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ENDOCRINE SURGERY
30
radionuclide scan can be performed to evaluate nodule function.
Thyroid FNA examination is also sensitive
and specific in the diagnosis of childhood nodular thyroid disorders [20–22]. Thyroid nodules
occur less frequently in children than in adults.
However, some studies have shown the frequency of malignancy appears to be higher in
children than in adults [20–22].
The FNA should be repeated for cases with
inadequate yields following the first attempt,
because repeating the aspiration provides an
adequate sample in as much as 50–88% of the
initially unsatisfactory cases [8]. In addition,
recent data strongly support the clinical usefulness of one repeat FNA after an initial benign
aspiration. The use of one repeat FNA increases
the sensitivity for malignancy from 81.7 to
90.4% and decreases the false-negative rate
from 17.1 to 11.4% [23].
Overall, FNA is preferred over thyroid scan
or ultrasonography as the initial diagnostic test
for thyroid nodules. However, a previous ultrasound may aid the physician performing the
aspiration of lesions that are difficult to palpate.
Contraindications and
Complications of Thyroid FNA
Because FNA of the thyroid is an invasive procedure, albeit minimally so, complications are
possible although extremely rare [9, 11, 24,
25]. Needle puncture may cause slight pain
and some skin discoloration at the aspiration
site(s). Bleeding complications occur only
infrequently as either localized swelling or
bruising after the procedure but are usually
avoided if firm pressure is applied to the
aspiration site. Tracheal injury is manifested
by minimal and transient hemoptysis. Needle
tract implantation of thyroid carcinoma is
extremely rare; it has been poorly documented
and is not considered a real problem by most
experts [9, 11, 24–27].
Although the use of anticoagulants or salicylates does not preclude FNA, it is recommended
that aspirin or other agents that affect coagulation should be discontinued for several days
before the procedure [12, 15]. Bleeding is more
likely with large needles [24, 25].
Technical Aspects of Thyroid
FNA
Selection of Technique
A thyroid nodule can be aspirated manually or
under ultrasound (US) guidance. Ultrasound
examination of thyroid nodules provides
structural information about the location,
number, size, and the gross morphology of
the nodules. Several studies have attested to
its value and have shown that this method can
effectively increase the sensitivity and specificity and decrease the nondiagnostic rate as
compared with manual thyroid FNA [28, 29].
This is especially true in thyroid lesions that
are
difficult to palpate due to smaller size;
arising in the posterior aspect of the thyroid;
nodules associated with diffuse pathological
processes such as lymphocytic thyroiditis,
and Graves’ disease;
palpable thyroid nodules that are deemed be
nondiagnostic on manual FNA due to extensive cystic change or fibrosis. In such cases,
US-guided FNA can easily target the solid
portion of the nodule to acquire diagnostic
material.
When FNAs are taken with ultrasound guidance
care must be taken to avoid contaminating the
cellular material with gel, which may render the
cytology difficult or impossible to interpret
accurately.
The initial step of thyroid FNA is localizing
the nodule or nodules to be aspirated, which is
followed by selection of the needles to be used.
Usually a 25- or a 27-gauge needle is preferred
[9, 24, 25]. The use of larger needles, 0.7 mm
(21 gauge) or more, in most cases results in a
rich admixture of peripheral blood, which is a
distinct disadvantage for cytological examination. In addition, more pain is caused by the use
of large needles. Local anaesthesia is however
not necessary.
Regardless of who carries out the procedure,
it is important for a second individual, preferably a cytopathologist or cytotechnologist to be
present to prepare the slides, assess adequacy of
the sample, and retain material if needed for
ancillary techniques.
31
FINE-NEEDLE ASPIRATION BIOPSY
Specimen Procurement
Although both suction and nonsuction techniques have been described for thyroid FNAbiopsy, it is generally recommended that the
nonsuction technique with a 25- or a 27-gauge
fine needle is used first [9, 24, 25, 30, 31]
(Fig. 3.1), as this technique is simple, produces
specimens that are less bloody and is particularly effective for aspirating small lesions.
However, the conventional suction technique
sometimes yields more material than the nonsuction technique and vice versa, so it is unwise
to use one technique to the exclusion of the
other. If a cyst is encountered during nonsuction FNA, suction with a larger needle attached
to a 10- or a20-ml syringe held by a ‘‘pistol-grip’’
device is recommended, to evacuate as much
fluid as feasible. If there is a residual solid area,
then a 25- or a 27-gauge needle may be used for
nonsuction sampling of this area.
The patient should be told before the procedure that more than one aspirate may be needed
to obtain enough material for diagnosis and
sometimes for extra tests. During the procedure
the patient is asked to keep still and to refrain
from swallowing. The needle is gently inserted
into the nodule and then moved in and out 5–10
times (Fig. 3.1). Aspirate flows into the needle
through capillary action and, as soon as aspirate
appears in the hub, the needle is withdrawn and
attachedto the syringe with air inside toexpel the
material onto glass slides (Fig. 3.1).
Firm pressure should be applied to the
biopsy site for at least 1 min immediately after
the needle is withdrawn, and the needle (or needle with a syringe and holder) should be handed
without delay to the person preparing the slides.
The needle should be turned away from the person receivingit or, preferably, should be placed
in a shallow container. The slides should be
prepared immediately to avoid clotting or cellular degeneration. As long as there is no significant bleeding, and any repeat aspirates
have been taken, an adhesive dressing may be
placed on the puncture site(s). The patient is
observed for a few minutes and, if there are no
problems, the patient is allowed to leave the
FNA clinic.
Although it has been suggested that more
aspirations will increase the diagnostic rates,
the optimal number of aspirations is a matter
of debate. It is generally recommended that a
minimum of two passes should be taken from
various portions of the nodule to decrease sampling error. Most reports indicate that two to
Fig. 3.1. Demonstration of nonsuction FNA of the thyroid
(modified from reference [28]). (A) The needle is held directly
between the thumb and the index finger. The nodule is immobilized with the index and middle fingers of the other hand. The
needle is moved back and forth several times within the nodule
with a rapid, gentle, stabbing motion. (B) After the needle is
withdrawn, an air-filled syringe with its plunger already retracted
is immediately attached to the needle. (C) The needle contents
are expelled onto clean glass slides. Thin, evenly spread smears
are prepared from the ejected material.
ENDOCRINE SURGERY
32
four aspirates per nodule are adequate [9, 24, 25,
30, 31], but, occasionally, as many as six needle
punctures may be required.
The on-site evaluation of thyroid specimens
with rapid cytology stains could dramatically
reduce nondiagnostic rates [32, 33]; however,
this may not be available in all clinical settings
but should always be recommended, especially
whereinadequateratesarehigh.Therearea
number of advantages to on-site evaluation,
which include assessment of adequacy of the
specimen, provisional classification of the
lesion and triage so that appropriate material may be collected for additional studies
such as immunocytochemistry, microbiological analysis, flow cytometry and genetic studies
[32, 33].
Specimen Preparation and Staining
Following needle aspiration, the aspirated cells
are immediately and gently expelled onto a glass
slide. Parallel preparation of alcohol-fixed and
air-dried smears from the aspirated material is
recommended [9, 24–26]. Wet-fixed smears are
usually prepared with a modified Papanicolaou
stain, which shows nuclear details such as
grooves and inclusions, which are crucial for
the diagnosis of papillary carcinoma [24–26].
Air-dried smears are often prepared with the
Romanowsky modified methods (Hemacolor,
May-Grunwald–Giemsa or Diff-Quik method),
which can highlight the background watery colloid and cell architecture (papillary, monolayer
sheets, and macro- and microfollicles) and distinguish between cell types (follicular, Hurthle,
lymphocytes, and macrophages) [24–26]. The
Romanowsky staining method is also one of
the best methods available in cytology for
immediate evaluation of thyroid FNA specimens [32, 33].
The following issues should be considered
when preparing the specimen:
It is important that a small drop of aspirated
material is used for smear preparation
because if a large drop of aspirate material
is used, a thick smear will be obtained (Fig.
3.2). This will lead to slow drying of the
smear and loss of cellular details, making
the cytological evaluation difficult.
It is also important that the material is
smeared immediately after being expelled as
air-drying of the droplet causes the cells to
crush when spread (Fig. 3.2).
Instead of direct smearing, cytospin preparations should be performed from the liquid
contents of cystic thyroid lesions.
For alcohol fixation, the smears must be
placed promptly in 95% alcohol or with a
commercial spray fixative, before any airdrying occurs. A delay in fixation will result
in air-dried artifactual changes with loss of
cellular details.
Any remaining material can be rinsed in
balanced salt solution. The rinses are held
in reserve to be used for cytospin, cell block
preparation or further ancillary tests at the
discretion of the cytopathologist.
Fig. 3.2. Preparing a direct smear is an art in itself, which should not be left to anyone who is unable to assess the cytology.
33
FINE-NEEDLE ASPIRATION BIOPSY
When blood clots or visible tissue fragments
are present, they may be gently removed and
used for cell block preparation, as needed.
If the aspirated material is to be used for
immunocytochemistry, direct smears can be
used; but in most instances it is preferable to
make a cell suspension in buffered saline. The
cells are then collected by centrifugation to
make thrombin-induced cell blocks or cytospin preparations. Cells may also be fixed in
formalin for commercial cell block techniques.
Newer techniques have been developed, for
example, liquid-based cytology. This allows
lysis of blood and thin layer preparation [34].
However, the cytological appearances with
liquid-based cytology are somewhat different
to those on conventional smears and further
experience of the technique is required. The
major disadvantage of thin layer preparations
is that the colloid, which is important for diagnosis, may not be fully preserved. Indeed,
some studies have suggested that liquidbased thin layer method appears to be not
ideal for use in thyroid aspirates [35, 36].
Immunocytochemistry and Other
Ancillary Techniques
Immunocytochemistry and Flow Cytometry
Several tumor markers have been shown to be
helpful in thyroid pathology [37–39]. Their
application to cytology has also been suggested,
but there are limitations, as shown by the lack of
specificity. Panels of these markers may yield
supportive information in the differential diagnosis of thyroid nodules.
Cytokeratin 19 (CK19) is a high-molecular
weight cytokeratin that is a sensitive but not a
specific marker of papillary carcinoma. It is
often diffusely expressed in papillary carcinomas [38, 39], but focal positive staining can also
be seen in some follicular lesions, chronic lymphocytic thyroiditis and even in compressed
nonneoplastic thyroid tissue around thyroid
lesions [38, 39].
HBME-1 (Hector Battifora and mesothelioma 1) is a monoclonal antibody that was
initially promoted as a marker of mesothelial
cells. In the thyroid, HBME-1 is almost exclusively expressed in malignant neoplasms,
including papillary carcinoma, whereas benign
lesions are negative [37–39]. HBME-1 is the
most specific marker of thyroid malignancy,
but it may not be very sensitive because oncocytic lesions are generally negative; also, not all
thyroid malignancies are stained by this antibody. HBME-1 positivity is characterized by
predominantly membranous staining with variable cytoplasmic staining.
Galectin-3 is a member of the lectin family
that has physiologic and pathological functions
including growth regulation, development, differentiation and cell–cell adhesion. Galectin-3
has been promoted as a marker of malignancy
in thyroid; however, its expression in some
cases of multinodular goiter and in thyroiditis
limits its application [37, 39].
Immunostaining with thyroperoxidase antibody has been reported to be of value in distinguishing benign and malignant follicular
lesions, the former being commonly stained
positively while the latter being often stained
negatively with this antibody [40].
Immunostaining for thyroid transcription factor-1 (TTF-1), thyroglobulin, and calcitonin may
be indispensable to identify the cell type in poorly
differentiated neoplasms. These markers are also
useful in examining tumors in metastatic sites.
Flow cytometry is a technique that helps
greatly in the cytologic evaluation of lymphoid
malignancies [41, 42]. By this ancillary technique
one can separate lymphoid neoplasms from a
reactive processes by establishing clonality.
Flow cytometry also helps separate lymphoid
malignancies into those of T- or B-cell origin as
well ashelping to further subclassify the different
lymphomas. Immunocytochemistry in conjunction with flow cytometry for lymphoid markers
is of great value in the diagnosis of lymphoid
infiltration of the thyroid [42]. The technique
described above for retaining cell washings in
balanced saline allows the option of flow cytometry or immunocytochemistry as indicated by the
morphology. A flow chart for processing needle
washingsandancillarytestsisshowninFig. 3.3.
DNA and Molecular Techniques
Molecular techniques including microarray
analysis and molecular profiling may have significant roles in the future evaluation of thyroid
nodules, while providing impetus for further
insight into the molecular pathogenesis of both
benign and malignant lesions [43, 44]. For
ENDOCRINE SURGERY
34
Fig. 3.3. Flow chart showing our local scheme for rapid on-site evaluation of thyroid FNAs.
instance, by analysis of cancer gene profiles for
a cohort of 62 thyroid samples, Finley et al. [44]
were able to distinguish between benign and
malignant thyroid tumors. They reported a sensitivity of 91.7% and a specificity of 96.2% for
the detection of thyroid carcinomas of various
types, including papillary and follicular carcinomas [44]. However, at the present time, clinical use of specific molecular markers to
improve the diagnostic accuracy of indeterminate thyroid nodules is not recommended.
Specimen Adequacy
Acquiring adequate and diagnostic specimens
from the thyroid remains one of the most challenging obstacles in thyroid FNA. Currently,
criteria for specimen adequacy vary from institution to institution. Several discussions of this
issue have been published [8, 9, 11, 24, 25].
Some investigators require that an adequate
sample should contain five to six groups of
well-preserved and well-visualized follicular
cells with each group containing ten or more
cells [8, 9, 11]. The Papanicolaou Society of
Cytopathology (PSC) has published guidelines
[26] that do not specify a certain minimal number of follicular cells, but instead stress the
importance of assessing the amount of colloid
in determining specimen adequacy (Table 3.1).
For instance, a benign colloid nodule may be
suggested if a large amount of thick colloid
material is present, regardless of the number
of follicular epithelial cell clusters. However,
one should be cautious in rendering a diagnosis
35
FINE-NEEDLE ASPIRATION BIOPSY
Table 3.1. Guidelines for the microscopic evaluation of specimen adequacy
Number of follicular cells Amount of colloid Interpretation
Numerous Variable Adequate for interpretation, diagnosis depends on cellular features
Few Scanty or Absent Inadequate or unsatisfactory for interpretation
Few follicular cells Abundant Benign colloid nodule
Numerous macrophages,
few follicular cells
*
One should be cautious in rendering a diagnosis of colloid nodule in a specimen which shows watery colloid, macrophages, and few follicular
cells, because aspirates of papillary carcinoma with extensive cystic degeneration may also give rise to specimens with abundant colloid-like
material, macrophages, and few follicular cells.
y
If malignant cells, irrespective of the number, are positively identified in an aspirate, a malignant diagnosis should be made. However, if small
numbers of follicular cells show atypical features short of overt malignancy, a ‘‘suspicious’’ diagnosis or a repeat aspiration may be suggested.
z
The report should contain a qualifier stating that the interpretation is limited by the paucity of follicular cells and repeat aspirate is
recommended if nodule growth is observed on follow-up.
x
Occasionally, a cystic papillary carcinoma may present a similar pattern. Check for residual solid areas, and re-aspirate if palpable. The risk of
malignancy is higher in large (greater than 4 cm) lesions and those that increase in size despite therapy.
Variable Probably benign cystic colloid goitre
z
x
*,y
of colloid nodule in a specimen showing watery
colloid, macrophages, and few follicular cells,
because aspirates of papillary carcinoma with
extensive cystic degeneration may also display a
similar cytological appearance. If a cell sample
contains one or two small clusters of malignant
or highly atypical cells, it should be reported as
malignant or suspicious for malignancy and
not as unsatisfactory or inadequate for cytodiagnosis. The British Society for Clinical
Cytology (BSCC) is in the process of preparing
Codes of Practice for FNA, endorsed by the
Royal College of Pathologists, which will be
available in 2009.
A repeat FNA may provide diagnostic smears
in up to 50% of cases [8]. In the Mayo Clinic
experience, repeating the FNA in the cases with
initial non-diagnostic needle aspirates revealed
diagnostic material in 30–80% of cases [8, 11]. If
the re-aspiration is still non-diagnostic, USguided FNA should be performed [28, 29].
Cytodiagnosis and Diagnostic
Categories
Thyroid FNA results are commonly divided into
four or five categories [15, 24–27]. In the fourtiered classification system, the FNA results
are categorized into nondiagnostic/inadequate,
benign, suspicious for neoplasm, and malignant. Typically, a benign cytological diagnosis
is reported for 50–90% of the specimens [8, 11,
19, 45, 46]. About 10–30% of FNA specimens
may be suspicious for malignancy or indeterminate [8, 11, 46]. A malignant or positive cytological diagnosis varies from 1 to 10% [46]. This
categorization does not identify follicular neoplasms, which are known mostly to be benign
but require excision to exclude malignancy. For
that reason, a five-tiered classification is favored
in the UK [15, 47].
In the five-tiered British Thyroid Association
(BTA) classification system [15, 47], the FNA
results are categorized into Thy1 (nondiagnostic/
inadequate), Thy2 (benign/nonneoplastic), Thy3
(follicular lesions), Thy4 (suspicious of malignancy), and Thy5 (diagnostic of malignancy).
The details of Thy classification and recommended action are listed in Table 3.2.
Recently, a six-tiered classification system has
been proposed at the NCI State of the Science
Conference in 2007 in Bethesda on thyroid FNA
which can be downloaded from www.thyroidfna/
gov/pages/conclusion. Briefly, the NCI Thyroid
FNA classification system subdivides thyroid
lesions into 1) benign, 2) follicular lesion of undetermined significance, 3) neoplasm (including
follicular neoplasm and Hurthle cell neoplasm),
4) suspicious for malignancy, 5) malignant and
6) nondiagnostic
Nondiagnostic or Inadequate FNA
Specimen (Thy1)
Inadequate specimens should be labeled ‘‘nondiagnostic’’ or ‘‘unsatisfactory.’’ The specimen
adequacy criteria (Table 3.1), as described
ENDOCRINE SURGERY
Table 3.2. Diagnostic categories for fine-needle aspiration (FNA) biopsy of thyroid nodules (BTA classification)
Diagnostic categories Proposed actions
Thy1 Unsatisfactory, nondiagnostic or inadequate
(specify reason)
Thy2 Nonneoplastic (features consistent with a
colloid nodule, nodular goiter, cystic goiter,
or thyroiditis)
Thy3 Cellular follicular lesions including hyperplastic
nodule, follicular neoplasm (adenoma and
carcinoma), and Hurthle cell lesions
Thy4 Abnormal, suspicious of malignancy
(suspicious, but not diagnostic, of papillary,
medullary, or anaplastic carcinoma or of
lymphoma)
Thy5 Diagnostic of malignancy with unequivocal
features of papillary, medullary or
anaplastic carcinoma, or of lymphoma or
metastatic tumor
FNA should be repeated
Ultrasound guidance may permit more targeted sampling
Two diagnostic benign results 3–6 months apart are required to
exclude neoplasia
In patients in a high clinical risk group (e.g., male gender,
extremes of age, with other features suggestive of tumor, with
a family history, or with a history of irradiation) the decision to
proceed to lobectomy may be made even with a benign FNA
diagnosis
This decision might also be made if there are pressure
symptoms or rapid growth
In addition, the patient should have the choice to have the
lesion removed if he/she so wishes
Lobectomy or watchful waiting depending on clinical features
Completion thyroidectomy will be necessary if the histology
proves malignant
Surgical intervention indicated for differentiated tumor
Further treatment will depend on the histopathology report
Indication for further investigation for anaplastic thyroid
carcinoma, lymphoma, or metastatic tumor
Surgical intervention indicated for differentiated thyroid
cancer, depending on tumor size, clinical stage, and other risk
factors such as gender and extremes of age
Indication for appropriate further investigation, radiotherapy,
or chemotherapy for anaplastic thyroid carcinoma, lymphoma,
metastatic tumor
36
above, should be followed regardless of radiological and clinical findings. The range of inadequate or unsatisfactoryspecimens reported in the
literature ranges from 2 to 21% (mean 17%) [13].
Factors that affect adequacy rate include variable
training and technique of operators, the vascular
nature of the thyroid, and the variably cellular
nature of thyroid nodules [8, 11, 24–27, 45, 46].
In general, an acceptable rate for inadequate
specimens is less than 15%.
Aspirators who consistently produce high
numbers of inadequate samples should be
identified and offered training.
Benign or Nonneoplastic Lesions
(Thy2)
This group includes lesions with the diagnosis
of colloid nodule, multinodular goiter, cystic
goiter, or thyroiditis. Whenever possible, a
specific cytological diagnosis should be
provided.
Benign Colloid Nodule or Multinodular Goiter
Aspirates obtained from multinodular goiters
show loosely cohesive sheets of follicular epithelium, colloid, blood, and macrophages. Colloid
nodules contain an abundance of colloid with
sparse follicular cells. There is considerable variation in the number of cells as well as the type
and amount of colloid present. Typical cytological features include [8, 11, 24–27, 45, 46]
abundant colloid, thick and/or thin (Fig. 3.4);
small to moderate number of follicular
epithelial cells in monolayered sheets, poorly
cohesive groups, and single cells. May have
oxyphilic or Hurthle cell change;
variable number of histiocytes and hemosiderin-laden macrophages;
may have degenerative changes: old blood,
debris, fragments of hyalinized stroma.
37
FINE-NEEDLE ASPIRATION BIOPSY
Fig. 3.4. FNA of a benign colloid nodule. (A) Abundant dark
blue-stained colloid material with cracking pattern in air-dried
smear (Hemocolor staining, 400). (B) Thin watery colloid with
macrophages in fixed smear (Papanicolaou stain, 400).
Cysts and Cystic Goiter
Benign cysts account for the majority of thyroid cystic lesions. They are formed as the result
of hemorrhagic degeneration of a benign colloid nodule. FNA from a benign colloid cyst
may show colloid admixed with benign follicular epithelial cells and hemosiderin-laden
macrophages (Fig. 3.5). However, any thyroid
neoplasm may undergo hemorrhagic cystic
change [9, 26, 48]. Of the thyroid neoplasms,
papillary carcinoma tends to undergo marked
hemorrhagic degenerative change. FNA from
the tumor commonly shows a large amount of
blood and the cystic lesion tends to recur
rapidly [26]. Thus, it is important to keep in
mind that
the presence of cystic change in thyroid tissue does not in itself imply a benign lesion;
Fig. 3.5. FNA of a cystic goiter shows colloid material admixed
with benign follicular epithelial cells and numerous hemosiderin-laden macrophages (A) Papanicolaou stain, 400.
(B) Hemocolor stain, 400).
a definitive diagnosis of benign nodular goiter
with cystic change requires adequate sam-
pling of any solid component;
if only cyst fluid-containing macrophages
with no epithelial cells is obtained, this
should be interpreted as nondiagnostic, as
an underlying neoplasm with cystic change
cannot be excluded;
Notably, the gross appearance of cyst fluid is
not helpful in distinguishing benign thyroid
cyst from neoplastic cyst. One study showed
little difference in the prevalence of neoplasm
in association with bloodstained fluid, brown
turbid fluid or straw-colored fluid [49].
Thyroiditis
Hashimoto’s thyroiditis and subacute thyroiditis commonly have fairly distinctive clinical
Fig. 3.6. FNA of lymphocytic thyroiditis. A sheet of follicular
epithelial cells is infiltrated by small mature lymphocytes and
plasma cells (Papanicolaou stain, 400).
and cytological findings. These lesions may
present as a nodular lesion mimicking a thyroid neoplasm.
Hashimoto’s thyroiditis is characterized by the
presence of numerous lymphoid cells admixed
with benign follicular cells (Fig. 3.6) and Hurthle
cells. Typical cytological features of Hashimoto’s
thyroiditis include [9, 24, 25]
mixed population of lymphocytes and
plasma cells;
lymphohistiocytic aggregates;
cohesive groups of follicular cells with onco-
cytic features;
little or no colloid.
Subacute (granulomatous) thyroiditis is a rare
condition in the context of a benign aspirate.
Typically, the smear shows multinucleated giant
cells, epithelioid histiocytes, and scattered
inflammatory cells.
Other Benign Lesions
Graves’ disease may rarely present as a nodular
thyroid lesion [9, 19, 24, 25]. It yields nonspecific cytological findings. Common cytological
findings include
bloodstained smear with little colloid;
moderate amounts of follicular epithelium
and some follicular or ring structures;
cells with abundant pale vacuolated cyto-
plasm; mild nuclear enlargement and mod-
erate anisokaryosis;
marginal vacuoles of the colloid.
ENDOCRINE SURGERY
Follicular Lesions (Thy3)
Cellular Microfollicular Lesions
Follicular lesions of the thyroid represent themost
problematic area of thyroid FNA [24–26, 50–53].
The major entities included in the differential
diagnosis are hyperplastic/adenomatoid nodule,
follicular neoplasm (adenoma and carcinoma),
and some cases of the follicular variant of papillary carcinoma. Follicular lesions are found in
15–30% of FNA specimens [50–53].
As with frozen section, FNA cannot reliably
distinguish between benign and malignant
follicular lesions [27]. Specimens from cellular
adenomatoid nodule, follicular adenoma, and
well-differentiated follicular carcinoma usually
give rise to a similar cytological appearance.
Definitive diagnosis requires histological examination of the excised nodule to demonstrate the
presence of capsular or vascular invasion. The
prevalence of malignancy in this group of
patients is approximately 15–20% [51–53].
Thus, a diagnosis of follicular neoplasm belongs
to the indeterminate category (Thy3) of thyroid
FNA classification [15].
Cytological features of follicular lesions
include
cellular, monotonous cell population (more
than 70% of specimen) scattered throughout
the smear (Fig. 3.7);
microfollicles and rosettes;
nuclear overlapping and crowding in syncy-
tial groups of cells without the nuclear fea-
tures of papillary carcinoma;
scanty or no colloid (except as inspissated
colloid in microfollicles).
Generally, two cytological subcategories of Thy3
can be recognized [25, 26]: cellular follicular
lesion (favor hyperplastic or adenomatous
nodule) and cellular follicular lesion (favor follicular neoplasm). As described above, this
subdivision within Thy3 results in a similar
six-tiered classification system proposed at the
NCI State of the Science Conference on thyroid
FNA (www.thyroidfna/gov/pages/conclusion).
Unless there are specific features suggesting
malignancy (see below) or nuclear features suggesting papillary carcinoma, it is better not to
comment on whether a follicular lesion favors a
benign or malignant neoplasm.
38
39
FINE-NEEDLE ASPIRATION BIOPSY
diagnostic challenge to separate them from
hyperplastic Hurthle cell nodules in Hashimoto’s
thyroiditis [12, 24, 25, 54, 55]. Thyroid nodules
that show exclusively Hurthle cells without a
background of thyroiditis on FNAs have a high
rate of Hurthle cell neoplasm [24, 25, 54, 55]. On
the other hand, a mixture of Hurthle cells and
‘‘normal’’ follicular epithelial cells is more consistent with a hyperplasticnodule and should not
be interpreted as evidence of Hurthle cell neoplasm [24, 25, 54, 55].
Hurthle cell lesions are cytologically charac-
terized by
cellular aspirates containing sheets and clusters of polygonal Hurthle cells with abundant, granular, eosinophilic, or basophilic
cytoplasm (Fig. 3.8);
Fig. 3.7. FNA of a microfollicular lesion. (A) A cellular aspirate
consists of a monotonous population of follicular cells arranged
in microfollicular pattern. Cells have round nuclei with no
significant nuclear atypia (Hemocolor stain, 200). (B) Excision
of the lesion reveals a well-circumscribed follicular adenoma
(H&E stain, 200).
Factors suggesting malignancy include male
gender, nodule size over 3 cm and age over
40 years [51]. Some cytological features are
also shown to be associated with increased cancer risk. These include an increased nuclear size
with marked nuclear atypia including significant nuclear pleomorphism and irregularity
[53]. Re-aspiration of a follicular lesion is
usually discouraged as it rarely provides useful
information.
Hurthle Cell Lesion
This group includes both Hurthle cell adenoma
and Hurthle cell carcinoma, which are generally
indistinguishable from one another on the basis
of cytological examination [8, 54, 55]. It is a
Fig. 3.8. FNA of a Hurthle cell lesion. (A) A monotonous
population of Hurthle cells arranged in the microfollicular
pattern. Cells have abundant, granular cytoplasm and round,
central, or eccentrically located nuclei (Papanicolaou stain,
400). (B) The excision biopsy shows a Hurthle cell adenoma
(H&E stain, 200).