DOI:10.2214/AJR.08.1820
AJR 2009; 193:207-213
© American Roentgen Ray Society
Pattern Recognition of Benign Nodules at Ultrasound of the Thyroid: Which Nodules Can Be Left Alone?
John A. Bonavita1,
Jason Mayo1,
James Babb1,
Genevieve Bennett1,
Thaira Oweity2,
Michael Macari1 and
Joseph Yee1
1 Department of Radiology, Langone Medical Center, New York University School of
Medicine, 550 First Ave., New York, NY 10016.
2 Department of Pathology, Langone Medical Center, New York University School of
Medicine, New York, NY.
Received September 12, 2008;
accepted after revision October 24, 2008.
Address correspondence to J. Bonavita
(john.bonavita{at}nyumc.org).
Abstract
OBJECTIVE. The purpose of this study was to evaluate morphologic
features predictive of benign thyroid nodules.
MATERIALS AND METHODS. From a registry of the records of 1,232
fine-needle aspiration biopsies performed jointly by the cytology and
radiology departments at a single institution between 2005 and 2007, the cases
of 650 patients were identified for whom both a pathology report and
ultrasound images were available. From the alphabetized list generated, the
first 500 nodules were reviewed. We analyzed the accuracy of individual
sonographic features and of 10 discrete recognizable morphologic patterns in
the prediction of benign histologic findings.
RESULTS. We found that grouping of thyroid nodules into reproducible
patterns of morphology, or pattern recognition, rather than analysis of
individual sonographic features, was extremely accurate in the identification
of benign nodules. Four specific patterns were identified: spongiform
configuration, cyst with colloid clot, giraffe pattern, and diffuse
hyperechogenicity, which had a 100% specificity for benignity. In our series,
identification of nodules with one of these four patterns could have obviated
more than 60% of thyroid biopsies.
CONCLUSION. Recognition of specific morphologic patterns is an
accurate method of identifying benign thyroid nodules that do not require
cytologic evaluation. Use of this approach may substantially decrease the
number of unnecessary biopsy procedures.
Keywords: fine-needle aspiration • nodule • thyroid • ultrasound
Introduction
One of the consequences of increased use of imaging has been the
discovery of incidentalomas, or pseudodiseases, that are common in the general
population but have no or minor clinical significance. Once such
incidentaloma, the thyroid nodule, is extremely common, found in some autopsy
series in as much as 50% of the general population
[1,
2]. Most of these nodules are
benign; the incidence of malignancy is quite low, 3-7%
[3-5].
In the late 1990s, articles began to appear questioning the reliability of
radiotracer uptake as a predictor of benignity, occasioning a rapid transition
from nuclear medicine to ultrasound for evaluation of the thyroid
[6-8].
The superior resolution of ultrasound images has resulted in discovery of a
large number of thyroid nodules that heretofore had been obscured
[9].
Since the late 1990s, several studies have been conducted to analyze the
relation between specific sonographic features of thyroid nodules and
malignancy [2,
10-16].
Although guidelines have been established, such as those of the Society of
Radiologists in Ultrasound, the American Thyroid Association, and the European
Thyroid Association [2,
17-22],
they are commonly confusing and at times ignored in everyday practice, largely
because of lack of familiarity with and trust in their validity. Common in the
studies is a persistent limitation of specificity and sensitivity of specific
ultrasound features in the prediction of malignancy. Some authors
[23,
24] advocate a changed
approach of recognition of specific patterns rather than individual ultrasound
features in separation of nodules that require biopsy from those that do not.
The purpose of our study was to evaluate the accuracy of such a morphologic
feature-oriented approach to the identification of benign thyroid nodules.
Materials and Methods
Patients
Among the records of 1,232 fine-needle aspiration (FNA) biopsies performed
jointly by the cytology and radiology departments at a single institution from
January 2005 to December 2007, the cases of 650 patients (436 women, 64 men;
average age, 54.7 years; range, 17-88 years) were identified in which both
pathology reports and ultrasound images were available. From the alphabetized
list generated, the first 500 nodules were reviewed. This HIPAA-compliant
study was approved by our institutional review board with a waiver of informed
consent. We analyzed the accuracy of individual sonographic features and of 10
discrete recognizable morphologic patterns in the prediction of benign
histologic findings.
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Fig. 1C —Individual ultrasound features of nodules. 36-year-old man
with papillary carcinoma. Ultrasound scan shows microcalcifications
(arrow), which are easily confused with comet-tail shadowing.
Important finding is hypoechogenicity of nodule.
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Ultrasound Technique
All diagnostic ultrasound examinations and FNA biopsies were performed with
an Acuson x300 or Antares unit (both Siemens Healthcare). All FNA
biopsies were performed by a group of four cytologists (average experience, 5
years) under ultrasound guidance by one of five radiologists (average
experience, 20.5 years). The biopsies were performed with 25-gauge spinal
needles in most instances; a 27-gauge needle was used for hypervascular
lesions. At least two passes were made for each nodule (average, 3.2 passes
per nodule; range, 2-6 passes). All specimens were evaluated immediately by
the cytologists to confirm sample adequacy.
Ultrasound Interpretation
In this retrospective study the ultrasound images of all nodules were
reviewed in consensus by two blinded radiologists: one an attending
radiologist with 31 years of ultrasound experience, the other a second-year
radiology resident. Each nodule was evaluated for the presence or absence of
individual sonographic features and was assigned one of 10 distinct
recognizable morphologic patterns.
Histologic Analysis
The final diagnosis was based on the cytologic result; final pathologic
confirmation was limited to the 20 malignant tumors resected. In the 20
patients with these tumors, there was no discrepancy between the initial
cytologic and the final pathologic result. The cytologic results were divided
into three categories: 1, benign nodules, including colloid nodules,
hyperplastic nodules, and localized thyroiditis; 2, intermediate nodules,
including follicular and Hürthle cell neoplasms; and 3, carcinoma. Type 1
nodules were determined to be nodules that did not require biopsy; types 2 and
3 were nodules requiring biopsy.
Data Analysis
The sensitivity, specificity, positive predictive value, and negative
predictive value were defined for each individual sonographic feature in the
detection of nonbenign masses. The Blyth-Still-Casella procedure for
construction of exact CI for a binomial proportion was used to derive a 95% CI
for the negative predictive value associated with each classification factor
when used to identify benign masses. All reported p values were
two-sided significance levels and were declared statistically significant at
less than 0.05. SAS software (version 9.0, SAS Institute) was used for all
statistical computations. Each p value was derived from a Fisher's
exact test performed to determine whether the classification factor was
associated with benignity.
Results
The individual ultrasound features of each nodule analyzed were size,
number, texture (Fig. 1A),
margination (Fig. 1B), presence
of internal densities or calcifications (Figs.
1C, and
1D), edge refraction, and
vascularity relative to the rest of the gland
[13,
25,
26]
(Fig. 1E). Analysis of the
presence or absence of individual sonographic features revealed no feature
with consistently high sensitivity or specificity for malignancy
(Table 1). In our study,
sensitivity for the presence or absence of specific features was 35-100% and
specificity, 8.9-97.8%. There was no correlation between diagnosis and nodule
size, which was categorized as less than 1 cm (n = 7), 1-2 cm
(n = 288), and larger than 2 cm (n = 206)
(Table 2). However, several
features were found to have a statistically significant negative predictive
value. These individual features, the absence of which was common in benign
disease, included calcification, halo, hypoechogenicity, isoechogenicity, and
ring or peripheral hypervascularity.
Each nodule was assigned to one of 10 discrete morphologic groupings. These
patterns, which were based on a previous report
[23] and expanded according to
our experience, were as follows: 1, spongiform without hypervascularity
(Fig. 2A); 2, cyst with
avascular colloid plug (Fig.
2B); 3, giraffe pattern (Fig.
2C) with blocks of hyperechogenicity, or white, separated by bands
of hypoechogenicity, or black; 4, uniform hyperechogenicity ("white
knight") (Fig. 2D); 5,
intense hypervascularity ("red light")
(Fig. 2E); 6, hypoechogenicity
(Fig. 2F); 7, isoechogenicity
without halo (Fig. 2G); 8,
isoechogenicity with halo (Fig.
2H); 9, "ring of fire," or nodules with intense
peripheral vascularity (Fig.
2I); and 10, other (Fig.
2J), or a mixed pattern or pattern that did not fit the other
categories (Table 3). A
distinct pattern emerged in which it became evident that there were specific
morphologic groupings or patterns that were accurate predictors of benign
disease. Specifically, there were no malignant nodules in the 303 patients
(61%) with patterns 1-4 (Table
4). Spongiform nonhypervascular masses were the most common type
of nodule seen, 210 of 210 being found benign at FNA biopsy. All 53 of the
cysts with internal colloid clot, all 23 giraffe pattern nodules, and all 17
hyperechoic nodules were benign. The results in patterns 5-10 were
unpredictable, ranging from 35 of 37 isoechoic nodules without halo biopsied
being benign to only 31 of 45 hypoechoic nodules being benign.
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Fig. 2B —Morphologic patterns. 52-year-old man with colloid cyst.
Ultrasound scan shows cyst with colloid clot. When cystic portion of nodule is
subtracted, type 1 or spongiform nodules remain.
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Discussion
A thyroid nodule is a discrete lesion, sonographically distinct from the
surrounding thyroid parenchyma
[27]. Rather than a single
disease, nodules are manifestations of a gamut of thyroid diseases
[28]. Although some thyroid
nodules may be discovered at physical examination, many are incidental
findings of other imaging studies, such as CT and MRI of the neck or chest and
carotid ultrasound imaging. FNA of thyroid nodules has replaced blind surgical
excision as the procedure of choice in the diagnosis of thyroid nodules. Use
of FNA has led to a considerable decrease in the number of surgical excisions
and to a twofold increase in the diagnosis of carcinoma
[4,
5,
29]. The relative ease of FNA
compared with surgery and the increased frequency and refinement of imaging
studies has resulted in what some authors have referred to as an epidemic of
thyroid nodules [3,
30].
In view of their ubiquity, it is not feasible to biopsy every thyroid
nodule discovered with ultrasound. Reasons for limiting thyroid biopsy, which
is relatively painless and safe, include the small percentage of malignant
lesions, the small number of cases of thyroid cancer in which early diagnosis
may actually have an influence, the economic and societal costs, the strain on
radiology resources, and the patient uncertainty and anxiety incumbent on a
potentially malignant diagnosis. Hence, reliable guidelines for nodules that
may not require biopsy have become essential.
Not surprisingly in view of the experience of other authors
[31], we concluded that no
individual sonographic feature had both high sensitivity and high specificity
in the detection of malignancy. Nonetheless, many of these previously
described high-risk features, such as calcification, hypoechogenicity, poor
definition, and hypervascularity, were found to be absent over and over again
in nodules that did not require biopsy.
The persistent combination of some of these common individual ultrasound
characteristics, or, more properly, their absence, led us to consider a more
pattern-oriented approach, such as that advocated by Reading et al.
[23] as an alternative to the
analysis of individual features. Those authors described eight typical
appearances of commonly encountered benign and malignant nodules, allowing
them to separate more than one half of thyroid nodules into those that could
be observed versus those requiring biopsy. According to their results, the
following four classic patterns necessitate biopsy: 1, a hypoechoic nodule
with microcalcifications; 2, coarse calcifications in a hypoechoic nodule; 3,
well-marginated, ovoid, solid nodules with a thin hypoechoic halo; and 4, a
solid mass with refractive shadowing from the edges, which is believed to
occur as a result of fibrosis. The four classic patterns of nodules that did
not require biopsy in that series were the following: 1, small (< 1 cm)
colloid-filled cystic nodules; 2, a nodule with a honeycomb appearance
consisting of internal cystic spaces with thin echogenic walls; 3, a large
predominantly cystic nodule; and 4, diffuse multiple small hypoechoic nodules
with intervening echogenic bands, which are indicative of Hashimoto's
thyroiditis.
Like Reading et al. [23],
we found that use of a pattern approach to thyroid nodules is highly sensitive
and specific for the presence of benignity. Our patterns differed somewhat
from those proposed previously, yet there are definite similarities. Analysis
of our data revealed four patterns that were invariably benign at FNA biopsy
(Table 5). The most common
overall pattern is a nodule with diffuse internal linear cysts, described as
spongiform or honeycomb, our type 1 pattern. In our cases, this finding was
commonly described as a "puff pastry" pattern similar to the
ultrathin layers of flaky pastry in desserts such as napoleons. This pattern
was characteristic of colloid nodules or goiter. The only spongiform nodule
not classically benign was a single nodule that also was intensely
hypervascular. Our type 1 or spongiform nodule consequently is defined as
avascular or, occasionally, isovascular in relation to the rest of the
gland.
The second pattern (type 2) was a cystic nodule containing a central plug
of avascular colloid, similar to the previously described small or large cyst
patterns [23]. In our initial
analysis of individual features, size of cyst was deemed insignificant.
Important, however, was the characterization of the plug as avascular and puff
pastry. All of these nodules were also colloid nodules. If the cystic portion
of the lesion is subtracted visually, a type 1 spongiform nodule remains. The
third pattern (type 3), or giraffe pattern, was characterized by globular
areas of hyperechogenicity surrounded by linear thin areas of
hypoechogenicity, similar to the two-tone blocklike coloring of a giraffe.
This pattern was quite characteristic of Hashimoto's thyroiditis. A variation
of this pattern is our type 4 "white knight," or hyperechoic,
nodule, which was found commonly to be a regenerative nodule of Hashimoto's
thyroiditis.
Analysis of our other patterns revealed more variability in final cytologic
findings (Table 6). Such
nodules included both insignificant and significant lesions with such
variability that prediction before biopsy was not reliable. These nodules had
the four biopsy-recommendation patterns described earlier, such as isoechoic
nodule with a surrounding halo or refractive edges, which came to be
simplified in our series as isoechoic nodules with or without a halo (types 7
and 8). A hypoechoic nodule with or without central microcalcification or with
central macrocalcification in other series
[25,
26,
32], for which biopsy was
recommended, was the most worrisome pattern (type 6) in our study.
We identified other common patterns, including the type 5 "red
light" pattern, or an intensely hypervascular lesion that on Doppler
images glowed like a red stoplight. This pattern was commonly seen in lesions
with abundant cellularity, including, commonly, follicular neoplasms and, less
commonly, hyperplastic nodules and carcinoma. Other nodule types included type
9 ring-of-fire nodules with intense peripheral vascularity and nodules
described as other (type 10), which did not fit any of the classic patterns.
Calcification, although commonly seen in nodules requiring biopsy, was never
seen as an isolated finding. The likelihood of benignity of these nodules
(type 5-10) ranged from 60% (type 9, ring of fire) to 91% (type 10, other).
Because of this lack of predictability, we believed that these nodules should
be considered for FNA biopsy.
The limitations of our study are related to the fact that most of the
diagnoses were based on cytologic rather than histologic findings, the
retrospective nature of the study, and the fact that nodule characterization
was dependent on only two observers. The readers were blinded to the cytologic
results at the time of nodule characterization. The period 2005-2007 was
chosen to minimize the potential for recall bias. To answer our concerns with
respect to these limitations, we are preparing a study in which we train
radiologists with varying degrees of experience in this pattern approach. A
series of consecutive thyroid biopsies will be chosen prospectively in the
weeks before their performance, and the images will be shown to these readers,
who will decide whether biopsy should be performed. Analysis of interobserver
variability for assigning nodules to a specific pattern will be analyzed, as
will the characterizations with final cytologic result.
We conclude that biopsy of a large number of thyroid nodules (in our study,
61%) can be avoided when a pattern approach to nodule characterization is
used. Specific morphologic patterns are highly predictive of benignity.
Specifically, a nodule that has a uniform nonhypervascular spongiform
appearance, is a cystic lesion with a colloid clot, has a giraffelike pattern,
or is diffusely hyperechoic can be observed rather than biopsied. If,
conversely, a nodule does not correspond to one of these four patterns,
according to our data biopsy should be performed regardless of the individual
features or pattern of the nodule.
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Abstract
Introduction
