Chronic sclerosing sialadenitis of the submandibular gland associated with idiopathic retroperitoneal fibrosis

We report a case of a 57-year-old man who developed a fibrosclerosing lesion in the submandibular gland and idiopathic retroperitoneal fibrosis (IRF) involving the unilateral periureteral region within a year. Both lesions were resected surgically because of the suspicion of neoplasm. Pathologic examination revealed similar histologic and immunohistochemical features for both lesions, namely, fibrosclerosis with prominent hyalinizing collagen bundles and proliferation of myofibroblastic cells, and a non-neoplastic reactive nature. There was infiltration by lymphocytes with prominent lymph follicles, plasma cells and macrophages. The histologic and immunohistochemical findings suggest that the two lesions were of a similar pathogenesis, which was possibly mediated by macrophages. We think that the present case may be an unusual form of multifocal fibrosclerosis. Although sialolithiasis is thought to be a major pathogenic factor for chronic sclerosing sialadenitis of the submandibular gland, the present case suggests that certain cases might have an etiology similar to IRF.     

Chronic sclerosing sialadenitis of the submandibular gland: an entity of IgG4-related sclerosing disease

Chronic sclerosing sialadenitis typically involves the submandibular gland. It usually occurs in the middle-aged and elderly adults with a slight male predominance. Recent evidences have suggested that it is an entity of IgG4-related sclerosing disease and has distinct histopathological features, such as a dense lymphoplasmacytic infiltrate, sclerosis and obliterative phlebitis. It is important to discriminate this entity from other diseases, trying to give effective treatment to the patients. In this report, we described a patient having chronic sclerosing sialadenitis in the submandibular gland.     

Chronic sialadenitis with psammoma bodies mimicking neoplasia in a fine-needle aspiration specimen from the submandibular gland

A 65-year-old woman with a submandibular gland nodule had a fine-needle aspiration specimen that contained groups of duct-type cells and a psammoma body, suggestive of adenocarcinoma. The resected gland showed chronic sialadenitis with sialolithiasis and psammoma bodies. In a series of 81 resected nonneoplastic submandibular glands from 72 patients, psammoma bodies, nonlaminated microcalcifications, or both were found in 46 (57%). They were located most commonly just outside of striated or intercalated ducts. When examining fine-needle aspiration specimens from the submandibular gland, it is important that one be aware that psammoma bodies may occur in normal, inflamed, irradiated, and neoplastic conditions.     

A case of granulomatous sialadenitis of the submandibular gland

Granulomatous inflammation of the major salivary glands is very rare and may be due to obstruction. Little attention has been paid to this condition. The reaction is caused by extravasation of mucus, as seen in the common mucocele of the minor salivary glands. A case of granulomatous inflammation of the submandibular gland caused by obstruction is presented. The etiology of granulomatous sialadenitis is reviewed.     

Lymphocyte subsets in irradiation-induced sialadenitis of the submandibular gland

AIMS: Irradiation-induced sialadenitis is a significant cause of morbidity in head and neck cancer patients receiving radiotherapy. Neither the exact aetiopathology of chronic irradiation-induced sialadenitis nor the mechanisms leading to atrophy of the glandular cells associated with an increase in extracellular matrix are understood. The aim of our study was to determine the phenotype of the inflammatory infiltrate and to study its distribution in the affected submandibular glands. METHODS AND RESULTS: Paraffin-embedded submandibular glands from a homogeneous group of 19 patients with advanced oropharyngeal cancer who received conventional radiotherapy to the primary site and upper neck were analysed. In all patients the radiation dose and field were approximately equal. The submandibular glands were obtained during neck dissection. To characterize the lymphoid infiltrate, all tissue sections were immunostained for T cells (CD3, CD4, CD8), cytotoxic T cells (granzyme B), B cells (CD20), and macrophages (Ki-M1p). A histopathological classification into four grades was established based on the degree of glandular atrophy, fibrosis and lymphocytic infiltration. Phenotypic analysis of submandibular gland sections revealed that the great majority of lymphocytic infiltrates were cytotoxic T cells associated with acinar cell destruction. CONCLUSIONS: The significantly elevated frequencies of cytotoxic cells in the submandibular glands of patients with irradiation-induced sialadenitis suggest that cell-mediated immune mechanisms may play a part in the pathogenesis of this disease.     

44例慢性硬化性颌下腺炎临床病理分析

目的探讨硬化性颌下腺炎的形态学特点和细胞因子在慢性硬化性颌下腺炎中的表达与纤维化的相关性。方法44例慢性硬化性颌下腺炎,根据颌下腺纤维化程度分期分为4组,用免疫组化方法分别观察4组中的TGF-β1、Ⅰ型胶原(colla-genⅠ,Col-Ⅰ)和纤维连接蛋白(fibronectin,FN)的表达,并与正常组对照,用图像分析仪测定并进行统计学分析。结果TGF-β1、Col-Ⅰ和FN的表达量均与颌下腺的病变程度成正比(各组均P<0·05);TGF-β1与Col-Ⅰ、FN的表达量成正相关(各组均P<0·05)。结论随着慢性硬化性颌下腺炎病变程度的加重,TGF-β1表达增加,可能通过促进细胞外基质(extracellular ma-trix,ECM)合成(Col-Ⅰ、FN等)而参与颌下腺纤维化发生,并在颌下腺纤维化形成过程中起重要作用。     

Suppression of immune responsiveness by a submandibular salivary gland factor.

Both tissue extracts prepared from submandibular salivary glands of male mice and epidermal growth factor isolated from these glands depressed the delayed type hypersensitivity response to 2,4-dinitro-1-fluorobenzene in mice. Extirpation of the submandibular salivary glands from male mice did not alter the delayed type hypersensitivity response. The role of salivary gland factors, particularly epidermal growth factor, in influencing the immune response has been discussed.     

Development of allergic sialadenitis in mice immunized with mumps virus-infected submandibular salivary gland.

This article reports that sialadenitis developed in female, rather than male, of CRJ:CD-1 mice thymectomized 3 days after birth and later immunized with murine submandibular salivary gland cells which were infected with mumps virus (MV) in vitro. Significant inflammatory changes did not develop in various control groups, including animals not thymectomized but immunized, animals thymectomized on the day of birth and immunized, animals thymectomized at Day 3 and immunized with the uninfected cells, and animals thymectomized at Day 3 and immunized with MV alone. The presence of antisalivary duct antibody was found in sera from mice with sialadenitis. MV antigen in the lesions as well as viremia was not detected. The lesions observed in mice with sialadenitis were mostly composed of small and medium-sized lymphocytes stained by anti-Thy 1.2 and Lyt 2 antibodies and in later stages by immunoglobulin-containing cells in the periphery of inflammatory lesions. Moreover, mild inflammatory lesions were observed in parotid salivary gland or pancreas in some mice that developed sialadenitis.     

The autologous mixed lymphocyte reaction is not primarily due to xenoantigenic stimulation

Autologous mixed lymphocyte reaction (AMLR) is an interesting in vitro system in which T lymphocytes proliferate when cultured with non-T cells from the same individual. Because this system has both memory and specificity and elicits help, suppression, cytotoxicity, and soluble mediators, it has been proposed that it reflects in vitro the complex interactions of the immunologic network as it operates in vivo. A recent study, however, has cast doubt on the significance of this reaction by implicating xenoantigens, present during separation and/or culture procedures (e.g., sheep red blood cells or fetal calf serum), in the proliferative response of T cells. This question is analyzed by performing AMLR studies with cells (from eight normal subjects) that were separated with and without the use of sheep erythrocytes, and incubated with either fetal calf serum on normal human AB serum. Results were similar in all circumstances and negate a primary role of xenoantigens in AMLR.     

The protective capacity of immune sera in experimental mouse salmonellosis is mainly due to IgM antibodies

Passive immunization was used to protect mice against a general infection caused by Salmonella typhimurium and our purpose was to compare the protective capacity of different immunoglobulin isotypes (classes and subclasses). Three antisera were studied, one pool of mouse serum against the envelope of rough bacteria, and two rabbit sera against smooth bacteria. Three different methods were used to separate isotypes. The consistent finding was that only IgM antibodies protected efficiently. A unit of IgG antibodies had an effect that was 1/50th of the IgM effect or less. This effect could have been due to a contamination by IgM. IgA appears to be non-protective like IgG. In two of the antisera a considerable proportion of protective antibodies were against a defined antigenic determinant (anti-0–4,5 or anti-0–9). IgG antibodies of these sera measured by the solid phase assay were also predominantly anti-0–4,5 or anti-0–9, respectively. This argues that the failure of IgG antibodies to protect cannot be explained by assuming that unlike IgM antibodies they are directed against “non-protective” determinants. We conclude that the observed difference between the protective capacities of IgM and IgG antibodies is due to C-region differences between the μ- and γ-chains.     

Chronic progressive panencephalitis due to rubella virus simulating subacute sclerosing panencephalitis.

Late-onset chronic progressive panencephalitis developed in a 12-year-old boy with congenital rubella syndrome from whose brain rubella virus was isolated. Progressive dementia began at eight, and ataxia, choreiform movements, myoclonic seizures, and fine perimacular pigmentation appeared at 11 years of age. The cerebrospinal fluid was minimally pleocytotic and had a total protein of 156 mg per deciliter, of which 52 per cent was gamma globulin. Electroencephalography demonstrated generalized medium and occasional high-voltage slowing without burst suppression. The antibody titer to rubella virus (hemagglutination inhibition) was 1:8192 in serum and 1:256 in cerebrospinal fluid. Antibody titer to measles virus (complement fixation) was less than 1:8 in serum. Microscopical study of biopsied brain tissue at the age of 11 disclosed panencephalitis similar to subacute sclerosing panencephalitis, but with perivascular deposits and without inclusion bodies. Rubella virus was isolated from the brain by cocultivation with CV-1 cells.     

Impaired vascular reactivity following angioplasty is mainly due to endothelial injury.

Vasoconstriction occurs frequently following coronary angioplasty and is implicated in the pathogenesis of abrupt closure and restenosis. Control of vasomotor tone is regulated in part directly by smooth muscle cells and indirectly through the endothelium. To study the mechanisms underlying vasoconstriction, the effect of angioplasty and endothelial denudation on endothelium-dependent and -independent relaxation was examined in 15 mongrel dogs. Percutaneous transluminal angioplasty and endothelial denudation of the right femoral artery were performed. Endothelial injury was assessed by adhesion of indium-111-labeled platelets. Endothelium-dependent and -independent relaxation were assessed using acetylcholine and nitroglycerin, respectively. Vessels precontracted with potassium chloride and exposed to acetylcholine showed impaired relaxation in both the angioplasty and denuded groups (angioplasty = 14 +/- 5%, denuded = 0 +/- 0%, normal = 73 +/- 12%; P less than 0.05 for both angioplasty and denuded compared to normal). Precontraction with phenylephrine yielded similar results (angioplasty = 16 +/- 8%, denuded = 4 +/- 2%, normal = 39 +/- 10%; P less than 0.05 only for denuded segment compared to normal). Segments precontracted with phenylephrine and exposed to nitroglycerin did not demonstrate impaired relaxation (angioplasty = 73 +/- 9%, denuded = 68 +/- 9%, normal = 71 +/- 7%, P = ns). Mean indium-111 counts were similar in both the angioplasty and denuded segments (2820 +/- 1481 and 2963 +/- 1228 counts/min/g, respectively) compared to a lower count in the normal segment (1514 +/- 956 counts/min/g). Thus, angioplasty produces significant vascular injury and impairment of vasodilator function, comparable to that caused by endothelial denudation alone. This implies that vasoconstriction seen following coronary angioplasty may be due to endothelial injury and the resultant loss of control of vasomotor tone.     

Reaction of the rat submandibular salivary gland to injury to the contralateral gland

After burns of resection of the submandibular salivary gland the intact contralateral gland in rats responds by increased proliferative activity. The number of mitoses reached a maximum 72 h after injury in the case of burns and 48 h after resection. Burns of the salivary gland cause lasting but weak compensatory hypertrophy of the contralateral gland. Hypertrophy of the gland is accompanied by an increase in size of the cells and nuclei, the area of which rises by 10 and 17% respectively. Resection of the salivary gland causes an increase in weight of the intact gland only in the early period of observation; by the 30th and 45th days after the operation the weight of the experimental glands was not significantly different from the control. Differences in compensatory growth of the intact glands observed after two types of injury of the contralateral gland evidently depend on the quantity of tissue breakdown products and the duration of their presence in the body.Department of Biology and General Genetics, Moscow Medical Stomatological Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR A. P. Avtsyn.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 82, No. 9, pp. 1108–1110, September, 1976.     

Suppression and enhancement of in vitro lymphocyte reactivity by factors in rat submandibular gland extracts.

The addition of crude extracts from rat submandibular (SM) glands to murine spleen and lymph node cell cultures stimulated with concanavalin A (Con A) induced either suppression (at high concentrations) or further stimulation (at lower concentrations) or further stimulation (at lower concentrations) of proliferative activity. Gel filtration of the extracts revealed that suppressive activity was due to factors of molecular weight in the 50,000-96,000 range, while stimulation was due to factors in the 13,000-35,000 molecular weight range. The suppressor activity of the higher molecular weight fractions was not due to a reduction of cell viability or of the uptake of tritiated thymidine. This was demonstrated by the fact that the addition of IL-2 to the cultures completely reversed the suppressive effect. Further fractionation of the suppressive and of the stimulatory gel filtration fractions with the chromatofocusing technique led to the identification of a single fraction with suppressor activity and of multiple discrete fractions with stimulatory activity.     

Blood flow and permeability changes in the immune lymphocyte transfer reaction.

Blood flow (133Xe clearance) and plasma exudation ([133I]HSA) have been measured in the immune lymphocyte transfer (ILT) reaction and skin grafts in rabbits. Injection of sensitised lymphocytes produced a dose-related increase in plasma exudation and blood flow at 48 hr, reached a maximum at day 3 and faded from day 5 to 8. There was an increased blood flow and plasma exudation on day 4 after grafting autografts and homografts, but the increase in plasma exudation was significantly higher in homografts. In the ILT reaction (48 hr) and the homografts (4 days) but not in autografts, prostaglandin synthetase inhibition caused a significant reduction in the increased blood flow, but did not abolish it nor did they affect the increased plasma exudation. It is concluded that the ILT reaction is a suitable model for the study of mediators of the vascular effects of the early phase of the skin graft reaction. The present experiments suggest that the vasodilatation is partly due to prostaglandin formation, but part of the vasodilatation and all the plasma exudation are mediated by substances other than prostaglandins.     

The inhibitory activity of serum to prevent bacterial adhesion is mainly due to apo-transferrin

A marked, up to 5-fold, reduction in bacterial adhesion to Tecoflex polyurethane (PU) surfaces was observed in the presence of bovine/human serum or plasma at 0.5% or higher concentrations in the medium. Further investigation of the phenomenon resulted in identification, isolation, and characterization of the serum component with the ability to significantly reduce bacterial adhesion. Upon fractionation of bovine serum by an anion exchange chromatography, protein pools were made and analyzed by immunoelectrophoresis and by polyacrylamide gel electrophoresis in the presence of SDS and were examined for their effect on the adhesion of Staphylococcus epidermidis to PU surfaces. The pool exhibiting a significant inhibitory effect was subjected to further biochemical tests, which resulted in the identification of transferrin (Tf) as its predominant protein. Bacterial adhesion studies in the presence of purified Tf revealed that holo-Tf (iron-containing form) had no influence on bacterial adhesion at any concentration. Only apo-Tf (iron-lacking form) exerted the inhibitory effect, in a dose responsive manner at concentrations of 10 microg/mL or higher. Bacteria remained viable when suspended at the low apo-Tf concentrations, sufficient to prevent bacterial adhesion.     

Chronic sclerosing sialadenitis as one of the immunoglobulin G4-related diseases: a clinicopathological study of six cases from Central Europe

Laco J, Ryska A, Celakovsky P, Dolezalova H, Mottl R & Tucek L (2011) Histopathology 58 , 1157–1163 Chronic sclerosing sialadenitis as one of the immunoglobulin G4‐related diseases: a clinicopathological study of six cases from Central Europe Aims: Chronic sclerosing sialadenitis (CSS) has been proposed recently to be a member of the group of IgG4‐related diseases in Japanese and American series. The aim of our study was to validate these results in a cohort of European patients. Methods and results: Our CSS series included four females and two males, aged 32–76 years, all presenting with unilateral swelling of submandibular gland. Microscopically, all CSS‐cases showed similar morphology with preservation of lobular architecture accentuated by cellular fibrous bands, dense lymphoplasmacytic inflammation and varied acinar atrophy. Ductal lymphocytes were detected in three cases. In five cases, the presence of intraductal secretory material accompanied by parenchymal neutrophils was observed. Obliterative phlebitis was seen in three cases. The inflammatory infiltrate was composed of T and B lymphocytes and polyclonal plasma cells. The median number of IgG‐positive plasma cells per high‐power field (HPF) was 157; median number of IgG4‐positive plasma cells per HPF was 133. Median value of the IgG4:IgG ratio was 0.84. Conclusions: This is the first European series to demonstrate that CSS belongs to the family of IgG4‐related disease. Unlike previous studies, in CSS we found rarely described ductal lymphocytes and parenchymal neutrophils. CSS displays consistent morphology with increased numbers of IgG4‐positive plasma cells, and should be regarded as a member of the IgG4‐related disease group.     

Carcinosarcoma of the submandibular gland. An autopsy case.

We present a rare case of submandibular gland carcinosarcoma occurring in a 45-year-old male patient. His clinical history revealed that the carcinosarcoma had developed from a carcinoma ex mixed tumor in three years. In spite of repeated resection, intensive chemotherapy and irradiation, the tumor recurred and grew rapidly, and the patient died of hemothorax caused by rupture of a pulmonary metastatic tumor. The fourth recurrent tumor and autopsy specimens showed features of carcinosarcoma consisting of three tumor components, i.e., undifferentiated carcinoma, and chondrosarcomatous and osteosarcomatous growth. The metastatic nodules in both lungs and pulmonary hilar lymph nodes showed the same pattern. Immunohistochemically, the chondrosarcomatous cells were positive for vimentin and S-100 protein, and for epithelial markers such as epithelial membrane antigen (EMA) and cytokeratin (MA-902). Undifferentiated carcinoma cells, on the other hand, were partially positive for muscle actin other than cytokeratin (KL 1). Ultrastructurally, desmosome-like structures were seen in the chondrosarcomatous cells. These findings suggest that the sarcomatous lesions might have originated from epithelial cells.     

Chronic pericarditis due to a streptomyces species.

Streptomyces species include a group of aerobic actinomycetes that are generally considered to be saprophytes. Effusoconstrictive pericarditis of mixed etiology developed in a previously healthy patient. The cause of the chronic pericarditis was a Streptomyces species.