative mortality is approximately 15% at 10 years and
dose of 1000 to 1500 mCi
30% at 20 years
Up to 500 mCi can be given with proper pretreatment dosimetry
Poor long-term prognosis 131
Table 38-7 Complications of Radioactive Iodine Therapy ( I) and Doses at
age over 50 years old at marked vascular invasion Which They Are Observed
presentation extrathyroidal invasion Long-Term
tumor size >4 cm distant metastases at the time of Acute
Neck pain, swelling, and tenderness Hematologic
higher tumor grade diagnosis 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
Hrthle Cell Carcinoma Vocal cord paralysis Increased spontaneous abortion rate
Nausea and vomiting (50450 mCi) Pulmonary fibrosis
3% of all thyroid malignancies Chronic sialadenitis, nodules, taste dysfunction
WHO classification: considered to be a subtype of follicular thyroid cancer Bone marrow suppression (200 mCi)
Increased risk of cancer
Also characterized by vascular or capsular invasion and can, therefore, not be Anaplastic thyroid cancer
diagnosed by FNAB Gastric cancer
Tumors contain sheets of eosinophilic cells packed with mitochondria, which are Hepatocellular cancer
derived from the oxyphilic cells of the thyroid gland Lung cancer
Breast cancer (>1000 mCi)
Bladder cancer
Hrthle cell tumors differ from follicular carcinomas in that Hypoparathyroidism
they are more often multifocal and bilateral (about 30%)
usually do not take up RAI (about 5%) External Beam Radiotherapy and Chemotherapy
more likely to metastasize to local nodes (25%) and distant sites occasionally required to control unresectable, locally invasive or recurrent
associated with a higher mortality rate (about 20% at 10 years) disease and to treat metastases in support bones to decrease the risk of
Hence, they are considered to be a separate class of tumors by some fracture
groups It also is of value for the treatment and control of pain from bony metastases
when there is minimal or no RAIU
Management is similar to that of follicular neoplasms, with lobectomy and Single and multidrug chemotherapy has been used with little success in
isthmusectomy being sufficient surgical treatment for unilateral Hrthle cell disseminated thyroid cancer, and there is no role for routine chemotherapy
Doxorubicin (Adriamycin) and paclitaxel (Taxol) are the most frequently
adenomas used agents
When found to be invasive on definitive paraffin-section histology, Doxorubicin acts as a radiation sensitizer and should be considered in
then total thyroidectomy should be performed patients undergoing external beam radiation
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
Thyroid Hormone
T4 is necessary not only as replacement therapy in patients after total or Diagnosis
near-total thyroidectomy, but has the additional effect of suppressing TSH Established by history, physical examination, raised serum calcitonin, or
and reducing the growth stimulus for any possible residual thyroid cancer CEA levels, and FNAB cytology of the thyroid mass
cells Attention to family history is important because about 25% of
TSH suppression reduces tumor recurrence rates patients with MTC have familial disease
T4 should be administered to ensure that the patient remains Because it is not possible to distinguish sporadic from familial
euthyroid, with circulating TSH levels at about 0.1 U/L in low-risk disease at initial presentation, all new patients with MTC should be
patients, or <0.1 U/mL in high-risk patients screened for RET point mutations, pheochromocytoma, and
The risk of tumor recurrence must be balanced with the side effects HPT
associated with prolonged TSH suppression, including osteopenia Calcitonin and CEA are used to identify patients with persistent or
and cardiac problems, particularly in older patients recurrent MTC [Calcitonin is a more sensitive tumor marker, but CEA is
a better predictor of prognosis]
Follow-Up of Patients with Differentiated Thyroid Cancer
Thyroglobulin Measurement Treatment
Tg levels in patients who have undergone total thyroidectomy should be <2 If patients are found to have a pheochromocytoma, this must be operated
ng/mL when the patient is taking T4 , and <5 ng/mL when the patient is on first
hypothyroid These are generally (>50%) bilateral
A Tg level >2 ng/mL is highly suggestive of metastatic disease or Total thyroidectomy is the treatment of choice for patients with
persistent normal thyroid tissue, especially if it increases when MTC because of the high incidence of multicentricity, the more
TSH levels increase when hypothyroid during preparation for RAI aggressive course, and the fact that 131I therapy usually is not
scanning or after recombinant TSH effective
Approximately 95% of patients with persistent or recurrent thyroid Central compartment nodes frequently are involved early in the
cancer of follicular cell origin will have Tg levels >2 ng/mL disease process, so that a bilateral central neck node dissection
Tg and anti-Tg antibody levels should be measured initially at 6- should be routinely performed
month intervals and then annually if the patient is clinically In patients with palpable cervical nodes or involved central neck
disease free nodes, ipsilateral or bilateral, modified radical neck dissection is
More recently, Tg measurements in FNAB aspirates have been recommended
shown to be useful in the detection of nodal metastatic disease
The role of prophylactic lateral neck dissection is controversial. However, in
Imaging patients with tumors >1 cm, ipsilateral prophylactic modified radical
After the first posttreatment scan, low-risk patients with negative TSH- neck dissection is recommended because >60% of these patients have
stimulated Tg and cervical ultrasound do not require routine diagnostic nodal metastases
whole body radioiodine scans If ipsilateral nodes are positive, a contralateral node dissection
diagnostic whole body scans 6 to 12 months after remnant ablation should be performed
may be of value in the follow-up of high or intermediate risk of In the case of locally recurrent or metastatic disease, tumor
persistent disease debulking is advised not only to ameliorate symptoms of flushing
also recommended that cervical ultrasound to evaluate the thyroid and diarrhea, but also to decrease risk of death from recurrent
bed and central and lateral cervical nodal compartments should be central neck or mediastinal disease
performed at 6 and 12 months postthyroidectomy and then
annually for at least 3 to 5 years, depending on the patients' risk External beam radiotherapy is controversial, but is recommended for
for recurrent disease and Tg status patients with unresectable residual or recurrent tumor
If RAI and ultrasound scans are negative but Tg levels remain There is no effective chemotherapy regimen
elevated, FDG PET scans can help to localize the disease Radiofrequency ablation done laparoscopically appears promising in
the palliative treatment of liver metastases >1.5 cm.

Medullary Carcinoma In patients who have hypercalcemia at the time of thyroidectomy, only
obviously enlarged parathyroid glands should be removed
5% of thyroid malignancies The other parathyroid glands should be preserved and marked in
arises from the parafollicular or C cells of the thyroid, which, in turn, are patients with normocalcemia, as only about 20% of patients with
derived from the ultimobranchial bodies (these cells are concentrated MEN2A develop HPT
superolaterally in the thyroid lobes, and this is where MTC usually When a normal parathyroid cannot be maintained on a vascular
develops) pedicle, it should be removed, biopsied to confirm that it is a
C cells secrete calcitonin, a 32-amino-acid polypeptide that functions to lower serum
calcium levels, although its effects in humans are minimal parathyroid, and then autotransplanted to the forearm of the
Female-to-male ratio is 1.5:1 nondominant arm
Most patients present between 50 and 60 years old, although patients with
familial disease present at a younger age Total thyroidectomy is indicated in RET mutation carriers once the
Most occur sporadically mutation is confirmed
However, approximately 25% occur within the spectrum of several inherited The procedure should be performed
syndromes such as familial MTC, MEN2A, and MEN2B before age 6 in MEN2A patients
All these variants are known to result secondary to germline before age 1 in MEN2B patients
mutations in the RET proto-oncogene When the calcitonin is increased or the ultrasound suggests a
genotype-phenotype correlations with specific mutations leading to thyroid cancer, a prophylactic central neck dissection is indicated
particular clinical manifestations
Postoperative Follow-Up and Prognosis
Patients with MTC often present with a neck mass that may be associated Annual measurements of calcitonin and CEA levels, in addition to
with palpable cervical lymphadenopathy (15 to 20%) history and physical examination
Pain or aching is more common Other modalities include ultrasound, CT, MRI, and more recently,
Local invasion may produce dysphagia, dyspnea, or dysphonia FDG PET scans (reported to be superior to other radionuclide-
Distant blood-borne metastases to the liver, bone (frequently based and routine morphologic imaging)
osteoblastic), and lung occur later in the disease Prognosis is related to disease stage
Medullary thyroid tumors secrete not only calcitonin and The 10-year survival rate is approximately 80% but decreases to
carcinoembryonic antigen (CEA), but also other peptides such as 45% in patients with lymph node involvement
calcitonin generelated peptide, histaminadases, prostaglandins E2 Survival also is significantly influenced by disease type
and F2, and serotonin It is best in patients with non-MEN familial MTC, followed by those
Patients with extensive metastatic disease frequently develop with MEN2A, and then those with sporadic disease
diarrhea, which may result from increased intestinal motility and Prognosis is the worst (survival 35% at 10 years) in patients
impaired intestinal water and electrolyte flux with MEN2B
About 2 to 4% of patients develop Cushing's syndrome as a result of Performing prophylactic surgery in RET oncogene mutation carriers
ectopic production of adrenocorticotropic hormone (ACTH) not only improves survival rates but also renders most patients
calcitonin free
Pathology
Unilateral (80%) in patients with sporadic disease and multicentric in familial Anaplastic Carcinoma
cases, with bilateral tumors occurring in up to 90% of familial patients approximately 1% of all thyroid malignancies in the United States
Familial cases also are associated with C-cell hyperplasia, which declining in incidence
is considered a premalignant lesion Women are more commonly affected
Microscopically, tumors are composed of sheets of infiltrating majority of tumors present in the seventh and eighth decade of life
neoplastic cells separated by collagen and amyloid
Marked heterogeneity is present; cells may be polygonal or spindle The typical patient has a long-standing neck mass, which rapidly enlarges
shaped and may be painful
The presence of amyloid is a diagnostic finding, but Associated symptoms such as dysphonia, dysphagia, and dyspnea
immunohistochemistry for calcitonin is more commonly used as are common
a diagnostic tumor marker The tumor is large and may be fixed to surrounding structures or
These tumors also stain positively for CEA and calcitonin gene may be ulcerated with areas of necrosis
related peptide 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