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Presentation by – Dr. Monika Nema
Dr. Monika Nema
Introduction
Fine needle aspiration is the removal of a
sample of cells using a fine needle from a
suspicious mass for diagnostic purposes.
Thyroid FNA is a currently “growth” area
in pathology. One of the most commonly
practiced areas in non gynecologic
cytopathology.
Dr. Monika Nema
Impact of Thyroid FNA
 Best initial test for evaluating thyroid nodules.
 Accurate, simple, safe, cost effective, specific and
sensitive.
 Decreased the number of patients requiring thyroid
surgery .
 Decreased the cost of managing thyroid lesions .
 Increased the yield of finding thyroid malignancies at
surgery.
Dr. Monika Nema
Pathologists don’t understand
clinicians and they don’t understand us
Dr. Monika Nema
NCI Thyroid Fine Needle
Aspiration State of the Science
Conference
Dr. Monika Nema
Dr. Monika Nema
Dr. Monika Nema
Format of the Report
 For clarity of communication, BSRTC recommends
that each thyroid FNA report begin with a general
diagnostic category.
 For some of the general categories, some degree of
subcategorization can be informative.
 Additional descriptive comments (beyond such
subcategorization) are optional and left to the
discretion of the cytopathologist.
 Notes and recommendations are not required but can
be useful in certain circumstances.
Dr. Monika Nema
Nondiagnostic/Unsatisfactory
Dr. Monika Nema
Nondiagnostic/Unsatisfactory
 A specimen is considered “Nondiagnostic” or
“Unsatisfactory” if it fails to meet the adequacy
criteria.
Dr. Monika Nema
Criteria for Adequacy
A specimen should display at least 6 groups of follicular cells, with each group
composed of at least 10 cells preferably on a single slide.
 There are 3 exceptions in which a cytodiagnosis of a thyroid lesion may be
made in the absence of an adequate number of follicular epithelial cells:
 A diagnosis of thyroiditis may be made if abundant inflammatory cells are
present.
 A benign colloid nodule may be diagnosed if abundant thick colloid is present
as the presence of abundant colloid reliably identifies most benign processes.
 A diagnosis of atypia or malignancy if atypical or malignant cells are identified.
Dr. Monika Nema
Extensive air-drying artifact
Extensive
clotting artifacts
Dr. Monika Nema
Nondiagnostic/Unsatisfactory
 Cyst fluid, with or
without histiocytes, and
fewer than six groups of
ten benign follicular
cells.
 The risk of malignancy is
low for these lesions if
they are simple and
under 3 cm.
 However, the possibility
of a neoplastic lesion
cannot be excluded.
Dr. Monika Nema
Nondiagnostic/Unsatisfactory
Reporting pattern:-
 Example 1 (cystic lesion):
• NONDIAGNOSTIC.
• Cyst fluid only.
• Specimen processed and examined, but nondiagnostic because the
specimen consists almost exclusively of histiocytes; interpretation is
limited by insufficient follicular cells and/or colloid.
Note: Recommend correlation with cyst size and complexity on
ultrasound to assist with further management of the lesion.
 Example 2:
• UNSATISFACTORY.
• Specimen processed and examined, but unsatisfactory due to poor
fixation and preservation.
• Note: A repeat aspiration should be considered if clinically indicated.
Dr. Monika Nema
Benign thyroid lesion
Dr. Monika Nema
Benign thyroid lesion
 Since most thyroid nodules are benign, a benign result
is the most common FNA interpretation.
 Nodular goiter (NG) is the most commonly sampled
lesion by FNA.
 Lymphocytic (Hashimoto’s) thyroiditis is the most
commonly encountered form of thyroiditis.
Dr. Monika Nema
Benign follicular nodule
 Applies to a cytologic sample that is adequate for
evaluation and consists predominantly of colloid and
benign-appearing follicular cells in varying
proportions.
Dr. Monika Nema
Benign Follicular Nodule
Criteria
 Specimens are sparsely to moderately cellular.
 Colloid is viscous, shiny, and light yellow or gold in
color (resembling honey or varnish) on gross
examination. It is dark blue-violet-magenta with
Romanowsky-type stains and green to orange-pink
with the Papanicolaou stain .
 It may be thin or thick in texture.
Dr. Monika Nema
Watery
colloid has
“thin
membrane/
cellophane
coating”
appearance
Thick colloid stained glass cracking”
appearance
“honeycomb-like
arrangement of
follicular cells
Three-dimensional, variably sized balls/
spheres are admixed with flat sheetsDr. Monika Nema
Follicular cell nuclei are dark, round to
oval and show a uniformly granular
chromatin pattern
Follicular cells may appear
shrunken and degenerated when
associated with abundant colloid
Minimal nuclear overlapping
and crowding can occur
Dr. Monika Nema
Graves’ Disease
 An autoimmune diffuse hyperplastic thyroid disorder.
 Commonly seen in middle-aged women .
 Usually diagnosed clinically due to hyperthyroidism.
 Do not require FNA for diagnosis.
Dr. Monika Nema
Graves’ Disease
 Aspirates similar features to non-Graves’ BFNs.
 Lymphocytes and oncocytes may be seen in the
background.
 Follicular cells are arranged in flat sheets and loosely
cohesive groups, with abundant delicate, foamy
cytoplasm.
 Nuclei are often enlarged, vesicular, and show
prominent nucleoli. Few microfollicles may be
observed.
Dr. Monika Nema
Graves’ Disease
Stimulated follicular cells in Graves disease showing abundant cytoplasm and
intracytoplasmic accumulation of thyroglobulin producing a pattern reminiscent of flame
Dr. Monika Nema
Lymphocytic (Hashimoto´s)
Thyroiditis
 Most commonly affects middle-aged women
 Patients often develop diffuse thyroid enlargement.
 The designation “Consistent with lymphocytic
(Hashimoto’s) thyroiditis” applies to a cytologic
sample composed of many polymorphic lymphoid
cells associated with Hürthle cells.
Dr. Monika Nema
Hürthle cell Also called Askanazy cell,
oxyphilic cell, and oncocyte.
Defined morphologically as a
thyroid follicular cell with an
abundance of finely granular
cytoplasm.
Most Hürthle cells have an
enlarged, round to oval
nucleus, and some have a
prominent nucleolus.
Considered metaplastic,
non-neoplastic follicular
cells in reactive/hyperplastic
conditions like lymphocytic
(Hashimoto’s) thyroiditis
(LT) and multinodular goiter
(MNG).Dr. Monika Nema
Lymphocytic (Hashimoto´s)
Thyroiditis
Hypercellular.
Polymorphic
lymphoid
population .
Hürthle cells.
Dr. Monika Nema
Granulomatous (subacute, de Quervain´s)
Thyroiditis
 Self-limited inflammatory condition of the thyroid.
 Criteria
 The cellularity is variable and depends on the stage of
disease.
 Clusters of epithelioid histiocytes, i.e., granulomas, are
present along with many multinucleated giant cells.
 The early stage demonstrates many neutrophils and
eosinophils, similar to acute thyroiditis.
 In later stages the smears are hypocellular. They show giant
cells surrounding and engulfing colloid , epithelioid cells,
lymphocytes, macrophages, and scant degenerated
follicular cells.
Dr. Monika Nema
Granulomatous (subacute, de Quervain´s)
Thyroiditis
Dr. Monika Nema
Acute Thyroiditis
 A rare infectious condition of the thyroid.
 More commonly seen in immunocompromised patients.
 Criteria
 Numerous neutrophils are associated with necrosis, fibrin,
macrophages, and blood.
 There are scant reactive follicular cells and limited to
absent colloid.
 Bacterial or fungal organisms are occasionally seen in the
background, especially in immunocompromised patients.
 Cultures and special stains for organisms may be helpful in
these situations.
Dr. Monika Nema
Acute Thyroiditis
There are numerous neutrophils, macrophages, and inflammatory debris
Dr. Monika Nema
Riedel´s Thyroiditis/Disease
 The rarest form of thyroiditis .
 Results in progressive fibrosis of the thyroid gland
with extension into the soft tissues of the neck.
 Criteria
The thyroid gland feels very firm on palpation.
The preparations are often acellular.
Collagen strands and bland spindle cells may be
present.
There are rare chronic inflammatory cells.
Colloid and follicular cells are usually absent.
Dr. Monika Nema
Benign
REPORTING PATTERN
 The general term Benign may be utilized in reporting.
 A more specific term may be used, depending on the associated clinical
presentation.
 Example 1:
BENIGN.
Benign-appearing follicular cells, colloid, and occasional Hürthle cells
consistent with a benign follicular nodule.
 Example 2:
BENIGN.
Numerous polymorphic lymphoid cells and scattered Hürthle cells.
NOTE: The findings are consistent with lymphocytic (Hashimoto’s)
thyroiditis in the proper clinical setting.
Dr. Monika Nema
Atypia of Undetermined
Significance/Follicular Lesion
of Undetermined Significance
Dr. Monika Nema
Atypia of Undetermined Significance/Follicular Lesion
of Undetermined Significance
 Specimens that contain cells (follicular, lymphoid, or
other) with architectural and/or nuclear atypia that is
not sufficient to be classified as suspicious for a
follicular neoplasm, suspicious for malignancy, or
malignant.
Dr. Monika Nema
Predominance of microfollicles are seen in a
sparsely cellular aspirate with scant colloid.
Interpretation of follicular
cell atypia is hindered by
air drying effect.
Interpretation of follicular cell atypia is
hindered by clotting artifacts.
Dr. Monika Nema
Atypical cyst-lining cells
Atypical cyst-lining cells
Focal features suggestive
of papillary carcinoma
Dr. Monika Nema
Follicular cells showing nuclear enlargement,
often accompanied by prominent nucleoli
from patients with a history of radioactive
iodine, carbimazole, or other pharmaceutical
agents
Atypical lymphoid cells
Atypical
lymphoid cells
predominance of Hürthle cells
Dr. Monika Nema
Atypia of Undetermined Significance/Follicular Lesion
of Undetermined Significance
 Reporting pattern:
 Example 1:
Atypia of Undetermined Significance.
Sparsely cellular aspirate comprised of follicular cells with architectural atypia.
Colloid is absent.
Note: A repeat aspirate after an appropriate interval of observation may
be helpful if clinically indicated.
 Example 2:
Atypia of Undetermined Significance.
Follicular cells with focal cytologic and architectural atypia, but obscuring blood
and clotting artifact preclude definitive evaluation.
Note: A repeat aspirate after an appropriate interval of observation might be
helpful if clinically indicated.
Dr. Monika Nema
Follicular Neoplasm/Suspicious
for a Follicular Neoplasm
Dr. Monika Nema
Follicular Neoplasm/Suspicious
for a Follicular Neoplasm
 This diagnostic category refers to a cellular aspirate
comprised of follicular cells, most of which are
arranged in an altered architectural pattern
characterized by significant cell crowding and/or
microfollicle formation.
Dr. Monika Nema
Microfollicle - <15 cells in a circle that is at least 2/3 rd complete
Dr. Monika Nema
Highly cellular aspirate
Follicular cells are normal-sized or enlarged
and relatively uniform, with scant or
moderate amounts of cytoplasm.
Colloid is scant or absent.
cellularity and microfolliclesDr. Monika Nema
Follicular Neoplasm/Suspicious
for a Follicular Neoplasm
REPORTING PATTERN
 On a sparsely cellular sample, interpret such cases as
ATYPIA OF UNDETERMINED SIGNIFICANCE.
 If the follicular cells show features of papillary thyroid
carcinoma, it is interpreted as “MALIGNANT,
Papillary thyroid carcinoma” or “SUSPICIOUS FOR
MALIGNANCY, suspicious for papillary thyroid
carcinoma,” depending on the quality and quantity of
the cytologic changes.
Dr. Monika Nema
Follicular Neoplasm/Suspicious
for a Follicular Neoplasm
 Fine needle aspirations of parathyroid adenomas are
composed of cells that resemble crowded and
overlapping follicular cells.
 Even when the FNA is performed with ultrasound
guidance, it may not be clear to the aspirator that the
lesion arises from a parathyroid gland rather than the
thyroid.
 When submitted as a “thyroid FNA” specimen,
parathyroid adenomas are often misinterpreted as
FN/SFN.
Dr. Monika Nema
Follicular Neoplasm/Suspicious
for a Follicular Neoplasm
REPORTING PATTERN
Example :
 Suspicious for a Follicular Neoplasm.
 Cellular aspirate composed predominantly of crowded
uniform cells without colloid. The features suggest a
follicular neoplasm, but the possibility of a parathyroid
lesion cannot be excluded.
 Correlation with clinical, serologic, and radiologic
findings should be considered.
Dr. Monika Nema
Follicular Neoplasm, Hürthle Cell
Type/Suspicious for a Follicular
Neoplasm, Hürthle Cell Type
Dr. Monika Nema
Follicular Neoplasm, Hürthle Cell Type/Suspicious for a
Follicular Neoplasm, Hürthle Cell Type
 The interpretation “Follicular neoplasm, Hurthle cell
type” or “Suspicious for a follicular neoplasm, Hürthle
cell type” refers to a cellular aspirate that consists
exclusively (or almost exclusively) of Hürthle cells.
 Oncocytic cells with nuclear features of papillary
carcinoma are excluded from this category.
Dr. Monika Nema
Population of Hürthle cells in small
crowded groups and as isolated cells in
a background that lacks colloid and
lymphocytes.
Consists exclusively of Hürthle
cells arranged in syncytial-like sheets and as
isolated cells. The cells exhibit
marked variation in cell and nuclear size
(mixed small and large cell dysplasia
Dr. Monika Nema
A cellular aspirate consists of noncohesive
Hürthle cells with both large and small cell
dysplasia. Colloid is absent, and a small
transgressing vessel is present in the center
This cellular aspirate consists of loosely
cohesive, markedly enlarged Hürthle
cells with marked anisonucleosis and
macronucleoli (large cell dysplasia)
Dr. Monika Nema
 Predominance of Hürthle cells is considerd as BENIGN
in–
Presence of abundant colloid.
Absence of atypia.
Dr. Monika Nema
 When Hürthle cell differentiation is clear cut but only
focal, it is advisable to follow the guidelines of the
WHO, which considers only those follicular neoplasms
that are comprised of >75% Hürthle cells to be a
HCNs.
 Thus, a suspicious FNA in which <75% of the
abnormal cells are well-developed Hürthle cells should
be diagnosed as “Follicular Neoplasm/Suspicious for a
Follicular Neoplasm” rather than FNHCT/SFNHCT.
Dr. Monika Nema
Follicular Neoplasm, Hürthle Cell Type/Suspicious for a
Follicular Neoplasm, Hürthle Cell Type
 Reporting pattern
 Example 1:
SUSPICIOUS FOR A HÜRTHLE CELL NEOPLASM.
Cellular aspirate consisting predominantly of Hürthle cells in syncytial
like sheets and crowded clusters in the absence of colloid.
 Example 2:
SUSPICIOUS FOR A HÜRTHLE CELL NEOPLASM.
Cellular aspirate composed of cells with abundant granular cytoplasm.
The findings raise the possibility of a Hürthle cell neoplasm, but a
parathyroid tumor cannot be excluded. Correlation with clinical findings,
imaging findings, and serologic testing results might be helpful.
Dr. Monika Nema
Suspicious for malignancy
Dr. Monika Nema
Suspicious for malignancy
 A specimen is suspicious for malignancy (SFM) when
some features of malignancy raise a strong suspicion of
malignancy , but the findings are not sufficient for a
conclusive diagnosis.
 A malignant diagnosis should be reserved for those
cases that show sufficient cellularity and most, if not
all, of the diagnostic features of an entity.
 Specimens that are suspicious for a follicular or Hürthle
cell neoplasm are excluded from this category.
Dr. Monika Nema
Suspicious for malignancy
 Suspicious for Papillary Carcinoma.
 Suspicious for Medullary Carcinoma.
 Suspicious for Lymphoma.
 Suspicious for malignancy, not otherwise specified.
Dr. Monika Nema
Suspicious for Papillary Carcinoma
 Pattern A (“Patchy Nuclear Changes Pattern”)
 Pattern B (“Incomplete Nuclear Changes Pattern”)
 Pattern C (“Sparsely Cellular Specimen Pattern”)
 Pattern D (“Cystic Degeneration Pattern”)
Dr. Monika Nema
Suspicious for Papillary Carcinoma Pattern A (“Patchy Nuclear
Changes Pattern”)
The sample is moderately
or highly cellular.
Benign follicular cells
(arranged predominantly
in macrofollicle
fragments)
are admixed with cells that
have nuclear enlargement,
nuclear pallor, nuclear
grooves, nuclear
membrane irregularity,
and/or nuclear molding.
Intranuclear
pseudoinclusions (INCIs)
are rare or absent.
Dr. Monika Nema
Suspicious for Papillary Carcinoma Pattern B (“Incomplete Nuclear
Changes Pattern”)
The sample is sparsely,
moderately, or highly
cellular.
There is generalized mild-
to-moderate nuclear
enlargement with mild
nuclear pallor.
Nuclear grooves are
evident, but nuclear
membrane irregularity
and nuclear molding are
minimal or absent.
Intranuclear
pseudoinclusions are rare
or absent.
Dr. Monika Nema
Suspicious for Papillary Carcinoma Pattern D (“Cystic Degeneration
Pattern”)
 There is evidence of cystic degeneration based on the
presence of hemosiderin laden macrophages.
 Scattered groups and sheets of follicular cells have
enlarged, pale nuclei and some have nuclear grooves, but
INCIs are rare or absent.
 There are occasional large, atypical, “histiocytoid” cells
with enlarged nuclei and abundant vacuolated cytoplasm.
 There are rare calcifications that resemble psammoma
bodies.
Dr. Monika Nema
Suspicious for Medullary Carcinoma
 The sample is sparsely or moderately cellular.
 There is a monomorphic population of noncohesive small
or medium sized cells with a high nuclear/cytoplasmic
(N/C) ratio.
 Nuclei are eccentrically located, with smudged chromatin
due to suboptimal preservation; there are no discernible
cytoplasmic granules.
 There may be small fragments of amorphous material -
colloid versus amyloid.
Dr. Monika Nema
Suspicious for Lymphoma
 The cellular sample is composed of numerous
monomorphic small- to intermediate- sized lymphoid
cells.
Dr. Monika Nema
Suspicious for malignancy
REPORTING PATTERN
 Example 1:
SUSPICIOUS FOR MALIGNANCY.
Suspicious for papillary thyroid carcinoma.
 Example 2:
SUSPICIOUS FOR MALIGNANCY.
Suspicious for medullary thyroid carcinoma.
Note: Correlation with serum calcitonin level or re-aspiration for immunohistochemical
studies might be helpful for definitive diagnosis if clinically indicated.
 Example 3:
Suspicious for malignancy .
Suspicious for lymphoma.
Note: Re-aspiration for immunophenotyping studies by flow cytometry might be helpful
for definitive diagnosis if clinically indicated.
Dr. Monika Nema
Papillary Carcinoma of Thyroid
Dr. Monika Nema
Papillary Carcinoma of Thyroid
 It is a malignant epithelial tumor derived from thyroid
follicular epithelium and displays characteristic
nuclear alterations.
 The most common malignant neoplasm of the thyroid.
 Occurs in all age groups.
 Peak incidence in the third to fourth decades.
 Risk factors include external radiation to the neck
during childhood, ionizing radiation, genetic factors,
and nodular hyperplasia.
• Carries a good prognosis
Dr. Monika Nema
Papillary Carcinoma of Thyroid
True papillary
tissue
fragments
Papillary-like
fragments
Microfollicle
sMonolayered sheet
Follicular cells are arranged in
Dr. Monika Nema
Monolayered sheet of Papillary Carcinoma of Thyroid v/s
macrofollicle fragment typical of benign follicular nodules
 Arrangement of the cells in the sheets (evenly spaced vs. crowded)
 Nuclear features of papillary carcinoma are larger, paler, more crowded,
and more irregular in contour
Benign
follicular
nodule
Papillary
Carcinoma
of Thyroid
Dr. Monika Nema
Papillary Carcinoma of Thyroid
Orphan Annie nuclei
Longitudinal nuclear grooves
Intranuclear cytoplasmic
pseudoinclusions
Pale nuclei with powdery chromatin
Dr. Monika Nema
Papillary Carcinoma of Thyroid
Orphan Annie nuclei Longitudinal nuclear grooves
 Psammoma bodies only are non-
specific.
 Psammoma bodies are also seen in
medullary thyroid carcinoma,
lymphocytic thyroiditis, Graves’
disease, and even nodular goiter.
Psammoma bodies
Multinucleated giant cells
Bubble-gum-like colloid
Dr. Monika Nema
Papillary Carcinoma of Thyroid
 Necrotic debris is extremely uncommon.
 Hürthle cell (oncocytic) metaplasia is sometimes seen.
 Squamous metaplasia is sometimes seen.
(moderate to abundant dense cytoplasm and cells that fit
together like paving stones)
Dr. Monika Nema
Variants of Papillary Thyroid
Carcinoma
 Variants of PTC, by definition, have the essential
nuclear features of PTC but
A different architectural pattern.
 Unusual cytoplasmic features.
 Different background features, such as the quantity
and texture of the colloid.
 The presence or absence of a prominent
lymphoplasmacytic infiltrate.
Dr. Monika Nema
Variants of Papillary Thyroid
Carcinoma
 Follicular variant of PTC.
 Macrofollicular Variant.
 Cystic variant.
 Oncocytic variant.
 Tall cell variant.
 Columnar cell variant.
 Hyalinizing Trabecular tumor.
Dr. Monika Nema
Follicular variant of PTC.
 The follicular variant of PTC (FVPTC) is a PTC in
which the tumor is completely or almost completely
composed of small to medium-sized follicles lined by
cells with the nuclear features of a PTC.
Dr. Monika Nema
Follicular variant of PTC.
 FVPTC is now the most common variant of PTC.
 In contrast to conventional PTC, the nuclear changes
are often subtle.
 The following features are usually absent or
inconspicuous: papillary and papillary-like fragments,
multinucleated giant cells, INCIs, psammoma bodies,
marked cystic change.
Dr. Monika Nema
Macrofollicular Variant
 The macrofollicular variant is a PTC in which over 50%
of the follicles are arranged as macrofollicles.
Dr. Monika Nema
Macrofollicular Variant
 Criteria
The sample consists of monolayered (two-
dimensional) sheets of atypical epithelium and/or
variably sized follicles.
Convincing nuclear changes of PTC must be present
for a definite interpretation of malignancy.
In contrast to conventional PTC, the diagnostic
nuclear features are often more subtle (as with
FVPTC).
Abundant thin colloid or fragments of thick colloid
may also be present.
Dr. Monika Nema
Macrofollicular Variant
Differential diagnosis includes
 Benign follicular nodule seen with nodular goiter.
 The follicular adenoma of macrofollicular type.
Easily overlooked at low magnification due to the
abundance of thin colloid, the low cellularity, and the
subtle and focal nuclear atypia. Thus, careful attention to
nuclear features is necessary.
Dr. Monika Nema
Cystic Variant
 The cystic variant is a PTC that is predominantly
cystic, comprised of thin, watery fluid, abundant
histiocytes, and hypervacuolated tumor cells.
 PTC is the most common malignant neoplasm of the
thyroid to undergo cystic change.
Dr. Monika Nema
Cystic Variant Intranuclear pseudoinclusions
Histocytes
Dr. Monika Nema
Cystic Variant
 Criteria
The neoplastic cells are typically arranged in small
groups with irregular borders; sheets, papillae, or
follicles may also be present.
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.
Dr. Monika Nema
Oncocytic Variant
 The oncocytic variant is a thyroid tumor with the
nuclear changes characteristic of PTC but composed
predominantly of oncocytic cells (polygonal cells with
abundant granular cytoplasm).
 Criteria
The sample is composed predominantly of oncocytic
cells, arranged in papillae, sheets, 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.
Dr. Monika Nema
Oncocytic Variant
.
Oncocytic cells with intranuclear pseudoinclusions
Lymphocytes are
absent
Dr. Monika Nema
Tall cell variant
 An aggressive form of PTC composed of papillae lined by a
single layer of elongated (“tall”) tumor cells (their height is
at least three times their width) with abundant dense
granular cytoplasm and the typical nuclear changes of PTC.
 Tends to occur in elderly patients.
 More frequent in men.
 It is often presented as a large and bulky tumor, often with
an extrathyroidal extension and vascular invasion.
 Has a higher incidence of local recurrence and distant
metastasis.
Dr. Monika Nema
Tall cell variant
Multiple INCI in
a nucleus giving
soap-bubble
appearance
Elongated neoplastic cells
more granular nuclear chromatin
Dr. Monika Nema
Columnar cell variant
 A rare aggressive variant of PTC.
 Characterized by columnar cells with hyperchromatic,
oval, and stratified nuclei and supranuclear or
subnuclear cytoplasmic vacuoles.
Dr. Monika Nema
Columnar cell
variant
Elongated and crowded nuclei with
distinct stratification.
Cells have dark chromatin, unlike the
typical powdery chromatin seen in the
other types of PTC
Generally lack colloid.
A crowded,
pseudopapillary fragment
of columnar tumor cells
Dr. Monika Nema
Columnar cell variant
 The neoplastic cells of the columnar cell variant may
be mistaken for benign cells like respiratory epithelial
cells (seen when the trachea is penetrated).
 The dark and stratified nuclei resemble those of a
colorectal neoplasm, and therefore the possibility of a
metastasis from a colorectal primary enters the
differential diagnosis.
Dr. Monika Nema
Hyalinizing Trabecular Tumor
 Rare tumor of follicular cell origin characterized by
trabecular growth, marked intratrabecular
hyalinization, and the nuclear changes of PTC.
 HTT is very difficult to recognize as such in an FNA
specimen.
 Because of its nuclear features, most HTTs are
interpreted as PTC or “suspicious for PTC.”
Dr. Monika Nema
Criteria
 Neoplastic cells are radially oriented
around amyloid-like hyaline stromal
material.
INCIs and nuclear grooves are numerous.
Occasional psammoma bodies may be
present.
Cytoplasmic paranuclear yellow bodies
may be present.
Dr. Monika Nema
Papillary Carcinoma of Thyroid
REPORTING PATTERN
 The general category “MALIGNANT” is used whenever the
cytomorphologic features are conclusive for malignancy.
 Descriptive comments that follow are used to subclassify
the malignancy and summarize the results of special
studies, if any.
 If the findings are suspicious but not conclusive for
malignancy, the general category “SUSPICIOUS FOR
MALIGNANCY” should be used.
 Example :
 Malignant .
 Papillary thyroid carcinoma.
Dr. Monika Nema
Medullary Thyroid Carcinoma
Dr. Monika Nema
Medullary Thyroid Carcinoma
 MTC is a malignant neoplasm derived from and/or
morphologically recapitulating the parafollicular cells
of the thyroid gland.
 Comprises approximately 7% of thyroid carcinomas.
 It occurs in sporadic and heritable forms.
Dr. Monika Nema
Medullary Thyroid Carcinoma
 MTC may occur at any age,
 Usually older adults with a mean age of 50 years.
 MTC is an aggressive tumor that spreads by
hematogenous and lymphatic routes.
 Common sites of metastasis include cervical lymph
nodes, lung, liver, bone, and adrenal glands.
 The possibility of metastatic MTC should be kept in
mind in a patient with a positive cervical lymph node
of unknown primary.
Dr. Monika Nema
moderate
to marked
cellularity
Isolated cells alternate
with syncytial-like
clusters
Cells are plasmacytoid, polygonal,
round, and/or spindle-shaped.
Have a round nucleus,
eccentrically placed with finely or
coarsely granular (“salt and
pepper”) chromatin within a
moderately abundant, granular
cytoplasm.
Dr. Monika Nema
 Amyloid is abundant and readily appreciated in some cases.
 Amyloid appears as dense, amorphous material that resembles thick
colloid. Dr. Monika Nema
Medullary Thyroid Carcinoma
REPORTING PATTERN
 The general category “MALIGNANT” is used whenever
the cytomorphologic features are conclusive for
malignancy.
 Descriptive comments that follow are used to
subclassify the malignancy and summarize the results
of special studies, if any.
 If the findings are suspicious but not conclusive for
malignancy, the general category “SUSPICIOUS FOR
MALIGNANCY” should be used.
Dr. Monika Nema
Medullary Thyroid Carcinoma
REPORTING PATTERN
Example :
 Malignant .
 Consistent with medullary thyroid carcinoma.
 Note: Cytomorphologic features are characteristic of
medullary thyroid Carcinoma. Serum chemistries for
calcitonin might be helpful.
Dr. Monika Nema
Poorly Differentiated Thyroid Carcinoma
Dr. Monika Nema
Poorly Differentiated Thyroid
Carcinoma
 Cellular preparations display an insular, solid, or trabecular cytoarchitecture.
 Insular pattern means group of cells outlined by a thin fibrovascular border.
Dr. Monika Nema
Poorly Differentiated Thyroid
Carcinoma
 There is a uniform population of follicular cells with scant
cytoplasm (sometimes plasmacytoid)Dr. Monika Nema
Poorly Differentiated Thyroid
Carcinoma
Apoptosis and mitotic
activity are present
Necrosis present.
Presence of poorly differentiated features like mitoses, necrosis, or small convoluted nuclei.
Dr. Monika Nema
Poorly Differentiated Thyroid
Carcinoma
 “A definitive diagnosis of poorly differentiated
carcinoma can be made only at the histological level.”
Reporting Pattern–
 If the findings are not conclusive for malignancy, the
general category “SUSPICIOUS FOR MALIGNANCY”
should be used.
 Many PDTCs overlap morphologically with follicular
neoplasms and are therefore inevitably interpreted as
“SUSPICIOUS FOR A FOLLICULAR NEOPLASM”
Dr. Monika Nema
Poorly Differentiated Thyroid
Carcinoma
Reporting Pattern–
Example :
• Malignant .
• Highly cellular aspirate with atypical follicular cells,
necrosis, and scant colloid, most consistent with
poorly differentiated thyroid carcinoma.
Dr. Monika Nema
Undifferentiated (Anaplastic) Thyroid Carcinoma
Dr. Monika Nema
Undifferentiated (Anaplastic) Thyroid
Carcinoma
 It is a high grade, pleomorphic, epithelial-derived
malignancy with epithelioid and/or spindle cell features.
Dr. Monika Nema
Cells are
epithelioid
in appearance.
Variation in cell
and nuclear size
is evident.
plasmacytoid
appearance
Spindle
shaped
Spindle
shaped cells in
storiform
patternDr. Monika Nema
Intranuclear cytoplasmic
pseudoinclusion.
Nuclear enlargement.
Contour irregularity.
Prominent nucleolus.
parachromatin
clearing
Extensive inflammation
Giant cell
Dr. Monika Nema
Squamous cell carcinoma of the thyroid
Dr. Monika Nema
Squamous cell carcinoma of the
thyroid
 Squamous cell carcinoma of the thyroid is a malignant
tumor that shows exclusively squamous differentiation.
Criteria :-
Cytologic samples are composed
almost exclusively of large,
pleomorphic keratinized cells
(orangeophilia of the cytoplasm).
Necrosis may be present.
Correlation with clinical and
imaging findings is essential for
excluding a metastasis
Dr. Monika Nema
REPORTING PATTERN
Example :
 Malignant .
 Undifferentiated thyroid carcinoma.
 Note: Advise immunohistochemical studies for further
evaluation
Dr. Monika Nema
Metastatic Tumors and Lymphomas
Dr. Monika Nema
Metastatic Tumors and Lymphomas
 Tumors of nearby structures that can involve the
thyroid include those of the pharynx, larynx,
esophagus, mediastinum, and nearby lymph nodes.
 The most common origins of metastases to the thyroid
are cancers of the lung, breast, skin (especially
melanoma), colon, and kidney.
Dr. Monika Nema
Metastatic Tumors
 Metastatic Renal cell carcinoma.- The distinction between clear
cell RCC and follicular and Hürthle cell neoplasms is difficult,
particularly if the RCC is occult, or if the history of RCC is not
provided
 Metastatic Malignant Melanoma.-Intracytoplasmic pigment is
not common but can be seen as fine granules in neoplastic cells
or coarse granules in histiocytes. Cells are usually
immunoreactive for S-100 protein, melanA, and HMB45.
 Metastatic Adenocarcinoma from the Breast.-Cells are often
immunoreactive for estrogen and progesterone receptors and
negative for TTF-1 and thyroglobulin
Dr. Monika Nema
Lymphoma involving the thyroid gland
Dr. Monika Nema
Lymphoma involving the thyroid
gland
 Hodgkin and non-Hodgkin lymphomas are
malignancies of lymphoid cells, most commonly B-
cells, and arise in the thyroid gland as a primary
malignancy or involve the thyroid gland secondarily.
 The majority of lymphomas arising within the thyroid
gland are non-Hodgkin lymphomas (NHL) of B-cell
phenotype and two-thirds are preceded by Hashimoto
thyroiditis.
 Most NHLs of the thyroid gland are either DLBL or
extranodal marginal zone B-cell lymphomas of
mucosa- associated lymphoid tissue (MALT).
Dr. Monika Nema
Lymphoma involving the thyroid
gland
 There are at least three different patterns of lymphoma on
FNA.
 One is characterized by mixture of small and large
lymphocytes. This pattern can be seen in Hashimoto
thyroiditis as well, but the absence of oncocytes, follicular
epithelial cells, and plasma cells favors lymphoma.
 The second pattern is characterized by a monotonous
population of large lymphoid cells and is morphologically
diagnostic of lymphoma.
 The third pattern is characterized by a monomorphous
population of small lymphocytes, which may represent
lymphoma or inactive thyroiditis.
Dr. Monika Nema
REPORTING PATTERN
Example :
 Malignant .
 Diffuse large B- cell lymphoma.
Example :
 Suspicious for malignancy.
 Suspicious for metastatic deposits.
Dr. Monika Nema
Benefits of The Bethesda system of
reporting Thyroid Cytopathology
 Uniform reporting system for thyroid FNA.
 Facilitate effective communication.
 Facilitates cytologic - histologic correlation for thyroid
diseases.
 Facilitates research .
 Allows reliable sharing of data.
Dr. Monika Nema
Thank you
Dr. Monika Nema

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Reporting thyroid fine needle aspiration by the bethesda system

  • 1. Presentation by – Dr. Monika Nema Dr. Monika Nema
  • 2. Introduction Fine needle aspiration is the removal of a sample of cells using a fine needle from a suspicious mass for diagnostic purposes. Thyroid FNA is a currently “growth” area in pathology. One of the most commonly practiced areas in non gynecologic cytopathology. Dr. Monika Nema
  • 3. Impact of Thyroid FNA  Best initial test for evaluating thyroid nodules.  Accurate, simple, safe, cost effective, specific and sensitive.  Decreased the number of patients requiring thyroid surgery .  Decreased the cost of managing thyroid lesions .  Increased the yield of finding thyroid malignancies at surgery. Dr. Monika Nema
  • 4. Pathologists don’t understand clinicians and they don’t understand us Dr. Monika Nema
  • 5. NCI Thyroid Fine Needle Aspiration State of the Science Conference Dr. Monika Nema
  • 8. Format of the Report  For clarity of communication, BSRTC recommends that each thyroid FNA report begin with a general diagnostic category.  For some of the general categories, some degree of subcategorization can be informative.  Additional descriptive comments (beyond such subcategorization) are optional and left to the discretion of the cytopathologist.  Notes and recommendations are not required but can be useful in certain circumstances. Dr. Monika Nema
  • 10. Nondiagnostic/Unsatisfactory  A specimen is considered “Nondiagnostic” or “Unsatisfactory” if it fails to meet the adequacy criteria. Dr. Monika Nema
  • 11. Criteria for Adequacy A specimen should display at least 6 groups of follicular cells, with each group composed of at least 10 cells preferably on a single slide.  There are 3 exceptions in which a cytodiagnosis of a thyroid lesion may be made in the absence of an adequate number of follicular epithelial cells:  A diagnosis of thyroiditis may be made if abundant inflammatory cells are present.  A benign colloid nodule may be diagnosed if abundant thick colloid is present as the presence of abundant colloid reliably identifies most benign processes.  A diagnosis of atypia or malignancy if atypical or malignant cells are identified. Dr. Monika Nema
  • 13. Nondiagnostic/Unsatisfactory  Cyst fluid, with or without histiocytes, and fewer than six groups of ten benign follicular cells.  The risk of malignancy is low for these lesions if they are simple and under 3 cm.  However, the possibility of a neoplastic lesion cannot be excluded. Dr. Monika Nema
  • 14. Nondiagnostic/Unsatisfactory Reporting pattern:-  Example 1 (cystic lesion): • NONDIAGNOSTIC. • Cyst fluid only. • Specimen processed and examined, but nondiagnostic because the specimen consists almost exclusively of histiocytes; interpretation is limited by insufficient follicular cells and/or colloid. Note: Recommend correlation with cyst size and complexity on ultrasound to assist with further management of the lesion.  Example 2: • UNSATISFACTORY. • Specimen processed and examined, but unsatisfactory due to poor fixation and preservation. • Note: A repeat aspiration should be considered if clinically indicated. Dr. Monika Nema
  • 16. Benign thyroid lesion  Since most thyroid nodules are benign, a benign result is the most common FNA interpretation.  Nodular goiter (NG) is the most commonly sampled lesion by FNA.  Lymphocytic (Hashimoto’s) thyroiditis is the most commonly encountered form of thyroiditis. Dr. Monika Nema
  • 17. Benign follicular nodule  Applies to a cytologic sample that is adequate for evaluation and consists predominantly of colloid and benign-appearing follicular cells in varying proportions. Dr. Monika Nema
  • 18. Benign Follicular Nodule Criteria  Specimens are sparsely to moderately cellular.  Colloid is viscous, shiny, and light yellow or gold in color (resembling honey or varnish) on gross examination. It is dark blue-violet-magenta with Romanowsky-type stains and green to orange-pink with the Papanicolaou stain .  It may be thin or thick in texture. Dr. Monika Nema
  • 19. Watery colloid has “thin membrane/ cellophane coating” appearance Thick colloid stained glass cracking” appearance “honeycomb-like arrangement of follicular cells Three-dimensional, variably sized balls/ spheres are admixed with flat sheetsDr. Monika Nema
  • 20. Follicular cell nuclei are dark, round to oval and show a uniformly granular chromatin pattern Follicular cells may appear shrunken and degenerated when associated with abundant colloid Minimal nuclear overlapping and crowding can occur Dr. Monika Nema
  • 21. Graves’ Disease  An autoimmune diffuse hyperplastic thyroid disorder.  Commonly seen in middle-aged women .  Usually diagnosed clinically due to hyperthyroidism.  Do not require FNA for diagnosis. Dr. Monika Nema
  • 22. Graves’ Disease  Aspirates similar features to non-Graves’ BFNs.  Lymphocytes and oncocytes may be seen in the background.  Follicular cells are arranged in flat sheets and loosely cohesive groups, with abundant delicate, foamy cytoplasm.  Nuclei are often enlarged, vesicular, and show prominent nucleoli. Few microfollicles may be observed. Dr. Monika Nema
  • 23. Graves’ Disease Stimulated follicular cells in Graves disease showing abundant cytoplasm and intracytoplasmic accumulation of thyroglobulin producing a pattern reminiscent of flame Dr. Monika Nema
  • 24. Lymphocytic (Hashimoto´s) Thyroiditis  Most commonly affects middle-aged women  Patients often develop diffuse thyroid enlargement.  The designation “Consistent with lymphocytic (Hashimoto’s) thyroiditis” applies to a cytologic sample composed of many polymorphic lymphoid cells associated with Hürthle cells. Dr. Monika Nema
  • 25. Hürthle cell Also called Askanazy cell, oxyphilic cell, and oncocyte. Defined morphologically as a thyroid follicular cell with an abundance of finely granular cytoplasm. Most Hürthle cells have an enlarged, round to oval nucleus, and some have a prominent nucleolus. Considered metaplastic, non-neoplastic follicular cells in reactive/hyperplastic conditions like lymphocytic (Hashimoto’s) thyroiditis (LT) and multinodular goiter (MNG).Dr. Monika Nema
  • 27. Granulomatous (subacute, de Quervain´s) Thyroiditis  Self-limited inflammatory condition of the thyroid.  Criteria  The cellularity is variable and depends on the stage of disease.  Clusters of epithelioid histiocytes, i.e., granulomas, are present along with many multinucleated giant cells.  The early stage demonstrates many neutrophils and eosinophils, similar to acute thyroiditis.  In later stages the smears are hypocellular. They show giant cells surrounding and engulfing colloid , epithelioid cells, lymphocytes, macrophages, and scant degenerated follicular cells. Dr. Monika Nema
  • 28. Granulomatous (subacute, de Quervain´s) Thyroiditis Dr. Monika Nema
  • 29. Acute Thyroiditis  A rare infectious condition of the thyroid.  More commonly seen in immunocompromised patients.  Criteria  Numerous neutrophils are associated with necrosis, fibrin, macrophages, and blood.  There are scant reactive follicular cells and limited to absent colloid.  Bacterial or fungal organisms are occasionally seen in the background, especially in immunocompromised patients.  Cultures and special stains for organisms may be helpful in these situations. Dr. Monika Nema
  • 30. Acute Thyroiditis There are numerous neutrophils, macrophages, and inflammatory debris Dr. Monika Nema
  • 31. Riedel´s Thyroiditis/Disease  The rarest form of thyroiditis .  Results in progressive fibrosis of the thyroid gland with extension into the soft tissues of the neck.  Criteria The thyroid gland feels very firm on palpation. The preparations are often acellular. Collagen strands and bland spindle cells may be present. There are rare chronic inflammatory cells. Colloid and follicular cells are usually absent. Dr. Monika Nema
  • 32. Benign REPORTING PATTERN  The general term Benign may be utilized in reporting.  A more specific term may be used, depending on the associated clinical presentation.  Example 1: BENIGN. Benign-appearing follicular cells, colloid, and occasional Hürthle cells consistent with a benign follicular nodule.  Example 2: BENIGN. Numerous polymorphic lymphoid cells and scattered Hürthle cells. NOTE: The findings are consistent with lymphocytic (Hashimoto’s) thyroiditis in the proper clinical setting. Dr. Monika Nema
  • 33. Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance Dr. Monika Nema
  • 34. Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance  Specimens that contain cells (follicular, lymphoid, or other) with architectural and/or nuclear atypia that is not sufficient to be classified as suspicious for a follicular neoplasm, suspicious for malignancy, or malignant. Dr. Monika Nema
  • 35. Predominance of microfollicles are seen in a sparsely cellular aspirate with scant colloid. Interpretation of follicular cell atypia is hindered by air drying effect. Interpretation of follicular cell atypia is hindered by clotting artifacts. Dr. Monika Nema
  • 36. Atypical cyst-lining cells Atypical cyst-lining cells Focal features suggestive of papillary carcinoma Dr. Monika Nema
  • 37. Follicular cells showing nuclear enlargement, often accompanied by prominent nucleoli from patients with a history of radioactive iodine, carbimazole, or other pharmaceutical agents Atypical lymphoid cells Atypical lymphoid cells predominance of Hürthle cells Dr. Monika Nema
  • 38. Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance  Reporting pattern:  Example 1: Atypia of Undetermined Significance. Sparsely cellular aspirate comprised of follicular cells with architectural atypia. Colloid is absent. Note: A repeat aspirate after an appropriate interval of observation may be helpful if clinically indicated.  Example 2: Atypia of Undetermined Significance. Follicular cells with focal cytologic and architectural atypia, but obscuring blood and clotting artifact preclude definitive evaluation. Note: A repeat aspirate after an appropriate interval of observation might be helpful if clinically indicated. Dr. Monika Nema
  • 39. Follicular Neoplasm/Suspicious for a Follicular Neoplasm Dr. Monika Nema
  • 40. Follicular Neoplasm/Suspicious for a Follicular Neoplasm  This diagnostic category refers to a cellular aspirate comprised of follicular cells, most of which are arranged in an altered architectural pattern characterized by significant cell crowding and/or microfollicle formation. Dr. Monika Nema
  • 41. Microfollicle - <15 cells in a circle that is at least 2/3 rd complete Dr. Monika Nema
  • 42. Highly cellular aspirate Follicular cells are normal-sized or enlarged and relatively uniform, with scant or moderate amounts of cytoplasm. Colloid is scant or absent. cellularity and microfolliclesDr. Monika Nema
  • 43. Follicular Neoplasm/Suspicious for a Follicular Neoplasm REPORTING PATTERN  On a sparsely cellular sample, interpret such cases as ATYPIA OF UNDETERMINED SIGNIFICANCE.  If the follicular cells show features of papillary thyroid carcinoma, it is interpreted as “MALIGNANT, Papillary thyroid carcinoma” or “SUSPICIOUS FOR MALIGNANCY, suspicious for papillary thyroid carcinoma,” depending on the quality and quantity of the cytologic changes. Dr. Monika Nema
  • 44. Follicular Neoplasm/Suspicious for a Follicular Neoplasm  Fine needle aspirations of parathyroid adenomas are composed of cells that resemble crowded and overlapping follicular cells.  Even when the FNA is performed with ultrasound guidance, it may not be clear to the aspirator that the lesion arises from a parathyroid gland rather than the thyroid.  When submitted as a “thyroid FNA” specimen, parathyroid adenomas are often misinterpreted as FN/SFN. Dr. Monika Nema
  • 45. Follicular Neoplasm/Suspicious for a Follicular Neoplasm REPORTING PATTERN Example :  Suspicious for a Follicular Neoplasm.  Cellular aspirate composed predominantly of crowded uniform cells without colloid. The features suggest a follicular neoplasm, but the possibility of a parathyroid lesion cannot be excluded.  Correlation with clinical, serologic, and radiologic findings should be considered. Dr. Monika Nema
  • 46. Follicular Neoplasm, Hürthle Cell Type/Suspicious for a Follicular Neoplasm, Hürthle Cell Type Dr. Monika Nema
  • 47. Follicular Neoplasm, Hürthle Cell Type/Suspicious for a Follicular Neoplasm, Hürthle Cell Type  The interpretation “Follicular neoplasm, Hurthle cell type” or “Suspicious for a follicular neoplasm, Hürthle cell type” refers to a cellular aspirate that consists exclusively (or almost exclusively) of Hürthle cells.  Oncocytic cells with nuclear features of papillary carcinoma are excluded from this category. Dr. Monika Nema
  • 48. Population of Hürthle cells in small crowded groups and as isolated cells in a background that lacks colloid and lymphocytes. Consists exclusively of Hürthle cells arranged in syncytial-like sheets and as isolated cells. The cells exhibit marked variation in cell and nuclear size (mixed small and large cell dysplasia Dr. Monika Nema
  • 49. A cellular aspirate consists of noncohesive Hürthle cells with both large and small cell dysplasia. Colloid is absent, and a small transgressing vessel is present in the center This cellular aspirate consists of loosely cohesive, markedly enlarged Hürthle cells with marked anisonucleosis and macronucleoli (large cell dysplasia) Dr. Monika Nema
  • 50.  Predominance of Hürthle cells is considerd as BENIGN in– Presence of abundant colloid. Absence of atypia. Dr. Monika Nema
  • 51.  When Hürthle cell differentiation is clear cut but only focal, it is advisable to follow the guidelines of the WHO, which considers only those follicular neoplasms that are comprised of >75% Hürthle cells to be a HCNs.  Thus, a suspicious FNA in which <75% of the abnormal cells are well-developed Hürthle cells should be diagnosed as “Follicular Neoplasm/Suspicious for a Follicular Neoplasm” rather than FNHCT/SFNHCT. Dr. Monika Nema
  • 52. Follicular Neoplasm, Hürthle Cell Type/Suspicious for a Follicular Neoplasm, Hürthle Cell Type  Reporting pattern  Example 1: SUSPICIOUS FOR A HÜRTHLE CELL NEOPLASM. Cellular aspirate consisting predominantly of Hürthle cells in syncytial like sheets and crowded clusters in the absence of colloid.  Example 2: SUSPICIOUS FOR A HÜRTHLE CELL NEOPLASM. Cellular aspirate composed of cells with abundant granular cytoplasm. The findings raise the possibility of a Hürthle cell neoplasm, but a parathyroid tumor cannot be excluded. Correlation with clinical findings, imaging findings, and serologic testing results might be helpful. Dr. Monika Nema
  • 54. Suspicious for malignancy  A specimen is suspicious for malignancy (SFM) when some features of malignancy raise a strong suspicion of malignancy , but the findings are not sufficient for a conclusive diagnosis.  A malignant diagnosis should be reserved for those cases that show sufficient cellularity and most, if not all, of the diagnostic features of an entity.  Specimens that are suspicious for a follicular or Hürthle cell neoplasm are excluded from this category. Dr. Monika Nema
  • 55. Suspicious for malignancy  Suspicious for Papillary Carcinoma.  Suspicious for Medullary Carcinoma.  Suspicious for Lymphoma.  Suspicious for malignancy, not otherwise specified. Dr. Monika Nema
  • 56. Suspicious for Papillary Carcinoma  Pattern A (“Patchy Nuclear Changes Pattern”)  Pattern B (“Incomplete Nuclear Changes Pattern”)  Pattern C (“Sparsely Cellular Specimen Pattern”)  Pattern D (“Cystic Degeneration Pattern”) Dr. Monika Nema
  • 57. Suspicious for Papillary Carcinoma Pattern A (“Patchy Nuclear Changes Pattern”) The sample is moderately or highly cellular. Benign follicular cells (arranged predominantly in macrofollicle fragments) are admixed with cells that have nuclear enlargement, nuclear pallor, nuclear grooves, nuclear membrane irregularity, and/or nuclear molding. Intranuclear pseudoinclusions (INCIs) are rare or absent. Dr. Monika Nema
  • 58. Suspicious for Papillary Carcinoma Pattern B (“Incomplete Nuclear Changes Pattern”) The sample is sparsely, moderately, or highly cellular. There is generalized mild- to-moderate nuclear enlargement with mild nuclear pallor. Nuclear grooves are evident, but nuclear membrane irregularity and nuclear molding are minimal or absent. Intranuclear pseudoinclusions are rare or absent. Dr. Monika Nema
  • 59. Suspicious for Papillary Carcinoma Pattern D (“Cystic Degeneration Pattern”)  There is evidence of cystic degeneration based on the presence of hemosiderin laden macrophages.  Scattered groups and sheets of follicular cells have enlarged, pale nuclei and some have nuclear grooves, but INCIs are rare or absent.  There are occasional large, atypical, “histiocytoid” cells with enlarged nuclei and abundant vacuolated cytoplasm.  There are rare calcifications that resemble psammoma bodies. Dr. Monika Nema
  • 60. Suspicious for Medullary Carcinoma  The sample is sparsely or moderately cellular.  There is a monomorphic population of noncohesive small or medium sized cells with a high nuclear/cytoplasmic (N/C) ratio.  Nuclei are eccentrically located, with smudged chromatin due to suboptimal preservation; there are no discernible cytoplasmic granules.  There may be small fragments of amorphous material - colloid versus amyloid. Dr. Monika Nema
  • 61. Suspicious for Lymphoma  The cellular sample is composed of numerous monomorphic small- to intermediate- sized lymphoid cells. Dr. Monika Nema
  • 62. Suspicious for malignancy REPORTING PATTERN  Example 1: SUSPICIOUS FOR MALIGNANCY. Suspicious for papillary thyroid carcinoma.  Example 2: SUSPICIOUS FOR MALIGNANCY. Suspicious for medullary thyroid carcinoma. Note: Correlation with serum calcitonin level or re-aspiration for immunohistochemical studies might be helpful for definitive diagnosis if clinically indicated.  Example 3: Suspicious for malignancy . Suspicious for lymphoma. Note: Re-aspiration for immunophenotyping studies by flow cytometry might be helpful for definitive diagnosis if clinically indicated. Dr. Monika Nema
  • 63. Papillary Carcinoma of Thyroid Dr. Monika Nema
  • 64. Papillary Carcinoma of Thyroid  It is a malignant epithelial tumor derived from thyroid follicular epithelium and displays characteristic nuclear alterations.  The most common malignant neoplasm of the thyroid.  Occurs in all age groups.  Peak incidence in the third to fourth decades.  Risk factors include external radiation to the neck during childhood, ionizing radiation, genetic factors, and nodular hyperplasia. • Carries a good prognosis Dr. Monika Nema
  • 65. Papillary Carcinoma of Thyroid True papillary tissue fragments Papillary-like fragments Microfollicle sMonolayered sheet Follicular cells are arranged in Dr. Monika Nema
  • 66. Monolayered sheet of Papillary Carcinoma of Thyroid v/s macrofollicle fragment typical of benign follicular nodules  Arrangement of the cells in the sheets (evenly spaced vs. crowded)  Nuclear features of papillary carcinoma are larger, paler, more crowded, and more irregular in contour Benign follicular nodule Papillary Carcinoma of Thyroid Dr. Monika Nema
  • 67. Papillary Carcinoma of Thyroid Orphan Annie nuclei Longitudinal nuclear grooves Intranuclear cytoplasmic pseudoinclusions Pale nuclei with powdery chromatin Dr. Monika Nema
  • 68. Papillary Carcinoma of Thyroid Orphan Annie nuclei Longitudinal nuclear grooves  Psammoma bodies only are non- specific.  Psammoma bodies are also seen in medullary thyroid carcinoma, lymphocytic thyroiditis, Graves’ disease, and even nodular goiter. Psammoma bodies Multinucleated giant cells Bubble-gum-like colloid Dr. Monika Nema
  • 69. Papillary Carcinoma of Thyroid  Necrotic debris is extremely uncommon.  Hürthle cell (oncocytic) metaplasia is sometimes seen.  Squamous metaplasia is sometimes seen. (moderate to abundant dense cytoplasm and cells that fit together like paving stones) Dr. Monika Nema
  • 70. Variants of Papillary Thyroid Carcinoma  Variants of PTC, by definition, have the essential nuclear features of PTC but A different architectural pattern.  Unusual cytoplasmic features.  Different background features, such as the quantity and texture of the colloid.  The presence or absence of a prominent lymphoplasmacytic infiltrate. Dr. Monika Nema
  • 71. Variants of Papillary Thyroid Carcinoma  Follicular variant of PTC.  Macrofollicular Variant.  Cystic variant.  Oncocytic variant.  Tall cell variant.  Columnar cell variant.  Hyalinizing Trabecular tumor. Dr. Monika Nema
  • 72. Follicular variant of PTC.  The follicular variant of PTC (FVPTC) is a PTC in which the tumor is completely or almost completely composed of small to medium-sized follicles lined by cells with the nuclear features of a PTC. Dr. Monika Nema
  • 73. Follicular variant of PTC.  FVPTC is now the most common variant of PTC.  In contrast to conventional PTC, the nuclear changes are often subtle.  The following features are usually absent or inconspicuous: papillary and papillary-like fragments, multinucleated giant cells, INCIs, psammoma bodies, marked cystic change. Dr. Monika Nema
  • 74. Macrofollicular Variant  The macrofollicular variant is a PTC in which over 50% of the follicles are arranged as macrofollicles. Dr. Monika Nema
  • 75. Macrofollicular Variant  Criteria The sample consists of monolayered (two- dimensional) sheets of atypical epithelium and/or variably sized follicles. Convincing nuclear changes of PTC must be present for a definite interpretation of malignancy. In contrast to conventional PTC, the diagnostic nuclear features are often more subtle (as with FVPTC). Abundant thin colloid or fragments of thick colloid may also be present. Dr. Monika Nema
  • 76. Macrofollicular Variant Differential diagnosis includes  Benign follicular nodule seen with nodular goiter.  The follicular adenoma of macrofollicular type. Easily overlooked at low magnification due to the abundance of thin colloid, the low cellularity, and the subtle and focal nuclear atypia. Thus, careful attention to nuclear features is necessary. Dr. Monika Nema
  • 77. Cystic Variant  The cystic variant is a PTC that is predominantly cystic, comprised of thin, watery fluid, abundant histiocytes, and hypervacuolated tumor cells.  PTC is the most common malignant neoplasm of the thyroid to undergo cystic change. Dr. Monika Nema
  • 78. Cystic Variant Intranuclear pseudoinclusions Histocytes Dr. Monika Nema
  • 79. Cystic Variant  Criteria The neoplastic cells are typically arranged in small groups with irregular borders; sheets, papillae, or follicles may also be present. 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. Dr. Monika Nema
  • 80. Oncocytic Variant  The oncocytic variant is a thyroid tumor with the nuclear changes characteristic of PTC but composed predominantly of oncocytic cells (polygonal cells with abundant granular cytoplasm).  Criteria The sample is composed predominantly of oncocytic cells, arranged in papillae, sheets, 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. Dr. Monika Nema
  • 81. Oncocytic Variant . Oncocytic cells with intranuclear pseudoinclusions Lymphocytes are absent Dr. Monika Nema
  • 82. Tall cell variant  An aggressive form of PTC composed of papillae lined by a single layer of elongated (“tall”) tumor cells (their height is at least three times their width) with abundant dense granular cytoplasm and the typical nuclear changes of PTC.  Tends to occur in elderly patients.  More frequent in men.  It is often presented as a large and bulky tumor, often with an extrathyroidal extension and vascular invasion.  Has a higher incidence of local recurrence and distant metastasis. Dr. Monika Nema
  • 83. Tall cell variant Multiple INCI in a nucleus giving soap-bubble appearance Elongated neoplastic cells more granular nuclear chromatin Dr. Monika Nema
  • 84. Columnar cell variant  A rare aggressive variant of PTC.  Characterized by columnar cells with hyperchromatic, oval, and stratified nuclei and supranuclear or subnuclear cytoplasmic vacuoles. Dr. Monika Nema
  • 85. Columnar cell variant Elongated and crowded nuclei with distinct stratification. Cells have dark chromatin, unlike the typical powdery chromatin seen in the other types of PTC Generally lack colloid. A crowded, pseudopapillary fragment of columnar tumor cells Dr. Monika Nema
  • 86. Columnar cell variant  The neoplastic cells of the columnar cell variant may be mistaken for benign cells like respiratory epithelial cells (seen when the trachea is penetrated).  The dark and stratified nuclei resemble those of a colorectal neoplasm, and therefore the possibility of a metastasis from a colorectal primary enters the differential diagnosis. Dr. Monika Nema
  • 87. Hyalinizing Trabecular Tumor  Rare tumor of follicular cell origin characterized by trabecular growth, marked intratrabecular hyalinization, and the nuclear changes of PTC.  HTT is very difficult to recognize as such in an FNA specimen.  Because of its nuclear features, most HTTs are interpreted as PTC or “suspicious for PTC.” Dr. Monika Nema
  • 88. Criteria  Neoplastic cells are radially oriented around amyloid-like hyaline stromal material. INCIs and nuclear grooves are numerous. Occasional psammoma bodies may be present. Cytoplasmic paranuclear yellow bodies may be present. Dr. Monika Nema
  • 89. Papillary Carcinoma of Thyroid REPORTING PATTERN  The general category “MALIGNANT” is used whenever the cytomorphologic features are conclusive for malignancy.  Descriptive comments that follow are used to subclassify the malignancy and summarize the results of special studies, if any.  If the findings are suspicious but not conclusive for malignancy, the general category “SUSPICIOUS FOR MALIGNANCY” should be used.  Example :  Malignant .  Papillary thyroid carcinoma. Dr. Monika Nema
  • 91. Medullary Thyroid Carcinoma  MTC is a malignant neoplasm derived from and/or morphologically recapitulating the parafollicular cells of the thyroid gland.  Comprises approximately 7% of thyroid carcinomas.  It occurs in sporadic and heritable forms. Dr. Monika Nema
  • 92. Medullary Thyroid Carcinoma  MTC may occur at any age,  Usually older adults with a mean age of 50 years.  MTC is an aggressive tumor that spreads by hematogenous and lymphatic routes.  Common sites of metastasis include cervical lymph nodes, lung, liver, bone, and adrenal glands.  The possibility of metastatic MTC should be kept in mind in a patient with a positive cervical lymph node of unknown primary. Dr. Monika Nema
  • 93. moderate to marked cellularity Isolated cells alternate with syncytial-like clusters Cells are plasmacytoid, polygonal, round, and/or spindle-shaped. Have a round nucleus, eccentrically placed with finely or coarsely granular (“salt and pepper”) chromatin within a moderately abundant, granular cytoplasm. Dr. Monika Nema
  • 94.  Amyloid is abundant and readily appreciated in some cases.  Amyloid appears as dense, amorphous material that resembles thick colloid. Dr. Monika Nema
  • 95. Medullary Thyroid Carcinoma REPORTING PATTERN  The general category “MALIGNANT” is used whenever the cytomorphologic features are conclusive for malignancy.  Descriptive comments that follow are used to subclassify the malignancy and summarize the results of special studies, if any.  If the findings are suspicious but not conclusive for malignancy, the general category “SUSPICIOUS FOR MALIGNANCY” should be used. Dr. Monika Nema
  • 96. Medullary Thyroid Carcinoma REPORTING PATTERN Example :  Malignant .  Consistent with medullary thyroid carcinoma.  Note: Cytomorphologic features are characteristic of medullary thyroid Carcinoma. Serum chemistries for calcitonin might be helpful. Dr. Monika Nema
  • 97. Poorly Differentiated Thyroid Carcinoma Dr. Monika Nema
  • 98. Poorly Differentiated Thyroid Carcinoma  Cellular preparations display an insular, solid, or trabecular cytoarchitecture.  Insular pattern means group of cells outlined by a thin fibrovascular border. Dr. Monika Nema
  • 99. Poorly Differentiated Thyroid Carcinoma  There is a uniform population of follicular cells with scant cytoplasm (sometimes plasmacytoid)Dr. Monika Nema
  • 100. Poorly Differentiated Thyroid Carcinoma Apoptosis and mitotic activity are present Necrosis present. Presence of poorly differentiated features like mitoses, necrosis, or small convoluted nuclei. Dr. Monika Nema
  • 101. Poorly Differentiated Thyroid Carcinoma  “A definitive diagnosis of poorly differentiated carcinoma can be made only at the histological level.” Reporting Pattern–  If the findings are not conclusive for malignancy, the general category “SUSPICIOUS FOR MALIGNANCY” should be used.  Many PDTCs overlap morphologically with follicular neoplasms and are therefore inevitably interpreted as “SUSPICIOUS FOR A FOLLICULAR NEOPLASM” Dr. Monika Nema
  • 102. Poorly Differentiated Thyroid Carcinoma Reporting Pattern– Example : • Malignant . • Highly cellular aspirate with atypical follicular cells, necrosis, and scant colloid, most consistent with poorly differentiated thyroid carcinoma. Dr. Monika Nema
  • 103. Undifferentiated (Anaplastic) Thyroid Carcinoma Dr. Monika Nema
  • 104. Undifferentiated (Anaplastic) Thyroid Carcinoma  It is a high grade, pleomorphic, epithelial-derived malignancy with epithelioid and/or spindle cell features. Dr. Monika Nema
  • 105. Cells are epithelioid in appearance. Variation in cell and nuclear size is evident. plasmacytoid appearance Spindle shaped Spindle shaped cells in storiform patternDr. Monika Nema
  • 106. Intranuclear cytoplasmic pseudoinclusion. Nuclear enlargement. Contour irregularity. Prominent nucleolus. parachromatin clearing Extensive inflammation Giant cell Dr. Monika Nema
  • 107. Squamous cell carcinoma of the thyroid Dr. Monika Nema
  • 108. Squamous cell carcinoma of the thyroid  Squamous cell carcinoma of the thyroid is a malignant tumor that shows exclusively squamous differentiation. Criteria :- Cytologic samples are composed almost exclusively of large, pleomorphic keratinized cells (orangeophilia of the cytoplasm). Necrosis may be present. Correlation with clinical and imaging findings is essential for excluding a metastasis Dr. Monika Nema
  • 109. REPORTING PATTERN Example :  Malignant .  Undifferentiated thyroid carcinoma.  Note: Advise immunohistochemical studies for further evaluation Dr. Monika Nema
  • 110. Metastatic Tumors and Lymphomas Dr. Monika Nema
  • 111. Metastatic Tumors and Lymphomas  Tumors of nearby structures that can involve the thyroid include those of the pharynx, larynx, esophagus, mediastinum, and nearby lymph nodes.  The most common origins of metastases to the thyroid are cancers of the lung, breast, skin (especially melanoma), colon, and kidney. Dr. Monika Nema
  • 112. Metastatic Tumors  Metastatic Renal cell carcinoma.- The distinction between clear cell RCC and follicular and Hürthle cell neoplasms is difficult, particularly if the RCC is occult, or if the history of RCC is not provided  Metastatic Malignant Melanoma.-Intracytoplasmic pigment is not common but can be seen as fine granules in neoplastic cells or coarse granules in histiocytes. Cells are usually immunoreactive for S-100 protein, melanA, and HMB45.  Metastatic Adenocarcinoma from the Breast.-Cells are often immunoreactive for estrogen and progesterone receptors and negative for TTF-1 and thyroglobulin Dr. Monika Nema
  • 113. Lymphoma involving the thyroid gland Dr. Monika Nema
  • 114. Lymphoma involving the thyroid gland  Hodgkin and non-Hodgkin lymphomas are malignancies of lymphoid cells, most commonly B- cells, and arise in the thyroid gland as a primary malignancy or involve the thyroid gland secondarily.  The majority of lymphomas arising within the thyroid gland are non-Hodgkin lymphomas (NHL) of B-cell phenotype and two-thirds are preceded by Hashimoto thyroiditis.  Most NHLs of the thyroid gland are either DLBL or extranodal marginal zone B-cell lymphomas of mucosa- associated lymphoid tissue (MALT). Dr. Monika Nema
  • 115. Lymphoma involving the thyroid gland  There are at least three different patterns of lymphoma on FNA.  One is characterized by mixture of small and large lymphocytes. This pattern can be seen in Hashimoto thyroiditis as well, but the absence of oncocytes, follicular epithelial cells, and plasma cells favors lymphoma.  The second pattern is characterized by a monotonous population of large lymphoid cells and is morphologically diagnostic of lymphoma.  The third pattern is characterized by a monomorphous population of small lymphocytes, which may represent lymphoma or inactive thyroiditis. Dr. Monika Nema
  • 116. REPORTING PATTERN Example :  Malignant .  Diffuse large B- cell lymphoma. Example :  Suspicious for malignancy.  Suspicious for metastatic deposits. Dr. Monika Nema
  • 117. Benefits of The Bethesda system of reporting Thyroid Cytopathology  Uniform reporting system for thyroid FNA.  Facilitate effective communication.  Facilitates cytologic - histologic correlation for thyroid diseases.  Facilitates research .  Allows reliable sharing of data. Dr. Monika Nema

Editor's Notes

  1. However, there was never an effective linkage between these clinical management plans and thyroid FNA reporting, thus undermining the clinical utility of cytopathologic diagnoses.
  2. In order to bridge this gap of communication, the National Cancer Institute (NCI) hosted the “NCI Thyroid Fine Needle Aspiration State of the Science Conference” on 2007 in Bethesda. One of the recommendations endorsed by this program was the establishment of a six-tiered diagnostic classification system
  3. Microfollicles- Crowded, flat groups of less than 15 follicular cells arranged in a circle that is at least two-thirds complete. Microfollicles tend to be relatively uniform in size (“equisized”). An important defining feature of the microfollicle is the crowding and overlapping of the follicular cells.
  4. Follicular cells are arranged in true papillary tissue fragments, comprised of fibrovascular cores lined by neoplastic cells. Follicular cells are arranged in papillary-like fragments (papillary shape but lacking a fibrovascular core) Follicular cells are arranged in microfollicles. Follicular cells are arranged as the monolayered sheet.
  5. The altered follicular cells exhibit characteristic nuclear features: Enlarged nuclei Oval or irregularly shaped, sometimes molded nuclei Pale nuclei with powdery chromatin (“Orphan Annie” nuclei) Marginally placed micronucleoli, solitary or multiple. Longitudinal nucleargrooves.- Results from a nucleus folded onto itself.
  6. The altered follicular cells exhibit characteristic nuclear features: Enlarged nuclei Oval or irregularly shaped, sometimes molded nuclei Pale nuclei with powdery chromatin (“Orphan Annie” nuclei) Marginally placed micronucleoli, solitary or multiple. Longitudinal nucleargrooves.- Results from a nucleus folded onto itself.