Transcript Thyroid Cancer 2005 - University of Wisconsin–Madison

Thyroid Cancer 2005
Nancy Fuller, M.D.
University of Wisconsin-Madison
1. 52 yo woman in good health; presented
with back pain of a musculoskeletal nature.
Exam of neck: palpable right sided thyroid
nodule approx 2x3 cm; gland otherwise not
enlarged and no other nodules or
lymphadenopathy.
Ultrasound: solid nodule; uptake scan: no
excess uptake in nodule
TFTs: normal
A FNA was performed.
DX: Hurthle cell neoplasia
2. 64 yo woman with hyperlipidemia;
presented for a preventive health
exam with no complaints.
Neck exam: 4x2 cm right sided
thyroid nodule, gland otherwise
normal, no lymphadenopathy.
Ultrasound-solid nodule, uptake scan
no excess uptake in nodule. TFTs
A FNA was performed.
DX: Hurthle cell neoplasia
3. 28 yo woman presented after having
a thyroid nodule found incidentally on
a carotid ultrasound being performed
as a normal control for a study.
Exam: 2x2 cm right sided thyroid
nodule, gland otherwise normal, no
lymphadenopathy. TFTs normal
Dedicated ultrasound: solid nodule;
FNA performed that day because of
availability of pathology support
DX: Papillary thyroid carcinoma
Learning objectives:
• To learn about the epidemiology, types,
behaviors, treatment and prognosis of
thyroid cancer.
• No financial disclosures
Epidemiology
• Thyroid nodules: very common
• Clinically detectable thyroid carcinoma:
rare: <1% of all cancers
• Female to male ratio- 2.5:1
• Median age at dx: 45-50
• Overall incidence is rising:
• In 1935: 1.3/100,000 women,
.2/100,000 men
• By 1991: 5.8/100,000 women,
2.5/100,000 men
• Incidence has continued to rise in past
10 years: most rapid rate of increase in
all tracked cancers
Reason for rise?
• Neck irradiation: used between 1910
and 1960
• Better diagnosis?
BUT: only rise is in papillary type; if
better diagnosis was reason, would
expect rise in all types
Algorithm for the Cost-Effective Evaluation and Treatment of a Clinically Detectable Solitary
Thyroid Nodule
Hegedus, L. N Engl J Med 2004;351:1764-1771
Thyroid cancer: epithelial
types
Differentiated:
Papillary: 70-75 % of all thyroid cancers
Follicular: 15-25%
Undifferentiated:
Anaplastic: 2-5%
Thyroid cancer: non epithelial
Medullary thyroid cancer
• Sporadic
• Familial
• MEN-2A and B
Others:
lymphoma, mets from breast, colon,
renal and melanoma
Papillary thyroid carcinoma
Pathogenesis:
1. Activation of tyrosine kinase receptors by
rearrangement or gene amplification
• Results in a chimeric gene
• Occurs either by radiation or sporadic
2. Point mutations in BRAF gene
• 10X increased risk of thyroid cancer in
relatives of thyroid cancer patients: suggests
a genetic link
PTC
Presentation:
• Solitary nodule most common
• Pathology: typically unencapsulated;
may be cystic
Papillae: 1 or 2 layers of tumor
surrounding fibrovascular core
Follicles and colloid are typically absent
PTC
• Psommoma bodies: scarred remnants
of tumor papillae that have infarcted
• Present in half of papillary thyroid
carcinomas
PTC
Growth and behavior: minor to major
• Microcarcinoma: occult papillary
carcinoma, with tumor <1cm
• Found in up to 50% of glands at
autopsy (rarer in children)
• Incidental finding of no clinical
importance
PTC
• Other end of spectrum: aggressive
metastasis through interthyroidal lymphatic
channels to form multifocal tumors
• Involves regional lymph nodes
• At diagnosis: clinically detectable nodes more
common in children (50%) than adults
• 2-10% distant mets at dx: 2/3 pulmonary, 1/4
skeletal; also brain, kidneys, liver, adrenals
PTC
Prognosis
• Most patients do not die of their disease
• 80-95% 10 year survival rates
• Patients between 20-45: best long term
survival
• Patients older than 45 with lymph node
recurrences are most likely to die from PTC
PTC
• Prognosis is poorer in patients with
large tumors: one large series showed
cancer related mortality of 6%/2-3.9cm,
16%/4-6.9cm and 50%7 cm and above
• Several variants have a worse
prognosis: tall cell variant=1% of PTC;
more aggressive and invasive
Survival Rate among 1701 Patients with Papillary or Follicular Carcinoma and No Distant
Metastases at the Time of Diagnosis
Schlumberger, M. J. N Engl J Med 1998;338:297-306
Follicular thyroid carcinoma
• Characterized by follicular differentiation and
encapsulation
• Invasion of the capsule and blood vessels is
the main determinant between adenomas
and carcinoma
• 2 main forms: minimally invasive and widely
invasive
• Multicentricity and lymph node involvement
are less frequent than in PTC
FTC
• Minimally invasive FTC behaves more
like PTC
• Widely invasive behaves more like
anaplastic thyroid carcinoma
• Hurthle Cell variant:more aggressive
• FTC is more likely than PTC to be
nonresponsive to I 131.
Anaplastic thyroid carcinoma
• Undifferentiated tumor of thyroid follicular
epithelium
• Very aggressive, with a disease specific
mortality approaching 100%
• 2/1,000,000 annual incidence
• Typical patient is older than differentiated
carcinoma, mean age 65
• <10% under 50
• 60-70% women
ATC
• 20% of ATC: history of differentiated
thyroid carcinoma, most papillary
• 10% of Hurthle cell carcinoma: has
anaplastic tumor within
• Up to 1/2 of ATC: history of multinodular
goiter
ATC
• Presentation:
• Nearly all present with a thyroid mass
• Regional or distant spread is present 90% of
the time at dx
• Lungs, bones, brain most common mets
• Rapidly enlarging tumor; often causes
compression symptoms like dyspnea,
dysphagia, hoarseness
• Constitutional symptoms like fatigue,
anorexia, wt loss
ATC
• 50% have palpable nodes at dx
• Dx: made by FNA, then CT neck and
mediastinum, CXR
• Prognostic factors: tumor size
<6 cm=25% 2 yr survival
>6cm=3-15% 2 yr survival
Others: older age, male sex, dyspnea at
presentation
• No effective treatment for advanced or
metastatic ATC: uniformly fatal, with median
survival 3-7 mo
Treatment of differentiated
thyroid carcinoma
• Surgery: goal is to remove all tumor
tissue from neck
• Total or near total thyroidectomy
because of risk of multicentricity
• Removal of local nodes in PTC, only
palpable nodes in FTC because of
lower rate of lymph node involvement
Treatment
• I 131: given post op: destroys any remaining
normal thyroid tissue, and may destroy occult
microcarcinomas
• Increases sensitivity of subsequent 1 131
total body scans
• 4-6 wks after surgery a total body scan off
thyroid replacement with low dose 1 131; if
any uptake, a treatment dose is given (2 mCi
vs. 30-100 mCi)
• Radiation: only if surgical excision is
impossible and tissue doesn’t take up I 131
Followup
Goals of followup:
• Maintain adequate thyroxine treatment
• Detect persistent or recurrent cancer
• Recurrences usually occur early but
may occur later so follow up for life
• Thyroxine treatment goals: initial serum
thyrotropin level 0.1 or less, serum free T3
normal
• Check U/S of thyroid area and nodal areas
• Serum thyroglobulin levels: TG produced by
follicular cells-should not be detectable after
total ablation; presence signifies persistent or
recurrent disease
• 80% of patients with TG >40 have detectable
foci or I 131 uptake
• I 131 scanning: needs to be done after
withdrawal of thyroxine tx, with TSH >30
needed
• Scanning is done 3 days after I 131
given
• Low risk patients with no I 131 uptake
after 1 year: TSH maintained at low but
detectable level (0.1-0.5)
• Local or regional mets: occur in 5-20%
• Excision/I 131 tx/ Radiation tx if no I 131
uptake
• Distant mets: If I 131 uptake, high dose
I 131 given + RT
Complications of treatment:
• I 131: nausea, sialadenitis common but mild
and short duration
• Genetic defects: can’t be given to pregnant
women
• Increased risk of miscarriage in pregnancies
within 1 year of tx
• Overall relative risk of a second type of
cancer only if high cumulative dose of I 131
and/or radiation
Medullary thyroid cancer
• Much less common than epithelial
thyroid cancers
• Involves abnormalities of parafollicular
C-cells
• Most cases are sporadic
MTC
• MEN 2 A: autosomal dominant disorder
characterized by MTC, pheochromocytoma,
and primary parathyroid hyperplasia
• MEN 2 B: same inheritance; MTC +
pheochromocytoma. Occurs at a younger
age; more aggressive.
• Familial MTC: like MEN 2 A but no other
associated abnormalities
MTC
• Female to male ratio=1:1
• MEN 2 A and familiar MTC: peak in
index cases in 3rd decade
• MEN 2 B: children and teens most
common age of presentation.
• Basal serum calcitonin: usually
correlates with tumor mass and is
almost always high with palpable tumor
MTC
•
•
•
•
MTC in MEN 2 B: more aggressive
Early onset
Surgery often not curative
Death from MTC: 50% of MEN 2 B,
10 % MEN 2 A
• Cases: recap and current status