Küttner's tumour of the submandibular gland

Küttner's tumour (chronic sclerosing sialadenitis) is a chronic inflammatory disease of the salivary glands that produces a firm and relatively painful swelling of the glands. Although Küttner's tumour is a common submandibular disease, many clinicians and pathologists have under-recognized this entity because of its superficial resemblance to neoplasia and the presence of only a few reports in the English literature. We report a case of Küttner's tumour in a 41-year-old male who presented with a painless submandibular mass, and discuss its histological and clinical characteristics.     

Abundant IgG4-positive plasma cell infiltration characterizes chronic sclerosing sialadenitis (Küttner's tumor)

Chronic sclerosing sialadenitis (CSS) is a cryptogenic tumor-like condition of the salivary gland(s). While immune-mediated processes are suspected in its pathogenesis, and CSS is occasionally reported to be associated with sclerosing pancreatitis, an IgG4-related disease, the exact immunopathologic processes of CSS remain speculative. In this study, we examined the clinicopathologic findings of CSS (12 cases) in comparison with sialolithiasis (8 cases) and Sjogren's syndrome (13 cases), and tried to clarify whether CSS is an IgG4-related disease or not. Submandibular gland(s) were affected in all cases of CSS. CSS cases could be divided into two types: 5 cases were associated with sclerosing lesions in extrasalivary glandular tissue (systemic type), while only salivary gland(s) were affected in the remaining 7 cases (localized type). In the former type, which showed male predominance, bilateral salivary glands were frequently affected, and eosinophilia and elevations of gamma-globulin and IgG in serum were frequently found. Histologically, all cases of CSS showed marked lymphoplasmacytic infiltration admixed with fibrosis and the destruction of glandular lobules. Obliterative phlebitis was found in the affected salivary glands in all cases of CSS. Immunohistochemically, the proportion of IgG4/IgG-positive plasma cells was more than 45% in CSS, while it was less than 5% in controls. The resemblance of the clinicopathologic features of CSS with those of sclerosing pancreatitis suggests the participation of a similar immunopathologic process with IgG4 disturbance in CSS. The abundance of IgG4-positive plasma cells in the lesions would be useful for distinguishing CSS from other forms of sialadenitis.     

Küpffer cells promote acute rejection via induction of Th17 differentiation in rat liver allografts

Background

Th17, a newly identified CD4+ T-cell subset, has been implicated in transplant rejection. Differentiation of Th17 cells is associated with transforming growth factor-β (TGF-β) and interleukin-6 (IL-6), which are the main products of Küpffer cells.

Objective

To determine whether Küpffer cells promote acute liver allograft rejection by inducing Th17 cell differentiation.

Methods

A rat model of allogeneic liver transplantation using Dark Agouti (DA) to Brown Norway (BN) rats was established with or without gadolinium chloride (GdCl₃) pretreatment. Isogeneic liver transplantation (BN to BN) was performed as a control. Concentrations of cytokines secreted by Küpffer cells or Th17-related cytokines detected in the liver and peripheral blood were analyzed using immunohistochemistry assays, flow cytometry, and enzyme-linked immunosorbent assays. Survival differences were compared between treatment groups. In vitro, Küpffer cells from liver grafts were isolated and co-cultured with naïve CD4 T cells.

Results

Both Küpffer cells and Th17 cells infiltrated liver allografts, accompanied by an increase in concentrations of IL-6 and TGF-β. Pretreatment with GdCl₃ attenuated intragraft infiltration of Küpffer cells and Th17 cells, and decreased IL-6 and TGF-β concentrations. Liver function improved after pretreatment, and mean (SD) survival time was prolonged, compared with the control group (16.33 [0.96] days vs 11.50 [0.99] days, respectively; P < .01). In vitro, Küpffer cells from livers with allografts secreted significantly higher concentrations of IL-6 and TGF-β and induced Th17 differentiation more effectively compared with livers with isografts (30.8% vs 8.1%, respectively).

Conclusion

Küpffer cells have the potential to induce Th17 cells by secreting IL-6 and TGF-β, and as a result, promote acute liver allograft rejection.     

Marginal zone B-cell lymphoma of the salivary gland arising in chronic sclerosing sialadenitis (Küttner tumor).

We report a case of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type of the salivary gland arising in a background of chronic sclerosing sialadenitis. Chronic sclerosing sialadenitis is a common fibrosing chronic inflammatory lesion of the submandibular gland, which is thought to be the result of sialolithiasis, and is not associated with a systemic autoimmune disease. Salivary MALT lymphomas are typically associated with lymphoepithelial sialadenitis (LESA) in a patient with or without Sj?gren's syndrome. Our case of salivary MALT lymphoma was neither preceded by Sj?gren's syndrome nor accompanied by LESA. This case suggests that chronic inflammatory processes other than Sj?gren's syndrome may provide a substrate for the development of MALT lymphoma.     

Morphometry of isolated tumor cells in breast cancer sentinel lymph nodes: metastases or displacement?

Iatrogenic displacement and mechanical transport of epithelial cells to the sentinel node (SN) has been suggested to result in false-positive findings in breast cancer patients, but little biologic evidence has yet been presented for this hypothesis. As malignant nuclei are larger than benign ones, nuclear morphometry of SN isolated tumor cells (ITC) could provide relevant information with regard to the malignant origin-or-not of epithelial cells in the SN. In patients with primary invasive breast cancer and SN ITC with (N=16) or without (N=45) non-SN involvement, nuclear morphometry was performed on the primary tumor as well as on the ITC in the SN. Nuclear size in the primary tumor was compared with that in the corresponding ITC. Patients with SN micrometastases (N=30) and SN macrometastases (N=30) served as controls. Nuclear size of ITC was significantly smaller compared with nuclear size of the corresponding primary tumor (P<0.0001). In contrast, there were no differences in nuclear size between SN micrometastases and macrometastases on the one hand and their corresponding primary tumors on the other. In addition, a subgroup of cases (10/61, 16%) with benign morphometric features of SN ITC nuclei (small and isomorph) could be discerned that had no non-SN metastases. In conclusion, nuclei of SN ITC are significantly smaller compared with the corresponding primary tumor and are often not associated with non-SN involvement. This supports the hypothesis that some of these deposits could represent benign epithelium or degenerated malignant cells lacking outgrowth potential.     

'Spindle cell oncocytoma' of the adenohypophysis: a tumor of folliculostellate cells?

We describe five primary tumors of the adenohypophysis featuring mitochondrion-rich spindle cells. The patient ages ranged from 53 to 71 years (mean 61.6 years); two were female. All presented with panhypopituitarism. Two also had visual field defect. On neuroimaging all tumors showed suprasellar extension and were indistinguishable from pituitary adenoma. None showed imaging or operative evidence of dural involvement. All were gross totally removed: four by transsphenoidal surgery and one by frontal craniotomy. Follow-up ranged from 2 to 68 months (mean 35.4 months). No recurrences were noted. The clinical workup was noncontributory in all but two patients: one (case no. 4) with an oncocytic thyroid adenoma and another (case no. 5) with squamous carcinoma of both the uterine cervix and of vocal cord. Histologically, the five tumors were composed mainly of fascicles of spindle cells with eosinophilic, granular cytoplasm. Mitoses were rare and necrosis was absent. Neoplastic cells were immunoreactive for vimentin, epithelial membrane antigen, S-100 protein, and galectin-3. Stains for pituitary hormones, synaptophysin, chromogranin, glial fibrillary acidic protein, cytokeratin CAM5.2, smooth muscle actin, CD34, and CD68 were negative. No thyroglobulin immunoreactivity was noted in the tumor of case no. 4. Ultrastructurally, the neoplastic cells contained numerous mitochondria with lamellar cristae. The neoplastic cells were linked by intermediate junctions and desmosomes. No secretory granules were noted. The histologic, immunohistochemical, and fine structural features of these tumors were unlike those of pituitary adenoma or any other primary sellar tumor. A derivation from adenohypophyseal folliculostellate cells is suggested.     

Detection of vital germ cell tumor cells in short-term cell cultures of primary tumors and of retroperitoneal metastasis —Clinical implications

By establishing short-term cell cultures derived from retroperitoneal metastasis after neoadjuvant chemotherapy, our aim was to improve the diagnosis and prognosis in patients with advanced testicular germ cell tumors. The histological evaluation of surgically removed metastatic tissue by retroperitoneal lymphadenectomy (RLA) is extremely complicated after previous chemotherapy, but knowledge of persistence of vital tumor cells in residual lesions is of great prognostic value and therapeutic consequence in patients with testicular germ cell tumors. We therefore investigated whether vital tumor tissue could be detected in short-term cell cultures derived from such metastatic lesions by measuring the concentration of the tumor markers beta human chorionic gonadotropin (HCG) and alpha-1 fetoprotein (AFP) in cell culture supernatants. We initially demonstrated the specificity of the determination in cell cultures of human transitional-cell carcinoma cell lines, human foreskin fibroblasts and normal testicular tissue. In a group of 20 patients with untreated primary testicular germ cell tumors, detection of HCG and AFP was increased about threefold in cell culture supernatants in comparison to the serum concentration. Finally, we prepared primary cell cultures from surgically removed retroperitoneal metastasis of 12 patients with testicular germ cell tumors after chemotherapy. The serum concentrations of HCG and AFP of all patients were at normal values when RLA was performed. However, pathologically increased concentrations of HCG (3/3) and AFP (2/3) in cell culture supernatants were found in 3 of 12 cell cultures. Interestingly, these three patients with a pathological increase in HCG and AFP as determined in the supernatant of the short-term cell cultures had tumor progression within a mean follow-up of 3 ± 1 months (P < 0,01), whereas 9 of 12 patients who had no pathological increase in HCG and AFP as determined in the supernatant of the short-term cell culture were in complete remission (CR) after a mean follow-up of 40 ± 11.6 months.     

Hürthle cell tumor of the thyroid: analysis of 188 cases

We reviewed 188 cases of Hürthle cell tumor of the thyroid (HCT) between 1982 and 1996. There were 160 women and 28 men with a mean age of 51.8 years. Thirty-one of the patients had cancer, and the others had adenoma. Age, size of the primary tumor, and preoperative thyroglobulin level were not significantly different in the cancer and adenoma patients. The gender ratio, however, was significantly different (p < 0.05). Recurrent HCT was observed in three patients with adenoma. Two patients had subcutaneous recurrence (suspected implantation), and the other patient had recurrence in the residual thyroid gland. All patients with recurrence of adenoma underwent partial lobectomy at the initial operation. Three cancer patients had recurrent disease. Locoregional recurrence was observed in one patient and distant metastases in two patients (lung in one, lung and bone in one). One of the patients with distant metastasis died from the disease, and the other is alive with the disease. Tumor implantation was observed in patients with adenoma, so intraoperative handling of the tumor requires care. It also means that this tumor, even though benign, is aggressive in terms of proliferative activity. All patients with Hürthle cell tumor should be treated by total lobectomy at least. The outcome of the cancer patients was not as poor as in previous reports.     

Complications of Küntscher intramedullary nailing in a child: a case report

A fracture of the femur in a 7-year-old boy who was treated with retrograde Küntscher nailing is described. The follow-up period was 8 1/2 years. Deep infection, physeal injury of the femoral head, and trochanteric epiphysiodesis were serious consequences of the surgery.     

Increased human tumor necrosis factor-α levels induce procoagulant change in porcine endothelial cells in vitro

Lee KG, Lee H, Ha JM, Lee YK, Kang HJ, Park C‐G, Kim SJ. Increased human tumor necrosis factor‐α levels induce procoagulant change in porcine endothelial cells in vitro. Xenotransplantation 2012; 19: 186–195. © 2012 John Wiley & Sons A/S. Abstract: Background: Intravascular thrombosis and systemic coagulation abnormalities are major hurdles to successful xenotransplantation and are signs of acute humoral rejection. Increased expression of tissue factor (TF) is associated with the development of microvascular thrombosis in xenografts. To develop an effective strategy to prevent accelerated coagulation in xenografts, we investigated the mechanism by which porcine endothelial cells (PECs) become procoagulant after contact with human blood. Methods: The changes in TF mRNA levels and activity in PECs after incubation with 20% human serum or human bioactive molecules, including C5a, tumor necrosis factor‐α (TNFα) and interleukin (IL)‐1α, were evaluated using real‐time PCR and the factor Xa chromogenic assay, respectively. The procoagulant changes in PECs by these agonists were evaluated by measuring the coagulation time of human citrated plasma suspended with PECs pretreated with each agonist. TF expression and coagulation times were also assessed in PECs transfected with short interfering RNA (siRNA) designed to knock down porcine TF. We also examined the production of proinflammatory cytokines in human whole‐blood or plasma after contact with PECs, which were screened using the cytometric bead array system. TNFα levels were measured using ELISA in whole‐blood after contact with PECs, with or without the addition of xenoreactive antibodies or C1 esterase inhibitor. Results: Porcine TF mRNA and activity in PECs were up‐regulated in response to human TNFα and IL‐1α but were not affected by C5a or 20% human serum. Up‐regulation of TF expression by human TNFα or IL‐1α shortened PEC‐induced coagulation time, while siRNA‐mediated knockdown of TF expression prolonged coagulation time. The incubation of PECs with human whole‐blood led to a significant increase in human TNFα levels in the blood, which was promoted by the addition of xenoreactive antibodies and prevented by C1 esterase inhibitor. Conclusions: Human TNFα level increases in human blood after contact with PECs, which is attributed to xenoreactive antibody binding and subsequent complement activation. Human TNFα induces procoagulant changes in PECs with increased TF expression. This study suggests that human TNFα may be one of the mediators linking complement activation with procoagulant changes in the xenoendothelium.