Chronic edema, monoclonal dysglobulinemia and profuse telangiectasia: a distinct entity?

INTRODUCTION: Monoclonal gammopathy and edema are features encountered during several diseases, especially systemic capillary leak syndrome. The diagnoses of POEMS syndrome, edematous systemic scleroderma and a fortuitous association may be also discussed. We report the cases of two patients which did not fulfill the criteria for such diagnoses. CASE REPORT: Although the 2 cases share some discrepancies, they have also similar and particular features: association of chronic edema, monoclonal gammopathy and profuse and acquired telangiectasias. DISCUSSION: The meaning of these cases remains to be clarified. It might be an entity close to the systemic capillary leak syndrome but characterized by the chronicity of edema and by a distinct cutaneous sign, the occurrence of numerous telangiectasias. These cases emphasize that the acquired and profuse telangiectasias belong to the wide range of cutaneous abnormalities which may be associated with monoclonal paraproteinemia.     

Multiple myeloma and AL amyloidosis mimicking Sj?gren''s syndrome

A 49-year-old white man had xerostomia, orthostatic hypotension, salivary gland enlargement, and a monoclonal gammopathy. Salivary gland biopsy revealed AL amyloidosis without histopathologic evidence of Sj?gren's syndrome; serologic evidence of Sj?gren's syndrome was also absent. Bone marrow biopsy revealed more than 30% plasma cells, and a diagnosis of multiple myeloma was made. The association of myeloma amyloidosis with salivary gland infiltration and xerostomia is rare. Unusual causes of xerostomia, such as myeloma amyloidosis, should be considered when histopathologic and serologic evidence of Sj?gren's syndrome are absent.     

Functional properties of postganglionic sympathetic neurones supplying the submandibular gland in the anaesthetized rat

Sympathetic neurones supplying the submandibular salivary gland innervate blood vessels, secretory and myoepithelial cells. Here we examined whether these functionally different sympathetic neurones show distinct reflex response patterns. In anaesthetized rats, single unit activity was recorded from postganglionic axons projecting to the gland. Neurones were tested for their responses to stimulation of baroreceptors, cutaneous nociceptors and cold receptors and to gustatory stimuli applied to the tongue. Respiratory modulation was also analysed. Only a few postganglionic neurones identified electrically (5-10%) were spontaneously active. They were excited by noxious and cold stimuli, inhibited by baroreceptor stimulation and exhibited respiratory modulation. None of the units responded to gustatory stimuli. Thus, in anaesthetized rats spontaneously active sympathetic neurones supplying the submandibular gland behave like vasoconstrictor neurones. Sympathetic neurones with other functions are probably silent.     

Neurofibromatosis I and multiple sclerosis. Apropos of a case

We report a case associating NF1 with multiple sclerosis. There are only seven cases of this association, so that it might be interpreted as resulting from chance. However, although the association is weak, it might be non fortuitous, owing to a particularity of the NF1 gene that embedded oligodendrocyte-myelin glycoprotein gene, even if the responsibility of structural genes of myelin have not been implicated in susceptibility to multiple sclerosis.     

Hepatitis C virus infection of salivary gland epithelial cells. Lack of evidence

BACKGROUND: Hepatitis C virus genome (HCV-RNA) has been detected in whole salivary gland tissue of chronically infected patients. However, contamination of the tissue by plasma or blood cells was not excluded by the previous reports. AIMS: To assess whether HCV infects the salivary gland epithelial cells in patients with chronic HCV liver disease. METHODS: Twenty unselected patients with chronic active hepatitis (11 cases) or active cirrhosis (nine cases) were examined. Serum and saliva samples were obtained from all patients, 12 of whom (seven, chronic active hepatitis; five, active cirrhosis) underwent salivary gland biopsy. PCR for HCV-RNA was performed on RNA extracted from serum, saliva and salivary gland epithelial cells collected by isokinetic gradient separation after trypsin digestion of whole salivary gland tissue. Saliva samples were also examined for the presence of secretory IgA anti-HCV by gel chromatography and ELISA testing. RESULTS: HCV-RNA was detected in all sera with titers ranging from 5.42 x 10(5) genome equivalents/ml to 123.2 x 10(5) genome equivalents/ml. Thirteen patients were infected with genotype 1b, four patients had genotype 1a, two patients had genotype 2a and one patient was unclassifiable. Low titer HCV-RNA (<2 x 10(5) genome equivalents/ml) was detected in 3/20 saliva samples (15%) from highly viremic patients infected with 1b genotype. RNA extracted from salivary gland epithelial cells consistently tested negative for HCV-RNA. In addition, all saliva specimens tested negative for secretory-IgA (S-IgA) anti-HCV, even after a 10-fold concentration of the samples. CONCLUSIONS: There was no evidence that HCV infects the salivary gland epithelial cells in our viremic patients with HCV chronic liver disease. Low level HCV-RNA in saliva is most probably due to virus spillover from blood.     

Observations on two cases of apparent submandibular gland cysts in HIV positive patients: MR and CT findings

OBJECTIVE: To present two cases of probable lymphoepithelial cysts of the submandibular glands in patients who were human immunodeficiency virus (HIV) positive and who also had lymphoepithelial cysts of the parotid glands. MATERIALS AND METHODS: Computed tomography and MRI of two HIV positive patients with lymphoepithelial cysts of the parotid glands and cysts in the submandibular glands were correlated with the histories and the possible presence of other known causes of submandibular gland multiple cysts. RESULTS: Because of the present treatment philosophy regarding HIV positive patients with major salivary gland cysts, surgical resection of these glands was not performed. All other known causes of multiple submandibular gland cysts were excluded by either history or laboratory data. CONCLUSION: Computed tomography and MRI on two patients with known HIV infection and bilateral parotid lymphoepithelial cysts are presented. Both patients also had bilateral multiple submandibular gland cysts and no evidence of obstructive glandular disease, autoimmune disease, or other organ system cysts. These cases of presumed submandibular gland lymphoepithelial cysts are rare in the literature. They are presented in the hope that other radiologists will be stimulated to document the occurrence of this entity.     

The role of Epstein-Barr virus in lymphoepithelioma-like carcinomas

Epstein-Barr virus (EBV) has been implicated in the pathogenesis of a variety of lymphoproliferative disorders and several epithelial neoplasms, including undifferentiated nasopharyngeal carcinoma (UNPC; lymphoepithelioma). Lymphoepithelioma-like carcinomas (LEC) are tumors with morphologic features identical to UNPC that occur outside the nasopharynx. To determine whether EBV is associated with LEC, the authors conducted a comprehensive literature review of all pathologically documented LEC reported to date in the English literature. In summary, EBV is associated consistently with LEC from only four anatomic sites: stomach, salivary gland, lung, and thymus. Racial and/or geographic factors influence the association of EBV with LEC in some of these organs. Specifically, the association of EBV with LEC of the salivary gland and lung is restricted to Asian patients, whereas the association of EBV with gastric and thymic LEC is independent of race. The presence or absence of EBV in LEC does not appear to be prognotically important in those cases studies to date.     

Malignant neoplastic disease of the parotid lymph nodes

OBJECTIVES: To review the management and outcome of patients with malignant neoplastic disease of the parotid lymph nodes excluding those with primary salivary gland tumors. STUDY DESIGN: Retrospective review of 14 patients who had malignant parotid lymph nodes from metastatic cutaneous malignancies, direct extension from primary cutaneous malignancies, or lymphoproliferative disorders. METHODS: Charts were reviewed from three institutions and tabulated for age, gender, histopathology, treatment, and outcome. RESULTS: Fourteen patients met the criteria for study. Ten patients had neoplastic nodes from cutaneous malignancies. Seven involved squamous cell carcinoma, two were metastatic from melanoma, and one was metastatic from basal cell carcinoma. Four patients had involvement from lymphoproliferative disorders. CONCLUSIONS: Metastatic disease to the parotid nodes or direct extension to nodes from primary cutaneous malignancy demonstrates a poor prognosis in this series. Prognosis of lymphoproliferative disorder is more favorable.     

Proximal myotonic myopathy (PROMM) and other proximal myotonic syndromes

Palmoplantar orthokeratotic filiform hyperkeratosis is characterized by multiple, spiny, keratotic projections. We report a new case, occurring in an 85-year-old woman, associated with typical Darier's disease involving her chest and groin, that may be not fortuitous. Three previous reports point out its possible association with underlying diseases, such as malignancy or Darier's disease.     

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.     

Improving the selection of children for health assessment at secondary transfer age: completing the audit cycle

In this study, we have further characterized the morphology and physiology of the neuroglandular synapse between the identified buccal neuron, B4, and the salivary gland of Helisoma. We demonstrate that the coupling coefficient between salivary cells within an individual acinus is approximately 1.0. We also demonstrate that synapses within the salivary gland are located near a superficial muscle layer. We examine the effects of glutamate on the salivary gland and on the B4-salivary gland EPSP. L-glutamate produces a transient, rapid onset depolarization of salivary gland cells. The response is mimicked by high concentrations of L-homocysteic acid, but not by NMDA, L-aspartate, D-glutamate or kainate. The response is blocked by the presence of L- or D-glutamate in the bath, but not by CNQX, DNQX, DGG, D-AP5, or L-AP3. The depolarization is primarily dependent on the presence of calcium in the bathing solution. When either L- or D-glutamate is present in the bathing solution, the amplitude of the B4-salivary gland EPSP is reversibly reduced. The similar pharmacological properties of the response of the salivary gland to glutamate and the B4 epsp indicate that L-glutamate is a strong candidate for the fast excitatory neurotransmitter at the Helisoma neuroglandular synapse.     

Melatonin does not increase IOP significantly in rabbits

Among 3236 pediatric necropsies over 23 years, abnormal position of thymic tissue was recorded in 34 cases. Cardiac anomalies, predominantly those seen in DiGeorge syndrome, were present in 24; 3 had noncardiac anomalies only, 4 had other diseases, and 3 were sudden infant deaths. Mediastinal thymic tissue was absent in 22 cases, small or unilateral in 7, and normal in 5. The maldescended thymic tissue was unilateral in 18, bilateral in 11, and multiple on one or both sides in 5. It was situated near the thyroid gland in 19, lower in the neck in 6, and higher in 9, including 7 medial to the submandibular salivary gland and 1 at the base of the skull. The maldescended tissue approached the size of a normal lobe of thymus in eight and was 2.4 to 0.1 cm in the remainder. Over the same period, in only two cases was no thymic tissue found. Among 68,000 surgical specimens over 40 years, there were 10 cases of ectopic thymus in the neck, including 1 cutaneous and 4 cystic. This frequency of thymic tissue in the neck may explain why lymphoid tissues are sometimes relatively normal in cases of absent mediastinal thymus and behooves a search in the submandibular salivary gland region and higher before diagnosing thymic agenesis.     

Triple arthrodesis with lateral column lengthening for treatment of severe planovalgus deformity

The occurrence of abnormal nuclear DNA content in major salivary gland adenomas is not well known and its correlation with tumor recurrence has not been documented previously. From 1987 to 1991, 119 consecutive major salivary gland adenomas were operated on at Turku University Central Hospital. These tumors were analyzed by flow cytometry and 100 (84%) were found to be diploid, 12 (10%) near-diploid and 7 (6%) aneuploid with DNA indexes > 1.15. The mean proliferation rate measured as a percentage of cells in the S-phase fraction was 2.5 +/- 1.6%. The histological slides were then blindly reclassified according to current World Health Organization classification. As a result histological classification was changed in 3 tumors: malignant cells were found in 2 aneuploid tumors and 1 diploid neoplasm. Preoperative cytological fine-needle aspiration biopsy had been considered as possibly malignant in 2 of these cases. Among all case material 10 specimens were recurrent tumors; although the tendency to recur depended on the extent and adequacy of the surgery performed, multiple recurrences were associated with non-diploid tumors.     

Colonic anastomosis-a new approach: preliminary report

A case of fetal death from abruptio placentae is reported in which the placenta was the seat of multiple chorangiomata. This association is believed not to have been fortuitous and a possible mechanism is suggested by which chorangioma may contribute to the pathogenesis of placental abruption. The incidence, morphological variation and clinical manifestations of placental chorangiomata are briefly discussed.     

Association of amyotrophic lateral sclerosis with scleroderma. Study of 2 cases

We report a clinical association of diffuse scleroderma and amyotrophic lateral sclerosis (ALS) in two patients. Scleroderma was diagnosed on skin, digestive, osteoarticular, pulmonary lesions and inflammatory syndrome. ALS was suspected on the association of diffuse amyotrophy, fasciculations, pyramidal tract involvement and electrophysiological data. Chronic medulla ischemia and or immune abnormalities are proposed as potential pathological mechanisms for ALS but fortuitous association can not be excluded.     

Discrimination between fortuitous and biologically constrained open reading frames in DNA sequences of Saccharomyces cerevisiae

The systematic sequencing of the yeast genome has raised the problem of the biological significance of the open reading frames (ORFs) revealed: it is possible that some of these are fortuitous. To avoid the analysis of such fortuitous ORFs, a minimum length of 100 sense codons was adopted. Nevertheless, the presence of fortuitous ORFs of more than 100 codons cannot be excluded. Thus, in the context of functional analysis, a method for discrimination between fortuitous and biologically active ORFs may be useful. The discrimination method described here is based on multiple criteria: ORF length, codon bias, and both amino-acid and dipeptide composition of the corresponding polypeptide. The thresholds for each criterion are based on the comparison between two learning sets: one drawn from random DNA sequences and the second from known genes. The method was validated by two test sets (one random and one biological) and then applied to the ORFs of chromosomes I, II, III, V, VIII, IX and XI. This method predicts 123 fortuitous ORFs among the 1773 identified on these chromosomes.     

Phlebotomus papatasi sand fly salivary gland lysate down-regulates a Th1, but up-regulates a Th2, response in mice infected with Leishmania major

A vertebrate host becomes infected with Leishmania major when the sand fly vector injects parasites into skin along with saliva. Previous studies showed that salivary gland lysate of the New World sand fly Lutzomyia longipalpis markedly enhanced L. major infection in CBA mice. However, L. major is an Old World parasite transmitted in nature by the Old World sand fly Phlebotomus papatasi. Here we examine the ability of P. papatasi salivary gland lysate to enhance infection (lesion size and parasite burden) by L. major. In addition, we examine the effects of salivary gland lysate on the immune response to L. major by monitoring the levels of cytokine mRNA from the lymph nodes draining cutaneous lesions. We found that P. papatasi salivary gland lysate dramatically exacerbated lesion development in disease-resistant CBA mice. This exacerbation of disease correlated with inhibition of the production of Thl cytokines and associated factors (IFN-gamma, IL-12, and inducible nitric oxide synthase), but with enhancement of the Th2 cytokine IL-4, whereas no changes in the levels of IL-10 and TGF-beta were noted. Importantly, salivary gland lysate directly up-regulated expression of IL-4 mRNA in mice in the absence of infection with L. major.     

cDNA cloning and characterization of rat C5a anaphylatoxin receptor

lnterleukin-2 (IL-2) is known to cause xerostomia and skin manifestations similar to graft-versus-host disease (GVHD). We therefore evaluated major salivary gland function in patients with hematological malignancies treated with IL-2 and interferon-alpha (IFN-alpha) after ABSCT. Eleven patients (seven male, four female) of median age 40 (24-47) were evaluated, seven with non-Hodgkin lymphoma (NHL); one with Hodgkin's disease (HD) and three with acute myelogenous leukemia (AML). Parotid and submandibular salivary gland function was assessed before, during and after IL-2/IFN-alpha administration by evaluation of the salivary flow rate and the composition of secreted saliva. Significant reductions in both the resting and stimulated parotid and submandibular salivary flow rates were observed during IL-2/IFN-alpha immunotherapy compared with the pre- and post-therapy values (P < 0.01), while no hyposalivation was observed in the control patients who underwent ABSCT and did not received IL-2. Sialochemical evaluation revealed a significant increase in potassium concentration (24.4+/-0.6 mEq/l to 28.9+/-1.4 mEq/l) and a significant decrease in sodium concentration (6.7+/-2.1 mEq/l to 3.3+/-1.0 mEq/l) (P < 0.05) in the stimulated parotid gland saliva secreted during IL-2/IFN-alpha administration. Salivary protein concentrations were not altered by the IL-2/IFN-alpha immunotherapy. Similar changes were previously observed in mice and humans with chronic GVHD. We conclude that IL-2 immunotherapy induces major salivary gland dysfunction in humans, similar to our previous observations in patients with chronic GVHD, which may indicate similar pathophysiologic mechanisms.     

A guide to salivary gland disorders

This article discusses salivary gland disorders and provides nurses with a broad base of knowledge for use in planning and implementing perioperative patient care. Salivary gland disorders may be caused by nonneoplastic conditions or neoplasms. Nonneoplastic conditions generally are related to inflammatory processes or are secondary to existing disease processes. Neoplasms manifest themselves as benign or malignant tumors of the salivary glands. Patients with nonneoplastic conditions may undergo surgical procedures for health problems unrelated to their salivary gland disorders; however, patients with salivary gland neoplasms usually undergo surgical excisions of their tumors and affected glands. Patients in both categories require skilled perioperative nursing care.     

Salivary gland malignant myoepithelioma: a clinicopathologic and immunohistochemical study of ten cases

BACKGROUND: Malignant myoepithelioma (MME) of the salivary gland, also known as myoepithelial carcinoma, is rare and its biologic behavior has not been clarified fully. METHODS: Ten cases of MME were analyzed for their clinicopathologic features and immunohistochemical characteristics, focusing on prognostic factors and tumor differentiation. In addition, six cases of benign myoepithelioma (BME) also were examined for comparison. RESULTS: The ten patients with MME (3 men and 7 women) ranged in age from 48-81 years (mean, 61.9 years). Seven cases of MME arose in the parotid salivary gland, two in the submandibular salivary gland, and one in minor salivary glands of the soft palate. In the current series, the incidence of MME was 0.45% among 1945 cases of major salivary gland tumors. Seven cases of MME developed from a benign preexisting tumor (six in pleomorphic adenoma and one in BME). Four of nine patients with MME died of the disease and two patients developed a recurrence. It was shown that MMEs were comprised of one cell type or a combination of two cell populations; these included, in order of incidence, epithelioid, spindle, and plasmacytoid cells. Patients with MME with marked cellular pleomorphism and perineural invasion had a poor prognosis. Immunohistochemically, putative myoepithelial markers such as muscle actins, cytokeratin 14, vimentin, and calponin, and S-100 protein were expressed highly in MME. High and low molecular weight cytokeratins and epithelial membrane antigen also frequently were positive in MME. p53 expression was observed in five MME cases, four of which either recurred or were fatal. Cellular proliferative activity assessed by mitotic count and the Ki-67 labeling index was significantly higher in MME cases than in BME cases. In limited cases, such cellular proliferative activity was shown to have prognostic value. Ultrastructurally, the tumor cells displayed certain myoepithelial characteristics. CONCLUSIONS: MME is a rare salivary gland tumor showing clinicopathologic diversity and presenting with various stages of myoepithelial differentiation. Histologic aggressiveness, marked cellular pleomorphism, p53 expression, and high cell proliferative activity were found to be correlated with a poor clinical outcome.