Risk Assessment of Salivary Gland Cytological Categories of the Milan System: A Retrospective Cytomorphological and Immunocytochemical Institutional Study
Nesreen H. HAFEZ, Eman S. ABUSINNA
Department of Pathology, National Cancer Institute, Cairo University, CAIRO, EGYPT
Keywords: Salivary glands, Fine needle aspiration cytology, Milan System for Reporting Salivary Gland Cytology, Risk of neoplasm, Risk of malignancy
The Milan System for Reporting Salivary Gland Cytology (MSRSGC) has been recently published to help communication between
cytopathologists and clinicians. The aim was to assess our institutional experience with salivary gland fine needle aspiration cytology (FNAC)
and the potential applicability of the MSRSGC for the estimation of the risk of neoplasm (RON) and risk of malignancy (ROM) for each category.
Material and Method: Salivary gland FNAC procedures performed at NCI, Cairo University in a three-year period from 2016 to 2018 and
had a corresponding histopathological diagnosis were included in the current study. Sensitivity, specificity, positive predictive value (PPV),
negative predictive value (NPV) and accuracy were estimated. Histopathological final diagnosis was the gold standard. Cytological diagnoses
were re-stratified according to MSRSGC with estimation of RON and ROM for each category.
Results: A total of 118 cases were included in the current work. Sensitivity, specificity, PPV, NPV and accuracy were 84.6%, 88.2%, 78.6%,
91.8% and 87%, respectively. Cytological diagnoses were re-classified as non-diagnostic (2.5%), non-neoplastic (14.4%), atypia of undetermined
significance (AUS) (6.8%), benign neoplasm (40.7%), salivary gland neoplasm of uncertain malignant potential (SUMP) (7.6%), suspicious for
malignancy (8.5%), and malignancy (19.5%). The RON and ROM for each category were as follows: non-diagnostic (100%, 33.3%), non-neoplastic
(17.6%, 11.8%), AUS (50%, 37.5%), benign neoplasm (97.9%, 2.1%), SUMP (88.9%, 44.4%), suspicious (90%, 60%), and malignancy (100% for
Conclusion: The Milan System for Reporting Salivary Gland Cytology is a helpful classification system. The calculated ROM for each category of
the studied cases was slightly above the published MSRSGC rates but still supported the recommended management for the patient.
Salivary gland neoplasms represent 4% to 6.5% of all
head and neck lesions. Malignancy rates of 82%, 43% and
25% have been recorded for the minor salivary gland,
submandibular gland and parotid gland, respectively (1).
Appropriate therapy of salivary gland tumors necessitates a
precise preoperative diagnosis. Non-neoplastic lesions can
be handled conservatively with medical therapy and followup,
while neoplastic lesions require surgical intervention
with major surgery for high grade malignancies (2).
The initial diagnostic workup of salivary gland lesions
is based on ultrasound, computed tomography (CT) or
magnetic resonance imaging (MRI) that determines the
exact location of the lesion within the salivary gland and
the imaging features of the nodules. They provide crucial
information that aid in the surgical planning (3). However,
imaging modalities failed to differentiate between benign
and malignant lesions with confidence in most cases (4).
Fine‐needle aspiration cytology (FNAC) has gained a
wide acceptance among clinicians for the preoperative
evaluation of salivary gland lesions over incisional biopsy
which has the risk of fistula formation, tumor implantation
and facial nerve damage in the parotid region (5). FNAC
is a quick, economical and less invasive test that is easily
applied in an outpatient setting (4). It is the favored
diagnostic technique to differentiate non-tumorous lesions
from tumors and to identify the malignant potential of
the tumors with an accuracy ranging from 81% to 98%.
This rate falls to 60-75% when specific tumor subtypes
are considered (6). Unnecessary surgery could be obviated
in about 33% of cases based on preoperative cytological
diagnosis and thus can decrease the overall management
cost of salivary gland tumors (7). The accuracy of salivary
gland FNAC relies on various factors such as the aspiration
technique (whether with image guidance or free handed),
cytological preparation (whether conventional or liquid
based), intra-tumor heterogeneity and experience of the cytopathologists (2). The considerable diversity of salivary
gland tumors with overlapping morphological features as
well as the rarity of these tumors create a major cytological
interpretation challenge in some cases (3). Therefore,
cytological interpretation that is descriptive without a
definitive diagnosis could confuse the clinicians in the
management choices (2).
Until recently, there was no uniform reporting system
for interpretation of salivary gland lesions, which made
it hard for clinicians to understand the reports and led
to management dilemmas (7). To create a standardized
practical reporting system that aids in the communication
between clinicians and cytopathologists, advance patient
care, as well as allow exchange of study data between various
laboratories, the American Society of Cytopathology (ASC)
and the International Academy of Cytology (IAC) have
suggested a classification system: The Milan System for
Reporting Salivary Gland Cytology (MSRSGC) (8). This
system is similar to the cytological reporting systems of
the thyroid, cervix, and the pancreaticobiliary, respiratory
and urinary systems (5). MSRSGC contains six diagnostic
categories that are associated with proposed risk of
malignancy (ROM) and recommendations for clinical
intervention (2). As this system is still novel, further studies
are required to determine its effectiveness and ROM of
each category of the system (2,4).
The aim of the current work was to determine the
cytological variety of salivary gland lesions presented to the
Egyptian National Cancer Institute (NCI) over a period of
3 years, determine the diagnostic accuracy of salivary gland
FNAC for distinguishing benign from malignant lesions,
re-classify the salivary gland cases based on MSRSGC
criteria, and define the risk of neoplasm (RON) and risk of
malignancy (ROM) for each category of MSRSGC in cases
which had histopathological follow-up.
This was a retrospective three-year study (2016-2018).
Review of the registry of the Cytology Unit, Pathology
Department, NCI, Cairo University in this period
revealed 245 cases with cytological diagnoses of salivary
gland lesions. Of these, only 118 cases (48.2%) had
corresponding histopathological diagnosis and these were
the cases included in the current study. Unavailability of
corresponding histopathological diagnosis for any case
may be due to non-surgical management of non-neoplastic
cases and some benign neoplasms or due to escape of some
patients from therapy. Informed consents were initially
obtained from all patients for the cytological and surgical
procedures and for the use of tissues for research purposes following the regulations of the Ethical Committee of the
National Cancer Institute.
Relevant patients’ demographic data including age, sex and
the anatomical location of the lesion were recorded from
patient files. Slides of the cases including cytology smear
and cell block slides were retrieved from the archive of the
Cytology Unit. All cytological aspirations were carried out
using 23-gauge needles with an average of 2 to 3 passes
depending on the size and yield of the lesion. Rapid onsite
evaluation (ROSE) for the adequacy of smears was
carried out at the time of aspiration using May-Grünwald
Geimsa (MGG) stain on one slide. The remaining slides
were immediately fixed in 95% ethyl alcohol. The retrieved
smear slides were stained using modified Papanicolau stain
and MGG, whereas the cell block sections were stained
with H&E. In addition, immunocytochemical slides were
available for some cases that required immunohistochemical
verification to reach a definitive diagnosis at the time of the
initial diagnosis. The slides of each case were reviewed to
confirm the diagnoses and the cytological diagnoses were
re-stratified according to the previously published criteria
of MSRSGC (3,8) by the two authors without knowing
the initial cytological interpretation or the final surgical
For statistical analysis, categories II (non-neoplastic),
III (atypia of undetermined significance, AUS) and IVA
(benign neoplasm) were combined in a negative group
whereas categories IVB (salivary gland neoplasm of
uncertain malignant potential, SUMP), V (suspicious for
malignancy) and VI (malignancy) were combined in a
positive group. This classification is based on the fact that
the categories in each group have almost similar therapeutic
management of their cases with minor discrepancies that
might have little clinical implication.
Upon comparing cytological diagnosis with its
histopathological counterpart, the cytological cases
were additionally sub-classified into true positives, true
negatives, false positives (interpreted inaccurately on
cytology as positive and proved to be benign on excision)
and false negatives (misdiagnosed cytologically as negative
and turned out to be malignancy on histopathology).
Sensitivity, specificity, positive predictive value (PPV),
negative predictive value (NPV) and diagnostic accuracy
of the cytological interpretation were estimated.
Histopathological final diagnosis was considered as the
Furthermore, the corresponding histological follow-up
of cytological cases was further differentiated into non
neoplastic lesions, benign neoplasm and malignant tumors.
The risk of neoplasm (RON) and the risk of malignancy
(ROM) for each of the six categories of the MSRSGC were
This retrospective study included a total of 118 cases that
underwent FNAC of salivary gland lesions during the
study period and had corresponding histopathological
follow-up (specimen or biopsy). Accordingly, the cytohistopathological
association could be assessed in all studied
cases. One hundred two cases (86.4%) were aspirated blindly and 16 cases (13.6%) were aspirated under image
guidance. The age of the studied 118 cases ranged from 6 to
86 years with a mean of 48.2±14.71. Of the studied cases, 66
(55.9%) were male and 52 (44.1%) were female. The male
to female ratio was 1.3:1. The most frequently involved
salivary gland was the parotid gland (109 cases, 92.4%)
followed by the submandibular gland (9 cases, 7.6%). No
cases with minor salivary gland affection were identified
in the current work. Most cases had left salivary gland
involvement (65 cases, 55.1%). Forty seven cases (39.8%)
had right gland lesions. Bilateral salivary gland lesions were
noticed in 6 cases making up 5.1% of the cases.
Re-categorization of the salivary gland cytological
diagnoses according to MSRSGC recommendations was
performed. The distribution of the preoperative cytological
interpretation in each diagnostic category of MSRSGC is
identified in Table I and Table II. Overall, the rate of the
non-diagnostic category (category I) was 2.5% (3/118).
Non-neoplastic category (category II) was reported in 14.4%
of cases (17/118) and chronic sialadenitis represented the
most common cytological diagnosis (9/17). AUS category
(category III) was noted in 6.8% of cases (8/118); most
of these cases had a descriptive cytology report revealing
various degrees of atypical lymphoid or epithelial cells but a
definite diagnosis could not be made. The benign neoplasm
category (category IVA) constituted the maximum number
of cases with 48/118 cases (40.7%) and the most common
diagnosis was pleomorphic adenoma (26/48) followed by
Warthin’s tumor (19/48) (Figure 1A,B-2). Category IVB
(SUMP) accounted for 9/118 cases (7.6%) where it was hard to define the exact subtype of the neoplasm with
the associated list of differential diagnoses. Suspicious of
malignancy (category V) was reported in 10/118 cases
(8.5%), while 23/118 cases (19.5%) were identified under
the malignant category (category VI) (Figure 3;4A,B;5A-C;
6A-C). The most common interpreted malignant tumor
was mucoepidermoid carcinoma (11/23).
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|Figure 1: Warthin’s tumor of the parotid gland. A) Smear featuring monolayered sheets of oncocytic cells in a lymphoid background
(Papanicolaou; x400). B) Cell block of the same case showing papillary structure lined by oncocytic cells with its core filled with lymphoid
cells (H&E; x400).
Click Here to Zoom
|Figure 2: Smear from a case of schwannoma of parotid gland
formed of proliferating benign-looking spindle-shaped tumor cells
embedded in an afibrillary eosinophilic matrix (Papanicolaou;
Click Here to Zoom
|Figure 3: Smear from a case of mucoepidermoid carcinoma
showing sheets of squamous cells with dense scanty cytoplasm
and scattered glandular cells having abundant fine vacuolated
cytoplasm (Papanicolaou; x400).
Click Here to Zoom
|Figure 4: Case of acinic cell carcinoma. A) Smear featuring sheet of acinic cells with round nuclei and abundant granular cytoplasm
(Papanicolaou; x400). B) Positive immunologic reaction of tumor cells to CK7 on cell block section (IHC; x400).
Click Here to Zoom
|Figure 5: Case of plasma cell myeloma of parotid gland.
A) Smear with dispersed plasmacytoid cells with binucleated forms
(Papanicolaou; x400). B) Positive immunocytochemical nuclear
staining of tumor cells with MUM-1 on cell block section (IHC;
x400). C) Positive membranous immunocytochemical reaction of
tumor cells to CD56 on cell block section (IHC; x400).
Click Here to Zoom
|Figure 6: Case of non Hodgkin’s lymphoma of the parotid gland.
A) Smear showing scattered atypical large round cells admixed
with small reactive lymphocytes (Papanicolaou; x400). B) Cell
block section showing tumor cells positively stained for CD20
(IHC; x400). C) Cell block with positive immunocytochemical
staining of reactive small lymphocytes to CD5 with large tumor
cells totally negative (IHC; x400).
Click Here to Zoom
|Table I: The distribution of preoperative cytological interpretation and final histopathological follow-up according to the categories I,
II, II and IVA of MSRSGC.
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|Table II: The distribution of preoperative cytological interpretation and final histopathological follow-up according to the categories
IVB, V and VI of MSRSGC.
After exclusion of non-diagnostic inadequate samples,
concordance and discordance between cytologic and
histopathologic diagnoses were calculated for the detection
of critical cytologically diagnosed cases that required more
serious and urgent therapy. Concordance was detected in 100/115 cases (87%), whereas 15/115 cases (13%) were
discordant with 6 false negative cases and 9 false positive
cases (Table III). The false positive and false negative rates
were 11.8% (95% confidence interval [CI] extended from
6.1%-21.2%) and 15.4% (95% CI extended from 6.9%-
30.1%), respectively. Diagnostic sensitivity was 84.6% (95%
CI extended from 69.9%-93.1%), whereas specificity was
88.2% (95% CI extended from 78.8%-93.9%). Positive and
negative predictive values were 78.6% (95% CI; 63.9%-
88.5%) and 91.8% (95% CI; 82.9%-96.5%), respectively.
Diagnostic accuracy was 87% with 95% CI extended from
79.5% to 92%.
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|Table III: Cyto-histopathological correlation of the 15 discordance cases.
The corresponding histological follow-up of the studied
cytological cases was further differentiated into nonneoplastic
lesions (21/118 cases, 17.8%), benign neoplasm
(57/118 cases, 48.3%) and malignant neoplasm (40/118
cases, 33.9%) (Table I and Table II). The RON and ROM were estimated for each diagnostic category of MSRSGC
(Table IV). The three cases of non-diagnostic interpretation
on cytology proved to be Warthin’s tumor, pleomorphic
adenoma and metastatic papillary thyroid carcinoma on
histopathological follow-up (Table I).
Click Here to Zoom
|Table IV: The risk of neoplasm and risk of malignancy across
categories of MSRSGC.
Non diagnostic category had 100% RON and 33.3% ROM
(Table IV). In the non-neoplastic category, one case was
histopathologically diagnosed as basal cell adenoma
and two were diagnosed as MALT lymphoma and
mucoepidermoid carcinoma (Table I). Therefore, nonneoplastic
category had RON of 17.6% and ROM of 11.8%
(Table IV). For the category of AUS, the RON was 50% and
the ROM was 37.5% (Table IV). Cases of the cytological
AUS category were diagnosed histopathologically as one
benign case of Warthin’s tumor, and three malignant cases
of mucoepidermoid carcinoma, acinic cell carcinoma and
MALT lymphoma (Table I). Among cases in the cytological
benign neoplasm category, one case was diagnosed
histopathologically as non-neoplastic and one case as
malignant tumor (epithelial/myoepithelial carcinoma)
(Table I). Benign neoplasm category (IVA) revealed 97.9%
RON and 2.1% ROM (Table IV). In the SUMP category,
the RON was 88.9% and ROM was 44.4%. On resection, 4
of these SUMP cases were benign, 4 cases were malignant and one case was non-neoplastic (Table II). The category
suspicious for malignancy had RON and ROM of 90% and
60% respectively. The RON and ROM for the malignant
category were 100% each.
In an effort to standardize cytological terms and organize
the therapeutic management of salivary gland lesions, the
MSRSGC was proposed with detection of ROM for each
diagnostic category and suggestions for management
(3,10,11). In order to support the available published data
of the MSRSGC and to report our institutional experience,
we retrospectively assessed the accuracy of salivary gland
FNAC over a three-year period, re-classified the cytological
materials based on the criteria of the MSRSGC, and
calculated RON and ROM for each category of MSRSGC.
In the present work, the diagnostic sensitivity, specificity,
PPV and NPV of salivary gland FNAC were 84.6%, 88.2%, 78.6% and 91.8% respectively. These were in accordance
with a previous work in which authors reported sensitivity,
specificity, PPV and NPV of 84%, 84%, 64% and 94%,
respectively (1). In the literature, overall sensitivity of
salivary gland cytology in most series was between 69.1%
and 98% and specificity of approximately 88% to 100% was
detected (3,4). The overall diagnostic accuracy achieved in
our study was 87% which fell near the lower limit of the
previously published range of 86% to 98% (4).
In the current work, three cases were categorized as nondiagnostic
due to inadequate cellularity. The suggested
MSRSGC management for cases in this category is to repeat
FNA or use clinical and radiological correlation (8). Our
cases were referred to excision without FNAC repetition;
probably due to suspicious clinical or radiological findings
that necessitated surgical intervention. One turned out to
be metastatic malignancy and two were benign tumors.
The rate of the non-diagnostic category (2.5%) in our
work was similar to the rate of less than 10% proposed by
the MSRSGC (8). Our result was in the range of 1.1% to
7.8% that was detected in a prior review study (10). Rossi
et al. (7) reported an allowed range of 10% to 15% for this
category’s incidence. However in some reports, the rate
reached up to 44% (12) or 50 % (9). The cause of these wide
variations in the incidence of the non-diagnostic category
between different studies might be related to the fact that
the adequacy of FNA materials of the salivary gland lesions
had no definite criteria and was widely related to variable
quantitative and qualitative restrictions for a long period of
time. Poor cellularity, non-mucinous cyst contents, needle
positioning outside of the target nodule or improperly
prepared and stained smears can be the reasons of nondiagnostic
reports (2). Lack of clinical and radiological
findings was also identified to be in this category (3).
Recently, sixty cells representative of the target lesion with
clinico-radiological correlation were suggested to be the
key for adequacy based on MSRSGC regulations (2,8). The
possible cause of the lower incidence rate in our work was
related to the application of rapid on site evaluation (ROSE)
of the yield to check the adequacy before discharging the
cases. In this study, the non-diagnostic category had 100%
RON and 33.3% ROM. A ROM of 25% was recommended
by MSRSGC (8). Our ROM was much higher than that
reported in another study (6.7%), but nearly similar to its
RON (95.6%) (1). In a previous comparable study, a much
lower RON of 64.5% and ROM of 16.1% were detected (2).
Maleki et al., 2019 (9) noticed a RON of 34% and ROM
of 10.6%. Some authors reported a ROM of 0% as they
found no malignancy on surgical follow-up of these cases
(3). The probable cause of the elevated ROM in the current study might be the small number of our studied cases. This
could also be attributed to the fact that our institution is
considered a referral center for malignant cases in Egypt.
the non-neoplastic category of the MSRSGC,
14.4% of our studied cases were found to be non-neoplastic
on FNAC. In the literature, this value ranged from 5.1% to
53.4% (1,10). Savant et al. (3) computed a lower incidence
rate of 2% for cases in this category (3). Our calculated
RON and ROM for the non-neoplastic category were
17.6% and 11.8%, respectively. The calculated ROM was
slightly higher than the ROM of 10% proposed by the
MSRSGC (8) and the ROM of 10.2% reported in a review
work (10). Rohilla et al. (13), Rossi et al. (14) and Song
et al. (2) reported relatively higher ROMs of 17.4%, 16%,
14.3%, respectively. A lower ROM of 7.1% was noticed in a
previous study (1). The lowest ROM of 0% was reported by
Savant et al. (3). The clinical management proposed for this
category by MSRSGC was clinical follow up and radiological
correlation (8). Within the non-neoplastic category, the
discordant cases with major clinical discrepancy on surgical
follow-up included a case of MALT lymphoma and a case
of mucoepidermoid carcinoma that were misdiagnosed
cytologically as chronic sialadenitis and retention/benign
cyst, respectively (false negative cases). Chronic sialadenitis
as well as nonspecific sialadenosis are recognized pitfalls
in salivary gland cytology as an associated malignancy
might be not aspirated leading to a false negative diagnosis
or presence of associated reactive cellular atypia leading
to an over-diagnosis with possible recommendation of
unnecessary surgery (1,13,14). A review of the smear of the
first false negative case revealed polymorphous lymphoid
cell population, frequent epithelioid histiocytic cells and
scattered epithelial cells. The features were still favoring
chronic sialadenitis. It is advised to use ancillary techniques
for any lymphoid-rich aspirate to rule lymphoid neoplasm
out and confirm the benign nature of the lesions (10).
Mucoepidermoid carcinoma is the commonest malignant
tumor and one of the most problematic neoplasms in
cytological interpretation (13). Recognition of mucinsecreting,
intermediate and squamous cells in smears
is essential for a precise diagnosis. However, all these
features are not clearly present in most cases. Cyst fluid
aspiration with only mucinous background with scattered
lymphocytes and rare mucus cells may cause this underdiagnosis
(2). On reviewing the smears of our second
false negative cases, there was mucin-like material in the
background with scattered chronic inflammatory cells
and debris. Based on the published recommendations,
the possibility of low grade mucoepidermoid carcinoma
cannot be ruled out in such situation (10).
In the present study, the bulk of the salivary gland lesions
(40.7%) were in the benign neoplasm category. This figure
was similar to that reported in previous studies (1-3). When
the benign neoplastic cytological diagnoses were correlated
with the corresponding final histopathological diagnoses,
the calculated RON and ROM were 97.9% and 2.1%. This
estimated ROM was consistent with the suggested rate of
MSRSGC (less than 5%), which recommended conservative
surgery or clinical follow-up as management for cases
in such category (8). Similarly, Song et al. (2) estimated
100% RON and 2.2% ROM. Higher ROMs were reported
by Viswanathan et al. (1), Rohilla et al. (13) and Rossi et
al. (14) where the estimated ROMs were 5%, 7.3% and
6%, respectively. The lowest ROM of 0.8% was noticed by
Savant et al. (3). The cause of the relatively accurate RONs
and ROMs in our study and other studies was related to the
fact that the cytomorphological features of benign salivary
gland tumors have been well described in the literature
and are highly reproducible and also because of the fact
that benign tumors are relatively common (12). These
high RON and low ROM values could enable the clinicians
to trust the cytological diagnosis and manage these cases
confidently. In the present work, the cause of ROM in the
benign neoplasm category was attributed to the presence
of a case of low grade epithelial myoepithelial carcinoma
on surgical follow-up that was cytologically misinterpreted
as pleomorphic adenoma (false negative case). The
reported ROM in other studies is caused by false negative
interpretation predominantly of carcinoma ex pleomorphic
adenoma (1,2) followed by low grade mucoepidermoid
carcinoma (13,14), adenoid cystic carcinoma (9,14),
epithelial myoepithelial carcinoma (14) and oncocytic
carcinoma (13). Epithelial myoepithelial carcinoma can
pose a diagnostic complexity to the cytopathologist. It shows
a bimodal pattern of epithelial and myoepithelial cells. The
appearance is usually dependent on the dominant cellular
population (14). In our case, myoepithelial cells were the
main cell population with hyaline basement material in
the background giving the appearance of pleomorphic
adenoma. At the same time, cellular atypia was mild.
In the present work, 19.5% of our studied cases were
identified within the malignant category. An incidence
rate of 13.8% was reported by others (2,9). Much lower
incidence rates of 11% and 9.4% were calculated by Savent
et al. (3) and Viswanathan et al.(1), respectively. The
estimated RON and ROM for the malignant category in our
work were 100% for each, which is relatively higher than
the incidence of 90% published by the MSRSGC (8) as well
as the incidence of 91.9% observed by others (10,12) and
the 92.3% (1) indicated previously. A nearly similar ROM of 98.5% was documented by Song et al. (2). In the current
study, there was no false positive case in this category.
The possible cause might be related to the fact that the
cytopathologists at our institution abide by the malignant
morphological characteristic. Any case with uncertain
malignant criteria was interpreted indeterminately with a
descriptive report. Thus, our malignant results had high
validity and reliability.
In spite of the adequacy of cytological smears, a definitive
diagnosis is not possible even in experienced hands in some
cases. It was noted that this indeterminate cytological interpretation
accounted for more than 30% of salivary gland
cytological diagnoses and fell into the MSRSGC categories
of “AUS”, “SUMP” or “suspicious for malignancy” (16).
These categories form a major problem for the clinicians.
In the current work, the AUS category was noted in 6.8% of
our cases and was similar to that reported by others (3). The
MSRSGC has recommended that the “AUS” category be
used wisely and that more effort is needed to decrease this
category to less than 10% (8). Pusztaszeri et al. (17), Song
et al. (2) and Rossi et al. (14) reported 10%, 10.8% and 11%
occurrence rates for the AUS category, respectively. Among
different institutions from the USA, Europe and China, the
reported frequency varies from 0.7% to 17.0% (16). A much
lower incidence of 0.6% was observed in another work (12).
Among our studied cases, the RON was 50% and the ROM
was 37.5% for the AUS category. Our results fell in the
RON range of 41.7% to 100% and the ROM range of 0% to
75.1% that were documented in a previous work done on
five different institutions (16). Our ROM was higher than
the ROM of 20% proposed by MSRSGC (8). A ROM of
100% was demonstrated by Rohilla et al. (13). Like others
(9), we noticed that the ROM of this category was found
to be between the ROMs of the non-neoplastic/benign and
malignant categories, which was in accordance with the
category description. The relatively high ROM rate of this
category in the present study supported the management
suggestion of surgery in the clinical-radiological worrisome
lesions and FNAC repetition in radiological non annoying
cases (3). Careful assessment of the smears and paying
attention to any specific features before reporting “AUS”
could reduce the frequency of this category and probably
lower the RON and ROM (2). In the present study, one
case was reported as “atypical epithelial cells indefinite for
neoplasm” and diagnosed as mucoepidermoid carcinoma
on histopathology (false negative case). The only significant
cytological feature in addition to the atypical epithelial cells
after meticulous re-examination of smears was the presence
of small amount of mucin in the background which was
not mentioned in the initial report. Some authors have suggested that smears with only mucin content should be
included in this category but that one should be suspicious
when atypical cells are present as well (5). Another AUS
case with atypical epithelial cells that was diagnosed as
Warthin’s tumor on excision also had an insignificant
amount of inflammatory cells in smears. Warthin’s
tumor with few or no lymphoid cells can cause diagnostic
difficulties (16). Another case of AUS had atypical epithelial
cells distributed in isolation and in small sheets with scant
finely granulated cytoplasm; features that still made the
precise interpretation of acinic cell carcinoma difficult
(false negative case). Another five AUS cases were found
to be reactive lymphoid hyperplasia in 3 cases, chronic
sialadenitis in one case and MALT lymphoma in one case
(one false negative case) on histopathological follow up,
reflecting the significance of utilizing ancillary techniques
like flow cytometry that helps detect the clonality of
lymphoid cells in any atypical lymphoproliferative disorder
(16) and reduces the rate of AUS by 50% or more (2). In the
current work, the unavailability of material for cell block
preparation or inadequate cell block materials prevented
the use of these techniques.
The category “SUMP” includes smears that are certainly
classified as neoplasm based on their cytomorphologic
features, but a clear differentiation between benign and
malignant cannot be made (5). Surgical resection is used
to identify the invasive nature of neoplasm and verify
malignancy (3). In the present work, SUMP was noted in
7.6% of cases. This was nearly similar to that reported in a
previous work as 8.2% (2). An occurrence rate of 11.9% was
estimated by others (3,9). Wei et al. (10) calculated a much
lower incidence rate of 1.4%. In the current study, the
estimated RON was 88.9% and ROM was 44.4%. Our results
were similar to those reported by others where the reported
RON and ROM were 93.5% and 41.9%, respectively (9). In
another similar study, the SUMP category had 100% RON
and 46.6% ROM (2). Our ROM was greater than the 35%
proposed by MSRSGC (8) but located within the declared
range in literature that extended from 24% to 50% (1,10,13).
The surgery was the only line of treatment for cases in this
Regarding the category of suspicious for malignancy, 8.5%
of our cases were in this category. This was superior to the
incidence of 1.6% and 2.2% mentioned in two previous
multi-institutional studies (10,18). Similarly, Song et al. (2)
noticed an incidence rate of 2.7%. A rate of 3.5% was detected
by other authors (9). The relatively higher incidence
in the present study might be explained by the fact that
any highly atypical or suspicious cells in the smears were
reported with recommendation of excision to avoid discharging the case with a probable serious diagnosis. In the
current study, the calculated RON and ROM were 90% and
60% respectively. The estimated ROM was comparable to
the reported MSRSGC incidence of 60% (8). The published
ROM for this category differed broadly from one institution
to another with a range from 58.6% to 100% (2,10,12). This
mostly reflected different institutional experiences and
cytopathologists’ skills. The recommended management
for this category is surgical intervention (3). Regarding the
over-diagnosed cases in this category (false positive), one
case was cytologically suspicious for lymphoid neoplasm
and reactive lymphoid hyperplasia was documented on
surgical follow-up. Reactive lymphoid hyperplasia creates
a cytological challenge. Aspiration from the germinal
lymphoid center could provide highly cellular smears and
might yield several large lymphoid cells (centroblasts and
dendritic cells) with many mitoses. This picture could raise
the possibility of malignant lymphoma. Flow cytometric
study allows accurate classification in such situations
(5). Two cases had initial cytological interpretation of
suspicious epithelial cells with squamoid morphology,
but histopathologically turned out to Warthin’s tumors.
Although cytological diagnosis of Warthin’s tumor is
straightforward in most cases, oncocytic epithelium might
undergo squamous metaplasia with a dirty background and
cause an over-diagnosis (2). One pleomorphic adenoma
case was over-diagnosed cytologically as having suspicious
epithelial cells. Pleomorphic adenoma can be misdiagnosed
as suspicious for malignancy or even as malignancy due to
the common mixture of cellular and hyaline, mucoid, or
myxoid matrix elements in some malignant tumors (2).
In general, the differences in the calculated ROM
between the current study and others could be influenced
by difference of sample sizes, patient demographics,
microscopic features and heterogeneity of the included
lesions, cytopathologists’ experiences and institutional
practice settings. Incidence of salivary gland tumors among
different geographical areas and races, where different
studies were carried out, could also refer to the recorded
difference in RON and ROM among different works (19).
Overall, we noticed that most of our calculated ROMs were
higher than the MSRSGC recommended rates; especially in
the non-diagnostic, AUS, SUMP and malignant categories.
These highly estimated ROMs might be due to calculation
of ROM only in surgically excised cases.
In conclusion, the diagnostic sensitivity, specificity, PPV,
NPV and accuracy of salivary gland FNAC were 84.6%,
88.2%, 78.6%, 91.8% and 87%, respectively. According to
MSRSGC, the benign neoplasm category had the largest
number of cases followed by the malignant category.
Non-diagnostic cases were the lowest in our research. We
noticed that most of our calculated ROM for each category
was above the recommended MSRSGC rates; especially in
the non-diagnostic, AUS, SUMP and malignant categories.
Among the various statistically negative categories, the
highest ROM was noticed in the AUS category (37.5%);
supporting the management recommendation of surgery in
the clinical-radiological worrisome lesions and repetition
of FNAC in non annoying lesions. The high accuracy
of RON and low ROM in the benign neoplasm category
could allow clinicians to trust the cytological diagnosis and
manage the case confidently. On the other hand, the highest
ROM for positive categories was of the malignant category
followed by the SUMP one; favoring the recommendation
of surgical intervention rather than conservative clinical
The included cases in the current study were of any age
and sex; however, only cases that had final corresponding
histopathological diagnoses were selected for accurate
estimation of RON and ROM and all other statistical
analyses. This selection could be a limitation of the current
work as it could influence the risk ratios.
CONFLICT of INTEREST
The authors declare no conflict of interest.
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