Cystic lesions of the salivary glands: cytologic features in fine-needle aspiration biopsies

A variety of neoplastic and nonneoplastic lesions of the salivary glands have a predominantly cystic architecture. Fine-needle aspirates of these lesions yield watery or mucoid material, frequently of low cellularity. Such aspirates may be obtained from mucus retention cysts, lymphoepithelial cysts, cystadenomas, Warthin's tumors, cystic pleomorphic adenomas, low-grade mucoepidermoid carcinomas, cystadenocarcinomas, and examples of polycystic disease of the parotid gland. The cellular component within the fluid obtained from these lesions may be exceedingly scant or absent, making cytologic diagnosis difficult and, at times, impossible. We studied a series of 56 cystic lesions of the salivary glands, including 38 Warthin's tumors, 6 benign cysts, 2 lymphoepithelial cysts, 5 low-grade mucoepidermoid carcinomas, 1 cystic pleomorphic adenoma, 2 cystadenomas, and 2 cystadenocarcinomas. Careful attention to the cellular elements present often allowed definitive cytologic diagnosis, with an overall accuracy rate of 84%. The presence of atypical squamous metaplasia in oncocytic lesions was a significant cause of false-positive diagnoses of carcinoma (4 cases, 7%). Aspirates of low-grade mucoepidermoid carcinoma may contain no epithelial cells and result in false-negative diagnoses (1 case, 2%).     

A murine model of bone marrow micrometastasis in breast cancer

Bone marrow (BM) is one of the most common sites and often the first clinical indication of metastatic progression of breast cancer. Multivariate analyses have shown that the presence of cytokeratin positive tumor cells in the marrow of women with newly diagnosed stage I, II or III breast cancer is an independent predictor of survival. The objective of this study was to develop an orthotopic model of spontaneous BM metastasis to facilitate studies of this process. A murine mammary adenocarcinoma cell line, Clone 66, was transduced with the neomycin resistance gene (Cl66^neo) and injected orthotopically into female Balb/c mice. Polymerase chain reaction (PCR) for the neo gene performed on BM cells harvested from tumor bearing mice demonstrated as few as 10² injected tumor cells produced BM micrometastases at 4 weeks post-injection. Small foci of tumor cells were identified in the mammary fatpad (mfp) without gross evidence of primary tumors. Higher doses of tumor cells produced BM micrometastases, detectable by PCR, at one week post-injection. Constructs containing green fluorescent protein (GFP) and the neomycin resistance gene (neo) were also transduced into Clone 66 cells (Cl66-GFP^neo) and injected into the mfp. GFP transduced tumor cells were identified in multiple tissues in addition to BM by flow cytometric analysis (FACS) but less 13% of the animals developed gross metastases. This model is a clinically relevant tool for the analysis of organ specificity of metastasis. This revised version was published online in July 2006 with corrections to the Cover Date.     

Light and ultrastructural features of lymphoepithelial lesions of the salivary glands in Mikulicz's disease

This investigation deals with the histogenesis of the so-called 'epimyoepithelial islands' in Mikulicz's disease of the major salivary glands and is based on light and electron microscopic study in six patients. The 'epimyoepithelial islands' represent collapsed acini prior to their complete involution and disappearance, the intraductal cellular proliferation, stratification and differentiation into luminal and peripheral myoepithelial cells with partial and complete obliteration of their lumina and finally, cord-like proliferation and formation of nests of residual pluripotential cells showing squamous metaplasia and occasional myoepithelial cell differentiation. A pink, homogeneous and hyaline material on light microscopic examination is multilayered and extracellular and is in close association with the basal lamina when viewed with electron microscope.     

Establishment of social rank among grouped male mice: relative effects on circulating FSH, LH, and corticosterone

Previously-isolated, adult, CF-1 male mice were grouped four per cage, killed after periods of time ranging from one hour to 14 days, and their plasma assayed for corticosterone, FSH and LH. Dominant and subordinate ranks were easily separable after 24 hr for comparison with each other and with isolated controls that were also killed throughout the 14-day experimental period. The one hour responses to grouping, during which all males were fighting intensely to establish rank, included a 5–6 fold increase in plasma corticosterone and concurrent depressions in circulating gonadotropins, 19% for FSH and a dramatic 94% for LH. Plasma corticosterone returned to baselevels between Days 1 and 3 in the case of dominant males and between Days 3 and 6 for subordinates. Adaptation was also observed for FSH in the plasma of dominants but later than that occurring for corticosterone. Plasma FSH in subordinates and circulating LH among both relative ranks were still depressed at the end of the 14-day period. A reciprocal relationship between adrenocortical activity and gonadotropin secretion was thus observed only during the early phases of dominance-subordination establishment; thereafter, secretory patterns for these three hormones functioned independently. Seminal vesicles were little affected by grouping but mean preputial weight increased markedly and progressively among dominant males and decreased with time in subordinates.     

Functional and morphologic studies of the adrenal cortex and kidney in ovine toxaemia of pregnancy

Functional and morphologic studies of the adrenal cortex and kidney have been carried out in pregnant sheep with spontaneous or dietary restriction-induced ovine toxaemia. It was found that proteinuria was an inconstant feature and no animal showed glomerular lesions analogous to those found in human preeclampsia; thus ovine toxaemia cannot be regarded as a precise experimental model for human toxaemia of pregnancy. The elevation of blood cortisol levels and the morphologic appearance of the adrenal zona fasciculata found in such animals suggest an adrenal response comparable to that caused by adrenocorticotrophic hormone. In addition, animals with severe disease showed evidence of stimulation of the renin-angiotensin-aldosterone system as reflected by elevated blood renin and aldosterone concentrations and raised renal juxtaglomerular indices. Ultrastructural changes in the adrenal zona glomerulosa and renal juxtaglomerular myoepithelioid cells in toxaemic animals resembled those described in non-pregnant sodium-depleted sheep. The finding of juxtaglomerular peripolar cell mitoses and granule exocytosis, the latter only being previously observed in sodium depleted sheep, together with the ultrastructural changes in the adrenal zona glomerulosa and juxtaglomerular myoepithelioid cells, suggest that sodium depletion may play a role in this disease.     

Functional State of Adrenocortical System in Rats with Manifest Alloxan-Induced Diabetes Mellitus

In the adrenals of male rats with manifest form of alloxan-induced diabetes mellitus (blood glucose >20 mmol/liter), the content of progesterone was higher by 1.6 times, deoxycorticosterone by 2.5 times, corticosterone by 3.3 times, and 11-dehydrocorticosterone by 1.8 times than in the adrenals of control animals. Increased concentration of corticosterone and 11-dehydrocorticosterone were also found in the serum of rats with alloxan diabetes, but the difference between the experimental and control groups by these parameters was less pronounced compared to parameters in the adrenal glands. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Suppl. 1, pp. 23–25, 2008     

Adenoid cystic carcinoma of minor salivary glands. Analysis of 86 cases

Summary 819 salivary gland tumors in surgical pathology files over a 25-year period were reviewed. Among 117 adenoid cystic carcinomas, 86 were located in minor salivary glands and were selected for a clinico-pathological analysis. Complementary histoenzymological investigations and electron microscopic study were performed on specimens from 7 and 13 patients respectively.Adenoid cystic carcinoma occured in older patients (mean age of 54 years) than the other salivary neoplasms. The sex ratio was 1/1. The tumor was located more often in the palate and, to a lesser degree in the buccal floor, tongue or gums.Histologically, epithelial nests contained characteristic cyst-like spaces (cylinders) and 3 varieties of such cylinders were described (mucoid, mucohyalin and hyalin). According to the predominant pattern, 3 types of tumors were shown: basaloïd, cribriform and trabecular. A comparison between histological results and clinical behaviour, available in 67 patients, demonstrated positive correlations. The basaloïd form had always a poor prognosis (numerous early recurrences and metastases, frequent lethal evolution). The cribriform type had an intermediate prognosis, better than basaloïd type and less good than trabecular group (100% of patients still alive at 8 years).Histoenzymological studies revealed high level of acid phosphatase, alkaline phosphatase and leucine aminopeptidase activities round cylindromatous cavities. On the other hand, high oxidative enzyme activities were evenly distributed in all cell types.Ultrastructural findings emphasized the immature characters of epithelial tumor cells. These cells contained numerous ribosomes, but few other organelles. Some more differentiated glandular or epidermoid cells were scattered in neoplastic islands. Rare myoepithelial cells lay in periphery of lobules. Cylinder-like spaces were filled with replicated basal lamellae, mucopolysaccharidic granules and fibrillar structures (microfibrils and periodic collagen fibrils).In the light of these results the histogenesis of this neoplasm was discussed. Like the pleomorphic adenoma, adenoid cystic carcinoma was thought to arise from intercalated ducts. Unable to acquire any high degree of differentiation, this blastomatous tumor had a cellular component almost similar to that shown in intermediate stage of salivary gland embryogenesis.The authors wish to thank M.A. Leost and M. Tacnet for their technical assistance     

Ultrastructure and histochemistry of human anterior lingual salivary glands (glands of blandin and nuhn)

Background: Speciamens of human anterior lingual salivary glans obtained by surgery and by dissection of cadavers were studied ultrastructurally and histochemically. Methods: Specimens were obtained by surgery for ultrastructural study. Other specimens for histochemistry were obtained by dissection of fresh cadavers. Tissues for electron microscopy were fixed and processed by conventional mesns. Formalin-fixed cadaver specimens were subjected to a battery of tests for glycoconjugates. Results: The anterior lingual salivary glands are composed predominantly of mucous tubules (which come in two distinct sizes: large and small), seromucous demilunes, and rare seromucous acini. Regardless of tubule size, mucous cells are typically in appearance and, like mucous cells in other human salivary glands, contain filamentous bodies. Histochemically, the larger tubules contain neutral glycoproteins, low concentrations of sialoglycoproteins, and large amounts of sulfated glycoproteins. The small mucous tubules contain neutral glycoproteins, much sialoglycoprotein, and relatively small amounts of sulfated glycoprotein. The seromucous cells, whether demilunar or acinar, are identical. They contain numerous secretory granules, which show a spectrum of internal patterns from one individual to another. These cells have considerable concentrations of neutral- and sialoglycoproteins and lower concentrations of sulfated gly-coproteins. Countrary to previously published reports, we could find no differences in the ratio of mucous to seromucous cells along the anteriorposterior lingual axis: there was no gradient of seromucous cells in our specimens. The ducts in the anterior lingual salivary glands are not precise counterparts of those in the major salivary glands, since the former have no capsules, hence lack lobulation. Without these familiar structural landmarks, the only duct that can be identified with certainty is the intercalated duct, and then only if it is in continuity with or lies close to a secretory endpiece. Such ducts consist of simple cuboidal epithelium of prosaic appearance. The ductular epithelium gradually thickens and gives rise to what appear to be excretory ducts consisting of columnar cells with few mitochondria. Scattered within the walls of the walls of the larger ducts are patches of typical striated ducts wherein the taller cells display basal striations resulting from highly folded basal plasma membranes and numerous, vertically oriented, virgulate mitochondria. In other atypical regions of the excretory duct, basal cells may have a primary cilium that juts into the intercellular space. Conclusions: There is a high degree of structural variability in human anterior lingual salivary glands. Because of the technical difficulties in collecting pristine saliva from these glands, the precise functions(s) of these organs remains unknown. © 1994 Wiley-Liss, Inc.     

Non-linearity of skin resistance response to intraneural electrical stimulation of sudomotor nerves

Intraneural electrical stimuli (0.3 mA, 0.2 ms) were delivered via a tungsten micro-electrode inserted into a cutaneous fascicle in the median nerve at the wrist in 16 normal subjects, and the effects on the sweat glands within the innervation zone were recorded as changes of skin resistance. In order to examine the relationship between the skin resistance level and the amplitude of transient resistance responses, trains of high frequency stimulation were used to reduce the skin resistance level and then transient resistance responses were evoked by single stimuli at 0.1 Hz. Regional anaesthesia of the brachial plexus in the axilla eliminated spontaneous sympathetic activity and reflex effects. At high skin resistance levels response amplitudes to single stimuli were low but they increased successively to a maximum at intermediate levels and then decreased again at low resistance levels. Repeated stimulation sequences evoked qualitatively similar response curves but quantitatively both response amplitudes and skin resistance levels were slightly reduced upon repetition. We suggest that the changes of response amplitudes are due to variable resistivity of the corneal layer. The shifts of the response curves with repetition of stimulation may result from increased hydration of the corneum. It is concluded that the variability of response amplitudes to constant stimuli makes the amplitude of a skin resistance response unsuitable as an indicator of the strength of sympathetic sudomotor nerve traffic.     

Ontogenesis of the secretory immune system and innate defence factors in human parotid glands

Immunoglobulin-producing cells and epithelial expression of secretory component (SC), amylase, lysozyme (Ly) and lactoferrin (Lf) were studied by immunohistochemistry to obtain information about the development of mucosal immunity. Tissue specimens were obtained from 20 fetal and 40 postnatal parotid glands. (1) Fetal specimens. Occasional IgM- and IgA- but no IgD-, IgG- or IgE- producing cells were seen (ratios, IgM:IgA:IgD:IgG:IgE approximately 4:1:0:0:0). The IgAl subclass dominated (median 90%, range 50-95%) and these cells were mostly J-chain-positive (median 97%, range 94-98%). Only few IgA2-producing cells were seen (median 10%, range 5-50%) and they were also mostly J-chain-positive (median 99%, range 98-100%). Amylase, Ly and Lf were most prominent in early fetal life, while only small amounts of SC were present. (2) Postnatal specimens. Secretory component increased markedly along with a growing number of IgA- and IgD-producing cells (IgA:IgM:IgD:IgG:IgE approximately 4:2:1:1:0). The IgAl subclass remained predominant (median 65%, range 50-90%) although the proportion of IgA2-positive cells tended to be raised (median 35%, range 10-50%). Most IgAl (median 97%, range 67-100%) and IgA2 (median 94%, range 75-100%) cells were J-chain-positive. These features probably reflected local activation of the immune system in response to environmental factors. The amount of amylase, Ly and Lf decreased shortly after delivery, perhaps because the cellular stores were emptied by postnatal increase in secretory activity.