Poorly differentiated extra-axial extraskeletal chordoma diagnosed by methylation profiling: case report and analysis of brachyury expression in SWI/SNF-deficient tumors.

Chordoma is a rare malignant tumor with notochordal differentiation, usually affecting the axial skeleton of young patients. We report a case of a high-grade epithelioid tumor involving the synovium and soft tissues of the knee in a 74-year-old male patient. The preliminary biopsy was inconclusive, but a diagnosis of metastatic clear-cell carcinoma of unknown origin was suggested. However, imaging studies did not reveal any primary lesions. The resection specimen consisted of nests and sheets of oval to polygonal cells with discernible cell borders, clear or lightly amphophilic cytoplasm, and round to oval nuclei with occasional well-visible eosinophilic nucleoli. Rare atypical mitoses, necrotic areas, and bizarre nuclei were noted. The biopsy and resection specimens underwent a wide molecular genetic analysis which included methylation profiling. The DKFZ sarcoma classifier assigned the methylation class chordoma (dedifferentiated) with a calibrated score of 0.96, and additionally, a loss of SMARCB1 locus was noted in the copy number variation plot. To verify these findings, T-brachyury and SMARCB1 immunostaining was performed afterward, showing diffuse nuclear positivity and complete loss in the tumor cells, respectively. To assess the prevalence of T-brachyury immunopositivity among SWI/SNF-deficient tumors and to evaluate its specificity for poorly differentiated chordoma, we analyzed a series of 23 SMARCB1- or SMARCA4-deficient tumors, all of which were negative. After incorporating all the available data, including the absence of any morphological features of conventional chordoma, the case was diagnosed as poorly differentiated chordoma. As illustrated herein, the utilization of methylation profiling in the diagnostic process of some carefully selected unclassifiable soft tissue neoplasms may lead to an increased detection rate of such extremely rare soft tissue tumors and enable their better characterization.

Wireless Capsule Enteroscopy in Healthy Volunteers.

INTRODUCTION: The aim of our prospective study was to define endoscopy appearance of the small bowel in healthy volunteers. METHOD: Forty-two healthy volunteers underwent wireless capsule endoscopy, clinical investigation, laboratory tests, and completed a health-status questionnaire. All subjects were available for a 36-month clinical follow-up. RESULTS: Eleven subjects (26%) had fully normal endoscopy findings. Remaining 31 persons (74%), being asymptomatic, with normal laboratory results, had some minor findings at wireless capsule endoscopy. Most of those heterogeneous findings were detected in the small intestine (27/31; 87%), like erosions and/or multiple red spots, diminutive polyps and tiny vascular lesions. During a 36-month clinical follow-up, all these 42 healthy volunteers remained asymptomatic, with fully normal laboratory control. CONCLUSIONS: Significant part of healthy subjects had abnormal findings at wireless capsule endoscopy. These findings had no clinical relevance, as all these persons remained fully asymptomatic during a 36-month follow-up. Such an endoscopic appearance would be previously evaluated as "pathological". This is a principal report alerting that all findings of any control group of wireless capsule endoscopic studies must be evaluated with caution.

Small intestinal injury in NSAID users suffering from rheumatoid arthritis or osteoarthritis.

The goal of this prospective study was to assess non-steroidal anti-inflammatory drug (NSAID)-induced enteropathy in patients with rheumatoid arthritis (RA) or osteoarthritis (OA) by means of non-invasive wireless capsule enteroscopy. A total of 143 patients (74 with RA, 69 with OA) treated with NSAIDs (>1 month) and 42 healthy volunteers were included. All subjects underwent capsule endoscopy, laboratory tests and filled in questionnaires. The severity of small bowel injury was graded as: mild (red spots or sporadic erosions), moderate (10-20 erosions) or severe (>20 erosions or ulcers). Capsule endoscopy identified small bowel lesions in 44.8 % of patients (mild 36.4 %, moderate 3.5 % and severe in 4.9 %). Mild non-specific lesions were found in 11.9 % healthy volunteers. There was a significantly higher prevalence of enteropathy in RA (56.8 %) compared to OA (31.9 %, p < 0.01). A significant difference between NSAID users (RA and OA) with and without enteropathy was observed in erythrocytes (p < 0.01), the leucocyte count (p < 0.05), haemoglobin (p < 0.05), haematocrit (p < 0.05), serum albumin (p < 0.01) and erythrocyte sedimentation rate (p < 0.05). No relationship was found between enteropathy and dyspepsia, gender or age. NSAID therapy is associated with a significant risk of small bowel injury. The risk is significantly higher in RA patients suggesting a possible influence of the underlying disease. TRIAL REGISTRATION NUMBER: DRKS00004940.