An unusual case of primary leptomeningeal marginal zone B-cell lymphoma

Primary leptomeningeal lymphomas are rare, and usually follow a rapid clinical course with early systemic involvement. A 60-year-old woman presented with a 3-year history of worsening seizures and memory loss. Neuroimaging showed widespread meningeal calcification. After extensive investigations a meningeal biopsy revealed a low-grade B-cell lymphoma categorized as an extranodal marginal zone B-cell lymphoma, attributed to the same histological group as the MALT (mucosa-associated lymphoid tissue) lymphomas described in the stomach, thyroid, salivary glands and orbit. There was no evidence of systemic involvement. The extensive meningeal calcification would appear to be a novel finding in primary leptomeningeal lymphoma whereas the unusually long clinical history in this case is possibly related to the particular histological type of low-grade B-cell lymphoma.     

Psychosomatic obstetrics and gynecology in the next millennium: some thoughts and observations

Diagnostic pitfalls exist when benign salivary gland diseases are mistakenly classified as malignant, with consequences for treatment and prognosis. Examples are necrotizing sialometaplasia, metaplastic Warthin tumour and sclerosing polycystic sialadenopathy. The proper diagnosis is of eminent importance to distinguish cases of primary tumours that have developed in salivary glands or their lymph nodes from cases of extraglandular tumours with metastases in these glands or their nodes. In these cases clinical data and additional immunocytochemical methods are necessary to clarify the exact diagnosis, especially when the primary salivary gland tumours have a structure largely identical to the metastases (e.g. squamous cell carcinoma). Nasopharyngeal or cervical chordomas can be mistaken for pleomorphic adenoma or mucinous adenocarcinoma. The initial stage of malignant MALT lymphomas in association with Sj?gren's syndrome demands identification of clonal rearrangement for therapeutic implication. The diagnostic criteria for proper classification are analysed in detail.     

Ethanol administration delays recovery from acute pancreatitis induced by exocrine hyperstimulation

A cholera toxin-sensitive, prostaglandin E2 (PGE2) specific receptor has been identified in the plasma membrane fraction of tick salivary glands. In the present study, we report that stimulation of dispersed salivary glands of the lone star tick Amblyomma americanum (L.) with 1 nM to 10 microM PGE2 increased the intracellular concentration of inositol trisphosphate (IP3) in a dose-dependent manner. Incubation of dispersed tissue with 1 nM to 10 microM PGE2 also stimulated release of 45Ca2+ from preloaded tissue. PGE2 (10 microM) did not stimulate an influx of 45Ca2+. Therefore, the PGE2 receptor in the salivary glands appears to activate a phosphoinositide phospholipase C signalling pathway to increase formation of intracellular IP3 and, thus, mobilize Ca2+ from intracellular stores. Incubation of dispersed salivary glands with 1 nM to 1 microM PGE2 stimulated secretion of anticoagulant protein, but not at < 1 nM or > 1 microM PGE2. In addition, the mammalian PGE2 EP1 receptor antagonist AH-6809 affected secretion of anticoagulant by dispersed salivary gland tissue at a low concentration supporting the hypothesis that the PGE2 receptor in tick salivary glands is EP1-like. We propose that a major function for PGE2 in tick salivary glands is to mobilize Ca2+ and stimulate secretion (exocytosis) of bioactive proteins into the tick's saliva during feeding.     

Verbal short-term memory deficit in Alzheimer''s disease: an examination with the free recall paradigm

To elucidate the presence and distribution of Endothelin-1 (ET-1) in tissues of human salivary glands, we performed an immunohistochemical analysis of ET-1 in 15 normal salivary glands, 8 adenolymphomas, 13 pleomorphic adenomas and 5 carcinomas, using the mouse monoclonal antibody against human ET-1. In normal glands, immunoreactivity for ET-1 was observed in the striated duct cells. In adenolymphomas, the columnar cells of the granular epithelium showed strong intracytoplasmic immunoreactivity. In carcinomas, moderate or strong immunoreactivity was observed in the tumor cells, whereas in pleomorphic adenomas, weak immunoreactivity was observed. A good relation was detected between the size of pleomorphic adenoma and ET-1 immunoreactivity, as well as between the duration of tumor in carcinoma and ET-1 immunoreactivity. The presence and distribution of ET-1 in salivary glands and salivary gland tumors suggests a possible role for ET-1 in the regulation of electrolytes and water transport in salivary glands, and as a growth-promoting factor for tumors.     

Diagnosis and prognosis of salivary gland tumors. An interpretation of new revised WHO classification

An exact morphological classification of salivary gland tumours is necessary for international comparison of clinical tumour studies. The basis is formed by the TNM system for determining tumour stage ("staging") and the WHO classification as the underlying principle of identifying the pathohistological tumour state and cellular tumour differentiation ("grading"). The second, revised edition of the WHO classification of salivary gland tumours differs from the first in that the exact definition of a considerably greater number of tumour entities is given and in the consideration of additional factors concerning prognosis and therapy. In the present interpretation of salivary gland tumours, not only are solitary tumour entities defined, but new findings are also considered concerning immunohistochemical tumour markers, proliferation markers (Ki-67 resp. MIB 1, AgNORs, PC-NA), oncogenes and cell receptors as well as cytogenetic alterations as prognostic factors. In particular the new tumour entities of adenomas (myoepithelial adenoma, basal cell adenoma, canalicular adenoma) and carcinomas (acinic cell carcinoma, mucoepidermoid carcinoma, polymorphous low-grade adenocarcinoma, salivary duct carcinoma, myoepithelial carcinoma) are characterized. In addition, the tumour-like lesions and differential diagnostic aspects are mentioned and a general review about new prognostic factors is presented.     

Salivary glands and human selection: a hypothesis

Stafne static bone defect (SSBD) of the mandible is the only described destructive bone lesion that is highly localized, nonprogressive, but nonhealing. This common defect in male is found in the region of the major salivary glands that produce a cornucopia of biologically active factors. We describe rare phenocopies caused by mandibular immobility that hold the gland in a constant position thus implicating a localized chronic "leak" of an osteoclast induction factor from the major salivary glands as the pathologic agent. This finding suggests that increased salivary gland size could simulate immobility by apposing the gland to bone, thus allowing the "leaked" factor's gradient to have an effect. In one step, the putative genetic enlargement of a critical gland that produces many factors important for survival, a broad biological vista would be available to the massive potential for both positive and negative selection. Positive selection was identified by observing a correlation between the prevalence of enhanced androgen-induced enlarge salivary glands (SSBD) as a marker, with a great preponderance of males) and the conjectured resulting increased production of immunoreactive factors, with pole-to-equator isotherm and broad ranged infection clines. Negative selection was observed among the slave ancestors of African Americans for a potential embryonic homeotic mutation causing larger salivary glands in both sexes (decreased prevalence of SSBD, with an equal sex ratio). The decreased production of saliva and electrolytes diminished the salt and water depletive effects of severe diarrhea and vomiting induced by enteric diseases, which killed many slaves. Data presented suggests that SSBD is a polymorphism and a marker of selection processes that cause variation in size, or structure, of the major salivary glands.     

Behavior and reproductive function of rat male offspring treated prenatally with 5-bromo-2''-deoxyuridine

OBJECTIVE: The aim of this study was to determine the effects of radiation on the secretion of saliva from mucous salivary glands in comparison with serous salivary glands. STUDY DESIGN: The minor salivary glands of the palate were used as an example of mucous glands, while the parotid glands were used as an example of a serous secretion organ. Serial flow rate measurements of the parotid and palatal glands were taken over a period of approximately 9 months in 13 patients who suffered from malignancies of the head and neck region. Twelve patients consented to take part in a second study in which salivary flow was stimulated by oral pilocarpine before and at the conclusion of radiotherapy and 7 months later. Complaints and symptoms were recorded at each time of measurement. RESULTS: After radiotherapy, the secretory performance of the parotid glands dropped off rapidly and irreversibly. Salivary secretion from the palatal glands was not totally diminished as a result of radiation. Clinical complaints and histologic findings indicate a serious alteration of the tissues irradiated; however, residual secretion from the remaining parenchyma of the mucous glands still remains. Pilocarpine produced a clinically significant increase of salivary flow from the palatal glands before and 7 months after radiation. Secretory performance of the parotid glands could not be sufficiently increased by stimulation with pilocarpine after radiotherapy. Clinical side effects and risks for the treatment of symptomatic postradiation xerostomia with pilocarpine were minimal. CONCLUSIONS: These findings emphasize the greater resistance and recoverability of the mucous secreting minor palatal glands in comparison with the serous secreting parotid glands. They also indicate the significant postradiation ability of the mucous secreting glands to be stimulated by pilocarpine.     

Tc-99m-HMPAO single photon emission computed tomography (SPECT) as an ancillary test in the diagnosis of brain death

Lipomatosis has not previously been reported in minor salivary glands. Its occurrence in the parotid gland is well recognized. We present the first reported case of lipomatosis of the minor salivary glands in the nasal cavity. We also review the tumours of the minor salivary glands, lipomas and lipomatosis of the parotid, and the few reported cases of lipomas of the sinonasal tract.     

Imaging of the salivary glands

The most common conditions affecting the salivary glands are calculi, inflammation and tumours. Plain radiography may be useful, especially in showing calculi. Sialography is the examination of choice for inflammatory diseases, whereas ultrasonography, computed tomography and magnetic resonance imaging are particularly useful in evaluating masses in the salivary glands. Radionuclide studies are sometimes helpful in evaluating inflammatory or tumoral diseases. Each technique has its place, and the methods are often complementary. In this review article the authors present the techniques that they use in evaluating diseases of the salivary glands.     

Expression of gross cystic disease fluid protein-15/Prolactin-inducible protein in rat salivary glands

Gross cystic disease fluid protein-15 (GCDFP-15)/prolactin-inducible protein (PIP) is present at moderate levels in human submandibular and sublingual glands and is barely detectable in human parotid gland. The rodent homologue, PIP, has previously been identified in adult submandibular and lacrimal glands. Here we present the molecular characterization of rat PIP and show that this protein is a product of neonatal and adult rat submandibular, sublingual, and parotid glands. cDNA clones encoding rat PIP were isolated and sequenced. The deduced amino acid sequence of rat PIP shows 56% overall identity and 80% similarity with mouse PIP. By SDS-PAGE, secreted rat PIP has an apparent Mr of 17,000, with a minor proportion present as Mr 20-22,000 N-glycosylated forms. PIP was localized in rat salivary glands by immunogold silver staining. PIP was identified in acinar cells of developing and mature submandibular and parotid glands and at very low levels in sublingual gland serous demilunes. Typically, rat submandibular gland secretory proteins are produced by either acinar cell progenitors (Type III cells) or mature acinar cells. The expression pattern observed for PIP is similar to that previously reported for salivary peroxidase, an important component of nonimmune mucosal defense.     

Biochemical, genetic, and metabolic adaptations of tumor cells that express the typical multidrug-resistance phenotype. Reversion by new therapies

Sebaceous carcinoma is an infrequent tumor of tardy increase, locally aggressive, potentially recurrent, with natural propensity for metastasize, both loco-regional or remote (lymphogenous or hematogenus metastases). Principal sitting are the annexed glands to ocular sense (Zeis glands and specially Meibomian's). Its origin in salivary glands is exceedingly uncommon, only those arising in the parotid have been reported. Our contribution are 2 cases which source were the sublingual gland and a minor palatine salivary gland, respectively. The perusal of the literature has been negative: no one previous case of sebaceous carcinoma could be discovered in the literature.     

Quantification of salivary gland function in thyroid cancer patients treated with radioiodine

PURPOSE: Damage to salivary gland function following external irradiation has been documented. However, the extent of damage following radioiodine (131I) therapy for thyroid cancer has not been adequately studied. We evaluated salivary dysfunction in Ca-thyroid patients treated with therapeutic doses of 131I. METHODS AND MATERIALS: A simple acquisition and analysis protocol using 99mTcO4- (pertechnatate) and a gamma camera computer system was planned. The uptake of 99mTcO4- by the salivary glands at 10 min and percent of excretion of 99mTcO4- from the glands in response to a sialogogue (lemon juice) was studied in 33 patients treated with 1.369-38.702 GBq of 131I (Mean = 10.16 GBq, standard deviation = 7.659 GBq) in addition to 14 athyreotic controls. RESULTS: Significant damage to the salivary gland in terms of abnormal percent uptake or excretion was noted in 72.73% of the patients. Forty-eight percent of the patients treated with 131I showed asymmetrical involvement of the salivary complexes as opposed to none of the controls. Reduction in uptake of 99mTc4- or response to sialogogue was dose dependent, being more marked with higher radioiodine doses. Parotid glands were more affected than submandibular glands following 131I therapy. CONCLUSIONS: 131I therapy produces a significant effect on salivary gland function that is dose related and becomes evident over a period of several months after treatment.     

Basal cell adenocarcinoma of the parotid gland: a rare tumor entity. Case report and review of the literature

Basal cell adenocarcinoma is a rare entity that was first defined as a malignant salivary gland tumor in 1991. We present another case report and discuss pathology, pathogenesis, differential diagnosis, therapy and prognosis on the basis of currently available literature. Although histomorphologic features of the tumors are similar to basal cell adenomas, proof of an infiltrative and destructive growth is essential for diagnosis. Adenoid cystic carcinoma and basaloid squamous carcinoma must also be considered in any differential diagnosis. Tumor development within a pre-existing basal cell adenoma and de novo development are discussed. Most of the tumors appear to be benign clinically. Facial pain is rare and facial nerve palsy was noted in only one case. Metastases have occurred in less than 10% of patients, with only one involving the lung. Due to their biologic behavior and prognosis, basal cell adenocarcinomas should be classified as low-grade carcinomas. The therapy of choice is parotidectomy with preservation of the facial nerve. Neck dissection has to be added in cases with cervical metastases. Radiation is advisable in patients with recurrent disease. Since there is a nearly 30% local recurrence rate, intensive follow-up is necessary.     

Salivary gland involvement in systemic diseases

The salivary glands participate in systemic illnesses because they are secretory structures allied with the gastrointestinal tract. Thus they are involved in systemic inflammatory, allergic, and neoplastic conditions. Perhaps the most common condition is that of mumps in the acute phase. Of the chronic diseases, Mikulicz's disease or Sj?gren's syndrome is most frequently noted. In most instances of systemic involvement, the salivary gland enlargement is the rule, with the gland being tense, soft, and enlarged, and with progressive growth over a period of time. Usually all glands are involved. The diagnosis should be suspected from the history and the physical examination, noting that all the glands are equally involved by the enlargement. If there is any question, a biopsy should be performed. In the case of Sj?gren's syndrome, the biopsy specimen may be taken either from a major salivary gland or from one of the minor ones, or the nasal mucous membrane or oral cavity. In general, definitive therapy is unsuccessful for the systemic illness involving the salivary glands, and in most instances has to be supportive.     

Biopsy of the accessory salivary glands. 5 years' experience

Biopsy of the minor salivary glands has become a routine examination ordered by physicians working in a wide range of disciplines in order to search for or eliminate the diagnosis of Gougerot Sj?gren's disease or another systemic disease. We emphasize the need to use this examinations as a part of a complete work-up of the buccal cavity and the salivary glands. We reviewed our experience with 1,500 biopsies. The glands biopsied were normal in 56% of the cases and led to the diagnosis of Gougerot Sj?gren's disease in 24%, chronic sialadenitis in 10% and diverse trophic problems in 5%. The clinical stage of Gougerot Sj?gren's disease is usually proposed according to the Chisholm classification which we propose to compare with the Chomette classification. Finally, we described the technique of minor salivary gland biopsy.     

Salivary gland scintigraphy in subjects with and without symptoms of dry mouth and/or eyes, and in patients with primary Sj?gren's syndrome

The major salivary glands were examined with 99m-Tc-pertechnetate scintigraphy in randomly selected subjects with (n = 30) and without (n = 12) symptoms of dry mouth and/or eyes, and in patients with primary Sj?gren's syndrome (1 degree SS, n = 17). The scans were quantitatively evaluated and compared to other objective tests used to diagnose 1 degree SS. As compared with those for asymptomatic subjects, most values for the scintigraphic variables were non-significantly lower for symptomatic subjects and the time-activity curves were slightly flatter for all major salivary glands. In patients with 1 degree SS most values for the scintigraphic variables were significantly lowered and the submandibular glands were the glands most affected, as reflected in a flat time-activity curve, while the parotid glands were mainly affected during stimulated secretion. The scintigraphic variables correlated with the self-rated dryness of mouth in symptomatic subjects and with the abnormality of sialometry results in patients with 1 degree SS. We conclude that salivary gland scintigraphy is a sensitive and valid method to measure salivary gland function and abnormalities.     

Abnormally high levels of cystatin S in submandibular glands, saliva, and gingiva of plaque-resistant rats

To identify salivary biomarkers of periodontal diseases, we used plaque-resistant and -susceptible rats as animal models. The levels of salivary cystatin S in saliva, salivary glands, and gingiva were tested in Nembutal-anesthetized young and adult plaque-resistant and -susceptible rats of both sexes with and without chronic treatment with isoproterenol. Isoproterenol was injected i.p. once a day for 4 or 6 consecutive days. Isoelectric focusing electrophoresis by the PhastSystem and the western blotting method were used to separate different proteins and to identify a salivary cystatin S band in these samples. The expression of salivary cystatin S mRNA was also determined by the northern blotting method. Depending upon the types of agonists, a few differences were observed in secretory functions between both strains of rats in both sexes, but the levels of salivary cystatin S in saliva elicited from the submandibular gland and in the extracts of the submandibular glands and gingiva were significantly higher in plaque-resistant rats when compared with those of plaque-susceptible rats in both sexes. However, no significant difference was seen between the strains after chronic treatment with isoproterenol. The N-terminal 26-amino-acid sequence of salivary cystatin S purified from submandibular saliva of plaque-resistant rats was identical with that purified from submandibular saliva of Sprague-Dawley rats subjected to chronic treatment with isoproterenol. The expression of salivary cystatin S mRNA was dramatic in the submandibular glands of the plaque-resistant rats and in the submandibular glands of Wistar rats subjected to chronic treatment with isoproterenol, but not in those of plaque-susceptible rats. These results suggest that salivary cystatin S might be a good biomarker in distinguishing between the two strains of rats and that its concentration is correlated with plaque resistance.     

Submandibular salivary proteases: lack of a role in anti-HIV activity

Whole human saliva contains a number of proteolytic enzymes, mostly derived from white blood cells and bacteria in the oral cavity. However, less information is available regarding proteases produced by salivary glands and present in salivary secretions. In the present study, we have analyzed submandibular saliva, collected without contaminating cells, and identified multiple proteolytic activities. These have been characterized in terms of their susceptibility to a series of protease inhibitors. The submandibular saliva proteases were shown to be sensitive to both serine and acidic protease inhibitors. We also used protease inhibitors to determine if salivary proteolytic activity was involved in the inhibition of HIV infectivity seen when the virus is incubated with human saliva. This anti-HIV activity has been reported to occur in whole saliva and in ductal saliva obtained from both the parotid and submandibular glands, with highest levels of activity present in the latter fluid. Protease inhibitors, at concentrations sufficient to block salivary proteolytic activity in an in vitro infectivity assay, did not block the anti-HIV effects of saliva, suggesting that the salivary proteases are not responsible for the inhibition of HIV-1 infectivity.     

Irradiation-induced effects on the innervation of rat salivary glands: changes in enkephalin- and bombesin-like immunoreactivity in ganglionic cells and intraglandular nerve fibers

When treating head and neck for cancer with the use of radiotherapy the salivary glands are usually within the treatment volume with ensuing dryness and discomfort. Since the autonomic nervous system is of pivotal importance for the salivary gland function and integrity, the irradiation-induced effects may involve an influence on the innervation of salivary glands. Therefore, the rat submandibular gland, including the submandibular ganglionic cells, has been subjected to immunohistochemical examination with respect to expression of neuropeptides following fractionated irradiation with high energy photons. A markedly enhanced expression of bombesin- and leu-enkephalin-(ENK)-like immunoreactivities (LI) in the ganglionic cells and a pronounced increase in the number of nerve fibers showing these immunoreactivities in the submandibular gland tissue following irradiation were observed 10 days after treatment. On the other hand, no changes in the patterns of VIP (vasoactive intestinal polypeptide)- and NPY (neuropeptide Y)-immunoreactivities occurred. Thus, the present study shows that alterations in the expression of certain neuropeptides take place in the submandibular gland and its associated ganglionic cells in response to irradiation of the head and neck region. These changes may add further explanation to the inherent radiosensitivity of salivary glands.     

Histochemical study of magellanic penguin (Spheniscus magellanicus) minor salivary glands during postnatal growth

The histological and histochemical features of the minor salivary glands during postnatal development have been generally associated with the type of food ingested. However, recent studies support the fact that these salivary glands develop independently of the diet; in fact, minor salivary glands have similar morphological and histochemical characteristics in adult individuals of species with different diet regimens. Thus, the aim of this study was to characterize the developmental morphology of the penguin minor salivary glands and to contrast them with minor salivary glands of other species. The tongue, palatine, and mouth cavity (bottom) minor salivary glands of newborn, 1- to 20-day-old, and adult magellanic penguins were studied with hematoxylin-eosin, periodic acid-Schiff, alcian blue, toluidine blue, and lectin histochemistry. Minor salivary glands were present at all ages, although they were only moderately developed in animals less than 15 days old. After this age, glands were abundant in all age groups; in addition, cells from the glandular epithelium were functionally mature and secreted mucins. Nevertheless, in newborn to 15-day-old penguins, mucins were located only at the apical cytoplasm of mucous cells. In all ages, mucous cells displayed periodic acid-Schiff-positive, alcianophilic, and metachromatic reactions; among mucous cells, other orthochromatic cells appeared interspersed. From 15 days on, histochemical reactions became more intense until adulthood, and the cytoplasm of secretory cells was filled with glycoproteins and sulfomucins. Moreover, lectins bound to different oligosaccharides in mucous cells, depending on the stage of maturation of the glands. In conclusion, penguin minor salivary glands are already present at birth, and show progressive and quantitative increases in mucous secretion during postnatal development. These changes are necessary not only for nutrient ingestion, but also for nonimmune protection of the buccal cavity.