JOURNAL OF EVIDENCE BASED MEDICINE AND HEALTHCARE

Table of Contents

2019 Month : November Volume : 6 Issue : 46 Page : 2926-2930

Study of the Cytomorphology of Salivary Gland Lesions Using the Milan System of Reporting in a Tertiary Care Hospital.

G.D. Pukhrambam1, R.S. Laishram2, A. Marina3, B.R. Reang4, H. Persy5, K. Kaur6, L. Leishangthem7, P.R. Pal8

1. Associate Professor, Department of Pathology, Regional Institute of Medical Sciences, Imphal, Manipur.
2. Associate Professor, Department of Pathology, Regional Institute of Medical Sciences, Imphal, Manipur.
3. Student, Department of Pathology, Regional Institute of Medical Sciences, Imphal, Manipur.
4. Student, Department of Pathology, Regional Institute of Medical Sciences, Imphal, Manipur.
5. Student, Department of Pathology, Regional Institute of Medical Sciences, Imphal, Manipur.
6. Student, Department of Pathology, Regional Institute of Medical Sciences, Imphal, Manipur.
7. Student, Department of Pathology, Regional Institute of Medical Sciences, Imphal, Manipur.
8. Student, Department of Pathology, Regional Institute of Medical Sciences, Imphal, Manipur.

Corresponding Author:
Dr. Rajesh Singh Laishram,
Associate Professor,
Department of Pathology,
Regional Institute of Medical Sciences,
Lamphelpat, Imphal- 795004, Manipur.
E-mail: rajeshlaishr@gmail.com
DOI: 10.18410/jebmh/2019/610

ABSTRACT
BACKGROUND
Salivary gland neoplasms account for 2-6.5% of all the neoplasms of the head and neck. Any unexplained salivary gland mass is an indication for Fine Needle Aspiration (FNA). Owing to the wide diversity of tumors arising in the salivary glands, diagnostic challenges occur and there is a lack of a uniform reporting system. The MILAN System for reporting salivary gland cytopathology provides a stage for a standardized international reporting system. This paper aims to study the various cytomorphological lesions of salivary gland and their cytological categorisation based on the MILAN system of reporting.

METHODS
A 4-year cross-sectional study (January 2015 to December 2018) on FNAC of salivary gland lesions was conducted in the Department of Pathology, RIMS, Imphal. All smears were studied based on the classical system and recategorized according to the MILAN Classification into six categories. Histological correlation was carried out for 47 cases and descriptive statistical analysis was done subsequently.

RESULTS
A total of 291 FNA cases were studied and the original diagnoses included 20 different categories. On categorization of the cases based on the MILAN system, maximum cases were non-neoplastic (52.7%) followed by benign neoplasms (28.8%), atypia of undetermined significance (8.6%), malignant (7.5%), non- diagnostic (1.4%), neoplasms of uncertain malignant potential and suspicious for malignancy (0.3% each). Out of 47 histopathology correlated cases, 39 cases (82.97%) were found to be concordant.

CONCLUSIONS
Categorization of the FNA findings according to the MILAN System provided a uniform, tiered system for reporting of salivary gland cytomorphology and a platform for a unified staging and risk stratification resulting in better and effective communication between the cytologist and the physician for appropriate management and overall improved patient care.

KEYWORDS
FNA, MILAN, Salivary Glands

How to cite this article

Pukhrambam GD, Laishram RS, Marina A, et al. Study of the cytomorphology of salivary gland lesions using the Milan system of reporting in a tertiary care hospital. J. Evid. Based Med. Healthc. 2019; 6(46), 2926-2930. DOI: 10.18410/jebmh/2019/610

BACKGROUND

Salivary glands are exocrine glands responsible for production and secretion of saliva and consist of the parotid, submandibular, sublingual and the minor glands that are numerous and located in the submucosa of the entire upper aero digestive tract, from the lips and nasal cavity to the major bronchi. Microscopically, these glands are composed of tubulo-alveolar structures embedded in a mixed supporting stroma and possess acinar and duct system.1 The glands may be of serous, mucinous or sero-mucinous type.2 The parotid is almost exclusively serous, the sub lingual gland is mixed with mucinous predominance and the sub mandibular is mixed with serous predominance.1 A number of disorders affect normal function of these glands. The diseases range from infections, inflammations, obstructions, functional impairment and neoplasms. Salivary gland neoplasms account for 2-6.5% of all the neoplasms of the head and neck.3 The diverse number of salivary gland tumors, tumor heterogeneity, overlapping cytomorphological features and inherent FNA pitfalls create a challenge to cytological interpretation.4 So a descriptive cytological report without a definite diagnosis often creates a confusion in the management options.5 These diagnostic challenges provide a stage where a unified staging and risk stratification is required on the initial cytological diagnostic level to guide the correct surgical management and follow- up.6 The standardization effort started in September 2015 at the European Congress of Cytology, held in Milan, Italy, under the umbrella of the American society of Cytopathology (ASC) and the International academy of Cytology (IAC), subsequent to which a standardized classification system designated The Milan System for Reporting Salivary gland Cytopathology (MSRSGC) was developed.7 This tiered classification scheme provides diagnostic information, risk stratification and specific recommendations for management as well as facilitates communication between the reporting cytopathologist and the clinician.5 The classification scheme comprise of 7 diagnostic categories, including the non-diagnostic (ND) (category I), benign non-neoplastic (NN) (category II), atypia of undetermined significance (AUS) (category III), benign neoplasm (NB) (category IVA), salivary gland neoplasm of uncertain malignant potential (SUMP) (category IVB), suspicious for malignancy (SFM) (category V), and malignant (M) (category VI).8 In order to assess our practice using the new reporting system and evaluate the MSRSGC as a tool for risk assessment, we herein document our institutional experience in a retrospective study by applying MILAN system categorization to cytologic diagnoses of salivary gland FNAs over a 4-year period.

METHODS

The study was carried out in the Department of Pathology, RIMS Hospital, Imphal for a period of four years starting from January 2015 to December 2018. A retrospective 4-year search for salivary gland FNA samples received in our department yielded 291 cases. Ethical clearance from the institutional ethics committee were obtained.

 

Category

Number

%

I. Non- diagnostic

4

1.4

II. Non- Neoplastic

154

52.9

III. Atypia of undetermined significance

25

8.6

IV (a). Benign neoplasm

84

28.9

IV (b). SUMP

1

3

V. Suspicious of malignancy

1

3

VI. Malignant

22

7.6

Total

291

100.0

Table 1. Distribution of All Cases According to the MILAN System of Salivary Gland Cytopathology

 

FNAC

Diagnosis

FNAC MILAN Category

HPE

Diagnosis

Change in

MILAN Category

2 PA

IVa

1 ADC

VI

1 CA EX PA

VI

1 AUS

III

1 CS

II

2 SMF

V

1 MEC

VI

1 BC Adenocarcinoma

VI

1 Sialadenosis

II

1 PA

IVa

1 Chronic Sialadenitis

II

1 Warthin’s Tumor

IVa

1 Warthin’s Tumour

IVa

1 MEC

VI

Table 2. Discordant Cases after Histopathology

PA- Pleomorphic adenoma, AUS- Atypia of undetermined significance, SM- Suspicious of malignancy, ADC- Adenoid cystic carcinoma, Ca Ex PA- Carcinoma ex pleomorphic adenoma, CS- Chronic sialadenitis, MEC- Mucoepidermoid carcinoma, BC Adenocarcinoma- Basal cell adenocarcinoma

 

Cytological Category

No. of Cases

Histopathological Diagnosis

ROM

Benign

Malignant

Non-Diagnostic

0

0

0

0

Non-Neoplastic

9

9

0

0

Atypia of undetermined significance

1

1

0

0

Benign neoplasm

26

23

3

13.4%

Suspicious of malignancy

2

0

2

100%

Malignant

9

0

9

100%

Total

47

33

14

 

Table 3. Cyto-Histological Correlation with the Cytological Categories According to MILAN System

 

Diagnostic Category

ROM

Management

Non-diagnostic

25%

Clinical and radiological correlation/ repeat FNA

Non-neoplastic

10%

Clinical follow-up and radiological correlation

AUS

20%

Repeat FNA or surgery

Neoplasm Benign

<5%

Conservative surgery Or clinical follow- up

Neoplasm SUMP

35%

Conservative surgery

SFM

60%

Surgery

Malignant

90%

Surgery

Table 4. Proposed Management Protocol Based on

Milan Classification20

 

The FNAs were performed using a direct percutaneous or transoral route using a 25-gauge needle with an average of 1 to 4 passes performed depending on the size and complexity of the lesion. Air-dried direct smears were stained with Giemsa stain. Papanicolaou staining following alcohol fixation was used whenever necessary. Relevant clinical details, including the age, sex, site, bilaterality, etc. and findings of local examinations done were noted. The final cytologic diagnoses of all the 291 cases were retrospectively classified according to the MSRSGC into seven different categories.

            The risk of malignancy (ROM) were calculated for each category. Briefly, the ROM is defined as the ratio of FNAs with malignant follow- up for that category. A total of 47 cases were available for histologic correlation, and Hematoxylin and eosin stained sections were subsequently studied. Data entry and analysis were done using SPSS IBM (21) version. The sensitivity, specificity, predictive values and accuracy were measured where the histologic diagnosis was considered as the gold standard for assessment.

Figure 1. Photomicrograph showing pleomorphic adenoma (Giemsa 100X and 400X); fibrillary chondromyxoid background with cells in singles and clusters (A and B); Mucoepidermoid carcinoma (Giemsa 100X and 400X); cohesive clusters and sheets of epithelial cells, intermediate and mucin-secreting cells (C and D)

 

RESULTS

Over a 4-year period (January 2015 – December 2018), 291 salivary gland FNAs were performed. It consists of 144 males (49.5%) and 147 females (50.5%), with the female-to-male ratio of 1.02: 1. Majority of the cases were in the age group of 41-50 years with the cases falling in a wide age range of 4-88 years. The most frequent site of involvement was the parotid gland (4.4%), followed by the submandibular gland and the minor salivary glands. Only one case of sublingual gland involvement was seen in our current study. Chronic sialadenitis was found to be the most common lesion. Most common benign neoplasm was pleomorphic adenoma and mucoepidermoid carcinoma was the most common malignant neoplasm. (Figure 1).

Based on the MSRSGC categorization, 4 cases were assigned to the ND category (1.4%), 154 cases to the NN category (52.9%), 25 cases to the AUS category (8.6%), 84 cases to the NB category (28.9%), 1 case to the SUMP category (3.0%), 1 cases to the SFM category (3.0%), and 22 cases to the M category (7.6%) (Table 1). As shown in Table 2, of the histologically correlated 47 cases (16.15%), 33 cases were benign (70.2%) and 14 were malignant (29.8%). On categorization of these 47 cases, 9 were classified as NN, 1 as AUS, 26 as NB, 2 as SFM and 9 were classified as M. All the 9 cases under category 2 NN cases had a benign outcome. The single case under AUS lesion in category 3 was found to be benign. In the category 4a NB cases, 23 were benign but 3 cases had a malignant outcome. The 2 cases under category 5 SFM turned out to be malignant. Finally, in the category 6 M lesions, all 9 cases were signed out as malignant. The ROMs for the individual categories of NB, SFM and M were 13.4%, 100% and 100% respectively, while it was not applicable for the remaining categories due to the paucity of cases under them available on histologic follow-up.

Out of the 47 histocorrelated cases, 39 cases (82.97%) were found to be concordant. The sensitivity, specificity, positive and negative predictive values were 78.57%, 96.96%, 91.60% and 91.4% respectively. Amongst the 8 discordant cases (Table 3), 3 cases were found to be false negative. Out of the 14 cases diagnosed as pleomorphic adenoma by FNAC, twelve cases were histologically confirmed. However, two cases were later diagnosed as adenoid cystic carcinoma and carcinoma-ex-pleomorphic adenoma. Another false negative case is that of Warthin’s tumor diagnosed as low-grade mucoepidermoid carcinoma on post-operative histopathological examination.

The “indeterminate group” are those categories (AUS, SUMP, SM) that do not definitely characterize the salivary gland lesion as either benign or malignant.6 On histologic follow-up of two cases without a definite cytological diagnosis but with features suspicious of malignancy, both cases turned out to be malignant with one showing features of a mucoepidermoid carcinoma and the other was revealed to be a case of basal cell adenocarcinoma, a rare entity. Another case showing atypical cells with inflammatory cells in a bloody background was later diagnosed as chronic sialadenitis with squamous metaplasia. Two cases that revealed a change in category after histopathological follow-up included a case of sialadenosis (category II) later given out as a case of pleomorphic adenoma (category IVA) and a case of chronic sialadenitis which was signed out as Warthin’s tumour.

DISCUSSION

FNA has gained popularity as well as widespread acceptance as the initial approach in the diagnostic workup of a patient with a new salivary gland lesion. It is a safe, easy to perform, well tolerated, relatively painless technique associated with minimal complications.9 Our study aims to highlight the role of this procedure in our setup to diagnose salivary gland lesions, with an effort to streamline the management of salivary gland lesions using the classification based on the MILAN system for reporting salivary gland cytopathology, which is a relatively new concept. The objective of this classification system is to create a uniform reporting system that will assist in the effective communication of the results between the pathologists and the clinicians as well as for data evaluation and comparison between institutions.8

Prior institutional studies have applied MSRSGC retrospectively to their patient cohorts so as to establish the ROM of each category as well as to document the usefulness of this classification scheme for reporting salivary gland cytology for appropriate clinical management.5,7,8,10

In our study, a total of 291 salivary gland FNA cases were studied and reclassified using the MILAN System with histological correlation available for 47 cases. In the present study, there were 144 males and 147 females with a slight female preponderance. The male: female ratio was 1:1.02; the results are in concordance with the study by Thiryayi S A et al7 and Lopez-Pazos P et al.11 The tumors of salivary glands are spread over a wide age range; in our present study it ranged from 4 to 84 years with the most common affected age group being 40-50 years. Other studies have also shown similar age wise distribution.10,11 Parotid glands was found to be the most commonly affected gland followed by the sub- mandibular and the minor salivary glands. These findings are consistent with those of several other studies.8,12-15 Amongst the benign neoplasms, pleomorphic adenoma was most commonly seen and muco- epidermoid carcinoma was the most frequently encountered malignant neoplasm.3,14,16 Chronic sialadenitis was the most commonly diagnosed lesion of salivary gland. Similar distributions of the tumor were noted in various studies.9,14,16

The present study demonstrated sensitivity of 78.57% and specificity as 96.96%. The positive and negative predictive values were found to be 91.60% and 91.40% respectively. These findings are in coherence with other studies.11,17 In the present study, two problems encountered in cytological diagnosis of salivary gland lesions are discrepancies in cytohistologically correlated cases and the cytologically inconclusive cases (“Indeterminate cases”). Out of the 47 cases available for histological follow-up, 8 cases (17.02%) showed disconcordance (Table 3).

Six cases were diagnosed as possible Warthin’s tumour (WT) on FNAC, five of which were confirmed histologically. One case was given out as low grade mucoepidermoid carcinoma (MEC). The differential diagnoses for WT are wide and the presence of the main components: oncocytes, lymphocytes and a fluid background are not pathognomonic of WT as they are encountered in several other conditions too. The intermediate squamous cells of MEC and the uncommon oncocytic metaplasia of pleomorphic adenoma may be confused with WT.

The other histologically malignant false negative cases included two cases of pleomorphic adenoma (PA) which were later diagnosed as carcinoma ex pleomorphic adenoma and adenoid cystic carcinoma. Adenoid cystic carcinoma and PA are often misdiagnosed due to shared cellular and matrix components.5 In the present study, the diagnostic error may be due to the similarity between the small hyaline stromal globules of adenoid cystic carcinoma with the extracellular myxoid matrix material of PA. Carcinoma ex pleomorphic adenoma and PA also pose diagnostic difficulty on FNA due to overlapping morphologic features and issues of adequate sampling where the malignant component is not captured on FNA. The main reason for these false negative results may be sampling errors, observational errors, underassessment of low-grade tumors due to their bland cytological features.9 In the current study, there were 3 false negative cases which are listed above.

False positive cases arise when there is over interpretation of reactive changes associated with inflammatory conditions.10 One such case in the current study was diagnosed as chronic sialadenitis with squamous metaplasia on histologic follow-up. FNA findings showed atypical cells with inflammatory cells in a bloody background which warranted its categorization under category III AUS.

Cases under SMF category show atypia concerning for malignancy but sample falling short qualitatively/ quantitatively to make a clear diagnosis.6 In the current study, one case under SMF category was revealed to be a mucoepidermoid carcinoma on histology while another case showed features of basal cell adenocarcinoma, a rare entity characterized by solid islands of malignant basaloid cells with peripheral palisading.

Chronic sialadenitis and sialadenosis are potential pitfalls in salivary gland cytopathology because an associated malignancy might not be aspirated leading to false negative diagnosis or presence of associated reactive cellular atypia leading to an over diagnosis with possible recommendation of unnecessary surgery.8,10 A case of chronic sialadenitis was later given out as warthin’s tumor on histological follow up. Such an under diagnosis of this benign neoplasm may be due to inadequate sampling, lack of lesional cells in the aspirate and pauci cellularity with chronic mononuclear inflammatory background. Similar pitfalls of FNA also lead to another discordant case of histologically proven case of pleomorphic adenoma diagnosed as sialadenosis cytologically. Low grade acinic cell carcinoma may mimic sialadenosis especially on aspiration smears.18 Naked nuclei are numerous in sialadenosis but absent in acinic cell carcinoma. There is an absence of other normal salivary gland structures such as duct epithelium and interstitial adipose tissue.19

The cases with available histopathological follow-up were further consolidated according to the proposed MSRSGC along with the risk of malignancy (ROM) calculated against each category (Table 3). The ROM for SFM and M categories were both 100%, while that for the NB category was 13.4%. Calculation of ROM for other categories were not applicable which may be attributed to the limited number of cases available for histological follow-up. Rossi et al highlighted the expected ROMs for the seven categories as 25%, 10%, 20%, <5%, 35%, 60% and 90% respectively20 (Table 4) and the discrepancy noted with the current study is attributable to the low sample size and the number of cases with surgical follow up.

The risk of malignancy represents a guide to the treating physicians on the likelihood of a possible malignant outcome that will further guide them towards appropriate management strategies.7 FNA has proven to be of significant value in the initial evaluation and diagnosis of salivary gland lesions. However, the diagnostically indefinite cases do cause uncertainty to even the most experienced cytopathologists. The creation of the indeterminate categories, encompassing AUS, SUMP and SFM in the MILAN System will provide the clinicians with at least a probabilistic result on which to base therapy. Certain limitations exist in the current study, like its retrospective design and the low sample size. However, it is a fact that the MSRSGC has not yet been adopted in most of the institution including ours and hence majority of the studies have been retrospective studies. This study is a humble attempt to examine the validity of applying MSRSGC in our institution for effective communication to the clinician for appropriate clinical management. Furthermore, analysis of the cases in the indeterminate categories with the final histopathological outcome will help to analyze the key cytomorphological features and pitfalls in the diagnosis in the future.

CONCLUSIONS

Use of the MILAN System of Reporting Salivary Gland Cytopathology can increase the overall effectiveness and communication with clinicians and between institutions thus improving the overall patient care.

ACKNOWLEDGEMENTS

The authors acknowledge technical staffs of the Department of Pathology, RIMS for their help.

REFERENCES

 

  1. McHugh JB. Major and minor salivary glands. In: Goldblum JR, Lumps LW, Mc Kenney JK, et al, eds. Rosai and Ackerman’s surgical pathology. 11th Philadelphia: Elsevier 2018:235-268.
  2. Mills SE. Salivary glands. In: Mills SE, Carter D, Greenson JK, et al, eds. Sternbergs diagnostic surgical pathology. 5th Philadelphia: Lippincott Williams and Wilkins 2010:824-859.
  3. Muthureddy Y, Kathirvel C, Marylilly, et al. Role of fine needle aspiration cytology in salivary gland pathology and its histopathological correlation: a five year descriptive study in a tertiary Car centre. Otolaryngol Online J 2015;5(4):24-30.
  4. Savant D, Jin C, Chau K, et al. Risk stratification of salivary gland cytology utilizing the Milan system of classification. Diagn Cytopathol 2019;47(3):172-180.
  5. Song SJ, Shafique K, Wong LQ, et al. The utility of the Milan System as a risk stratification tool for salivary gland fine needle aspiration cytology specimens. Cytopathol 2018;30(1):91-98.
  6. Rossi ED, Faquin WC, Baloch Z, et al. The Milan System for reporting salivary gland cytopathology: analysis and suggestions of initial survey. Cancer Cytopathol 2017;125(10):757-766.
  7. Thiryayi SA, Low YX, Shelton D, et al. A retrospective 3-year study of salivary gland FNAC with categorisation using the Milan reporting system. Cytopathol 2018;29(4):343-348.
  8. Viswanathan K, Sung S, Scognamiglio T, et al. The role of the Milan System for reporting salivary gland cytopathology: a 5- year institutional experience. Cancer Cytopathol 2018;126(8):541-551.
  9. Yegin Y, Celik M, Olgun B, et al. Diagnostic value of fine needle aspiration biopsy in parotid gland neoplasm. Int J Otorhinolaryngol Head Neck Surg 2016;2(2):56-60.
  10. Rohilla M, Singh P, Rajwanshi A, 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 Cytopathol 2017;125(10):767-775.
  11. Lopez-Pazos P, Peres-Sayans M, Chamoro-Petronacci C, et al. Fine needle aspiration cytology- efficacy in pre- surgical diagnosis of salivary gland tumors. Biomed Res 2018;29(13):2863-2865.
  12. Fernandes H, D'souza CR, Khosla C, et al. Role of FNAC in the preoperative diagnosis of salivary gland lesions. J Clin Diagn Res 2014;8(9):1-3.
  13. Jain R, Gupta R, Kudesia M, et al. Fine needle aspiration cytology in diagnosis of salivary gland lesions: a study with histologic comparison. Cytojournal 2013;10:5.
  14. Kakoty S, Baruah TD, Babu CPG. FNAC and histopathological correlation of salivary gland lesions: an observational study. Int Surg J 2017;4(7):2148-2152.
  15. Rossi ED, Wong LQ, Bizzarro T, et al. The impact of FNAC in the management of salivary gland lesions: institutional experiences leading a risk-based classification scheme. Cancer Cytopathol 2016;124(6):388-396.
  16. Verma S. Fine needle aspiration cytology of salivary gland lesions: a study in a tertiary care hospital of North Bihar. Int J Res Med Sci 2016;4(9):3869-3872.
  17. Piccioni LO, Fabiano B, Gemma M, et al. Fine needle aspiration cytology in the diagnosis of parotid lesions. Acta Otorhinolaryngol Ital 2011;31(1):1-4.
  18. Henry-Stanley MJ, Beneke J, Bordales RH, et al. Fine needle aspiration of normal tissue from enlarged salivary gland: Sialosis or mixed target? Diagn Cytopathol 1995;13(4):300-303.
  19. Jagtap SV, Aramani SS, Mane A, et al. Sialosis: cytomorphological significance in the diagnosis of an uncommon entity. J Cytol 2017;34(1):51?52.
  20. Rossi ED, Baloch Z, Pusztaszeri M, et al. 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(3):111-118.