Thyroid cancer approach

outlines
 Surgical anatomy of thyroid, lateral lymph node, central lymph node.
 General rules for thyroid ca surgery.
 Types of thyroid cancer (DTC, MTC,ATC, thyroid lymphoma).
 Approach to thyroid nodule:
- Important points in History and physical exam.
- Role of Ultrasound.
- Bethesda (FNA cytology report).
- Genetic study (1-DNA genotyping, 2-GEC)
 Other investigations.
 Staging: (TNM, age, grade, size, extrathyroidal extension).
 Prognosis (AGES, AMES, MACIS)
 Options of thyroid surgery in malignancy.
 Radioactive iodine therapy, hormonal therapy.
 Important Post op. complications (hypocalcemia, hematoma)

Surgical anatomy
 Anatomy, Blood supply, nerve supply to the thyroid.
 Strap muscles
 Lymph node levels:
- Central L.N & Lateral L.N
 Steps of thyroidectomy
 Important sturctures: RLN, SLN, parathyroid glands.

Thyroid anatomy
 The thyroid is a highly vascular, brownish-red gland located anteriorly in the lower neck,
extending from the level of the fifth cervical vertebra down to the first thoracic. The
gland is formed by 2 elongated lateral lobes with superior and inferior poles connected
by a median isthmus. Thyroid gland lie over the second to sixth tracheal rings. The
isthmus is encountered during routine tracheotomy and must be retracted (superiorly or
inferiorly) or divided. Occasionally, the isthmus is absent, and the gland exists as 2
distinct lobes.
 pyramidal lobe often ascends from the isthmus or the adjacent part of either lobe (more
often the left) toward the hyoid bone.
 The thyroid gland is covered by a thin fibrous capsule, which has an inner and an outer layer.
The outer layer is continuous with the pretracheal fascia, attaching the gland to the cricoid
and thyroid cartilages,via a thickening of the fascia to form the posterior suspensory ligament
of thyroid gland also known as Berry's ligament. This causes the thyroid to move up and down
with swallowing.The inner layer extrudes into the gland and forms the septae that divides the
thyroid tissue into microscopic lobules.
 Typically four parathyroid glands, two on each side, lie on each side between the two layers of
the capsule, at the back of the thyroid lobes.
 The inferior parathyroid glands usally located anterior to the RLN while the superior
parathyroid glands usually located posterior to the RLN.

anatomy
 Thyroid gland located lateral and anterior to the trachea, at the level of C5-T1 vertebrae.
 Composed of two lobes that are connected by isthmus, also pyramidal lobe may be present
(33%) extending upward from the isthmus.
 Isthmus cross tracheal cartilage 2-4
 The follicular part of the thyroid gland originate from endodermal invaginations (1st
branchial pouch) located at the base of the tongue (foramen cecum) and descends in the
midline downward through thyroglossal duct anterior to the hyoid bone to the lower part of
the neck.
 Follicular glands produce T4,T3
 parafollicular cells (c cells, clear cells) produce calcitonin  originate from pharyngeal
pouch)
 Thyroglossal duct usually disappear after birth, if persist it will form thyroglossal cyst.
 .

Blood, lymph and nerve supply:
 The thyroid is supplied with arterial blood from the superior thyroid artery, a
branch of the external carotid artery, and the inferior thyroid artery, a branch of
the thyrocervical trunk, and sometimes by an anatomical variant the thyroid ima
artery, which has a variable origin.
 The superior thyroid artery splits into anterior and posterior branches supplying the
thyroid, and the inferior thyroid artery splits into superior and inferior branches. The
superior and inferior thyroid arteries join together behind the outer part of the
thyroid lobes.
 The venous blood is drained via superior and middle thyroid veins, which drain to
the internal jugular vein, and via the inferior thyroid veins. The inferior thyroid
veins originate in a network of veins and drain into the left and right brachiocephalic
veins.
 Lymphatic drainage frequently passes the prelaryngeal lymph nodes (precricoid
or delphian L.N), and the pretracheal and paratracheal lymph nodes.
 The gland receives sympathetic nerve supply from the superior, middle and
inferior cervical ganglion of the sympathetic trunk. The gland receives
parasympathetic nerve supply from the superior laryngeal nerve and the
recurrent laryngeal nerve

Strap muscles
 The infrahyoid muscles (strap muscles) are a group of four pairs of muscles
in the anterior (frontal) part of the neck. The four infrahyoid muscles are: the
sternohyoid, sternothyroid, thyrohyoid and omohyoid muscles.
 The infrahyoid muscles either originate from or insert on to the hyoid bone.
 The term infrahyoid refers to the region below the hyoid bone, while the term
strap muscles refers to the long and flat muscle shapes which resembles
a strap. The stylopharyngeus muscle is considered by many to be one of the
strap muscles, but is not an infrahyoid muscle.
 The sternohyoid and sternothyroid muscles are joined in the midline by an
avascular fascia that must be incised to retract the strap muscle laterally in
order to access the thyroid gland during thyroidectomy. If strap muscles are
to be transected for better exposure, do so high in the neck, because the
motor nerve supply from the ansa cervicalis enters these muscles
inferiorly.

Lymph node levels
 Lymph nodes in the neck are grouped into levels I-VI,
corresponding with the submandibular and submental
nodes (level I); upper, middle, and lower jugular nodes
(levels II, III, IV); posterior triangle nodes (level V) and
central lymph nodes (level VI).
 Level VII lymph nodes are also related to the neck,
they represent the infraclavicular and mediastinal
lymph nodes.

 Level I: Submental and submandibular nodes
 Level Ia: Submental - within the triangular boundary of the anterior belly
digastric muscles and the hyoid bone.
 Level Ib: Submandibular triangle - within the boundaries of the anterior
belly of the digastric muscle, the stylohyoid muscle and the body of the
mandible
 Level II: Upper jugular nodes (Subdigastric nodes) - around the upper
third of the internal jugular vein and adjacent accessory nerve. The upper
boundary is the base of the skull and the lower boundary is the inferior border
of the hyoid bone. The anterior/medial boundary is the stylohyoid muscle and
the posterior/lateral one is the posterior border of the sternocleidomastoid
muscle.
 Level IIa: Anterio-medial to the vertical plane of the accessory nerve.
 Level IIb: Postero-lateral to this plane.
 Level III: Middle jugular nodes - around the middle third of the internal
jugular vein, from the inferior border of the hyoid to the inferior border of the
cricoid cartilage. Antero-medially they are bounded by the lateral border of the
sternohyoid muscle and postero-laterally by the posterior border of the
sternocleidomastoid.

 Level IV: Lower jugular nodes - around the lower third of the internal jugular vein
from the inferior border of the cricoid to the clavicle, anteromedially by the lateral border
of the sternohyoid and posterolaterally by the posterior border of the
sternocleidomastoid.
 Level V: Posterior triangle nodes - around the lower half of the spinal accessory nerve
and the transverse cervical artery, and includes the supraclavicular nodes. The upper
boundary is the apex formed by the convergence of the sternocleidomastoid and
trapezius muscles, and inferiorly by the clavicle. The anteromedial border is the posterior
border of the sternocleidomastoid and the posterolateral border is the anterior border of
the trapezius.
 Level VA: Above the horizontal plane formed by the inferior border of the anterior
cricoid arch, including the spinal accessory nodes.
 Level VB: Lymph nodes below this plane, including the transverse cervical nodes
and supraclavicular nodes (except Virchow's node which is in IV).
 Level VI: central compartment nodes - Pretracheal, paratracheal, precricoid (Delphian)
and perithyroid nodes, including those on the recurrent laryngeal nerve. The upper
border is the hyoid, the lower the suprasternal notch, and the lateral borders the
common carotid arteries.
 The American Joint Committee on Cancer (AJCC) system differs from the above by
including Level VII (the infraclavicular and mediastial L.N)

Steps of thyroidectomy
 1. Anesthesia: General anesthesia with Endotracheal intubation
 2. Position: Supine with neck hyper-extended by placing a sand-bag
under shoulder; table titled to 30° anti-trendelenburg position to
reduce venous engorgement.
 3. Kocher’s thyroid incision: Transverse “collar” incision, 2 finger
breadths above the suprasternal notch from one sternocleidomastoid
to another
 4. Development of subplatysmal plane:
 Skin flaps retracted together with platysma – upper flap raised upto
thyroid cartilage and lower flap upto sternoclavicular joint.
 Investing layer of deep cervical fascia is opened longitudinally
between strap muscles and between anterior jugular veins.
 5. Retraction of strap muscles: Away from thyroid

Steps of thyroidectomy
 6. Exposure of thyroid gland: through vertical division of pretracheal fascia
 7. Ligation of middle thyroid vein: 1st vein to be ligated
 8. Mobilization of thyroid and ligation of vessels in series: Superior
followed by inferior
 9. Division of Berry’s ligament: Separation of isthmus and thyroid lobe
from trachea
Note: Parathyroids must be identified and Recurrent laryngeal nerve should
be identified and saved in Beahr’s or Riddle’s triangle formed by Common
carotid artery, Inferior thyroid artery and tracheo-esophageal groove.
 10. Removal of thyroid: Based on the type of thyroidectomy – the
procedure may be repeated on the other side as well
 11. Wound closure:

General rules of thyroid ca surgery
 There is many controversy thyroid cancer management, but general rules are similar in
all centers around the world.
 Exceptions are always present in approaching thyroid cancer.
 Approach to thyroid nodule depend on 4 essential parameters:
1- history and physical exam 2-TSH, T4
3- neck US 4-FNA (bethesda)
 No single parameters is sufficient to give you a final decision.
 Assessment of lateral L.N is done before surgery by physical exam and US and FNA for
any enlarged lateral Lymph nodes. Also preceding to thyroidectomy before evaluation of
lateral lymph groups is not an option.
 Assessment of central lymph node by direct inspection intra-operatively.
 Modified Lateral neck dissection is done only for pathology confirmed (by FNA) involved
lymph nodes.
 No rule for prophylactic lateral neck dissection in thyroid cancer in contrast to
prophylactic central neck dissection.
Prophylactic central neck dissection usually done in 4 cases: 1- for all MTC, 2- for DTC larger
than 4 cm in size, 3- for any patient with lateral lymph node involvement, 4-MEN2
syndrome.

 The decision to perform lateral neck dissection must be taken before performing thyroid surgery.
 The entire lymph node level should be removed, no berry picking of lymph node.
 Baseline surgery for MTC is total thyroidectomy and central neck dissection.
 Baseline surgery for PTC is total thyroidectomy (exception might be is papillary microcarcinoma)
 FTC cannot be diagnosed by FNA so diagnostic lobectomy with completion thyroidectomy within 2 weeks might be an
option.
 Theraputic Lobectomy or subtotal thyroidectomy are not acceptable options for management of thyroid CA except in
papillary microcarcinoma).
 Routine Laryngoscopy is essential before thyroid surgery in almost all centers.
 Thyroglobulin might be used for follow up surveillance to screen for recurrence of DTC only if total thyroidectomy was
performed.
 Bethesda 5 and bethesda 6 are approached in the same way (unless you have a pathology ward at your hospital with the
ability to perform frozen section biopsy so the pathologist will give you a final diagnosis while you still in the operation
room).
 The patient must be euthyroid before surgery.
 Assessment of carotid arteries by stethoscope is essential before surgery.
 Test for RET mutation, pheochromocytoma and calcium level is essential before surgery for MTC.
 RAI therapy works for DTC (PTC, FTC) because they originate from follicular cells, it does not work for MTC (originate
from parafollicular cells) or ATC.
 Drain placement do not protect the patient from hematoma formation postop.
 Post op. Hematoma must be evacuated without delay (at bedside if the patient have respiratory compression, or in the
OR if the patient is stable).

Types of thyroid ca
1- Differentiated Thyroid Cancer (papillary TC, follicular TC):
- most common thyroid CA.
- Good prognosis, respond to RAI (with few exceptions)
- Originate from follicular cells.
- Many subtypes the worst is insualr variant.
- Psammoma bodies in PTC.
- PTC spread via L.N, FTC spread via blood.
- Hurthle cell carinoma is subtype of folicular CA, it’s usually multifocal,
bilateral with low iodine uptake.
- The general approach and management is almost similar in PTC and
FTC, with little differences:
- Cytopathology (FNA) cannot differentiate between follicular CA and
benign follicular adenoma  histopathology (diagnostic lobectomy) is
required.
- BRAF mutation.

Papillary thyroid cancer
 Pathology
 Papillary thyroid cancer gets its name from the papillae among its cells, visible on
microscopy.
 Characteristic Orphan Annie eye nuclear inclusions (nuclei with uniform staining, which
appear empty due to powdery chromatin and marginal micronucleoli), and psammoma
bodies on light microscopy. The former is useful in identifying the follicular variant of
papillary thyroid carcinomas.
 Lymphatic spread is more common than hematogenous spread
 Multifocality is common
 The so-called Lateral Aberrant Thyroid is actually a lymph node metastasis from
papillary thyroid carcinoma.
 Papillary microcarcinoma is a subset of papillary thyroid cancer defined as measuring
less than or equal to 1 cm. Management strategies for incidental papillary
microcarcinoma on ultrasound (and confirmed on FNAB) range from total
thyroidectomy with radioactive iodine ablation to observation alone.
 Several variants are recognized, although classical papillary thyroid carcinoma is the
most frequent; microscopic, follicular variant, diffuse sclerosing variant, tall cell
variant, columnar cell variant, hobnail variant, insular variant.
 Thyroglobulin can be used as a tumor marker for recurrence if total thyroidectomy was
done.

Follicular Thyroid cancer
FTC
 It is impossible to distinguish between follicular adenoma and carcinoma on
cytological grounds.
 If fine needle aspiration cytology (FNAC) suggests follicular neoplasm, thyroid
lobectomy should be performed to establish the histopathological diagnosis.
 Histologic Features for the diagnosis of follicular carcinoma are capsular
invasion and vascular invasion by tumor cells.
 Still, focuses of the capsular invasion should be carefully evaluated and
discriminated from the capsular rupture due to FNA penetration resulting in
WHAFFT (worrisome histologic alterations following FNA of thyroid).
 Follicular carcinoma tends to metastasize to lung and bone via the
bloodstream.
 Hurthle cell thyroid cancer is often considered a variant of follicular cell
carcinoma. Hurthle cell forms are more likely than follicular carcinomas to be
bilateral and multifocal and to metastasize to lymph nodes. Like follicular
carcinoma, unilateral hemithyroidectomy is performed for non-invasive
disease, and total thyroidectomy for invasive disease.
 Thyroglobulin can be used as a tumor marker for recurrence if total
thyroidectomy was done.

3- medullary thyroid cancer (MTC):
- Originate from Parafollicular cells which produce calcitonin.
- Usually spread via lymph nodes.
- Calcitonin is a marker, also CEA.
- Amyloid deposits seen in cytopatholgy.
- 25% of MTC are familial (MEN2a, MEN2b, FMTC).  RET oncogene.
- Before operation of patients with MTC, the patient should be tested for RET
mutation, pheochromocytoma and parathyroid hyperplasia should be
investigated and managed before preceding to MTC surgery.
- In MEN2 syndromes priority of surgery is for pheochromocytoma.
- 1st family members should also be screened for RET mutations and prophylactic
thyroidectomy should be offered for any family member with RET mutation.
- -baseline surgery for MTC is total thyroidectomy with central neck dissection.
- Prophylactic thyroidectomy for affected famliy members is done as early as
possible (early in infancy for MEN2B, within 5 years of age for MEN2A).

4- anaplastic thyroid ca:
- Rare tumor, aggressive type, usually present in
advanced stages, surgery as palliative treatment for
respratory compression.
- Poor iodine uptake, worst prognosis

5- primary thyroid lymphoma:
-usually associated with hashimoto’s thyroiditis.
Hashimoto thyroiditis is type 4 autoimmune disease (lymphocyte
mediated so there is increase risk of lymphoma)
-present as rapidly enlarging neck mass.
-large B-cell non-hodgkin lymphoma.
-FNA might not diagnose it, flowcytometry increase the diagnostic
accuracy, core biopsy might be indicated for final diagnosis.
-B symptoms of lymphoma might be present (night sweating, weight loss,
itching)
-treatment with chemotherapy (CHOP prtocol) and radiotherapy.
-rule of surgery: for core biopsy and for refractory disease not responding
to chemoradiotherapy (total thyroidectomy), and for compressing
symptoms).
**CHOP protocol (Cyclophosphamide, Hydroxydaunorubicin, Oncovin,
Prednisone).

MEN2 syndromes
RET mutation
 Multiple endocrine neoplasia-2 (MEN2a & MEN2b) are associated with
increased risk for MTC.
 RET oncogene mutation results in the development of MTC and other
endocrine tumors in MEN2 syndromes.
 MEN2a: PTHP, MTC, pheochromocytoma,:
- Patients with MEN2a syndrome should be offerred close follow up and
screening with US and calcitonin levels. And should undergo
prophylactic total thyroidectomy before age of 5 years.
- Bilateral central neck dissection should be performed if thyroid nodule
> 5mm is detected on US or if calcitonin levels are elevated.
- MEN2B: MTC, Pheo, marfanoid body habitus, neuromas:
- Patients with MEN2B (more aggressive mutation) should be offerred
prophylactic total thyroidectomy and bilateral central neck dissection
immediately after birth and not beyond 1 year of age.

Rule of surgery in thyroid cancer
 Surgerical options for thyroid cancers is indicated for 4 main reasons, including the following:
1- therapeutic:
-Theraputic total thyroidectomy or near total thyroidectomy in PTC, FTC, MTC.
-theraputic lobectomy (hemithyroidectomy) in papillary microcarcinoma (if the patient have no risk factors in history and
physical exam and no lymph node involvement).
2-diagnostic:
-diagnostic lobectomy might be performed if FNA report was bethesda 4 (follicular neoplasm), the excised lobe well be
sent for histopatholgy, if FTC is diagnosed then completion thyroidectomy within 2 weeks is recommended.
-diagnostic lobectomy in case history & physical exam or US findings are inconsistent with FNA report (e.g. if us sound
features are suspicious of malignancy but FNA report is reassuring (benign or normal)).***
-diagnostic lobectomy in case of bethesda 5 might be performed with completion thyroidectomy in the next 2 weeks if the
histopatholgy confirm maligancy.***
-diagnostic incisional biopsy if thyroid lymphoma is suspected and the FNA report is equivalent.
3-prophylactic:
-prophylactic total thyroidectomy in case of carriers of RET mutation (MEN2 syndromes)
4-palliative:
Palliative isthmectomy or total thyroidectomy in ATC or refractory thyroid lymphoma.
*** if your hospital has pathology ward that is able to perform frozen section of the excised lobe and give you the final
diagnosis while you still in operation room , then you might proceed to total thyroidectomy (if malignancy was
confirmed by frozen section).
***frozen section works for diagnosing MTC,ATC, PTC but it cannot diagnose FTC (same as FNA issue).

Intraoperative consultation
and
Frozen section during diagnostic lobectomy
 The frozen section procedure is a pathological laboratory procedure
to perform rapid microscopic analysis of a specimen. It is used most
often in oncological surgery. The technical name for this procedure
is cryosection.
 The intraoperative consultation is the name given to the whole
intervention by the pathologist, which includes not only frozen section
but also gross evaluation of the specimen, examination of cytology
preparations taken on the specimen (e.g. touch imprints), and
aliquoting of the specimen for special studies (e.g. molecular pathology
techniques, flow cytometry).
 Usually intraoperative consultation is done for 3 main reasons:
1- to confirm malignancy (in case of suspicious lesion or indeterminate
lesion).
2-to confirm negative margins during resection of a lesion.
3- to evaluate sentinel lymph nodes (especially in breast cancer).

 The reason to perform a frozen section biopsy of the thyroid gland during an
operation is to provide a rapid diagnosis that will determine the extent of
surgery.
 After the thyroid is removed, while the patient is still asleep, the surgeon sends
it to the pathology to be examined under the microscope.
 frozen section biopsies performed for certain types of thyroid nodules
(follicular or Hurthle cell neoplasms) is of limited value because the
pathologist needs to examine the entire nodule to see if there is growth (i.e.
invasion) of cells outside the nodule. Typically a frozen section will only look at
one or two slices of the nodule and not the whole thing.
 Intraoperative consultation (frozen section) is most useful when a biopsy
before surgery reveals findings suspicious for papillary thyroid cancer or
findings that are indeterminate. Up to 50-75% of patients with a preoperative
biopsy, suspicious for papillary thyroid cancer, are found to have cancer in their
surgical specimen.
 Since papillary carcinoma has distinct findings that can be evaluated
adequately under the microscope during surgery, the diagnosis of papillary
carcinoma can be made in the majority of cases with a frozen section.
Intraoperative consultation
and
Frozen section during diagnostic lobectomy

Case 1
 30 y/o male present to clinic for incidental finding of
thyroid nodule by CT scan, the patient does not
complain of neck pain or dysphagia or hoarsness of
voice, no weight loss, no B symptoms, thyroid function
test within normal, no palpable cervical lymph nodes,
US was done to evaluate the nodule and the lateral
neck nodes reveal a pure cystic thyroid nodule
measure 1 cm in size, FNA was done and the report was
bethesda 2 (benign lesion), what is the next step?

Case 1
 Next step is take good history, because the patient have
family history of 3 first degree relatives died of thyroid
cancer, one died due to malignant HTN during elective
operation for inguinal hernia.
 This patient is considered at high risk for thyroid cancer
mostly he have RET mutation and MEN2 syndrome.
 So you need history, physical exam, US, FNA all together to
make a decision.
 Next step will be genetic study to confirm RET mutation,
then total thyroidectomy and central neck dissection is a
must if RET mutation is present.

Case 2
 40 y/o female previously healthy present to clinic
when she noticed swelling in her neck, the patient
have no alarming symptoms, no history of radiation
exposure, no family history of thyroid cancer, physical
exam reveal right lobe thyroid mass move with
swallowing, no lateral lymph node enlargement,
thyroid function test is normal, US reveal 4 cm
spongiform nodule within right thyroid lobe, FNA
report bethesda 2 (benign), what is the next step?

Case 2
 Again Next step is take good history.
 The patient have 2 first degree relatives died of colon
cancer, due to APC gene mutation (familial adenomatous
polyposis syndrome), also the patient is carrier for this
mutation.
 FAP is assoscicted with many cancers including colon
cancer and thyroid cancer.
 Also the size of the nodule is suspicous of malignancy (4
cm).
 Even if FNA reporort suggest benign disease, the history
and the size of nodule by US measures are suggestive of
cancer, so always hope for the best but expect the worst.

Case 2
 This nodule need further investigations, reassuring the
patient is not appropriate in this scenario.
 Either we repeat FNA or perform diagnostic
lobectomy, or offer genetic study.
 If diagnostic lobectomy is reassuring then close
observation (every 3-6 months) would be a good
choice.
 Also the patient should be advised to do colonoscopy
to r/o colon cancer because she is APC carrier and
prophylactic total colectomy is recommended.
 Screening Mammogram is also recommended.

Case 3
 60 y/o radiologist present to clinic c/o neck pain for
the past 4 months, no alarming signs or symptoms, no
family history of thyroid cancer or cancers associated
with thyroid cancer, physical exam for both the
thyroid gland and lateral lymph nodes is reassuring,
thyroid fucntion test within normal, US done to
evaluate thyroid and lateral lymph nodes reveal 5 mm
hypoechoic lesion with irregular borders and
microcalcification in the right thyroid nodule, US
guided FNA was done and report bethesda 3 (atypia
with undetermined significance), what is the next
step?

Case 3
 Being a radiologist put this patient at increased rick of
thyroid malignancy due to accidental radiation
exposure, also neck pain for 4 months duration is not
reassuring, although the size of nodule is small (5mm),
other US features are suspicious for malignancy,
putting all these alarming findings with FNA report of
bethesda 3, the propability of having thyroid cancer is
extremely high.
 Options in this case include:
1- repeat FNA or 2-do genetic study for the FNA
sample or 3-perform diagnostic lobectomy.

Case 4
 30 y/o female present to clinic c/o heat intolerance,
weight loss, tremor, and irregular menstrual cycle for
the past 4 months, no family history of malignancy, no
history of radiation exposure, no hoarseness of voice,
physical exam reveal diffusely enlarged thyroid gland,
TSH level is below normal range and T4 is elevated.
 What is the next step?

Case 4
 This patient have signs, symptoms and lab findings of
hyperthyroidism, so the next step is to perform
radioactive iodine uptake scan to evaluate the thyroid
gland.
 The patient underwent RAI scan, and the results are
shown in the next slide 

Case 4
 The RAI image represent a clod nodule in the left thyroid lobe, with diffuse
increase uptake in the remaining gland. (cold nodule and graves disease at
the same time)
 this cold nodule was incidentally found during RAI study (thyroid
incidentaloma).
 Any thyroid incidentaloma must be evaluated with US and FNA.
 So this cold nodule need further investigations with US, FNA.
 This is a true case-report of Warthin variant of Papillary thyroid
carcinoma with lymph nodal metastases in a patient with Graves'
disease.

Approach to thyroid nodule
 Usually thyroid CA present as thyroid nodule, other presentation might include
hoarsness of voce, neck pain, dysphagia, etc…
 Approach to thyroid nodule depend on 4 essential parameters:
1- history and physical exam 2-TSH, T4
3- neck US 4-FNA (bethesda)
- It’s important to see if the nodule is hot or cold nodule because the approach differ.
- Hot nodules rarely to be malignant, In contrast to cold nodule which have 5% risk
of malignancy.
- The first step in assessment is history, important questions include asking the
patient about symptoms of hyperthyroidism or hypothyroidism, history of ionizing
radiation exposure (accidental, diagnostic, theraputic), personal history of cancer,
family history of cancer, compressive symptoms, hoarsness of voice, B-symptoms,
symptoms related to any cancer associated with thyroid cancer
(pheochromocytoma, hypercalcemia, colon ca (FAP is associated with thyroid ca),
carney complex, cowden syndrome, neuromas).
- 2nd step is physical exam, full exam focusing on neck exam including both central
and lateral neck, and supraclavicular L.N, assessment of the nodule.

- 3rd step is TSH, free T4, to assess for thyroid status.
- If patient have symptoms of hypothyroidism or the patient is euthyroid (normal TSH, T4) then
the nodule should be evaluated by US.
- If the patient have signs and symptoms of hyperthyroidism or have elevated T4 or decrease
level of TSH then the next step should be Radioactive Iodine uptake scan to see if the nodule is
hot or cold nodule.
- If there is single hot nodule (toxic adenoma) or multiple hot nodule (multinodular goiter
“plummer disease”) or diffuse increase uptake (graves disease) then act accordingly.
- - nodule + hyperthyroidism  RAI scan
- - nodule + euthyroid or hypothyroid  US
- If any cold nodule is present regardless of how many hot nodules are there, then US is
recommended.
- Any cold nodule should be evaluated by US and usually FNA is required thereafter.
- As we said before no single parameter is sufficient to give you a clear roadmap for
management, you have to consider all the 4 parameters all together in order to make a decision.

Which of the following need FNA?

Ultrasound in thyroid disease
 Ultrasound is recommended for any cold nodule found by RAI scan or for any euthyroid or
hypothyroid patient with thyroid nodule.
 US must assess both the thyroid nodule and the lateral lymph node groups.
 US findings (with history and physical exam) decide if you need to do FNA or not.
 Almost always you will do FNA for cold nodule with one exception **
 What is important in US is size and characteristics of the nodule.
 Size of nodule is extremly important as nodule greater than 4 cm in size very likely to be
malignant and must be evaluated with FNA even if the characterstics are suggestive of benign lesion.
 Characteristics suggestive of malignancy include:
Irregular borders, incomplete halo, solid component, hypoechogenicity, microcalcification,
punctuate calcification, coarse calcification, central vascularity, rim calcification, taller than width.
 Characteristics of benign disease include:
hyperechogenicity, regular borders, purely cystic, peripheral vascularity, complete halo, peripheral
calcification, spongiform feature.
 Any nodule with suspicous features on US must be evaluated by FNA regardless of the size.
 Any nodule in a patient who have risk factors of thyroid CA by history or physical exam must be
evaluated by FNA.
** cold nodule that are less than 1 cm in size and us characterstics are completely bengin and the patient
does not have any risk of malignancy in the history and physical exam might be closely observed
without FNA.
 So almost all cold nodules must be evaluated by FNA.

TIRAD
Thyroid Imaging Report And Data system

Thyroid FNA report (Bethesda)
 By doing FNA we sample cells for pathology assessment (cytopathology) which
mean you evaluate features of cells (N:C ratio, chromatin content, mitotic activity,
size of cell, size of nucleus, shape of cell, degree of differentiation).
 Cytopathology do not assess the tissue as a whole and do not assess for invasion,
which is a job of Histopatholgy.
 The sensitivity and specificity ratios for FNAC in published series range between
65% and 98% for sensitivity and 73-100% for specificity.
 In follicular cancer and in follicular variant of PTC (FVPTC) the cells looks similar
to normal thyroid cells so we cannot diagnose follicular cancer based on FNA
(because it assess the cells), in order to diagnose follicular CA we need to see if
there is invasion of the thyroid capsule or blood vessels (histopatholgy assessment
by excisional biopsy).
 Bethesda is the FNA cytology report of thyroid disease.
 Bethesda have 6 categories; the management differ for each category.

General rules in Bethesda report
 1st and most important rule is you have to consider history, physical exam, US in addition
to FNA to guide you for management, you cannot rely on FNA alone to make a decision.
 Bethesda 1 (nondiagnostic/unsatisfactory) simply we repeat FNA under US guidance.
 Bethesda 2 (benign)  clinical follow up.
 Bethesda 3 (undetermined significance)  genetic study (syqthyII “BRAF”, GEC), or
repeat FNA, or close observation, or diagnostic lobectomy.
 Bethesda 4 (Follicular neoplasm), here we are not sure about what we are dealing with, it
could be FTC or benign follicular adenoma or FVPTC. In this case we have many options
to do, either diagnostic lobectomy with completion thyroidectomy within 2 weeks if
cancer is confirmed, or total thyroidectomy, or genetic study, or repeat FNA, or close
observation. ***
 bethesda category 5 (suspicious for malignancy (PTC,MTC,ATC))  either diagnostic
lobectomy or total thyroidectomy.
 Bethesda category 6 (proved malignancy (PTC,MTC,ATC))  total thyroidectomy +-
central neck dissection
 ***in case of bethesda 4 and the patient have high risk by history (radiation
exposure) or if the nodule is larger than 4 cm or there is another nodule in the
contralateral thyroid lobe then total thyroidectomy is the preferred choice.

Genetic study
 Two types of genetic tests are available when dealing with or
suspecting thyroid cancer.
 1st test use DNA genotyping (ThySeqII) to test for 115 mutations
in genes including BRAF, RET, RAS, PAX8 and other common
mutations in thyroid cancer.
 2nd test use mRNA microarray (Gene Expression Classifier GEC)
also known as “Afirma test” to test for 142 gene expression
mutations related to thyroid cancer.
 These tests are used in three situations:
1- in case of bethesda 3 or bethesda 4 to rule out or rule in
thyroid cancer.
2- in case we already diagnose MTC and before doing surgery, we
have to test for RET oncogene to r/o MEN2 syndrome.
3- for screening family members of a patient with thyroid cancer.

Other investigations
 Other investigations might be necessary for staging thyroid
cancer including CT, PET/CT, FDG-PET, MRI, I-whole body
scan, bone scan.
 For DTC further investigations are not routinely done
unless there is evidance of extrathyroidal extension by
ultrasound.
 some centers recommend PET/CT scan as part of routine
investigations for any patient with MTC.
 CT, PET/CT is indicated in case of ATC to assess for and
distant metastasis which makes the tumor unresectable.
 CT or PET scan might be ordered if the history, physical
exam or routine laboratory tests suggest metastasis.

Staging of thyroid CA
 Staging of thyroid CA differ according to the type:
1- for DTC staging depends on TNM, age, extrathyroidal
extension, size, grade.
Age is important in staging DTC, because The TNM stage
groupings for these cancers take this fact into account. So,
all people younger than 45 years with these cancers are
stage I if they have no distant spread and stage II if they
have distant spread.
2- for ATC: All anaplastic thyroid cancers are considered
stage IV, reflecting the poor prognosis for people with this
type of cancer.
3- MTC: Age is not a factor in the stage of medullary thyroid
cancer.

Prognostic Indicators in
Differentiated Thyroid Carcinoma
 The most important indicator for prognosis in DTC is the TNM stage as
early stages indicate good prognosis.
 Other important indicators including the age at presentation (which
also affect staging), tumor grade, size, extrathyroidal extension, among
others.
 Several models are available to estimate the overall prognosis
including: AGES, AMES, MACIS, EORTC, OSU, MSKCC, NTCTCS.
 AGES = patient age, histologic grade of the tumor, tumor extent
(extrathyroidal invasion or distant metastases), and size of the primary
tumor.
 AMES = patient age, presence of distant metastases, extent and size of
the primary tumor.
 MACIS = metastasis, patient age, completeness of resection, local
invasion, and tumor size.

Surgical options for thyroid cancer
 Surgery for thyroid cancer have 3 main parts including:
1- the thyroid gland (thyroidectomy)
2-central lymph nodes (central neck dissection)
3-lateral lymph nodes (modified radical neck
dissection)
 Depending on cancer type, the extent of the disease
and the risk factors; the management vary from close
observation up to total thiroidectomy with central
neck dissection and modified lateral neck dissection.

thyroidectomy
 Options of thyroidectomy in thyroid cancer include the following:
1- diagnostic lobectomy in some cases of follicular neoplasm (bethesda4) or
suspecious of malignancy (bethesda 5) or even in bethesda 3 (AUS) or when
the FNA results does not match with the history and US findings. (completion
thyroidectomy might be necessary).
2-therapeutic lobectomy in low risk patients with small PTC <1 cm, with no lymph
node involvment and no extrathyroidal extension and no high risk from the
history.
3-therapeutic total or near-total thyroidectomy: in PTC.
4-theraputic total thyroidectomy with central neck dissection in MTC.
5-prophylactic total thyroidectomy and central neck dissection: in patients with
MEN2b syndrome.
6- 5-prophylactic total thyroidectomy +- central neck dissection: in patients with
MEN2a syndrome.  central neck dissection if calcitonin is elevated or in the
presence thyroid nodule > 5mm.
7-isthmectomy: as palliative treatment of ATC with respiratory compression.

thyroidectomy
 Types:
1-total thyroidectomy
2-near total thyroidectomy: removal of entire thyroid gland and keeping less than 1 gram of thyroid tissue
in one or both sides near ligament of berry.
3-subtotal thyroidectomy: removal of entire thyroid tissue and keeping more than 1 gram on one or both
side. Subtotal thyroidectomy is not an option in thyroid malignancy.
4- hemithyroidectomy
5- Completion thyroidectomy: when you perform diagnostic lobectomy and the results reveals
malignancy, you complete total thyroidectomy preferred within 2 weeks, to avoid adhesions and
difficult anatomy.
------------------------------------------------------------------------------------------------------------------------------
 Follicular neoplasm (bethesda 4) we have many options: either total thyroidectomy or diagnostic
lobectomy with completion thyroidectomy in 2 weeks if FTC was diagnosed by lobectomy.
 PTC total thyroidectomy is indicated (unless the tumor is < 1 cm in size, no risk factors from history,
no lymph nodes involved, low grade tumor, in this case lobectomy might be a choice).
 MTC: basline surgery is total thyroidectomy with central neck dissection regardless of size, even if
lymph nodes are not involved.
 ATC: usually palliative treatment.

Lateral neck dissection
 Lateral neck dissection:
- Lateral neck dissection is only done for pathology proven
involvement of lateral lymph node groups.
- Lateral lymph nodes should be assessed with US, and FNA
for any enlarged or suspicious L.N.
 Types of lateral neck dissection include:
1- radical neck dissection
2-modified radical neck dissection
3-selective neck dissection
 Modified lateral neck dissection spares the SCM muscle,
internal jugular vein and the spinal accessory nerve (CN11).

Radical Neck Dissection:
 This procedure is an en bloc clearance of all fibrofatty
tissue from one side of the neck, including the lymph
nodes from levels I-V and lymph nodes that surround the
tail of the parotid gland, the spinal accessory nerve, the
internal jugular vein, and the sternocleidomastoid muscle.
 Radical neck dissection does not include the removal of
the postauricular, suboccipital, perifacial, buccinator,
retropharyngeal, or central compartment nodes.
 Previously used for neck cancer of any stage, from
microscopic to bulky nodal disease, this procedure is now
limited to patients with advanced neck disease, recurrent
disease after chemoradiation, or gross extracapsular spread
to the spinal accessory nerve, sternoclaidomastoid muscle,
and the internal jugular vein.

Modified Radical Neck Dissection
 This operation involves the removal of the same lymph node
groups as those involved in the radical neck dissection (levels I-
V) but requires preservation of 1 or more of the following 3
nonlymphatic structures: the spinal accessory nerve, the
internal jugular vein, and the sternomastoid muscle. The
structure or structures preserved should be specifically indicated
in the name of the procedure (eg, modified radical neck
dissection with preservation of accessory nerve and internal
jugular vein).
 Modified neck dissection is indicated for clinically palpable
metastatic neck disease.
 Conversion to the radical neck dissection becomes necessary
upon gross involvement of the nerve, vein, and muscle, although
the involvement of all 3 is unusual, except in very advanced (N3)
disease.

Selective Neck Dissection
 This term refers to a type of neck dissection in which
one or more lymph node groups are preserved.
 selective neck dissections classified into the following
categories: supraomohyoid neck dissection (levels I, II,
III), lateral neck dissection (levels II, III, IV), anterior
compartment neck dissection (VI), and posterolateral
neck dissection (levels II, III, IV, V).

Central neck dissection:
- Central lymph nodes include pretracheal, paratracheal and
the delphian lymph nodes.
- Central neck dissection is indicated in the following
conditions:
1- any MTC.
2- DTC larger than 4 cm.
3- lateral lymph nodes involvement.
4-any enlarged central lymph nodes seen during
thyroidectomy for cancer.
5-prophylactic dissection in patients with MEN2b or in
MEN2a syndrome when a thyroid mass >0.5 cm is
identified during close observation.

Radioactive iodine therapy
 Iodine 131 is used for theraputic purposes in DTC. (iodine-123 is used for diagnostic
purposes).
 Iodine-131, in higher doses than for thyrotoxicosis, is used for ablation of remnant thyroid
tissue following complete thyroidectomy to treat DTC.
 131I ablative treatment of differentiated thyroid cancer with radioiodine should be
considered in the postsurgical management of patients with:
1- a maximum tumor diameter greater than 1.0 cm
2- or with a maximum tumor diameter less than 1.0 cm in the presence of high-risk
features such as aggressive histology (Hürthle cell, insular, diffuse sclerosing, tall cell,
columnar cell, trabecular, solid, and poorly differentiated subtypes of papillary
carcinoma),
3- lymphatic or vascular invasion, lymph node or distant metastases,
4-multifocal disease,
5- capsular invasion or penetration, perithyroidal soft-tissue involvement.
5- an elevated antithyroglobulin antibody level after thyroidectomy (so that scintigraphy
can be used for surveillance).
 The treatment of very low and low-risk thyroid cancers with 131I is controversial, as most
data suggest no statistically significant improvements in disease-specific survival,
although the recurrence rates may decrease

RAI
 Patient preparation:
- A state of iodine deficiency should be induced to increase 131I uptake. For
a sufficient time before the contemplated therapy, patients must
discontinue use of iodide-containing preparations and other
medications that could potentially affect the ability of the thyroid
tissue to accumulate iodide. Water-soluble iodinated contrast medium
should not have been administered for at least 6–8 wk
- The serum TSH should exceed about 30 μIU/mL to maximize 131I uptake.
The data to support 30 μIU/mL as a number representing the threshold
of optimal stimulation is more a matter of consensus than the result of
detailed scientific study. This may be achieved in 1 of 2 ways. First,
thyroid hormones may be withheld for a time sufficient to permit an
adequate rise in TSH (>30 μIU/mL). This is at least 10–14 d for
triiodothyronine (T3) and usually 3 wk for thyroxine (T4) . TSH may
not rise to this level if a large volume of functioning tissue remains or if
hypopituitarism is present. Second, thyrotropin-α (rhTSH) may be
used.

RAI Administration of I-131 for ablation
 Typical therapeutic doses of I-131 are between 2220-7400 megabecquerels (MBq). Because
of this high radioactivity and because the exposure of stomach tissue to beta radiation
would be high near an undissolved capsule, I-131 is sometimes administered to human
patients in a small amount of liquid. Administration of this liquid form is usually by
straw which is used to slowly and carefully suck up the liquid from a shielded container.
 Post-treatment isolation
- Ablation doses are usually administered on an inpatient basis, and the International
Basic Safety Standards recommend that patients are not discharged until the activity falls
below 1100 MBq.
- Patients receiving I-131 radioiodine treatment may be warned not to have sexual
intercourse for one month (or shorter, depending on dose given), and women told not to
become pregnant for six months afterwards.
- I-131 will be eliminated from the body over the next several weeks after it is given. The
majority of I-131 will be eliminated from the human body in 3–5 days, through natural
decay, and through excretion in sweat and urine. Smaller amounts will continue to be
released over the next several weeks, as the body processes thyroid hormones created
with the I-131. For this reason, it is advised to regularly clean toilets, sinks, bed sheets and
clothing used by the person who received the treatment. Patients may also be advised to
wear slippers or socks at all times, and avoid prolonged close contact with others. This
minimizes accidental exposure by family members, especially children

Thyroid hormonal replacement after
surgery
 levothyroxin is the drug of choice, and replacment usually start after RAI
therapy or immediately after surgery if RAI is not planned.
 Thyroid hormone replacement therapy after thyroidectomy in thyroid cancer is
not only required to replace endogenous TH, but it is generally thought to
inhibit tumor growth indirectly by its negative feedback effects on pituitary
TSH secretion.
 Differentiated thyroid cancer expresses the TSH receptor on the cell membrane
and responds to TSH stimulation by increasing the expression of several
thyroid-specific proteins (thyroglobulin, sodium-iodine symporter) and by
increasing the rates of cell growth.
 Suppression of TSH, using supraphysiological doses of L-T4, is used
commonly to treat patients with thyroid cancer in an effort to decrease the risk
of recurrence.

Levothyroxin after surgery
 Current ATA guidelines recommend the following:
- maintaining TSH levels below 0.1 mU/L in patients with
persistent disease indefinitely in the absence of specific
contraindications.
- In patients with a biochemically incomplete response to therapy
the serum TSH should be maintained between 0.1 and 0.5 mU/L,
taking into consideration the initial ATA risk classification.
- In patients who are clinically and biochemically free of disease,
but who presented with high-risk disease, consideration should
be given to maintaining TSH suppression with TSH levels of 0.1–
0.5 mU/L for 5 years.
- In patients free of disease and with low risk for recurrence the
serum TSH may be kept within the low normal range (0.5–2
mU/L)

Post op complications
1- hematoma: because of the limited space in neck
region, hematoma formation might compress the
trachea and lead to airway obstruction and it’s
considered a life threatening condition.
Neck hematoma must be evacuated immediately, either
at bed side if the patient is unstable, or at the OR if the
patient is stable.
Post op drain placement do not protect the patient from
hematoma formation.
Evacuate the hematoma by opening the skin, platysma
and strap muscles.

 Hypocalcemia:
- transient (most common) due to manipulation of parathyroid glands during
operation.
- Permanent due to resection of parathyroid glands.
- Signs & symptoms of hypocalcemia include: perioral numbness, muscle spasm,
chovestk’s sign, trossuos’s sign.
- If parathyroid glands were accidently removed during operation, they must be
autotransplanted (small 1mm slices) in the SCM, arm, or forearm.
 Some centers recommend measuring PTH 2-4 hours after thyroidectomy in
order to identify any parathyroid injury.
 Measuring calcium levels 6 hours after surgery help recognize and manage
hypocalcaemia early to prevent any life threatining arrhythmia.
 IV calcium glocunate is the treatment of choice for life threatining
hypocalcaemia.
 Daily Oral calcium supplementation is the treatment of choice for permanent
hypoparathyroidism.
Post op complications

Thyroid cancer approach

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