Cytohistological Correlation Of Malignant Thyroid Lesions Cytology Of Malignant Thyroid Lesions Histology Of Malignant Thyroid Lesions

1. CYTOHISTOLOGICAL
APPROACH TO MALIGNANT
THYROID LESIONS
PRESENTOR: DR. POOJA DWIVEDI (JR 2 M.D. PATHOLOGY)
MODERATOR: DR. SHALINI BHALLA (M.D. PDCC)
Department Of Pathology
King Georges Medical University, Lucknow

2. INTRODUCTION
A ‘Thyroid Nodule’ is defined as a discrete lesion in thyroid gland which is
radiologically distinct from surrounding thyroid parenchyma.
• Noted by patient, or as an incidental finding
• May be
Palpable or impalpable,
Functioning or non-functioning

4. Thyroid Scintigraphy :
Should be performed in patients with low
serum TSH
• Utilizes one of iodine radioisotopes ( I123)
or technetium-99m pertechnetate
• Others : Thallium-201 scan, Gallium-67,
Tc-99m sestamibi
• Most benign and virtually all malignant
thyroid nodules concentrate both
radioisotopes less avidly

5. Ultrasound Scanning : Thyroid Imaging Reporting And Data System
• Noninvasive and inexpensive
• Detect non palpable nodules
• Differentiate between cystic and solid
nodules
• Identify hemiagenesis and contralateral
lobe hypertrophy misdiagnosed as
thyroid nodule
• Detect cervical nodes that may contain
early clinically occult metastatic disease
• HRUSG NECK operator-dependent
though non-invasive, accessible
portability cost-effectiveness lack of
ionizing radiation. Allows high resolution
imaging of the thyroid (7 – 12 MHz)
Gold standard Features –
• Size
• Echogenicity
• Composition
• Calcification
• Margin
• Halo

6. THYROID IMAGING REPORTING AND DATA SYSTEM
Sonographically suspicious criteria for malignancy
Each criterion is assigned a point in the final score
If suspicious cervical lymph nodes are detected, an additional point is added to the score for
categorizing nodules on TI-RADS classification
• Hypoechogenicity
• Microcalcifications
• Partially cystic nodule with eccentric location of the fluid portion and lobulation of the solid
component
• Irregular margins
• Perinodular thyroid parenchyma invasion
• Taller-than-wide shape
• Intranodular vascularity
 Size does NOT seems to correlate with malignancy

7. TI-RADS CATEGORIES: 6 Categories
• TI-RADS 6: Biopsy-proven malignancy
• TI-RADS 5: Probably malignant nodules (>85%
risk of malignancy) Score of 5 or higher
• TI-RADS 4:
• 4a – Undetermined nodules (5-10% risk of
malignancy) Score of 1.
• 4b – Suspicious nodules (10-50% risk of
malignancy) Score of 2.
• 4c – Highly suspicious nodules (50-85% risk of
malignancy) Score of 3-4
• TI-RADS 3: Probably benign nodules

8. TI-RADS 1 TI-RADS 2
Normal Thyroid Gland Simple Thyroid Cyst

9. TI-RADS 2 TI-RADS 2
Solid Nodule With Central
Cyst
Nodule With Homogenous
Peripheral Calcification

10. TI-RADS 2 TI-RADS 3
Spongiform Nodule

11. TI-RADS 4a TI-RADS 4b

12. TI-RADS 4c

13. TI-RADS 5

14. Thyroid nodule diagnostic FNA is recommended for:
A) Nodules > 1cm in greatest dimension with high suspicion sonographic pattern
B) Nodules > 1 cm in greatest dimension with intermediate suspicion sonographic pattern
C) Nodules > 1.5cm in greatest dimension with low suspicion sonographic pattern
D) Nodules > 2cm in greatest dimension with very low suspicion sonographic pattern
Any nodule >1cm is suspicious for malignancy.

15. BETHESDA CLASSIFICATION ON FNAC

17. The Bethesda System for Reporting Thyroid Cytopathology: diagnostic
categories

18. IV. Follicular Neoplasm/Suspicious for a Follicular Neoplasm
Diagnostic category “follicular neoplasm” or “suspicious for a follicular neoplasm” refers to-
• A moderately/ high cellular aspirate comprised of follicular cell, pattern characterized by
significant cell crowding and/or micro-follicle formation
• Sparsely cellular aspirates are excluded from this category and interpreted as atypia of
undetermined significance or follicular lesion of undetermined significance
• Follicular-patterned aspirates with mild nuclear changes, such as –
• Increased nuclear size Classified as FN/SFN
• Nuclear contour irregularity true papillae and intranuclear
• Chromatin clearing pseudo-inclusions absent
• Some nuclear features raise the possibility of an invasive follicular variant of papillary
carcinoma or non-invasive follicular thyroid neoplasm with papillary-like nuclear features
(NIFTP) can be included in it

19. • Cytologic preparations are
moderately or markedly cellular
• With significant alteration in
follicular cell architecture,
characterized by cell crowding,
microfollicles, and dispersed
isolated cells
• Follicular cells are normal-sized or
enlarged, relatively uniform
• Cytoplasm- scant or moderate
• Nuclei- round and slightly
hyperchromatic
• Nucleoli- inconspicuous

21. Encapsulated Follicular- Patterned Neoplasms

22. ENCAPSULATED FOLLICULAR PATTERNED NEOPLASM

23. 1.Follicular adenoma
• Follicular adenoma is a benign
encapsulated most common thyroid
neoplasm that shows evidence of follicular
cell differentiation and lacks:
(1) Evidence of capsular, vascular or any
other type of invasion
(2) Nuclear features of the papillary family of
neoplasms
The differential diagnosis of follicular
adenoma includes
1) A dominant nodule of nodular
hyperplasia
2) Minimally invasive follicular carcinoma
3) Follicular variant of papillary carcinoma

25. Follicular adenoma with bizarre nuclei

26. 2. Follicular carcinoma
• Any malignant thyroid tumor exhibiting
evidence of follicular cell differentiation
• Follicular carcinoma is a rare neoplasm
whose identification depends on the
presence of invasion of the capsule, blood
vessels
• Focal or extensive cytoplasmic clear
changes can be seen
• Mitotic activity and nuclear atypia are
usually seen
• Psammoma bodies are absent and
squamous metaplasia is rare
Follicular carcinoma
Minimally Invasive
Encapsulated
i. With capsular (but no vascular) invasion
ii. With limited (<4) vascular invasion
(with or without capsular invasion)
iii. With extensive (>4) vascular invasion
(with or without capsular invasion)
Widely invasive
Now in WHO 2017 Classification of
Thyroid Tumors these comes under
Encapsulated Angioinvasive Carcinoma

27. Microscopically:
• The vessels involved are located in or immediately
outside the capsule (rather than within the tumor)
• Contain one or more clusters of tumor cells attached
to the wall and protruding into the lumen
• Intravascular tumor masses covered by endothelium,
in a fashion similar to that of an ordinary thrombus

28. Interpretatin of the presence or absence of capsular invasion

29. Follicular Carcinoma: Subtypes
Minimally invasive follicular carcinoma
 For tumors showing definite capsular invasion and no PTC-type nuclear changes:
Follicular carcinoma
 For tumors showing questionable capsular invasion:
Follicular tumor of uncertain malignant potential (FT-UMP): if PTC-type nuclear changes
are absent
Well-differentiated tumor of uncertain malignant potential (WDT-UMP): if PTC-type
nuclear changes are questionable
Widely invasive follicular carcinoma

31. Non-invasive follicular thyroid neoplasm with papillary-like nuclear features
• Diagnostic criteria for non-Invasive folllcular thyroid
neoplasm with papillary-like nuclear features
1. Encapsulation or clear demarcation
2. Follicular growth pattern with all of the following:
< 1% papillae
No psammoma bodies
< 30% solid, trabecular, or Insular growth pattern
3. Nuclear features of papillary carcinoma
(I.e. nuclear score of 2-3)
4. No lympho-vascular or capsular Invasion
5. No tumour necrosis
6. No high mitotic activity
(< 3 mitoses per 10 high-power fields)

33. Follicular Neoplasm, Hürthle Cell (Oncocytic) Type/Suspicious for a
Follicular Neoplasm, Hürthle Cell (Oncocytic) Type
• Category under which cellular aspirate consists exclusively Hürthle cells
• Hürthle cells with nuclear features of papillary carcinoma are excluded from this category
Hürthle cells:
• Variable size cells as isolated cells or in crowded groups, colloid is absent
• Enlarged, central or eccentrically located, round nucleus
• Prominent nucleolus
• Small cells with high nuclear/cytoplasmic (N/C) ratio (small-cell dysplasia)
• Large cells with at least two times variability in nuclear size (large-cell dysplasia)

35. Hürthle cell (oncocytic) tumors
Grossly:
• Tumors are characteristically solid, tan,
and well vascularized
• Well encapsulated
• Invasive tumors tend to grow into the
parenchyma in a multinodular fashion
that can be under-interpreted as nodular
hyperplasia

36. Hürthle cell tumors: On Histology
• Pattern of growth- follicular, trabecular/solid, or
papillary
• Follicles separated by long and thin fibrovascular
septa
• Nuclei show pleomorphism and prominent
nucleoli, with isolated bizarre forms
• Hürthle cell tumors with follicular or
solid/trabecular patterns also capsular and/or
blood vessel invasion should be used as the main
criterion for malignancy

37. V. Suspicious for Malignancy
The diagnostic category “suspicious for malignancy” (SFM) is used when-
• Some cytomorphologic features (most often those of PTC) raise a strong suspicion of
malignancy but the findings are not sufficient for a conclusive diagnosis
• Specimens that are suspicious for a follicular or Hürthle cell neoplasm are excluded from
this category
• For SFM category, the morphologic changes are of such a degree that a malignancy is
considered more likely than not

38. 1. Suspicious for Papillary Thyroid Carcinoma
• A) Pattern A (Patchy Nuclear Changes
Pattern)
• Moderately or highly cellular
• Unremarkable follicular cells
predominantly in macrofollicle fragments,
admixed with cells having nuclear
enlargement, nuclear pallor, nuclear
grooves, nuclear membrane irregularity,
and/or nuclear moulding
• Intranuclear pseudo-inclusions (INCIs)
are very few or absent
• Psammoma bodies and papillary
architecture are absent

39. B) Pattern B (Incomplete Nuclear Changes Pattern)
• The sample is sparsely, moderately, or
highly cellular
• Features are almost similar to pattern A
except in nuclear membrane irregularity
and nuclear molding are minimal or
absent
C) Pattern C (Sparsely Cellular
Specimen Pattern)
Sparsely cellular with features of PTC

40. D) Pattern D (Cystic Degeneration Pattern)
• Evidence of cystic degeneration based on
presence of hemosiderin-laden
macrophages
• Scattered groups and sheets of follicular
cells have enlarged, pale nuclei and some
have nuclear grooves
• INCIs are very few or absent, and
psammoma bodies or papillary
architecture is absent
• Presence of large, atypical, “histiocytoid”
cells with enlarged nuclei and abundant
vacuolated cytoplasm

41. 2. Suspicious for Medullary Thyroid Carcinoma
• Sparsely or moderately cellular smear with
monomorphic population of non-cohesive
small- or medium-sized cells with a high
nuclear/cytoplasmic (N/C) ratio
• Ill-defined cell borders and plasmacytoid
contours of cells
• Relatively uniform eccentrically located larger
stripped nuclei
• Prominent nucleoli smudged chromatin, no
cytoplasmic granules
• Small fragments of amorphous material –
colloid or amyloid seen

42. 3. Suspicious for Lymphoma
• Sparsely cellular sample composed of
numerous monomorphic small- to
intermediate sized atypical lymphoid
cells
• To confirm a diagnosis of lymphoma we
use flow cytometery or
immunohistochemical studies

43. 4. Suspicious for Malignancy, Not Otherwise Specified
• Other primary thyroid malignancies like-
• undifferentiated (anaplastic) carcinoma
• poorly differentiated carcinoma are
encountered in the thyroid, as are
metastases

44. Modified Version of WHO Classification of Nonmedullary Thyroid Tumors

45. MALIGNANT TUMORS OF THYROID
1. Papillary Thyroid Carcinoma,
Variants, and Related Tumors
2. Medullary Thyroid Carcinoma
3. Undifferentiated (Anaplastic)
Carcinoma and Squamous Cell
Carcinoma of the Thyroid
4. Metastatic Tumors,
Lymphomas, and Rare Tumors
of the Thyroid
• From a histogenetic/differentiation
standpoint, it is preferable to divide
thyroid neoplasms into three major
categories, depending on the cell types
involved, and subdivide them into the
various benign and malignant categories:
1) Tumors exhibiting follicular cell
differentiation
2) Tumors exhibiting C-cell
differentiation
3) Tumors exhibiting follicular and C-cell
differentiation

46. 1. Papillary Thyroid Carcinoma, Variants, and Related Tumors
• PTC is a malignant epithelial tumor
derived from the thyroid follicular
epithelium
GROSS:
• The size of the primary tumor ranges
from microscopic to huge
• A very high proportion of thyroid cancers
measuring less than 1 cm in diameter are
of papillary type
• Most cases are solid, whitish, firm, and
clearly invasive

47. Criteria – On Cytology
• Cells arranged in papillae and/or
monolayers
• Cellular swirls (“onion-skin” or
“cartwheel” patterns)
• Enlarged and crowded nuclei, often
moulded
• Oval or irregularly shaped nuclei
• Longitudinal nuclear grooves
• Intranuclear cytoplasmic pseudo-
inclusions (INCIs)
• Pale nuclei with powdery chromatin
• Thick nuclear membranes
• Marginally placed micronucleoli, solitary
or multiple
• Psammoma bodies
• Multinucleated giant cells
• Variable amount of colloid; may be
stringy, ropy, or “bubblegum”-like
• “Hobnail” cells
• Oncocytic (Hürthle cell) metaplasia
• Squamoid metaplasia
• “Histiocytoid” cells

48. Microscopically
• Typical papillary carcinoma contains-
numerous true papillae
• Papillae are usually complex, branching,
and randomly oriented, with a central
fibrovascular core and a single or
stratified lining of cuboidal cells, some of
which may have hobnail features

49. • These nuclear features (which we will
herein refer to as PTC-type nuclei)
consist of:
• Ground glass (optically clear) nuclei
• Nuclear pseudo-inclusions
• Nuclear grooves
• Nuclear microfilaments
• Mitoses are very scanty or absent in
papillary carcinoma
• Psammoma bodies are seen in
approximately half of the cases

52. Variants of Papillary Thyroid Carcinoma
1) Follicular Variant and NIFTP
2) Macrofollicular Variant
3) Cystic Variant
4) Oncocytic Variant
5) Warthin-Like Variant
6) Tall Cell Variant
7) Columnar Cell Variant
8) Solid Variant
9) Diffuse Sclerosing Variant
10) Cribriform-Morular Variant
11) Hobnail Variant

53. 1. Follicular Variant Vs NIFTP
Follicular variant of PTC
• The follicular variant of PTC (FVPTC) is
completely composed of small- to
medium-sized follicles
• Lined by cells with variable nuclear
features of PTC
Non-invasive follicular thyroid neoplasm with
papillary-like nuclear features
• An encapsulated or well-demarcated
neoplasm with follicular-patterned
morphology and variable nuclear features
of PTC, without capsular or vascular
invasion
• This term was introduced to recognize
the indolent behaviour of thyroid
neoplasms previously classified as non-
invasive FVPTC.

54. Criteria: On Cytology
• Samples hypercellular, with syncytial-like fragments containing microfollicles (“rosettes”)
• Dispersed microfollicular clusters, isolated neoplastic follicles, and some sheets with
branched irregular contours may also be present
• Some colloid may be present, typically dense-staining, thick, and sometimes within
neoplastic follicles
• The following features are usually absent or inconspicuous:
Papillary and papillary-like fragments, multinucleated giant cells, INCIs, psammoma
bodies, and marked cystic change

55. Follicular Variant NIFTP

56. 2. Macrofollicular Variant
• Criteria: On Cytology
• The sample consists of monolayered
(two-dimensional) sheets of neoplastic
epithelium and/or variably sized follicles
• Nuclear changes of PTC must be present
for a definite interpretation of
malignancy
• Papillary structures and psammoma
bodies are not seen
• Abundant thin colloid or fragments of
thick colloid may be present

57. 3. Cystic Variant
Criteria: On Cytology
• Neoplastic cells typically arranged in small
groups with irregular borders; sheets, papillae,
or follicles
• Tumor cells look “histiocytoid”
(hypervacuolated)
• Macrophages, often containing hemosiderin, are
present
• There is a variable amount of thin or watery
colloid
• Convincing nuclear changes of PTC must be
present for a definite diagnosis of malignancy
• In contrast to conventional PTC, fine, powdery
chromatin is usually less prominent

58. 4. Oncocytic Variant
• Criteria: On Cytology
• The sample is composed predominantly
of oncocytic cells (polygonal cells with
abundant granular cytoplasm), arranged
in papillae, sheets, microfollicles, or as
isolated cells
• Convincing diagnostic nuclear changes
of PTC must be present for a definite
diagnosis of PTC
• Lymphocytes are absent or few in
number

59. 5. Warthin-Like Variant
• Criteria: On Cytology
• The neoplastic cells are oncocytic and
arranged in papillae and as dispersed
cells
• A lymphoplasmacytic background is
present
• The lymphocytes and plasma cells
permeate the fibrovascular stalk and are
intimately associated with the tumor cells
• Convincing nuclear changes of PTC
must be present for a definite diagnosis
of malignancy

60. 6. Tall Cell Variant
• Criteria: On Cytology
• The neoplastic cells are most commonly
polygonal with centrally located nuclei
but can be elongated and cylindrical with
an eccentrically placed nucleus (“tail-like
cells” or “tadpole cells”)
• They have granular cytoplasm with
prominent cytoplasmic borders
• Some lymphocytes may be present
• Convincing nuclear changes of PTC
must be present for a definite diagnosis
of malignancy

61. Tall Cell Variant: On Histology
Tall cell variant is a type of papillary
carcinoma characterized by-
• Papillae lined by a single layer of ‘tall’
cells (the height being at least three times
the width)
• Aabundant acidophilic (oncocytoid)
cytoplasm
• These features should be present in at least
half of the tumor for it to be placed in this
category
• Nuclear pseudo-inclusions are particularly
prominent
• Extensive lymphocytic infiltration of the
stroma may seen

62. 7. Columnar Cell Variant
• Criteria: On Cytology
• Smears are cellular and generally lack
colloid
• The neoplastic cells are arranged as
papillae, clusters, and flat sheets,
sometimes with small tubular structures
• The nuclei are elongated and
pseudostratified
• Focal cytoplasmic vacuolization may be
present
• Convincing nuclear changes of PTC must
be present for a definitive diagnosis of
malignancy
In contrast to conventional PTC:
• The nuclear features of PTC (grooves,
INCIs) are much less prominent
• The nuclear chromatin tends to be
hyperchromatic rather than pale and
powdery
• Colloid and cystic changes (macrophages)
are typically not seen

63. Columnar Cell Variant

64. Columnar Cell Variant: On Histology
In columnar cell carcinoma, there is-
• Prominent pseodostratification
• Cytoplasm is clear (sometimes with
subnuclear vacuolization, reminiscent of
early secretory endometrium) rather than
acidophilic
• Nuclei usually lack the optically clear
appearance, grooves, and pseudo-
inclusions

65. 8. Solid Variant
• Criteria: On Cytology
• Smears variably cellular and generally
lack colloid
• Neoplastic cells appear as cohesive,
syncytial-type three-dimensional tissue
fragments, microfollicles/trabeculae, or
noncohesive, single cells
• Nuclei usually show the typical nuclear
features of PTC, but they may be less
elongated (rounder) and darker than
those of conventional PTC
• True papillary formations with
fibrovascular cores are scant or absent

66. Solid Variant: On Histology
• This variant, which is particularly
common in children
• Develops when proliferation
predominates over secretion
• Characterized by solid nests of generally
round shape that can be viewed as filled-
up follicles

67. 9. Diffuse Sclerosing Variant
• Criteria: On Cytology
• Smears moderately to highly cellular with
scant or absent colloid
• Neoplastic cells arranged in three-
dimensional ball-like clusters and cohesive
clusters intermingled with inflammatory
cells
• Conventional monolayered syncytial and
papillary clusters may also be present
• Neoplastic cells are round, polygonal, or
columnar, with dense cytoplasm and
distinct cytoplasmic borders
• Hobnail cells protruding from cell clusters
are often present
• In contrast to conventional PTC:
• There is less chromatin pallor
• There are fewer INCIs and nuclear grooves
• Large septate or unilocular cytoplasmic
vacuoles are common
• Squamous metaplastic changes are
common
• Numerous lymphocytes and psammoma
bodies are present in the background

68. Diffuse Sclerosing Variant

69. Diffuse Sclerosing Variant: On Histology
Diffuse involvement of one or both thyroid
lobes with features-
• Dense sclerosis
• Abundant psammoma bodies
• Extensive solid foci
• Squamous metaplasia
• Heavy lymphocytic infiltration
• Extensive lymph vessel permeation

70. 10. Cribriform-Morular Variant
• Criteria: On Cytology
• Smears are hypercellular and Colloid is absent
• Tall, columnar neoplastic cells have a papillary-like
arrangement
• Round to oval slit-like empty spaces formed by spindle to
ovoid cells within cell clusters are present (cribriform
pattern)
• Cell clusters with eddy formation (morules) are present
• Spindle-shaped tumor cells are present in the background
• Pale-staining nuclei with thickened nuclear membranes
(peculiar nuclear clearing) is present focally
• Nuclear grooves are present, but INCIs are less common
than in the conventional PTC

71. 2. MEDULLARY THYROID CARCINOMA

72. MEDULLARY THYROID CARCINOMA: Cytology
• Moderate to marked cellularity with numerous isolated cells
alternate with syncytium-like clusters in variable proportions
• Cells are plasmacytoid, polygonal, round, and/or spindle-shaped
• Neoplastic cells usually show only mild to moderate
pleomorphism
• Binuclear cells, nuclei are round, oval, or elongated and often
eccentrically placed, with finely or coarsely granular (“salt and
pepper”) chromatin
• Nucleoli are usually inconspicuous but can be prominent in some
cells
• Nuclear pseudo-inclusions are occasionally noted, Nuclear
grooves rare or absent
• Cytoplasm is granular and variable in quantity.
• Amorphous amyloid is often present

75. Medullary Thyroid Carcinoma Vs Poorly Differentiated Thyroid Carcinoma

76. MEDULLARY THYROID CARCINOMA: Histology
• MTC is a malignant neuroendocrine
neoplasm derived from the parafollicular
cells (C cells) of the thyroid gland
Grossly:
• Tumor is solid, firm, and non-
encapsulated but relatively well
circumscribed and has a gray to
yellowish cut surface
• If greatest diameter of the tumor is 1 cm
or less, tumor is referred to as medullary
microcarcinoma

77. Microscopically: 1.Solid Variant
Classic presentation-
• Solid proliferation of round to polygonal
cells with granular amphophilic cytoplasm
and medium-sized nucleus, separated by a
highly vascular stroma, hyalinized collagen
• Pattern of growth can be carcinoid-like,
paraganglioma like, trabecular, glandular
(tubular and follicular)
• Stroma may be scanty, hemorrhagic,
ossified, or edematous.
• Amyloid deposition may be widespread,
limited to small psammomatoid
concretions, or altogether absent

78. 2. Pseudopapillary
Tumor cells may be-
• Plasmacytoid (because of nuclear
peripheralization)
• Spindle shaped
• Oncocytic
• Squamoid
• Squamous
• Or exhibit bizarre features so-called
‘anaplastic’ or ‘giant cell’ type
• Not to be equated with bona fide
undifferentiated carcinoma

79. 3.Oncocytic variant: Medullary Thyroid Carcinoma
• Oncocytic variety of medullary
carcinoma has resemblance to oncocytic
(Hürthle cell) neoplasms of follicular cell
• Diagnosis of oncocytic medullary
carcinoma should be suspected if:
Oncocytic cells are-
Amphophilic rather than brightly
eosinophilic
If the tumor is divided into nests by
sharply outlined fibrous bands

80. 4.Clear cell Variant
• Clear cell carcinoma is not a specific tumor type
• Clear cell changes can also occur in follicular adenomas and carcinomas, papillary
carcinoma, undifferentiated carcinoma and exceptionally – medullary carcinoma
• The stroma is usually heavily hyalinized and with punctate calcification
• Change may be of degenerative nature and the expression of an arrest of folliculogenesis:
o Signet ring type-
o Lipid-rich cell adenoma- in which the cytoplasmic vacuolization is due to the
accumulation of neutral fat

81. 3. Poorly Differentiated Thyroid Carcinoma
On Cytology:
• Cytoarchitecture- insular, solid, or
trabecular
• Uniform population of malignant
follicular cells with scant cytoplasm
(sometimes plasmacytoid)
• Individual cells have a high
nuclear/cytoplasmic (N/C) ratio with
variable nuclear atypia
• Colloid is scant
• Apoptosis and mitotic activity are present
• Necrosis is often present

83. Poorly differentiated carcinoma: Histology
Microscopically:
• Nesting (‘insular’) pattern of growth
• Solid to microfollicular arrangement
• Small uniform tumor cells
• Variable mitotic activity
• Fresh tumor necrosis resulting in a
peritheliomatous pattern
• The insular pattern may result in a
mistaken diagnosis of medullary
carcinoma

85. 4.Undifferentiated (Anaplastic) Carcinoma: Cytology
• Variable cellularity, neoplastic cells arranged as isolated
cells and/or in variably sized groups
• Cells are epithelioid (round to polygonal) and/or spindle-
shaped and range in size from small- to giant-sized.
• “Plasmacytoid” and “rhabdoid” cell shapes seen
• Nuclei show enlargement, irregularity, extreme
pleomorphism, clumping of chromatin with parachromatin
clearing, prominent irregular nucleoli, intranuclear pseudo-
inclusions, eccentric nuclear placement, and
multinucleation
• Necrosis, extensive inflammation (predominantly
neutrophils, “abscess-like”), and/ or fibrous connective
tissue may be present
• Mitotic figures numerous and abnormal
• Osteoclast-like giant cells (nonneoplastic) in some cases

87. Undifferentiated carcinoma: Histology
• Undifferentiated (anaplastic) carcinoma
usually presents in
• elderly patients
• Rapidly growing mass
• A/w hoarseness, dysphagia, and dyspnea
• Extrathyroidal extension is encountered at
the time of initial presentation
Grossly:
• A highly necrotic and hemorrhagic solid
tumor mass seen replacing large portions of
the organ

88. Microscopically:
• Does not make follicles, papillae, or even
trabeculae or nests
• Tumor retains an unmistakable epithelial
appearance on morphologic and
immunohistochemical grounds
• This pattern referred to as squamoid, may
blend with clear cut foci of keratinization

90. 5. Squamous Cell Carcinoma of the Thyroid: Cytology
Cytology:
Samples contains large, pleomorphic keratinized cells
• Necrosis may be present
Histology:
• Squamous cells can be found in the thyroid as a result
of persistence of thyroglossal duct or structures derived
from the branchial pouch (such as thymic epithelium)
• As an expression of squamous metaplasia in Hashimoto
thyroiditis, papillary carcinoma, or other pure squamous
cell carcinomas
• If squamous cell carcinoma of thyroid present, the
possibility of secondary direct involvement from a
tumor of larynx or trachea or a metastasis from lung or
other sites should also be considered

91. Mucoepidermoid carcinoma
• A low-grade thyroid neoplasm
combining foci of squamous change with
mucin production
• Originate from solid cell nests, which in
turn are thought to be of ultimobranchial
body derivation
• Tumors of ground glass nuclei and
psammoma bodies suggest that they may
represent instead papillary carcinomas
with an extreme degree of squamous and
mucinous metaplasia

92. 6. Metastatic Malignancy: a) Metastatic Renal Cell Carcinoma
• Moderate to high cellularity
• Cells are dispersed individually and in
small clusters, fragmented papillae, or
sheets
• Cytoplasm- abundant pale, finely
granular, clear, or vacuolated
• Nuclei- round to oval, often with large
nucleoli
• Samples are frequently bloody

93. b) Metastatic Breast Carcinomas
• Moderate to high cellularity with a
uniform population of oval or polygonal
cells
• Cells lie singly and in small clusters; the
isolated cells retain their cytoplasm

94. Metastatic tumors: Histology

95. c) Lymphoma Involving the Thyroid Gland: Cytology
• Markedly cellular and composed of non-
cohesive round to slightly oval cells
• Background contains numerous
lymphoglandular bodies
• Cells of marginal zone lymphoma are
about twice the size of a small mature
lymphocyte
• Nuclei have vesicular (“open”)
chromatin and small nucleoli

96. Lymphoid Tumor: Histology
Grossly:
• The tumor shows a solid white cut
surface with a fish-flesh appearance
Microscopically:
• Majority of the cases are of diffuse
large B-cell
• Sclerosis may be focally prominent

97. d) Hodgkin lymphoma

98. 7. Spindle Epithelial Tumor With Thymus-like Differentiation
• Characterized by a lobulated architecture
and biphasic cellular composition
featuring spindly epithelial cells that
merge into glandular structures
• The carcinoma must be differentiated
from synovial sarcoma, metastatic
spindle cell carcinoma, and ectopic
thymoma
• It is a slow-growing tumor with good
prognosis

99. 8. Other Neuroendocrine tumors
• Paraganglioma can occur adjacent to or
within the thyroid, sometimes in
association with carotid body tumors
• Their differential diagnosis with
medullary carcinoma and follicular
adenoma can be very difficult

100. References
1. Baloch ZW, Cibas ES, Clark DP, Layfield LJ, Ljung BM, Pitman MB, et al. The National Cancer Institute thyroid fine needle
aspiration state of the science conference: a summation. Cytojournal. 2008;5:6.
2. Baloch ZW, LiVolsi VA, Asa SL, Rosai J, Merino MJ, Randolph G, et al. Diagnostic terminology and morphologic criteria for
cytologic diagnosis of thyroid lesions: a synopsis of the National Cancer Institute Thyroid Fine-Needle Aspiration State of the
Science Conference. Diagn Cytopathol 2008;36(6): 425–37
3. Belge G, Roque L, Soares J, Bruckmann S, Thode B, Fonseca E, Clode A, Bartnitzke S, Castedo S, Bullerdiek J. Cytogenetic
investigations of 340 thyroid hyperplasias and adenomas revealing correlations between cytogenetic findings and histology. Cancer
Genet Cytogenet 1998, 101: 42–48.
4.Campbell WL, Santiago HE, Perzin KH, Johnson PM. The autonomous thyroid nodule. Correlation of scan appearance and
histopathology. Radiology 1973, 107: 133–138.
5.Carcangiu ML, Zampi G, Pupi A, Castagnoli A, Rosai J. Papillary carcinoma of the thyroid. A clinicopathologic study of 241
cases treated at the University of Florence, Italy. Cancer 1985, 55: 805–828.
6.Farbota LM, Calandra DB, Lawrence AM, Paloyan E. Thyroid carcinoma in Graves’ disease. Surgery 1985, 98: 1148–1152
7. Chong GC, Beahrs OH, Sizemore GW, Woolner LH. Medullary carcinoma of the thyroid gland. Cancer 1975, 35: 695–704.
8.Dominguez-Malagon H, Delgado-Chavez R, Torres-Najera M, Gould E, Albores-Saavedra J. Oxyphil and squamous variants of
medullary thyroid carcinoma. Cancer 1989, 63: 1183–1188.

101. THANK YOU!