| Abstract|| |
Context and Background: Cytological grading of salivary gland lesion, which is a simple, cost-effective, and reproducible method, can be used as a tool for the selection of treatment modality. The proposed Milan classification establishes one guideline for reporting of salivary gland cytology and thus helps in individualized treatment and follow-up. Aims and Objectives: (1) The aims and objectives of this study were to establish the validity and reliability of the Milan classification of cytological grading in salivary gland swelling and (2) to calculate the malignancy risk. Materials and Methods: This prospective study was designed in clinically diagnosed salivary gland swelling at the Department of Pathology of a tertiary care referral hospital. Fine-needle aspiration (FNA) was done, and stained smears were examined under light microscope and cytological findings were noted according to the Milan classification. Tissue for the histopathological study was obtained in 119 cases. The previous cytological findings were compared to subsequent histopathology report. Results: Among 119 FNAs, 2.5% were nondiagnostic and 55.4% were nonneoplastic. While no samples were placed in the atypia of undetermined significance category, benign tumors accounted for 25.2%. About 1.7% was grouped in the salivary gland neoplasm of uncertain malignant potential, 2.5% of cases were categorized as suspicious of malignancy, and 12.6% of cases comprised as malignant tumors. Overall, malignancy risk was observed to be the highest (93.3%) in Category 6 and lowest (3.0%) in nonneoplastic category. Conclusions: The six-tier diagnostic categories of the Milan classification scheme help in segregating patients with salivary gland lesions into the management categories of follow-up, conservative surgery, and radical surgery with/without chemotherapy.
Keywords: Fine-needle aspiration, histopathology, Milan classification, salivary glands
|How to cite this article:|
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
|How to cite this URL:|
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 [serial online] 2019 [cited 2020 Nov 25];62:379-83. Available from: https://www.ijpmonline.org/text.asp?2019/62/3/379/263494
| Introduction|| |
Fine-needle aspiration (FNA) is the preferred initial biopsy method because incisional or core needle biopsy is associated with an increased risk of infection and potential contamination of surgical planes. FNA, in contrast, is a cost-effective technique that poses minimal risk to the patient. Fine-needle aspiration cytology (FNAC) could prevent unnecessary excision of a considerable number of salivary gland swellings which do not require surgery. Some patients have a nonneoplastic lesion (e.g., chronic sialadenitis, lymphoepithelial cysts, and granulomatous diseases); others have a benign neoplasm because they are poor surgical candidates and knowledge of its benignity provides reassurance that surgery can be avoided; and still others have malignancy for which surgical excision is not appropriate (e.g., lymphoproliferative disease and metastasis). Even when surgery is indicated, FNA guides preoperative strategy (e.g., partial or total parotidectomy, facial nerve resection, and neck dissection) providing reassurance to both patient and surgeon.
Current reporting system incorporates a wide diversity of diagnostic categories and also a number of descriptive reports without any definite conclusion on the malignancy risk. The wide heterogeneity of the surgical pathology terminologies along with the fact that many salivary gland tumors share the similar cellular constituents results in diagnostic dilemmas especially in basaloid tumors, oncocytic lesions, and mucous-containing cystic neoplasms. Unified staging and risk stratification are required on the initial cytological diagnostic level to guide the suitable surgical management and follow-up.
The Milan system of classification of the salivary gland lesions was sponsored by the ASC and the IAC. The goal is to produce a practical classification system that will be user-friendly and internationally accepted. The system will be evidence-based and will provide a useful and uniform format for clinicians who treat salivary gland disease.
| Materials and Methods|| |
This prospective study was carried out in the Department of Pathology in collaboration with the Department of Otorhinolaryngology over 1½ years. Institutional Ethical Committee approval was obtained. After taking valid consent from the patient, clinical examination was done. Inclusions criteria were as follows: (1) clinically palpable salivary gland swelling and (2) patients who gave the consent and fully cooperative during the study process.
FNA was performed under the strict aseptic condition of the salivary gland swelling. The procedure was done with the patient either in a supine or sitting position. 23G needles and 10 cc syringes were used. In cystic nodules, the cyst contents were aspirated centrifuged, and the slides were made from the sediment for microscopic examination. Four slides were prepared of passes one and two by a cytopathology technologist for each case. Two slides were air dried and stained with Leishman-Giemsa stain. Two slides were fixed in 95% ethyl alcohol and stained with Papanicolaou stain. Stained slides were examined under a light microscope, findings were recorded, and provisional diagnosis was given. Subsequently, the cases were categorized according to the Milan classification.
The subsequent surgically resected specimen for histopathological examination (HPE) was received in 119 cases. First, a careful gross examination was done. After proper processing of the representative sections, slides were stained with hematoxylin and eosin stain. Histopathological categorization was done according to the WHO classification after examining the slides under a light microscope. Cytological and histological findings were evaluated by two separate pathologists. Results of cytology and histopathology were compared and the malignancy risk was calculated.
| Results|| |
A total of 119 cases of thyroid lesions were included in the present study, of which were 58 males (41.8%) and the rest 61 were female (58.2%). Cytological diagnoses were broadly classified according to the proposed Milan system of salivary gland cytopathology [Table 1].
|Table 1: Distribution of all cases according to the Milan system of salivary gland cytopathology (total case=119)|
Click here to view
No defined adequacy criteria are currently accepted for salivary gland FNA; however, it has been suggested that low cellularity results in higher discrepancy rates. A total of three cases were grouped under this category. This category consisted of smears that had a very sparse cell population and necrotic cell debris in the background. A few cases showed only cystic aspirate, and no cytological diagnoses could be rendered.
This group comprised major number of cases (66 cases). All cases were further classified into sialadenitis, acute on chronic sialadenitis, chronic sialadenitis, lymphoepithelial sialadenitis, granulomatous sialadenitis, and cystic lesions of the salivary gland. The smears from these aspirates did not show any cytological evidence of malignancy, but only acinar or ductal epithelial cells and/or an inflammatory background with only reactive epithelial cells.
Atypia of undetermined significance
No cases were placed under this category.
A total of 30 cases were placed in this category [Figure 1]. Pleomorphic salivary adenoma (PSA) and Warthin's tumor having clear cytologic and definitive criteria were easy to group. Other neoplasms appearing benign (no or minimal to mild cytological atypia) generally had a fibrillary or myxoid stroma and were grouped as either basaloid or oncocytic neoplasms.[Figure 2].
|Figure 1: Cytological and histopathological features of benign salivary lesions|
Click here to view
|Figure 2: Cytological and histopathological features of suspicious of neoplasm|
Click here to view
Those smears which were high in cellularity (>75%), with a moderate amount of atypia was subgrouped into the category of salivary gland neoplasm of uncertain malignant potential (SUMP).
Suspicious for malignancy
Three cases were reported under this category. Cytological findings were qualitatively or quantitative insufficient for definitive diagnosis of any carcinoma or malignant neoplasm of the salivary gland.
Mucoepidermoid carcinoma (MEC) was the mostly accounted malignancy (8 of 15 cases) in our study followed by adenoid cystic carcinoma. Few other rare malignant tumors such as squamous cell carcinoma, acinic cell carcinoma, and few others which cytologically could not be diagnosed except for the term “malignant tumor” were encountered and included in the study.[Figure 3]
|Figure 3: Cytological and histopathological features of malignant lesions|
Click here to view
Cytohistological correlation was done in 119 cases. Sensitivity was calculated at 96.84%, specificity at 80.95%, positive predictive value at 95.83%, and negative predictive value at 85%. Malignancy risk was calculated for each category. Overall malignancy risk was the highest (93.3%) in Category 6 (malignant) and lowest (6.6%) in Category 2 (benign) [Table 1] and [Table 2].
|Table 2: Cytohistological correlation and evaluation of malignancy risk (n=119)|
Click here to view
| Discussion|| |
FNAC has proven to be of significant value as an early step in the diagnosis and management of salivary gland lesions.,, Incorporation of evidence-based algorithms in reporting of salivary gland FNAC can improve communication between cytopathologist and clinicians. According to Griffith et al., salivary gland FNA categorization into commonly encountered morphologic categories provide risk stratification, which translates into a simplified classification scheme of benign, neoplasm of uncertain malignant potential, suspicious, and malignant similar to that currently accepted in other organs such as the thyroid. Several publications have documented the sensitivity, specificity, and diagnostic accuracy for salivary gland FNA (87%–100%), which might be due to the heterogeneous sampling and morphologic similarity between the various tumor types and observer experience.,,,,,
In the present study, among 119 FNAs, 2.5% were nondiagnostic, 55.4% were nonneoplastic, 25.2% were benign, 1.7% were SUMP, 2.5% were “suspicious” for malignant neoplasm, and 12.6% were malignant.
Histological follow-up of the three cases diagnosed with unsatisfactory. One case turned out malignant (salivary duct carcinoma) resulting in malignancy risk of 33.3%. This higher rate of malignancy risk could be attributed to the small sample size. This was due to cystic degeneration of the tumor which resulted in aspiration of only cyst fluid and a background of necrotic debris. The other two nondiagnostic cases were reported as a chronic sialadenitis on HPE. This discrepancy may be contributed to the sampling error and can be prevented by multiple aspirates.
In the nonneoplastic category, of 66 cases two cases were diagnosed with malignant on histopathology (malignancy risk 3%). One case diagnosed with cystic lesion was later found to be low-grade MEC on HPE. This failure on the part of cytological diagnosis was mainly due to the absence of squamous differentiation and hypocellularity in the cystic aspirate. A high degree of caution should be exercised both during aspiration and reporting a cystic lesion of the salivary gland. Attempt should be made to take multiple passes both from the cystic as well as the solid area if possible. One case of intraparenchymal lymphoma on histopathology was reported as lymphoepithelial sialadenitis on cytology. The differential lymphoepithelial sialadenitis with lymphoma on cytology has been documented in the literatures.
Of the 30 cases were placed in the benign category, on histopathology, one case reported as PSA on FNAC turned out to be adenoid cystic carcinoma and one case listed as warthin's tumor turned out to be MEC on histopathology. Overall, the nonneoplastic and benign neoplasms (80.6%) predominated over the malignant neoplasms (12.6%). Similar findings were recorded in studies conducted by Boccato et al. and Jayaram and Dashini.
Malignancy risk in suspicious for malignancy z and malignant category were 67% and 93.3%, respectively. The pitfall of cytological diagnosis in this category was misinterpretation of adenoid cystic Ca as PSA and one case of PSA as MEC on cytology. Morphological similarity between PSA and adenoid cystic carcinoma such as the presence of hyaline globules and myxoid stroma as described by Klijanienko and Vielh leads to the wrong interpretation. More caution and emphasis on the cellular details should eradicate this problem.
Malignancy risk of our study was compared to other studies.,, The findings were on par expect the nondiagnostic category. Categorizing the FNAC findings into the Milan classification provided sensitivity at 96.84%, specificity at 80.95%, positive predictive value at 95.83%, and negative predictive value at 85%. P value was calculated at <0.001 (extremely significant). These findings are in concordance with numerous studies done till date on the cytohistological correlation, while providing the cytopathology's an easy template-based classification system, which marginalizes diagnostic discrepancies to a minimum.
| Conclusion|| |
FNA cytology is a safe, reliable, and yet economically effective technique in diagnosing salivary gland lesions. However, the worldwide diagnostic difficulties and the heterogeneous approach to the salivary gland tumors necessitated the need for a risk-based broad stratification scheme for effective clinical and surgical managements. The Milan classification tries to address this requirement by providing an effective six-tiered initial grading system.
Financial support and sponsorship
This study was financially supported by the Department of Otorhinolaryngology.
Conflicts of interest
There are no conflicts of interest.
| References|| |
Kakoty S, Baruah TD, Babu CP. FNAC and histopathological correlation of salivary gland lesions: An observational study. Int Surg J 2017;4:2148-52.
Layfield LJ, Gopez E, Hirschowitz S. Cost efficiency analysis for fine-needle aspiration in the workup of parotid and submandibular gland nodules. Diagn Cytopathol 2006;34:734-8.
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 of initial survey. Cancer Cytopathol 2017;125:757-66.
Tabatabai ZL, Auger M, Kurtycz DF, Laser A, Souers RJ, Laucirica R, et al.
Performance characteristics of adenoid cystic carcinoma of the salivary glands in fine-needle aspirates: Results from the college of American pathologists nongynecologic cytology program. Arch Pathol Lab Med 2015;139:1525-30.
Hughes JH, Volk EE, Wilbur DC; Cytopathology Resource Committee, College of American Pathologists. Pitfalls in salivary gland fine-needle aspiration cytology: Lessons from the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology. Arch Pathol Lab Med 2005;129:26-31.
Griffith CC, Pai RK, Schneider F, Duvvuri U, Ferris RL, Johnson JT, et al.
Salivary gland tumor fine-needle aspiration cytology: A proposal for a risk stratification classification. Am J Clin Pathol 2015;143:839-53.
Wang H, Fundakowski C, Khurana JS, Jhala N. Fine-needle aspiration biopsy of salivary gland lesions. Arch Pathol Lab Med 2015;139:1491-7.
Pitman MB, Layfield L. The Papanicolaou Society of Cytopathology System for Reporting Pancreaticobiliary Cytology: Definitions, Criteria and Explanatory Notes. 1st
ed. Cham, Switzerland: Springer International Publishing AG; 2015.
Stenman G. Fusion oncogenes in salivary gland tumors: Molecular and clinical consequences. Head Neck Pathol 2013;7 Suppl 1:S12-9.
Weinreb I, Piscuoglio S, Martelotto LG, Waggott D, Ng CK, Perez-Ordonez B, et al.
Hotspot activating PRKD1 somatic mutations in polymorphous low-grade adenocarcinomas of the salivary glands. Nat Genet 2014;46:1166-9.
Rossi ED, Wong LQ, Bizzarro T, Petrone G, Mule A, Fadda G, et al.
The impact of FNAC in the management of salivary gland lesions: Institutional experiences leading to a risk-based classification scheme. Cancer Cytopathol 2016;124:388-96.
Salehinejad J, Mohtasham N, Bagherpour A, Abbaszadeh-Bidokhty H, Ghazi A. Evaluation of c-kit protein (CD117) expression in common salivary gland neoplasms. J Oral Maxillofac Pathol 2014;18:177-82.
] [Full text]
Wang H, Hoda RS, Faquin W, Rossi ED, Hotchandani N, Sun T, et al.
FNA biopsy of secondary nonlymphomatous malignancies in salivary glands: A multi-institutional study of 184 cases. Cancer Cytopathol 2017;125:91-103.
Mukunyadzi P, Bardales RH, Palmer HE, Stanley MW. Tissue effects of salivary gland fine-needle aspiration. Does this procedure preclude accurate histologic diagnosis? Am J Clin Pathol 2000;114:741-5.
Harris NL. Lymphoid proliferations of the salivary glands. Am J Clin Pathol 1999;111:S94-103.
Jayaram G, Dashini M. Evaluation of fine needle aspiration cytology of salivary glands: An analysis of 141 cases. Malays J Pathol 2001;23:93-100.
Klijanienko J, Vielh P. Fine-needle sampling of salivary gland lesions. III. Cytologic and histologic correlation of 75 cases of adenoid cystic carcinoma: Review and experience at the Institut Curie with emphasis on cytologic pitfalls. Diagn Cytopathol 1997;17:36-41.
Cohen EG, Patel SG, Lin O, Boyle JO, Kraus DH, Singh B, et al.
Fine-needle aspiration biopsy of salivary gland lesions in a selected patient population. Arch Otolaryngol Head Neck Surg 2004;130:773-8.
Riley N, Allison R, Stevenson S. Fine-needle aspiration cytology in parotid masses: Our experience in Canterbury, New Zealand. ANZ J Surg 2005;75:144-6.
Ashraf A, Shaikh AS, Kamal F, Sarfraz R, Bukhari MH. Diagnostic reliability of FNAC for salivary gland swellings: A comparative study. Diagn Cytopathol 2010;38:499-504.
244 AJC Bose Road, Kolkata - 700 020, West Benga
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]