Accuracy of fine-needle aspiration cytology of salivary gland lesions ...

ACCURACY OF FINE-NEEDLE ASPIRATION CYTOLOGY OF
SALIVARY GLAND LESIONS IN THE NETHERLANDS
CANCER INSTITUTE
Rolf J. Postema, MD, 1 * Mari-Louise F. van Velthuysen, MD, PhD, 2
Michiel W. M. van den Brekel, MD, PhD, 1,3 Alfons J. M. Balm, MD, PhD, 1,3
Johannes L. Peterse, MD 2
1 Department of Head & Neck Oncology, The Netherlands Cancer Institute—Antoni van Leeuwenhoek
Hospital, Amsterdam, The Netherlands
2 Department of Pathology, The Netherlands Cancer Institute—Antoni van Leeuwenhoek Hospital,
Amsterdam, The Netherlands. E-mail: m.v.velthuysen@nki.nl
3 Department of Otorhinolaryngology, Academic Medical Center, Amsterdam, The Netherlands
Accepted 5 November 2003
Published online 20 April 2004 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/hed.10393
Abstract: Background. To evaluate the accuracy of fineneedle
aspiration cytology (FNAC) in salivary gland lesions in a
tertiary referral center.
Methods. A cytohistologic correlation study was performed
using an automated pathology database of 1023 patients
diagnosed with a salivary gland lesion.
Results. In 388 cases, both cytology and histology were
available. Using cytologic confirmation of malignancy as the
starting point, the sensitivity, specificity, and accuracy of FNAC in
this study were 88%, 99%, and 96%, respectively. Exact typespecific
concordance of the malignant diagnosis was achieved in
66 (88%) of 75 cases and in 211 (95%) of 223 benign cases. Of
the 19 cases with a cytologic diagnosis ‘‘cyst,’’ four proved to be
Correspondence to: M. L. F. van Velthuysen
*Present address: Department of Otorhinolaryngology, Groningen University
Hospital, P.O. Box 30.001, 9700 RB Groningen, The Netherlands.
This study was presented as a poster at the fall meeting of the
Netherlands Society of ORL and Cervicofacial Surgery in 2001,
Amsterdam, The Netherlands.
B 2004 Wiley Periodicals, Inc.
malignant. A non-neoplastic lesion at cytology proved to be
correctly classified in 53 (68%) of 80 patients.
Conclusions. Our data show that cytology is a reliable and
accurate technique to assess lesions of the salivary glands. The
cytologic diagnosis of ‘‘cysts’’ and ‘‘non-neoplastic lesions’’
should be interpreted with caution. A 2004 Wiley Periodicals,
Inc. Head Neck 26: 418–424, 2004
Keywords: fine-needle aspiration; salivary gland lesions; cytologic
diagnosis
There is widespread acceptance of the importance
of fine-needle aspiration cytology (FNAC) in
the diagnosis of salivary gland lesions. 1–10 Nevertheless,
the relative value of FNAC in distinguishing
among the various types of malignancies
and the assumed minor influence of FNAC on
treatment planning are sometimes used as arguments
against cytology. 11,12 In the literature, the
diagnostic accuracy of FNAC ranges from 84%
13 – 19
to 99%.
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Table 1. All patients (n = 388) included in the study.*
No. patients by cytology
Histologic diagnosis Benign Malignant Non-neoplastic
Too few
cells, uncertain
Total
Benign tumor 220 4 18 2 244
Malignant tumor 2 73 8 3 86
Non-neoplastic 1 54 2 57
Uncertain diagnosis 1 1
Total 223 77 80 8 388
*The eight patients with uncertain cytologic diagnoses were left out of the analysis.
Preoperatively taken core biopsies or frozen
sections for treatment planning carry serious risks
of tumor spill, bleeding, or inflammation and damage
to the facial nerve (branches), whereas complications
of FNAC are almost negligible.
7,19 – 21
Preoperative information about the malignant
nature of a parotid lesion can also be helpful in
assessing and establishing a policy toward the
neck lymph nodes, achieving wide tumor-free
excision margins, preventing treatment delay,
and informing the patient more appropriately on
the treatment plan and on the possible risk of
facial nerve injury. Thus in case of a benign tumor,
surgery can be postponed or the patient can
be followed if the general health or other medical
conditions pose a major surgical risk. Therefore, in
our institute, FNAC is routinely performed in all
salivary gland lesions. In the ongoing process of
quality control of our diagnostic procedures and to
learn from previous faults, we investigated the sensitivity,
specificity, and accuracy of FNAC in salivary
gland lesions of the last decade (1991–2001).
PATIENTS AND METHODS
All 1023 patients diagnosed with salivary gland
lesions in The Netherlands Cancer Institute from
1991 to July 2001 were retrieved from a database
(PALGA: Dutch Automated Pathology Database).
A cytohistologic correlation study was performed.
Five parameters were studied to evaluate FNAC
results: positive predictive value, sensitivity, specificity,
accuracy, and rate of concordance with
histologic typing. In this analysis, the cytologic
diagnosis of a malignant salivary gland tumor or
a metastasis was classified as a positive result,
whereas diagnosis of a benign tumor or a nonneoplastic
lesion was classified as a negative
result. Aspirates with too few cells that were
scored as ‘‘uncertain diagnosis’’ were left out of
the analysis.
Histology
Monomorphic
Adenoma
Table 2. Cytohistologic correlation of 223 benign tumors.
Pleomorphic
adenoma
No. tumors by cytology
Warthin’s
tumor Lipoma Myoepithelioma Oncocytoma Total
Cyst 1 1
Benign lymphoepithelial 1 1
lesion
Monomorphic adenoma 4 2 6
Pleomorphic adenoma 1 145 1 147
Warthin’s tumor 1 57 58
Lipoma 2 2
Myoepithelioma 2 2
Oncocytoma 1 1 2
Leiomyoma 1 1
Oncocytic cystadenoma 1 1
Adenocarcinoma 1 1
Malignant lymphoma 1 1
Total 5 149 63 2 3 1 223
Fine-Needle Aspiration Cytology of Salivary Gland Lesions HEAD & NECK May 2004 419

Table 3. Cytohistologic correlation of 77 cytologically malignant tumors.
No. tumors by cytology
Histology
Acinic cell
carcinoma
Adenoid cystic
carcinoma Adenocarcinoma Carcinosarcoma
Mucoepidermoid
carcinoma
Myoepithelial
carcinoma
Large cell
carcinoma Lymphoma Metastasis Total
Acinic cell
carcinoma
Adenoid cystic
carcinoma
10 1 11
12 12
Adenocarcinoma 2 12 1 15
Carcinosarcoma 1 1 2
Mucoepidermoid
carcinoma
(Myo)epithelial
carcinoma
Undifferentiated
large cell
carcinoma
3 1 4
1 1 1 3
3 3
Lymphoma 6 6
Metastasis 2 15 17
Monomorphic
adenoma
Pleomorphic
adenoma
2 2
1 1
Lipoma 1 1
Total 14 15 13 1 5 2 6 6 15 77
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In general, the pathologist performs FNA of
palpable salivary gland lesions. FNA material
was routinely processed in smears, air dried, and
stained with Giemsa stain. A Quick Diff stain
(Dade-Behring, Düdingen, Switzerland) was performed
in cases for immediate diagnosis or, if
repeated FNA was considered, in case of doubtful
adequacy of puncture material.
RESULTS
FNAC was performed for 360 cases but not
followed by surgery in our hospital; in another
275 cases, only histologic slides were available.
This last group consisted of patients who underwent
surgery elsewhere and who were only referred
for radiotherapy in our institute. In the
remaining 388 cases, both cytology and histology
of the same salivary gland lesions were available.
In the fine-needle aspirate of eight of these
patients, too few cells were found, leading to uncertain
diagnoses (Table 1). As a consequence, the
study population consisted of 380 patients, of
whom 242 proved by histology to have a benign
tumor, 55 a non-neoplastic lesion, and 83 a malignancy
(Table 1).
The most common cytologic benign diagnosis
was adenoma (pleomorphic/monomorphic)
(154 cases), followed by Warthin’s tumor (63 cases).
Two hundred twenty of 223 cytologically benign
cases were confirmed to be benign at histology.
Two patients had a malignant tumor. Both were
cytologically diagnosed as Warthin’s tumors: one
proved to be a metastasis and the other a non-
Hodgkin’s lymphoma (NHL). One patient had a
salivary gland cyst. Exact type-specific correlation
of the diagnosis was achieved in 211 out of 223
cases (95%).
One hundred fifty-two (99%) of 154 cytologically
diagnosed adenomas (pleomorphic and
monomorphic) were correctly classified, as proven
by histology. Neither of the two misclassified
lesions was a malignant tumor: one proved to be a
Warthin’s tumor and one a leiomyoma.
Fifty-seven (90%) of 63 cytologically diagnosed
Warthin’s tumors were correctly assessed. Of the
other six cases, two involved a malignant tumor
(mentioned above); one a cyst and one a benign
lymphoepithelial lesion. The other two had benign
neoplastic lesions: one oncocytoma and one oncocytic
cystadenoma.
The cytologic diagnoses in the cases with lipomas
and oncocytomas were correct. Two of
three cases cytologically diagnosed as myoepitheliomas
matched with histology, and the other had a
pleomorphic adenoma and was therefore correctly
classified as a benign tumor. The cytohistologic
correlations of 223 cytologic benign tumors are
summarized in Table 2.
A cytologic diagnosis of a malignancy was
confirmed by histology in 73 of 77 cases. Four
had a benign tumor, resulting in a positive predictive
value of 95%. The most common cytologic
diagnoses were adenoid cystic carcinoma
(15 cases), metastatic carcinoma (15 cases), acinic
cell carcinoma (14 cases), and adenocarcinoma not
Histology
Table 4. Cytohistologic correlation of 80 cytologically non-neoplastic lesions.
Inflammation
No. lesions by cytology
No tumor
cells
Cyst
Reactive
lymphoid
Total
Normal tissue 7 7
Inflammation 17 14 1 32
Cyst 3 11 1 15
Monomorphic adenoma 1 1
Pleomorphic adenoma 4 4
Warthin’s tumor 1 3 3 7
Benign lymphoepithelial
1 1
lesion
Lipoma 4 4
Hemangioma 1 1
Acinic cell tumor 2 2 4
Mucoepidermoid carcinoma 2 2
Adenocarcinoma 1 1
Metastasis 1 1
Total 19 39 19 3 80
Fine-Needle Aspiration Cytology of Salivary Gland Lesions HEAD & NECK May 2004 421

Table 5. Sensitivity, specificity, and accuracy of salivary gland cytology as reported by
several authors.
First author No. of cases Sensitivity Specificity Accuracy
Positive
predictive value
Orell 8 325 85.5 99.5 98.5
Stewart 14 341 92 100 98
Al-Khafaji 18 154 82 86 84
Schröder 19 336 93 99 98.6 93.1
Zbären 20 228 64 95 86 83
Atula 21 218 55 92
van Heerde 22 294 89 96 93 95
Zurrida 23 246 87 61.1
Cajulis 24 151 91 96
Mean 229 81 95 91 86
This study 380 88 99 96 95
otherwise specified (13 cases). Three of the four
false-positive cases were from the group of 15 cytologically
diagnosed adenoid cystic carcinomas.
They proved to be a monomorphic or pleomorphic
adenoma at histology. In the fourth case, FNAC
from the salivary gland was consistent with an
acinic cell carcinoma, whereas histology revealed
a lipoma between the superficial and deep lobe of
the parotid gland. Table 3 shows the correlations
between 77 cytologically malignant tumors and
the respective histologies.
Exact type-specific concordance of the malignant
diagnosis was achieved in 63 (81%) of 77
cases. Ten of 14 acinic cell tumors diagnosed by
cytology matched histology. The other four cases
were two adenocarcinomas, one epithelial–myoepithelial
carcinoma, and one lipoma.
Twelve of 15 cytologic adenoid cystic carcinomas
were correctly classified, whereas the three
remaining cases had an adenoma at histology
(see above). Twelve of 13 cases with an adenocarcinoma
at cytology matched histology, whereas
one had a carcinosarcoma. Three of five cytologically
diagnosed mucoepidermoid carcinomas
matched histology. The other two cases concerned
an acinic cell carcinoma and an (myo)epithelial
carcinoma. All six cases cytologically diagnosed as
malignant lymphomas and 15 cases cytologically
diagnosed as metastasis matched. For the diagnosis
of metastasis, the clinical context was,
however, indispensable.
Histology matched the FNA diagnosis in 53
(68%) of 80 cytologically diagnosed non-neoplastic
lesions. In 18 of these 80 cases, a benign tumor was
diagnosed; in eight cases, a malignancy was diagnosed.
Of the 19 cases with a cyst at cytology, this
diagnosis was confirmed histologically in 11 cases.
In the other eight cases, three patients had a
Warthin’s tumor, two an acinic cell carcinoma, two
a mucoepidermoid carcinoma, and one an inflammation
of the gland. Table 4 shows the cytohistologic
correlations of 80 non-neoplastic lesions.
The cytologic diagnosis ‘‘no evidence of tumor
cells’’ was confirmed histologically in 24 of 39 cases:
inflammation (14 cases), a cyst (three cases), or
no lesion at all (seven cases). Twelve of these
39 cases had a benign tumor: a lipoma (four cases),
a pleomorphic adenoma (four cases), a Warthin’s
tumor (three cases), or a hemangioma (one case).
Three of these 39 cases turned out to be malignant:
two acinic cell carcinomas and one adenocarcinoma.
Seventeen (89%) of 19 cytologically diagnosed
cases with inflammation were histologically
confirmed. The other two cases had a Warthin’s
tumor or a metastatic carcinoma. Of the three
cases with aspiration of reactive lymphoid tissue,
histology showed a cyst, a monomorphic adenoma,
and a benign lymphoepithelial lesion, respectively.
For the calculations of overall quality assurance
measures, the cytologic confirmation of a
malignancy is used as a starting point, which leads
to the following values: sensitivity, 88%; specificity,
99%; positive predicting value, 95%; negative
predicting value, 97%; and accuracy, 96%.
DISCUSSION
FNAC may be performed for salivary gland lesions
to guide operation planning and to provide patient
information. To evaluate the reliability of FNAC
and to examine the sources of false-positive and
false-negative results, we analyzed the results of
422 Fine-Needle Aspiration Cytology of Salivary Gland Lesions
HEAD & NECK May 2004

10-year salivary gland FNAC at our institute,
comparingFNACdiagnosiswithhistologicfindings
in 388 cases.
The overall accuracy of FNAC in this study was
96%, which is comparable to our previous results 22
and to the results described by others 23,24 (see
Table 5). We believe that these good results can be
obtained only in a setting with close collaboration
of head and neck surgeons, radiologists, and
cytopathologists. A negative FNA from salivary
gland lesions will always be followed by a second
puncture. In these cases, the multidisciplinary
team makes the decision whether this can be done
under ultrasound guidance or under palpation.
Sensitivity of FNAC in diagnosing malignancy
was 88%, as 73 of the 83 malignant tumors were
diagnosed by this procedure. Eight of the 10 falsenegative
cases had been cytologically diagnosed as
non-neoplastic lesions owing to the absence of
representative material in the FNA smears. Poor
cell yield or aspiration of nonrepresentative material
is a major source of misdiagnosis. This is
further illustrated by the fact that a non-neoplastic
lesion at cytology proved to be correctly classified
in only 53 (66%) of 80 patients. In 27 of these
80 patients, an underlying salivary gland tumor
was missed at the FNA procedure. However,
because in this study only surgically treated patients
were included, there might be a selection
bias because nonsurgically treated patients probably
did not have tumors clinically.
Another cause of misdiagnosis is aspiration of
cystic lesions. Seven of 19 cases diagnosed as cyst
proved to be a Warthin’s tumor, acinic cell tumor,
or mucoepidermoid carcinoma. A negative FNA
diagnosis in case of a clinically obvious lump,
and especially cystic lesions, should always be regarded
with suspicion, as many have reported before.
25,26 In these cases, repeated, preferably
ultrasound-guided FNA, is advocated. 27
This series contained four false-positive cases,
of which three monomorphic or pleomorphic adenomas
had cytologically been mistaken for adenoid
cystic carcinoma. This is a well-known pitfall
due to the similarity of cellular and stromal
components of these lesions, 28,29 which can only
be avoided when the clinical and radiologic
contexts are taken into account. The fourth falsepositive
case was a lipoma. In this case, because of
nonrepresentative sampling, normal acinic cells
were mistaken for an acinic cell tumor.
The specificity of the diagnosis of malignancy
was 99%, as 293 of 297 nonmalignant lesions were
correctly classified as nonmalignant. This high
specificity warrants that, in case of the FNA
diagnosis ‘‘malignancy,’’ a complete work-up is performed.
In our institute, this consists of preoperative
ultrasound-guided FNAC staging of the
neck, an MRI of the primary tumor, a chest x-ray,
and intraoperative frozen section of the subdigastric
lymph nodes. Exact type-specific concordance
of a malignant diagnosis could only be achieved in
66 (88%) of 75 cases. In benign tumors, this percentage
was significantly higher (95%; 211 of 223).
The most frequent cytologic diagnosis in our series,
pleomorphic adenoma (149 cases), was highly
accurate (145 cases histologically confirmed). This
high specificity warrants a wait-and-see policy in
selected elderly patients with a high surgical risk
and a cytologic diagnosis of a benign tumor.
In conclusion, we believe that cytology is a reliable
technique to assess the nature of salivary
gland lesions. As the lack of representative material
is the major source of mistakes, repeated
FNAC and in some cases ultrasound-guided FNAC
are sometimes indicated. Using clinical assessment
together with preoperative cytology, and in
selected cases imaging, can improve patient
counseling and treatment planning.
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