Download Medullary thyroid cancer

MEDULLARY THYROID
CANCER
Dr. M. Sofi MD; FRCP (London);
FRCPEdin; FRCSEdin
Medullary thyroid cancer (MTC) is a form of thyroid
carcinoma which originates from the parafollicular cells (C
cells), which produce the hormone calcitonin. Medullary
tumors are the third most common of all thyroid cancers.
Sporadic, or isolated, MTC accounts for 75% of cases, and
inherited MTC constitutes the rest.
Inherited MTC occurs in association with multiple endocrine
neoplasia (MEN) type 2A and 2B syndromes, but non-MEN
familial MTC also occur
Outcome depends on extent of disease, nature of tumor
biology, and overall efficacy of surgical treatment.
Advances in genetic testing in have revolutionized the
management of this disease
Characteristics of Medullary Thyroid Cancer
• Occurs in 4 clinical
settings and can be
associated with other
endocrine tumors
• More common in
females than males
(except for inherited
cancers)
• Regional metastases
(spread to neck lymph
nodes) occurs early in
the disease
• Spread to distant organs
occurs late and can be
to the:
–
–
–
–
Liver,
Bone
Brain
Adrenal medulla
• Usually originates in the
upper central lobe of
the thyroid
Characteristics of Medullary Thyroid Cancer
• Poor prognostic factors
include mean:
• Older than 50 years old
• Distant spread
(metastases)
• In patients with other
endocrine tumors due to
MEN II-B syndrome.
• Residual disease
(following surgery) or
recurrence can be
detected by measuring
calcitonin hormone:
• Should be measured
every 4 months for the
first few years and then
every 6 months for the
rest of life
History
A specific constellation of symptoms of medullary thyroid
carcinoma (MTC) is not usually noted; however, one or more of
the following symptoms may be observed:





Patients may describe a lump at the base of the neck, which
may interfere with swallowing or become more prominent
Patients with locally advanced disease may present with
hoarseness, dysphagia, and respiratory difficulty
Although uncommon, patients may present with various
paraneoplastic syndromes, including Cushing or carcinoid
syndrome
Diarrhea may occur from increased intestinal electrolyte
secretion secondary to high plasma calcitonin levels
Distant metastases (e.g., lung, liver, bone) may result in
weight loss, lethargy, and bone pain
Common symptom
Neck lump: A single lump on • Coughing: Thyroid cancer
the front of the neck is the
can sometimes cause a
most common symptom. It’s
persistent cough.
often discovered during a
• Trouble swallowing
routine physical exam.
(dysphagia): If a thyroid
• Neck pain: Pain in the front
tumor becomes large enough,
of the neck may be related
it can press on the esophagus
to the growth of a thyroid
and make swallowing
tumor. This pain can also
difficult.
extend to the ears.
• Shortness of breath
• Hoarseness: If cancer has
(dyspnea): Similar to trouble
spread to that vocal cord, it
swallowing, if a thyroid tumor
can affect the quality of
is large enough it can push
voice.
against the windpipe and
interfere with breathing.
Common symptom
• Severe diarrhea: The
tumor produces high levels
of a hormone-calcitonin, a
prostaglandin that may
cause severe diarrhea.
• Cushing syndrome:
Although uncommon,
patients may present with
various paraneoplastic
syndromes, including
Cushing or carcinoid
syndrome
• Facial flushing: A red face,
neck, or chest paired with
warm or burning sensations
may occur
• Bone pain: People with
medullary thyroid cancer
may have bone pain if the
cancer has spread to form
bone lesions.
• Lethargy: Many people with
advanced cancer may feel
physically, emotionally, or
mentally tired.
• Weight loss: Unusual
weight loss is a symptom of
advanced medullary thyroid
cancer that has spread
beyond the thyroid into
other organs.
Physical
• Physical examination may
demonstrate a dominant
thyroid nodule at the base
of the neck.
• Palpable cervical
lymphadenopathy signifies
disease that has progressed
locally.
• Abdominal pain, jaundice,
and rarely, bone
tenderness may occur in
patients with systemic
metastases.
Causes
Medullary carcinoma of
thethyroid (MTC) has a
genetic association with
multiple endocrine
neoplasia (MEN) 2A and
2B; however, it is heritable
by a non-MEN mode of
transmission.
Sporadic MTC occurs in 75%
of patients, and familial
MTC constitutes the other
25%. Mutations in RET can
lead to MTC development
in cells derived from neural
crest tissue.
Classification of multiple endocrine neoplasia type 2
Type 2A
Type 2B
MEN2A classical (medullary thyroid
cancer, pheochromocytoma,
Medullary thyroid cancer
primary hyperparathyroidism)
MEN2A with cutaneous lichen
Pheochromocytoma
amyloidosis
MEN2A with Hirschsprung disease Other
Familial medullary cancer without
pheochromocytoma or parathyroid
hyperplasia
Mucosal neuromas
Intestinal ganglioneuromas
Marfanoid habitus
Differential diagnosis
• Anaplastic Thyroid
Carcinoma
• De Quervain
Thyroiditis
• Follicular Thyroid
Carcinoma
• Goiter
• Graves Disease
• Hyperthyroidism
• Intestinal Carcinoid
Tumor
• Medullary Thyroid
Carcinoma
• Papillary Thyroid
Carcinoma
• Thyroid Lymphoma
• Thyroid Nodule
• Toxic Nodular Goiter
• Type 2 Multiple
Endocrine Neoplasia
Laboratory Studies
Preoperative laboratory testing in patients with possible
medullary thyroid carcinoma (MTC) has three purposes:
1. To predict the extent of metastatic disease; this will
determine the extent of preoperative imaging and may
alter the surgical approach
2. In patients with MEN 2, to identify primary
hyperparathyroidism and/or pheochromocytoma —
comorbid conditions that alter the surgical approach
and surgical priorities
3. To identify RET mutation carriers so that testing of
appropriate family members can allow for early
diagnosis and treatment of affected individuals
Calcitonin
• Calcitonin is the principal
biochemical marker in
MTC; it is used for
detection, staging,
postoperative management,
and prognosis. The higher
that the calcitonin levels are
above normal, the greater
the likelihood of MTC; basal
levels of >100 pg/mL have
been found to have 100%
positive predictive value for
MTC.
Screening studies in
patients with MEN
• 24-hour urinalysis for
catecholamine metabolites
(e.g., VMA, metanephrine)
to rule out concomitant
pheochromocytoma in
patients with MEN type 2A
or 2B.
• Pheochromocytoma must
be treated before MTC.
• Obtain screening for the
development of familial
MTC in family members of
patients with a history of
MTC or MEN 2A or 2B
Imaging Studies
Patients in whom medullary
thyroid carcinoma (MTC) is
diagnosed or suspected on
the basis of fine needle
aspiration findings or
calcitonin levels should
undergo preoperative
ultrasonography to detect
lymph node metastases.
The study should include the
superior mediastinum and
the central and lateral neck
compartments
Patients with regional lymph
node involvement or calcitonin
levels >400 pg/mL should
undergo preoperative CT
scanning of the chest and neck,
as well as 3-phase, contrast
enhanced, multidetector liver
CT or contrast-enhanced MRI
imaging (MRI) to detect
metastatic disease
Fine-needle aspiration yields
cytologic information, allowing
diagnosis of MTC.
Medullary
thyroid
carcinoma on
ultrasound
with typical
small
calcifications
(arrows)
Fine needle aspirate with immunostaining for calcitonin in medullary cancer of the
thyroid. The nuclei of the tumor cells are placed eccentrically and are larger and more
pleomorphic than those of normal follicular cells. Immunocytologic staining for
calcitonin is positive (brown staining which is best seen at the arrow). The background
contains many red cells that nonspecifically take up the stain.
Surgical specimen showing typical histologic appearance
of medullary cancer.
Treatment
Surgery and radiation
therapy have been the
major treatments for
medullary thyroid
carcinoma.
A total thyroidectomy with
bilateral neck dissection
is the gold standard for
treating medullary
thyroid cancer, and is the
most definitive means of
achieving a cure in
patients without distant
metastases or extensive
nodal involvement.
Treatment
Radiation
• External beam
radiotherapy is
recommended when there
is a high risk of regional
recurrence, even after
optimum surgical
treatment
• Unlike other differentiated
thyroid carcinoma, there is
no role for radioiodine
treatment in medullarytype disease
Protein kinase inhibitors
• Block the abnormal kinase
proteins involved in the
development and growth of
medullary cancer cells,
response in 10-30%
• Vandetanib the first drug
approved by FDA for latestage (metastatic) MTC in
patients ineligible for surgery.
• Side effects of this drug
include hypertension,
nausea, diarrhea, cardiac
electrical abnormalities,
thrombotic or bleeding
episodes.