Keywords
warthin tumor - papillary cystadenoma lymphomatosum - cytology - pathology
Introduction
After pleomorphic adenoma, Warthin tumor (WT) gets its popularity as the second most
common benign neoplasm of the parotid gland. It accounts for 15% to 30% of all parotid
tumors.[1]
[2]
[3]
[4]
[5]
[6]
[7]
[8]
[9]
[10] Among its unique features, especially in the fifth and sixth decades of life, the
tumor tends to affect more the population of male smokers.[1]
[2]
[3]
[4]
[5]
[6]
[7]
[8]
[9]
[10] It typically presents as an asymptomatic, slow-growing mass, usually located in
the tail (inferior) portion of the parotid gland, and multicentric occurrence is observed
more often with WT than with any other salivary-gland tumor.[3] These tumors have a tendency toward multiplicity and bilaterality.[6]
[7]
[8]
[9]
[10]
[11] Recently, many reports[7]
[8]
[9]
[10] have presented patients with clinical features that differ from that of the traditional
tumors in some way, with an increasing incidence among females, higher rates of tumor
multiplicity and bilaterality,[7]
[8]
[9] and superadded differences in the regional, national and racial occurrences.[10] With less than 1% of risk of malignant evolution, WT differs from pleomorphic adenomas.[12] This makes surgery not the first-line treatment when the diagnosis is certain preoperatively
as it is harboring the risk of facial nerve injury.[13]
[14]
Warthin tumor was previously called cystadenoma papilliferum, a term coined by Alfred
Warthin in 1929. It is a peculiar entity with two distinct cellular components in
variable proportions. Its origin is also debatable, with one theory suggesting it
originates from epithelial cell rest in the lymph node, and another stating that it
is an adenoma with lymphocytic infiltration. Subsequent molecular studies[5]
[6] have shown that it is not a true neoplasm. The most accepted hypothesis is that
it originates from salivary-duct inclusions in the lymph nodes.[15]
Salivary-gland lesions have been fairly accurately diagnosed on fine-needle aspiration
cytology (FNAC), with an accuracy ranging from 74% to 97%.[]
[]
[16-18] However, the diagnostic accuracy of FNAC for WT has been a source of concern and
a subject of debate.[19]
[20]
[21]
[22]
Fine-needle aspiration cytology is the most cost-effective and minimally-invasive
way to determine the histological character of a parotid-gland tumor. But it is not
always conclusive, because the material may be insufficient. Furthermore, in the case
of WT, which contains inflammatory cells, FNAC may be responsible for an inflammatory
flare, with pain and an increase in the volume of the lesion.[23]
Fine-needle aspiration (FNA) is a valuable tool in the diagnosis of head and neck
lesions, with a proven high accuracy.[24]
[25]
[26] This is particularly true for salivary-gland neoplasms, because the FNA diagnosis
guides the decision of the clinician regarding the management of the patients. In
most patients, careful interpretation of the cytomorphologic findings renders an accurate
diagnosis, enabling the conservative management of the patients with benign lesions.[25]
Warthin tumor has a cystic appearance, with a double layer of oncocytes surrounding
a lymphoid stroma. There are two main cellular components: the epithelial and lymphoid
components. The typical features on cytology include oncocytic cells in cohesive,
monolayered sheets, background lymphocytes, and amorphous, cystic debris.[25]
[26]
[27]
Despite its well-defined histological appearance, the often variegated cytomorphology
of WT may lead to an erroneous cytopathological interpretation. We conducted the study
to determine the accuracy of FNAC in the diagnosis of WT.
Methods
A retrospective study of patient records was performed between 2014 and 2018 after
a formal review and waiver by the institutional review board (IRB). A total number
of 243 FNACs were performed for parotid lesions. A histopathological correlation was
established in 74 out of these 243 cases to reveal the accuracy of FNAC in the diagnosis
of WT tumor.
Fine-needle aspiration biopsy (FNAB) was performed by a cytopathologist using a 23-gauge
fine needle attached to a 10-ml plastic syringe and employing a Cameco gun (Precision
Dynamics Corporation, Valencia, CA, US). Slides were air-dried for Diff-Quik (MICROPTIC
S.L., Barcelona, Spain) staining, and an on-site, provisional cytopathological diagnosis
was rendered on all slides. Additional smears were prepared and fixed immediately
in 95% ethanol for subsequent Papanicolaou staining. In a few cases, needle rinses
with balanced salt solution were used to make paraffin cell blocks, and 4-mm thin
sections were stained with hematoxylin and eosin. A histopathological correlation
of the result of the FNAB with the surgical specimen was established to confirm the
accuracy of the cytological diagnosis.
Results
A total of 243 FNACs for parotid lesions were performed, and a histopathological correlation
was established in 74 (30.4%) cases. Later, we confirmed that 16 (21.6%) out of these
74 operated patients had cases of WT, 15 (20.3%) of which were confirmed on the initial
cytology, which revealed a true positive concordance between the cytology and the
final histological diagnosis; 55/74 (74%) were true negative results; on the other
hand, 1/74 (1.4%) was a false negative result, and 3/74 (4.1%) were false positive
results ([Table 1]). The sensitivity of the FNAC in the diagnosis of WT was of 93%, while the specificity
was of 94.8%, and the accuracy, 94.6% ([Table 2]).
Table 1
Fine-needle aspiration cytology and histological diagnosis
|
Fine-needle aspiration cytology
|
Histological diagnosis
|
|
|
Warthin positive
|
Warthin negative
|
Total
|
|
Warthin positive
|
15 (true positive)
|
3 (false positive)
|
18
|
|
Warthin negative
|
1 (false negative)
|
55 (true negative)
|
56
|
|
Total
|
16
|
58
|
74
|
Table 2
Results of the fine-needle aspiration cytology
|
Fine-needle aspiration cytology
|
%
|
|
Sensitivity
|
93
|
|
Specificity
|
94.8
|
|
Accuracy
|
94.6
|
Discussion
Of all salivary-gland tumors present in the patients in the sample, 5% to 10% were
WTs.[19] It is an asymptomatic disease, but it may present with pain because of the effects
of the pressure exerted due to the rapid growth or because of the superadded inflammation.[15] The group mostly affected is comprised of male patients at an older age, but nowadays,
due to the rise in the habit of smoking, women are also being affected.[15]
[19] Although the parotid gland is the main site of origin, WT is also found in the submandibular
gland.[15]
[19]
Fine-needle aspiration cytology of the salivary-gland lesions has been shown to reduce
the number of patients undergoing surgery by ∼ 30%.[28]
[29] For this reason, FNAC is a widely-used procedure. Through FNA, a salivary gland
lesion can be classified into one of two categories:[1] inflammatory or non-neoplastic, and[2] neoplastic. This simple triage approach is often appropriate, and may determine
the medical or surgical therapy. However, further diagnostic accuracy is desirable,
and can be achieved with knowledge of the pitfalls and limitations.[30]
There are few case reports[20]
[22]
[30] demonstrating a malignant tumor adjacent to a benign Warthin lesion. Most of these
cases were associated with previous radiotherapy.[31] Obviously, misdiagnosis of a malignant tumor in patients with preoperative benign
cytological examination falsely interpreted as a WT is the error that must be avoided.
The question is whether this error is of practical concern in a large hospital with
experienced cytopathologists. This concern has not been specifically addressed.[32]
In a study by Parwani and Ali,[21] 74% (31) of the patients with a histologically-confirmed WT had the same preoperative
cytological diagnosis. Similar findings were presented by Ballo et al,[19] who analyzed 16 patients; in their study, the cytological accuracy was of 81% (3
cases were submitted to preoperative FNAs, which suggested a malignant tumor).[19] In the study by Flezar and Pogacnik,[33] 37 (79%) out of 47 patients had a correct FNA diagnosis confirmed by histology.[33] Nir et al[32] described an accuracy of the FNAC of 78.7% in 48 out of 61 patients who had diagnoses
of WT, and Lewis et al[34] reported that 21 (65%) out of 32 patients had a preoperative diagnosis of WT tumor.
In the present study, 15 (93.8%) out of 16 cases operated for WT had a preoperative
correlation established by FNAC, while 1 (6.2%) out of these16 cases (6.2%) was FNAC
as pleomorphic preoperatively. As results, we had a sensitivity of 93%, a specificity
of 94.8%, and an accuracy of 94.6%; this was incompatible with the results obtained
by Dong et al:[35] sensitivity of 60.2%, specificity of 0%, and accuracy of 60.2%, while Neelam and
Borah[30] obtained an accuracy of 79%. Based on multiple previous studies,[19]
[21]
[34]
[36] the sensitivity, specificity and diagnostic accuracy of FNAC in diagnosing WT ranges
from 74% to 100%. The two main sources of error include failure to obtain a representative
sample and the variable cytological appearance of WT.[21]
[34]
[37] The former can be minimized by recruiting a cytopathologist to perform the procedure.
This has the added advantage of limiting histological alterations after biopsy, another
major operator-related problem.[37]
In the present study, there were four cases with revision of the results, two by core
biopsy and two by FNAC, which confirmed the diagnosis of WT before proceeding to surgery.
The need for preoperative FNA is a debatable issue. It is considered an acceptable
surgical practice to excise parotid masses without a preoperative FNA. We are of the
opinion that this practice may be outmoded, as a preoperative FNA may obviate the
need for surgery of a WT, which is the second most common benign parotid tumor. In
any case, cytological interpretations should be considered in the context of the history,
physical examination findings, and imaging exams. In any case in which the clinical
judgment is of suspicion of a malignant lesion, surgical excision is mandatory, regardless
of the result of the FNA.[32]
Conclusion
In the present study, the diagnostic accuracy of the FNAC was high, reaching 94%.
In addition, the accuracy increased with the increase in sample size with a multicenter
comprehensive study. Revision of the results assists in the diagnostic accuracy and
makes it possible to avoid unnecessary operations.
Summary
-
Warthin tumor is the second most common benign parotid tumor.
-
In any case, cytological interpretations should be considered in the context of the
history, physical examination findings, and imaging exams.
-
In any case in which the clinical judgment is of suspicion of a malignant lesion,
surgical excision is mandatory, regardless of the result of the FNA.
-
The diagnostic accuracy of the FNAC was high, reaching 94%.
-
In addition, the accuracy increased with the increase in the sample size with a multicenter
comprehensive study.
