Infarction of pleomorphic adenoma: a rare complication of fine-needle aspiration obscuring definitive diagnosis.
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Fine needle aspiration cytology (FNAC) of salivary gland lesions is a safe, effective diagnostic technique. Several amply illustrated reviews are available in the English literature. The reported diagnostic accuracy varies between 86% to 98%. The sensitivity ranges from 62% to 97.6% and specificity is higher from 94.3% to 100%. In this present study, we have analyzed 172 cases of salivary gland aspirates and the histopathological diagnosis was available in 45 cases. There was discordance in cytological and histopathological diagnosis in nine cases. Five cases had discrepancies in benign versus malignant diagnosis with four cases being false negative. The errors in these FNA diagnoses were due to sampling error, observational error and interpretational error. Therefore, this study illustrates high diagnostic accuracy of FNAC in salivary gland lesions and shows that FNAC offers valuable information that allows the planning of subsequent patient management.
The utilization of fine-needle aspiration (FNA) biopsy in salivary tumors is hindered by the reluctance of many cytopathologists to report adenoid cystic carcinoma (ACC) because its cylindromatous stroma is observed occasionally in pleomorphic adenoma (PA) and basal cell adenoma (BA), and a diagnosis of ACC results in radical surgery. The aim of this study is to identify dependable features to distinguish the look-alike entities and illustrate their ultrastructural base. We compared 20 cases of ACC to 15 cases of cylindromatous PA and 9 cases of BA. All were direct smears stained with Diff-Quik, hematoxylin and eosin, Papanicolaou, or Ultrafast Papanicolaou (UFP) stain. In addition to the presence of cylindromatous pattern, the amount of cytoplasm in the neoplastic cells and nuclear features were compared. Tissue was dissected from paraffin blocks and processed for electron microscopy in selected cases. The difference in nuclear features can be distinguished in UFP-stained smears and electron microscopy. The nuclei of ACCs were heterochromatic with coarse chromatin and irregular nucleoli, whereas the nuclei of PAs were euchromatic with fine chromatin and small compact nucleoli. The nuclei of BAs were hyperchromatic but finely textured. The cytoplasm of PAs was detectable with every stain at 40x objective, but the cytoplasm of BAs required UFP stain and 100x objective to be detected. The cytoplasm of majority of neoplastic cells of ACCs are invisible, because the thin rim of cytoplasm measured <1 microm ultrastructurally, well beyond the resolution of a light microscope. Rare cohesive fragment of epithelial cells in ACC have scanty blue cytoplasm in UFP stain and can be recognized as ductal cells. In conclusion, in our analysis of salivary tumors with a cylindromatous pattern, the seemingly naked nuclei of neoplastic cells with their coarse nuclear chromatin and irregular nucleoli, as revealed by the UFP stain, reliably distinguished ACC from cylindromatous adenomas.
Chromosome rearrangements involving 12q13-15 are frequent among several tumors, including pleomorphic adenomas. The common molecular target for these aberrations is the HMGA2 gene, but various fusion partners of HMGA2 have been reported in tumors. Here we report the identification of the WNT inhibitory factor 1 (WIF1) gene as a novel HMGA2 fusion partner in a salivary gland pleomorphic adenoma. In normal salivary gland tissue WIF1 is expressed at a high level and HMGA2 is not expressed. However, in the pleomorphic adenoma expressing the HMGA2/WIF1 fusion transcript, we observed re-expression of HMGA2 wild-type transcripts and very low levels of WIF1 expression. These data suggest a possible synergistic effect between upregulation of HMGA2 and downregulation of WIF1. We screened 13 additional benign and malignant salivary gland tumors and detected WIF1 rearrangement in one out of two carcinomas ex-pleomorphic adenoma analyzed. In this malignant tumor, the rearrangement of one WIF1 allele coexists with loss of the other allele, a classic signature of a tumor suppressor gene. WIF1 is an antagonist of the Wnt signaling pathway, which plays a critical role in human cancer. In transgenic mouse models, Wnt activation leads to a high frequency of benign and malignant salivary gland tumors. To our knowledge, this is the first report suggesting that WIF1 is a recurrent target in human salivary gland oncogenesis and that downregulation of WIF1 plays a role in the development and/or progression of pleomorphic adenomas.
BACKGROUND: Lymphoepithelioma-like carcinomas (LEC) of salivary glands represent rare epithelial malignancies, with most cases affecting the parotid gland. To our knowledge, there was only one LEC arising from the minor salivary gland described in the English-language literature. METHODS: We report the second LEC of the minor salivary gland in the buccal area of a 50-year-old Taiwanese woman, who underwent surgical resection and adjuvant radiotherapy and remained alive and well after 120 months of follow-up. Histologically, irregular tumor nests of undifferentiated epithelial cells with syncytial cell boundaries were found embedded within rich lymphoplasmacytic stroma. The tumor cells also showed strong c-KIT expression and evidence of Epstein-Barr virus (EBV) infection. CONCLUSIONS: Our case suggests potential pathogenic implications of both c-KIT and EBV in LEC of the minor salivary gland that can be cured by the combination of surgery and radiotherapy and has a very favorable long-term prognosis.
The cytologic findings of 51 smears obtained by fine needle aspiration biopsy from salivary gland masses were compared with the histologic findings of permanent sections. The overall concurrence rate between cytologic and histologic findings for being and malignant lesions was 91%. The diagnostic accuracy (exact histologic diagnosis) for the benign lesions was 87% and for the malignant tumors 60%. One case showed false-positive results and 1 case false-negative results. Fine needle aspiration biopsy has been found to be safe, free of complications, and helpful in the planning of treatment.
Sharing a common ectodermal origin with salivary duct epithelium, the myoepithelial cell is two-sided in several respects. It lies between the epithelial cells and the basal lamina, with one side facing the duct or acinar cells and the other facing the stroma. It has a fine structure not unlike that of smooth muscle, and one of its functions is to contract. Despite its electron-optic similarity to smooth muscle, the myoepithelial cell's principal filamentous protein is cytokeratin, which is found only in epithelial cells. Myoepithelial cells do not have a demonstrable secretory capability, but they can store glycogen in abundance. In some tumors of the salivary glands, myoepithelial cells do not participate in histogenesis. These tumors arise from portions of the salivary duct system in which myoepithelial cells are not normally found. In tumors originating from intercalated ducts, myoepithelial cells may assume one of two roles; a passive presence or an active and integral formation of the tumors. Mixed tumors, clear cell tumors, plasmacytoid (hyaline cell) and fibroblastic myoepitheliomas, and terminal duct adenocarcinomas are examples of tumors in which the myoepithelial cell is prominent or dominant.
It is an interesting parallel that the myoepithelial cell with its hybrid epithelial and mesenchymal structural and functional phenotype has a dual role in such salivary gland tumors as pleomorphic adenoma. This cell is responsible for considerable proportions of the epithelial component of this tumor, including squamous metaplasia, and is also the agent principally involved in the synthesis, organization, and cytologic modifications of the chondromyxoid regions. Neoplastically modified myoepithelial cells are also generally accepted to be a significant component of salivary gland tumors such as epithelial-myoepithelial carcinoma, certain adenocarcinomas, and, of course, myoepitheliomas. The range of myoepithelial cell alterations can be appreciated via ultrastructural assessment of the above four classes of salivary gland tumors. An electron microscopic survey of monomorphic adenomas, adenoid cystic carcinomas, and mucoepidermoid carcinomas reveals some having a tumor cell component with structural modifications and localization similar to the modified myoepithelial cells in pleomorphic adenomas and the adenocarcinomas noted above. Such ultrastructural findings have important implications for clarifying diagnostic problems, for understanding histogenetic relationships, and for improving the classification of salivary gland tumors.
Adenoid cystic carcinoma (ACC) is one of the most common malignant tumors of the salivary glands. It tends to grow slowly but is associated with a poor prognosis compared to other malignant salivary gland tumors. To identify specific markers of ACC, we examined protein expression profiling in ACC xenograft and normal salivary glands (NSG) using fluorescent 2-dimensional differential in-gel electrophoresis (2-D-DIGE), an emerging technique for comparative proteomics, that improves the reproducibility and reliability of differential protein expression analysis between the samples. To identify the proteins, matrix-assisted laser desorption/ionization time-of-flight peptide mass fingerprinting was carried out. Using these strategies, we detected 4 upregulated proteins and 5 downregulated proteins in ACC xenograft. Maspin and stathmin were selected for further analyses. Western blotting and immunohistochemical staining showed a higher expression of these proteins in ACC xenograft and clinical ACC tissue compared to NSG. Furthermore, Expression of these proteins was correlated with the histologic grading of ACC (n = 10). Therefore, our data indicate that maspin and stathmin may be not only useful biomarkers of ACC but also markers of biologic behavior in this tumor.
PURPOSE: We undertook this retrospective study to describe the sonographic findings in patients with malignant lymphoma of the major salivary glands. METHODS: We reviewed the sonograms and medical records of 7 patients with histologically proven lymphoma of the parotid (3 patients) or submandibular glands (4 patients). RESULTS: Primary lymphoma was found in 1 parotid gland and 2 submandibular glands. The remaining 4 cases were secondary lymphomas. One patient had been diagnosed with Sjögren's syndrome and had been followed up with sonography. In parotid glands, both parenchymal and intraparotid nodal lymphomas were found. All submandibular gland tumors were parenchymal. Intraparotid nodal involvement appeared as multiple small nodules with relatively smooth margins, whereas the parenchymal parotid and submandibular gland lymphomas were larger (25 to 45 mm in longitudinal diameter) and showed various degrees of margin irregularity. All tumors were hypoechoic relative to the normal parenchyma. The primary parotid lymphoma and intraparotid nodal lymphomas had a homogeneous echotexture; the secondary parotid lymphomas and submandibular gland lymphomas were heterogeneous. One submandibular gland lymphoma showed intratumoral echogenic stripes. Neither calcification nor cystic degeneration was observed within the lesions. CONCLUSIONS: Lymphomas of the salivary glands present a variety of sonographic appearances, ranging from multiple small, hypoechoic nodules to an irregularly shaped heterogeneous mass without cystic areas or calcifications.
Electron microscopy has a limited role in the diagnosis of primary salivary gland tumors, although it can be helpful in metastatic lesions of possible salivary gland origin. The diversity of subtypes in salivary gland tumors, as well as the range of histomorphology within any one subtype, is unparalleled in any other human tumor. This and their relative infrequency causes diagnostic problems for pathologists. Ultrastructural techniques have been of major importance in determining the inter-relationship of these tumors for classification purposes, revealing the subtle variations in common cellular differentiation pathways, determining the organization of tumor cells, and displaying the importance of extracellular matrix materials in establishing diagnostic criteria for each of the many subtypes. Electron microscopy has also been valuable in non-neoplastic salivary gland disease and has an increasing role in experimental studies involving tissue from human and animal salivary parenchyma.
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An immunocytochemical study was carried out on normal salivary gland tissue and ten salivary gland pleomorphic adenomas. Antibodies to myosin were used to stain myoepithelial cells. Duct cells were stained using an antibody to total keratin and a subpopulation of basal duct cells with an antibody to 45/46K keratins. Basement membranes were stained with anti-type IV collagen. The results demonstrated that myoepithelial cells are relatively rare in the majority of pleomorphic adenomas and that many of the cells which have been classically described as myoepithelial in routine histological preparations do not clearly show this type of differentiation. However, the tumors presented a spectrum of differentiation patterns from those that were mainly ductal to the rare tumour which was largely myoepithelial. It is further suggested that the 45/46K keratin antibody is capable of identifying a subpopulation of cells which could possibly be important in the histogenesis of this tumour.
Control of keratin (K) gene expression may be important for cell differentiation in complex epithelia such as salivary gland. To investigate differences in distribution between keratin mRNAs and their respective proteins, a combined in situ hybridization (ISH) and immunohistochemical study was undertaken on nine normal salivary glands and seven pleomorphic adenomas. ISH employed riboprobes to K7, K8, K14, K18, and K19. Immunohistochemistry was performed on adjacent sections using monoclonal antibodies (MAbs) to the same keratins. Normal luminal cells showed abundant hybridization with probes for K7, K8, K18, and K19. Keratin 14 mRNA was present in basal and myoepithelial cells at a low level of expression. Proteins of their keratins were strongly stained. Neoplastic cells showed variable expression of mRNA and protein for K7, K8, K18, and K19. There was a high level of K14 mRNA but variable protein. The findings provide evidence that expression of these keratins in normal salivary epithelia is regulated transcriptionally and that in neoplasia this system is in considerable disarray.
Pleomorphic adenomas are benign epithelial tumors originating from the major and minor salivary glands. Extensive cytogenetic studies have demonstrated that they frequently show chromosome abnormalities involving chromosome 8, with consistent breakpoints at 8q12. In previous studies, we have shown that these breakpoints are located in a 9-cM interval between MOS/D8S285 and D8S260. Here, we describe directional chromosome walking studies starting from D8S260 as well as D8S285. Using the CEPH and ICRF YAC libraries, these studies resulted in the construction of two nonoverlapping YAC contigs of about 2 and 5 Mb, respectively. Initial fluorescence in situ hybridization (FISH) analysis suggested that the majority of 8q12 breakpoints clustered within the 2-Mb contig, which was mapped to the centromeric part of chromosome band 8q12. This contig has at least double coverage and consists of 34 overlapping YAC clones. The localization of the YACs was confirmed by FISH analysis. On the basis of mapping data of landmarks with an average spacing of 65 kb as well as restriction enzyme analysis, a long-range physical map was established for the chromosome region spanned by the 2-Mb contig. The relative positions of various known genes and expressed sequence tags within this contig were also determined. Subsequent FISH analyses of pleomorphic adenomas using YACs as well as cosmids revealed that all but two of the 8q12 breakpoints in the primary tumors tested mapped within a 300-kb interval between the MOS proto-oncogene and STS EM156. The target gene affected by the chromosome aberrations mapping within this interval was recently shown to be the PLAG1 gene, which encodes a novel zinc finger protein.
Ultrastructural features and cytokeratin expression of inverted ductal papillomas of minor salivary gland origin were studied. Under the electron microscope, an increased number of desmosomes and mucus-like granules in some cells were the most striking features. Immunohistochemical study revealed that tumor cells displayed strongly positive reactions with cytokeratins 13 and 14, and less strong reactions with cytokeratins 7, 8, 18 and 5D3. These results support the hypothesis that an inverted ductal papilloma can be derived from the proximal portion of a salivary gland excretory duct.
The vast field encompassed by the non-tumorous diseases of the salivary glands poses difficult problems for their diagnosis and therapy. In order to facilitate comprehension of the pathological processes and the therapeutical possibilities for their treatment, physiological and biochemical aspects of salivary gland function are presented in the introduction. There are also mentioned in detail most of the diagnostic methods clinically applied today and stress is laid on their respective diagnostic values. In contrast to the opinion of many authors, exploratory excision and puncture are shown to be very important diagnostic tools in salivary gland pathology. The specific application of these methods is often the only means for a reliable diagnosis. The classification of the diseases follows Seifert's (1971) proposal. The chronic diseases of the salivary glands are specifically mentioned with the chronic recurrent and the chronic myoepithelial sialoadenitis taking first place. The sialoses are presented in a larger chapter. An attempt was made to correlate clinical and experimental results, to establish working hypotheses concerning the development of sialoses, to suggest therapeutical possibilities and, last not least, to give an idea of the many clinical and patho-anatomical difficulties to be overcome for a satisfactory understanding of such pathological processes. Finally, various forms of salivary gland fistulas and their treatment are mentioned. The long list of references merely gives an approximation of the abundance of publications dealing with the problems of this field.