case history and management of papillary thyroid carcinoma

1. Papillary thyroid
carcinoma
CPC SBW
Dr. Nadia Gulnaz

3. CASE SCENARIO :
A 65-years female patient from
Takhtbhai presented to us with
• Swelling front of Neck-------- 1- year.
• Pain in the swelling --------- 8- months.
• Hoarseness ---------3- months
• Dyspnoea and Dysphagia --------- 2
months.
• Weight loss and Lethargy--------2
months.

4. CASE SCENARIO :
• There is no history of heat or cold
intolerance or palpitations.
• Normal bowel and Micturation. No
radiations in the past.
• No bone or joint pain.
• She had a swelling 4 years back on
the left side of the neck for which
she underwent surgery but the
record is not available

5. • Her sleep is disturbed because of SOB
• No fits.
• No eye problem
• No chest pain
• No jaundice
• No family history for thyroid diseases
• She is post-menopausal with 5 children.
• No history of blood transfusions or allergies.
• No significant history of any medications
except antibiotics and painkillers. She belongs
to a poor socio-economic class.

6. General physical
examination
• well oriented middle age woman with
hoarse voice and difficult breathing
• Anemic
• Not jaundiced
• No sign of oedema.

7. Local examination
• A large thyroid swelling with overlying
engorged veins
• Non tender
• Impalpable trachea.
• Cervical lymphadenopathy
• right side carotid pulse is not palpable.
• No hands or eyes signs of thyrotoxicosis.
• No scalp and dorsolumbar tenderness.

8. Systemic examination
• She has mild stridor, with
retrosternal extension and there is
no sign of pleural effusion.
• Heart sounds are normal.
• No hepatomegally
• No ascites.

9. LABS:
• Hb : 9.5,
• Tlc : 6300
• Platletts: 381000
• LFTS :
• Billirubin: 0.56 mg/dl
• SGPT : 39
• Alk. Phos: 211
• Albumin : 4.5

10. Labs :
• PT: 14/19, APTT: 29/31
• ELECTROLYTES : Na:134, K: 3.91, Cl:
95
• RFTS :
• Urea: 42
• Creatinine : 1.3

11. Labs:
TFTS :
• TSH :1.00 uiU/ml (0.47-5.01)
• T3 : 1.19 ng/ml (0.8-1.8)
• T4 : 7.95 ug/ml (4.5-12.0)
• Calcium : 9.2
• Calcitonin ; not done (Bx proven
Pappilary)
• Thyroglobulins : no role pre-
operatively

12. Radiology
Ultrasound:
• both lobes of thyroid are enlarged having
multiple solid hypoechoic lesions with
increased vascularity and calcifications.
There is some retrosternal extension on
the right side. There are multiple cervical
lymphnodes on both sides.
Chest x-ray:
• retrosternal extension
• Mass occupying superior mediastinum

14. Radiology
Ct scan: enhancing lobulated mass is
seen involving right lobe of the
thyroid encasing trachea and
displacing it towards left.
• Infiltrating, larynx and oropharynx
causing obstruction.
• Also involving proximal oesophagus
with infiltration of prevertebral
fascia.

15. Ct scan contin…..
• Inferiorly it has retrosternal
extension in right para tracheal and
retro tracheal region.
• Laterally involves the right sub
mandibular and deep cervical regions
displacing the carotids anteriorly.
• Right deep cervical lymphnodes are
enlarged. ( T4N1Mx)

17. Radiology
• Thyroid scan: large cold nodule
occupying whole of the right lobe and
isthmus of the thyroid gland.
• Bone scan: NO Mets
• Biopsy: papillary carcinoma. (cervical
lymph node) (3/12/14)
• IMMUNOHISTOCHEMICAL STAIN :
TTF-1 : Positive in tumor cells.

19. Further Work up
ENT examination :
mass coming through inlet of larynx
IRNUM opinion :
• advised total thyroidectomy followed
by Radioiodine-131 work-up and
ablation. (5/12/14)
• Inoperable; needs palliative EBRT.
(13/12/14)
• CARDIOLOGY : low to moderate risk
SURGEONS: ???palliation

20. Anatomy

21. THYROID TUMORS
BENIGN MALIGNANT
PRIMARY
DIFFERNTIATED
FOLLICULAR
PAPILLARY
UNDIFFERENTIATED
ANAPLASTIC
PARAFOLLICULAR
MEDULLARY
LYMPHOID
LYMPHOMA
SECONDARY

22. Background
• most common tumor.
• History of exposure to
radiation.
• Presents as irregular solid or
cystic mass or nodule
• invade lymphatics.
• 11% present with metastases

23. Pathophysiology
proto-oncogenes:
• RET and TRK genes
• BRAF mutation
• RAS mutation
• P53 tumor suppression gene
mutation……rare
• Involves mutation of chromosomes 10
and 11 in 30-35% of the cases

24. Pathophysiology conti….
• Closely associated to prior neck irradiation
• 3-33% PTC……RET mutation unassociated
with irradiation
• 60-80% PTC……associated with
irradiation(Japan ,Chernobyl incident)
• RAS causes early tumorogenesis
 could be completely distinguished from
sporadic PTC on the basis of gene
expression patterns involving i.e SFRP1,
MMP1, ESM1, PAGE1 etc

25. Pathophysiology conti….
Other causes:
• EBRT…. Childhood…………latency period at
least 5 years
• risk maximal at 20 years
• remain high for about 20 years
• dose dependant …….10gy-1500gy
• more than 1500gy risk decreases
• after age 15-20 yrs risk decreases.

26. Pathophysiology conti….
Iodine intake:
More common in patients with
adequate iodine while follicular and
anaplastic more common in iodine
deficient patients.
• familial adenomatous polyposis/ APC
• Cowden disease
• 3% familial

27. Epidemiology
• <1 % of all cancers
• Of all thyroid cancers……..74-80% of cases
• age (45-50 years)
• Female to male ratio..2-4 times increased
• Microcarcinoma less than 1 cm……..found in
5-36% of adults autopsy

28. Mortality/Morbidity
• almost always curable.
• Most grow slowly
• favorable prognosis.
• Distant spread very uncommon.
• The mean survival rate after 10 years is
higher than 90%, and 100% in minimal disease
• The 5-year relative survival rates by stage :
• All stages: 96.7%
• Local: 99.7%
• Regional: 96.9%
• Distant: 56%

29. Presentation
• mostly asymptomatic
(microcarcinoma)
• Solitary Thyroid Nodule.
• First sign lymphnode mets.
• Rarely lungs or bones mets.
• Hoarsness…..dysphagia……cough….dysp
noea signify advanced disease.
• Family history
• Radiation history

30. Physical Examination
• Single/multiple nodule/s move with
swallowing
• Hard, irregular, Painless
• Ill-defined borders
• Fixed in respect to surrounding tissues
• Ipsilateral L.N
• Compressive symptoms
• Euthyroid
• Average size of less than 5 cm

31. Differential Diagnoses
• Calcification of a nodule of a nodular
goiter.
• Carcinoma
• Tyroiditis.

32. Prognostic Risk Classification for Patients
With Well-Differentiated Thyroid Cancer
(AMES or AGES)
LOW RISK HIGH RISK
Age <40 years >40 years
Sex Female Male
Extent No local extension, intrathyroidal, no
capsular invasion
Capsular invasion, extrathyroidal
extension
Metastasis None Regional or distant
Size <2 cm >4 cm
Grade Well differentiated Poorly differentiated

33. WORK UP

34. Approach Considerations
• TSH: sensitive for hypo and
hyperthyroidism, but does not rule out
malignancy.
• FNAC
• Serum thyroglobulin…….used as tumor
marker post op.
• Thyroid ultrasound
• RET proto-oncogene
• CEA…….false positive in pregnant women
and heavy smokers.

35. Approach Considerations
• Thyroid scan
• Chest radiography
• computed tomography
• magnetic resonance imaging
• CT or MRI used only for the evaluation
of fixed, bulky, or substernal lesions
• FDG-PET)/CT
 PET scan do not provide any
additional information compared with
neck sonography

36. Fine Needle Aspiration
• First intervention in evaluation of a nodule.
• Inexpensive, easy, few complications.
• Need a good cytopathologist.
• Sensitivity 83%, specificity 92%
• False positive 2.9%, negative 5.2%

37. Fine Needle Aspiration
• THY1
• Non-diagnostic
• THY2
• Non-neoplastic (not malignant)
• THY3
• Follicular lesion or suspected follicular
cancer
• THY4
• Suspicious of cancer
• THY5
• MALIGNANT

38. Histological Findings
• multifocal, and a net invasion of the lymphatics
• Complete or partial papillary architecture with
some follicles.
• The thyrocytes are large and show an abnormal
nucleus and cytoplasm with several mitoses.
– Orphan Annie nucleus
– psammoma bodies
– On immunohistochemistry may exibhit
• Carcinoembryonic antigen (CEA)
• Calcitonin
• Thyroglobulin
• Keratin

41. TREATMENT &
MANAGEMENT

42. Approach Considerations
• Surgery is the definitive management
• after surgery radioiodine therapy to
detect and destroy any metastasis and
residual tissue in the thyroid.
• External beam radiotherapy as adjuvant
therapy in older than 45 years and locally
invasive disease.
• lifelong thyroxin therapy especially after
total thyroidectomy.

43. Surgical Care
• Controversy about extent of surgery
• Total thyroidectomy.
• Some thyroid tissue may still remain and is
detected by I-131 scan.
• near total thyroidectomy….2-3 gm thyroid tissue
remains……. Low recurrence
• Lobectomy……in less than 1.5 cm unifocal,
interlobar disease….. treated by lymphnode
dissection level 6
• Modified neck dissection if palpable lymph
nodes….but leads to no improvement in recurrence
rate

44. Surgical Care
National Comprehensive Cancer Network
guidelines recommends total
thyroidectomy for patients who meet any
of the following criteria
• Radiation history
• Known distant metastases
• Bilateral nodularity
• Extrathyroidal extension
• Tumor > 4 cm in diameter
• Cervical lymph node metastases
• Poorly differentiated tumor

45. Complications
• Hypothyroidism
• Dysphagia due to damage of the
superior laryngeal nerve
• Vocal cord paralysis due to damage of
recurrent laryngeal nerve
• Hypoparathyroidism due to
parathyroid gland damage.

46. Radioiodine Therapy
• Low risk patient……no need
• High risk patient…..needed because:
• Destroys remaining normal thyroid tissue
• increased sensitivity to subsequent I 131
therapy
• increased specificity of thyroglobulin level
• destroy occult microscopic carcinoma
decrease recurrence.
• For mets. Post ablative I 131 total body
scanning is needed for the presence of
Persistant carcinoma.

47. Radioiodine Therapy
• Normally Done 4-6 weeks after surgery
• Can be given in diagnostic and therapeutic
doses.
• thyroid hormone is stopped and then I-131
scan performed.
• Total ablation with 100mci in total/near
total thyroidectomy gives 80% ablation.

49. External beam
radiotherapy
• External radiotherapy to the neck
and mediastinum is indicated only in
patients in whom surgical excision is
incomplete or impossible and the
tumor tissue does not take up iodine-
131.

50. Complications
• Radiation thyroiditis
• transient thyrotoxicosis in patients
with simple lobectomy
• Sialoadenitis
• Nausea, anorexia, and headache
(uncommon)
• Pulmonary fibrosis in patients with
large lung metastases
• Brain edema

51. Complications
• Permanent sterility or transient
oligospermia or menstrual irregularities.
• Teratogenesis and spontaneous
abortions
• A small increase in the risk for leukemia
• breast and bladder carcinomas
• Avoidance of pregnancy for at least 1
year after radioiodine treatment is
advised.

52. Treatment of Advanced
Disease
• ultrasound-guided percutaneous ethanol injections
an alternative to surgery in patients with a limited
number of neck metastases
• In stage T4 disease, external beam radiation
therapy (EBRT) can be used;
– to control local tumor growth
– large, unresectable tumor
– Limited uptake of radioiodine
– intractable bone pain exists.
• Chemotherapy with cisplatin or doxorubicin has
limited efficacy

53. LOCAL AND REGIONAL
RECURRENCES
• 5 to 20 percent of patients with
differentiated thyroid carcinomas have
local or regional recurrences.
Causes
• Thyroid remnant/lymph node/aggressive
tumor
• Treated by excision, Full body scan with
iodine 131 and External beam radio
therapy.

54. DISTANT
METASTASES
• Mets in lungs and bones, occur in 10 to
15% of patients.
• Lung mets….young pts
• Bone metastases are more common in older
patients and in those with follicular
carcinomas.
• mets in brain, liver and skin also my occur.
Symptoms:
• Uncommon in lung mets.
• pain, swelling, or fracture occurs in more
than 80 percent of patients with bone
metastases

55. DISTANT
METASTASES
Diagnosis:
• chest x/ray
• total body scan,
• ct scan
• bone scan
• MRI
• High thyroglobulin

56. DISTANT
METASTASES
Treatment
• Palliative surgery is required for bone
metastases
• Surgery may also be useful to debulk large
tumor
• Patients with metastases that take up
iodine should be treated with 100 to 150
mCi (3700 to 5550 MBq) every four to six
months

57. DISTANT
METASTASES
• Chemotherapy is not effective and
should be reserved for patients with
progressive metastases that do not
take up iodine-131
• Complete response to treatment is
seen in 45 % of patients with distant
metastases that take up iodine-131

58. DISTANT
METASTASES
Over all survival
• overall survival rate 10 years after
the discovery of distant metastases
is about 40%
• The poor prognosis of patients with
bone metastases is linked to the
bulkiness of the lesions

59. FOLLOW UP

60. Aproach considerations
• To maintain adequate thyroxine therapy
• Routine palpation
• Ultrasound
• Chest Radiography
• Serum Thyroglobulin Measurements
• Iodine-131 Total-Body Scanning

61. Long-term Monitoring
• Required to maintain adequate thyroxine therapy
and to detect persistent or recurrent thyroid
carcinoma
• Low TSH levels reduces tumor growth&
recurrence rates.
• Thyroxine Treatment
• Dose in adults is between 2.2 and 2.8 μg/kg
• monitored by measuring serum thyrotropin three
months after treatment
• initial goal……serum thyrotropin concentration of
0.1 μU per milliliter or less and a serum free T3
concentration within the normal range

62. Long-term Monitoring
• Routine palpation
• Ultrasound :In high risk patients and for
taking biopsy
• Chest Radiography
• Required when serum thyroglobulin
concentration are abnormal
• Serum Thyroglobulin Measurements
• signifies the presence of persistent or
recurrent disease
• False positive in the presence of serum
antithyroglobulin antibodies found in 15
percent of patients
• Base line serum thyrotropin needed for
interpreting

63. Long-term Monitoring
• Iodine-131 Total-Body Scanning
• Stop T4 for 6 weeks.
• patients should be instructed to avoid
iodine-containing medications and iodine-
rich foods,
• and urinary iodine should be measured in
doubtful cases
• pregnancy should be ruled out.
• If scan positive give ablative dose and
again follow up.

64. CONCLUSIONS
• Most patients with papillary
carcinomas can be cured
• However, both the initial treatment
and follow-up should be individualized
according to prognostic indicators
and any subsequent evidence of
disease