The Journal of International Medical Research
2012; 40: 350 – 357 [first published online ahead of print as 40(1) 7]
Correlation between Thyroid Nodule
Calcification Morphology on Ultrasound
and Thyroid Carcinoma
C SHIa, S LIa, T SHI, B LIU, C DING
Fourth Department of Surgery, The Second Affiliated Hospital of Harbin Medical University,
Harbin, China
OBJECTIVE: This study investigated the
detection of thyroid nodule calcifications
on ultrasound and their relationship to
thyroid carcinoma. METHODS: Micro-
calcifications (≤ 2 mm) and macro-
calcifications (> 2 mm) on preoperative
ultrasound examination of thyroid and
lymph nodes were compared with
postoperative pathological diagnoses in
4186 patients undergoing thyroid surgery.
RESULTS: Higher incidences of micro- and
macrocalcifications were found in
patients with thyroid carcinoma than in
those with benign disease. The incidence
of malignant disease was significantly
higher in patients with micro-
calcifications than those with
macrocalcifications, suggesting that the
presence of microcalcifications is a better
KEY WORDS: CALCIFICATION; THYROID NODULE;
Introduction
With the widespread use of high-frequency
ultrasonography and colour Doppler blood
flow imaging, ultrasound has become one of
the most important techniques for the
preoperative screening of patients with
thyroid disease. Intranodular calcifications
aC Shi and S Li contributed equally to this article.
350
AND H QIN
predictor of malignant thyroid carcinoma
than other calcification types. The
specificity of microcalcifications for a
diagnosis of malignant thyroid carcinoma
was 96.5%. Microcalcifications were
significantly more frequent in patients
aged ≤ 45 years, but there was no
difference between genders. The incidence
of malignancy was significantly higher in
patients with single nodule calcifications
than in those with multiple nodule
calcifications. Lymph node calcifications
were seen in 12 patients, all of whom had
papillary carcinoma. CONCLUSIONS:
Thyroid microcalcifications are strongly
associated with thyroid carcinoma,
especially micropapillary carcinoma.
When cervical lymph node calcification is
present, immediate surgery is required.
THYROID CARCINOMA; ULTRASOUND; LYMPH NODES
are commonly seen in thyroid images in
both benign and malignant diseases.1,2 The
worldwide incidence of thyroid carcinoma is
rising3,4 and accounts for roughly 1% of all
new malignant disease.5
Recognition of the correlation between
thyroid malignant transformation and
intragland calcification6,7 has led to ultrasonic
examination becoming a crucial method for
 C Shi, S Li, T Shi et al.
Thyroid nodule calcification and thyroid carcinoma

preoperative thyroid screening.8 – 10 The macrocalcifications (Fig. 2). The shape,

present study investigated the relationship
between thyroid intranodular calcification,
as revealed by ultrasound scan, and the
incidence of thyroid carcinoma.
Patients and methods
STUDY POPULATION
All patients admitted for thyroid surgery to
The Second Affiliated Hospital of Harbin
Medical University, Harbin, China, between
January 2005 and January 2010 were
included in the study. The inclusion criteria
were: (i) age 18 – 76 years old; (ii)
preoperative diagnosis of thyroid disease;
(iii) surgery for thyroid disease performed at
The Second Affiliated Hospital of Harbin
Medical University; and (iv) pathological
confirmation of thyroid disease.
The study protocol was approved by the
Ethics Committee of The Second Affiliated
Hospital of Harbin Medical University,
Harbin, China. Written informed consent
was obtained from all study participants.
echogenicity, size and location of
calcification in the lymph nodes were noted.
The final diagnosis was determined from
pathology reports. A round hypoechoic
nodule with a longitudinal/transverse ratio
of < 2 was indicative of metastasis.
PATHOLOGICAL ASSESSMENT
Thyroid samples obtained during surgery
were flash frozen for postoperative
pathological examination. Micropapillary
carcinomas were ≤ 10 mm in diameter and
macropapillary carcinomas were > 10 mm
diameter.11
NODULAR CALCIFICATIONS AND AGE
The incidence of nodular calcifications
according to age was examined based on the
latest thyroid carcinoma data from the
International Union Against Cancer,12 which

ULTRASOUND EXAMINATION
All patients underwent routine preoperative
examination of the thyroid using high-
frequency ultrasound (Vivid™ 7 colour
Doppler ultrasound scanner, GE Healthcare
Bio-Sciences, Piscataway, NJ, USA) with a
probe frequency of 15 MHz. The size,
location, morphology, boundary, envelope,
echo behaviour, and intratumoural and
peripheral blood flow of the lesion site were
examined. The morphology and distribution
of any calcification was recorded. Bright and
granular calcification echo points ≤ 2 mm in
diameter, with or without acoustic shadows,
were considered to be microcalcifications FIGURE 1: Representative ultra-
(Fig. 1); all other calcifications with sonograph of the thyroid, showing
maximum diameter > 2 mm, including a microcalcification (arrow) as a
bright and granular calcification
lumpy, irregular calcifications, with or echo point ≤ 2 mm in diameter
without acoustic shadows, were defined as

351
 C Shi, S Li, T Shi et al.
Thyroid nodule calcification and thyroid carcinoma

statistical comparisons. A P-value of < 0.05

was considered to be statistically significant.
Data analyses were performed using SAS®
statistical software, version 9.1 (SAS Institute,
Cary, NC, USA).

FIGURE 2: Representative ultra-
sonograph of the thyroid,
showing a macrocalcification
(arrow) which was regarded as a
bright calcification echo point
with maximum diameter > 2 mm
indicates that the prognosis is significantly
different in patients ≤ 45 years old compared
with those > 45 years old. A cut-off point of 45
years old was, therefore, chosen for the analysis
of nodular calcifications according to age.
STATISTICAL ANALYSES
The χ2-test or Fisher’s test was used for
Results
A total of 4186 patients aged between 18 and
76 years (mean ± SD 47.6 ± 18.4 years)
admitted for thyroid surgery were included
in the study. Of these, 648 were male and
3538 were female (male : female ratio of
1.00 : 5.46). Thyroid diseases diagnosed at
surgery included thyroid carcinoma, nodular
goitre, thyroid adenoma, Hashimoto’s
thyroiditis, hyperthyroidism and subacute
thyroiditis.
The incidences of microcalcifications and
macrocalcifications in benign and
malignant thyroid disease are summarized
in Table 1. There were 1391 malignant cases
(225 males, 1166 females; male : female
ratio 1.00 : 5.18) and 2795 benign cases (423
males, 2372 females; male : female ratio
1.00 : 5.61). Positive calcification signs were
seen during preoperative ultrasound
examination in a total of 1725 (41.2%)
patients; of these, 916 (53.1%) cases were
malignant and 809 (46.9%) cases were
benign (not statistically significant). The
incidence of malignancy was 96.5%
(360/373) for patients with micro-

TABLE 1:
Calcification status on preoperative ultrasound examination in patients undergoing
thyroid surgery, according to disease status
Macrocalcification Microcalcification
Disease status n (> 2 mm) (≤ 2 mm) Total
Benign disease 2795 796 (28.5) 13 (0.5) 809 (28.9)
Malignant disease 1391 556 (40.0)a 360 (25.9)b 916 (65.9)
Total 4186 1352 (32.3) 373 (8.9) 1725 (41.2)
Data presented as n or n (%).
aP < 0.0001 compared with macrocalcification in benign disease, χ2-test or Fisher’s test.
bP < 0.0001 compared with microcalcification in benign disease, χ2-test or Fisher’s test.

352
 C Shi, S Li, T Shi et al.
Thyroid nodule calcification and thyroid carcinoma

calcifications and 41.1% (556/1352) for
patients with macrocalcifications (P < 0.01).
Of the 1725 patients with calcifications,
659 (38.2%) showed a single nodular area of
calcification; of these, 193 (29.3%) were
benign and 466 (70.7%) were malignant.
The remaining 1066 patients (61.8%) had
multiple nodular calcifications; of these, 543
(50.9%) were benign and 523 (49.1%) were
malignant. The incidence of malignancy
was significantly higher in patients with
single nodular calcification than in those
with multiple calcifications (P < 0.05).
A breakdown of the incidence of macro-
and microcalcifications in patients with
benign thyroid disease, according to
pathological diagnosis, is given in Table 2.
Calcifications were seen in 809 of 2795
patients with benign thyroid disease (28.9%).
The incidence of microcalcifications in
benign thyroid disease was 0.5%, which was
significantly smaller than that in malignant
cases (25.9%; P < 0.0001; Table 1).
A breakdown of the incidence of macro-
and microcalcifications in patients with
malignant thyroid disease, according to
pathological diagnosis, is given in Table 3.
Calcifications were seen in 916 of 1391
patients with malignant thyroid disease
(65.9%). Of these 916 patients, 36 (3.9%)
were found to have lymph node metastasis.
In thyroid carcinoma, the incidence of
microcalcifications (25.9%; 360/1391
patients) was lower than that of
macrocalcifications (40.0%; 556/1391
patients), but this difference was not
statistically significant (Table 3). In
micropapillary carcinomas, however, the
incidence of microcalcifications (47.4%;
161/340 patients) was significantly higher
than that for macrocalcifications (12.4%;
42/340 patients; P < 0.0001). The incidence
of microcalcifications was significantly
higher in micropapillary carcinomas
(47.4%; 161/340 patients) than in macro-
papillary carcinomas (19.9%; 192/963
patients; P < 0.0001).
The incidence of calcifications according
to age and gender is given in Table 4. There
was no significant difference in the overall
incidence of calcifications in the two age
groups; however, the incidence of
microcalcifications was significantly higher
in patients ≤ 45 years old compared with
older patients (P < 0.0001; Table 4) and the
incidence of macrocalcifications was
significantly lower in patients ≤ 45 years old
compared with older patients (P < 0.0001;

TABLE 2:
Calcification status on preoperative ultrasound examination in patients with benign
thyroid disease undergoing thyroid surgery, according to pathological diagnosis
Macrocalcification Microcalcification Statistical
Pathological diagnosis n (> 2 mm) (≤ 2 mm) Total significancea
Nodular goitre 2152 751 (34.9) 8 (0.4) 759 (35.3) P < 0.0001
Adenoma 359 13 (3.6) 1 (0.3) 14 (3.9) P = 0.0012
Hashimoto’s thyroiditis 231 29 (12.6) 4 (1.7) 33 (14.3) P < 0.0001
Hyperthyroidism 38 2 (5.3) 0 (0.0) 2 (5.3) NS
Subacute thyroiditis 15 1 (6.7) 0 (0.0) 1 (6.7) NS
Total 2795 796 (28.5) 13 (0.5) 809 (28.9) P < 0.0001
Data presented as n or n (%).
NS, not statistically significant (P > 0.05)
a
Within-group comparison between macrocalcification and microcalcification incidence, χ2-test or Fisher’s test.

353
 C Shi, S Li, T Shi et al.
Thyroid nodule calcification and thyroid carcinoma

TABLE 3:
Calcification status on preoperative ultrasound examination in patients with malignant
thyroid disease undergoing thyroid surgery, according to pathological diagnosis
Macrocalcification Microcalcification Statistical
Pathological diagnosis n (> 2 mm) (≤ 2 mm) Total significancea
Papillary carcinoma
Micro (≤ 10 mm) 340 (26.1) 42 (12.4)b 161 (47.4)c 203 (59.8) P < 0.0001
Macro (> 10 mm) 963 (73.9) 479 (49.7) 192 (19.9) 671 (69.7) P < 0.0001
Follicular carcinoma 26 7 (26.9) 2 (7.7) 9 (34.6) NS
Undifferentiated cancer 13 8 (61.5) 2 (15.4) 10 (76.9) NS
Medullary carcinoma 45 19 (42.2) 3 (6.7) 22 (48.9) P < 0.0001
Carcinoma metastasized
from lung carcinoma 1 1 (100.0) – 1 (100.0) –
Othersd 3 – – – –
Total 1391 556 (40.0) 360 (25.9) 916 (65.9) NS
Data presented as n or n (%).
NS, not statistically significant (P > 0.05).
a
Within-group comparison between macrocalcification and microcalcification incidence, χ2-test or Fisher’s test.
b
Incidence of macrocalcification was significantly lower in micropapillary carcinomas than in macropapillary
carcinomas (P < 0.0001, χ2-test or Fisher’s test).
c
Incidence of microcalcification was significantly higher in micropapillary carcinomas than in macropapillary
carcinomas (P < 0.0001, χ2-test or Fisher’s test).
d
Others include thyroid carcinomas metastasized from renal cell carcinoma (two patients) and melanoma
(one patient).

Table 4). There was no significant difference
between males and females in the incidences
of micro- or macrocalcifications, or in the
overall calcification incidence (Table 4).
Localized lymph node calcification was
seen in 12 patients. All of these patients had
a pathological diagnosis of papillary
carcinoma; eight patients (66.7%) had
thyroid microcalcifications and four (33.3%)
had macrocalcifications. No lymph node
calcification was seen in patients with benign
disease or other types of malignant disease.
Discussion
The incidence of thyroid disease can vary
depending on factors such as the patient
population and the examination technique
used.13,14 In recent years, high-resolution
ultrasonography has been widely used to
screen for thyroid disease, but its value in
differentiating benign from malignant
disease is still under debate. A number of
studies have shown a close relationship
between calcification and thyroid
carcinoma. For example, Kakkos et al.15
reported that 54% of thyroid nodules with
calcification were malignant, which is
consistent with the 53.1% malignancy rate
seen in cases with calcification in the present
study. Similar findings were reported by Taki
et al.16 It is, therefore, apparent that
calcification is correlated with thyroid
carcinoma. In addition, the incidence of
calcification in malignant thyroid
carcinoma (65.9%) was higher than that in
nodular goitre (35.3%) in the present study;
this is consistent with the results of Consorti
et al.,6 who reported incidences of 39.4% and
20.1% in thyroid carcinoma and goitre,
respectively.
Ultrasound has been previously reported
to have a specificity and sensitivity in
detecting thyroid nodule calcifications of
91.3% and 43.1%, respectively,1 suggesting

354
 C Shi, S Li, T Shi et al.
Thyroid nodule calcification and thyroid carcinoma

that ultrasonography can be used as the first

step in thyroid nodule calcification
Calcification status on preoperative ultrasound examination in patients undergoing thyroid surgery, classified according to age

significancea
Statistical screening. Some previous studies,1,17

NS

NS
however, did not include the effect of
different calcification forms on the correct
prediction of malignant disease. In the

aBetween-group comparison of calcification incidence (age ≤ 45 years versus > 45 years; and male versus female), χ2-test or Fisher’s test.
present study, the incidence of malignancy
was significantly higher in patients with
807 (42.5)
918 (40.2)

295 (45.5)
1430 (40.4) microcalcifications (96.5%) compared with
Total

those with macrocalcifications (41.1%),

suggesting that the occurrence of
microcalcifications may be a reliable
predictor of thyroid carcinoma. Wang et al.18
significancea

previously also reported a close correlation

P < 0.0001
Statistical

between microcalcifications detected on

NS

ultrasound and carcinoma, with a specificity

of 96.7% and Chammas et al.19 reported
similar findings, thereby indicating that the
Microcalcification

presence of microcalcifications may be a

319 (16.8)

68 (10.5)
(≤ 2 mm)

specific predictor for thyroid carcinoma.

54 (2.4)

305 (8.6)

In the present study the incidence of

microcalcifications (25.9%) in malignant
thyroid carcinoma was significantly lower
than for macrocalcifications (40.0%);
however, the fact that 96.5% of patients with
significancea
P < 0.0001
Statistical

microcalcifications had malignancy, means

NS

that the presence of microcalcifications is

highly specific for malignancy and has
important diagnostic value. The incidence of
Macrocalcification

microcalcifications was only 0.5% in benign

thyroid diseases, which is notably lower than
488 (25.7)
864 (37.8)

227 (35.0)
1125 (31.8)
(> 2 mm)

the rate in thyroid carcinoma (25.9%);

Data presented as n of patients, or n (%).
NS, not statistically significant (P > 0.05).

therefore the presence of microcalcifications

can reduce the incidence of false-positive
results. In the present study, patients with
nodular goitre had the highest calcification
1901
2285

648
3538

incidence among all benign cases, consistent

n

with the findings of others.17

Calcifications can occur in metastasized
Disease status
and gender

lesion sites as well as in primary tumours. In

> 45 years
≤ 45 years
TABLE 4:

the present study, the incidence of papillary

Female
Gender
Male

carcinoma in the limited number of patients

Age

with localized lymph node calcification was

100%. This suggests that, once a patient with

355
 C Shi, S Li, T Shi et al.
Thyroid nodule calcification and thyroid carcinoma

thyroid disease is shown to have cervical is in contrast to an earlier report in which

lymph node calcification on ultrasound,
immediate surgery is required. Of these
patients, 66.7% had microcalcifications,
further supporting microcalcification as a
specific diagnostic indicator for papillary
carcinoma.
A previous study found that patients < 40
years of age with calcification had a risk of
thyroid carcinoma that was 1.52-fold higher
than older patients (≥ 40 years), and the
specificities of calcification for a malignant
tumour diagnosis in the two age groups were
87% and 57%, respectively.15 In the present
study, there was no difference in the overall
incidence of calcification in patients younger
or older than 45 years. The incidence of
microcalcifications, however, was
significantly higher in the younger group,
which is consistent with a previous report.18
There was no difference in the calcification
incidence between males and females,
suggesting the same calcification
mechanism occurs in both genders.
In the present study, the incidence of
micropapillary carcinoma was significantly
higher in patients with microcalcifications
than in those with macrocalcifications and
the incidence with which microcalcifications
were associated with macropapillary
carcinomas was significantly smaller than
the association with micropapillary
carcinomas. This suggests that an
ultrasound finding of microcalcifications is
of more value than a finding of
macrocalcifications in the diagnosis of
micropapillary carcinoma and that the
detection of microcalcifications is of more
clinical significance in the diagnosis of
micropapillary carcinoma than in the
diagnosis of macropapillary carcinoma. This
• Received for publication 8 September 2011 • Accepted subject to revision 22 September 2011
• Revised accepted 3 January 2012
Copyright © 2012 Field House Publishing LLP
there was no difference between micro- and
macropapillary carcinomas in their
association with microcalcifications.18
A previous study found that 50% of
patients with single nodular calcifications
had malignant thyroid disease.20 In the
present study, a significantly higher
percentage of patients with single nodular
calcifications (70.7%) had malignant
thyroid disease compared with those with
multiple nodular calcifications (49.1%),
suggesting that single nodular calcifications
are more closely associated with malignancy
than multiple nodular calcifications, and is
in agreement with the findings of others.21
More precise preoperative diagnosis of
thyroid carcinoma would require a
combination of ultrasound examination and
other methods, such as needle aspiration
cytology and other highly sensitive
techniques.22 – 24 In particular, if the nodule is
substantive, lacks the halo sign or a strong
internal echo signal, or if the echoing
structure is heterogeneous with ambiguous
boundaries and no signs of
microcalcifications are present, needle
aspiration cytology is recommended.
In summary, microcalcifications detected
by colour Doppler ultrasound are highly
specific for the diagnosis of thyroid
carcinoma, particularly papillary thyroid
carcinoma, and have important clinical
value in the diagnosis of micropapillary
carcinomas. When cervical lymph node
calcification is present, immediate surgery is
required.
Conflicts of interest
The authors had no conflicts of interest to
declare in relation to this article.

356
 C Shi, S Li, T Shi et al.
Thyroid nodule calcification and thyroid carcinoma

References 14 Choi WH, Chung YA, Han EJ, et al: Clinical

1 Khoo ML, Asa SL, Witterick IJ, et al: Thyroid
calcification and its association with thyroid
carcinoma. Head Neck 2002; 24: 651 – 655.
2 Chen G, Zhu XQ, Zou X, et al: Retrospective
analysis of thyroid nodules by clinical and
pathological characteristics, and
ultrasonographically detected calcification
correlated to thyroid carcinoma in South
China. Eur Surg Res 2009; 42: 137 – 142.
3 Lee JW, Yoon DY, Choi CS, et al: Anaplastic
thyroid carcinoma: computed tomographic
differentiation from other thyroid masses. Acta
Radiol 2008; 49: 321 – 327.
4 McNeil C: Annual cancer statistics report raises
key questions. J Natl Cancer Inst 2006; 98: 1598
– 1599.
5 Sherman SI: Thyroid carcinoma. Lancet 2003;
361: 501 – 511.
6 Consorti F, Anello A, Benvenuti C, et al: Clinical
value of calcifications in thyroid carcinoma
and multinodular goiter. Anticancer Res 2003;
23: 3089 – 3092.
7 Paschke R, Hegedüs L, Alexander E, et al:
Thyroid nodule guidelines: agreement,
disagreement and need for future research. Nat
Rev Endocrinol 2011; 7: 354 – 361.
8 Füessl HS: Management of nodular goiter: a
solution for thyroid nodules. MMW Fortschr Med
2011; 153: 14 – 17 [in German].
9 Shapiro RS: Management of thyroid nodules
detected at sonography: Society of Radiologists
in Ultrasound Consensus Conference
Statement. Thyroid 2006; 16: 209 – 210.
10 Yoon DY, Lee JW, Chang SK, et al: Peripheral
calcification in thyroid nodules:
ultrasonographic features and prediction of
malignancy. J Ultrasound Med 2007; 26: 1349 –
1355.
11 Piersanti M, Ezzat S, Asa SL: Controversies in
papillary microcarcinoma of the thyroid.
Endocr Pathol 2003; 14: 183 – 191.
12 Döbert N, Menzel C, Oeschger S, et al:
Differentiated thyroid carcinoma: the new
UICC 6th Edition TNM Classification System in
a retrospective analysis of 169 patients. Thyroid
2004; 14: 65 – 70.
13 Lee HK, Hur MH, Ahn SM: Diagnosis of occult
thyroid carcinoma by ultrasonography. Yonsei
Med J 2003; 44: 1040 – 1044.
value of integrated [18F]-fluoro-2-deoxy-D-
glucose positron emission
tomography/computed tomography in the
preoperative assessment of papillary thyroid
carcinoma: comparison with sonography. J
Ultrasound Med 2011; 30: 1267 – 1273.
15 Kakkos SK, Scopa CD, Chalmoukis AK, et al:
Relative risk of cancer in sonographically
detected thyroid nodules with calcifications. J
Clin Ultrasound 2000; 28: 347 – 352.
16 Taki S, Terahata S, Yamashita R, et al: Thyroid
calcifications: sonographic patterns and
incidence of cancer. Clin Imaging 2004; 28: 368
– 371.
17 Seiberling KA, Dutra JC, Grant T, et al: Role of
intrathyroidal calcifications detected on
ultrasound as a marker of malignancy.
Laryngoscope 2004; 114: 1753 – 1757.
18 Wang N, Xu Y, Ge C, et al: Association of
sonographically detected calcification with
thyroid carcinoma. Head Neck 2006; 28: 1077 –
1083.
19 Chammas MC, de Araujo Filho VJ, Moysés RA,
et al: Predictive value for malignancy in the
finding of microcalcifications on
ultrasonography of thyroid nodules. Head Neck
2008; 30: 1206 – 1210.
20 Rago T, Vitti P, Chiovato L, et al: Role of
conventional ultrasonography and color flow-
doppler sonography in predicting malignancy
in ‘cold’ thyroid nodules. Eur J Endocrinol 1998;
138: 41 – 46.
21 Cooper DS, Doherty GM, Haugen BR, et al:
Management guidelines for patients with
thyroid nodules and differentiated thyroid
cancer. Thyroid 2006; 16: 109 – 142.
22 Kwak JY, Kim EK, Son EJ, et al: Papillary thyroid
carcinoma manifested solely as
microcalcifications on sonography. AJR Am J
Roentgenol 2007; 189: 227 – 231.
23 Ohmori N, Miyakawa M, Ohmori K, et al:
Ultrasonographic findings of papillary thyroid
carcinoma with Hashimoto’s thyroiditis. Intern
Med 2007; 46: 547 – 550.
24 Lyshchik A, Moses R, Barnes SL, et al:
Quantitative analysis of tumor vascularity in
benign and malignant solid thyroid nodules. J
Ultrasound Med 2007; 26: 837 – 846.

Author’s address for correspondence

Dr Huadong Qin
Fourth Department of Surgery, The Second Affiliated Hospital of Harbin Medical University,
Xue Fu Road, Nangang District, Harbin 150086, Heilongjiang Province, China.
E-mail: aitiantang83@126.com

357