general anesthesia and the influence of FNAB on surgical
decision making.
Methods
Institutional review board approval was obtained from the
University of Pittsburgh. Patients aged 0 to 21 years were
retrospectively identified in a cytopathology database for
having undergone FNAB of a HNM. Consecutive subjects
from July 2007 to July 2014 were included, and there were
no exclusion criteria. All patients were seen in the pediatric
otolaryngology or endocrinology departments where the
need for FNAB was determined and consent was obtained
for the procedure.
The decision to proceed with nonthyroid FNAB was
typically based on persistence of a neck mass beyond 4
weeks despite treatment with antibiotics. Cases atypical for
benign lymphadenopathy were referred for FNAB sooner
(eg, unusual location, rapid enlargement, weight loss, night
sweats, skin changes, fixed/immobile mass). All nonthyr-
oid FNABs were performed because the patient was con-
sidered a potential surgical candidate, the mass was
atypical, and/or the family or medical team desired a
pathologic diagnosis. Given the high rate of malignancy in
pediatric thyroid nodules, patients with lesions greater than
1 cm or smaller with concerning ultrasonographic features
(hypoechogenicity, irregular margins, or increased vascu-
larity) were offered FNAB.
Fine-needle aspiration biopsies were subsequently per-
formed in the otolaryngology clinic or inpatient ward by the
cytopathologist, the interventional radiology suite (IR) by a
radiologist, or the operating room (OR) by the surgeon or
cytopathologist. Topical (4% lidocaine cream), general, or
topical plus sedative anesthesia was used. As a standard
practice at our institution, all biopsies performed in the IR
suite used image guidance, and all others were performed
by palpation. Most thyroid nodules were biopsied with ultra-
sound guidance, consistent with current recommendations.
6
A 25- to 27-gauge needle was used, and approximately 3
to 5 passes were performed for each targeted site, represent-
ing a single FNAB. Patients with multiple FNABs therefore
had more than 1 targeted HNM, multiple encounters, or
both. Aspirated material was used for smear preparation,
including air-dried slides stained with Diff-Quik and
alcohol-fixed slides stained with the Papanicolaou stain.
Residual material was submitted for ThinPrep (Hologic Inc,
Marlborough, Massachusetts) processing, microbial cultures,
molecular studies, flow cytometry, and/or cell block pre-
paration, depending on the immediate interpretation. Cell
block sections were stained with hematoxylin and eosin
stain, and additional levels were used for immunostains,
special stains, or other ancillary testing. The FNABs were
interpreted by 1 of 9 cytopathologists, although most (88%)
were interpreted by 1 of 2 cytopathologists with pediatric
expertise. Nonthyroid cases received diagnoses with an ade-
quacy interpretation (unsatisfactory, less than optimal, or
satisfactory), a primary interpretation (nondiagnostic, nega-
tive for malignant cells, atypical cells present, suspicious
for malignant cells, or positive for malignant cells), and a
free text explanatory diagnosis. Thyroid cases received an
adequacy interpretation, a primary interpretation using The
Bethesda System for Reporting Thyroid Cytopathology
(TBSRTC),
4
and a free text explanatory diagnosis.
The determination of a nonsurgical (negative) vs surgical
(positive) FNAB result was made for each patient. Final out-
comes were then established either through correlation to sur-
gical histopathology or clinical follow-up. Histopathology
based on surgical biopsy (incisional or excisional) is consid-
ered the reference standard in the diagnosis of an HNM.
Clinical follow-up is included as a secondary reference given
that most pediatric HNMs are benign and do not undergo sur-
gery and therefore histopathologic evaluation.
True positives were cytopathologic results that warranted
surgical treatment and were confirmed as such histopatholo-
gically. True negatives were cytopathologic results that did
not indicate a need for surgery and were confirmed histo-
pathologically as such. Clinical true negatives were cyto-
pathologically negative conditions that resolved or did not
progress without surgical intervention. False positives were
cytopathologic results that indicated a need for surgical
treatment but histopathology demonstrated a nonsurgical
condition. False negatives were cytopathologic results that
did not indicate a need for surgery but were histopathologi-
cally proven to be conditions where surgery was indicated.
Pathologists interpreting surgical histopathology were dis-
tinct from our cytopathologists and neither was blinded to
clinical information or pathology results.
Certain conditions, such as atypical mycobacterial infec-
tion, cervicofacial abscess, lymphovenous malformations,
and lymphoma, may warrant surgical diagnosis or treatment
but may also appropriately proceed directly to medically
therapy. These cases were all considered positive on the
basis that surgery could be indicated. If surgery was pursued
and histopathology confirmed the cytopathologic result, the
case was a true positive. If the appropriate medical therapy
was initiated and was effective, the result was a clinical true
positive.
Individual diagnoses and demographic data such as age
at first encounter and sex are presented on a patient level.
Features unique to each encounter such as complications,
FNAB venue, and level of anesthesia are presented on an
encounter level. Specificity, sensitivity, and nondiagnostic
results are presented on an FNAB level.
SPSS version 21 (SPSS, Inc, an IBM Company, Chicago,
Illinois) was used to analyze the data. Sensitivity, specifi-
city, and positive and negative predictive values were calcu-
lated using the definitions as detailed above. Nondiagnostic
results were not included in these statistics, and no missing
data were encountered. A
P
value
\
.05 was considered sig-
nificant. Age at first encounter was compared between the
high and low level of anesthesia and thyroid/nonthyroid
groups using an independent sample
t
test. Age was com-
pared between the thyroid/nonthyroid groups using
Pearson’s
x
2
test. Generalized estimating equations were
used to compare the number of nondiagnostic results
Huyett et al
191