PhiliPPine Journal of otolaryngology-head and neck Surgery Vol. 29 no. 2 July – december 2014

ORIGINAL ARTICLES

PhiliPPine Journal of otolaryngology-head and neck Surgery 15

ABSTRACT
Background: Thyroid nodules are a common disease entity occurring in 5-10% of the general
population and increasing with age. Their detection on ultrasonography ranges from 13% to
67%. Calcifications on ultrasound may occur in both benign and malignant diseases but have
been cited for increased risk of thyroid carcinoma.

Objective: To determine the association of calcifications found on thyroid ultrasonography and
the different types of calcifications with thyroid carcinoma.

Methods:
Design: Retrospective Study
Setting: Tertiary Private Hospital
Participants: 126 patients with pre-operative thyroid or neck ultrasonography who

subsequently underwent thyroidectomy (total or subtotal, with or without frozen section)
were selected from a database covering a one-year period from January to December 2012.
The presence and type of calcification on ultrasonography was correlated with the final
histopathologic report for a diagnosis of thyroid carcinoma. Sensitivity, specificity, positive and
negative predictive values were obtained.

Results: 51 out of 126 studies (40%) were observed to have calcifications of any description in
both histologically benign (41%) and malignant (59%) nodules. Calcifications seen in malignancy
arose from papillary carcinoma (86%). Follicular carcinoma and others (Plasmacytoma and
Lymphoma) accounted for 7% each. The peripheral type of calcification was most prevalent
accounting for 37% (11 out of 30). The sensitivity of detecting calcifications on ultrasonography
is 58.82%, specificity 81.33%, positive predictive value 68.18% and negative predictive value
74.38%. Chi square test computed was 21.54 (P <0.05).

Conclusion: There was an association between calcification found on ultrasonography and
thyroid carcinoma and 86% of the calcifications were peripheral patterns mostly found in papillary
thyroid carcinomas. Ultrasonography alone is not sufficient in diagnosing thyroid carcinoma but
may increase the suspicion of malignancy depending on the type of calcification.

Keywords: Thyroid carcinoma, papillary carcinoma, calcifications, ultrasonography

Calcifications in Thyroid Ultrasonography
and Thyroid Carcinoma

Maria Christina D. Sio, MD
Jacqueline Austine U. Uy, MD
Ronaldo G. Soriano, MD

Department of Otolaryngology
Head and Neck Surgery
St. Luke’s Medical Center

Correspondence: Dr. Ronaldo G. Soriano
Department of Otolaryngology
Head and Neck Surgery
St. Luke’s Medical Center
279 E. Rodriguez Ave., Quezon City 1102
Philippines
Phone: (632) 727 5543
Fax: (632) 723 1199 (H)
Email: slmcearnosethroat@yahoo.com
Reprints will not be available from the author.

The authors declared that this represents original material
that is not being considered for publication or has not been
published or accepted for publication elsewhere in full or in
part, in print or electronic media; that the manuscript has been
read and approved by all the authors, that the requirements
for authorship have been met by each authors, and that each
author believes that the manuscript represents honest work.

Disclosures: The authors signed disclosures that there are no
financial or other (including personal) relationships, intellectual
passion, political or religious beliefs, and institutional affiliations
that might lead to a conflict of interest.

Presented at Philippine Society of Otolaryngology- Head
and Neck Surgery, Descriptive Research Contest (2nd Place),
September 19, 2013, Natrapharm, The Patriot Bldg., KM 18
SLEX, Paranaque City. Philipp J Otolaryngol Head Neck Surg 2014; 29 (2): 15-18 c Philippine Society of Otolaryngology – Head and Neck Surgery, Inc.

PhiliPPine Journal of otolaryngology-head and neck Surgery Vol. 29 no. 2 July – december 2014

ORIGINAL ARTICLES

16 PhiliPPine Journal of otolaryngology-head and neck Surgery

A B

Thyroid nodules are common and occur in 5-10% of the general
population with increasing age.1 They have a relative frequency of
4-7% by palpation alone and 13-67% by sonography.4 The incidence
of thyroid nodular disease is quite high spontaneously occurring at
a rate of 0.08% per year starting in early life and extending into the
eighth decade. Although thyroid nodules represent a wide spectrum of
disease, most are colloid nodules, adenomas, cysts and focal thyroiditis
with only a few (5%) being carcinoma.2

The most recent ATA guidelines for the evaluation of thyroid
nodules and cancer emphasize the use of thyroid ultrasound to guide
the clinician on which nodule requires biopsy to exclude malignancy.
Microcalcifications are frequently cited with increased risk of thyroid
malignancy specifically papillary thyroid carcinomas.7

Diagnosis of thyroid carcinoma includes a comprehensive history,
physical examination and the aid of diagnostic tests. High-resolution
ultrasonography is commonly used but frequently misperceived
as unhelpful for identifying features that distinguish benign from
malignant nodules. Although individual ultrasonographic findings may
be of limited value, multiple signs of thyroid malignancy that appear in
combination can make a more accurate prediction.

Calcifications on ultrasound may occur in both benign and malignant
diseases.5 According to the literature, microcalcifications are one of the
most specific ultrasound findings suggestive of a thyroid malignancy.3
Thyroid calcifications can be classified as microcalcification, coarse
calcification or peripheral.3

Because most thyroid nodules are benign, calcifications may seem
to appear more in benign nodules, thus being neglected by clinicians.
This study aims to determine the association of calcifications found
in thyroid or neck ultrasonography and of their types with thyroid
carcinoma. This study will also determine the predictive value for
malignancy of calcifications determined by thyroid ultrasonography.

METHODS
Subjects

This is a retrospective study analyzing 126 thyroidectomy patients
selected from a database covering a one-year period between
January to December 2012 at our institution. All patients included
in the study underwent pre-operative thyroid or neck ultrasound in
the same institution. Patients who underwent thyroidectomy where
ultrasonography was done at a different institution were excluded.

All data was retrieved from the Healthcare Database System,
which included official results of the procedures including the final
histopathological report after each operation. Board-certified radiology
and pathology consultants interpreted the ultrasonographic and
histopathologic studies.

Calcifications on Ultrasonography
These studies were stored at the Picture Archiving and

Communication Systems (PACS) system and were reviewed using the
BARCO Coronis Fusion 6 MegaPixel DL (MDCC-6130) system (Barco Pte
Ltd, Singapore). Its technical specifications include the following: TFT
AM Color LCD Dual Domain IPS-Pro, Native 6 MegaPixel 3280 x 2048
display, 654 x 409 mm active screen size and 800 cd/m2 maximum
luminance (500 cd/m2 DICOM calibrated).

Each ultrasound result had already been officially tandem-read by
two radiology consultants (reader A) and then re-read by the co-author,
a senior radiology resident (reader B) to ascertain the presence or
absence of calcifications and to describe the types of calcifications with
the reviewer blinded to the final histopathology.

Calcifications were defined as hyperechoic signals observed in
the periphery or within a thyroid nodule or mass. Calcifications were
further subdivided into (1) probably benign (inspissated colloid
calcifications with typical reverberation artifacts) and (2) probably
malignant. Subtypes of the latter include (2.a) microcalcifications
(round laminar and punctate hyperechoic focus), (2.b) coarse (larger
hyperechoic structures, either spicule or granular) and (2.c) peripheral
(either rim or arc and further described as stippled, curvilinear smooth
and irregular).

Statistical Analysis
A certified statistician at our institution then analyzed the data using

Statistical Package for the Social Sciences SPSSv16.0 (IBM, New York,
USA). Sensitivity, specificity, positive predictive and negative predictive
values were then calculated.

RESULTS
Out of the 126 patients with thyroid mass who underwent

ultrasonography, 17 were male, 109 female, with ages ranging from 10
to 73 years old (median age 45). There were 81 benign and 45 malignant
final diagnoses by histopathology. Table 1 summarizes the findings.

Benign Number of patients

Multiple Colloid Adenomatous Goiter
(MCAG)
Follicular Adenoma
Nodular Hyperplasia
Hashimoto’s Thyroiditis
Tuberculosis
Hurthle Cell Adenoma
Unremarkable
Total

4
11
5
1
1
1

Table 1. Summary of the histopathologic findings

PhiliPPine Journal of otolaryngology-head and neck Surgery Vol. 29 no. 2 July – december 2014

ORIGINAL ARTICLES

PhiliPPine Journal of otolaryngology-head and neck Surgery 17

Of the 126 patients included, 51 studies (40%) were observed to
have calcifications of any description in both histologically benign and
malignant nodules. Out of the 51 studies with calcifications, 30 (59%)
studies were seen in malignancies and 21 (41%) in benign conditions.
(Figure 1)

The studies reviewed by the co-author revealed reader disagreement
in 14 studies or only 11%. They differed in the types of calcification
reported (ex. peripheral, coarse or microcalcification). The co-author
based the description of the type of calcification reported from literature
published by Hoang and his colleagues.3 These discrepant readings are
listed in Table 2 with the final histopathology results.

Malignant Number of patients

Papillary Carcinoma
Papillary Microcarcinoma
Follicular Carcinoma
Hodgkin’s Lymphoma
Plasmacytoma
Total

34
6
3
1
1

Figure 1. Breakdown of malignant and benign cases with and without calcifications

Figure 2. Types of calcifications seen in malignant cases

Majority of the calcifications in malignant cases were seen in those
diagnosed with Papillary Carcinoma (26 out of 30 malignancies, 86%).
The rest were seen in Follicular Carcinoma (2 out of 30 malignancies,
7%) and other cancers-- Hodgkin’s lymphoma and Plasmacytoma (2 out
of 30 malignancies, 7%).

Calcifications secondary to inspissated colloid were described and
all five examinations with this type of calcification were proven benign
(multiple colloid adenomatous goiter). It should be noted that out of
all the calcifications under the umbrella of malignant subtypes, there
were more of the peripheral type of calcification seen in 37% followed
by microcalcifications 33% and lastly the coarse types which accounted
for 30%. (Figure 2)

Reader A Reader B
(Co-author)

Final
Histopathology

Presence or
Absence of

Calcification
Calcification

Calcification

Peripheral
Calcification

Peripheral
Calcifications

Calcifications

Peripheral
calcifications

Calcifications

Peripheral
calcification
Coarse
calcification

Peripheral
calcification
Microcalcification

Coarse
calcifications

Microcalcifications

Coarse and
microcalcifications

Coarse
microcalcifications

Coarse and
microcalcifications

Microcalcifications

Coarse
calcifications
Coarse
calcifications

Coarse
calcifications

Papillary Thyroid
Carcinoma
Multiple Colloid
Adenomatous
Goiter
Papillary Thyroid
Carcinoma
Multiple Colloid
Adenomatous
Goiter
Multiple Colloid
Adenomatous
Goiter
Multiple Colloid
Adenomatous
Goiter
Papillary Thyroid
Carcinoma
Multiple Colloid
Adenomatous
Goiter
Multiple Colloid
Adenomatous
Goiter with Nod-
ular Hyperplasia
Multiple Colloid
Adenomatous
Goiter
Multiple Colloid
Adenomatous
Goiter
Papillary Micro-
carcinoma
Multiple Colloid
Adenomatous
Goiter
Multiple Colloid
Adenomatous
Goiter

Present

Table 2. Reader discrepancy between Reader A and Co-author with final histopathology

The sensitivity of the type of calcification in predicting malignancy
on ultrasonography was calculated to be 58.82%, specificity was
81.33%. On the other hand, predicting thyroid malignancy based on

PhiliPPine Journal of otolaryngology-head and neck Surgery Vol. 29 no. 2 July – december 2014

ORIGINAL ARTICLES

18 PhiliPPine Journal of otolaryngology-head and neck Surgery

REFERENCES
Wang N, Xu Y, Ge C, Guo R, Guo K. Association of sonographically detected calcification 1.
with thyroid carcinoma. Head Neck. 2006 Dec; 28(12):1077-83.
Kakkos SK, Scopa CD, Chalmoukis AK, Karachalios DA, Spiliotis JD, Harkoftakis JG, 2. et al.
Relative risk of cancer in sonographically detected thyroid nodules with calcifications.
J Clin Ultrasound. 2000 Sep; 28(7):347–52.
Hoang JK, Lee WK, Lee M, Johnson D, Farrell S. US Features of thyroid malignancy: 3.
pearls and pitfalls. Radiographics. 2007 May-Jun; 27(3):847-65.
Yunus, M, Ahmed Z. Significance of ultrasound features in predicting solid malignant 4.
thyroid nodules: need for fine needle aspiration. J Pak MedAssoc.2010 Oct; 60(10):848-
53.
Rahman GA, Abdulkadir AY, Braimoh KT. Thyroid calcification: radiographic patterns 5.
and histological significance. AMA. 2008 Nov 18; 37:99-105
Yoon DY, Lee JW, Chang SK, Choi CS, Yun EJ, Seo YL, 6. et al. Peripheral calcification in
thyroid nodules, ultrasonographic features and prediction malignancy. J Ultrasound
Med. 2007 Oct; 26(10):1349-55.
Lu Z, Mu Y, Zhu H, Luo Y, Kong Q, Duo J, 7. et al. Clinical value of using ultrasound to
assess calcification patterns in thyroid nodules. World J Surg. 2011 Mar; 23(3):14-5.
Khoo ML, Asa SL, Witterick IJ, Freeman JL. Thyroid calcification and its association with 8.
thyroid carcinoma. Head Neck. 2002 Jul; 24(7):651–655.
Taki S, Terahata S, Yamashita R, Kinuya K, Nobata K, Kakuda K, 9. et al. Thyroid
calcifications: sonographic patterns and incidence of cancer. Clin Imaging. 2004 Sep-
Oct; 28(5):368–371.

the type of calcification had a positive predictive value of 68.18% and
negative predictive value of 74.39%. (Table 3)

tells us that 81% of patients who do not have thyroid carcinoma will
test negative for the test (calcification on ultrasonography). Therefore
a positive result from this means a high probability of the presence
of the disease. Sixty-eight (68) % of those with calcification detected
on thyroid ultrasonography will actually have a thyroid carcinoma
(whether papillary or follicular). Lastly, the probability of not having
thyroid carcinoma given a negative thyroid ultrasound test is 74%.

This study can guide clinicians in diagnosing thyroid nodules
particularly in pre-operative evaluation and counseling patients
and relatives. Ultrasound can help direct the biopsy toward areas of
calcification with a high probability of disease. The limitation of this
study is small sample size.

In conclusion, there was an association between calcifications found
on ultrasonography and thyroid carcinoma and 86% of the calcifications
were peripheral patterns mostly found in papillary thyroid carcinomas.
Ultrasonography alone is not sufficient in diagnosing thyroid carcinoma
but may increase the suspicion of malignancy depending on the type
of calcification.

Parameter Percentage

Sensitivity
Specificity
PPV
NPV

58.82%
81.33%
68.18%
74.39%

Table 3. Statistical analyses of calcification found on ultrasonography

Chi square test to determine the association of presence or absence
of calcifications with benign and malignant disease was statistically
significant at 21.54 (P < 0.05).

DISCUSSION
Calcifications detected on thyroid ultrasonography may appear

coarse or dense as microcalcifications or peripheral rim-like.6 Among
these, the microcalcification and coarse types are known to be
associated with increased likelihood of malignancy.6 Based on the study
by Hoang et al. in 2007, microcalcifications are found in 29% to 59%
of all primary thyroid carcinomas, most commonly in papillary thyroid
carcinoma. This subtype is one of the most specific features of thyroid
malignancy with a specificity of 85.8%–95% and a positive predictive
value of 41.8%–94.2%.3

In our study, there were more peripheral types of calcification at
33%. Similar studies were published by Yoon et al. in 2007 and Park et al.
in 2011 on peripheral calcification seen on ultrasonography, its pattern
and association with thyroid malignancy.

On histopathology, thyroid calcifications are divided into
psammomatous and dystrophic types. Psammomatous calcifications
consist of laminated round calcium deposits in the epithelium which
are formed in papillary thyroid carcinomas. These are detected
as microcalcifications on ultrasonography. In contrast, dystrophic
calcifications consist of non-laminated amorphous deposits in fibrous
tissue septa. This type of calcification is thought to correspond to coarse
calcifications on ultrasonography, which can occur in both benign and
malignant conditions. Peripheral calcifications on the other hand,
are patterns of dystrophic calcification located around nodules. They
were generally thought to be more frequently associated with benign
conditions but cases of papillary thyroid carcinoma associated with this
type of calcification have been reported.6 The results of the this study
are congruent with these reports.

Based on statistical analysis, the presence of calcification on thyroid
ultrasound will yield a positive result 59% of the time in patients with
thyroid carcinoma. However, it will yield false positive results in 19%
of patients without thyroid carcinoma. On the other hand, the study