Perivascular epithelioid cell neoplasms (PEComas) are a family of mesenchymal neoplasms with features of both melanotic and smooth muscle differentiation. PEComa morphology is highly variable and encompasses epithelioid to spindle cells often with clear cytoplasm and prominent nucleoli. Molecularly, most PEComas are defined by a loss of function of the TSC1/TSC2 complex. Additionally, a distinct small subset of PEComas harboring rearrangements of the TFE3 (Xp11) gene locus has been identified. By presenting a series of three case reports with distinct features, we demonstrate diagnostic pitfalls as well as the importance of molecular work-up of PEComas because of important therapeutic consequences.

Prostate cancer is one of the leading causes of cancer mortality in men worldwide. An unusual but unique environment for studying tumor cell processes is provided by microgravity, either in space or simulated by ground-based devices like a random positioning machine (RPM). In this study, prostate adenocarcinoma-derived PC-3 cells were cultivated on an RPM for time periods of 3 and 5 days. We investigated the genes associated with the cytoskeleton, focal adhesions, extracellular matrix, growth, survival, angiogenesis, and metastasis. The gene expression of signaling factors of the vascular endothelial growth factor (VEGF), mitogen-activated protein kinase (MAPK), and PI3K/AKT/mTOR (PAM) pathways was investigated using qPCR. We performed immunofluorescence to study the cytoskeleton, histological staining to examine the morphology, and a time-resolved immunofluorometric assay to analyze the cell culture supernatants. When PC-3 cells were exposed to simulated microgravity (s-µg), some cells remained growing as adherent cells (AD), while most cells detached from the cell culture flask bottom and formed multicellular spheroids (MCS). After 3-day RPM exposure, PC-3 cells revealed significant downregulation of the VEGF, SRC1, AKT, MTOR, and COL1A1 gene expression in MCS, whereas FLT1, RAF1, MEK1, ERK1, FAK1, RICTOR, ACTB, TUBB, and TLN1 mRNAs were not significantly changed. ERK2 and TLN1 were elevated in AD, and FLK1, LAMA3, COL4A5, FN1, VCL, CDH1, and NGAL mRNAs were significantly upregulated in AD and MCS after 3 days. After a 5-day culture in s-µg, the PC-3 cells showed significant downregulations of VEGF mRNA in AD and MCS, and FN1, CDH1, and LAMA3 in AD and SCR1 in MCS. In addition, we measured significant upregulations in FLT1, AKT, ERK1, ERK2, LCN2, COL1A1, TUBB, and VCL mRNAs in AD and MCS, and increases in FLK1, FN1, and COL4A5 in MCS as well as LAMB2, CDH1, RAF1, MEK1, SRC1, and MTOR mRNAs in AD. FAK1 and RICTOR were not altered by s-µg. In parallel, the secretion rate of VEGFA and NGAL proteins decreased. Cytoskeletal alterations (F-actin) were visible, as well as a deposition of collagen in the MCS. In conclusion, RPM-exposure of PC-3 cells induced changes in their morphology, cytoskeleton, and extracellular matrix protein synthesis, as well as in their focal adhesion complex and growth behavior. The significant upregulation of genes belonging to the PAM pathway indicated their involvement in the cellular changes occurring in microgravity.

The aim of this study was to assess the value of ¹⁸F-FDG PET/CT for quantitative assessment of hepatic metabolism in patients with different stages of liver fibrosis/cirrhosis. ¹⁸F-FDG PET/CT scans of 37 patients either with or without liver fibrosis/cirrhosis, classified according to the METAVIR score (F0-F4) obtained from histopathological analysis of liver specimen, were analyzed retrospectively and classified as follows: no liver fibrosis (F0, n = 6), mild liver fibrosis (F1, n = 11), advanced liver fibrosis (F2, n = 6), severe liver fibrosis (F3, n = 5), and liver cirrhosis (F4, n = 11). The liver-to-blood ratio (LBR, scan time corrected for a reference time of 75 min) was compared between patient groups. Patients with liver fibrosis or cirrhosis (≥ F1; LBR 1.53 ± 0.35) showed a significant higher LBR than patients with normal liver parenchyma (F0, 1.08 ± 0.23; P = 0.004). In direct comparison, LBR increased up to the advanced stage of liver fibrosis (F2; 2.00 ± 0.40) and decreased until liver cirrhosis is reached (F4, 1.32 ± 0.14). Functional changes in liver parenchyma during liver fibrosis/cirrhosis affect hepatic glucose metabolism and significantly differ between stages of liver fibrosis/cirrhosis, classified according to the METAVIR scoring system, as demonstrated by LBR quantification by ¹⁸F-FDG PET/CT.

Background and Aims: Amyloidosis is a group of systemic disorders caused by extracellular deposition of misfolded serum proteins. Gastrointestinal (GI) involvement is associated with a higher risk of GI bleeding, especially if mucosal lesions are present. Our study aims to evaluate the frequency of GI manifestations in patients with amyloidosis, to clinically characterize these patients and to describe the endoscopic and histopathologic findings in GI amyloidosis. Methods: A retrospective, single-center study of all patients admitted with amyloidosis and GI manifestations was conducted at a German University Hospital between July 2003 and June 2023. Clinical, endoscopic, and histopathological data was retrieved from medical records. Results: Between July 2003 and June 2023, 63 patients with different types of amyloidosis were included into the study. Twenty-three (36,5%) were diagnosed with GI involvement of amyloidosis (60.9% male, median age 62 ± 18.28 years). The distribution of the types of amyloidosis were amyloid light chain (AL) at 52.5%, transthyretin (ATTR) at 21.7%, amyloid A (AA) at 13.0%, and unknown at 18%. Initial GI symptoms were present in 78.3% of the patients and included mainly diarrhea (34.8%), and abdominal pain (30.4%) Affected GI organs were primarily the colon (60,8%) and the stomach (39.1%). Endoscopic findings were ulcerations (47.8%), mucosal inflammation (43.5%), polyps (26.1%), erosions (13.0%), vascular malformation, polypoid protrusion, submucosal hematoma, erythema, metaplasia, and diverticulum. Histopathological findings included vascular wall thickening, (peri-)vascular and interstitial amyloid deposition. Gastrointestinal bleeding occurred in 39.1% of the patients. The mortality rate 5 years after diagnosis was 47.8%. Conclusions: Gastrointestinal amyloidosis can present with multiple symptoms and endoscopic findings, rendering diagnosis a challenge. Of clinical relevance, GI bleeding was a frequent event in our patient cohort. Therefore, clinicians must be aware of GI bleeding as a manifestation of amyloidosis and definite diagnosis should be achieved based on biopsy results.

Autologous lipotransfer is a promising method for tissue regeneration, because white adipose tissue contains a heterogeneous cell population, including mesenchymal stem cells, endothelial cells, immune cells, and adipocytes. In order to improve the outcome, adipose tissue can be processed before application. In this study, we investigated changes caused by mechanical processing. Lipoaspirates were processed using sedimentation, first-time centrifugation, shear-force homogenization, and second-time centrifugation. The average adipocyte size, stromal vascular cell count, and adipocyte depot size were examined histologically at every processing step. In addition, the adipose derived stem cells (ADSCs) were isolated and differentiated osteogenically and adipogenically. While homogenization causes a disruption of adipocyte depots, the shape of the remaining adipocytes is not changed. On average, these adipocytes are smaller than the depot adipocytes, they are surrounded by the ECM, and therefore mechanically more stable. The volume loss of adipocyte depots leads to a significant enrichment of stromal vascular cells such as ADSCs. However, the mechanical processing does not change the potential of the ADSCs to differentiate adipogenically or osteogenically. It thus appears that mechanically processed lipoaspirates are promising for the reparation of even mechanically stressed tissue as that found in nasolabial folds. The changes resulting from the processing correspond more to a filtration of mechanically less stable components than to a manipulation of the tissue.

(1) Background: molecular tumor boards (MTBs) are crucial instruments for discussing and allocating targeted therapies to suitable cancer patients based on genetic findings. Currently, limited evidence is available regarding the regional impact and the outreach component of MTBs; (2) Methods: we analyzed MTB patient data from four neighboring Bavarian tertiary care oncology centers in Würzburg, Erlangen, Regensburg, and Augsburg, together constituting the WERA Alliance. Absolute patient numbers and regional distribution across the WERA-wide catchment area were weighted with local population densities; (3) Results: the highest MTB patient numbers were found close to the four cancer centers. However, peaks in absolute patient numbers were also detected in more distant and rural areas. Moreover, weighting absolute numbers with local population density allowed for identifying so-called white spots—regions within our catchment that were relatively underrepresented in WERA MTBs; (4) Conclusions: investigating patient data from four neighboring cancer centers, we comprehensively assessed the regional impact of our MTBs. The results confirmed the success of existing collaborative structures with our regional partners. Additionally, our results help identifying potential white spots in providing precision oncology and help establishing a joint WERA-wide outreach strategy.