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Table of Content - Volume 20 Issue 2 - November 2021


 

Classification of salivary gland lesions using Milan system for reporting salivary gland cytopathology (MSRSGC) - A Six-year retrospective study in our institution

Priya Patil1, Rujuta Datar2*, Rekha Haravi3, Shreekant Kittur4, Aruna Sharanappa5, Meena Jadhav6, Rashmi Patil7, Geethamala K8

1,2,8Assistant Professor, 3,5,6,7Associate Professor, 4Professor & HOD, Department of Pathology, Department & Institution, Belagavi Institute of Medical Sciences, Belagavi, INDIA.
Email: rujpath15@gmail.com
Abstract Background: Role of fine needle aspiration cytology (FNAC) in salivary gland lesions (SGL) is well established due to its ease, rapid diagnosis and preoperative distinction of benign and malignant lesions. The current cytopathology reporting of SGL poses challenges due to diversity of diagnostic categories and hence there is a general agreement on the need for a defined set of diagnostic categories for salivary gland FNAC to communicate the diagnostic information between
pathologists and clinicians. The Milan system for reporting salivary gland cytopathology (MSRSGC) is one such recently proposed system that hopes to standardize the reporting of salivary gland FNAC. Any newly introduced classification system requires robust testing in terms of validity and reproducibility. Hence, this study aims to classify the SGL based on MSRSGC Methods: A 6-year retrospective study of FNAC of SGL reported from 2014 to 2019 in our academic institution were included in the study. The aspirates were categorized according to the Milan system as follows: Non-diagnostic, non-neoplastic, atypical, benign neoplasm, neoplasm of uncertain malignant potential (NUMP), suspicious for malignancy and positive for malignancy. Results: A total of 147 salivary gland aspirates were evaluated of which 23 cases had histopathological correlation .15 (10.20%) SGL were non- diagnostic, 73 (49.65%) were non-neoplastic lesions, 50 (34.01%) were benign tumors, 1 (0.68%) each in uncertain malignant potential category and suspicious of malignancy and 7 (4.76%) were malignant tumors. Diagnostic sensitivity and specificity of FNAC for salivary gland lesions was 62.5% and 86.6% respectively. The positive predictive value was 71.4% and negative predictive value was 81.2%. The diagnostic accuracy to differentiate between benign and malignant lesions was 78.2%. Conclusion: Our data showed consistent results compared to many similar studies and Milan system for reporting salivary gland lesions serves as a very useful tool for reporting salivary gland lesions
Key words: FNAC, Parotid, Pleomorphic adenoma

INTRODUCTION
Salivary gland lesions are a diverse entity composed of non-neoplastic and neoplastic lesions representing 3–6% of all tumors of the head and neck region.1 FNAC is a very valuable tool in diagnosing SGL. The diagnostic sensitivity ranges from 81% to 100%, specificity from 94% to 100% and the accuracy from 61% to 80%.2 FNAC and reporting of SGL is a challenging area due to heterogeneity and overlapping cytomorphological features of various lesions resulting in inter-observer variations. To have uniformity in cytopathological reporting of SGL worldwide and to improve communication between pathologists and clinicians, American Society of Cytopathology (ASC) and the International Academy of Cytology (IAC) met in September 2015 at the European Congress of Cytology, held in Milan, Italy, to propose Milan System3. 40 participants from 14 countries participated and based upon the evidence in literature and experience of multidisciplinary group of leading experts in the field of salivary gland cytopathology they proposed the Milan System for Reporting Salivary Gland Cytopathology (MSRSG).This system comprises of six diagnostic categories which includes non-diagnostic, non-neoplastic, atypia of undetermined significance(AUS), neoplastic- a) benign or b) uncertain malignant potential, suspicious of malignancy and malignant. Each of diagnostic categories is linked with overall risk of malignancy (ROM) and a brief management plan.4 Following the proposal of MSRSG, various retrospective and prospective studies have been done to evaluate its utility in practice. In one of the studies, Rohilla et al.5 retrospectively classified a series of 631 salivary gland aspirates according to diagnostic categories proposed in the MSRSGC. In their study, 2.2% of 631 aspirates were non- diagnostic, 55.8% non-neoplastic lesions and 40.4% neoplastic lesions. The authors also calculated overall ROM for each of the category-7.4% for the non-neoplastic category, 100% for the atypical category, 7.3% for the benign neoplasm category, 50% for the NUMP category, and 96% for the positive-for-malignancy category. The study thus highlights the clinical significance of implementing the MSRSGC. Inspired by many such comparable studies, we took up this study of utilising Milan system to categorise SGLs retrospectively on reported cases to understand its feasibility and significance so that we can incorporate this system in routine reporting of SGL in future.

MATERIALS AND METHOD

This is a 6-year retrospective study done on all cases of salivary gland swelling (SGS) which underwent FNAC in the department of pathology between January first 2014 to December thirty-first 2019. Institutional ethical clearance for the study was obtained(IEC-102/2020-21). Demographic data, detailed clinical history of patients and FNA slides were retrieved from the department archives. Oral informed consent was obtained from each patient before routine FNA of salivary gland lesions. Major and minor salivary gland swellings, including intraoral lesions were aspirated via a direct percutaneous or trans-oral route using a 10ml disposable syringe and 22- or 23-gauge needle under aseptic precaution without local anaesthesia. Repeat aspiration was done if the aspirate was insufficient. The character of the material aspirated was noted. Routine smears were prepared, Giemsa staining was done on the air‐dried smears while those fixed in 95% alcohol were stained by Papanicolaou’s method and hematoxylin and eosin stain in few cases. The retrieved slides were reviewed and categorised into one of the six categories of Milan system3- Non-diagnostic, non-neoplastic, atypia of undetermined significance, neoplastic- a) benign or b) uncertain malignant potential, suspicious of malignancy and malignant. The corresponding histopathological diagnosis of surgical specimens was correlated with the preoperative FNA diagnosis of salivary gland lesions wherever available. The results and statistical data were represented in the form of summation and tabular format.

 

RESULTS

A total of 147 patients visited for FNAC of SGL at our FNAC clinic over a period of six years. Of 147 patients, 82(55.78%) were male and 65 (44.21%) were female. Overall, the highest incidence was found in 41-50 years age group (26.71%) and also the highest incidence in male and female patients was found in same age group comprising 23/81 (28.39%) and 16/65 (24.61%) respectively as shown in Table 1. Male: female ratio was 1.2:1. Parotid gland was the most common salivary gland to be involved (N = 96; 65.75%) followed by submandibular gland (N = 45; 30.82%) and minor salivary gland (N = 06; 04.08%). The distribution of SGL among various categories of MSRSGC is as shown in Table 2. Majority of the SGL in our study were in category II, i.e. non-neoplastic lesions (N = 73; 49.65%) followed by category IVa, i. e., benign neoplasm (N=50; 34.01%). 15(10.20%) SGL were labelled under category I(Non-diagnostic), 7(4. 76%) in category VI (malignancy) and 1 (0.68%) each in category IVb and V respectively. None of the cases in our study were categorised as atypia of undetermined significance (Category III) Histopathological correlation was available in 23 cases (Table 3). 18/23 cases were concordant and 5 cases were discordant. Of 15 SGL of Category I, four had only haemorrhagic material even on repeat aspirates and none of the patients came back for follow up. Remaining 11 SGL of category I had only benign salivary acini on cytology. One of the cases of category I was a 47-year-old male who presented with left submandibular swelling, showed few salivary acini with benign features on cytology and underwent biopsy which was reported as metastatic squamous cell carcinoma. The patient also had tongue lesion which was reported as squamous cell carcinoma.

The MSRSGC Category II consisted of chronic sialadenitis (30.13%) as the most common lesion followed by sialadenosis (19.17%). 7 SGL in category II were lymphoepithelial cysts associated with HIV infection. There was one case of 22 -year male who presented with right parotid enlargement. FNA smears showed non caseating granulomas in the background of lymphocytes and clusters of benign salivary acini(Figure 1) and hence a differential diagnosis of granulomatous sialadenitis and intra-parotid granulomatous lymphadenitis was considered. The patient was lost for follow up. Histopathology follow-up was available in one SGL of Category II which was reported as bilateral chronic sialadenitis on FNA. On histopathology, it was reported as benign lymphoepithelial cyst of right parotid and granulomatous parotitis of left parotid. In category IVa, among benign tumors pleomorphic adenoma was most common (90%). There were 3 SGL reported as benign spindle tumor. Histopathological correlation was available in 2 cases with diagnosis of chronic sialadenitis in 1 case and the other was reported as chronic inflammatory lesion with foreign body giant cell reaction. 14/45 SGL reported as PA had histopathological correlation. 12 were concordant and 2 were discordant (1 case was reported as low grade mucoepidermoid carcinoma and other as carcinoma-ex pleomorphic adenoma(Figure 2) on histopathology). There was 1 case of 37 year male with left parotid swelling. On FNA smears, there was moderate cellularity with presence of clusters, sheets and singly scattered spindle, ovoid and plasmacytoid cells with scanty chondromyxoid background. Also, there were few squamoid cells (? metaplastic cells), vacuolated cells and cyst macrophages. Hence, a differential diagnosis of pleomorphic adenoma with cystic change and low grade mucoepidermoid carcinoma was considered and placed in category IVb. On histopathology, it was reported as low grade mucoepidermoid carcinoma. 1 case in category V was of parotid swelling in a 45-year male with cytology showing few squamoid cells with mild nuclear pleomorphism, occasional mucoid cells in the background of neutrophils and histiocytes. Possibility of reactive changes following acute inflammation couldn’t be ruled out hence was reported as suspicious of malignancy and biopsy was advised but the patient didn’t turn up for biopsy.

Of 7 malignant tumors, mucopeidemoid carcinoma(MEC) was most common (N=3, 42.85%). Of 3 cases of MEC, 2 had subsequent excision and histopathological diagnosis was concordant with low grade MEC. There was 1 SGL reported as Acinic Cell Carcinoma(ACC-Figure 3 ) and the histopathological diagnosis was concordant with ACC(Figure 4). 1 SGL among malignant category VI was reported as Adenoid cystic carcinoma(Figure 5) and another SGL as high grade salivary gland carcinoma but excision biopsy was not available in both of them. 1 SGL was from soft palate and was reported as high-grade carcinoma on cytology and the biopsy from the lesion was reported as infiltrating malignant tumor with differential of high grade mucoepidermoid carcinoma and adenosquamous carcinoma A statistical analysis was performed for the 23 cases in which histopathological correlation was available. Diagnostic sensitivity and specificity of FNAC for salivary gland lesions was 62.5% and 86.6% respectively. The positive predictive value was 71.4% and negative predictive value was 81.2%. The diagnostic accuracy to differentiate between benign and malignant lesions was 78.2%.


 

Table 1: Age and sex distribution of patients with SGL

Age group (years)

Number of cases

Male

Female

<10

09

03

06

11-20

19

11

08

21-30

17

12

05

31-40

22

12

10

41-50 39

39

16

16

51-60

21

10

11

>60

20

11

09

Total

147

82(55.78%)

65(44.52%)

 

Table 2: Categorization of SGL according to Milan system
SlNo. Cytological diagnosis of
salivary gland lesions Category of MSRSGC Number of cases (%)
1.
i) Scant cellularity with only haemorrhage
ii) Benign salivary aspirate Non-diagnostic (Category I)
04(2.73%)

11(13.09%) 15(10.20%)
2.
i) Acute sialadenitis
ii) Chronic sialadenitis
iii)Acute on chronic sialadenitis
iv) Sialadenosis

v) Lymphoepithelial lesion
vi) Benign cystic lesion
vii) Granulomatous sialadenitis/?Intraparotid granulomatous lymphadenitis
Non-neoplastic (Category II)
06(8.21%)
22(30.13%)
13(17.80%)

14(19.17%)
07(9.58%)
10(13.69%)
01(1.36%) 73(49.65%)

3. Atypia of undetermined significance(AUS)(Category III) 0
4.

i)Pleomorphic adenoma (PA)
ii)Benign spindle cell lesion
iii)Benign salivary gland neoplasm
Neoplastic- Benign (Category IVA)
45(90%)
03(6%)

02(4%)
50(34.01%)

5. Differential diagnosis of PA/?MEC Salivary gland neoplasm of uncertain malignant potential (SUMP) (Category IVB)

1(0.68%)
6. Suspicious for malignancy(Category V)
1(0.68%)
7.
i) Mucoepidermoid carcinoma(MEC)
ii) Adenoid cystic carcinoma(AdCC)
iii) Acinic cell carcinoma(AcCC)
iv) High grade salivary gland carcinoma Malignant(category VI)
03
01
01
02 7(4.76%)


Table 3: Cyto-histopathological correlation available in 23 cases

Sl. No

Category of MSRSGC

Number of cases

Cytology diagnosis

Histopathology diagnosis

Concordance

Discordance

1.

I

1

Benign salivary aspirate

Metastatic squamous cell carcinoma

 

Discordant

2.

II

1

Chronic sialadenitis

-Bilateral parotid swelling

Right parotid-Benign lymphoepithelial cyst

Left parotid-Granulomatous parotitis

Concordant with benign

diagnosis

 

3.

III

-

 

 

 

 

4.

IVa

14

 

 

 

 

 

 

2

PA

 

 

 

 

 

 

Benign spindle cell tumor

 

 

 

 

 

 

 

 

1. Chronic sialadenitis

2. Chronic inflammatory lesion with foreign body giant cell reaction.

 

12 cases concordant with PA

 

 

 

 

 

2 discordant

[MEC(01)

Carcinoma-expleomorphic adenoma(01)]

 

Discordant

5.

IVb

1

Tumor of uncertain malignant potential

(?PA

?MEC)

MEC(01)

Concordant

 

6

VI

2

 

1

1

MEC

 

ACC

High grade carcinoma

MEC(low grade) ACC

Infiltrating malignant tumor-DD-1)MEC 2)SCC

Concordant

Concordant

Concordant

 

 

Figure 1                                                            Figure 2

Figure 3                                                          Figure 4                                            Figure 5

Figure 1: Granulomatous sialadenitis (Big arrow pointing to normal salivary acini and small arrow pointing to non-caseating granuloma); Papanicolaou stain(10X); Figure 2: Capsular infiltration in Carcinoma ex pleomorphic adenoma; H and E stain(40X); Figure 3: Fragments of acinar cells (10X) with abundant granular cytoplasm(Inset;40X) in Acinic cell carcinoma; Giemsa stain; Figure 4: Microcystic pattern of arrangement of malignant acinar cells in Acinic cell carcinoma; H and E(10X); Figure 5: Adenoid cystic carcinoma; Giemsa (40X)

DISCUSSION
FNAC as a first line diagnostic modality for patients presenting with salivary gland lesions is accepted widely among clinicians.6-11 The technique is advantageous as it is rapid, minimally invasive, cost-effective and can be performed in the outpatient setting with minimal recovery time and low risk of Complications.12-15 In our retrospective study on cytology of SGL, highest incidence of SGL was found in 41-50 age group whereas Karuna et al.16 reported highest incidence in 31-40 age group. The male-to- female ratio in our study was 1.2:1 similar to that reported by Rohilla et al.5 which was 1.7:1, whereas in study by Karuna et al.16 it was reported to be 2.2:1. In our study, parotid gland was the most common salivary gland involved (65.75%) followed by submandibular gland (30.82%) and minor salivary gland (4.08%) similar to that observed by Rohilla et al.5 (61.3%, 35.7% and 3% respectively) and Karuna et al.16(59.05%, 31.43% and 9.52% respectively). Non-neoplastic lesions accounted for 49.65% and neoplastic 40% in our study similar to that observed by Rohilla et al.5 55.8%, and 40.4%, respectively. In our study, maximum number of cases were in category II (non-neoplastic), followed by category IV (neoplastic; benign), category I(non-diagnostic) and VI (malignancy) as compared to studies conducted by Karuna et al.16, Sheetal et al.17 and Yogambal et al.18, maximum number of cases in their study were seen in category IV (neoplastic; benign), followed by category II (non-neoplastic), and VI (malignancy).
Category I- In our study, Category I accounted to10.2% of all the cases and presence of only benign salivary acini [11 cases] constituted major cases in this category as compared to similar study done by Rohilla et al.5 where category I cases accounted to 2.2% as they categorised benign salivary aspirates in non-neoplastic category (category II). As per Milan system, institutional Nondiagnostic category should be below 10%. Majority of studies done in India found the share of non-diagnostic cases to be ranging from 2.08% to 6.1%16,19-21. However, few studies have reported a higher proportion of non-diagnostic cases ranging from 18.4%to 23% 22-25. Applying adequacy criteria strictly as per MSRSGC increases the number of non-diagnostic cases but at the same time decreases the number of false-negative cases of malignancy as observed by Chen et al.22 Griffith et al.26 have proposed adequacy criterion of more than four high‐power fields of epithelial cells. In the initial survey of Milan system, specimen adequacy was one of the topic extensively debated and the responses were varied. Some participants felt that such a number has not been established in the literature, few others suggested that a specimen adequacy be defined taking into consideration the clinical situation and radiological findings. Some participants offered minimum of 60 cells similar to criteria adopted for reporting thyroid cytology. As there were varied responses, a common guideline for specimen adequacy was not established in Milan system27. This appears to be one of the drawback of Milan system. Histopathological correlation was available in only 1 case of category I. It was a case of 47-year male patient with left submandibular swelling. On FNAC, only benign salivary acini were noted and subsequent biopsy was reported as metastatic squamous cell carcinoma. Benign salivary gland elements can be observed in many salivary gland cytology smears along with abnormal tissue and also in cases of missing target lesions28. Rohilla et al.5 in their study noted a high rate of benign aspirates for submandibular gland FNA in patients presenting with submandibular region swelling to rule out the possibility of metastasis.
Category II-This category constituted 49.65% of all cases and was the most common category in our study. Most common lesion in this category was chronic sialadenitis (30.13%) as similarly observed by Karuna et al.16(41.17% in their study). Only 1case in this category had histopathological correlation. It was a case of 48-year male with bilateral parotid swelling and cytological diagnosis of chronic sialadenitis was done. On histopathology, it was reported as benign lymphoepithelial cyst of right parotid and granulomatous parotitis of left parotid gland. Another case of granulomatous sialadenitis/?Intraparotid granulomatous lymphadenitis was reported but histopathological correlation was not available. In both the cases the etiology of granuloma was not known and there was no history of pulmonary tuberculosis in these cases. The incidence of granulomatous sialadenitis reported in literature is 38.1% in one study by Malhotra and co-authors29 of which 11.9% of the swellings were due to tuberculosis. In another study by Sharma et al.30, 12.1% of the swellings showed granulomatous inflammation of which 1.9% were due to tuberculosis.
Category III- In our study none of the cases were categorised as AUS(0) as similar to that observed in study by Mishra et al.19whereas Karuna et al.16 reported 2.85 % cases in category III. The category AUS is reserved for cases with limited atypia and a neoplastic process cannot be excluded. AUS category should include <10% of all salivary gland FNAs. Higher quotes probably constitute overuse of this category whilst different interpretations are more appropriate. The recommended management is a repeat FNA and surgery31.
Category IVa- This category of benign neoplasm included 34.01% of all cases and 2nd most common category in our study. Pleomorphic adenoma was the most common benign tumor (90%) as similarly observed by Karuna et al.16 (75.9%). 80% of pleomorphic adenoma occurred in parotid gland, 1.3% in submandibular gland and 0.8% in minor salivary glands in our study. In 14/45 cases of pleomorphic adenoma, histopathological correlation was available.12/14 were concordant with the diagnosis of pleomorphic adenoma and 2 cases were discordant. 1 case was reported as MEC and the other as carcinoma-ex pleomorphic adenoma on histopathology. Low-grade MEC is very often associated with a false-negative diagnosis. This tumor is misdiagnosed as a benign lesion on cytology because smears from this tumor are usually paucicellular with presence of mucus, occasional macrophages and scattered neoplastic mucinous cells, which can be mistaken for histiocytes.28, 32 2 of 3 cases reported as benign spindle cell tumor had subsequent excision biopsy. Both the cases were located in submandibular region. One case was reported as chronic non-specific sialadenitis and the other as chronic inflammatory lesion with foreign body giant cell reaction. Presence of fibroblasts in these chronic inflammatory lesions led to a misleading diagnosis of benign spindle cell tumor on cytology.
Category IVb- 1 case was categorised as tumor of uncertain malignant potential. It was a case of 37-year male with left parotid swelling. Presence of ductal cells and stromal fragments favoured the diagnosis of pleomorphic adenoma, however due to presence of occasional scattered mucus cells the possibility of mucoepidermoid carcinoma couldn’t be ruled out. Hence, was placed in this category. Excision biopsy was reported as low grade mucoepidermoid carcinoma.
MEC is the commonest malignant tumor and poses diagnostic difficulties in cytological interpretation5. Recognition of mucin- secreting, intermediate and squamous cells in smears is essential for a precise diagnosis. Very often this tumor is under diagnosed as all these features are not clearly present in most of the cases and presence of only mucinous background with scattered lymphocytes and rare mucus cells may hinder the diagnosis33.
Category V- 1 case was categorised as suspicious for malignancy. It was a case of 45 year male with left parotid swelling. The smears were cellular with presence of occasional clusters of squamoid cells having nuclear pleomorphism with few nuclei showing prominent nucleoli(?reactive change) in the background of histiocytes and neutrophils. Though there was a strong suspicion for malignancy the possibility of reactive change following acute inflammation couldn’t be ruled out. The patient was lost for follow up.
The risk of malignancy for Category V ranges from 0-100% in various studies but Milan system recommended that it should be around 60%3.
Category VI- Malignant tumors constituted 4.76% of all SGL in our study. The most common malignant tumor was MEC (42.8%) in our study as similarly observed by Karuna et al.16(75.92%). The other malignant tumors in our study were 1 case of adenoid cystic carcinoma, 1 case of acinic cell carcinoma and 2 cases of high grade salivary gland carcinoma. 4/7 had histopathological correlation and all cases (100%) were concordant with cytological diagnosis (Table 3). The sensitivity of FNAC for separating benign lesions from malignant lesions varies from 54% to 98% with high specificity values of 88% to 99%5. In the current study, the sensitivity was 62.5%, and the specificity was 86.6%. Rohilla et al.5reported sensitivity of 79.4% and specificity 98.1%. The positive and negative predictive values were 71.4% and 81.2% respectively. Rohilla et al.5 in their study reported 96.4% positive predictive value and 89.2% negative predictive value. The precision of FNA for salivary gland tumor ranges from 62% to 80%34,35. In a study by Daneshbod et al.35 of 376 cases, 17 cases were wrongly subtyped. In another study by Rajwanshi et al.36, 9 of 45 cases were misclassified. In the study done by Rohilla et al.5, 16 of 85 cases were wrongly subtyped. In the current study, 5 of 23 cases were wrongly subtyped. In the current study, there were 3 false-negative and 2 false-positive cases. Rohilla et al.5 reported 8 false-negative cases and 1 false-positive case. False-negative results arise due to in correct sampling techniques, paucicellular smears, cystic lesions with scant cellularity and under assessment of low-grade tumors due to their bland cytological features. False-positive results arise mainly due to over interpretation of reactive changes associated with inflammatory conditions.37, 38 We faced certain limitations in our study like small sample size and lack of histopathological correlation in many cases. This institutional retrospective study was undertaken to classify the salivary gland lesions based on Milan system to know the practical feasibility, accuracy and reliability and to validate this system. The categories- atypia of undetermined significance (Category III), tumor of uncertain malignant potential (category IV b) and suspicious for malignancy (category V) though serve as a very useful reporting tool, they should be used very judiciously when definitive diagnosis cannot be rendered and also by categorising these lesions into such categories we convey the significance of these terminologies to the physician so that further management can be planned accordingly. Application of Milan system for reporting of salivary gland lesions not only brings in uniformity worldwide but also aids the clinician for appropriate management of salivary gland lesions as seen with reporting of thyroid lesions using Bethesda system.

 

CONCLUSION
Our data showed consistent results compared to many similar studies and Milan system for reporting salivary gland lesions serves as a very useful tool for reporting salivary gland lesions

REFERENCES
1. Artur CV, Felipe N, Luise M, Gabriela S, Lelia BS, Pablo AV, et al. Clinicopathological analysis of salivary gland tumors over a 15‐year period. Bio Reprod 2016;30:1‐2.
2. Stewart CJ, MacKenzie K, McGarry GW, Mowat A. Fine-needle aspiration cytology of the salivary gland: a review of 341 cases. Diagn Cytopathol. 2000;22(3):139-46.
3. American Society of Cytopathology. The Milan System for Reporting Salivary Gland Cytopathology.http://www.cytopathology.org/the-milan-system-for-reporting-salivary-gland-cytopathology/.
4. Esther DR, Zubair B, Marc P, William CF. The Milan system for reporting salivary gland cytopathology (MSRSGC): An ASC‐IAC‐sponsored system for reporting salivary gland fine‐needle aspiration. J Am Soc Cytopathol 2018;7:111‐8.
5. Rohilla M, Singh P, Rajwanshi A, Gupta N, Srinivasan R, Dey P et al. Three-Year Cytohistological Correlation of Salivary Gland FNA Cytology at a Tertiary Center With the Application of the Milan System for Risk Stratification. Cancer cytopathology 2017;125:767-75.
6. Layfield LJ, Glasgow BJ. Diagnosis of salivary gland tumors by fine-needle aspiration cytology: a review of clinical utility and pitfalls. Diagn Cytopathol. 1991;7:267-72.
7. Behzatoglu K, Bahadir B, Kaplan HH, Yucel Z, Durak H, Bozkurt ER. Fine needle aspiration biopsy of the parotid gland. Diagnostic problems and 2 uncommon cases. Acta Cytol. 2004; 48:149-54.
8. Mukunyadzi P. Review of fine-needle aspiration cytology of salivary gland neoplasms, with emphasis on differential diagnosis. Am J Clin Pathol. 2002;118:S100-115.
9. Boccato P, Altavilla G, Blandamura S. Fine needle aspiration biopsy of salivary gland lesions. A reappraisal of pitfalls and problems. Acta Cytol. 1998;42:888-98.
10. Cajulis RS, Gokaslan ST, Yu GH, Frias-Hidvegi D. Fine needle aspiration biopsy of the salivary glands. A five-year experience with emphasis on diagnostic pitfalls. Acta Cytol. 1997;41:1412-20.
11. Cardillo MR. Salivary gland masses: the diagnostic value of fine- needle aspiration cytology. Arch Anat Cytol Pathol. 1990;38:26-32. 

12. Rimm DL, Stastny JF, Rimm EB, Ayer S, Frable WJ. Comparison of the costs of fine-needle aspiration and open surgical biopsy as methods for obtaining a pathologic diagnosis. Cancer. 1997;81:51-56.
13. Mairembam P, Jay A, Beale T, et al. Salivary gland FNA cytology: role as a triage tool and an approach to pitfalls in cytomorphology. Cytopathology. 2016;27:91-96.
14. Kim BY, Hyeon J, Ryu G, et al. Diagnostic accuracy of fine needle aspiration cytology for high-grade salivary gland tumors. Ann Surg Oncol. 2013;20:2380-87.
15. Pastore A, Borin M, Malagutti N, Di Laora A, Beccati D, Delazer AL, et al. Preoperative assessment of salivary gland neoplasms with fine needle aspiration cytology and echography: a retrospective analysis of 357 cases. Int J Immunopathol Pharmacol. 2013;26:965-71. 

16. Karuna V, Gupta P, Rathi M, Grover K, Nigam JS, Verma N. Effectuation to Cognize malignancy risk and accuracy of fine needle aspiration cytology in salivary gland using “Milan System for Reporting Salivary Gland Cytopathology”: A 2 years retrospective study in academic institution. Indian J Pathol Microbiol 2019;62:11-6.
17. Sheetal GG, Mani K, Gautam NG. Study of cytological and histopathological correlation in salivary gland lesions. NJMDR 2016; 5:25‐2. 

18. Yogambal M, Chandramouleeswari K, Marylilly SA. Role of fine needle aspiration cytology in salivary gland pathology and its histopathological correlation: A five year descriptive study in a tertiary care centre. Otolaryngol Online J 2015;5:1‐7.
19. Mishra S, Ray S, Sengupta M, Sengupta A. A cytohistological correlation in salivary gland swelling with special reference to the proposed Milan system. Indian J Pathol Microbiol 2019; 62:379-83.
20. Kala C, Kala S, Khan L. Milan system for reporting salivary gland cytopathology: An experience with the implication for risk of malignancy. J Cytol 2019;36:160-4.
21. Pujani M, Chauhan V, Agarwal C, Raychaudhuri S, Singh K. A critical appraisal of the Milan system for reporting salivary gland cytology (MSRSGC) with histological correlation over a 3‐year period: Indian scenario. Diagn Cytopathol 2019;47:382-8.
22. Chen YA, Wu CY, Yang CS. Application of the Milan system for reporting salivary gland cytopathology: A retrospective study in a tertiary institute. Diagn Cytopathol 2019;47: 1160-7.
23. Thiryayi SA, Low YX, Shelton D, Narine N, Slater D, Rana DN. A retrospective 3-year study of salivary gland FNAC with categorisation using the Milan reporting system. Cytopathology. 2018;29:343-8.
24. Maleki Z, Baloch Z, Lu R, Shaque K, Song SJ, Viswanathan K, et al. Application of the Milan system for reporting submandibular gland cytopathology: An international, multi‐institutional study. Cancer Cytopathol 2019;127:306-15.
25. Vallonthaiel AG, Kaushal S, Jangir H, Rajendran HK. Application of the Milan system for risk strati cation and its comparison with a previous reporting system of parotid gland cytopathology in a tertiary care centre. Acta Cytol 2018;62:352-9.
26. Griffith CC, Pai RK, Schneider F, Duvvuri U, Ferris RL, Johnson JT, et al. Salivary gland tumor ne‐needle aspiration cytology: A proposal for a risk stratification classification. Am J Clin Pathol 2015;143:839‐53.
27. Rossi ED, Faquin WC, Baloch Z, Barkan GA, Foschini MP, Pusztaszeri M, et al. The Milan system for reporting salivary gland cytopathology: Analysis and suggestions from initial survey. Cancer Cytopathol 2017;125:757‐66.
28. Sun J, Yang X. A review of cytology of salivary gland lesions: old, updated and new. N Am J Med Sci. 2015;8:31-37.
29. Malhotra P, Saraf A, Bansal N. Granulomatous pathology in salivary glands: a secondary health care center experience. Trop J Pathol Microbiol.2020;6:118-23.
30. Sharma T, Joshi D, Khurana A, Gupta V, Kapoor N. Bilaterally enlarged parotids and sicca symptoms as a presentation of sarcoidosis-Pivotal role of aspiration cytology in diagnosis. J Cytol. 2015;32:281-283.
31. Marc P, Zubair B, William CF, Esther DR, Tabatabai ZL. Atypia of undetermined significance. In:William CF, Esther DR, editors. The Milan System for Reporting Salivary Gland Cytopathology. 1st ed. American Society of Cytopathology. Springer International Publishing AG; 2018. p. 43‐2.
32. Tyagi R, Dey P. Diagnostic problems of salivary gland tumors. Diagn Cytopathol. 2015;43:495-509.
33. Song SJ, Shafique K, Wong LQ, LiVolsi VA, Montone KT, Baloch Z. The utility of the Milan System as a risk stratification tool for salivary gland fine needle aspiration cytology specimen. Cytopathology. 2019;30:91-8.
34. Orell SR. Diagnostic difficulties in the interpretation of fine needle aspirates of salivary gland lesions: the problem revisited. Cytopathol. 1995;6:285-300.
35. Daneshbod Y, Daneshbod K, Khademi B. Diagnostic difficulties in the interpretation of fine needle aspirate samples in salivary lesions: diagnostic pitfalls revisited. Acta Cytol. 2009;53:53-70.
36. Rajwanshi A, Gupta K, Gupta N, Shukla R, Srinivasan R, Nijhawan R, et al. Fine-needle aspiration cytology of salivary glands: diagnostic pitfalls--revisited. Diagn Cytopathol. 2006;34:580-4.
37. Cohen MB, Ljung BM, Boles R. Salivary gland tumors. Fine- needle aspiration vs frozen-section diagnosis. Arch Otolaryngol Head Neck Surg.1986;112:867-69.
38. Hajdu SI, Melamed MR. Limitations of aspiration cytology in the diagnosis of primary neoplasms. Acta Cytol. 1984;28:337-45.


 












 

 






















 








 




 








 

 









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