|Year : 2018 | Volume
| Issue : 1 | Page : 93-106
|A review of research on cytological approach in salivary gland masses
Arvind Babu Rajendra Santosh1, Shobha Rani Bakki2, Suvarna Manthapuri3
1 School of Dentistry, Faculty of Medical Sciences, The University of the , Mona Campus, Kingston, Jamaica, West Indies
2 Department of Oral and Maxillofacial Pathology, Meghna Institute of Dental Sciences, Nizamabad, India
3 Department of Oral Pathology and Microbiology, SVS Institute of Dental Sciences, Mahabubnagar, Telangana, India
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|Date of Web Publication||12-Feb-2018|
| Abstract|| |
To evaluate the diagnostic accuracy of fine-needle aspirations (FNAs) in salivary gland pathologies. A comprehensive literature search was conducted in the PubMed database using related Medical Subject Heading terms “sensitivity and specificity of FNA in salivary gland” and “diagnostic accuracy of FNA in salivary gland” for the period 1980–2016, and we found that 414 research studies had been published. PRISMA technology was utilized to prepare flow chart for displaying data search strategy. A total of 385 articles were excluded based on the established inclusion and exclusion criteria of the study. Twenty-nine research studies were included. Those twenty-nine studies on the sensitivity and specificity of FNAs in salivary gland pathology consisted of 5274 cases of benign, malignant and inflammatory salivary gland lesions. The present study identified a range of 87%–100% sensitivity and 90%–100% specificity for the usefulness of FNAs in distinguishing benign and malignant salivary gland lesions. Although a considerable number of studies have been identified that reported on sensitivity and specificity of FNAs in salivary gland pathologies, each study had a different approach in reporting the sensitivity and specificity. We emphasize that standardized reporting protocols of sensitivity and specificity report supported with checklists would help future researchers to interpret this cytological method and make more accurate clinical utility and usefulness reports on salivary gland pathologies.
Keywords: Cytology, diagnosis, fine needle aspiration, pathology, salivary gland
|How to cite this article:|
Rajendra Santosh AB, Bakki SR, Manthapuri S. A review of research on cytological approach in salivary gland masses. Indian J Dent Res 2018;29:93-106
|How to cite this URL:|
Rajendra Santosh AB, Bakki SR, Manthapuri S. A review of research on cytological approach in salivary gland masses. Indian J Dent Res [serial online] 2018 [cited 2019 Jun 19];29:93-106. Available from: http://www.ijdr.in/text.asp?2018/29/1/93/225235
| Introduction|| |
Cytology focuses at the cellular level on the structure, function and biochemical characteristics whereas cytomorphometric analysis is a qualitative and quantitative measurement of nuclear area, cytoplasmic area and nuclear to cytoplasmic ratio of normal cells. The principles of cytology are applied in diagnostic pathology diagnosis to observe the significance in the difference between normal and diseased cells. Fine needle aspirations (FNAs) are the most common cyto-methodology in salivary gland pathology practice., FNA is a cytological method that is used to describe the morphological findings of individual cells, groups of cells, and microparticles in tissue from samples that were acquired using a needle.
The conventional biopsy procedure has a possible risk of intraoperative tumor cell implantation and damage to the facial nerve in parotid gland pathologies. FNAs are minimally invasive, simple, cost-effective, and minimal risk procedure than conventional biopsy procedure. Schröder et al. mentioned that FNAs have a minimal incidence of complication, have a reduced risk of tumor cell implantation (<1%). In addition, complications from surgical procedures such as hemorrhage, facial nerve damage and inflammatory reaction at the surgical site are rare.
In routine FNAs practice, the needle used in aspiration is 25-gauge (i.e., 0.5 mm) and 10-mL syringe. Perkins in 2002 reported that larger syringes do not produce better specimens. In Sweden, a syringe holder is used, whereas in France a puncture is made without syringe aspiration. The material aspirated can be either prepared as direct smears or as cell blocks. The cell blocks are useful and are suitable for histochemical and immunocyto/histochemical staining methods. FNA methodology thus helps in recognizing inflammatory, reactive, cystic, benign, or malignant conditions of salivary gland tissue.
The focus of the pathologist, while evaluating the aspirated specimen, is on: (1) Whether the clinical condition had originated from salivary gland tissue? (2) The type of pathology (inflammatory, cystic, benign or malignant), (3) When the lesion is identified as malignant, the focus is made on detection of low grade versus high grade, (4) How specifically can the cytological diagnosis be derived? and (5) Cytological specimens that indicate atypical or malignant features mandate the need for surgical biopsy.
This review of the cytological approach to salivary gland masses will focus on the normal salivary gland cytology, report on FNA research that focused on sensitivity and specificity of salivary gland pathologies, cytological diagnosis in salivary gland pathology, specific cytological features of major salivary gland pathologies and problems, as well as pitfalls, in cytodiagnosis of salivary gland aspirates.
| Descriptive Analysis on Research Report of Sensitivity and Specificity of Fine Needle Aspiration in Salivary Gland Pathology|| |
The search for a reliable adaptation of FNA in salivary gland pathology practice has developed rapidly, encouraged by the fact that collecting a specimen is relatively easy, minimally invasive, economical, and rarely associated with complications. We conducted a comprehensive literature search in PubMed database using related Medical Subject Heading terms “sensitivity and specificity of FNA in salivary gland,” “diagnostic accuracy of FNA in salivary gland” from the early 1980s until the present, four hundred and fourteen research studies have been published in the PubMed database. The research papers were included based on (1) full-text availability, (2) research papers that were available in English language, and (3) papers having Information on sensitivity and specificity of FNAs in salivary gland pathologies. However, research papers were excluded based on: (1) duplication of titles, (2) studies that focused on genetic and/or salivary analysis, and (3) incorrect weblink for full-text accessibility. Three hundred and eighty-five articles were excluded, 29 research studies were included [Figure 1].
The 29 studies on the sensitivity and specificity of FNAs in salivary gland pathology were all retrospective and consisted of 5274 cases of benign, malignant and inflammatory salivary gland lesions. The largest number of studies were reported from the Department of Pathology ,,,,,,,,,,,, (13 studies, 44.82%), followed by Departments of Otorhinolaryngology ,,, (four studies, 13.79%), Head and Neck ,,, (four studies, 13.79%), Surgery ,, (three studies, 10.34%), Surgical Oncology, (one study, 3.44%), Radiology  (one study, 3.44%), Stomatology  (one study, 3.44%), Laboratory Medicine  (one study, 3.44%), and one study  that did not specify their department details (one study, 3.44%) [Figure 2]. The rate of publication on sensitivity and specificity of FNAs has increased during the past 10-year period [Table 1].
|Figure 2: Distribution of department that reported research studies on sensitivity and specificity of fine needle aspirations in salivary gland pathologies|
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|Table 1: Data extraction from sensitivity and specificity research of fine aspiration in salivary gland pathology|
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A predominant number of studies focused on determining the diagnostic value of sensitivity and specificity of FNAs in salivary gland pathology. The overall accuracy rate of reporting on distinguishing benign from malignant salivary gland lesions was 87%–100% with a specificity of 90%–100%. A Taiwanese study evaluated the efficacy of Ultrasonography-Guided Fine Needle Aspiration Biopsy on malignant salivary gland lesions and revealed a sensitivity of 66.7% and specificity of 98.2%. So far, only three studies have been exclusively focused on FNAs sensitivity and specificity on parotid gland pathologies. Piccioni et al. assessed diagnostic accuracy of FNAs on benign and malignant parotid swellings that included Pleomorphic adenoma, Warthin's tumor, mucoepidermoid carcinoma, adenocarcinoma, lymphoma, adenoid cystic carcinoma (ADCC), ductal carcinoma, oncocytoma, monomorphic adenoma and lipoma; and reported 81% sensitivity and 99% specificity on FNAs. Awan and Ahmad evaluated the usefulness and accuracy of FNA cytology in the diagnosis of parotid gland tumors that included oncocytoma, mucoepidermioid carcinoma, pleomorphic adenoma and reported 74% sensitivity and 97% specificity. Zurrida et al. assessed the accuracy of FNAs in planning therapy for parotid disease such as pleomorphic adenoma, Whartin's tumor, oncocytoma, monomorphic adenoma, myoepithelioma, basal cell adenoma (BCA), acinic cell carcinoma, mucoepidermoid carcinoma, ADCC, malignant myoepithelialoma, metastatic squamous cell carcinoma and non-Hodgkin's lymphoma by comparing the preoperative FNAs diagnosis with the postsurgical biopsy based specimen diagnosis; and reported 100% sensitivity and 90.40% specificity. The results show higher specificity than sensitivity. Another study from the United States determined the accuracy of FNAs for establishing the diagnosis in lymphoproliferative, reactive and neoplastic salivary gland lesions as 100% sensitivity and 87% specificity.
Two of the studies studied the preoperative efficacy of FNAs in salivary gland pathologies. Singh et al. established sensitivity and specificity of FNAs by correlating FNAC diagnosis with histopathology in benign, malignant, and nonneoplastic salivary gland lesions and revealed 76.90% sensitivity and 97.10% specificity. Their results concluded that FNAs can be used preoperatively to avoid unnecessary surgery and discomfort associated with open biopsy. Tahoun and Ezzat evaluated the diagnostic accuracy of preoperative FNAs in benign and malignant salivary gland lesions and revealed 91.7% sensitivity and 92.5% specificity. Their results suggested that FNAC is complementary in usefulness for malignant salivary gland tumors. In contrast, FNAs does not influence the management of benign salivary gland lesions and routine FNAs for every patient may not be cost-effective.
| Approach to Analyze Diagnostic Accuracy of Fine Needle Aspirations Via Sensitivity and Specificity Report in Salivary Gland Cytodiagnosis|| |
The sensitivity and specificity report of benign, malignant, and nonneoplastic salivary gland lesions on FNA cytology is shown in [Table 1]. The benign salivary gland conditions observed in present study are pleomorphic adenoma, Warthin's tumor, lipoma, lipoma, oncocytoma, monomorphic adenoma, myoepithelioma, and schwannoma. The malignant salivary gland conditions observed in the present study are ADCC, acinic cell carcinoma, squamous cell carcinoma, mucoepidermoid carcinoma, carcinoma ex-pleomorphic adenoma, epithelial-myoepithelial carcinoma, adenocarcinoma, lymphoma, non-Hodgkin's lymphoma, multiple myeloma, undifferentiated carcinomas, oncocytic carcinoma, ductal carcinoma, metastatic Merkel cell carcinoma, carcinosarcoma, rhabdomyosarcoma, lymphoepithelial carcinoma, polymorphous low-grade adenocarcinoma (PLGA), nasopharyngeal carcinoma, myxoid liposarcoma, and basaloid squamous cell carcinoma.
The significance of utilizing FNA cytology practice in salivary gland pathology diagnosis is controversial due to lack of reliable recognition of true positive, true negative, false positive, or false negative cases. To achieve the reliable adaption of FNAs in salivary gland diagnosis, the preferred statistical tools to assess the positive and negative predictive values of FNA methodology were analyzed using sensitivity and specificity tests. If the FNAs were able to measure fewer false positives but more false negative cases, then the FNAs is highly specific but not very sensitive. Similarly, if the FNAs are able to measure fewer false negatives but more false positives, then the FNAs is highly sensitive but not very specific. When FNAs report was able to produce 100% sensitivity and 100% specificity results on the identification of salivary gland pathology then the FNAs should be considered as gold standard test and that it would never make an error. However, in routine practice that categorized a test as a gold standard may not be true gold standard because the gold standard is regarded as the best test under reasonable conditions.
The present study observed sensitivity of FNAs in recognition of salivary gland pathology was at a range of 57%–100% and specificity 80.95%–100%. Based on the current observation, the results can be generalized that FNAs are low sensitivity and highly specific, which means that there are many false negatives and few false positive results. Interestingly, the studies that focused only on benign salivary gland or inflammatory salivary gland conditions generated highly sensitive and highly specific results. The later observation is convenient to state that FNAs are useful diagnostic test in distinguishing benign and malignant salivary gland conditions. However, observations of the present study cannot be concluded as FNAs in salivary gland practice displays low sensitivity and highly specific reports due to the following reasons (1) the variation in reporting approach, (2) reports produced were clustered with benign, malignant and/or nonneoplastic salivary gland lesions, and (3) many studies did not show any evidence of standardized sample size calculation for reporting their results. The present study is the descriptive analysis of available reports on sensitivity and specificity of FNAs and the interpretations presented is not statistically acceptable. Systematic reviews are the best research tool to assess the diagnostic accuracy of FNAs in salivary gland diagnosis by investigating sensitivity and specificity reports of FNAs. The systematic reviews will come out with research questions on diagnostic accuracy with inclusion and exclusion criteria for selection of research reports. Following to the data collection from the reports available in literature, data analysis will be employed using statistical analysis. The results of the systematic reviews will be presented in the discussion exploring areas arising from research questions.
| Normal Cytological Characteristics of Salivary Gland Aspirate|| |
The three major salivary gland tissues are the parotid, submandibular, and sublingual. The normal cytological characteristics of salivary gland tissue are studied from the unintentional aspiration of normal tissue while aspirating abnormal tissue. FNAs of the normal salivary gland aspirate shows glandular (i.e., acinic cells), ductal elements, adipose tissue and scattered inflammatory cells. The acinic cells are either serous or mucous. The acinic cells are seen as cohesive ball like/grape-like arrangements, whereas ductal elements are identified as cohesive orderly sheets or more rarely as tubules and elongated myoepithelial cells attached to the epithelial elements., Acinic cells appear as a background field of bare nuclei. The acinic cells are composed of pyramidal cells that have uniform eccentric nuclei, and cytoplasm of serous cells is finely granular, foamy or vacuolated compared to the cytoplasm of ductal elements. Whereas ductal cells appear crowded, are smaller than acinar cells, and have less cytoplasm. When the nuclei of the ductal cells lose their cytoplasm, it is easy to misdiagnose these cells as lymphocytes.,
| Cytological Characteristics of Aspirates from Salivary Gland Pathology|| |
In responding to the call for detection of aspiration cytology diagnosis, oral and maxillofacial pathologists are expected to be knowledgeable of the cytological details of both normal as well as pathological conditions. Several excellent case studies and reviews have been previously published concerning the fine needle cytology diagnosis of various salivary gland pathologies. The microscopic characteristics of fine needle aspirate of salivary gland pathology are listed in [Table 2].
| Miller's Approach in Salivary Gland Cytodiagnosis|| |
The complexity of salivary gland lesions predisposes the cytodiagnosis to be challenging. Miller devised a five group approach to salivary gland cytodiagnosis: (1) myxoid-hyalin, (2) basaloid, (3) oncocytoid, (4) lymphoid, and (5) squamoid lesions [Figure 3]. The lesions that are included in myxoid hyaline lesions are benign mixed tumors, ADCC, carcinoma ex benign mixed tumor, PLGA; the lesions that show myxoid hyaline but are not of salivary gland origin are schwannoma, myxoma, myxoid lipoma, and myxoid neurofibroma. The basaloid lesions included BCA, basal cell carcinoma, solid variant of ADCC, PLGA, and small cell undifferentiated carcinoma. Intraglandular oncocytic lesions included Wharthin's tumor, oncocytoma, acinic cell carcinoma; and extraglandular oncocytic lesions include paraganglioma, carcinoid, granular-cell tumor, rhabdoid tumors, renal cell carcinoma, melanoma, medullary carcinoma, Hurthle cell carcinoma, and hepatocellular carcinoma. Lymphoid lesions included chronic sialadenitis, benign lymphepithelial lesions, intra-/peri-salivary gland lymph nodes. The misdiagnosis of lymphoid lesions included neoplastic lesions that are associated with lymphocytes such as Whartin's tumor, lymphoepithelial carcinoma, and metastasis to intra-/peri-parotid lymph node. Squamoid lesions include retention cyst/mucoceles, squamous cell carcinoma and benign congenital cysts extrinsic to salivary glands such as branchial cleft, thryroglossal duct, thymic, and dermoid/epidermal inclusion cysts.
| Conclusion|| |
The present study identified that the usefulness of FNAs in distinguishing benign and malignant salivary gland lesions were at a range of 87%–100% sensitivity and 90%–100% specificity. Although a considerable number of studies have been identified that reported on sensitivity and specificity of FNAs in salivary gland pathologies, each study had a different approach in reporting the sensitivity and specificity. Hence, the present study results may not be conclusive to make a statement on overall sensitivity and specificity reports on FNA in salivary gland pathologies. However, we emphasize that standardized reporting protocols of sensitivity and specificity report with the means of checklists, would help future researchers interpret this cytological method and make more accurate clinical utility and usefulness reports on salivary gland pathologies.
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Dr. Arvind Babu Rajendra Santosh
Oral and Maxillofacial Pathologist, Lecturer and Research Coordinator, School of Dentistry, Faculty of Medical Sciences, The University of the West Indies, Mona Campus, Kingston, Jamaica
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]
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