Diagnostic difficulties in the interpretation of fine needle aspirates of salivary gland lesions: the problem revisited

Diagnostic difficulties in the interpretation of he needle aspirates of salivary gland lesions: the problem revisited
Cases of salivary gland lesions ( n =325), mainly neoplastic but including a small number of non-neoplastic lesions, investigated by fine needle aspiration (FNA) and with histological correlation, are reviewed. The review identified a number of differential diagnostic problems which are discussed in some detail. One false-positive and eight false-negative diagnoses had been made resulting in a 99.5% specificity and a 85.5% sensitivity. If type-specific diagnoses are made only when all defined diagnostic criteria are present and if any uncertainty is clearly conveyed to the clinician, FNA is a safe and accurate tool in the investigation of salivary gland lesions.     

Oncocytic nodule. An unusual case of a submaxillary gland mass in an elderly patient

A submaxillary gland mass in an elderly woman was diagnosed as an oncocytic nodule by cutting needle biopsy and was followed with serial fine needle aspiration (FNA) biopsy for seven years. All specimens showed pure populations of oncocytes. Oncocytic nodules of the salivary gland are unusual lesions that may represent hyperplastic proliferations or true neoplasms. Although oncocytic metaplasia is commonly identified in the salivary glands of elderly patients, oncocytes rarely form masses that are targets for needle biopsy. This case suggests that FNA biopsy may be a useful method of evaluating salivary gland lesions in elderly patients who are not candidates for surgery.     

Fine needle aspiration biopsy diagnosis of mucoepidermoid carcinoma. Statistical analysis

Fine needle aspiration (FNA) biopsy is an increasingly popular method for the evaluation of salivary gland tumors. Of the common salivary gland tumors, mucoepidermoid carcinoma is probably the most difficult to diagnose accurately by this means. A series of 96 FNA biopsy specimens of salivary gland masses, including 34 mucoepidermoid carcinomas, 51 other benign and malignant neoplasms, 7 nonneoplastic lesions and 4 normal salivary glands, were analyzed in order to identify the most useful criteria for diagnosing mucoepidermoid carcinoma. Thirteen cytologic criteria were evaluated in the FNA specimens, and a stepwise logistic regression analysis was performed. The three cytologic features selected as most predictive of mucoepidermoid carcinoma were intermediate cells, squamous cells and overlapping epithelial groups. Using these three features together, the sensitivity and specificity of accurately diagnosing mucoepidermoid carcinoma were 97% and 100%, respectively.     

Fine needle aspiration cytology of parotid sarcoidosis

Granulomatous lesions of the salivary gland are rare; as such, there have been few reports of the cytologic features of granulomatous sialadenitis in general, and salivary gland sarcoidosis in particular. A case of systemic sarcoidosis involving both parotid glands, diagnosed initially by fine needle aspiration (FNA) cytology, is presented. The specific cytologic features included histiocytes of both epithelioid and giant multinucleated types, without background necrosis. The FNA cytologic differential diagnosis of bilateral parotitis is discussed.     

Posters. P19 Cervical carcinoma with metastases to the tympanic membrane: an unusual presentation

Introduction Fine needle aspiration (FNA) is a well‐established diagnostic technique which is frequently used to diagnose head and neck neoplasms. Clinical decisions concerning treatment of malignant salivary gland tumours, the extent of surgery and advisability of pre‐operative irradiation can be helped by prior knowledge of tumour type. Aim The aim of this study was to do an audit of all salivary gland FNAs carried out in Beaumont Hospital over a 14‐year period. Methods All salivary gland FNAs between 1989 and 2002 were reviewed. Where available, the corresponding follow‐up histological specimens were studied. Results During this 14‐year period, 305 patients with salivary gland lesions had FNA of the lesion performed. The total number of aspirates performed was 343. Of these, 184 had histologies available for follow‐up. Eighty‐nine aspirates were reported as inadequate; 89 as inflammatory, normal or consistent with cyst contents. One hundred and thirteen aspirates were diagnosed as a benign entity. Thirty‐three aspirates were reported as malignant (21 of which were felt to be primary to the salivary gland and 12 metastatic). Sixteen cases were called suspicious. Good correlation between FNA findings and histology was seen in the majority of cases (145 of 183). Some diagnostic problem areas were identified. These included the following: lymphomas (seven called benign on FNA), Warthin's tumour (seven not diagnosed or misdiagnosed on FNA) and mucoepidermoid carcinoma (one reported as pleomorhic adenoma and one as benign/cystic on FNA). Seven pleomorphic adenomas were not diagnosed on FNA pre‐operatively, predominantly due to inadequacy of the specimen. Three other malignancies (acinic cell carcinoma, lymphoepithelial carcinoma and carcinoma ex‐pleomorphic adenoma), while not diagnosed on FNA, were called suspicious, with re‐biopsy advised. Conclusion FNA cytology of salivary glands is an accurate method for evaluation of both benign and malignant lesions, enabling optimum surgical and adjuvant therapy decision‐making pre‐operatively. Well‐defined problem areas are identified and, therefore, clinicopathological correlation is required in these cases.     

Adenoid cystic carcinoma metastatic to the lung. Report of a case diagnosed by fine needle aspiration biopsy cytology

Cytologic examination of a fine needle aspiration (FNA) biopsy specimen served to diagnose a lung metastasis in a patient with an adenoid cystic carcinoma primary in a minor salivary gland of the hard palate. The aspiration cytologic features of the metastatic adenoid cystic carcinoma were similar to those of primary adenoid cystic carcinoma, including uniform tumor cells with scant cytoplasm surrounding transparent, mucoid spherical bodies. FNA biopsy cytologic diagnosis of metastatic adenoid cystic carcinoma is accurate, particularly if mucoid spherical bodies are present.     

Cytopathology and diagnostics of Warthin's tumour

Warthin's tumour (WT) is a benign epithelial salivary tumour, one type of salivary adenoma. Histologically, WT is structured of two components, epithelial tissue that often lines cystic formations and lymphoid tissue in the tumour stroma. FNA is a reliable diagnostic approach in the diagnosis of salivary gland lesions allowing a highly accurate categorization of benign tumour‐like lesions, benign tumours and malignant tumours. In the proposed Milan reporting system of salivary gland lesions, WT is categorized in the IVA group of benign neoplasms. Accurate cytological diagnosis is straightforward when three characteristic components are present: oncocytes, either isolated or associated in clusters, lymphocytes and lymphoid cells and often an inflammatory/necrotic‐like substance. Also, specific features of scintigraphy and radiological imaging contribute to the diagnosis of WT. WT is categorized according to Seifert G. et al in 4 types, depending on the proportions of the epithelial component and lymphoid stroma. Differential cytopathological and pathohistological diagnosis include other salivary gland lesions with lymphoid, oncocytic epithelial and cystic components. In some cases, such as the metaplastic WT variant, there are additional cytopathological and histological diagnostic difficulties. Moreover, bilateral, multicentric or multiple and infrequently seen extra‐salivary localizations of WT are associated with further cytopathological diagnostic difficulties. Also, a rare possibility of malignant transformation of the epithelial or lymphoid component of WT as well as possible association with other primary tumours remains a challenge in accurate cytopathological and histological diagnosis of WT.     

Fine needle aspiration in a malignant lymphoepithelial lesion: a case report

BACKGROUND: A primary malignant lymphoepithelial lesion (MLEL) of the salivary gland is a rare tumor. Though histologic morphology of this lesion is well documented, the cytologic findings regarding fine needle aspiration (FNA) are not yet well described. CASE: A 56-year-old Thai woman from Udonthanee was admitted to Srinagarind Hospital with a 2-year history of a painless mass in the left parotid gland. FNA of the left parotid mass was performed, and findings suggestive of malignancy were discovered. A wide local excision was performed 1 year later, and MLEL with metastasis to the regional lymph nodes was diagnosed by histopathology. CONCLUSION: We report our first experience of cytologic findings from FNA of histologically diagnosed MLEL. The aspirate comprised groups of cohesive and isolated malignant epithelials with a background of numerous lymphocytes. Cytotechnologists should be reminded of this rare lesion when confronted with a lymphocytic background from either benign or malignant lesions.     

Papillary-cystic variant of acinic cell carcinoma of the salivary gland diagnosed by fine needle aspiration biopsy. A case report

BACKGROUND: Fine needle aspiration (FNA) biopsy is reliably used to classify most conditions involving the salivary glands. It is useful for establishing, or at least suggesting, the diagnosis in unusual cases or narrowing the differential diagnosis. CASE: A 25-year-old male presented with a slowly enlarging mass of the left parotid. FNA biopsy of the parotid gland was performed, and a diagnosis of papillary-cystic variant of acinic cell carcinoma was suggested. The patient underwent incomplete resection of the lesion, which was interpreted as acinic cell carcinoma. CONCLUSION: Papillary-cystic variant of acinic cell carcinoma is rarely seen, especially in young people. FNA biopsy is a useful diagnostic procedure that can help diagnose this relatively uncommon type of salivary gland neoplasm and guide its management.     

Small cell undifferentiated carcinoma of the parotid gland. Cytologic, histologic, immunohistochemical and ultrastructural features of a neuroendocrine variant

A case of primary small cell undifferentiated carcinoma (SCUC) of the parotid gland, diagnosed initially by fine needle aspiration (FNA) cytology and confirmed by histology, immunohistochemistry and transmission electron microscopy (TEM), is presented. The FNA cytologic features that enabled an accurate diagnosis of this rare salivary gland tumor included nuclear granularity and markedly angular nuclear molding of numerous small cells that were usually present as large syncytia in an inflammatory background. Numerous mitotic figures were also present in this vascular lesion. These features were also evident in the surgical specimens. Immunohistochemistry demonstrated neuron-specific enolase positivity while TEM demonstrated intracytoplasmic neurosecretory granules in this case, indicating a neuroendocrine derivation for this neoplasm instead of the more usual origin of salivary gland SCUCs in ductal epithelial or myoepithelial tissue.     

Fine needle aspiration cytology of a sebaceous lymphadenoma: a case report

BACKGROUND: Sebaceous lymphadenoma is a rare, benign neoplasm, histologically characterized by proliferating islands of epithelium with sebaceous glandular differentiation in a dense, lymphocytic background. The parotid gland is the most common site, and the patient usually presents with a well-circumscribed, enlarging and painless mass. Primary sebaceous lesions of the salivary glands are very rare entities and must be differentiated from more common, potentially malignant tumors. CASE: A 75-year-old male presented with a 6-month history of a mass in the tail of the parotid gland. The mass was not fixed or tender to palpation, was well delineated and measured 4 cm in greatest dimension. Fine needle aspiration (FNA) revealed a mixed population of large and small lymphocytes, including plasma cells and occasional tingible body macrophages. Scattered among the lymphocytes were 3-dimensional, cohesive aggregates of epithelial cells, many demonstrating the characteristic cytoplasmic vacuolization of sebocytes, surrounded by layers of basaloid cells. No mitoses or cellular pleomorphism was identified. These findings suggested a sebaceous lymphadenoma, confirmed on biopsy. CONCLUSION: Although sebaceous lymphadenoma is encountered infrequently, FNA findings can result in its accurate diagnosis.     

Necrosis of a Warthin's tumor following fine needle aspiration

Fine needle aspiration (FNA) biopsy of a parotid mass demonstrated features diagnostic of a Warthin's tumor. Resection of the mass six weeks later yielded a necrotic nodule lacking distinguishing characteristics. This case illustrates infarction of the target lesion, a rare complication of FNA biopsy of salivary gland neoplasms. Correlation of the histology with the cytology will prevent diagnostic difficulties in such instances.     

Human kallikrein 6 expression in salivary gland tumors.

Human kallikrein 6 (hK6), also known as zyme/protease M/neurosin), is expressed in many normal glandular tissues. The aim of this study was to determine whether hK6 is expressed in salivary gland tissues and salivary gland tumors (both benign and malignant), using an immunohistochemical method. Pleomorphic adenomas (PA), adenoid cystic carcinomas, polymorphous low-grade adenocarcinomas, acinic cell carcinomas, mucoepidermoid carcinomas, and adenocarcinomas not otherwise specified of both minor and major salivary glands were examined. Cells lining duct-like structures and non-duct-like cells were scored. Only in PA of minor salivary gland origin was overall staining higher in duct-like than in non-duct-like cells. In all other tumors exhibiting both types of cells, hK6 staining was similar in both duct-like and non-duct-like cells. Tumors that exhibited non-duct-like cells only also exhibited cytoplasmic staining. Results of this study show that salivary gland tumors express hK6, apparently downregulated in comparison with normal salivary gland tissue, and that this expression is not specific for any of the tumors studied.     

Salivary duct carcinoma of the parotid gland: report of a rare case with a comparative study of aspiration cytology and histomorphology

BACKGROUND: Salivary duct carcinomas affecting primarily the parotid gland are extremely rare (0.2-2% of all salivary gland tumors). These carcinomas are considered to be of high grade malignancy, with mortality in up to 70% of cases. They usually affect elderly males and less often young adults. Despite the fact that the histomorphologic characteristics of this tumor are always necessary for its classification, several authors have reported that the cytopathologic approach, using fine needle aspiration (FNA) cytology, can establish the final diagnosis. The aim of this paper is to present a rare case of salivary duct carcinoma of the parotid gland with no typical microscopic findings that was diagnosed by FNA cytology through a combination of techniques on biopsy material. CASE: A 56-year-old male presented with a right parotid mass measuring 6 cm in diameter. The mass appeared to expand subcutaneously and infiltrate the skin of the neck region. Biopsy material from both the mass and skin was obtained using FNA and processed with conventional, cell block and liquid-based cytology techniques. A core biopsy was also performed on the mass for histologic evaluation. CONCLUSION: The findings were consistent with a salivary duct carcinoma of the parotid gland and were confirmed by the histologic report. FNA cytology combined with such techniques as liquid-based cytology provides the potential for the final diagnosis. Liquid-based cytology can improve the cellular morphology of the material and allows immunocytochemistry and other diagnostic techniques. The application of such techniques is significantly restricted by conventional processing; thus, combining liquid-based cytology with other techniques expands the boundaries of cytology as a diagnostic test.     

Fine needle aspiration cytology of head and neck masses. Seven years' experience in a secondary care hospital

OBJECTIVE: To study the value of fine needle aspiration (FNA) in the diagnosis of head and neck masses in a secondary care hospital. STUDY DESIGN: FNA from 225 patients with head and neck masses were reviewed. The results were analyzed, according to anatomic location, into 3 groups: inflammatory, congenital and neoplastic. FNA diagnoses were retrospectively correlated with available histologic findings or with the outcome of treatment. Accuracy, sensitivity, specificity, positive predictive value and negative predictive value in the diagnosis were computed. The numbers of lymph node biopsies performed before and after introduction of the procedure were compared. RESULTS: The most common diagnoses were reactive/nonspecific lymphadenitis and tuberculous (TB) lymphadenitis (33% and 21%, respectively). Sensitivity and negative predictive value for TB were 97% and 93%, respectively. The next most common masses were malignant neoplasms, cysts, benign neoplasms and sialadenitis, in 13%, 11%, 9% and 5%, respectively. Carcinomas metastatic to the lymph node were the most common type of cancer, followed by lymphoma and salivary gland carcinoma. The primary site of metastatic carcinomas were nasopharynx (44%) and thyroid (22%). The sensitivity and negative predictive values for the diagnosis of cancer were 95% and 96%, respectively, but reached 100% when lymphoma was excluded. The introduction of FNA reduced the number of lymph node biopsies performed in this hospital by 90%. CONCLUSION: FNA of head and neck masses proved to be a very useful diagnostic tool in separating inflammatory lesions (no surgical excision required) from cystic and neoplastic lesions. It enhanced surgical planning for malignant diseases, allowing rapid referral of lymphomas and cancer cases to tertiary care centers for management. FNA is simple, cost effective and suitable for developing countries and small, secondary care hospitals with limited resources. Skilled personnel and routine audits are the keys to success.     

Human kallikrein 3 (prostate specific antigen) and human kallikrein 5 expression in salivary gland tumors

The human kallikrein 5 protein (hK5) is expressed in many normal tissues, most notably in skin, breast, salivary gland and esophagus. It has also been shown to be a potential biomarker for breast, ovarian and testicular cancer. Human kallikrein 3 (hK3; prostate-specific antigen) is the most useful marker for adenocarcinoma of the prostate gland. The aim of this study was to determine whether hK3 and hK5 are expressed in salivary gland tissues and salivary gland tumors (both benign and malignant), in order to compare normal with tumor tissues. Pleomorphic adenomas, adenoid cystic carcinomas, polymorphous low-grade adenocarcinomas, acinic cell carcinomas, mucoepidermoid carcinomas and adenocarcinomas not otherwise specified of both minor and major salivary glands were examined. The results of this study indicate that most salivary gland tumors do not show high levels of expression of hK5. Staining was most prominent in keratinizing epithelia in pleomorphic adenomas. hK3 is not expressed in salivary gland tumors.     

Investigation of Susceptibility Genes Triggering Lachrymal/Salivary Gland Lesion Complications in Japanese Patients with Type 1 Autoimmune Pancreatitis

Autoimmune pancreatitis (AIP) is a unique form of chronic pancreatitis characterized by high serum IgG4 concentration and a variety of complicating extra-pancreatic lesions. In particular, lachrymal/salivary gland lesions tend to manifest in a highly active AIP disease state, and several genes are speculated to be associated with the onset of this complication. We therefore searched for candidate susceptibility genes related to lachrymal/salivary gland lesions in a genome-wide association study (GWAS) with the GeneChip Human Mapping 500k Array Set (Affymetrix, CA) that was followed by fine mapping of additional single nucleotide polymorphisms (SNPs) in strongly significant genes with TaqMan assays. Venous blood samples were obtained from 50 type 1 AIP patients with lachrymal/salivary gland lesions (A group) and 53 type 1 AIP patients without (B group). The mean values of IgG and IG4 were both significantly different (P<0.05) between the groups. SNPs that showed a significant association with the A group at the genome-wide level (P<0.0001) were identified and subsequently used in fine SNP mapping of candidate genes. In total, five SNPs had a positive association with complicated AIP (most notably rs2284932 [P=0.0000021]) and five SNPs possessed a negative association (particularly rs9371942 [P=0.00000039]). Among them, KLF7, FRMD4B, LOC101928923, and MPPED2 were further examined for complication susceptibility using additional SNPs that were not included in the GWAS. Individual genotyping of KLF7 rs2284932 revealed that the frequency of the minor C allele was significantly increased (P=0.00062, Pc=0.0018, OR=2.98, 95%CI=1.58-5.65) in group A. The minor T allele of rs4473559 in FRMD4 demonstrated a significant association in the A group (P=0.00015, OR=3.38, 95%CI=1.77-7.65). In the LOC101928923 gene, the frequency of the minor C allele of rs4379306 was significantly decreased in group A in both TaqMan and GWAS analyses. Lastly, the minor C allele of MPPED2 rs514644 carried a significantly increased risk of complications. These four genes may be linked with the onset of lachrymal/salivary gland lesions in type 1 AIP patients and require further study.     

Fine needle aspiration biopsy of the parotid gland. Diagnostic problems and 2 uncommon cases

OBJECTIVE: To describe the diagnostic problems and present our findings in 2 uncommon tumors, malignant myoepithelioma and small cell undifferentiated carcinoma, by examining fine needle aspiration (FNA) biopsies of parotid gland masses. STUDY DESIGN: The study group consisted of 34 females and 41 males 12-80 years old, with an average of 44. Excluding inflammatory results, all adequate aspirates were confirmed histologically to determine the correlation. RESULTS: Sensitivity of FNA cytology was 91%, with specificity of 98%. We encountered some difficulties, and therefore misdiagnoses, in evaluating specific neoplasms, such as adenoid cystic carcinoma and Warthin's tumor, which have well-established cytologic diagnostic criteria. Two cases of uncommon neoplasms of salivary glands, small cell undifferentiated carcinoma and malignant myoepithelioma, were cytologically found to be malignant but not further classified. In addition, tuberculous parotitis, with its well-defined features, should to be referred since unnecessary surgery can be avoided by using FNA cytology. CONCLUSION: FNA is a sensitive and specific diagnostic tool for parotid gland masses. However, specific classification of neoplasms may sometimes be difficult. Pathologists should be aware of specific entities, such as malignant myoepithelioma, when evaluating high grade neoplasms.     

Polyploidy In Pleomorphic Adenomas With Cytological Atypia

Occasionally, in fine-needle aspirates of pleomorphic salivary gland adenomas, considerable cytonuclear atypia is present, which may give rise to a false-positive diagnosis. In this study DNA cytophotometry was performed on Feulgen restained smears prepared from material obtained by needle aspirates of normal salivary glands (n = 4), pleomorphic adenomas with (n = 5) and without (n = 4) atypia and a carcinoma in a pleomorphic adenoma. The results showed a clear diploid DNA histogram in the specimens of normal salivary gland and pleomorphic adenomas without atypia. In contrast, in the pleomorphic adenomas with atypia a distinct polyploid pattern was present in three out of the five DNA histograms with DNA values in 2c, 4c and 8c ranges. In two of these cases a 16c peak was also present and in the two remaining cases tetraploidy was demonstrated. In the carcinoma a main stemline at 4c was found. This report once more emphasizes the possible atypia which may be present in FNA of pleomorphic adenomas of the salivary gland. The atypia is due to polyploidy in a histologically benign tumour.