[Massive pancarditis-autopsy report]. / Massive Pankarditis ­ ein Autopsiebericht.

We report on a 69-year-old man suffering from chronic progressive oligoarthritis (localized in metacarpal and knee joints), which clinically was interpreted as steroid-sensitive seronegative chronic arthritis. The patient died from sudden death at the emergency department after a 4-week history of increasing cough and dyspnea (meanwhile obtaining negative testing results for SARS-CoV-2). During the autopsy, we found massive pancarditis affecting all cardiac compartments, in particular exhibiting constrictive pericarditis, myocarditis, and multivalvular endocarditis. Microscopically, interstitial myocarditis could be observed. Performing extensive molecular analyses, we detected Tropheryma whipplei in the tissue specimens of the heart, but not in various duodenal tissue probes or in the synovial membrane. Taken together, in the present case the cause of death was acute cardiac failure due to multivalvular pancarditis due to T. whipplei. Besides from classical symptoms and morphological signs, Whipple's disease may present with various features. Regarding the differential diagnosis of a chronic multisystem disorder with aspects of hitherto unknown arthralgia, Whipple's disease should be considered.

[Uncommon tumor of the gastric wall]. / Ungewöhnlicher Magenwandtumor.

We report on a 72-year-old male patient suffering from weight loss, diarrhea, and epigastric pain. By means of endosonographic ultrasound, a well-circumscribed tumor mass was found in the gastric wall, suggesting a gastrointestinal stromal tumor (GIST). Biopsies were taken and processed for standard histopathological analysis. The microscopy revealed uniform, small, round cells with central nuclei and prominent cell borders embedded in vascularized stroma. Immunohistochemistry demonstrated the expression of actin, but showed negativity for cytokeratin, CD34, CD117, DOG­1, desmin, and CD45. The tumor was diagnosed as a gastral glomus tumor. The diagnosis was confirmed in the wedge resection specimen. Gastral glomus tumors are rare intramural tumors of the stomach. GIST and neuroendocrine tumor (NET) present the main differential diagnoses. Especially with regard to the epithelioid variant of GIST, clear separation can be difficult. Besides standard histological examination, immunohistochemistry and molecular analysis can be helpful since gastral glomus tumors do not obtain c­Kit- or PDGFRα mutations. Based on the fact that this tumor most commonly shows a benign biological behavior, the prognosis of gastral glomus tumors is favorable.

[Bronchoalveolar lavage in hairy cell leukemia with pulmonary infiltration]. / Bronchoalveoläre Lavage bei Haarzellleukämie mit Lungeninfiltration.

We report a 78-year-old male patient suffering from hairy cell leukemia, presenting clinically mainly with dyspnea. Radiology exhibited bilateral ground-glass shadows. In order to prevent pneumonia as a possible side effect due to conventional chemotherapy, it was decided to first treat the patient with rituximab; however, dyspnea persisted. Therefore, bronchoscopy was performed and specimens were sampled for both histological examination and bronchoalveolar lavage (BAL) analysis. BAL showed lymphocytosis (28.7%), and by means of immunocytochemistry a few CD79a+ B­lymphocytes as well as lymphoid cells positive for the hairy cell marker DBA44 were observed. In addition, molecular study revealed the BRAF V600E mutation. Thus, the findings of BAL were interpreted as lung infiltration by hairy cell leukemia. This result was confirmed by histology. Following a therapy switch to cladribine, a significant improvement was reached. Pulmonary infiltrates by hairy cell leukemia were rarely described. This case represents the first report of hairy cell leukemia diagnosed by means of BAL. It may be difficult to clearly separate between lymphoma infiltration of the lung and medicamentous pneumonitis, but this differential diagnosis can be supported by morphological methods.

[Sarcoma of the spleen with MDM2 expression]. / Sarkom der Milz mit MDM2-Expression.

Primary sarcomas and sarcoma metastases are a rarity in the spleen. We report on the case of a 69-year-old male patient presenting with unclear abdominal symptoms and computed tomography (CT) revealed a tumor mass in the spleen. Histologically the tumor mass predominantly showed features of a spindle cell sarcoma with lymphoid infiltrates. The expression and amplification of MDM2 could be demonstrated by means of immunohistochemistry and fluorescence in situ hybridization (FISH). Furthermore, staging examinations did not reveal indications of any other primary tumors. These preliminary findings were suggestive of a dedifferentiated liposarcoma; however, in the further diagnostic work-up the tumor showed strong expression of CD21 and CD23 and was ultimately diagnosed as a follicular dendritic cell sarcoma (FDCS). The case emphasizes that MDM2 expression represents a possible pitfall in the diagnosis of spindle cell tumors. The differential diagnostic distinction between FDCS and a dedifferentiated liposarcoma is discussed.

The ganglioside antigen G(D2) is surface-expressed in Ewing sarcoma and allows for MHC-independent immune targeting.

BACKGROUND: Novel treatment strategies are needed to cure disseminated Ewing sarcoma. Primitive neuroectodermal features and a mesenchymal stem cell origin are both compatible with aberrant expression of the ganglioside antigen G(D2) and led us to explore G(D2) immune targeting in this cancer. METHODS: We investigated G(D2) expression in Ewing sarcoma by immunofluorescence staining. We then assessed the antitumour activity of T cells expressing a chimeric antigen receptor specific for G(D2) against Ewing sarcoma in vitro and in vivo. RESULTS: Surface G(D2) was detected in 10 out of 10 Ewing sarcoma cell lines and 3 out of 3 primary cell cultures. Moreover, diagnostic biopsies from 12 of 14 patients had uniform G(D2) expression. T cells specifically modified to express the G(D2)-specific chimeric receptor 14. G2a-28ζ efficiently interacted with Ewing sarcoma cells, resulting in antigen-specific secretion of cytokines. Moreover, chimeric receptor gene-modified T cells from healthy donors and from a patient exerted potent, G(D2)-specific cytolytic responses to allogeneic and autologous Ewing sarcoma, including tumour cells grown as multicellular, anchorage-independent spheres. G(D2)-specific T cells further had activity against Ewing sarcoma xenografts. CONCLUSION: G(D2) surface expression is a characteristic of Ewing sarcomas and provides a suitable target antigen for immunotherapeutic strategies to eradicate micrometastatic cells and prevent relapse in high-risk disease.

Intracardiac erythropoietin injection reveals antiinflammatory potential and improved cardiac functions detected by Forced Swim Test.

Systemic administration of erythropoietin (Epo) protects the myocardium from an ischemic insult and promotes beneficial remodeling. We hypothesized that intracardiac injection of Epo may exhibit cardioprotective potential with reduced systemic toxicity. Following myocardial infarction (MI), Epo was injected directly into the border of the infarction. Six weeks after an MI, we evaluated infarction size, angiogenesis, and pathologic effects of the treatment. Myocardial performance was assessed with a Forced Swim Test adapted to the study. Anti-inflammatory and cellular proliferative effects of Epo were analyzed by measuring expression of integrin-beta and CdK4 by reverse transcriptase-polymerase chain reaction (RT-PCR). The findings indicated improved cardiac status with direct Epo administration. Exercise capacity detected by the Forced Swim Test was significantly increased. There was radical reduction of absolute infarction size, ventricular dilatation, and hypertrophy in the Epo group. Integrin-beta was down-regulated and CdK4 expression was increased significantly with Epo. In conclusion, the study demonstrated that intramyocardial Epo injection, following MI, reduced inflammation, enhanced angiogenesis and proliferation, improved myocardial functions, and did not lead to intramural thrombus formation.