Diagnostic Value of Labial Minor Salivary Gland Biopsy: Histological Findings of a Large Sicca Cohort and Clinical Associations.

(1) Background: The aim of this study was to analyze labial minor salivary gland biopsy (MSGB) findings of a large sicca cohort and to examine their associations with Sjogren's syndrome (SS)-associated laboratory markers, phenotypic characteristics and systemic manifestations. Moreover, we sought to explore the ability of MSGB to identify SS patients among subjects with pre-diagnosed fibromyalgia (FM). (2) Methods: Included were all patients of three rheumatology departments having undergone a diagnostic MSGB within 9 years. Next to the examination of histological and immunohistochemical findings, we focused on activity and chronicity parameters of the underlying disease, autoantibodies, presence of systemic and hematologic involvement, as well as chronic pain and SS comorbidities. (3) Results: Among the 678 included patients, 306 (45.1%) had a positive focus score (FS). The remaining patients (n = 372) served as control subjects. There were significant correlations between FS and hypergammaglobulinemia (p < 0.001), ANA and rheumatoid factor positivity (both; p < 0.001), a weak significant correlation with erythrocyte sedimentation rate (rho = 0.235; p < 0.001) and a negative correlation with nicotine use (p = 0.002). Within the primary SS subgroup, FS was associated significantly with glandular enlargement (p = 0.007) and systemic hematologic manifestations (p = 0.002). Next to FS, CD20 cell staining showed an excellent diagnostic performance in the diagnosis of SS by an area under the curve of 0.822 (95%CI 0.780-0.864; p < 0.001). Interestingly, 42.1% of all patients with fibromyalgia (FM) having received an MSGB could be diagnosed with SS. (4) Conclusion: By examining one of the largest cohorts in the literature, we could show that MSGB histological and immunohistochemical findings not only play a key role in the classification and diagnosis of SS but could also provide important information regarding SS phenotype and systemic manifestations. Furthermore, MSGB may help differentiate patients with FM from patients with subclinical SS who suffer primarily from chronic pain.

Intra-abdominal EWSR1/FUS-CREM-rearranged malignant epithelioid neoplasms: two cases of an emerging aggressive entity with emphasis on misleading immunophenotype.

CREB family (CREB1, ATF1, and CREM) gene fusions are defining markers in diverse mesenchymal neoplasms (clear cell sarcoma, angiomatoid fibrous histiocytoma, and others). However, neoplasms harboring EWSR1-CREM/FUS-CREM fusions are rare and poorly characterized. We describe two cases (55-year-old male with 7.5 cm renal mass and 32-year-old female with 5.5 cm mesenteric mass) illustrating their misleading immunophenotypes. Histologically, both showed eosinophilic and focally clear epithelioid cells arranged into sheets, nests, and trabeculae. Immunohistochemistry showed ALK, EMA, and AE1/AE3 immunoreactivity suggesting ALK-rearranged renal cell carcinoma (Case 1) and coexpression of keratin, EMA, synaptophysin, and chromogranin-A, suggesting neuroendocrine neoplasm (Case 2). Targeted RNA sequencing revealed EWSR1-CREM (Case 1) and FUS-CREM (Case 2) fusions. These cases add to the spectrum of CREM fusion-positive intra-abdominal epithelioid neoplasms. Their unusual immunophenotype and unexpected sites represent major pitfalls, underline a wide differential diagnosis, and emphasize the value of molecular testing in correctly diagnosing them.

[Very rare cases of periprosthetic malignant neoplasms : Data from 4000 cases of endoprosthetic joint replacements from the histopathologic implant register]. / Nachweis hoch seltener periprothetischer maligner Neoplasien : Ergebnisse von 4000 Gelenkendoprothesen aus dem histopathologischen Implantatregister.

BACKGROUND: In 2016, the AG 11 (work group for implant-material-intolerance) of the German society for Orthopaedics and Orthopaedic Surgery (DGOOC) created a histopathologic implant register (HIR). The goal was to conduct a retrospective data analysis based on the revised SLIM-consensus-classification, which defines eight different failure mechanisms. QUESTIONS: The analysis of 4000 cases of endoprosthetic joint replacements addressed the following questions: 1. What is the frequency distribution of different SLIM-types? 2. How does durability of endoprosthetic joint replacements differ among SLIM-types? 3. What kind of periprosthetic malignant neoplasia can be detected and how often? RESULTS: SLIM-type I was diagnosed in 1577 cases (n = 1577, 39.4%), SLIM-type II in 577 cases (n = 577; 14.4%), SLIM-type III in 146 cases (n = 146; 3,7%), SLIM-type IV in 1151 cases (n = 1151; 28.8%), SLIM-type V in 361 cases (n = 361; 9.0%), SLIM-type VI in 143 cases (n = 143; 3.6%), SLIM-type VII in 42 cases (n = 42; 1.0%), and SLIM-type VIII in 3 cases (n = 3; 0.075%). There was statistical significance in implant durability between the different SLIM types. Among the different reasons for endoprosthetic joint replacement failure, non-infectious causes have the biggest share at 81%, with SLIM-type I (39.5%), and SLIM-type IV (29.4%) being the predominant SLIM types. Three cases of periprosthetic malignant neoplasia (SLIM-type VIII) were detected: one case of small B lymphocytic lymphoma/BCLL (C85.9; ICD-O: 9670/3), one case of diffuse large B­cell lymphoma/DLBCL (C83.3; ICD­O 9680/3), and one case of anaplastic large cell lymphoma (C84.7; ICD-O: 9714/3), with the latter ones being the causes for joint replacement , which indicates that malignant neoplasia is a very rare cause of endoprosthetic joint replacement (n = 2; 0.05%). DISCUSSION: These data are complete new, especially as concerns arthrofibrosis (SLIM-type V), adverse inflammatory reactions (SLIM-type VI), and the very rare cases of periprosthetic malignant neoplasia, SLIM-type VIII, as a reason for revision. Since neither the annual review (2017) of the EPRD, nor the national evaluation report (2017) of the IQTIG provide sufficient data, this indicates the relevance of the HIR of the AG 11 of the DGOOC.

Trefoil factor 3 expression in epithelial ovarian cancer exerts a minor effect on clinicopathological parameters.

The role of trefoil factor 3 (intestinal) (TFF3) has been analyzed in numerous cancers, such as breast and gastrointestinal cancer, and has been associated with poor prognosis. However, the role of TFF3 in ovarian cancers is not clear. Expression analysis of TFF3 in 91 ovarian cancer patients was performed by immunohistochemistry of primary paraffin-embedded tumor samples. The results were scored according to staining intensity and percentage of positive tumor cells resulting in an immune-reactive score (IRS) of 0-12. These results were correlated with clinicopathological characteristics and survival. TFF3 expression in our patient cohort exhibited a tendency towards improved overall and progression-free survival (PFS). In TFF3-positive serous and high-grade serous ovarian cancers, the median PFS was 27.6 months [95% confidence interval (CI): 0-55.7] vs. 15.2 months in TFF3-negative tumors (95% CI: 13.8-16.6) (P=0.183). The median overall survival was 53.9 months in TFF3-positive tumors (95% CI: Non-applicable) vs. 44.4 months in TFF3-negative cases (95% CI: 30.5-58.3) (P=0.36). TFF3 negativity was significantly associated with higher tumor grade (P=0.05). Based on our results, further studies are required in order to elucidate whether survival and chemosensitivity are affected by TFF3 expression in ovarian cancer.

Imaging mass spectrometry to discriminate breast from pancreatic cancer metastasis in formalin-fixed paraffin-embedded tissues.

Diagnosis of the origin of metastasis is mandatory for adequate therapy. In the past, classification of tumors was based on histology (morphological expression of a complex protein pattern), while supportive immunohistochemical investigation relied only on few "tumor specific" proteins. At present, histopathological diagnosis is based on clinical information, morphology, immunohistochemistry, and may include molecular methods. This process is complex, expensive, requires an experienced pathologist and may be time consuming. Currently, proteomic methods have been introduced in various clinical disciplines. MALDI imaging MS combines detection of numerous proteins with morphological features, and seems to be the ideal tool for objective and fast histopathological tumor classification. To study a special tumor type and to identify predictive patterns that could discriminate metastatic breast from pancreatic carcinoma MALDI imaging MS was applied to multitissue paraffin blocks. A statistical classification model was created using a training set of primary carcinoma biopsies. This model was validated on two testing sets of different breast and pancreatic carcinoma specimens. We could discern breast from pancreatic primary tumors with an overall accuracy of 83.38%, a sensitivity of 85.95% and a specificity of 76.96%. Furthermore, breast and pancreatic liver metastases were tested and classified correctly.

Abdominal pseudocysts following peritoneal dialysis-associated peritonitis: a report of 3 cases.

Common complications of peritoneal dialysis are peritonitis, leakages, hernias, catheter dislocation, and loss of ultrafiltration. We describe 3 cases of abdominal pseudocysts with progressive difficulty instilling and draining peritoneal dialysis fluid. The 3 patients had been treated with peritoneal dialysis for 1, 2, and 6 years. Two patients had experienced previous episodes of peritonitis and 1 had signs of peritonitis when the pseudocyst was first detected. In all 3 patients, ultrasound and computed tomographic scans, obtained because of progressive decreases in solute clearance, showed dialysate entrapped in a cyst that enclosed the inner tip of the Tenckhoff catheter. The cyst was resected in 2 patients, and the Tenckhoff catheter was removed in 1 patient. Histologic samples were not suggestive of encapsulating peritoneal sclerosis. Abdominal pseudocysts are a rare complication after peritoneal dialysis therapy, but are reported in 1% of patients with ventriculoperitoneal shunts. The outcome of our described patients was good, although they had to be switched to hemodialysis therapy.

Modification of human platelet adhesion on biomaterial surfaces by protein preadsorption under static and flow conditions.

Biomaterial-induced thrombosis remains one of the main complications of vascular implant devices. Preadsorbed proteins on the biomaterial/blood interface will modify the adhesion and activation of platelets (PTLs) during the initial contact-phase. Our results clearly show that PTL-adherence on biomaterials is influenced not only by protein preadsorption, but also by flow conditions. The covalent coating of TCPS and glass by phosphorylcholine (PC) induces a significant decrease of PTL adhesion but leads to a slight, but nevertheless significant activation of PTL, which was detected by the induction of P-selectin expression using FACS analysis. Methodologically, the visualization of PTL adhesion gave more reliable results for measurement of PTL adhesion than the cell-enzyme immunoassay (EIA) for P-selectin. Human citrated plasma caused an inhibition of PTL. It is probable, that the contained sodium citrate may inhibit PTL adhesion by its calcium ion-binding capacity. The flow experiment as dynamic system is in our view absolutely essential for the evaluation of biomaterials for vascular prosthesis, and is in accordance with the international standards. The results of the experiments also suggest that investigations under static and flow conditions are needed to determine the influence of protein adsorption on mixed blood cell populations, for example, on PTL and PMN mixtures/co-cultures in order to achieve a better simulation of the in vivo situation.

Small intestinal submucosa for pubourethral sling suspension for the treatment of stress incontinence: first histopathological results in humans.

PURPOSE: Small intestinal submucosa (SIS), a biomatrix of porcine origin, is used in pubourethral sling operations for female urinary stress incontinence, among other urological and surgical indications. To our knowledge we report the first histopathological examination of this biomatrix in human subjects. MATERIALS AND METHODS: In a series of 15 patients with pubourethral sling procedures using SIS 3 reoperations were necessary because of recurrent urinary stress incontinence at a mean of 12.7 months. Biopsies were taken from the implantation site of the SIS band under the vaginal mucosa. Several immunohistochemical reactions were used to identify any inflammatory reaction. RESULTS: The biopsies under investigation showed nothing more than focal residues of the SIS implant without any evidence of a specific tissue reaction. There were no changes that might point to a foreign body reaction. There was likewise no evidence of any significant immunological reaction and in particular no evidence of any chronic inflammatory reaction. CONCLUSIONS: The morphological findings point to outstandingly good biocompatibility of SIS. During healing the material is incorporated into the body without any foreign body or inflammatory reaction. The results of the first histological investigation of SIS in human subjects emphasize the special status of SIS among implant materials.

Myocardial angiogenesis resulting in functional communications with the left cavity induced by intramyocardial high-frequency ablation: histomorphology of immediate and long-term effects in pigs.

A previous study in rabbit hearts demonstrated the feasibility of creating transmyocardial channels by application of temperature-regulated high-frequency (HF) energy. Feasibility of creating non-transmural channels using a transvascular approach was tested in 14 pigs which were followed for 1 h, and 3 and 9 weeks (group A, B and C). Myocardial channels were found to be highly reproducible and patent in more than two thirds in group A. Channels were replaced by connective tissue during follow-up which contained newly formed small vessels. A functional communication between the left ventricular cavum and newly formed vessels of the channel remnants could be demonstrated in one heart of group C. Thus, intramyocardial HF ablation can be performed with high reproducibility to induce local angiogenesis.

Modification of human polymorphonuclear neutrophilic cell (PMN)-adhesion on biomaterial surfaces by protein preadsorption under static and flow conditions.

Biomaterials induce a specific reaction after implantation in the human body. This reaction depends on the chemical and physico-chemical properties of the material as well as on the site and type of implantation. We have used a dynamic model, the parallel-plate flow-chamber, to examine the interactions of different biomaterials with polymorphonuclear neutrophilic cell (PMN) and how these interactions are influenced by protein preadsorption. Our results clearly show that for hydrophobic materials, glass and PE, which induce a prominent adhesion of PMN, the mixture of albumin and fibrinogen induces the best inhibitory effect. On hydrophilic biomaterial surfaces, untreated TCPS and PC-coated TCPS, reveal only a minor influence of adsorbed proteins on PMN adhesion because of a primary low adhesive surface for PMN and proteins as well. Human citrated plasma leads only to a slight inhibition of PMN adhesion. On the hydrophobic materials, glass and PE, bovine serum albumin (BSA) had the best anti-adhesive potential with respect to PMN. The coating using phosphorylcholine is an excellent surface modification to prevent PMN-adhesion and protein adsorption. The results of our experiments suggest that investigations under static and flow conditions are also needed to determine the influence of protein adsorption on other relevant blood cell populations, for example, platelets and monocytes.

New aspects in the histological examination of polyethylene wear particles in failed total joint replacements.

The most important long-term complication in total joint replacements is aseptic osteolysis. Wear particles such as polyethylene (PE) debris are considered to be one of the causes that play a central role. Several studies indicated that PE can be visualised in paraffin-embedded tissue sections not only by polarised light, but also after oil red staining. To determine whether oil red staining enables sensitive detection of PE, we examined staining of mechanically-produced PE particles by oil red. Furthermore, we studied oil red staining of paraffin-embedded tissue specimens of patients with failed uncemented and cemented total knee and hip prostheses. We applied double labelling of sections by immunohistochemistry using the macrophage marker anti-CD68 and oil red staining. We found that oil red stains both isolated PE particles and PE particles in paraffin-embedded tissue sections. Polymethylmethacrylate particles in failed cemented arthroplasties did not stain in paraffin sections. Double labelling showed strong colocalisation of CD68 and PE. We suggest that oil red staining is a sensitive method to detect PE particles. Oil red staining is particularly helpful in these cases which show a characteristic histological feature of aseptic prosthesis loosening without particles being detectable with routine microscopy and polarised light. We also established that immunohistochemical methods can be applied together with the oil red staining method.

Impact of vessel curvature on the accuracy of three-dimensional intravascular ultrasound: validation by phantoms and coronary segments.

BACKGROUND: Three-dimensional intravascular ultrasound (IVUS) is used for volumetric assessment of arteriosclerotic plaque burden and restenotic tissue at follow-up after coronary interventions. However, the accuracy of these measurements, especially in tortuous vessels, is unclear. METHODS: A commercially available electrocardiogram (ECG)-gated 3-dimensional-IVUS system was tested in volume-validated straight and curved hydrocolloid phantoms and in volume-validated coronary specimens. Catheter withdrawal (30 MHz, 3.2F) was triggered using standardized ECG source with 0.2-mm step intervals per cardiac cycle simulation. RESULTS: On the basis of automated phantom volume measurements, IVUS overestimated true phantom volume (relative error = [measured V - true V]/true V x 100) by a median of 0.9%, 0.25%, and 1.96% for straight, mildly curved, and severely curved segments, respectively. The true volume of the coronary specimens was overestimated by a median of 5.79%. CONCLUSION: A median percentage deviation of 3-dimensional-IVUS-measured volumes from the true volumes of less than 10% in phantoms and coronary artery segments can be achieved.

Software-supported image quantification of angiogenesis in an in vitro culture system: application to studies of biocompatibility.

Healing of soft tissue trauma and bone discontinuities following implantation involves acute inflammatory reactions and the formation of blood vessels (angiogenesis). During angiogenesis new capillary vessels arise from the existing vasculature. Endothelial cells (EC) are the major cell type involved in angiogenesis. Corrosion of orthopaedic metallic implant materials (e.g. CoCr alloys) can cause locally high concentrations of heavy metal ions in the peri-implant tissues. Some divalent metal ions (Co2+, Ni2+, Zn2+) lead to the activation of EC in vitro. Upon exposure to these ions. EC release cytokines and chemokines and increase the expression of cell surface adhesion molecules, which represents the pro-inflammatory phenotype. In this study we have examined whether metal ions influence the other endothelial aspect of wound healing, the angiogenic response. Therefore, we utilized an in vitro model of angiogenesis and examined the effects of divalent cobalt ions on the in vitro vessel formation. The quantification of the cobalt/ion-exerted effects on angiogenesis in vitro was performed using a contrast-rich vital staining and analysed by software-supported image quantification.

Discrimination of early/intermediate and advanced/complicated coronary plaque types by radiofrequency intravascular ultrasound analysis.

Radiofrequency intravascular ultrasound (IVUS-RF) analysis, as an extension of conventional IVUS imaging, may provide more accurate plaque discrimination. Thirty-two autopsy atherosclerotic coronary arteries were investigated. Corresponding sectors in different plaques were matched by histologic and RF analysis. Histologic analysis utilized the American Heart Association plaque classification. The backscattered ultrasound RF signal was analyzed by fast-Fourier transform, providing the underlying frequency components of its power spectrum. The normalized backscattered signal power (in decibels [dB]) for frequencies between 15.3 and 40.3 MHz was then measured for plaque discrimination. Advanced/complicated plaque types showed a higher signal power at all frequencies than early/intermediate lesion types (p <0.001 to p = 0.005). Discrimination of advanced/complicated lesion types was best at 15.3 MHz, with a cut-off point of 2.5 dB (sensitivity 93%, specificity 79%), and second best at 17.6 MHz (sensitivity 87%, specificity 71%, cut-off point 1.9 dB). With conventional IVUS, plaque discrimination was weaker; the best sensitivity for diagnosing early/intermediate lesion types was reached for "soft plaque" (sensitivity 63%, specificity 73%). Compared with conventional IVUS, IVUS-RF can discriminate between advanced/complicated and early/intermediate coronary atherosclerotic lesions with relatively high sensitivity and specificity in vitro.