1
ADEQUACY OF THE SAMPLE IN THYROIDAL ASPIRATES.
An accurate diagnosis depends on an adequate and representative sample interpreted
correctly in the clinical context (not in a vacuum). At present there is no consensus
among pathologists as to what represents an adequate sample. The Papanicolaou Society
of Cytopathology acknowledges that it is not an easy task to define an adequate sample of
a thyroidal FNA and that these guidelines are still a work in progress.
The specimen must be:
1. Representative of the lesion.
2. Adequate in amount.
3. Technically well prepared.
4. Interpreted in the clinical context and also taking the practice setting into
consideration.
1.- The specimen must be representative of the lesion:

The sample has to be from the appropriate location; a sample showing only normal
tissue is an unsatisfactory specimen.

A single aspirate might not be representative of the lesion. On average, for 1.0 - 2.0
cm nodules, we recommend three samples (from the center, top, and bottom) of the
lesion or nodule (1). There is one exception to this rule: when the lesion is cystic, all
the fluid is evacuated during the first aspiration, and there is no residual lesion
palpable. In such an instance the FNA is diagnostic and therapeutic. In general, the
larger the lesion, the more samples. Multiple samples will reduce the inadequacy rate
and the “false negative rate.”
2.- The cellular composition of the specimen must be adequate in amount:
AdeqPapSoc 6/10/06
1
2
How much is enough? Several discussions of this issue have been published, as follows:
“Five to six groups of well preserved (follicular) cells, with each group consisting of 10
or more cells.”(2, 3) “At least six aspirates from each nodule, and at least two smears
had to contain at least six clusters of benign cells each.”(4) “A total of at least 10 large
clusters of follicular cells containing more than 20 cells each, present on all available
smears.”(5) “A minimum of 8-10 tissue fragments of well-preserved follicular epithelium
on each of two slides.”(6)
The Papanicolaou Society of Cytopathology has remarked previously that “The
cellularity of a specimen, however, is greatly influenced by the intrinsic nature of the
lesion from which the specimen was obtained. Many cases of benign colloid goiter yield
abundant colloid but few follicular cells.”….“Similarly, a cystic lesion that yields
numerous macrophages with scant or no follicular cells may be reported as consistent
with benign thyroid cyst.” PSC recommends that the cytopathology report include a
qualifier indicating that the cytologic interpretation is limited by the paucity of follicular
cells.(7)
We have to be aware of interobserver variation. We have to acknowledge that
subjectivity is involved in the science and art of making a pathologic diagnosis. (8)
3.- The specimen must be technically well prepared:
Aspirates should be smeared promptly (to avoid clotting artifacts) and thinly, and they
should be well stained. If hematological stains are going to be used, the smears are airdried. If Papanicolaou stain is preferred, the smears must be promptly spray-fixed, or
wet-fixed in 95% ethanol.
AdeqPapSoc 6/10/06
2
3
4.- The specimen must be interpreted in the clinical context and taking the setting of
the practice into consideration.
Clinical features and information have to be taken into consideration: size of the lesion,
its consistency—soft, rubbery, firm,--fixation to surrounding structures, response to
suppressive therapy, history of head and neck irradiation, patient’s age and sex,
sonographic findings when available, and family history. Some nodules may feel firm on
palpation and consequently are clinically worrisome. If several aspirates (from the center,
top, and bottom of the lesion, taken at different depths and close to the surface) yield
many fragments of fibrocollagenous tissue and small follicular cells, one can safely
assume that the nodule is fibrotic and not malignant. If in addition to the fragments of
fibrous tissue, numerous lymphoid cells (more than expected from peripheral blood) are
seen in a hemorrhagic background, one should suspect the false negative pattern of
lymphocytic thyroiditis.(9) Sampling the contralateral lobe might yield a more classic
pattern or an earlier phase of Hashimoto’s thyroiditis. Also, if fluid is obtained from a
firm nodule, with complete collapse of the lesion, the firmness has to be interpreted as
fluid under tension. Likewise, if dense colloid (rather than thin colloid) is obtained, this
would explain the increased consistency of the lesion. We have described only a few of
the multiple and varied lesions encountered in daily practice to make the point that
cytologic interpretation cannot be just about number of cells. This approach would be too
rigid and simplistic. We reiterate that: “The pathologist should know how to count, but it
is more important that the pathologist knows what counts.”(1)
The three most common practice settings are: (1) the pathologist performs the
aspiration, (2) the endocrinologist performs the aspiration and submits the smears to the
AdeqPapSoc 6/10/06
3
4
laboratory, or (3) the radiologist performs the aspiration assisted by the pathologist or
cytotechnologist to determine whether the specimen is adequate or not. Probably an
example will clarify this situation. An endocrinologist or a surgeon submits smears to the
cytopathology laboratory, from a “thyroid aspiration.” The specimen contains many
fragments of adipose tissue and no follicular epithelial cells. Hence, it is interpreted as
“unsatisfactory for accurate cytologic diagnosis due to lack of follicular epithelial cells.”
No clinical history or differential diagnosis (rule out lipoma) is provided. The diagnosis
will be based on microscopic findings only. If the cytopathologist performs the aspiration
and obtains only adipose tissue, he/she will insert multiple needles of different lengths
and gauges to ensure that the sample does not represent subcutaneous fat and that it is a
lipoma of the anterior neck mimicking a thyroid nodule.(10)
In summary: Adequacy of the sample does not depend exclusively on numbers of cells.
If you are an “interventional pathologist,” evaluate the specimen based on your clinical
appraisal of the lesion. Remember that as a diagnostician you have to meld the clinical
data with the cytologic findings and make the best possible decision in each case. If you
are interpreting submitted smears, ask yourself: If this was a nodule in my thyroid, do I
believe it was sampled appropriately? Always be concerned about the possibility of
thyroidal carcinoma.
The PSC stresses that the keys to success are: mastering the best possible
aspiration technique, interpreting the smears using sound clinical judgment, and utilizing
close collaboration between endocrinologists, radiologists, surgeons, and
cytopathologists.
AdeqPapSoc 6/10/06
4
5
REFERENCES:
1.
Oertel YC. Extensive personal experience: A pathologist trying to help
endocrinologists to interpret cytopathology reports from thyroid aspirates. Journal
of Clinical Endocrinology & Metabolism 87: 1459-1461, 2002.
2.
Goellner JR, Gharib H, Grant CS, Johnson DA. Fine needle aspiration cytology of
the thyroid, 1980 to 1986. Acta Cytologica 31: 587-590, 1987.
3.
Grant CS, Hay ID, Gough IR, McCarthy PM, Goellner JR. Long term followup of
patients with benign thyroid fine needle aspiration cytologic diagnoses. Surgery
106: 980-986, 1989.
4.
Hamburger JI, Hussain M. Semiquantitative criteria for fine-needle biopsy
diagnosis: reduced false negative diagnoses. Diagnostic Cytopathology 4: 14-17,
1988.
5.
Nguyen G-K, Ginsberg J, Crockford PM. Fine-needle aspiration biopsy cytology
of the thyroid: its value and limitations in the diagnosis and management of
solitary thyroid nodules. Pathology Annual 23: 63-80, 1991.
6.
Kini SR. Thyroid. 2nd ed. New York: Igaku-Shoin, p. 521, 1996.
7.
Papanicolaou S. Guidelines of the Papanicolaou Society of Cytopathology for the
examination of fine-needle aspiration specimens from thyroid nodules. The
Papanicolaou Society of Cytopathology task force on standards of practice.
Modern Pathology 9: 710-715, 1996.
8.
Baloch ZW, Hendreen S, Gupta PK, LiVolsi VA, Mandel SJ, Weber R, Fraker D.
Interinstitutional review of thyroid fine-needle aspirations: Impact on clinical
management of thyroid nodules. Diagnostic Cytopathology 25: 231-234, 2001.
AdeqPapSoc 6/10/06
5
6
9.
Oertel YC, Oertel JE. Diagnosis of benign thyroid lesions: Fine-needle aspiration
and histopathologic correlation. Annals of Diagnostic Pathology 2: 250-263,
1998.
10.
Butler SL, Oertel YC. Lipomas of anterior neck simulating thyroid nodules:
Diagnosis by fine-needle aspiration. Diagnostic Cytopathology 8: 528-531, 1992.
AdeqPapSoc 6/10/06
6