by Dr.

LILY DENEKE(GSR2)

Moderator Dr.TADESSE(Oncologist)

MEDULLARY THYROID CANCER

 INTRODUCTION

 Thyroid malignancy occurs with relative

infrequency.
 In the US, thyroid cancer accounts for <1% of all
malignancies (2% of women and 0.5% of men)
and
 is the most rapidly increasing cancer in women.
 Papillary thyroid ca represents around 80% of the
caes followed by follicular ca 10% and MTC 5-10%
 Anaplasic ca accounts for 1-2% cases
 In Ethiopia in reseach done in Tikur anbessa and
Gonder hospital the prevalance of thyroid ca was
around 7.3%
 In the research the leading malignancy was
PTC- 45.2%
FTC-29%
Hurtle cell 1.6%
MTC 1.6%
 The incidence of the disease is 3x higher in women
than in male
 Most patients present with a palpable
swelling in the neck, which initiates
assessment through a combination of history,
physical examination,and FNAB.
 Medullary thyroid ca

 MTC accounts for about 5% of thyroid

malignancies.
 arises from the parafollicular or C cells of the
Thyroid.
C cells are neural crest cell and produce
calcitonine, lowers serum calcium level
 These cells are concentrated superolaterally
in the thyroid lobes, and this is where MTC
usually develops.
 The 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
 About 75% of MTC occur sporadically
 25% are familial
 FMTC consists MEN 2A,MEN2B, And FMTC
 They are inherited in autosomal dominant pattern
 Children born with inheriting FMTC have a 100%
risk of developing FMTC
 MEN2A consists of mtc,pheochromocytoma in
50% and hyperthyrodism mostly develops during
second decades of life
 MEN2B
consistsMTC,pheochromocytoma,marfanoid
habitus and gangloneuromatosis and has the
most aggressive behavior developing by the age
of 10 year
 FMTC consists only MTC,usually develops during
adulthood
 All these variants are known to result secondary
to germline mutations in the RET proto-
oncogene
 The syndromes also are characterized by
genotype-phenotype correlations, with
specific mutations leading to particular
clinical manifestations.
 Clinical presentation

 neck mass
 palpable cervical lymphadenopathy(15% to 20%)
 Pain or aching is more common in patients with
these tumors,
 local invasion may produce symptoms of
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 CEA, but also other peptides such
as calcitonin gene–related peptide,
histaminadases, prostaglandins E2 and F2α, and
serotonin.
 Patients with extensive metastatic disease
frequently develop diarrhea,
 About 2% to 4% of patients develop Cushing’s
syndrome as a result of ectopic production of
ACTH
 PATHOLOGY

 Fairy well circumscribed

 Unencapsulated
 Tannish pink and often contain yellow granular
region
 Sporadic tumors are unilateral, and inherited forms
usually involve both thyroids lobes
 In stroma cxc of amyloid deposits are observed and
this a unique feature to MTC
 This amyloid has typical green birefringece on
congo red staining
 The unique feature of FMTC is finding of C
cell hyperplasia which help in distinguishing
familial cases from sporadic cases
 Diagnosis

 The diagnosis of MTC is established by

history,physical examination, raised serum
calcitonin, or CEA levels,and FNAB cytology of
the thyroid mass.
 Attention to family hx,risk of FMTC is 25%
 all new patients with MTC should be screened for
RET point mutations, b/c difficult to distinguish
familial from sporadic
 Calcitonin and CEAare used to identify patients
with persistent or recurrent MTC.
 Stimulating calcitonine release by using iv
pentagstrine
 Primary tumor (T)
 TX = Primary tumor cannot be assessed
 T0 = No evidence of primary tumor
 T1 = Tumor ≤2 cm in greatest dimension limited to the thyroid
 T1a = Tumor ≤1 cm in greatest dimension limited to the thyroid
 T1b = Tumor >1 cm but ≤2 cm in greatest dimension limited to the thyroid
 T2 = Tumor >2 cm but ≤4 cm in greatest dimension limited to the thyroid
 T3 = Tumor >4 cm limited to the thyroid, or gross extrathyroidal extension invading only strap muscles
 T3a = Tumor >4 cm limited to the thyroid
 T3b = Gross extrathyroidal extension invading only strap muscles (sternohyoid, sternothyroid, thyrohyoid,
or omohyoid muscles) from
 a tumor of any size
 T4 = Includes gross extrathyroidal extension beyond the strap muscles
 T4a = Gross extrathyroidal extension invading subcutaneous soft tissues, larynx, trachea, esophagus, or
recurrent laryngeal nerve from
 a tumor of any size
 T4b = Gross extrathyroidal extension invading prevertebral fascia or encasing the carotid artery or
mediastinal vessels from a tumor of
 Regional lymph nodes (N)
 NX = Regional lymph nodes cannot be assessed
 N0 = No evidence of locoregional lymph node metastasis
 N0a = One or more cytologically or histologically confirmed benign lymph nodes
 N0b = No radiologic or clinical evidence of locoregional lymph node metastasis
 N1 = Metastasis to regional nodes
 N1a = Metastasis to level VI or VII (pretracheal, paratracheal, or
prelaryngeal/Delphian, or upper mediastinal) lymph nodes. This can
 be unilateral or bilateral disease.
 N1b = Metastasis to unilateral, bilateral, or contralateral lateral neck lymph
nodes (levels I, II, III, IV, or V) or retropharyngeal lymph nodes
 Distant Metastasis (M)
 M0 = No distant metastasis
 M1 = Distant metastasis
 Management

 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 prophylactic centralneck node
dissection should be routinely performed.
 neck and chest CT and a triplephase liver CT
or contrast-enhanced MRI and an axial
MRI/bone scan is recommended to asses
distant mets
- if there is palpable cervical LN
- calcitonin level >500 pg/mL,
-symptoms and signs of distant disease
 In patients with no distant disease but nodal
involvement, an ipsilateral or bilateral lateral
neck dissection (levels IIA, III, IV, and V) is
performed.
 prophylactic lateral neck dissection if central
neck lymph nodes are involved or if the
primary tumor is ≥1.5 cm.
 In the case of locally recurrent or widely
metastatic disease,tumor debulking is
advised not only to ameliorate symptoms of
pain, flushing, and diarrhea, but also to
decrease risk of death from recurrent central
neck or mediastinal disease.
 External-beam radiotherapy can be considered for
patients
-with resected T4 disease
- for patients with unresectable residual or
recurrent tumor
- symptomatic bony metastases
 Liver metastases tend to be multiple and are
typically not amenable to resection, percutaneous
ethanol ablation,or radiofrequency ablation.
chemoembolization may be helpful
 therapies directed against the RET kinase
 Vandetanib and cabozantinib for the
treatment of advanced and progressive MTC
they prolong progression-free survival, in
addition to reducing secretion of calcitonin
and CEA.60,61
 They are recommended as first-line systemic
therapy in symptomatic patients with
advanced MTC
Prophylactic total
thyroidectomy

 Children with MEN2A (designated high-risk)

are advised to undergo thyroidectomy at <5
years of age
 those with MEN2B-related mutations
(designated highest-risk) should undergo the
procedure before age 1
 In general, in patients with less aggressive
mutations (designated ATA moderate-risk),
thyroidectomy may be delayed >5 years,
- if there is a normal annual serum calcitonin,
neck ultrasound, less aggressive
family history, or family preference
 When the calcitonin is increased or the
ultrasound suggests a thyroid cancer, a
prophylactic central neck dissection is indicated
Postoperative Follow-Up and
Prognosis.
 Patients are followed by annual
measurements of calcitonin and CEA levels, in
addition to history and physical examination
 Prognosis is related to disease stage
 The 10-year survival rate is approximately
80% but decreases to 45% in patients with
lymph node involvement
 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 of 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.
 Referance

 Shwartz’s principles of surgery 11th ED

 Sabiston textbook of surgery 21st ED
 Uptodate 2020
 Medscape