EPIDEMIOLOGY & STATISTICS ; RISK FACTORS & GENETICS ; CLASSIFICATION PATHOGENESIS, CLINICAL FEATURES & PATHOLOGY

1. THYROID CARCINOMA. 02
ü EPIDEMIOLOGY & STATISTICS
ü RISK FACTORS & GENETICS
ü CLASSIFICATION
ü PATHOGENESIS, CLINICAL FEATURES & PATHOLOGY
PRESENTER: JAPNEET
MBBS BATCH 2K17
MODERATOR: DR. ZAHID IQBAL MIR
MBBS, MS, DNB

2. GLOBOCON 2020
EPIDEMIOLOGY & STATISTICS

7. “A belt of thyroid cancer”
-coastal districts of Kerala,
Karnataka, and Goa.

8. RISK FACTORS
Ø GENDER
• 3 times more common in women
Ø AGE
• Male :peak at 50s to 70s
• Female :peak at 40s to 60s
Ø FAMILY HISTORY
ü MEN SYNDROME
• Medullary thyroid cancer:2 out of 10 MTC result from inheriting an abnormal gene

9. ØFAMILY HISTORY
• history of thyroid cancer in a first-degree relative,or a family
history of a thyroid cancer syndrome
COWDEN’s syndrome PTEN Interstinal hamartomas FTC
FAP APC Colon polyps and cancer PTC
WERNER’s syndrome WRN Adult progeroid syndrome PTC,FTC,
anaplastic cancer
Carney complex PRKA
R1α
Cutaneous and cardiac myxomas PTC,FTC
McCune-Albright
syndrome
GNAS
1
Polyostotic fibrous dysplasia,endocrine
abnormalities,
café-au-lait spots
PTC clear cell
DICER 1 syndrome Pleuropulmonary blastoma,
cystic nephroma,
ovarian sex cord-stromal tumour
Multinodular goiter,
thyroid cancer

10. WERNER’S SYNDROME MCCUNE-ALBRIGHT
SYNDROME

11. ØRADIATION EXPOSURE
• Therapeutic uses of radiation (eg,treatment of childhood
malignancies)
• Environmental exposure secondary to fallout from atomic
weapons (eg,Nagasaki/Hiroshima,Japan)
• Nuclear power plant accidents (eg,Chernobyl)
üRisk increases with
1. Larger doses
2. Younger age at treatment
• Children treated with low doses of radiation for acne,fungus infections
of the scalp (ringworm),or enlarged tonsils or adenoids
• Radiation therapy in childhood for Hogkin lymphoma, Wilms tumour
and neuroblastoma

12. MUSHROOM CLOUDS
HIROSHIMA( L ) & NAGASAKI ( R )
LITTLE BOY FAT MAN

13. After the Chernobyl disaster, a significant increase in thyroid cancer was
reported among children and adolescents exposed to radioactive iodine released at
the time of the accident in Belarus, Russia, and the Ukraine

14. ØASSOCIATIONWITH IODINE &THYROID DISORDERS
• Follicular thyroid cancers - Area where diet is low in iodine.
• Papillary carcinoma – iodine sufficient areas
• Pre existing long standing MNG – FTC
• Hashimoto’s thyroiditis – PTC
ØOTHER POTENTIAL RISK FACTORS
• Occupational and environmental exposure
• Hepatitis C related chronic hepatitis
• Increased parity and late age at first pregnancy
• Obesity and overweight :risk increases with increase in BMI

15. CLASSIFICATION
DUNHILL CLASSIFICATION:
ØDIFFERENTIATED –
1. Papillary carcinoma
2. Follicular carcinoma
3. Hurthle cell carcinoma
4. Papillofollicular carcinoma
Ø UNDIFFERENTIATED
Ananplastic carcinoma
Ø MEDULLARY CARCINOMATHYROID
Ø MALIGNANT LYMPHOMA
Ø SECONDARIES from colon ,kidney ,melanoma ,breast – rare

16. PAPILLARY CARCINOMA
• Most common type of thyroid cancer (84% of all incident
cases).
• 3:1 female to male ratio
• Peak incidence is in the third to fifth decades of life.
• Reported in thyroid sufficient areas
• Radiation exposure ( PTC assoc.with radiation exposure is
more aggressive)
• BRAF mutation
• RET/ PTC mutations [RET / PTC 3 more aggressive than
RET/PTC 1]
PATHOGENESIS, CLINICAL FEATURES & PATHOLOGY

17. CLINICAL FEATURES
üMost patients are euthyroid.
üPresents as slow-growing ,painless mass in the neck [MC]
FEATURES SUGGESTIVE OF MALIGNANCY
• Rapid nodular growth
• fixation of the nodule to surrounding tissues
• new-onset hoarseness or vocal cord paralysis
• presence of ipsilateral cervical lymphadenopathy

18. • Disseminates primarily via the lymphatic route and affects the cervical
lymph nodes in the central and lateral compartments
• Among patients who undergo a modified radical neck dissection,up to
80 % have lymph node metastases (half are microscopic),
• Patients with papillary microcarcinomas who have prophylactic central
node dissection,microscopic metastases have been reported in 37 to 64
percent
• At diagnosis,clinically detectable regional lymph node metastases are
more common in children (approximately 50 %) than
adults.
üVascular invasion is seen in only approximately 5 to 10 percent.

19. üCompression features are uncommon
Acute pain is more typical of a benign process such as:-
- thyroiditis
- acute bleed into a benign cyst;
however,pain can also be indicative of less common and
more aggressive thyroid cancers such as
MTC,primary thyroid lymphoma,and ATC.

20. ØDISTANT METASTASIS
• 2 to 10 percent of patients have metastases beyond the
neck at the time of diagnosis
ü 2/3rd have pulmonary and 1/4th have skeletal
metastases.
ü Rarer sites of metastasis are the brain,kidneys,liver,and
adrenals

21. HISTOPATHOLOGY FINDINGS
• Papillae with fibrovascular
core
• Psammoma bodies :microscopic
foci of dystrophic calcification
• Orphan annie - eye nuclei :
large pale optically clear nucleus
• Ground glass appearance :
nuclei appear optically clear
• Nuclear grooving :coffee bean
nuclei

22. Psammoma bodies Nuclear grooving
Papillae with fibrovascular core

23. Orphan annie - eye nuclei

24. VARIANTS OF PAPILLARY CARCINOMA THYROID
ØLindsay tumor :follicular variant of papillary thyroid cancer[FVPTC]
• Classified as papillary carcinomas because they behave biologically as
papillary carcinomas
• Two main subtypes of FVPTC are recognized:encapsulated and
nonencapsulated (infiltrative)
ØOther variants
üTall cell variant
üColumnar call variant
üDiffuse sclerosing variant
üClear cell variant
• Variants are associated with a worse prognosis.

25. FOLLICULAR CARCINOMA
• 2nd Mc DTC (12% of all thyroid cancer)
• Occurs in older adults,(4th to 6th decades)
• 3:1 female-to-male ratio
• Seen in iodine deficient areas
• a/w Long standing multinodular goitre

26. Factors associated with follicular thyroid cancer include:
üRAS mutation
üPAX8-PPAR gamma 1
üOther factors-
• p53,c-myc,c-fos,
• Telomerase reverse transcriptase (TERT) promoter mutations
• Thyroid-stimulating hormone (TSH) receptor mutations,
üRare a/w BRAF ,RET/PTC
PATHOGENESIS

27. CLINICAL FEATURES
üFirm or hard and nodular neck swelling
üPresent as solitary thyroid nodule
üHistory of
• Rapid size increase
• Long-standing goiter may be present ocassionally
üTracheal compression/infiltration and stridor
üRLN involved :Hoarseness
üPain is uncommon

28. ØSPREAD
• Pattern of spread is hematogenous,typically to the lungs and
bone
• Regional nodal metastases occur in 8-13% cases.
• Distance metastasis occur in 10-15% cases
• The clinical features of secondaries in skull
1. Warm
2. Vascular
3. Rapidly growing
4. Pulsatile swelling
• Dysponea,haemoptysis,chest pain when there are lung secondaries

29. METASTATIC FOLLICULAR CANCER
USG showing mass in the left
lobe of the thyroid
Pathology demonstrated
follicular cancer
CT chest - multiple
pulmonary metastases
CT head - left parietal bone
metastasis.

30. HISTOPATHOLOGY
• usually solitary lesions
• Cells are arranged in follicles
• Architectural patterns depend
on the degree of
differentiation of the tumor
• Capsular invasion

31. HURTHLE CELL CARCINOMA
üless common
üDistinct and more aggressive behavior
üOccurs in older adults (6th to 7th decades)
üHCC is less RAI-avid compared to other DTCs (38%)
• RAI treatment is associated with improved survival in patients
with HCCs that are 2 to 4 cm.

32. üPreviously considered to be a variant of follicular thyroid cancer.
üOxyphillic cells
[with eosinophillic cytoplasm]
• Rich in mitochondria
• Secretes thyroglobulin
üMore spread to lymph nodes as compared to Follicular cell
carcinoma
üHigher bony metastasis rate

33. MEDULLARY CARCINOMA
ü2% of thyroid malignancies
üArises from parafollicular‘C’cells of thyroid
• Which in turn arise from ultimobranchial bodies from neural
crest
• which secrete calcitonin
• Concentrated superolaterally in the thyroid lobes [MTC
usually develops]

35. Ø SPORADIC MTC
• Mc presentation - solitary thyroid nodule (75 to
95%)
• Already metastasized at the time of diagnosis.
• 70 % - clinically detectable cervical lymph node
involvement
• 15 % - upper aerodigestive tract compression or invasion
such as dysphagia or hoarseness
• 5 to 10 % - distant metastatic disease (liver,lung,bones,
and,less often,brain and skin)

36. Ø INHERITED MTC
üYounger age compared to sporadic MTC
• Familial MTC or MEN2A – 3rd decade
• MEN2B – prior to 2nd decade.
• Can present very early in life within the first months to
year
üHereditary MTC often presents as multifocal disease.
üCan present during the diagnosis and workup of an
associated disease,

37. ØMEN 2 SYNDROME
• RET proto-oncogene mutation
• Chromosome 10
MTC only
Exon 618
mutation
Exon 634 mutation
•MTC
•Parathyroid adenoma
•Pheochromocytoma
•Megacolon
MEN 2A / SIPPLE
SYNDROME
Exon 918 mutation
•MTC
•Medullated corneal nerve
fibres
•Mucosal neuromas
•Marfanoid features
•Megacolon
MEN 2 B / MEN 3 /
GORLIN SYNDROME

38. CLINICAL FEATURES
• Firm / hard Thyroid swelling > 5 years history
• Recent onset of hoarseness of voice
• Local invasion produces symptoms of dysphagia,dyspnea,
dysphonia
• Diarrhoea (Serotonin )
• Flushing ( Histamine )
• Cushing disease ( ACTH)

39. HISTOPATHOLOGY
ü Composed of sheets of infiltrating polygonal to spindle shaped cells
• Nests
• Trabaculae
• Follicles
üAcellular amyloid deposits
ücytoplasmic positivity on calcitonin staining
üCongo red stain :apple green birefringence
H&E - plasmacytoid morphology with eccentric
round nuclei,“salt-and-pepper”chromatin,
small nucleoli,and amyloid infiltrate.

40. ANAPLASTIC CARCINOMA
ü1% of all thyroid malignancies
üExtremely aggressive undifferentiated tumor of follicular cell
origin
üMean age at diagnosis - 65 years
ü2:1 female :male ratio
ü60 to 70 % of tumors occur in women

41. CLINICAL FEATURES
Ø Antecedent thyroid disease
ü 20 % - history of DTC
ü20 to 30 % - coexisting DTC ( PTC > FTC > HCC )
üEarly events - BRAF and RAS mutation
üLate events - Mutations in p53 tumor suppressor protein,16p,
Catenin (cadherin-associated protein),beta 1,and PIK3CA
üUp to one half of patients have a history of multinodular goiter
üSome have a history of partial thyroidectomy for goiter.

42. • Presents as a long-standing neck mass,which rapidly enlarges (85%) and
may be painful
• Very hard swelling
Ø LOCAL
Neck pain and tenderness,and compression (or
invasion) of the upper aerodigestive tract:
•Dyspnoea ( 35%)
•Dysphagia (30 %)
•Hoarseness (25 %)
•Cough (+- hemoptysis,25%)
Less common - Chest pain,bone pain,headache,
confusion,or abdominal pain from metastases
Ø DISTANT
METASTASIS
(15-50% at initial
presentation)
• MC lungs (90%)
•Bone (5-15%)
•Brain (5%)
•Lymph nodes usually are
palpable at presentation
CLINICAL FEATURES

43. Tracheal compression - stridor
(scabbard trachea:radiological finding)
Berry’s sign positive :
infiltration of carotid sheath
Hoarsness:
Local invasion of RLN

44. HISTOPATHOLOGY
• Sheets of cell with marked heterogenisity
• Patterns are:-
üSpindle cells
üSquamoid cells
üPleomorphic giant cells
with mitotic figures,atypical mitoses,and extensive necrosis
H&E - marked nuclear pleomorphism, oval to spindle-
shaped cells, and multinucleated tumor cell.

45. REFRENCES