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Introduction: The cytopathology and diagnostic accuracy of salivary gland (SG) polymorphous adenocarcinoma (PAC) is the subject of a limited number of reports. We undertook a review of our experience with fine needle aspiration (FNA) biopsy and PAC., Materials and Methods: A search was made of our cytopathology files for PAC cases that also had histopathological confirmation. FNA biopsy smears and cell-blocks were performed and examined using standard techniques., Results: Eight FNA biopsy cases of histologically proven PAC from 7 patients [F:M = 1.3:1, age 39-75 years, mean = 58] met study inclusion. Metastatic aspirates were most common (4), followed by 3 primary cases and 1 locally recurrent neoplasm. Primary FNA sites included hard palate (1 case), lip (1), and lateral tongue (1); all metastatic sites were in the neck. A precise cytologic diagnosis was made in 38% of cases; however, when applying the Milan classification system, 100% could be categorised as either malignant or of uncertain malignant potential. Ancillary immunohistochemical testing performed in 44% of the cases was non-specific. Cytologic smears showed cellular uniformity and structural variety of cell groups with tubular, branching, cribriform, and convex patterns as well as variable, but occasionally abundant globular myxoid stroma leading to confusion with adenoid cystic carcinoma., Conclusion: The imitative cytopathology of PAC with other SG neoplasms as well as its infrequency in routine FNA biopsy practice makes specific interpretation difficult, but using a classification system allows for appropriate patient management. Molecular testing in future specimens holds promise for enhancing diagnostic accuracy., (© 2021 John Wiley & Sons Ltd.)

Aims: There is a widespread perception among clinicians and pathologists that the histomorphological assessment of minor salivary gland (MinSG) tumours is more difficult and hampered by more misdiagnoses than that of major salivary gland tumours. This is based on a vague, subjective clinical impression, lacking scientific proof. The aim of the present study was to identify and statistically verify potential reasons that could explain this difference., Methods and Results: We identified 14 putative clinical, pathological and combined clinicopathological reasons that, altogether, could explain the phenomenon of the perceived greater diagnostic difficulty associated with MinSG tumours. We performed a comprehensive literature search and a statistical comparison of data from a large personal consultation series (biased for difficult cases) with cumulated data from straightforward, unselected (non-consultation) series from the literature. By performing this comparison, we identified, with statistical significance, a comprehensive series of reasons, as well as of consequences, of the greater difficulty in diagnosing MinSG tumours., Conclusions: Among the 14 criteria, high frequencies of initial incisional biopsies and of a low-grade category in malignant tumours emerged as the two most important reasons for enhanced diagnostic difficulty. Very rare entities, unusual locations, shortcomings in clinicopathological communication, and pecularities of the special anatomical location of the hard palate, such as tumour necrosis, mucosal ulceration, pseudoinvasion, and the peculiar phenomenon of 'tumoral-mucosal fusion', contribute to further diagnostic difficulties. The awareness of these shortcomings and pitfalls enables us to provide a series of recommendations for clinicians and pathologists that might aid in assessment and reduce the rate of misdiagnosis of MinSG tumours., (© 2021 John Wiley & Sons Ltd.)

Pleomorphic adenoma (PA) is the most common salivary gland neoplasm, and its diagnosis is straightforward in the majority of cases. However, not infrequently, PA shows unusual and uncommon histological features that can be confused with those of malignancy. The difficulties in diagnosing PA arise from its ability to mimic invasion, show atypical or metaplastic cytomorphology, and show morphological features that overlap with those of established salivary gland carcinomas. In addition, recognising early malignant transformation to carcinoma ex-pleomorphic adenoma continues to be a frequent challenge. This review describes the diagnostic pitfalls of PA, and offers a systematic approach to avoid them by combining classic histopathology with novel immunohistochemical and molecular tests., (© 2021 John Wiley & Sons Ltd.)

Fine needle aspiration cytology (FNAC) is generally characterized by a high diagnostic accuracy in differentiating non-neoplastic/inflammatory lesions from neoplastic lesions of the salivary glands. Lymphoepithelial sialadenitis/myoepithelial sialadenitis is exceedingly rare in paediatric patients and is characterized by a diffuse, often bilateral, salivary gland enlargement and the differential diagnosis may sometimes be difficult. We report the case of a 10-year-old boy who presented with a swelling of the left parotid gland investigated by ultrasound salivary gland FNAC., (© 2020 John Wiley & Sons Ltd.)

Spindle cell lesions of the salivary glands are rare and account for less than 3% of the salivary gland aspirates. A definitive classification of salivary gland neoplasms by fine needle aspiration is possible for the most common lesions but remains a challenge for the less common entities. We present a case of a 72-year-old male with a solitary fibrous tumour (SFT) of the submandibular gland mimicking a myoepithelial-rich pleomorphic adenoma (PA). In this article, we discuss novel insights that help differentiate SFT from PA and other spindle cell lesions., (© 2020 John Wiley & Sons Ltd.)

Background: To differentiate pleomorphic adenoma (PA) and adenoid cystic carcinoma (ACC) on fine needle aspiration cytology (FNAC) is often challenging to cytologists., Aims: In the present study, we tried to make an artificial neural network (ANN) model from the FNAC smears to differentiate PA from ACC., Methods: The detailed cytomorphological features were analysed on the FNAC of histopathology proven cases of PA (n = 35) and ACC (n = 33) and enumerated semi-quantitatively by two independent observers. These data were used to make an ANN model to distinguish PA from ACC on FNAC material. We used neuro-intelligence software to build the ANN model. The network architecture was 10-2-1. The heuristic search engine was applied to have this model. We used backpropagation neural network to teach ANN. At least 500 iterations were done to train the model. The efficacy of this ANN model was assessed with the help of the confusion matrix and receiver operating characteristic curve., Result: The data were separated automatically by the software as a training set (n = 48), validation set (n = 10) and test set (n = 10). The ANN model was able to differentiate every case (10/10) of PA and ACC in the final test set. The area under the receiver operating characteristic curve was 1., Conclusion: The currently built ANN model is competent to identify PA and ACC cases on FNAC. Additional parameters and new cases can be incorporated into this open-ended ANN model to make it more robust., (© 2019 John Wiley & Sons Ltd.)

Aims: Pleomorphic adenoma gene 1 (PLAG1) gene rearrangement is the most common genetic abnormality in pleomorphic adenoma (PA), resulting in overexpression of PLAG1 protein. PA and carcinoma ex pleomorphic adenoma (CA ex-PA) can mimic various benign and malignant salivary gland tumours. The aims of this study are to evaluate the sensitivity and specificity of PLAG1 immunohistochemistry (IHC) in the differential diagnosis of PA and CA ex-PA and to compare the PLAG1 immunohistochemical results to PLAG1 gene abnormalities as detected by fluorescence in-situ hybridisation (FISH)., Methods and Results: PLAG1 immunostaining was performed on 83 salivary gland tumours, including 23 PA, 15 CA ex-PA and 45 other salivary gland tumours. In addition, PLAG1 FISH was performed in 44 cases for the presence of gene rearrangements/amplifications. The results showed high sensitivity of PLAG1 IHC in 96% of PA; however, discordant results between PLAG1 FISH abnormalities and IHC were noted in 15 of 44 cases (34%). Seven PA, four de-novo myoepithelial carcinomas and one basal cell adenocarcinoma had negative FISH results, but were positive for IHC; while three salivary duct carcinomas (SDC) ex-PA were positive for FISH but negative for IHC. PLAG1 IHC can differentiate CA ex-PA from de-novo SDC (P = 0.02), but not from de-novo myoepithelial carcinoma. PLAG1 IHC is a sensitive marker for PA. This could be due to PLAG1 gene abnormalities beyond FISH resolution., Conclusions: A negative PLAG1 IHC might be helpful in excluding a PA diagnosis. Interestingly, in the context of CA ex-PA, FISH is more sensitive than IHC in detecting PLAG1 abnormalities., (© 2017 John Wiley & Sons Ltd.)

Objective: In order to evaluate the possibility of a specific cytological recognition of basal cell adenoma (BCA) we reviewed our experience with 35 histologically proven cases. Few series describing cytological features of BCA are available and diagnostic cytological criteria are not well established., Methods: This study was based on 41 cytology samples from 35 patients with BCA. Thirty-five aspiration procedures were performed pre-operatively and six on tumour recurrence. Nineteen of the 35 patients were men and 16 women. The mean age at diagnosis was 55 years old (range 24-92). The series includes one non-representative case. Except for one tumour located in the upper lip, all of them involved the parotid gland., Results: Aspirates were cellular, showing groups with dense, homogeneous metachromatic stroma and single cells. Relevant features were the trident-like configuration of groups, intimate relationship between neoplastic cells and stroma and cellular polymorphism. In approximately half of the cases a precise diagnosis was given. Most of the remaining tumours were diagnosed as benign but they were difficult to differentiate from pleomorphic adenoma. Regarding malignancy, there were two misdiagnoses of acinic cell carcinoma, due to high epithelial cellularity along with scarcity of stroma, and one case was considered to be suspicious of malignancy., Conclusion: BCA shows characteristic cytological features that allow a precise diagnosis. The main differential diagnosis is epithelial-rich pleomorphic adenoma, while acinic cell carcinoma is a potential false positive., (© 2011 Blackwell Publishing Ltd.)

Aims: This study tests the hypothesis that histopathological fingerprinting of galectins, which are emerging multifunctional effectors in cell sociology, could refine the differential diagnosis of salivary tumours., Methods and Results: We applied non-crossreactive polyclonal antibodies against galectin-1 (Gal-1), galectin-3 (Gal-3), galectin-7 (Gal-7) and galectin-8 (Gal-8) for immunohistochemical analysis of salivary gland tumours (72 cases with benign disease and 39 cases with malignancy) and 29 control specimens. The principal positivity of cases, the site of signal presence and the quantitative parameters concerning percentage of positive cells and labelling intensity were determined. Acinic cell and adenoid cystic carcinomas (specifically tubular and cribriform types) shared the expression signature of Gal-1, Gal-3 and Gal-8 presence combined with Gal-7 absence. Mucoepidermoid carcinomas presented a unique profile based on cytoplasmic Gal-1, Gal-3, Gal-7 and Gal-8 localization in the intermediate cells. Adenomas were separable from malignancy by a consistent decrease in the labelling index (LI) for Gal-7 and Gal-8 (LI Gal-7, P<10(-6) ; LI Gal-8, P=0.001). When present, staining for the tumour suppressor p16(INK4a) coincided with Gal-1 presence., Conclusions: Expression profiling of the four tested galectins in salivary gland tumours revealed non-uniform staining patterns with discriminatory potential based on intracellular localization and quantitative aspects., (© 2011 Blackwell Publishing Limited.)

Aims: To evaluate cytokeratin (CK) 7/20 expression patterns in salivary gland neoplasia., Methods and Results: Formalin-fixed paraffin embedded tissue from 153 salivary gland tumours were evaluated for CK7/20 immunoreactivity. The tumours included pleomorphic adenoma (n = 24), myoepithelioma (n = 9), papillary cystadenoma (n = 3), oncocytoma (n = 2), adenoid cystic carcinoma (n = 22), mucoepidermoid carcinoma (n = 21), polymorphous low-grade adenocarcinoma (n = 21), carcinoma ex-pleomorphic adenoma (n = 11), acinic cell carcinoma (n = 17), epimyoepithelial carcinoma (n = 7), oncocytic carcinoma (n = 3), hyalinizing clear cell carcinoma (n = 1), papillary cystadenocarcinoma (n = 1), salivary duct carcinoma (n = 3), adenocarcinoma (not otherwise specified) (n = 4) and squamous carcinoma (n = 4). Immunohistochemical procedures were performed using monoclonal antibodies CK7 (OV-TL 12/30), CK20 (Ks 20.8) and M3515 cytokeratin (AE1/AE3) in the presence of appropriate controls. The results were expressed semiquantitatively, according to the estimated percentage of positive tumour cells: 1+, 5-25%; 2+, 26-75%; and 3+, 76-100%. All salivary gland neoplasms showed a CK7+/CK20- immunoprofile ranging from 5 to 100%. Squamous carcinoma showed negative CK7/20 immunoexpression., Conclusions: Although the CK7/20 immunoprofile is not useful in distinguishing the various types of salivary gland neoplasms or between benign and malignant salivary gland tumours, it may facilitate differentiation of primary salivary gland neoplasia from metastatic tumours and squamous carcinoma, and the diagnosis of metastatic salivary gland tumours.

Aims: To investigate cyclin A expression in pleomorphic adenoma (PA) and carcinoma expleomorphic adenoma (CXPA) of the parotid gland with a view to assessing its potential value as a diagnostic marker for CXPA., Methods and Results: Cyclin A expression in PA and CXPA was studied using semiquantitative immunohistochemistry. The epithelial component of the tumours expressed cyclin A in a statistically significantly (P < 0.005) higher number of CXPA cases (86%) compared with the PA cases (39%). Cyclin A was not expressed in normal salivary tissues of PA and CXPA., Conclusions: High cyclin A expression is a useful marker for the pathological diagnosis of CXPA.

Fifty-four dogs with nasal tumours were included in this study. Based on histopathology 52 tumours were malignant (36 epithelial and 16 mesenchymal) and two were benign (one oncocytoma and one pleiomorphic adenoma). Malignancy was significantly more frequently diagnosed by imprint cytology (81 per cent of the cases) than by brush cytology (56 per cent). Brush cytology was a significantly more sensitive technique in epithelial than in mesenchymal tumours, while the sensitivity of imprint cytology was not affected by the histological type. Brush cytology determined an epithelial origin in 88 per cent of epithelial tumours, and imprint cytology in 90 per cent. In mesenchymal tumours, the scores were significantly lower, the histological type being determined in only 20 per cent and 50 per cent, using brush and imprint cytology, respectively.

Between 1987 and 1993 14 patients with a parapharyngeal space tumour were imaged by magnetic resonance imaging (MRI). The vagal body tumours, presenting in the poststyloid compartment, all showed flow voids with anterior and medial displacement of the internal carotid artery. None of the salivary gland tumours, all presenting in the prestyloid compartment with posterior displacement of the internal carotid artery, showed flow voids. MRI is superior compared with other modalities in evaluating the differential diagnosis, especially regarding vascular vs non-vascular tumours. It should encompass T1 SE images to assess the presence or absence of flow voids. In vascular tumours angiography must be used to assess feeding vessels, multiplicity, and sides involved. T1 GE images are useful as they allow superior identification of the internal carotid artery and its relation with the tumour accordingly. In addition to T1 SE images, T2 SE images may help in the evaluation of the differential diagnosis. In all non-vascular tumours aspiration cytology is required to differentiate between benign and malignant disease.

An unusual coexpression of glial fibrillary acid protein (GFAP), keratin and vimentin occurs in pleomorphic adenoma of salivary gland. We designed this study to see if coexpression of the markers was also present in monomorphic adenoma of the salivary gland and whether monomorphic adenoma could be distinguished from other salivary gland tumours by marker studies. Immunocytochemical markers were used on fine needle aspiration samples from four cases of monomorphic adenoma, two cases of oncocytic adenoma, three cases of adenoid cystic carcinoma and four cases of pleomorphic adenoma. While positivity for cytokeratin, vimentin and S-100 was consistently found in all cases of monomorphic adenoma, only cytokeratin was expressed in adenoid cystic carcinoma. In pleomorphic adenoma, GFAP, cytokeratin and vimentin were coexpressed while in cases of oncocytic adenoma none of the markers was localized. Thus, it appears that by using a combination of GFAP, cytokeratin, vimentin and S-100 a distinction between these neoplasms may be possible. However, a larger study is needed to establish the usefulness of this approach.

The anatomy of the parapharyngeal space is described and experience with 23 patients with parapharyngeal tumours seen over a 10-year period is reported. Despite reaching a large size, these tumours may be relatively asymptomatic, or be discovered incidently. CT scan, MRI, arteriography and fine needle aspiration are useful in establishing a diagnosis. The most common histological type (13/23 patients) was pleomorphic adenoma and these tumours were managed by transoral removal if small, or a combined transoral-external approach if large. No patient required a mandibulotomy for access and no benign tumour recurred. The outcome was poor in the 5 patients with malignant tumours and a more radical approach, midline mandibulotomy, should be considered if malignancy is suspected.

Thirty-one patients with a suspected inflammatory or neoplastic lesion of a major salivary gland were investigated with ultrasound, and in 27 of them sialography was carried out in addition. The results of the diagnostic procedures were compared. Lesions of the gland parenchyma and intra and extra-glandular duct ectasia were demonstrated by ultrasound. Salivary stones were demonstrated by this method and ultrasound allowed assessment of periglandular structures. Sialography is indispensable for detailed assessment of the salivary ducts. The present report shows that ultrasound is superior to sialography in the assessment of salivary gland disease. The investigation is non-invasive, cheap, and requires neither contrast nor radiation and can be repeated at will for follow-up.