Glial fibrillary acid protein immunoreactivity in fine-needle aspiration of salivary gland lesions: a useful adjunct for the differential diagnosis of salivary gland neoplasms

The value of immunocytochemical staining for glial fibrillary acid protein (GFAP) in salivary gland lesions was investigated in 33 fine-needle aspiration smears. The study utilized cytologic material from ten pleomorphic adenomas, six normal salivary glands, three cases of chronic sialadenitis, three Warthin's tumors, two adenoid cystic carcinomas, three adenocarcinomas, two malignant mixed tumors, one acinic cell carcinoma, and three mucoepidermoid carcinomas. All tested pleomorphic adenomas stained positively. The adenoid cystic carcinomas and the cases of chronic sialadenitis, along with the low-grade mucoepidermoid carcinoma, were negative for GFAP immunoreactivity. These results indicate that immunostaining for GFAP may be a valuable aid in the diagnosis of pleomorphic adenoma; GFAP may be especially helpful in distinguishing those cases for which the differential diagnosis includes the aforementioned salivary gland neoplasms.     

Fine-needle aspiration cytology of lymphangioma of the parotid gland in an adult

Lymphangioma or cystic hygroma is an uncommon benign congenital tumor of lymphatics that is seen in children and, rarely, adults. Lymphangioma primarily involving the parotid gland is an extremely uncommon occurrence in adults. We report on the cytologic findings of a parotid lymphangioma in a 34-yr-old man which showed 13 cc of yellow fluid with red blood cells, lymphocytes, and rare fragments of benign-appearing salivary gland epithelium. The differential diagnosis of cystic parotid gland lesions in adults may include Warthin's tumor, lymphoma, benign lymphoepithelial lesions, branchial cleft cysts, chronic sialadenitis, cystic low-grade mucoepidermoid carcinoma, and cystic pleomorphic adenoma. In this case, the fine-needle aspiration findings along with the magnetic resonance imaging (MRI) findings of a multiloculated cystic mass in the parotid gland allowed the diagnosis of lymphangioma.     

Aspiration cytology of salivary glands

Although mass lesions of the salivary glands are readily accessible to examination by fine-needle aspiration, the use of this modality has been limited. In part, this may be related to the difficulty differentiating between benign and malignant neoplasms in some cytologic specimens. Marked atypia in reactive non-neoplastic epithelium also could result in a false-positive diagnosis. In addition, aspiration of hypocellular material from cystic neoplasms, eg, well-differentiated mucoepidermoid carcinoma, may lead to false-negative cytologic reports. However, the diagnostic specificities claimed by a number of authors for this method are excellent. Furthermore, aspirates of certain specific neoplasms may yield highly distinctive cellular samples, such as the uniform tumor cells and extracellular hyaline spheres in many adenoid cystic carcinomas. Another example is the characteristic transition between the epithelial and myoepithelial cells of pleomorphic adenomas, which may contain prominent myxoid matrical material. With the increasing recognition of such features, the reported levels of diagnostic accuracy are improving.     

Fine needle aspiration biopsy of salivary gland tumours. Problems and pitfalls

A review of all fine needle aspiration biopsies of salivary gland lesions performed at the Flinders Medical Centre during a 9-year period revealed a number of cases in which there was a discrepancy between the initial cytology report and the definitive diagnosis by histology examination. The most common problem was that of atypical features in pleomorphic adenoma, raising a suspicion of a low-grade malignant tumour in 4 cases. One mucoepidermoid carcinoma and one acinic cell carcinoma had been wrongly diagnosed as Warthin's tumours on the basis of the presence of sheets of bland epithelial cells with oncocyte-like cytoplasm. One trabecular monomorphic adenoma was misdiagnosed as adenoid cystic carcinoma, and one adenoid cystic carcinoma as pleomorphic adenoma. The cytologic patterns of these cases are presented and discussed.     

涎腺细针吸取细胞学分类诊断价值和存在问题

目的 分析涎腺疾病细针吸取细胞学（FNAC）形态学特点和准确分类,探讨涎腺FNAC的诊断价值和存在问题。方法 回顾113例涎腺FNAC形态学特征、免疫表型和分类诊断,并结合临床、组织病理学分析。结果 FNAC失败2例,诊断非肿瘤12例、肿瘤99例（良性肿瘤82例,恶性17例）。富于细胞多形性腺瘤、腺样囊性癌和基底细胞腺瘤相似,鉴别诊断困难。腮腺淋巴上皮癌与未分化型鼻咽型鳞状细胞癌转移完全一致,鉴别需结合临床分析。与组织学比较发现,FNAC误诊3例,分别为淋巴结反应性增生疑为非霍奇金淋巴瘤、黏液表皮样癌诊为“少量异型细胞”和淋巴上皮癌疑为良性淋巴上皮病变。FNAC区分良、恶性准确率97．4％（110／113）,良性病变99．0％（95／96）,恶性肿瘤88．2％（15／17）。总体分类准确率90．3％（102／113）,特异性91．9％（102／111）;良性病变准确率91．7％（88／96）,特异性92．6％（88／95）;恶性肿瘤准确率82．4％（14／17）,特异性87．5％（14／16）。结论 FNAC诊断涎腺良、恶性病变敏感、可靠,可提供准确的分类诊断,但诊断某些肿瘤仍有局限性,需要活检证实。     

Nucleolar organizer regions in malignant salivary gland tumors.

Proliferative activity of carcinomas arising from salivary glands was analyzed by enumeration of argyrophilic nucleolar organizer regions (AgNORs). The mean numbers of AgNORs in the various tumors were as follows: mucoepidermoid carcinoma, 2.20; acinic cell carcinoma, 2.51; adenoid cystic carcinoma (ACC), 2.57; carcinoma in pleomorphic adenoma, 1.00 (benign component) and 3.99 (cancer-bearing area); salivary duct carcinoma, 4.49; polymorphous low-grade adenocarcinoma, 3.37; sebaceous carcinoma, 2.57; oncocytic carcinoma, 4.63; adenocarcinoma, 4.53. Cells of most tumors showed heterogeneous activity within the same tumor. In mucoepidermoid carcinoma, the mucous cells had suppressed activity in comparison with the epidermoid cells and intermediate cells. In ACC, the activity of the tumor cells increased according to growth pattern in the order tubular, glandular and solid. In carcinoma in pleomorphic adenoma, vigorous proliferative activity was observed in the malignant component, whereas less active cells were seen in the myxoid or chondroid matrix. AgNOR staining was useful for distinguishing benign from malignant regions in carcinoma in pleomorphic adenoma. Our results suggest that mucoepidermoid carcinoma, acinic cell carcinoma and ACC, except for that with a solid growth pattern, may be considered as low-grade malignancies, whereas solid-type ACC, the cancer component in carcinoma in pleomorphic adenoma and some of the other carcinomas have high-grade malignant behavior.     

Fine-needle aspiration cytology of salivary gland: a review of 341 cases

Three hundred and forty-one salivary gland fine-needle aspiration (FNA) cytology specimens taken over a 6-yr period were reviewed and correlated with clinical and/or histological findings. The aspirates were derived from parotid gland (212 cases), submandibular gland (124 cases), and minor salivary gland (5 cases). The major diagnostic categories were unsatisfactory (10 cases), normal (100 cases), sialadenitis (74 cases), cyst (34 cases), lipoma (5 cases), pleomorphic adenoma (55 cases), Warthin's tumor (36 cases), and malignancy (27 cases). The latter included 14 primary salivary neoplasms (4 lymphomas of mucosa-associated lymphoid tissue (MALT) type, 3 adenocarcinomas, 2 squamous carcinomas, 2 adenoid cystic cacinomas, and one case each of carcinoma ex pleomorphic adenoma, undifferentiated carcinoma, and high-grade mucoepidermoid carcinoma), and 13 metastases, 9 of which were derived from squamous carcinomas of head and neck origin. Clinicopathological review showed that 88 of 91 (97%) benign epithelial tumors and 27 of 31 (87%) malignant neoplasms with adequate FNA sampling were accurately diagnosed cytologically. False-negative results were caused by sampling error (7 cases), most notably in cystic tumors, or were due to misinterpretation of uncommon neoplasms (3 cases). The overall sensitivity, specificity, and accuracy were 92%, 100%, and 98%, respectively. FNA cytology provides accurate diagnosis of most salivary gland lesions and contributes to conservative management in many patients with nonneoplastic conditions.     

Cytologic diagnosis of adenoid cystic carcinoma of salivary glands.

The cytomorphologic features in fine-needle aspiration (FNA) biopsies from 31 primary and 33 recurrent adenoid cystic carcinomas (ACC) were investigated. The correct FNA diagnosis was established in 24 of 31 primary ACC (77%). The diagnostic clue in aspirates from ACC are large globules of extracellular matrix, partially surrounded by basaloid tumor cells. In FNAs with predominance of basaloid tumor cells, but lacking characteristic globules, all other benign and malignant salivary gland tumors of epithelial-myoepithelial differentiation should be considered in the cytologic diagnosis. Pleomorphic adenoma is most frequently confused with ACC, and therefore, the cytologic findings in FNAs from 50 pleomorphic adenomas were compared with those diagnosed as ACC. Furthermore, rare neoplasms of salivary glands with epithelial-myoepithelial cell differentiation, including basal-cell adenoma and carcinoma, epithelial-myoepithelial carcinoma, and polymorphous low-grade adenocarcinoma, as well as some nonsalivary gland neoplasms presenting an adenoid cystic pattern, must be considered. The cytologic features of these entities are discussed in detail with respect to the cytologic diagnostic criteria of ACC.     

Benign lymphoepithelial cysts of the parotid gland. A histologic, cytologic, and ultrastructural study

Five cases of benign lymphoepithelial cysts (BLCs) of the parotid gland are reported, and the histologic, aspiration cytologic, and ultrastructural findings are described in detail. These uncommon parotid lesions contain epithelium-lined cystic spaces encased by abundant lymphoid tissue with germinal centers. The epithelium was "mucoepidermoid" in three of our cases and squamous in two. Familiarity with the morphologic features of BLCs should make it possible to distinguish them from similar-appearing cystic lesions, especially low-grade cystic mucoepidermoid carcinoma and cystic types of benign lymphoepithelial lesion (so-called Mikulicz's disease). These distinctions, however, are difficult on aspiration cytology specimens.     

Gross cystic disease fluid protein-15 in salivary gland tumors

Gross cystic disease fluid protein-15 (GCDFP-15) is a 15-kd glycoprotein that is expressed by normal apocrine epithelia and in a majority of breast carcinomas. However, recent studies have demonstrated that this substance is also present in tumors of the salivary glands, sweat glands, and prostate gland. To determine whether the expression of CGDFP-15 might aid in the differential diagnosis of salivary gland lesions, the anti-GCDFP-15 monoclonal antibody D6 was applied to paraffin sections of 133 such neoplasms. Benign tumors (76% reactive) were more often labeled than malignant lesions (28% reactive) by this antibody; overall, 53 (41%) of 133 cases were positive for GCDFP-15. Notably, the tubuloglandular components in 17 (81%) of 21 pleomorphic adenomas were reactive, but no example of either adenoid cystic carcinoma or polymorphous low-grade adenocarcinoma were labeled. In contrast, 24% of adenocarcinomas stained with this antibody. The apparent expression of GCDFP-15 by a spectrum of salivary gland tumors supports their biologic relationship to lesions of the cutaneous apocrine glands and breast. Furthermore, the demonstration of this determinant may be of use in suggesting the salivary gland nature of poorly differentiated carcinomas of the head and neck, and it may facilitate the separation of pleomorphic adenoma from histologically similar malignant neoplasms in the salivary glands themselves.     

Mucin production by pleomorphic adenomas of the parotid gland: a cytologic spectrum

Mucinous salivary gland aspirations represent a special differential diagnostic problem. Considerations include pleomorphic adenoma, Warthin's tumor, chronic obstructive sialadenitis, and low-grade mucoepidermoid carcinoma. We herein discuss three cases that illustrate a spectrum of mucin production by pleomorphic adenomas. The literature is reviewed, and the possible distinction of pleomorphic adenoma from low-grade mucoepidermoid carcinoma is considered.     

Fine-needle aspiration biopsy of the salivary gland: Problem cases

Among 582 fine-needle aspiration (FNA) biopsies of major and minor salivary glands performed between 1974 and 1990, lack of cytological histologic correlation was noted in 21 cases. Of these, the cause in 10 FNAs was inadequate cytological sampling of the lesion. [One case of malignant hemangiopericytoma was tentatively diagnosed as a monomorphic adenoma on FNA, a polymorphic T-cell lymphoma was diagnosed as granulomatous inflammation on aspiration biopsy, a benign lymphoepithelial lesion was diagnosed as a reactive lymph node, a branchial cleft cyst was called benign mixed tumor (BMT), one case of chronic sialoadenitis was called BMT by FNA, two cases of benign lymphoepithelial lesion (BLEL) were diagnosed as cystic Warthin's tumor, two low-grade mucoepidermoid carcinomas were called BMT, and a BMT was cytologically diagnosed as a Warthin's tumor with squamous metaplasia versus low-grade mucoepidermoid carcinoma. One case of low-grade mucoepidermoid carcinoma was diagnosed only as a “cyst.”] Review of these cases identifies constant features that permit differentiation between Warthin's tumor and BLEL, and among BMT, mucoepidermoid carcinoma, and chronic sialoadenitis. Despite a few problem cases, FNA of the salivary gland is accurate in the preoperative diagnosis and classification of salivary gland neoplasms.     

High-grade papillary cystadenocarcinoma of the tongue

Aims: Salivary gland tumours of the tongue are rare. The most common type is low-grade mucoepidermoid carcinoma followed by adenoid cystic carcinoma. Papillary cystadenocarcinoma of salivary glands are uncommon lesions with low-grade histological and clinical features. We report a high-grade papillary cystadenocarcinoma in an 80-year-old man who presented with a tongue mass and metastatic disease in the neck. Methods and results: He was treated with partial glossectomy and bilateral neck dissection but developed local and regional recurrences 6 months later. The tumour had a prominent cystic appearance and had areas of necrosis. The cyst lumen was occupied by numerous papillae lined by pseudostratified columnar cells with a high nuclear–cytoplasmic ratio. The cytoplasm was eosinophilic, the nuclei were pleomorphic and exhibited irregular nuclear membranes, vesicular chromatin and prominent eosinophilic nucleoli. The mitotic activity was high and there were occasional abnormal mitotic figures. Metastatic carcinoma was present in four lymph nodes. The differential diagnosis of this unusual lesion includes cystadenoma, salivary duct carcinoma and metastases. Conclusions: This case and a review of the literature indicates that papillary cystadenocarcinomas of salivary gland origin exhibit a wider morphologic spectrum than described in the latest World Health Organization (WHO) classification which defines these lesions as low-grade neoplasms.     

Nucleolar Organizer Regions in Malignant Salivary Gland Tumors

Proliferative activity of carcinomas arising from salivary glands was analyzed by enumeration of argyrophilic nucleolar organizer regions (AgNORs). The mean numbers of AgNORs in the various tumors were as follows: muco-epidermoid carcinoma, 2.20; acinic cell carcinoma, 2.51; adenoid cystic carcinoma (ACC), 2.57; carcinoma in pleomorphic adenoma, 1.00 (benign component) and 3.99 (cancer-bearing area); salivary duct carcinoma, 4.49; polymorphous low-grade adenocarcinoma, 3.37; sebaceous carcinoma, 2.57; oncocytic carcinoma, 4.63; adenocarcinoma, 4.53. Cells of most tumors showed heterogeneous activity within the same tumor. In mucoepidermoid carcinoma, the mucous cells had suppressed activity in comparison with the epidermoid cells and intermediate cells. In ACC, the activity of the tumor cells increased according to growth pattern in the order tubular, glandular and solid. In carcinoma in pleomorphic adenoma, vigorous proliferative activity was observed in the malignant component, whereas less active cells were seen in the myxoid or chondroid matrix. AgNOR staining was useful for distinguishing benign from malignant regions in carcinoma in pleomorphic adenoma. Our results suggest that mucoep-idermoid carcinoma, acinic cell carcinoma and ACC, except for that with a solid growth pattern, may be considered as low-grade malignancies, whereas solid-type ACC, the cancer component in carcinoma in pleomorphic adenoma and some of the other carcinomas have high-grade malignant behavior. Acta Pathol Jpn 42: 727–733, 1992.     

Histologic and fine-needle aspiration cytologic features of polycystic disease of the parotid glands: case report and review of the literature

Polycystic disease of the parotid glands is a rare disorder, with only eight examples to our knowledge being reported in the literature. The disease presents as a painless enlargement of one or both parotid glands and does not appear to be associated with other disease processes within the head and neck, or with polycystic disease of the kidney, pancreas, or congenital fibrosis of the liver. The histology has been well described. The overall glandular architecture is preserved but the lobules are markedly distended by cysts whose lining appears to be intercalated duct in differentiation. Characteristic eosinophilic laminated spheroliths lie in many of the cystic spaces. Aspirate smears are characterized by a relatively clean background in which are distributed histiocytes, red blood cells, and small clusters of ductal epithelial cells. Polycystic disease of the parotid glands must be differentiated cytologically from mucous retention reaction, mucoceles, benign lymphoepithelial cysts, and cystic neoplasms, including Warthin's tumor, low-grade mucoepidermoid carcinoma, cystadenoma, and papillary cystadenocarcinoma.     

Squamous cells in needle aspirates of subcutaneous lesions: a diagnostic problem

Analysis of 1,000 cases of fine-needle aspiration biopsies of subcutaneous lesions revealed 430 cases diagnosed as malignant. Squamous cell carcinoma represented 37% of the malignant neoplasms, and many of these cases were highly differentiated tumors. Although the presence of keratinized squamous cells in superficial aspirates is strongly suggestive of squamous cell carcinoma, other lesions may produce atypical squamous cells on aspiration biopsy and should be considered in the differential diagnosis. These include acanthotic ameloblastomas, metaplastic adenocarcinomas and Warthin's tumors, branchial cleft cysts, odontogenic keratocysts, and epidermal inclusion cysts. Two-needle aspirates from these cases were incorrectly interpreted as squamous cell carcinoma. The cytologic and some of the histologic characteristics of these lesions that may pose a diagnostic problem are presented. Careful evaluation of nuclear and cytoplasmic features, cellular background, clinical findings, and history is essential to avoid a false positive diagnosis of squamous cell carcinoma.     

Myoepithelial cells in salivary gland tumors. An immunohistochemical study

Normal salivary glands and 55 salivary gland tumors were examined by immunostaining (immunoperoxidase [IMP] and immunofluorescence [IMF]) to identify myoepithelial cells (MCs) and speculate on their role in the histogenesis of the tumors. The classic (C) MCs of normal salivary glands stained by IMP with antibodies to cytokeratin and S100 protein and stained by IMF with the same antibodies and with antibodies to vimentin and actin. Modified (M) MCs of pleomorphic adenomas stained positively by IMP and IMF with all of the preceding antibodies. In many mucoepidermoid carcinomas, adenoid cystic carcinomas, and basal cell adenomas, variable numbers of CMCs and MMCs stained positively by IMP with anti-cytokeratin and anti-S100 protein antibodies. No MCs were detected in adenolymphomas or acinic cell carcinomas. We believe that MCs play a major role in the histogenesis of pleomorphic adenomas and may also be important in many mucoepidermoid carcinomas, adenoid cystic carcinomas, and basal cell adenomas.     

The myoepithelial immunophenotype in 135 benign and malignant salivary gland tumors other than pleomorphic adenoma.

BACKGROUND: We have previously studied the immunoreactivity of 3 novel smooth muscle-specific proteins, alpha-smooth muscle actin, smooth muscle myosin heavy chains, and calponin, to assess myoepithelial differentiation in pleomorphic adenomas. OBJECTIVE: To further expand our knowledge of myoepithelial differentiation in other benign and malignant salivary gland tumors. DESIGN: Formalin-fixed paraffin sections of 135 salivary gland tumors with associated normal glands were stained with monoclonal antibodies using the avidin-biotin complex immunoperoxidase method and enzymatic and microwave heat-induced epitope retrieval. RESULTS: In adenoid cystic carcinomas and epithelial-myoepithelial carcinomas, all 3 markers exclusively highlighted the myoepithelial cell components and the epithelial cells were entirely negative. No immunostaining was detected in canalicular adenomas, oncocytomas, Warthin tumors, acinic cell carcinomas, mucoepidermoid carcinomas, squamous cell carcinomas, and polymorphous low-grade adenocarcinomas. Salivary duct carcinomas and adenocarcinomas, not otherwise specified had a distinctive pattern of uniform periductal staining of reactive myofibroblastic cells, and in salivary duct carcinomas some ducts retained a peripheral immunoreactive myoepithelial cell layer. CONCLUSION: Immunoreactivity for these 3 smooth muscle-specific proteins confirms the known neoplastic myoepithelial component of adenoid cystic carcinomas and epithelial-myoepithelial carcinomas. The consistently positive staining pattern in adenoid cystic carcinomas may be diagnostically useful in discriminating histologically similar but consistently negative polymorphous low-grade adenocarcinomas. Periductal linear staining in adenocarcinoma, not otherwise specified and salivary duct carcinomas is distinctive and appears to represent a tight cuff of myofibroblasts associated with the infiltrating glands.     

Cytologic diagnosis of acinic-cell carcinoma of salivary glands

The cytologic findings in fine-needle aspiration (FNA) biopsies obtained from 40 primary and 18 recurrent acinic-cell carcinomas (ACC) were retrospectively analyzed. Cytomorphologically, ACC is characterized by acinar differentiated tumor cells. In addition to these diagnostic clue cells, other types of neoplastic cells including vacuolated cells, cells resembling oncocytes, and nonspecific glandular cells are encountered. A pronounced lymphocytic reaction is a hallmark in 10% of ACC aspirates. Both the variety of tumor cell differentiation and the pronounced lymphocytic reaction observed in ACC aspirates may result in confusion with other salivary gland lesions. The differential diagnosis of ACC encompasses adenocarcinoma, mucoepidermoid carcinoma, pleomorphic adenoma, Warthin tumor, sebaceous lymphadenoma, benign lymphoepithelial lesion, sialoadenosis, sialadenitis caused by radiotherapy, and lymphadenitis. Primary ACCs were correctly diagnosed in 68%; additionally, ACC was suspected or included in the differential diagnosis in 15%. Increased familiarity with the spectrum of cytomorphologic findings and the potential diagnostic pitfalls in ACC will improve the cytodiagnosis of this neoplasm. Diagn. Cytopathol. 16:402–412, 1997. © 1997 Wiley-Liss, Inc.     

Epithelial tumors of the lacrimal glands: a clinicopathologic study.

We report the clinicopathologic features of epithelial tumors of the lacrimal gland apparatus, which are rare and therefore represent a major challenge for diagnosis and treatment. Histologic material from 22 lesions was studied by light microscopy, histochemistry, and immunohistochemistry. A comparison with major and minor salivary gland tumors was performed to analyze the relative distribution of these tumors and to establish whether salivary glands and lacrimal gland tumors are similar or different in their pathologic appearance and clinical behavior. There were three benign pleomorphic adenomas and 19 malignant tumors. The gender distribution was equal. The ages of the patients ranged from 10 to 73 years (mean age, 46 years). Among the malignant tumors, adenoid cystic carcinoma was the most common (nine cases), followed by mucoepidermoid carcinoma (three cases). There were two cases each of malignant mixed tumor and adenocarcinoma. All mucoepidermoid carcinomas and the adenocarcinomas were histologically high grade. There also was one case each of salivary duct carcinoma, spindle cell carcinoma, and oncocytic adenocarcinoma. Of 14 patients in whom clinical follow-up was available, seven had distant metastases and four died of their disease. The only case occurring in a child was an adenoid cystic carcinoma that recurred locally after 14 years. The clinical and pathologic features of lacrimal gland tumors resemble those lesions that arise in the intraoral minor salivary glands. The greater relative proportion of malignant cases in this series probably reflects a selection bias.