• Also called hyperplastic or adenomatoid
• Unilateral painless mass
• Arises in a background of nodular goiter
• Can show complete or partial encapsulation
• Usually contain a mixture of macrofollicules
and microfollicules or indl single pattern.
• Asymptomatic & accidentally discovered.
• Pressure symptoms
• Toxic adenomas
• Investigations : USG, FNAC, excision biopsy
• Nodules are not showing any specific growth pattern
even if they are solitary.
• It occurs in a normal thyroid showing only
microscopic evidence of nodular goiter( so called
dominant hyperplastic nodule)
• Some nodules may be hyperfunctional and
morphologically represent hyperplastic nodule or
• If multiple nodules are hyperfunctioning than it
called Toxic nodular goiter.
Points to remember
• Solitary nodules
• Nodules in younger pts
• Nodules in males
• H/O radiation therapy to head
& neck region
• Hot nodules are more likely to be benign
• Discrete solitary masses (follicular adenomas)
Simple colloid adenomas [macrofollicular]
Fetal/microfollicular, embryonal, trabecular
• Nonfunctional, most of the times
• Hormone production in functional adenomas is
independent of TSH stimulation( Toxic Adenomas)
• Cellular smear with numerous follicular cells and
little or no colloid.
• Most of the follicular cells arranged in syncytial
fragments and exhibit a microfollicular pattern.
• Microfollicules consists of 6-12 nuclei in a small
ring with central dot of colloid
•In macrofollicular adenoma cells are arranged in
monolayer sheets with abundant colloid.
• FA are immunoreactive for Cytokeratins,
Thyroglobuline and TTF-1.
• But non reactive for CK-19, Calcitonin or pan-
Variants of FA
- Oncocytic Adenoma
- FA with papillary hyperplasia
- Fetal Adenoma
- Singnet ring cell FA
- Mucinous FA
- Clear cell FA
- Toxic Adenoma
- Atypical Adenoma
- FA with bizarre nuclei
• Malignant epithelial tumor showing evidence
of follicular cell differentiation and lacking of
diagnostic nuclear features of papillary
• 10-15% of thyroid malignancy.
• More common in female and peak age 50 yrs.
• Rarely occur in children
• Incidence is dramatically decreased due to
adequate dietary supplementation of iodine
and exclusion of FVPTC from this category.
• Iodine deficiency and irradiation is the most
common etiological factor.
• Most common site is normally situated thyroid
and ectopic thyroid tissue( struma ovarii)
• Most common presentation asymptomatic
intrathyroidal mass lesions.
• Ipsilateral lymphadenopathy is less common
than PC ( less than 5%)
• Cold on scintigraphic scan.
• Hoarseness, dysphegia and dyspnea rare but
may occur in widely invasive FC.
• No definit precursor lesions but may arise
• Multifocality is uncommon.
• Recurrence rate is high in residual tumor after
• Lymph node metastases uncommon.
• Most common site for distant metastases are
lung and bone.
Cytology: Follicular carcinoma
• Hypercellular with a dispersed microfollicular
arrangement of tumor cells and scant colloid.
• Microfollicules consists of 6-12 nuclei forming
a small ring like structure.
• Presence of nuclear atypia does not correlate
with malignancy since FC may shows bland
cytological characteristic and FA may shows
considerable nuclear atypia.
Cellular smear single cell & microfollicles pattern, diagnosed by
histopath as follicular carcinoma with vascular invasion.
• FC shows variable morphological pattern
ranging from well formed colloid containing
follicles, solid, trabecular to poorly form
follicles to atypical pattern ( cribriform).
• Neither architectural pattern nor cytological
features are reliable for its diagnosis
• FC diagnosed on the basis of invasiveness.
• Minimally invasive FC have limited capsular
and vascular invasion.
• Widely invasive FC have widespread
infiltration of adjacent thyroid tissue or
• Capsular invasion- Defined by tumor
penetrating through the tumor capsule
unassociated with the site of previous FNAC.
• Vascular invasion- Defined by presence of
intravascular tumor cells either covered by
endothelium or associated with thrombus.
- Involved vessels must be within or
beyond the tumor capsule.
- Foci of vascular invasion should be
distinguish from sub endothelial collection of
tumor cells and retraction artifacts.
FOLLICULAR CARCINOMA MINIMALLY INVASIVE TYPE: (A) TUMOR DEMONESTRATE
COMPLETE PENETRATION OF THE CAPSULE AND HAS MUSHROOM LIKE
CONFIGURATION. (B) MINIMAL CAPSULAR AND VASCULAR INVASION. (C) FOCAL
INVASION OF A CAPSULAR VESSELS.
FOLLICULAR CARCINOMA WIDELY INVASIVE TYPE (A) MULTIFOCAL AREAS OF INVASION
OF CAPSULAR VESSELS. (B) TUMOR HAS EXTENDED BEYOUND THE CAPSULE AND IS
PRESENTS WITHIN VASCULAR SPACE. (C) MULTIPLE FOCI OF VASCULAR INVASION ARE
Variants of FC
• Oncocytic variant
- 3-4% thyroid malignancy.
- other name oxyphil and hurthle cell
- Median age 61yrs
- 30% cases associated with nodal
metastases. Distant metastases is rare
• Clear cell variant
- Composed predominantly of clear cells.
- Contain glycogen, mucin, lipid or dilated
- Signet ring follicular cell may sometime
major component of this variant.
• Immunoreactive to Thyroglobulin, TTF-1 and
• CK-19 and lewis blood antigen are focally
positive but rare in FA and NG. But strong
positivity in PC
• Galectin-3, HBME-1, CD-15 & CD44v6 positive.
• E-cdherin and beta catenin shows
membranous positivity but also positive in
case of normal thyroid, benign follicular
lesions and FVPTC.
• Bcl-2 positive, TP53 negative, display low level
of cyclin D1 and high levels of P27 with low
• Telomerase expression is higher than FA and
Follicular variant of PC
• Tumors resemble encapsulated follicular
neoplasm composed of small to medium sized
irregularly shaped follicles with virtually no
• Variable amount of colloid may appear
hypereosinophilic and scalloped.
• Majority of the cells lining in the follicles
contain large clear nuclei with grooves and
• Intrafollicular multinucleated giant cells are
frequent but stromal sclerosis and psammoma
bodies are occasional.
• Despite complete encapsulation, lymph node
and rarely distant metastases can occur.
• Cytology smear shows non-cohesive cells
arranged in follicles found in a background of
little colloid. Nuclear crowding with powdery
chromatin and grooves are seen. Intranuclear
inclusions are less as compared to
FVPTC, tumor is encapsulated and
grossly resemble a follicular
FNAC shows nuclear crowding with
powdery chromatin and grooves.
Follicular variant of medullary
• Extremely rare and also called mixed
• Presence of follicular or glandular structures in
a medullary carcinoma can result true
follicular pattern growth or entrapment of
neighboring follicles by invasive tumor.
• Immunoreactivity to calcitonin and
Poorly differentiated carcinoma
• Morphologically and behaviorally an intermediate
position between differentiated ( FC, PC) and
undifferentiated carcinoma (anaplastic).
• Etiology is unknown but most likely arise de novo
or preexisting Papillary and follicular carcinoma.
• Large solitary thyroid masses, cold by scintigraphy
and with or without concurrent enlargement of
regional lymph node.
-Highly cellular with numerous
dyscohesive small to medium sized
cells, microfollicules and scant
- Nuclei are bland with fine
chromatin and small nucleoli.
- Necrosis and mitosis are common.
- Definitive diagnosis is made out in
-More than 3 cm in diameter at the
time of diagnosis
- Solid gray white with frequent
foci of necrosis.
- Most tumor have pushing borders
and rarely thick capsule.
-Invasive peritumoral growth leads
to satellite nodules within the
• Three different growth pattern Insular, trabecular
• Diagnosis relies on the identification of these
• Infiltrative growth pattern, necrosis and vascular
• Well defined nest surrounded by fibrovascular
septae. Tumor cells are small, uniform, round
hyperchromatic to vesicular nuclei with indistinct
nucleoli. Mitotic figures are common.
• Immunoreactive for thyroglobuline and TTF-1.
• Focal TP53 nuclear positivity.
• Increased Ki-67 (MIB-1) index.
• Absence of E-cadherin membranous expresion
• Highly malignant tumors that histologically
appear wholly or partially composed of
• Occurs mainly in the elderly, only 25%
patients are younger than 60yrs.
• Female are affected more M:F = 1: 1.5
• Presented as rapidly expanded neck mass.
• Most important sign and symptoms are
- Hoarseness (80%)
- dysphagia (60%)
- Vocal cord paralysis (50%)
-Cervical pain (30%)
- Dyspnea (20%)
• Tumor may fixed and hard(75%), single(60%),
multiple nodules(40%) and B/L (25%) cases
• Surrounding structures are frequently
involved, muscles(65%), trachea(50%),
esophagus(45%), laryngeal nerve(30%) and
• 40% patients have cervical lymphadenopathy
and distant metastases.
• 50% involved lungs, 15% bone and 10% brain.
• Highly cellular, cells are singly or clusters and
marked nuclear pleomorphism.
• The cells types are squamoid, giant and
spindle with bizarre single and multiple nuclei.
• Coarsely clumped chromatin, single and
multiple prominent nucleoli.
• Mitotic figures are numerous.
• Background shows necrotic debris,
inflammatory cells and occasional osteoclast
like giant cells.
• Majority of UTC are widely invasive tumor
composed of an admixture of spindle cell,
pleomorphic giant cells and epithelioid cells.
• Percentage of cells component varies.
• Extensive coagulative necrosis with irregular
borders and palisading is often seen.
• Infiltration of vascular walls accompanied by
obliteration of the vascular lamina is common.
(A) Anaplastic carcinoma undermining laryngeal mucosa. Note the large atypical cells.
(B) High-power view of anaplastic carcinoma showing large atypical cells with mitoses.
(C) Anaplastic carcinoma with sheets of intermediate cells associated with focal
osteoclast-like giant cells and extensive hemorrhage. (D) A focus of well-differentiated
thyroid carcinoma identified adjacent to an anaplastic carcinoma
• Cytokeratin - most frequently expressed about
40-100% of cases.
• EMA (30-50%) and CEA(< 10%) less commonly
• TTF-1 rarely expressed and thyroglobulin is
• TP-53 strongly positive.
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