3. Thyroid is located opposite C5,C6,C7 ,C8 vertebrae.
Weighs – 25g
Each lobe-5X3X2
Capsules:
Inner/true capsule- formed by peripheral
condensation of the fibrous stroma of gland.
Outer/false capsule- formed by splitting of pretracheal
fascia.
4. APEX- inferior constrictor medially
sternothyroid laterally
BASE- inferior thyroid artery
recurrent laryngeal nerve
LATERAL SURFACE-sternothyroid
sternohyoid
superior belly of omohyoid
MEDIAL SURFACE-trachea and esophagus
inferior constrictor and cricothyroid
cricoid and thyroid
POSTERIOLATERAL SURFACE- carotid sheath and its contents
ANTERIOR BORDER- anterior branch of superior thyroid artery
POSTERIOR BORDER-anastomosis between superior and
inferior thyroid arteries; parathyroid glands
5.
6. 1.Tumours of thyroid follicular or metastatic epithelium
i) Follicular adenoma( including Hurthle cell adenoma)
ii) Follicular carcinoma(including Hurthle cell carcinoma)
iii)Papillary carcinoma
iv)Mucoepidermoid carcinoma
v)Sclerosing mucoepidermoid carcinoma with eosinophilia
vi)Mucinous carcinoma
vii)Poorly differentiated thyroid carcinoma
viii) Undifferentiated (anaplastic)carcinoma including squamous cell
carcinoma
7. 2. Tumours showing C-cell differentiation
i) Medullary cell carcinoma
3. Tumours showing both follicular and C-cell
differentiation
i)Collision tumour: follicular/papillary and medullary carcinomas
ii)Mixed medullary and follicular cell carcinoma
4. Tumours showing thymic or related branchial pouch
differentiation
i) Ectopic thymoma
ii)Spindle epithelial tumour with thymus like
differentiation(SETTLE)
iii)Carcinoma showing thymus like element (CASTLE)
8. 5. Tumors of lymphoid cells
i)Malignant lymphoma
ii) Extramedullary plasmacytoma
6. Intrathyroid parathyroid tumours
i) Parathyroid adenomas
ii) Parathyroid carcinoma
7. . Mesenchymal and other tumors
i) Benign and malignant mesenchymal tumours
ii) Paraganlioma
iii) Teratoma
9. TX- primary tumour cannot be assessed
T0-no evidence of primary tumour
T1a- Tumour <1cm; limited to thyroid
T1b- Tumour >1 cm but not > 2cm in greatest dimension
limited to thyroid
T2 – tumour >2 cm but not > 4 cm
limited to thyroid
T3- tumour > 4cm in greatest dimension limited to thyroid
or
any tumour with minimal extrathyroid extension
T4a- tumour of any size extending beyond the thyroid capsule to invade
subcutaneous soft tissues, larynx, trachea, esophagus, or recurrent
laryngeal nerve
T4b- tumour invading prevertebral fascia or encasing carotid artery or
mediastinal vessels
ALL ANAPLASTIC TUMOURS ARE CONSIDERED T4 TUMOURS
10. NX- regional lymph nodes cannot be assessed
NO- no regional lymph node metastasis
N1a- metastasis to level VI( PRETRACHEAL, PARATRACHEAL,
PRELARYNGEAL/DELPHIAN LYMPH NODES)
N1b- metastasis to unilateral, bilateral or contralateral CERVICAL
( level I,II,III,IV or V) or RETROPHARYNGEAL or SUPERIOR
MEDIATINAL LYMPH NODES (level VII)
MX- distant metastasis cannot be assessed
M0- no distant metastasis
M1- distant metastasis
11. Most common type of thyroid malignancy
Defined as a “malignant epithelial tumor showing
evidence of follicular cell differentiation and
characterized by distinctive nuclear features.’’
Sex- Female predominance (M/F 1 : 2.5)
Age- any age group; mean age 40 years
Presentation-painless thyroid or neck mass. Some
may initially present with lymph node metastasis
12. Following factors may increase risk of papillary
carcinoma-
1.Previous irradiation to the head and neck region
2. Radiation exposure from nuclear accident (e.g., the
Chernobyl accident) or atomic bomb (e.g., survivors of
the atomic bomb explosion from Hiroshima)
3. Hashimoto thyroiditis
18. 1.Ground glass appearance(orphan annie eye)-
empty-looking nuclei with scanty marginated dusty
chromatin
2.Nuclear pseudoinclusion-invaginations of cytoplasm
and appear as sharply outlined round acidophilic vacuoles
3.Nuclear grooves-deep folding of the nuclear membrane;
oocur in oval or spindle nuclei; arranged along the longest
nuclear axis
4.Nuclear microfilaments-seen in few cases; nuclear
clearing is because of accumulation of thread like fibrils
19. large, crowded, ovoid, ground-glass
(hypochromatic) nuclei;
Up and down placement of nuclei
Mitotic figures are generally absent or sparse
22. Dense hyaline fibrosis has been suggested to be a useful feature for distinguishing
papillary carcinoma (89% of cases) from follicular carcinoma (18% of cases).
Desmoplastic stromal reaction
24. Calcified colloid materials, which are fairly
common in Hürthle cell neoplasms and
hyalinizing trabecular adenoma, are
distinguishable from psammoma bodies by their
exclusive location in the follicular lumens.
25. 1.FOLLICULAR VARIANT:
-Composed of follicles throughout; no papillae
-infiltrative type
-encapsulated type=LINDSAY TUMOUR
-The diagnosis rests on identification of the
typical nuclear features of papillary carcinoma.
38. 1)Locally invasive
2) Lymphatic spread
lymph node metastasis in approximately 40% cases
Cervical lymph nodes involvement common
3) Distant metastasis is rare, mostly to the lungs if it
occurs. Can involve bones, soft tissues, central
nervous system, pancreas, breast.
39.
40. Markers reported to be useful for differentiating
follicular variant of PTC from follicular adenoma:
1)HBME-1
2)CK-19
3)Galectin 3
But not used widely; diagnosis ultimately rests on
H&E.
41. ACTIVATION OF MAP KINASE (MITOGEN
ACTIVATED PROTEIN KINASE) PATHWAY
Rearrangements of Point mutations in
RET or NTRK1 BRAF
42. 10q11
Encodes for transmembrane tyrosine kinase not normally
expressed in follicular cells.
PAPILLARY CANCERS-
i)paracentric inversion of chr.10
ii) reciprocal translocation between chr 10 and 17
RET/PTC fusion protein(RET/PTC-1 fusion is the most
common, followed by RET/PTC-3)
constitutive activation of tyrosine kinase
activation of MAP kinase pathway
43. NTKR1 (neurotrophic tyrosine kinase receptor 1)
1q21
Paracentric inversions or translocations fusion proteins
constitutively expressed activation of MAP kinase
pathway
BRAF GENE
Gain of function mutation thymine to adenine
transversions in nucleotide 1799 of exon 15 valine to
glutamate change on codon 600 (V600E)
a/w adverse prognostic factors like metastatic disease and
extra-thyroidal extension
RAS GENE
confined to the encapsulated follicular variant
44. Indolent neoplasm with an excellent long-term
prognosis
Total thyroidectomy
For more advanced cancers, such as T3 or T4
tumors, or cancers that have spread to lymph
nodes or distant sites, RAI therapy is often given
Areas of distant spread that do not respond to RAI
may need to be treated with external beam
radiation therapy, targeted therapy,
or chemotherapy.
45. Less common(10%-15%)
DEFINITION-Follicular epithelial cell
differentiated thyroid neoplasm, not belonging to
thyroid papillary carcinoma, with evidence of
invasion (i.e., capsular and/or vascular invasion)
and/or metastatic disease
Types-
1.MINIMALLY INVASIVE
2.WIDELY INVASIVE
46. Sex-Female predominance (M/F 1 : 2.5 to 1 : 4)
Age- Minimally invasive type: mean 48 yr
Widely invasive type: mean 55 yr
Presentation- Slow-growing thyroid nodule; some
present with fast-growing thyroid mass or distant
metastasis
Always UNIFOCAL
47. 1.Minimally invasive follicular carcinoma-
-solid, fleshy, and tan to light brown
-Well encapsulated; grossly indistinguishable from
follicular adenomas.
-size ranges from less than 1 cm to over 10 cm
2. Widely invasive follicular carcinomas-
-may lack a discrete capsule
-extensive invasion of surrounding gland and/or soft
tissue beyond thyroid
48. Patternwell-formed follicles to solid to trabecular
Nuclei round to oval with granular chromatin
Mitotic activity present
Necrosis absent
Oncocytic variant(hurthle cell )major variant
51. WHO definition-
1) involves blood vessels located within or outside the
fibrous capsule
2)presence of intravascular tumour cells either
covered by endothelium or associated with thrombus.
52.
53. polypoid tumor plug within blood vessel
attachment to the wall
this is not an essential criterion for recognition of vascular invasion
54. tumor plug lying within the vascular
lumen covered by endothelium
tumor plug within the vascular
space is not covered by endothelium
but associated with thrombus
55. WHO DEFINITION-
Tumour penetration through the capsule not caused
by previous fine needle aspiration
Complete transgression of the fibrous capsule must
be seen i.e. the tumor bud has to extend beyond an
imaginary line drawn through the external contour
of the capsule
Invasion needs to be definitive and takes shape of
‘’mushrooming ‘’of tumour outward
56.
57. tumor bud penetrated through the
fibrous capsule, reaching beyond the
external contour of the capsule
58. High risk counterpart of minimally invasive subtype
Widespread infiltration of blood vessels and/or
adjacent thyroid tissue
Lacks encapsulation
59. Follicular carcinoma classified as:
1) ENCAPSULATED
- With capsular ( but no vascular invasion)
-with limited (<4) vascular invasion ( with or
without capsular invasion)
- With extensive (>4)vascular invasion ( with or
without capsular invasion)
2) WIDELY INVASIVE
60. Reactive for thyroglobulin
TTF-1
low molecular weight keratins
EMA
basement membrane components
61. ACTIVATION OF PHOSPHATIDYLINOSITOL-3-
KINASE(PI-3K)/AKT PATHWAY
i) gain of function point mutations of RAS and
PIK3CA
ii) amplification of PIK3CA
iii)loss of mutations of PTEN
t(2;3)(q13;p25)fusion of PAX8 and peroxisome
proliferator-activated receptor gene(PPRAG)
62. 1) Low tendency for local spread beyond the
thyroid capsule except widely invasive types
2) Lymph node metastasis uncommon
3) Blood borne metastasis- common
most common sites- lungs and bone;
kidney , skin
THROGLOBULIN and/or TTF-1 staining is
essential in confirming the thyroid origin of
metastatic tumour
63. Major histopathological variant of follicular
carcinoma
Comprises 20% to 25% of all follicular carcinomas
DEFINITION- Should be composed of atleast 75%
oncocytic cells with abundant ,brightly
eosinophilic, granular cytoplasm (caused by
accumulation of mitochondria) and
nuclei vesicular ; prominent single nucleoli
64. Most Hurthle cell neoplasms are follicular in
pattern, the criterion for distinguishing benign from
malignant is the same as for follicular neoplasms -
identification of capsular or vascular invasion
66. Growth pattern:the follicular(most common in
adenoma), trabecular/solid, or papillary
Can show calcifications, which may be confused
with psammoma bodies, but these calcifications are
present within the colloid
nuclei may show pleomorphism and prominent
nucleoli, with occurrence of isolated bizarre forms,
these not being features of malignancy
Proof of malignancy is vascular and capsular
invasion
68. DIFFERNTIAL
DIAGNOSIS
HISTOPATHOLOGY IHC
1)Follicular adenoma
( from minimally
invasive type)
Lack of capsular and
vascular invasion
2) Medullary carcinoma
of thyroid
MTC- rarely follicular;
nuclei are spindle shaped
MTC +ve for neuroendocrine
markers,CEA, calcitonin( -ve
in follicular carcinoma)
-ve for thyroglobulin(+ve in
follicular carcinoma)
3)Poorly differentiated
( insular) carcinomas
(differentiated from
widely invasive type)
Insular carcinoma- less
cytoplasm; minimal
follicular archietecture;
marked mitotic activity ;
marked necrosis
4)Hashimoto thyroiditis
and dyshormogenesis
Lack of capsular and
vascular invasion
69. Total thyroidectomy + central compartment or
modified neck dissection (if lymph nodes are
involved)
Spread to nearby lymph nodes and to distant sites
that shows up on the scan can be treated by
radioactive iodine (RAI)
Distant metastases may need to be treated with
external beam radiation therapy, targeted therapy,
or chemotherapy if they do not respond to RAI
70. DEFINITION-evidence of follicular differentiation;
morphologically and biologically fits between well-
differentiated and undifferentiated thyroid carcinomas
More common in women(F/M = 1.6 : 1-2 : 1)
Age- after 60 years
Presentation-asymptomatic masses
GROSS-large; solid grey to white nodules; necrosis
common
71. solid and firm, with a gray-
white cut surface; areas
of necrosis and hemorrhage
are frequently present
75. Small uniform tumour cells;round
hyperchromatic nuclei;mitotic figures seen;
absence of nuclear features of papillary
carcinoma
76. Positive for TTF-1
PAX-8
thyroglobulin
Decreased expression of the cyclin-dependent kinase
inhibitor p27 and increased Ki-67 index are seen-
Helps to differentiate from differentiated thyroid
carcinomas
77. 1)MEDULLARY
CARCINOMA
MTC more prominent vasculature, granular
cytoplasm, and finely stippled chromatin
+ve for calcitonin
Insular +ve for thyroglobulin
2)SOLID VARIANT OF
PAPILLARY CARCINOMA
extensive presence of typical nuclear features of
papillary carcinoma
3)UNDIFFERENTIATED
THYROID CARCINOMA
POORLY DIFFERENTIATED-
Maintenance of follicular cell differentiation;
Immunoreactivity for thyroglobulin and TTF-1;
UNDIFFERENTIATED-
Completely lacks evidence of follicular
cell differentiation ;prominent nuclear
pleomorphism and frequent mitoses;
Immunostaining for thyroglobulin and TTF-1 is
generally negative
78. Incidence-2-3%
M/F ratio 1 : 1.1 to 1 : 2
Mean age-70 years
Etiological factors-a)iodine deficiency
b)radiation exposure
c)pre existing thyroid disease
(long-standing goitre)
Presentation- rapidly growing neck mass with local signs
and symptoms like hoarseness, dysphagia,pain,vocal cord
paralysis
79. fleshy and white-tan,
with frequent necrosis and
hemorrhage; entirely
replacing the gland and
extending into the
surrounding skeletal muscle
80. Two major categories:
1.Squamoid
2.Sarcomatoid: spindle cell and giant cell
Undifferentiated carcinoma of the
spindle cell type
Undifferentiated carcinoma of giant
cell type
81. Cells have moderate amount of eosinophilic
cytoplasm
Brisk mitotic activity
Abundant apoptosis.
82. Positive for cytokeratin(80% cases)
EMA(30-50% cases)
Useful when there is no obvious carcinomatous
differentiation present on H& E. IHC helps to confirm
that the neoplasm is a carcinoma rather than high grade
sarcoma
Lack of staining with epithelial markers doesn’t exclude
the diagnosis of UTC
Nuclear reactivity PAX 8(80% cases)
83. TTF-1 and thyroglobulin- typically negative
Calcitonin and neuroendocrine makers- negative
84. TP53 mutation
Mutations in the β-catenin (CTNNB-1) gene
RAS mutation (approximately 30%),BRAF mutation
(approximately 30%), or RET/PTC fusion gene may
be seen in some cases
85. 1)SARCOMA any “sarcoma looking”tumor of the thyroid should
be regarded as undifferentiated carcinoma unless
strong proof exists otherwise
2)SOLID VARIANT OF
PAPILLARY
CARINOMA
Solid variant- nuclear features of papillary
carcinoma
Lack of mitosis
3)LARGE CELL
LYMPHOMA
Lymphoma- less cellular cohesion; presence of
plasmacytoid cytoplasm or stuffing of follicular
lumina
IHC can readily differntiate
4)PARATHYROID
CARCINOMA
It shows presence of clear cells, a mixture of cell
types, and paucity of mitotic figures
5)POORLY
DIFFERENTIATED
CARCINOMA
86. surgery is often not helpful .Goal of surgery is to
remove as much cancer in the neck area as possible
Radioactive iodine treatment- no role
External beam radiation therapy may be used alone or
combined with chemotherapy:
1)To try to shrink the cancer before surgery to increase
the chance of complete tumor removal
2)After surgery to try to control any disease that
remains in the neck
3)When the tumor is too large or widespread to be
treated by surgery
87. DEFINITION-Medullary carcinoma is a malignant
tumor showing parafollicular C-cell differentiation
Characteristically secretes calcitonin
Incidence-5-10%
20% cases are familial; strong association with
MEN type 2
88. SPORADIC AND NON-
MEN FAMILIAL MTC FAMILIAL MTC
50-60 years
Unilateral
MEN2A- younger age
group(mean age third
decade); multifocal;
bilateral
MEN2B- adolescence or
childhood
98. Screening for pheochromocytoma is particularly
important( MEN2a) , since the unknown presence of
this tumor can make anesthesia and surgery extremely
dangerous
Stages I and II: Total thyroidectomy+ bilateral central
compartment or modified radical neck dissection
Stages III and IV: Surgery is the same as for stages I
and II .
When the tumor is extensive and invades many
nearby tissues or cannot be completely
removed, external beam radiation therapy may be given
after surgery
99. Genetic testing can find mutations in
the RET gene
close family members should be tested as well
anyone who has a RET gene mutation
prophylatically thyroidectomy is done
Solid, white, firm, often multifocal (65%), encapsulated (10%). encapsulated cases can be grossly indistinguishable from a follicular adenoma. The cut surfaces may be gritty because of the presence of psammoma bodies and calcifications.
Marked cystic changes seen in 10% cases. Particularly in lymph node metastasis. And the bulk of nodal metastasis may far outstrip the volume of tumour in the thyroid gland. Cystic metastases are particularly problematic, because they may be mistaken for branchial cysts or benign cysts clinically or histologically
Nuclear grooving page 1184 fletchers
These represent invaginations of the cytoplasm and appear as sharply outlined (nuclear membrane-bound) round acidophilic vacuoles - ackerman
Over half of the cases show extensive fibrosis, usually in the form of sharply outlined bands traversing the tumor; the appearance of this fibrosis may range from sclerohyaline to highly cellular (Fig. 9.36). Elastic tissue is usually abundant in the tumor stroma – ackerman.
The dense hyaline fibrosis has been suggested to be a useful feature for distinguishing papillary carcinoma (89% of cases)
from follicular carcinoma (18% of cases).- fletchers
particularly common in children; distinguished from insular carcinoma and other forms of poorly differentiated carcinoma because the nuclear features remain those of papillary carcinoma- ACKERMAN
papillary carcinoma totally surrounded by a capsule; nodal metastases may be; distant metastases or tumor death is nearly zero; should be distinguished from the hyperplastic nodule with central cystic degeneration and papillary or pseudopapillary fronds in the wall -ACKERMAN
children and young adults; diffuse involvement of one or both thyroid lobes; dense sclerosis, abundant psammoma bodies, extensive solid foci, squamous metaplasia, heavy lymphocytic infiltration, and extensive lymph vessel permeation ; may be misdiagnosed as Hashimoto thyroiditis; Nodal metastases are nearly always present, lung metastases are common, multiple brain metastases may supervene, and the disease-free survival rate is lower -ACKERMAN
“composed predominantly of cells whose heights are at least three times their widths” tends to affect older patients more often than the conventional form, extrathyroidal extension is more common, and the clinical course is said to be more aggressive
Ret or NTRK1-
Always unifocal
Both qualifies for vascular invasion
Fletchers 1223
TURIN CRITERIA FOR HISTOLOGICAL DIAGNOSIS of poorly differentiated carcinoma
A. solid islands (insular pattern) separated by delicate sclerotic septa.