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7 Medullary Thyroid Cancer
57
Treatment [2, 4]
• Surgery is the only available potentially curative therapy for MTC.
• The extent of surgery is determined by preoperative ultrasound and intraopera-
tive ndings.
• Patients with MTC and no evidence of lymph node involvement on ultrasound
should undergo total thyroidectomy with bilateral central neck (level VI) lymph
node dissection due to high rates of locoregional lymph node metastases.
– If positive nodes are found in the central neck, lateral neck dissection of the
involved side may be considered.
• Patients with MTC with evidence of lateral neck (levels II, III, IV) lymph node
involvement should undergo total thyroidectomy with central neck lymph node
dissection AND modied radical neck dissection of the involved side(s).
• Patients with known MEN syndrome may undergo prophylactic total thyroidec-
tomy and bilateral central neck lymph node dissection at an early age in accordance with guidelines for MEN.
• Controversy exists on the role of prophylactic lateral neck dissection in the
absence of lymph node involvement for patients with known heritable MTC.
• There is no role for thyroid lobectomy in patients with a known preoperative
diagnosis of MTC.
• If MTC is diagnosed in a surgical specimen after a thyroid lobectomy, comple-
tion thyroidectomy or observation with serial calcitonin/CEA measurements and
thyroid ultrasounds can be utilized.
• All patients with incidental MTC and a RET germline mutation diagnosed post-
operatively require completion thyroidectomy and bilateral central neck lymph
node dissection. The lateral neck may be managed based on imaging ndings.
Post-Operative Management [1, 2, 4]
• All patients will need to initiate therapy with thyroid hormone replacement fol-
lowing total thyroidectomy.
• Thyroid function tests should be evaluated 4–6weeks after initiating therapy,
and dose adjustment performed based on TSH levels. There is no role for suppression of TSH as C-cells are not responsive to TSH.
• There is no role for adjuvant radioactive iodine in the treatment of MTC as
C-cells do not concentrate iodine.
• Adjuvant external beam radiation can be considered in select cases at high risk
for recurrence, or for treatment of recurrent disease.
58
Stage Definion Treatment Ten-Year Survival**
and tumor characteriscs.
J. E. Passman and H. Wachtel
Surveillance andManagement of Recurrent Disease [1, 2, 4]
• Cancer staging is determined after surgery and incorporates imaging and histo-
pathologic ndings (Fig.7.2).
• Serum calcitonin and CEA should be measured 2–3months after surgery and
then regularly surveilled thereafter. Serum calcitonin and CEA doubling times
are sensitive and specic markers for disease progression. As part of surveillance, patients should also receive periodic physical examination and neck
ultrasound.
• Detectable calcitonin levels after surgical resection are concerning for residual or
recurrent disease. Neck ultrasound or CT should be performed to assess for local
recurrence.
• Elevated calcitonin levels (>150pg/mL) after surgery may be indicative of dis-
tant metastases or persistent disease. Cross-sectional imaging of the chest, abdomen, pelvis, and bone scans should be performed. The liver is the most common
site for distant metastases (45% of patients with advanced disease).
• Patients with persistently very high calcitonin levels (>500pg/mL) after surgery
may be best evaluated with FDG PET CT.
• Surgical excision or radiation can be used for localized disease.
• Widespread systemic disease is treated with systemic targeted therapies.
• Conventional chemotherapies are not effective.
I Tumors < 2cm without spread beyond the
II Tumors >2cm contained to the thyroid or
III Tumors of any size with metastac central
IV Tumors of any size with distant metastases,
** Paents with sporadic and inherited MTC generally have the same survival rates accounng for age
Fig. 7.2 Staging of medullary thyroid cancer [1–3, 8]. ** Patients with sporadic and inherited
MTC generally have the same survival rates accounting for age and tumor characteristics
thyroid
tumors of any size with gross extrathyroidal
extension involving the strap muscles
neck lymph node involvement, with or
without extra-thyroidal extension to the
strap muscles
lymph node involvement in the lateral neck,
or gross invasion of other structures in the
neck beyond the strap muscles
Total thyroidectomy
with central neck lymph
node dissecon
Total thyroidectomy
with central neck lymph
node dissecon
Total thyroidectomy
with central AND lateral
neck lymph node
dissecon
Dependent on extent of
local and distant disease
100%
93%
71%
21%
7 Medullary Thyroid Cancer
59
References
1. Hadoux J, Pacini F, Tuttle RM, Schlumberger M.Management of advanced medullary thyroid
cancer. Lancet Diabetes Endocrinol. 2016;4(1):64–71.
2. Tuttle RM. Medullary thyroid cancer: surgical treatment and prognosis. Waltham, MA:
UptoDate; 2021.
3. Tuttle RM.Medullary thyroid cancer: clinical manifestiations, diagnosis and staging. Waltham,
MA: UptoDate; 2022.
4. Wells SA Jr, Asa SL, Dralle H, Elisei R, Evans DB, Gagel RF, et al. Revised American
Thyroid Association guidelines for the management of medullary thyroid carcinoma: the
American Thyroid Association guidelines task force on medullary thyroid carcinoma. Thyroid.
2015;25(6):567–610.
5. Cameron JL, Cameron AM. Current surgical therapy E-book. Amsterdam: Elsevier Health
Sciences; 2016.
6. Randle RW, Balentine CJ, Leverson GE, Havlena JA, Sippel RS, Schneider DF, etal. Trends
in the presentation, treatment, and survival of patients with medullary thyroid cancer over the
past 30 years. Surgery. 2017;161(1):137–46.
7. Cornellis J, Lips DWB.Clinical manifestation and diagnosis of multiple endocrine neoplasia
type 2. Waltham, MA: UptoDate; 2021.
8. Rosen J, Lloyd R, Brierley J, Grogan R, Haddad R, Hunt J, et al. Thyroid—medullary. In:
AJCC cancer staging manual; 2017. p.891–901.
Chapter 8
Anaplastic Thyroid Cancer, Metastasis
totheThyroid, andThyroid Lymphoma
JessicaLiuMcMullin andAndreaGillis
Anaplastic Thyroid Cancer
Introduction
– Anaplastic thyroid cancer (ATC) is a rare and very aggressive form of thyroid
cancer that exhibits rapid growth at the time of presentation.
– ATC is a very invasive tumor that often metastasizes both locally in the neck and
to distant organs.
Epidemiology
– ATC represents ~2% of thyroid cancers, but accounts for ~30% of thyroid cancer-
related deaths [1].
– Affects one to two million people per year with a median survival of 4–5months
and a 1year survival rate of ~10–20%, making it one of the most deadly malig-
nancies in humans [2, 3].
– Median age at presentation is 60–70years with a 2–3:1 female to male ratio [4].
– 50% of all ATC patients present with metastatic disease at diagnosis [5].
J. L. McMullin
Department of Surgery, University of Utah, Salt Lake City, USA
e-mail: Jessica.McMullin@hci.utah.edu
A. Gillis (*)
Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA
e-mail: agillis@uabmc.edu
Switzerland AG 2024
R. M. Gartland, J. A. Lee (eds.), Endocrine Surgery Clerkship, Contemporary
Surgical Clerkships, https://doi.org/10.1007/978-3-031-62091-1_8
61© The Author(s), under exclusive license to Springer Nature
62
J. L. McMullin and A. Gillis
Staging
– Given their aggressive nature, all ATCs are considered Stage IV thyroid cancer.
– With the most recent American Joint Committee on Cancer (AJCC) 8th edition
Tumor, Node, Metastasis (TNM) system, anaplastic tumors now use the same T
category denition as for differentiated thyroid cancers [6].
Stage IVA includes T1–T3a disease without lymph node disease and no distal
metastasis.
Stage IVB includes T1–T3a disease with positive lymph nodes, or T3b–T4
disease with any nodal status.
Stage IVC is any ATC with distant metastasis [6].
History andPhysical Exam
– Patients with ATC will often present complaining of a rapidly growing neck mass.
– This growth can occur in patients without any previously known thyroid disease
as well as in patients with known thyroid cancer or goiters that suddenly grow.
– Other symptoms include compression from mass effect causing dyspnea, dys-
phagia, dysphonia, voice hoarseness, and/or neck pain/tightness.
– It is important to examine for cervical lymphadenopathy, as ATC has often
metastasized to local lymph nodes by the time of presentation.
Diagnosis
– A ne-needle aspiration (FNA) should be performed in order to diagnose
ATC.This can be done with the assistance of ultrasound guidance.
– Patients should also undergo basic labs including thyroid function tests.
– ATC can be difcult to diagnose by biopsy alone and it may not be diagnosed
until after (attempted) surgical resection.
Imaging
– Imaging should be performed with an ultrasound to examine the tumor size,
tumor borders (often irregular), the involvement of surrounding structures, and to
examine the local cervical lymph node involvement.
– A computerized tomography (CT) scan of the neck may also be helpful to iden-
tify the local extent of disease (Fig.8.1).
8 Anaplastic Thyroid Cancer, Metastasis totheThyroid, andThyroid Lymphoma
Fig. 8.1 Example CT scan of the neck of a 66-year-old male patient with anaplastic thyroid cancer; *=Thyroid cancer; Arrow=example of tracheal deviation caused by mass effect; +=lateral
neck lymphadenopathy on both right and left
63
– A CT scan of the chest can also be utilized to localize distant metastasis which
tend to occur in the lung rst [5].
– ATCs and their metastasis can also be detected by positron emission tomography
(PET) scans of the chest, abdomen, and pelvis, which may be a helpful additional
imaging modality.
Treatment
– Treatment for ATC involves a multi-disciplinary approach and includes conver-
sations on prognosis and goals of care.
– Treatment options may include complete surgical resection, systemic chemo-
therapy, external beam radiation therapy (EBRT), and/or targeted therapeutics in
a variety of sequences.
– Even with aggressive treatments, the 1-year mortality is reported at 81% accord-
ing to a study using the Surveillance, Epidemiology, and End-Results (SEER)
database [3].
Surgery
– While surgical resection remains the most effective treatment for cure, the
advanced presentation of ATC can often limit the effectiveness of surgical treat-
ment with only a small percentage of patients receiving a complete R0 resection
(margins negative for microscopic disease).
– Surgery is most helpful in those with limited locoregional disease (Stages IVA
and IVB).
64
J. L. McMullin and A. Gillis
– Symptomatic relief may be provided with palliative tumor debulking, which may
reduce the effect of compressive symptoms. However, palliative surgical inter-
vention is controversial and should be tailored toward the patients’ goals of care.
– The ideal operation is a total thyroidectomy with selective lymphadenectomy to
clear as much disease as possible.
Systemic Chemotherapy
– Systemic chemotherapy, most often with cisplatin, doxorubicin, and taxanes, can
be used in the treatment of ATC although the survival benet is unclear.
External Beam Radiotherapy
– External beam radiotherapy (EBRT) is another treatment option available
for ATC.
– EBRT is typically started 2–3weeks after surgery when being used.
– EBRT can be used for denitive therapy with curative intent or for palliative
purposes to improve symptoms and control airway compression.
Targeted Therapeutics
– It is recommended that molecular proling of tumor samples be sent in all
patients with ATC to identify if there are any targeted therapeutics available for
treatment.
– One of the most common mutations in ATC is BRAF V600E. Those with this
mutation have been shown to benet from a combination treatment of therapeu-
tics such as Dabrafenib and Trametinib (MEK inhibitor) [7].
– There are numerous clinical trials currently being conducted on various targeted
therapies for ATC.
Surveillance
– Following treatment for ATC, frequent surveillance with cross-sectional imaging
every 1–2months for the rst year followed by every 4–6months for the follow-
ing year should be considered [1].
8 Anaplastic Thyroid Cancer, Metastasis totheThyroid, andThyroid Lymphoma
Metastasis totheThyroid
Introduction/Epidemiology
– Metastatic disease to the thyroid gland is a rare occurrence.
– In a series over an 8-year period in a single high-volume institution, only 10
cases of metastatic disease to the thyroid gland were found [8].
– In a systematic review, tumor metastasis occurred more frequently in women
with a ~1.4:1 ratio [9].
– The most common clinically detected metastasis to the thyroid gland is from
renal cell carcinoma, followed by lung, colorectal, and breast cancer [9].
– Often metastasis to the thyroid is not clinically apparent. In patients who died of
metastatic cancer, one study on autopsy evaluation found that there was metasta-
sis to the thyroid most commonly in melanoma patients, followed by breast,
lung, and renal cell cancer [10, 11]. Only 5–10% of these patients had clinically
detectable metastasis.
Diagnosis
– A thyroid metastasis is often detected incidentally during surveillance or work
up for other cancers with imaging such as CT scans, positron emission tomogra-
phy (PET) scans, neck ultrasounds, or octreotide scans.
– A thyroid metastasis may present as far out as decades after the initial cancer
diagnosis, potentially making it difcult to identify the primary tumor [9].
– Completion staging to identify additional distant metastases should be performed.
– Fine needle aspiration is the best method to diagnose metastases to the thyroid.
– Thyroglobulin antibody staining with immunohistochemistry is helpful in dif-
ferentiating between a metastasis to the thyroid and a primary thyroid malignancy.
65
Treatment
– In patients with limited metastatic disease, there may be a role for thyroidectomy
in order to conrm diagnosis or provide control of the disease in the neck.
– Typically, treatment is with a total thyroidectomy. However, the benet of surgi-
cal intervention in this patient population remains largely unknown.
– The survival of patients with thyroid metastasis is dependent on the extent of
metastases to the body as well as the staging of the primary cancer more so than
the presence of the metastasis to the thyroid [12].
66
J. L. McMullin and A. Gillis
Thyroid Lymphoma
Introduction
– Thyroid lymphoma is a rare malignancy, with an incidence of 2 per million per
year [13].
– Thyroid lymphoma can generally be divided into diffuse large B-cell lymphomas
(more common) and mucosa-associated lymphoid tissue (MALT) lymphoma.
Epidemiology
– Thyroid lymphoma typically presents between ages 50–80 and has 3:1 female to
male ratio [14].
History andPhysical Exam
– Patients often present complaining of a rapidly growing neck mass.
– Compressive symptoms are common, including pressure in the neck, stridor,
voice hoarseness, and dysphagia.
– Of those with B-cell lymphoma, up to 10% will complain of “classic” B symp-
toms such as night sweats, weight loss, and fever.
– Physical exam will demonstrate a xed, rm, and enlarged thyroid gland.
– Local lymph nodes are commonly enlarged and palpable on physical exam.
Diagnosis
– Thyroid lymphoma is often clinically confused with anaplastic thyroid carci-
noma (ATC).
– A ne needle aspiration (FNA) should be performed preoperatively to identify
thyroid lymphoma and is accurate in up to 88% of cases [15].
Imaging/Staging
– A thyroid ultrasound is often the rst imaging modality obtained (Fig.8.2).
– A computerized tomography (CT) scan of the neck should be obtained and will
demonstrate a diffusely enlarged thyroid gland.
8 Anaplastic Thyroid Cancer, Metastasis totheThyroid, andThyroid Lymphoma
Fig. 8.2 Example cervical ultrasound of a 76-year-old female patient with thyroid lymphoma. The
thyroid appears enlarged, with diffuse heterogeneous echotexture and occasional septations
*=trachea, +=strap muscles and subcutaneous tissue, solid arrow=area of diffuse heterogeneous
texture, dotted arrow=septation, bracket=enlarged adjacent lymph nodes, C=carotid, J=internal jugular vein
67
– There is often invasion into adjacent structures as well as diffuse lymphadenopa-
thy identied on CT scan.
– After diagnosis, a CT neck, chest, abdomen, and pelvis are recommended to
complete staging.
Treatment
B-Cell Lymphoma
– The standard treatment for thyroid B-cell lymphoma is typically external beam
radiation therapy (EBRT) and chemotherapy: CHOP (cyclophosphamide, doxo-
rubicin, vincristine, and prednisone).
– There is no role for surgical intervention in B-cell lymphoma.
MALT Lymphoma
– Unlike B-cell lymphoma, MALT lymphoma may benet from surgical
intervention.
– MALT lymphoma is more indolent and patients tend to present in earlier stages
of disease, thus the disease is typically conned to the thyroid.
MALT lymphoma can also be treated with EBRT, especially for extrathyroidal
disease.DisclosuresNone.