Fine-needle aspiration cytology: a reliable tool in the diagnosis of salivary gland lesions

J Oral Pathol Med (2012) 41 : 106–112 Background: Fine‐needle aspiration cytology (FNAC) is used as the main initial diagnostic investigation for lumps in the head and neck region. Major salivary glands and some minor salivary glands are easily accessible; therefore, they are optimal targets for FNAC. The aim of this study was to discuss the advantages and pitfalls of FNAC as compared to histopathology in the salivary gland lesions. Material and methods: A total of 127 FNAC were carried out on salivary gland lesions from January 2006 to December 2010 – a 5‐year period. Histopathological follow‐up data were obtained in 56 cases. The study was conducted to examine the sensitivity, specificity, and accuracy of FNAC for salivary gland swellings in comparison with histopathology. Results: The male‐to‐female ratio was 2.4:1. Parotid gland was involved in 51.1%, submandibular gland in 37%, sublingual gland in 4.7%, and minor salivary glands in 7% of patients. There were 55.9% cases of non‐neoplastic lesions and 44.1% cases of neoplastic lesions on biopsy. Sensitivity, specificity, positive predictive value, and negative predictive value of FNAC for malignant neoplastic lesions were 84.61%, 86.48%, 68.75%, and 94.11%, respectively, whereas for benign neoplastic lesions, they were 84.61%, 91.66%, 91.6%, and 85%, respectively. Conclusion: Fine‐needle aspiration cytology is found to be a good sensitive and specific technique for the diagnosis of most of the salivary gland lesions. FNAC should be adopted as an initial investigation for all salivary gland swellings in conjunction with other investigations where appropriate.     

Salivary gland tumours: immunoexpression of integrins β1, β3 and β4

BACKGROUND: Integrins, heterodimeric transmembranic adhesion molecules composed of alpha and beta subunits, have been implicated in normal and neoplastic biological processes. We investigated the patterns of expression of integrins subunits beta 1, beta 3 and beta 4 in neoplasms derived from the terminal segment of salivary glands in order to understand their expression patterns in the different structures of these tumours. METHODS: Immunohistochemistry using 'catalized signal amplification' (CSA) detection system was applied to paraffin-embedded specimens of polymorphous low-grade adenocarcinoma, adenoid cystic carcinoma and acinic cell carcinoma. Normal salivary glands were used as controls. RESULTS: Immunoexpression of integrins showed that neoplastic structures of the tumours studied tend to mimic the patterns seen in the normal structures of salivary glands from which they are derived. Anaplastic cells were negative for all integrins. CONCLUSIONS: This study revealed detailed topography of integrins in malignant tumours derived from intercalated acinar segment of salivary gland and this might be useful in the diagnosis of these lesions, especially of fine-needle aspiration (FNA) products or small specimens derived form incisional biopsies.     

Analysis of efficacy and safety of core-needle biopsy versus fine-needle aspiration cytology in patients with cervical lymphadenopathy and salivary gland tumour

In this study, we compared the diagnostic accuracy and safety of fine-needle aspiration cytology and core-needle biopsy in patients with cervical lymphadenopathy or salivary gland tumour, and provided a basis for selecting the appropriate diagnostic method in clinical situations. A total of 278 patients were included in this study. The sensitivities of fine-needle aspiration cytology and core-needle biopsy were 66.7% and 100%, respectively, and negative predictive values were 92.6% and 100%, respectively, for diagnosing malignancy. In diagnosing lymphoma, fine-needle aspiration cytology gave false-negative results in all patients. In diagnosing tuberculous lymphadenopathy, the sensitivities of fine-needle aspiration cytology and core-needle biopsy were 33.3% and 91.15%, respectively, and the negative predictive values were 90.0% and 95.1%, respectively. The sensitivities of fine-needle aspiration cytology and core-needle biopsy were 42.9% and 100% in diagnosing malignant salivary gland tumours, and the negative predictive values were 91% and 100%, respectively. The results of this study showed that core-needle biopsy was superior in diagnosing and distinguishing critical diseases such as malignant lymphadenopathy and tuberculosis in patients with cervical lymphadenopathy and salivary gland tumour.     

Demonstration of c-erbB-2 oncogene overexpression in salivary gland neoplasms by in situ hybridization

The level of c-erbB-2 cellular mRNA in 18 salivary gland tumours and in 7 normal salivary glands was determined by in situ hybridization using [³⁵S] labelled RNA probes. Computer assisted quantitation of the autoradiographic signal indicated a significantly higher c- erb B-2 expression in the tumour group (22.64 grains per cell ±3.79; 95% CI) as compared to the non-neoplastic salivary gland tissue (4.11 ±0.90; 95% CI). The c-erbB-2 expression as measured by grain counts per cell for the pleomorphic adenomas (16.29± 1.87; 95% CI), mucoepidermoid carcinomas (31.52 ±0.08; 95% CI) and the acinic cell carcinomas (44.24± 17.11; 95% CI) were significantly greater than the expression for the normal group. The acinic cell carcinomas exhibited the greatest level of expression. As observed at the individual cell level, the autoradiographic signal was distributed uniformly in the neoplastic tissues, regardless of the cell type. This study confirms the hypothesis that the c-erb B-2 oncogene is overexpressed at the mRNA level in salivary gland tumours.     

Fine-needle aspiration cytology of salivary gland tumours: a 10-year retrospective analysis

Introduction

The aim of this study was to evaluate the sensitivity, specificity, diagnostic accuracy, positive predictive value (PPV) and negative predictive value (NPV) of fine-needle aspiration cytology (FNAC) of salivary gland tumours performed at a tertiary cancer hospital over a time period of 10?years.

Materials and methods

A retrospective analysis was carried out between 1995 and 2004 to review the cases of patients with salivary gland tumours who had undergone pre-operative FNA and for whom definite histology was either by tru-cut biopsy or by histopathological examination of the operative specimen.

Results

A total of 107 cases of salivary gland tumours were treated during that period, but only 82 cases diagnosed by FNAC could be correlated with histological and clinical data and were considered for this study. The sensitivity, specificity, diagnostic accuracy, PPV and NPV were estimated considering 54 benign and 28 malignant cases. Sensitivity was 90% (28/31), specificity was 98% (54/55), diagnostic accuracy was 95.1% (82/86), PPV was 96% and NPV was 94%.

Discussion

This study confirms that FNA cytology is a technique that offers high sensitivity, specificity and diagnostic accuracy in salivary gland tumour diagnosis.     

Cytoplasmic expression of p53 protein and its morphological features in salivary gland lesions

An immunohistochemical study of p53 protein was carried out on 45 salivary gland lesions using a monoclonal antibody, Bp53–12, raised to the intracellular domain of the p53 protein. p53 protein expression was found in 34.4% of 32 salivary gland carcinomas. Nuclear p53 expression was detected in tumor cells but not in non-neoplastic cells, except in one salivary duct carcinoma. The perinuclear cytoplasm of luminal duct cells was specifically positive for the antibody used here. Cytoplasmic p53 expression was observed mostly in non-neoplastic cells. There was a tendency for the Cytoplasmic staining of p53 protein to be observed in the normal cells adjacent to p53-positive carcinomas, but none of the normal cells were positive in the tissues surrounding p53-negative carcinomas. Cytoplasmic expression of p53 protein in salivary gland tissues seems to be correlated with tumorigenesis.     

The accuracy of fine needle aspiration cytology in the clinical diagnosis of minor salivary gland tumours

The objective of this study was to investigate the accuracy of fine needle aspiration cytology (FNAC) and biopsy for the clinical diagnosis of minor salivary gland tumours (MSGTs). This retrospective study of 32 MSGT cases was conducted over a 5-year period. Clinical features including age, sex, and location of the tumour were obtained from the patient clinical records. All cases were also assessed histologically according to the 2017 World Health Organization Classification of Head and Neck Tumours. The results of FNAC and biopsy were correlated with those of histopathology, and their sensitivity, specificity, and diagnostic efficacy were calculated using histopathology as the gold standard. Eighteen malignant MSGTs (56.3%) and 14 benign MSGTs (43.8%) were diagnosed by pathological diagnosis. The most common malignant tumour was mucoepidermoid carcinoma (seven cases, 38.9%). Most benign cases were pleomorphic adenomas (13 cases, 92.9%). FNAC was performed for 23 cases and biopsy for 13 cases. The sensitivity and specificity of FNAC were 66.7% and 91.0%, respectively, while those of biopsy were 90.0% and 100.0%, respectively. Although FNAC is a minimally invasive and cost-effective procedure, it is less accurate than biopsy in the assessment of MSGTs. Repeated FNAC or biopsy should be considered in negative and unsatisfactory FNAC cases.     

Primary malignant lymphoma of the salivary gland: a tumor of mucosa-associated lymphoid tissue

The clinical, morphologic and immunohistochemical features of 10 cases of the low-grade mucosa-associated lymphoid tissue (MALT) lymphoma of salivary glands are described. Although the initial histologic diagnosis in nine of these cases was myoepithelial sialadenitis, the diagnosis of primary salivary gland MALT lymphoma was based on the demonstration of light chain restriction and on morphologic characteristics. Histologic study showed a characteristic cytology, which included centrocytoid cells (composed of small centrocytes and monocytoid B cells) and a varying degree of plasma cell differentiation; the occurrence of epithelial or acinar invasion by neoplastic centrocytoid cells; and the presence of reactive lymph follicles among the neoplastic cells. Furthermore, multinucleate giant cells resembling Warthin-Finkeldey cells were detected in seven cases. In the light of these findings, cases previously diagnosed as myoepithelial sialadenitis require careful assessment and nine out of 32 cases are, in reality, examples of primary salivary gland MALT lymphomas. Immunohistochemical analysis of paraffin sections revealed the following characteristic immunophenotype of MALT lymphoma: L26, KiB3 and LN2 positive, and a monotypic immunoglobulin pattern (predominantly IgM/kappa). It was of interest that salivary gland parenchyma, infiltrated by neoplastic centrocytoid cells, reacted with LN3 for cells expressing human leukocyte antigen-DR (HLA-DR) antigens. Whereas salivary gland epithelia devoid of a neoplastic invasion were invariably negative for LN3. This suggests a lymphocyte-mediated role in salivary epithelial HLA-DR expression. It appears that HLA-DR expression is an inducible phenomenon in MALT lymphomas of salivary gland.     

Current concepts in research related to oncogenes implicated in salivary gland tumourigenesis: a review of the literature

Background:  Salivary gland tumours are relatively uncommon and there exists considerable difficulty in decisions regarding prognosis and management, as well as diagnostic uncertainty that has implications for treatment.
Method:  Literature pertaining to individual oncogenes has been reviewed and commented upon, specifically looking at the role of these as diagnostic and prognostic markers and as potential targets for treatments.
Results:  kit , PLAG1, Mect1-Maml2 , HMGIC, HER2/ neu , ras , c-fos and Sox-4 all have seminal small-scale studies in the literature with potential for further research and eventual clinical applications.
Conclusion:  A wide variety of oncogenes are implicated in salivary gland tumourigenesis, with evidence being confined to small murine or in vitro studies more often than not. There are possible roles for different oncogenes in therapeutics, prognosis and management of specific salivary gland tumours.     

Migration‐stimulating factor as a novel biomarker in salivary gland tumours

J Oral Pathol Med (2011) 40 : 747–754 Background: The identification of novel stratification biomarkers would benefit the clinical management of patients with salivary gland tumours. Migration‐stimulating factor (MSF) is a potent stimulator of cell invasion, matrix remodelling and angiogenesis. The aim of this study was to determine whether MSF was expressed in salivary gland tumours and its potential value as a diagnostic biomarker. Methods: Paraffin‐embedded archival specimens of small salivary gland tumours were stained with an MSF‐specific antibody. The specimens included 27 malignant and seven benign tumours; histologically normal salivary gland adjacent to the tumour was present in 16 specimens. MSF expression was assessed by consensus of 2–4 independent observers according to various indices, including ‘overall MSF grade’, ‘percentage of area stained’ and ‘intensity of the staining’. The motogenic effect of MSF on a salivary gland tumour cell line, HSG, was examined in the transmembrane assay. Results: Overall MSF expression increased significantly in a step‐wise fashion from normal salivary gland to benign and malignant tumours (P = 0.04–0.0001); with moderate/strong positive specimens representing 6%, 33% and 74% of the normal, benign and malignant specimens, respectively. MSF was heterogeneously expressed in both carcinoma and stromal cell compartments, its expression being higher in malignant than benign tumours regarding various MSF indices. In tissue culture studies, exogenous MSF stimulated the migration of HSG cells. Conclusions: These immunohistochemical and functional studies suggest that MSF expression is a potentially useful biomarker of salivary gland tumour progression.     

Salivary gland tumours: an epidemiological review of non-neoplastic and neoplastic pathology

Salivary gland tumours (SGT) demonstrate geographical variation. The primary objective of this study was to determine the types, frequency, distribution, and demographics of non-neoplastic and neoplastic salivary gland pathology at Waikato Hospital, New Zealand (NZ) over a 10-year period. Following this we conducted a 10-year retrospective review of SGT epidemiology from international literature. In total 825 patients were identified, 31% (256/825) with non-neoplastic salivary gland pathology, 34% (284/825) with benign neoplastic pathology, 14% (118/825) with primary malignant lesions, 18% (146/825) with metastatic SGTs, and 3% (21/825) with lymphoma. Patients had a mean (range) age of 58 (3–102) years, were predominantly male (58%, 476/825), and NZ European (65%, 536/825). Tumours were most prevalent in the parotid gland (85%, 484/569), of which 44% (211/484) were malignant. Pleomorphic adenoma was the most common benign (71%, 203/284) and overall (36%, 203/569) tumour, while mucoepidermoid carcinoma (25%, 29/118) and squamous cell carcinoma (SCC) (73%, 106/146) were the most common primary malignant and metastatic SGTs, respectively. Our literature review identified 18 studies consisting of 33,933 patients, of whom 71% (24,013/33,933) had benign SGTs. Pleomorphic adenoma (68%, 16404/24013) and mucoepidermoid carcinoma (29%, 2826/9621) were the most common benign and malignant SGTs, respectively. Low numbers of non-neoplastic and metastatic SGTs were reported in the literature. This research provides a greater understanding of differences in their global distribution. Consistent with previous literature, pleomorphic adenoma and mucoepidermoid carcinoma were the most common benign and malignant SGTs. In NZ, we found high rates of malignant SCC to the parotid gland, consistent with the epidemiology of non-melanoma skin cancer in the country.     

涎腺肿块的细针吸取细胞学诊断研究

目的 通过对细针吸取细胞学(fine needle aspiration cytology,FNAC)与病理诊断的比较,评价本组细针吸取细胞学在涎腺肿块术前诊断的价值.方法 采用"友谊式"细针穿刺器,对81例涎腺肿块进行FNAC检查,将其结果与术后组织病理结果对照,得出FNAC诊断准确率,同时计算微小组织病理学诊断的准确率.结果 本组FNAC定性诊断准确率达92.59%,误诊率7.41%;组织学分类完全符合率达67.90%,基本符合率24.69%,不符合率7.41%;微小组织病理学诊断准确率达85.71%,误诊率14.29%.结论 FNAC对涎腺肿块的定性诊断的准确性较高,对术前诊断有重要的参考意义.由于FNAC诊断不同类型涎腺肿块的完全符合率不同,其临床可参考性也不同.     

The role of operator experience in fine needle aspiration cytology of head and neck masses

Fine needle aspiration cytology (FNAC) was performed on 95 patients presenting with a mass in the head and neck region, where a subsequent surgical pathological diagnosis and adequate documentation were available. In this group, 70% of the samples were found to be of diagnostic yield. Of these, the number of true-positives was 27, and true-negatives 35. This gives a sensitivity and specificity of 90% and 97%, respectively. The accuracy was 100% when performed by a consultant and 91% when performed by junior staff. These sensitivity and specificity levels compare favourably with those reported in other studies using FNAC in head and neck lesions. Greater experience of the operator appears to improve the accuracy rate. FNAC is a useful diagnostic tool for head and neck tumours, as shown by the high specificity and sensitivity rates in this study.     

Diagnostic value of ultrasound-guided core needle biopsy in patients with salivary gland masses

The salivary glands are unique in the diversity and complexity of their pathologies. Because fine needle aspiration cytology and frozen section are associated with major diagnostic difficulties, the authors analyzed the use of core needle biopsy (CNB) for the histologic assessment of salivary gland lesions. A systematic observational clinicopathologic quality assessment study was performed over 81 months including 161 CNB procedures in 76 patients with salivary gland pathologies. Adequate samples containing the target tissue were obtained in 73 patients. These samples revealed malignant disease in 45 (62%) patients, benign disease in 26 (36%) patients, and were inconclusive in 2 (3%) patients. Follow-up uncovered no false-positive or false-negative results. On the basis of secondary histologic and clinical follow-up, the statistical parameters were calculated as follows: sensitivity 94%; specificity 100%; accuracy 96%; positive predictive value 100%; negative predictive value 90%. The advantages and potential limitations of CNB in patients with salivary gland masses are discussed. CNB is a reliable biopsy technique for the assessment of salivary gland pathologies, although limitations remain for the subclassification of some neoplastic lesions. The authors recommend CNB as the biopsy technique of choice for a selection of indications.     

Pleomorphic Adenoma of Minor Salivary Gland in a 14 year Old Child

Salivary gland tumours are rare in childhood, and almost all of them occur in parotid gland. Minor salivary gland tumours are even rarer, pleomorphic adenoma being the most frequently found tumour. Only seventeen cases of pleomorphic adenoma arising in the minor salivary gland tumour have been reported in children and adolescents. Pleomorphic adenoma of minor salivary gland represents about 45% of all the tumours of the minor salivary glands. Pleomorphic adenoma is slowly enlarging tumour indistinguishable from adenoid cystic carcinoma clinically, except for pain and ulceration, which is more common in the latter. Carcinoma arising from pleomorphic adenoma has been reported in 3% cases amongst the minor salivary gland tumours. This report presents a case of pleomorphic adenoma of minor salivary gland in a 14 year old female patient with a brief review of literature.     

1878例涎腺肿瘤WHO组织病理学新分类的统计分析

目的 根据ＷＨＯ１９９０年涎腺肿瘤组织病理学新分类标准对１８７８例涎腺肿瘤及肿瘤样疾病进行重新分类,并重点对涎腺上皮性肿瘤的临床发病情况进行统计分析。方法 统计描述。结果 １８７８例涎腺肿瘤以诞腺上皮性肿瘤为主,为１４３１例,占７６．２０％,其中腺瘤发病居首位,其次是涎腺癌,涎腺肿瘤样疾病居第三位;多形性腺瘤是涎腺肿瘤中最常见者,恶性多形性腺瘤为最常见的涎腺癌,特别注意了腺癌亚分类中的几种少见类型     

Fine needle aspiration cytology (FNAC) of salivary gland tumours: Repeat aspiration provides further information in cases with an unclear initial cytological diagnosis

Introduction

Fine needle aspiration cytology (FNAC) for salivary gland tumours requires expertise in interpretation. When a diagnosis is not clear (despite a cellular aspirate), published work is lacking on the value of repeating the test.

Methods

A retrospective study of 135 patients who had FNAC followed by definitive excision for a suspected salivary gland tumour. Accuracy was compared among those requiring repeat FNAC on one more occasion because of a non-diagnostic initial cytology report.

Results

33 patients (24% of study group) had repeat FNAC. A definite cytological diagnosis was subsequently made in 27/33 patients (82%). The sensitivity (84%) and specificity (93%) of repeat FNAC in distinguishing benign from malignant tumours was similar to initial FNAC (70% and 95%, respectively).

Conclusions

Repeat FNAC may provide a cytological diagnosis in cases where the initial diagnosis is not clear, although cytology should be used in conjunction with other investigations of salivary tumours, including image-guided biopsy examination where appropriate. Ideally salivary gland FNAC should be interpreted by a specialist pathologist.     

DNA ploidy analysis in salivary gland tumours by image cytometry

AIM: To determine whether DNA ploidy by image cytometry is a good diagnostic tool to distinguish benign and malignant salivary gland tumours. METHODS: A total of 62 salivary gland tumours were studied. Cases were histologically diagnosed [haematoxylin and eosin (H&E)]. According to the World Health Organization (WHO) classification, there were 14 mucoepidermoid carcinomas (MEC), 11 adenoid cystic carcinomas (ACC), 10 pleomorphic adenomas (PA), 10 carcinoma ex PA (CEPA), 9 acinic cell carcinomas (ACCa), 3 polymorphous low-grade adenocarcinomas (PLGA), 2 papillary cystadenocarcinomas (PC), 1 myoepithelial carcinoma (MC), 1 undifferentiated carcinoma (UC) and 1 mucinous adenocarcinoma (MA). Paraffin sections (40 microm) were micro-dissected to isolate tumour areas; cell nuclei were extracted and Feulgen-stained cytospin monolayers were analysed using a DNA image cytometry system. For each case, DNA index (DI) was calculated relative to internal controls (lymphocytes; DI=1.0). Cases were categorized as diploid or aneuploid and the proportion of cells over 5c was also calculated. RESULTS: Fifty-three of 62 salivary gland tumours were uniformly diploid. Only nine cases were aneuploid: five CEPA, one low-grade MEC, one PC, one UC and one MA. CONCLUSIONS: The vast majority of salivary gland tumours were diploid. High-grade malignancies may be aneuploid, and ploidy may be useful to identify malignant change in atypical PA. Further, larger studies are needed to confirm our results and to further evaluate the usefulness of the technique in high-grade lesions.     

Epidermal growth factor receptor immunoexpression evaluation in malignant salivary gland tumours

Objective:  The aim of this study was to determine epidermal growth factor receptor (EGFR) expression in malignant salivary gland tumours and its possible relationships with clinical and morphological findings, disease course and prognosis.
Patients and methods:  The study sample comprised 88 patients diagnosed and treated for primary malignant salivary gland tumours between January 1992 and December 2002. We analysed EGFR expression using immunohistochemistry on formalin-fixed, paraffin embedded surgical specimens of all patients. Statistical analysis was used to investigate possible relationships between EGFR expression and clinical findings, histological findings, disease course and patients survival.
Results:  Of all cases, 32 (36.4%) were EGFR positive. There was a statistically significant correlation between EGFR expression and histological grade. No other variable was correlated with EGFR expression including the overall and disease-free survival. Stage classification was the only parameter in multivariate analysis that was an independent predictor of low overall and disease-free survival.
Conclusion:  EGFR is not a useful indicator of prognosis in malignant salivary gland tumours. However, the EGFR expression in salivary gland cancers like adenocarcinomas, undifferentiated carcinomas, mucoepidermoid carcinomas or salivary duct carcinomas suggests that these tumours may be a candidate for therapy investigation directed at EGFR.     

DNA content in malignant salivary gland tumours

Objective:  Our aim was to evaluate the DNA content in malignant salivary gland tumours using image cytometry and its possible relationships with clinical and morphologic findings, disease course and prognosis.
Patients and methods:  The study sample comprised 31 patients diagnosed and treated for primary malignant salivary gland tumours. Formalin-fixed, paraffin-embedded surgical specimens of all patients were Feulgen-stained for DNA content analysis by image cytometry. Statistical analysis was used to investigate possible relationships between DNA content variables and clinical and histological findings, disease course and patient survival.
Results:  Seventeen (55%) cases of our sample were graded as DNA diploid, four (13%) as DNA aneuploid and 10 (32%) as DNA multiploid. In 15 (48%) cases, the 5c exceeding rate (5cER) was higher than 1.7%. DNA ploidy correlated with N stage and tumour size. DNA ploidy and 5cER had a statistically significant prognostic influence on overall and disease-free survival in univariate analysis. However, in multivariate analysis, stage classification was the only parameter with an independent prognosis value.
Conclusion:  Abnormal DNA content is a common finding in salivary gland cancers. Our results suggest an important role of DNA content analysis in the evaluation of these tumours.