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How To Approach MTC

Sara Al-Ghanem

+Objectives

Introduction

Pathology

Classification & clinical pic.

Approach to MTC

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+ History ( from the patient )

33 y\o female pt ,G7P4+2

Medically free

No s\p

No hx of allergy

She was will till 1 year ago , when she started to suffer from neck pain in the

RT side .

While she was eating her daughter accidently noted that she has a neck

swelling on rt side .

The swelling increased in size with time

There was no skin changes or discharge coming from it

No other swelling in the body

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+

She has symptoms suggesting hypothyroidism in the form of :

cold intolerance, wt gain & malaise

also she is having compressive symptoms , like dysphagia

,hoarseness

No hx of aspiration or respiratory distress

No hx of neck radiation in childhood

FHx: her aunt has a thyroid problem ? She did know the dx &

no surgery was done for her

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+Hospital course

Initially she was dx with lymphadenitis in PHC & received a

course of Ab . But she did not improve.

U\S was arranged & upon the finding , they FNA was requested

FNA showed hashimoto thyroididtis

after that she was referred to GS , & they did excisional LN

biopsy for her .

Finally we received the pt in ENT clinic as a case of met

medullary Ca in RT cervical LN

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+ENT Plan

The patient was admitted in the hospital on Tuesday under care

of Dr.Al-Saab for further evaluation & multidisciplinary

assessment with other teams before surgery

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+On EX

By inspection of the neck:

1- there is goiter more prominent in RT side

2- scar in RT side of neck measuring about 3 cm ( in level II)

By palpation :

There swelling is located in center of the neck

moving with deglutition

More prominent in RT side ( 3*2.5 cm ) , left side ( 2*2)

Firm, not fixed to underlying skin

With no substernal extension

Bil cerviacl lymphadenopathy ( level II)

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+Labs

Calcitonin

Calcium

Metanephrine ?

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+Imaging

CT of chest & neck ?

It was done yesterday but we are waiting the report

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+Surgery Plan ?

That what I am looking for

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+Introduction

Medullary thyroid cancer (MTC) is a neuroendocrine tumor of the parafollicular

or C cells of the thyroid gland

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+Gross pathology

the tumors of MTC are typically slow-growing, and gray and

firm in appearance. Familial forms are usually multi-focal and

bilateral.

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+Microscopic features ( histology )

Histologically, MTC is characterized by uniform polygonal cells with central nuclei and finely granular eosinophilic cytoplasm.

The finding of stromal amyloid is a distinguishing feature of MTC, but is present in only one-third of cases.

C-cell hyperplasia is a precursor to malignant transformation, and is most commonly seen in familial MTC

The presence of amyloid is a diagnostic finding, but immunohistochemistry for calcitonin is more commonly used as a diagnostic tumor marker.

These tumors also stain positively for CEA and calcitonin gene–related peptide.

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+PATTERNS OF METASTASES

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MTC frequently metastasizes to regional lymph nodes, and

these metastases are often apparent at the time of diagnosis.

The frequency has been reported to be over 50% in patients

who present with palpable, established primary tumors. Spread

is most frequent to the central compartment (Level VI), followed

by the ipsilateral jugular chain of nodes (Levels II through V)

and the contralateral cervical nodes.

Spread is also seen to the upper and anterior mediastinum

Hematogenous spread may occur to the lungs, liver, bones,

brain, and soft tissues .

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+

Medullary thyroid carcinoma

(MTC) comprises 5– 10% of all

thyroid cancers.

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+MTC is a sporadic malignancy in the

majority of cases (75%), with the

remainder comprising three familial

syndromes: MEN 2A, MEN 2B, and

familial non-MEN MTC (FMTC).

MEN 2A, the most common syndrome

(up to 80% of hereditary cases)

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+Sporadic MTC

Sporadic MTC accounts for about 80 %

The typical age of presentation is in the fifth or sixth decade .

there may be a slight female preponderance

The most common presentation of sporadic MTC is that of a

solitary thyroid nodule

In most patients, the disease has already metastasized at the

time of diagnosis.

50%of patients have clinically detectable CLN involvement

15% have symptoms of upper aerodigestive tract compression.

5% have distant metastatic

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+Sporadic MTC

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Systemic symptoms may occur due to hormonal secretion

by the tumor.

Tumor secretion of calcitonin, calcitonin-gene related

peptide, or other substances can cause :

diarrhea

or facial flushing in patients with advanced disease.

In addition, occasional tumors secrete corticotropin (ACTH),

causing ectopic Cushing's syndrome.

+Inherited MTC

MEN2 is subclassified into three distinct syndromes, each

of which is transmitted in an autosomal dominant fashion

and is associated with MTC:

MEN2A

MEN2B

and familial medullary thyroid cancer (FMTC).

These syndromes result from different mutations in the

RET proto-oncogene.

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MEN2A

the most common syndrome (up to 80% of hereditary cases).

M = multi-focal, bilateral MTC 100% penetrance

P = pheochromocytoma 42% penetrance

H = hyperpar- athyroidism 10 – 30% penetrance

Less commonly, this syndrome includes a skin condition,

lichen planus amyloidosis, and/or Hirschsprung disease.

2 MPH or 2 Miles Per Hour

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+MEN 2B

MTC (also with 100% penetrance),

Marfanoid habitus.

Mucosal neuromas,ganglioneuromatosis of the gastrointestinal tract, and

megacolon. ( variable presence )

Pheochromocytoma (40% penetrance)

MMMP (Think: 3M Plastics)

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+

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FMTC is characterized by development

of MTC alone .

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+the clinical presentation and

manifestations of MEN2-associated

MTC are similar to those of sporadic

MTC.

The most common presentation is that

of a solitary thyroid nodule or cervical

lymphadenopathy.

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+Hx & PE

FNA biopsy

aided by immunocyto- chemical staining

for calcitonin.

genetic testing for

a hereditary syndrome.

Serum calcitonin and CEA

Radiologic evaluation

Testing for coexisting

tumors

STAGING

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+

Immunocytologic staining for calcitonin is

positive (brown staining which is best seen

at the arrow).

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ultrasonography of the neck is indicated to look for cervical lymph node

involvement.

For patients with local lymph node metastases on ultrasound or with

preoperative serum basal calcitonin >400 pg/mL :

indicating high risk of local or distant metastatic disease

additional imaging is required to assess for metastatic disease:

chest CT, neck CT, three-phase contrast-enhanced liver CT or contrast-

enhanced liver MRI

Radiologic evaluation

+genetic testing for a hereditary syndrome

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All patients presenting with clinically evident MTC should have

genetic testing to evaluate for a hereditary syndrome.

Approximately 6–10% of patients who present with MTC with no

family history will be found to have a germline RET mutation.

In patients at-risk for familial MTC, the availability and accuracy of

genetic screening for RET mutations has replaced yearly screening

calcitonin measurement as the primary diagnostic tool

because identification of a mutation allows diagnosis and treatment prior

to the C-cell proliferation (either through hyperplasia or cancer) necessary

to elevate calcitonin levels

+genetic testing for a hereditary syndrome

In patients at-risk for MEN 2B, genetic testing should be done

immediately after birth, because MTC is usually already established

by that time and early thyroidectomy is necessary to increase

chance for cure.

In patients at-risk for FMTC or MEN 2A, genetic screening may be

done in early childhood (before age 5 or 6), to allow planning for

preventative thyroidectomy.

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+

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Stage I —

MTCs that are less than 2 cm in diameter

without evidence of disease outside of the thyroid

gland

Stage II —

Any tumor between 2 and 4 cm

without evidence of extrathyroidal disease

Stage III —

Any tumor greater than 4 cm,

or level VI nodal metastases

or microscopic extrathyroidal invasion regardless of

tumor size

Stage IV —

Any distant metastases,

or lymph node involvement outside of level VI,

or gross soft tissue extension

+SURGICAL STRATEGY FOR MTC

the operative procedure recommended is a total thyroidectomy with a

central compartment lymphadenectomy

and parathyroid auto- transplantation,

and ipsilateral functional neck dissection (Levels II – V)

Bilateral neck dissections may be considered.

Radioactive iodine, external beam radiation therapy (EBRT), and

conventional chemotherapy have not been effective.

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Points to Remember 33

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A characteristic feature of this tumor is the production of calcitonin.

Most cases are sporadic

Medullary thyroid cancer (MTC) is a neuroendocrine tumor of the

parafollicular or C cells of the thyroid gland

For patients diagnosed with MTC on the basis of cytologic evaluation of a

thyroid nodule, evaluation should include measurement of serum

calcitonin, carcinoembryonic antigen , U\S of the neck, genetic testing for

germline RET mutations, and biochemical evaluation for coexisting

tumors, especially pheochromocytoma

Genetic analysis, along with imaging and calcitonin testing aid in

optimizing surgical resection in these cases.

+References

Current approaches to medullary thyroid

carcinoma, sporadic and familial.

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