Dr. Salim Rashid Al-Qasmi and Dr. Mohammed Salim Al- Ajmi provide an outline on the approach, history, examination, investigation, diagnosis, and management of papillary and follicular thyroid cancer. The document discusses the relevant history, symptoms, and examination findings for thyroid disorders. It also covers the investigations, including thyroid function tests, ultrasound, fine needle aspiration, and diagnosis. The management of papillary thyroid cancer is then discussed in detail, including surgery, lymph node dissection, radioactive iodine therapy, thyroid hormone suppression, and prognostic factors.

1. Thyroid Malignancy
Dr. Salim Rashid Al-Qasmi
Dr. Mohammed Salim Al- Ajmi

2. Outline
Approach
Papillary thyroid cancer
Follicular thyroid cancer

3. History
Examination
Investigation
Diagnosis
Management

4. Relevant History in thyroid disorder
• The symptoms related to thyroid disorders are broadly the
following. These may be:
1. Related to the thyroid swelling
2. Pressure symptoms
3. Related to function- hyperthyroidism or hypothyroidism

5. Slow growing over years
Rapid growth over weeks to few months
Sudden growth increase in size over hrs. or days
Benign
Malignant
Hemorrhage within gland
Thyroiditis (viral/bacterial)
• Associated with pain:
1- Hemorrhage when sudden in nature
2- Related to thyroiditis
3- In later stages of advanced malignancy with local infiltration
• Location of neck swelling
• the onset
• Progression
Related to thyroid swelling:

6. Related to pressure:
• The most common obstructive symptom is difficulty in
breathing (occurs when the tracheal diameter is less than 8
mm).
• Stridor or wheezing occurs at rest (If tracheal compression
becomes severe (luminal diameter less than 5 mm).
• Cough and choking sensation
• Goiter may contribute to obstructive sleep apnea
 Esophageal compression: Dysphagia
 Compression of a recurrent laryngeal
nerve :Transient or permanent vocal
cord palsy, resulting in hoarseness
 Compression of the cervical sympathetic
chain: Horner's syndrome
Jugular vein compression or
thrombosis: dilated veins in the
neck and chest , congestion of face
and eyes

7. Asymptomatic
Hyperthyroidism
Hypothyroidism
the majority of patients with goiter are asymptomatic and biochemically euthyroid.
Hashimoto’s thyroiditis or severe iodine deficiency
Multinodular goiter (with autonomy) or Graves’ disease
Related to function:

10. Drug history:
1. Thyroxine
2. Goitrogenic substances:
 Medication: including lithium, phenylbutazone, iodide preparation (cough syrups)
 Vegetables: that contain high levels thiocyanates (cabbage, turnip)
 History of head and neck irradiation or radioiodine exposure
 History of iodine intake
 Family history of:
 Benign or malignant thyroid disease
 Autoimmune diseases (MEN syndrome)
Relevant History in thyroid disorder

11. HypothyroidismHyperthyroidism
Slow movement, looks
sleepy and tired
Nervous, anxious, agitatedBehavior
obese( fatty neck, and
shoulders
thin, wasting ( face)Body built
Wrapped up but still coldunder-clothed and sweatyDressing
Examination in thyroid disorder

12. HypothyroidHyperthyroid
Puffy, Cold, dryHands: Muscle wasting , Sweaty, moist, warm
Thyroid acropathy- clubbing of finger
due to soft-tissue swelling of the
hands
Palmar erythema
Pulse rate: BradycardiaPulse rate: Tachycardia
Rhythm: regular / irregularly irregular - atrial fibrillation
Fine tremor
Non pitting edemapreitibial myxedema
(grave’s )
Examination in thyroid disorder

13. Eye Examination:
Eye
examinations
Hyperthyroidism
(graves)
Exophthalmos
Lid lag and
retraction
Ophthalmople
gia and
diplopia Chemosis
Visual flied
defect
hypothyroidism
Periorbital
puffiness

14. Grave’s Orbitopathy
Exophthalmos
Protrusion of eyeball
Sclera become visible below the lower edge
of the iris
 result from increase retro-orbital fat,
edema and cellular infiltration
Lid lag: lid retraction in downgaze
Dalrymple sign: upper lid retraction in
primary gaze
Resulting from over-activity and local adhesion of levator paloebrea muscle to fixed
orbital tissue

15. Grave’s orbitopathy
Chemosis:
Edema of the conjunctiva
Caused by obstruction of normal venous and
lymphatic drainage of the conjunctiva by increased
retro-orbital pressure.

16. Neck Examination:
Local examination
Inspection
Swelling is in the
thyroid gland
Lower border of
extension
Skin changes and
prominent veins
Swallowing +
tongue protrusion
Palpation
Thyroid
Cervical LN
Carotid pulse and
trachea
Percussion
Retrosternal
extension or
enlarged
mediastinal
nodes
Auscultation
Bruit

17. Nodule related factors (from
the examination):
• Very firm or hard nodule
• Fixed to adjacent structures
• Associated with enlarged
lymph nodes
• Causes vocal cord paralysis
• Rapidly growing
• Symptoms if invasion of neck
structures
Features Suggestive of Thyroid malignancy
Patient related factors (from the
history):
• Age <15 years and > 60 years
• Male patients with solitary nodule
are at greater risk
• History of head and neck
irradiation particularly in childhood
• Family history of thyroid cancer or
Presence of familial syndrome
associated with thyroid cancer( eg
Gardners , FAP, Carney Complex,
MEN type 2A, 2B)

18. Investigations
• Thyroid function test (TFT):
Subclinical Hypo

19. Thyroid radioactive scan: using technetium scan
or radioactive iodine123(half life few hours)
Indications:
• assess the nature of solitary nodules (cold/
warm or hot nodules)
• Diagnosis of secondary thyrotoxicosis (to
detect the nodule which is toxic in the
presence of multiple nodules, so definitely
excised during subtotal thyroidectomy.
Investigations
Description Diagnosis
Diffuse increased uptake Graves disease
Diffuse decreased uptake Hashimoto thyroiditis
Focal areas of increased uptake and focal
areas of decreased uptake
multinodular goiter
“hot” nodule (show increased uptake
compared to the rest of the thyroid )
Benign
Low risk to be malignant
“cold” nodule 10% malignant

20. Diagnosis TSH Free T4 Notes
Thyrotoxicosis
(e.g. Graves'
disease)
Low High In T3
thyrotoxicosis
the free T4
will be normal
Primary
hypothyroidis
m (primary
atrophic
hypothyroidis
m)
High Low
Secondary
hypothyroidis
m
Low Low Replacement
steroid
therapy is
required prior
to thyroxine
Sick euthyroid
syndrome*
Low** Low Common in
hospital
inpatients
T3 is
particularly
low in these
patients
Subclinical
hypothyroidis
m
High Normal
Poor
compliance
with
thyroxine
High Normal
Steroid
therapy
Low Normal
Findings of Hyperthyroidism, what’s ur next step? >> Go
for uptake scan
Findings of Hypothyroidism, what’s ur next step? >> Go for
US (look for the criteria of malignancy), then FNAC (C1-C6)

21. Investigations
Features suggest thyroid cancer:
1- Hypoechoic
2-Solid Nodule
3-Irregular margin
4- Micro calcification
5- increase vascularity
6- nodule height more than its wide (ie, greater in its anteroposterior
dimension than its transverse dimension) has a 93% specificity for
malignancy
7-Invasion and lymph node involvement
Ultra-sound: assess the number of nodules and their nature (solid/ cystic or mixed echogenicity)

22. Investigations
Fine needle aspiration cytology (FNAC): useful in diagnosing benign conditions
( colloid goiter, thyroiditis, hemorrhagic nodule, benign cysts) and malignancy
like papillary carcinoma, medullary carcinoma, lymphoma, anaplastic
carcinoma).
C1: non-diagnostic Insufficient sample
C2:Benign 95%benign
C3:Atypia 15%malignant (FTC)
C4:Folicular neoplasm or suspicious follicular
neoplasm
25% malignant(FTC)
C5:Suspicious for malignancy 75% malignant
C6:Malignancy 95% malignant

23. A 49 year old male patient presented with a thyroid swelling of
9 months duration. It has been gradually increasing in size and
in the last 6 weeks it has been increasing more rapidly. He has
also noticed some hoarseness of voice in the past 1 month.
There is no family history of thyroid malignancy
Case Discussion
What is the most likely diagnosis?
Thyroid malignancy

24. • What features in the history will support the diagnosis?
Age
Gender.
Rapid growth of tumor.
Hoarseness of voice.
• What additional history do you need to ask to support the
diagnosis and possible predisposing factors for malignancy?
Case Discussion

25. On examination there was 4x4 cm thyroid nodule in the
right lobe. It was hard in consistency. There were
multiple cervical nodes palpable in the right lateral group
(III and IV), which are shown below.
Case Discussion
• What additional examination would you carry
out in this patient?
• What is the likely diagnosis? What abnormal clinical findings
would support your diagnosis?
• What sites would you look for blood borne metastasis?

26. What is the likely diagnosis? What abnormal clinical
findings would support your diagnosis?
• Papillary carcinoma, because of lymph nodes
involvement.
What sites would you look for blood borne
metastasis?
• Lungs, liver, bone and brain.

27. Thyroid Cancer
Primary
Well-differentiated (95%)
Papillary(80%)
Follicular(15%)
Poor differentiated(5%)
Medullary(4%)
Anaplastic (0.5%)
Lymphoma(0.5%)
Secondary

28. Type Percentage
Papillary 70% Often young females - excellent prognosis
Follicular 20%
Medullary 5% Cancer of parafollicular (C) cells, secrete calcitonin, part of MEN-
2
Anaplastic 1% Not responsive to treatment, can cause pressure symptoms
Lymphoma Rare Associated with Hashimoto's thyroiditis
Type Notes
Papillary carcinoma •Usually contain a mixture of papillary and colloidal filled follicles
•Histologically tumour has papillary projections and pale empty nuclei
•Seldom encapsulated
•Lymph node metastasis predominate
•Haematogenous metastasis rare
Follicular adenoma •Usually present as a solitary thyroid nodule
•Malignancy can only be excluded on formal histological assessment
Follicular carcinoma •May appear macroscopically encapsulated, microscopically capsular invasion is seen. Without this finding the lesion is a follicular adenoma.
•Vascular invasion predominates
•Multifocal disease raree
Medullary carcinoma •C cells derived from neural crest and not thyroid tissue
•Serum calcitonin levels often raised
•Familial genetic disease accounts for up to 20% cases
•Both lymphatic and haematogenous metastasis are recognised, nodal disease is associated with a very poor prognosis.
Anaplastic carcinoma •Most common in elderly females
•Local invasion is a common feature
•Treatment is by resection where possible, palliation may be achieved through isthmusectomy and radiotherapy. Chemotherapy is ineffective.
•Management of papillary and
follicular cancer
total thyroidectomy
•followed by radioiodine (I-131) to
kill residual cells
•yearly thyroglobulin levels to
detect early recurrent disease

29. Papillary Thyroid Cancer

30. Papillary Thyroid Cancer
The dramatic increase in incidence of papillary thyroid cancer
in the United States appears to be due in part to an
increased detection of small papillary cancers
Most common Thyroid cancer .

31. Most prevalence before the age of 40years
Female : male 2.5:1
Predisposing
previous head and neck radiation.
Family history of thyroid cancer in a first-degree relative
Lymph nodes spread is common but distant metastasis is
rare
Appears as irregular solid or cystic
mass or nodule in a normal
thyroid parenchyma
Papillary Thyroid Cancer

32. • Thyroid cancer typically presents as a thyroid nodule:
• history of rapid nodular growth
• fixation of the nodule to surrounding tissues
• new onset hoarseness or vocal cord paralysis
• the presence of ipsilateral cervical lymphadenopathy
all raise the
suspicion that a
nodule may be
malignant.
Papillary thyroid carcinoma:
clinical presentation

33. Papillary thyroid carcinoma:
Histology
• Most are characterized by the presence of papillae
consisting of one or two layers of tumor cells
surrounding a well-defined fibrovascular core.
• Variant forms:
 Follicular (most common)
 Tall cell / columnar
 Diffuse / sclerosing/ clear cell
 Trabecular / Hurthle cell
 Poorly differentiated
variants particularly tall cell and poorly
differentiated have aggressive course
and associated
with a poorer prognosis and may
require
aggressive treatment

34. Follicular variant
Columnar cell variant

35. • The diagnosis is established by characteristic cellular feature.
Nuclear grooves
Nuclear overlapping
Nuclear crawding
Nuclear inclusion
Nuclear clearing
Psammomma body (fibrovascular stroma with calcium deposits)
Orphan Annie nucleus (intranuclear cytoplasmic inclusion)
Papillary thyroid carcinoma: FNAC

36. Psammomma body

37. Pre-op investigations :
• CBC/coagulation screen/LFT/U&E, blood grouping, cross match
• blood sugar, ECG, CXR
• TFT: medical management of hyperthyroidism→ to avoid the risk of thyroid storm
• A serum calcium level
• Laryngoscopy
• US and CT neck: extension, tracheal deviation, endoscopic intubation, to create a cervical node map!)
Papillary thyroid carcinoma:
Management

38. Total thyroidectomy is the optimal surgery, Why?
• Because it commonly multicentric and multifocal
• Facilitates post operative radioactive iodine screening for
micrometastasis of thyroid cancer by removal of all thyroid tissue in the
neck
• To monitor the recurrence of the tumor (thyroglobulin)
Papillary thyroid carcinoma:
Management
 Surgery:
- If less than 1 cm and no LN > Hemithyroidectomy
- If 1 cm or more + LN >> Total Thyroidectomy

39. Papillary thyroid carcinoma:
Management
 Lymph node dissection
• Carried out only when there is clinical evidence of lymph node metastasis
on examination or when detected on ultrasound.
• Prophylactic dissection has not been shown to improve survival in these
patients. Moreover it increases the risk of recurrent laryngeal nerve and
permanent hypoparathyroidism

40. Lymph node dissection involves:
1. central lymph node clearance
2. functional lymph node dissection
3. radical node lymph node dissection
4. berry picking

41.  Radioiodine therapy :
• The most effective adjuvant therapy for papillary carcinoma in form of Iodine131
• About 4-6 weeks after surgery.
• Causes cytotoxicity by emission of short path length (1 to 2mm) beta radiation
Radioiodine uptake is dependent upon adequate stimulation by TSH→ This is reduced by
the presence of excess stable iodine intake
Precautions to be taken before
performing radioactive iodine
screening:
 avoid all iodine containing medications
+ limit dietary intake of iodine for at
least one week
 IV contrast for CT scan containing large
iodine load
Uses:
1. adjuvant ablation of residual
thyroid tissue and possible
metastatic disease
2. imaging for possible
metastatic disease
3. treatment of known residual
or metastatic thyroid cancer
In Brief
-Decreases recurrence
- Tx persistent cancer

42.  Thyroid Hormone Suppression:
• Levothyroxine therapy.
• Advantage:
 To prevent hypothyroidism
 To minimize potential TSH stimulation of tumour growth
• Disadvantages:
 Osteoporosis
 Atrial fib
 Cardiac dysfunction
Papillary thyroid carcinoma: Management

43. • prognosticate the outcome of patients with thyroid malignancy and decide the modality of treatment and
extent of surgery
• The prognostic scoring system include
1. AGES
2. AMES
3. MACIS
Papillary thyroid carcinoma:
Prognostic factors
A= ages (<40 years or > 40 years)
G= grade (well differentiated or poorly
differentiated)
E= extrathyroidal involvement
S = size of the lesion (<1 cms or >1cms)
I= invasiveness
C=completeness of initial surgery
M=metastases
• Low risk cancer:
• Age <40 yrs
• Size <1 cm
• Intrathyroid with no local extension or metastasis
25 years cancer risk mortality of 2%
• High risk cancer:
• Age >50 yrs
• Large size lesion
• With local invasion or metastasis
cancer related mortality at 25 years is 46%

45. Papillary thyroid carcinoma:
postoperative management
Day zero postop:
• Check plasma Ca++ daily
• Look for early complications
Every 3 - 6 mo: Follow up includes:
Physical examination
Biochemical tests:
-TG estimation ( to assess recurrence)
-Free thyroxin and TSH ( to assess adequate
suppression of TSH)
-Ca level
Radiological imaging: Neck US, radioactive
iodine scan
if normal tests at end of 2 yrs, follow up can be done every 2 yrs
for 5-10 yrs or earlier if symptoms arise.
•Complications following surgery
Anatomical such as recurrent
laryngeal nerve damage.
•Bleeding. Owing to the confined space
haematoma's may rapidly lead to
respiratory compromise owing to
laryngeal oedema.
•Damage to the parathyroid glands
resulting in hypocalcaemia.

46. Follicular Carcinoma

47. Compared to papillary carcinoma:
• Older age: 40-60 years
• more typically uninodular
• Hematogenous spread more than lymph nodes involvement
• Distal metastasis to bone (pulsatile mass in bone, with lytic
lesions) and lung
• RISK FACTORS — similar to those for papillary thyroid cancer
Follicular Carcinoma

48. Normal, well-differentiated
epithelium with follicular
development and colloid
Poorly-differentiated with solid
growth, absence of follicles,
marked nuclear atypia, and
extensive
vascular and/or capsular
invasion
Poor prognosisGood prognosis
Follicular carcinoma: Histology
• The cytological feature of cells are not diagnostic
(FNAC cannot differentiate between follicular adenoma and carcinoma)
• US (no specific features confirm the diagnosis)

49. minimally invasive follicular
cancer (MIFC)
widely invasive follicular
cancer (WIFC)
extends beyond the tumor
capsule into blood vessels and
adjacent thyroid parenchyma
microscopic penetration of the
tumor capsule without vascular
invasion
Follicular carcinoma
So how to confirm the diagnosis?
Is this solitary thyroid nodule ,
adenoma or carcinoma?
Vascular and capsular invasion in carcinoma and not in follicular adenoma
Diagnostic
hemithyroidectomy

50. National Comprehensive Cancer Network (NCCN) guidelines
• Lobectomy plus isthmusectomy as the initial surgery →with prompt
completion of thyroidectomy if invasive follicular thyroid carcinoma (FTC) is
found on the final histologic section.
• Total thyroidectomy as the initial procedure only if invasive cancer or metastatic
disease is apparent at the time of surgery, or if the patient wishes to avoid a second,
completion thyroidectomy
• About 4-6 weeks after surgical thyroid removal, patients must have radioiodine to
detect and destroy any metastasis and any residual tissue in the thyroid
Follicular Carcinoma: treatment
Dr’s notes = if less than 1 cm >> hemi
 More than Or = 4 cm >> total
 2-3 cm pt’s decision

51. Symptoms ,raised TG, or positive whole body scintigraphy patient may need
either surgery or iodine therapy
Recurrence
• Most recurrence of differentiated thyroid cancer occurs within the
first 5 years after initial treatment.
• But recurrence may occur many years or even decades later
particularly in patients with papillary carcinoma.

52. • What structures are commonly involved in direct infiltration? In which type of
thyroid malignancy is this commonly seen?
• How would you establish the diagnosis?
• Which type of malignancy are not diagnosed by FNAC and why? What
characteristic features you see in papillary carcinoma of thyroid
• What investigations would you order to stage thyroid malignancy in the neck and at
distant site?
• If the patient in scenario 1 is diagnosed to have papillary carcinoma of thyroid, how
would you manage the patient?
• What preoperative investigations would you carry out to look for fitness of the
patient and investigations specific for patients undergoing thyroid surgery?
Case Discussion

53. • What features in thyroid malignancy would categorise the patient to low
risk and high risk group of thyroid malignancy (AGES/ AMES/ MACIS/
TNM).
• What is the optimum treatment of a patient with papillary carcinoma of
thyroid? What is the role of lymph node clearance? Which group of
cervical nodes are usually cleared?
• What is the post-operative management of this patient? When would you
do a radioactive iodine scan and what precautions are required prior to
carrying it out. What is the role of suppressive thyroxine dose and what
are its long term complications.
• How often do you follow up these patients and what investigations are
carried out.
• What is the long term outcome of this patient?
Case Discussion

54. Comment on radiological investigations of 2 patients with
follicular carcinoma of thyroid (in terms of cause/
complications/ and findings).
How do you treat?
• Radiolucent lesions in the
bones due to bone
metastasis. Might be
complicated by
pathological fractures
• Treatment: radiotherapy
Case Discussion

55. • A 37 year old lady presents with
goitre of 6 months duration
which has been progressively
increasing in size.
• She also has noticed multiple
swellings in her tongue for the
past 3 months.
• On examination she has a goitre
measuring 4x3 cm and cervical
lymph node enlargement.
Case Scenario (3)

56. Medullary carcinoma
• Is a neuroendocrine tumor of the parafollicular or C cells of the thyroid gland.
• Accounts for approximately 1 to 2 % of thyroid cancers in the united states
• The production of calcitonin is a characteristic feature of this tumor.
• Most medullary thyroid carcinomas are
sporadic (75%)
• However, approximately 25 % are
familial as part of the type 2 (MEN2)
syndrome.
Overview:

57. MEN 1 AND 2:

58. Clinical presentation:
Sporadic:
• Age of presentation fourth and sixth decades of life
• The most common presentation  solitary thyroid nodule (75-95%) , in the upper portion of
the gland
• In most patients with MTC, the disease has already metastasized at the time of diagnosis:
 70 % of patients have clinically detectable cervical lymph node involvement
 15 % have symptoms of upper aerodigestive tract compression or invasion such as
dysphagia or hoarseness
 5 to 10 % have distant metastatic disease (liver, lung, bones, and, less often, brain and
skin. )
• Systemic symptoms:
 Secretion of calcitonin: cause diarrhea or facial flushing in patients with advanced
disease
 Secretion of corticotropin (ACTH), causing ectopic Cushing's syndrome.

59. Clinical presentation:
Inherited:
• Multiple endocrine neoplasia type 2  (MEN2A and MEN2B)
• Same clinical presentation, except for:
 The age  third decade of life
 characteristic prevalence of the extrathyroidal manifestations
 MEN 2B  develops at an earlier age and may be more aggressive than MEN 2A

60. Staging of MTC:

61. Staging of MTC:
Stage I • MTCs that are less than 2 cm in diameter without evidence of disease outside of the
thyroid gland
Stage II • Tumors >2 cm confined to the thyroid or tumors of any size without lymph node
metastasis that demonstrate gross extrathyroidal extension invading only the strap
muscles (sternohyoid, sternothyroid, thyrohyoid, or omohyoid muscles)
Stage III • Tumors of any size demonstrating metastatic lymph node involvement in the
central neck (levels VI or VII; pretracheal, paratracheal, or prelaryngeal/Delphian,
or upper mediastinal lymph nodes) with or without gross invasion into the strap
muscles (sternohyoid, sternothyroid, thyrohyoid, or omohyoid muscles)
Stage IV • Any distant metastases, or lymph node involvement outside of the central neck
(level VI/VII), or gross invasion into other structures of the neck (beyond just strap
muscle involvement)

62. The diagnosis of MTC:
 FNA biopsy
- The sensitivity is 50 to 80 %
- higher sensitivity  by the addition of immunohistochemical staining for calcitonin
 If the clinical suspicion for MTC is high (eg, patient with diarrhea, flushing, and a thyroid
nodule), calcitonin can be measured in the washout of the FNA biopsy needle
• The nuclei placed eccentrically and are
larger and more pleomorphic than those of
normal follicular cells
• Immunocytologic staining for calcitonin is
positive

63. The diagnosis of MTC:
 The diagnosis of MTC can be made after thyroid lobectomy for a
suspicious or indeterminate FNA biopsy.
Findings in surgical histology
Spindle-shaped and frequently
pleomorphic cells without follicle
development because these cells
originate from the calcitonin-
producing parafollicular C cells
of the thyroid

64. National Comprehensive Cancer Network (NCCN) and American Thyroid Association (ATA) Guidelines for Management of Medullary Thyroid Cancer
Evaluation of patient diagnosed with MTC by FNA:
Serum calcitonin and CEA:
• To look if the tumour is capable of hyper secreting the hormones, if so, the values can be
compared with postoperative values.
• Postoperatively, results may provide a prognostic factor and sensitive markers for
progression and aggressiveness of metastatic MTC
Radiologic evaluation (US):
- To look for cervical lymph node involvement.
- For patients with local lymph node metastases on ultrasound or with preoperative serum
basal calcitonin >500 pg/mL (indicating high risk of local or distant metastatic disease)
metastatic workup: chest CT, neck CT, liver CT or liver MRI, axial MRI
Genetic screening in sporadic MTC:
• Germline RET testing in all patients with newly diagnosed C cell hyperplasia or apparently
sporadic MTC.
Testing for coexisting tumors
• Particularly pheochromocytoma and hyperparathyroidism prior to thyroidectomy
• For patients with unknown RET mutational status and for patients who have a germline RET
mutation, measure:
1. Serum calcium  to rule out hyperparathyroidism
2. Plasma fractionated metanephrines  the initial screen for pheochromocytoma
• In a patient with negative RET proto-oncogene testing and no family history of MEN2 syndrome,
biochemical testing for coexisting tumors is typically not required.

65. Evaluation of patient diagnosed with MTC by FNA:
National Comprehensive Cancer Network (NCCN) and American Thyroid Association (ATA) Guidelines for Management of Medullary Thyroid Cancer

66. National Comprehensive Cancer Network (NCCN) and American Thyroid Association (ATA) Guidelines for Management of
Medullary Thyroid Cancer
1. No US evidence of cervical LN involvement: prophylactic bilateral dissection of the central lymph node
compartment without prophylactic lateral neck dissection
2. US evidence of cervical LN involvement: bilateral central and lateral compartment dissection

67. Hypoechoic
Irregular margin
Microcalcification
Total
thyroidectomy
specimen
showing
multifocal
lesion in MTC
Total
thyroidectomy
specimen with
LN clearance

68. MTC
confined to
the neck
 Total thyroidectomy rather than unilateral lobectomy is the preferred surgical
approach.
1. No US evidence of cervical LN involvement: prophylactic bilateral
dissection of the central lymph node compartment without prophylactic
lateral neck dissection
2. US evidence of cervical LN involvement: bilateral central and lateral
compartment dissection
Locally
advanced or
metastatic
MTC
• Total thyroidectomy with resection of involved lymph node compartments is
recommended in most patients.
• Since the goals of surgery are largely palliative in this setting, a less aggressive
surgical approach to the thyroid and to lymph node dissection in order not to
impair speech, swallowing, parathyroid function, and shoulder mobility
MTC
diagnosed
after
lobectomy
• Management options include:
1. Completion thyroidectomy (eg, removal of the remaining thyroid tissue) or
2. Observation with monitoring of serum calcitonin levels.

69. Postoperative Management:
1- Monitor for postoperative complications:
• Nerve damage
• External branch of superior laryngeal nerve.
• Recurrent laryngeal nerve.
• Hyoparathyroidism
• Hemorrhage
2- Thyroxine therapy:
• Thyroxine (levothyroxine, T4) therapy immediately after surgery
• Initial dose is 1.6 mcg/kg of body weight
• The goal is to restore and maintain a euthyroid state
3- Serum calcitonin and CEA measurement: two to three months after surgery to detect the
presence of residual disease.

70. 1. Normal serum CEA and undetectable serum calcitonin values  Biochemically cured
• F/u:
• PE twice yearly for two years and then yearly thereafter.
• Measurement of serum calcitonin and CEA levels twice yearly for two years and then yearly
thereafter.
• Neck ultrasound 3 to 12 months postoperatively (depending on the extent of lymph node
involvement prior to surgery) to establish a baseline.
2. Persistent hypercalcitoninemia , 3 or more months after surgery  Evidence of residual disease
• Treatment options include:
1. Observation/active surveillance
2. Surgical resection
3. EBRT
4. Other (such as radiofrequency ablation, cryoablation, embolization) or systemic therapies.

71. Age and stage of disease at the time of diagnosis
5 year disease-free survival rates are higher among patients 40 years old or less as
compared with patients over age 40 years
(95 % versus 65 % respectively)
Prognosis:

72. • A 72 years old gentleman presented with 6
weeks history of rapidly increasing thyroid
swelling.
• He also complains of hoarseness of voice for
the past 3 weeks and difficulty in
swallowing and occasional stridor.
• On examination the thyroid is enlarged and
feels hard in consistency.
Case Scenario (2)

73. Case outline
1. What is the most likely diagnosis?
1. What features in history support the diagnosis?
2. What additional history would you ask?
3. What further examination would you carry out?
4. How would you confirm the diagnosis?
5. What additional investigations need to be carried out?
6. What features in inspection is supportive of the diagnosis.
7. This patient undergoes a procedure. What procedure has he undergone and why?
8. How would you treat this patient?
9. Comment on the survival of patients with this condition

74. • Are undifferentiated tumours of the thyroid follicular epithelium.
• Extremely aggressive tumour, with a disease-specific mortality approaching 100 %.
• End-of-life issues and plans for comfort care measures are an integral part of initial disease
management planning.
• The annual incidence 1-2 per million persons
• Account for 0.9 to 9.8 % of all thyroid cancers globally
• the mean age at diagnosis is 65 years
Anaplastic carcinoma
• 20% of patients have a history of differentiated thyroid cancer
• 20 to 30 % have a coexisting differentiated cancer
• Support to the hypothesis that anaplastic cancer develops from more differentiated
tumors (activating mutations in BRAF and RAS )  early events in the progression
pathway

75. Rapidly enlarging neck mass (85%)
• Causing  neck pain and tenderness, and compressive symptoms: dyspnea, dysphagia, hoarseness, cough
(and sometimes hemoptysis).
• Less commonly: chest pain, bone pain, headache, confusion, or abdominal pain.
• Constitutional symptoms: anorexia, weight loss, fatigue, and fever of unknown origin
Clinical presentation:

76. • Bilateral but asymmetric thyroid enlargement.
• Hard and nodular and may be tender.
• A dominant nodule is often present.
• Fixed to the surrounding structures and does not move with
swallowing.
• Usually > 5 cm in diameter
• 50% of patients have enlarged cervical lymph nodes.
• Other findings of local extension of the disease
• The skin overlying the tumor may be erythematous or
even ulcerated
Physical examination:
Our patient

77. • Cytologic examination of cells obtained by FNA biopsy or of tissue obtained by large needle or
surgical biopsy
• The morphologic patterns cancer include:
1. Spindle cell, pleomorphic giant cell, and/or squamoid (many have mixed morphology of two
or all three patterns)
2. Numerous mitotic figures and atypical mitoses are present
Diagnosis:
Staging:

78. Laboratory
evaluation
Findings on
cytopathology
Imaging studies
Evaluation:
• Thyroid function tests (TSH)
• Free thyroxine [T4]
• CBC
• Electrolytes
• Blood urea nitrogen (BUN)
• Creatinine
• LFTs
• Serum calcium and phosphorus
• Serum thyroglobulin
• US neck
• PET scan
• MRI or CT
20 to 30 % of patients with anaplastic thyroid cancer have
coexisting differentiated thyroid cancer, the presence of
metastases does not automatically indicate that they
originate from anaplastic thyroid cancer  how to
differentiate?
The serum thyroglobulin level and/or PET scan

80. American Thyroid Association (ATA) and the National Comprehensive Cancer Network (NCCN) guidelines
Evaluation of anaplastic thyroid malignancy:
1- Tumour localized to the thyroid or locally advanced operable disease:
• Complete resection followed by combined radiotherapy and chemotherapy:
- May provide prolonged survival rate(>2 years)
- Total thyroidectomy with complete tumor resection vs ipsilateral thyroid
lobectomy  does not prolong survival and is associated with a higher
complication rate.
- Some experts prefer total thyroidectomy with central and lateral neck lymph
node dissection  can you think why?
Resection is rarely curative in the early stage, but the main goal of
surgery is to relive the tracheal compression and alter the manner of
death to avoid Asphyxiation

81. 2- Locally advanced inoperable disease:
• Combined radiotherapy and chemotherapy for local
control of disease.
• Surgical resection for residual tumor could be
considered if the disease is responsive.
3- Metastatic disease:
• No effective therapy, and the disease is uniformly
fatal.
• The aim of treatment: palliation of symptoms
• Locoregional resection may be necessary for
palliation of airway or esophageal obstruction  death
is usually attributable to upper airway obstruction and
suffocation (often despite tracheostomy) in 50-60% of
patients and to a combination of complications of
local and distant disease in the remainder.
4- End-of-life care:
• End-of-life issues and plans for comfort care measures
.

82. On univariate analysis metastatic disease, extracapsular disease, size > 5 cm
and involvement of lymph nodes were the markers of worst prognosis.
Prognosis:

83. • Principle and practice of surgery 6th edition
• NCCN Clinical Practice Guidelines
• American Thyroid Association (ATA)
• https://www.uptodate.com
References
َ‫ين‬ِ‫م‬َ‫ل‬‫ا‬َ‫ع‬ْ‫ل‬‫ا‬ ِ‫ب‬َ‫ر‬ ِ ‫ه‬ ِ‫ّلِل‬ ُ‫د‬ْ‫م‬َ‫ح‬ْ‫ل‬‫ا‬ ِ‫ن‬َ‫أ‬ ْ‫م‬ُ‫ه‬‫ا‬َ‫و‬ْ‫ع‬َ‫د‬ ُ‫ر‬ ِ‫آخ‬َ‫و‬

84. • Harrison, Tinsley Randolph et al. Harrison's Principles Of Internal
Medicine. New York: McGraw Hill Education, 2015. Print.
• Uptodates
• Medscape
• Dr.Norman surgical notes
References