Institute For Hematopathology Hamburg

Gout is a common metabolic disorder caused by hyperuricemia, which results in the deposition of monosodium urate crystals in various parts of the body. In the present case, a large gout tophus was detected based on gout disease. Although gouty tophi might occur in many locations during a long-standing gout disease, the vast majority are located in the articular tissue. An 80-year-old female patient was admitted to the emergency room complaining of persistent nausea and vomiting for two days. In addition, she reported abdominal pain and cramps that she had not experienced before. A CT scan revealed a large calcified mesenteric mass in the right side of the abdomen. The patient underwent surgery and removal of the mesenteric mass including 55-cm jejunal resection. Histologically, sections showed a capsule-like boundary of varying widths, mostly cell-poor lesions, as well as siderophages and strong lymphatic infiltrate at the margins, corresponding to residual lymph node tissue. In the periphery of the lesion, brace-shaped dystrophic calcifications completed the histological image of a gouty tophus. In this case report, we describe an extremely rare case of a mass in the area of the small intestine mesentery caused by monosodium urate crystals. Even if patients do not present with articular manifestation of gout, deposition in other tissues is possible and presents a risk factor for the development of diseases. For patients with unclear abdominal masses suffering from hyperuricemia, despite being rare, a gout tophus should be thought of.

Background: ESR1 mutations are biomarkers in breast cancer patients who develop metastatic disease after endocrine therapy (ET). Recently, the Food and Drug Administration (FDA) and European Medicines Agency (EMA) have approved Elacestrant, a selective estrogen receptor degrader for patients harboring ESR1 mutations. This has necessitated the establishment of reliable and sensitive NGS- or PCR-based assays to detect these ESR1 resistance mutations in liquid biopsy samples. Methods: We evaluated NGS results of a pan-cancer cohort of almost 6000 patients from two major German institutes of pathology, to show that the occurrence of ESR1 mutations is extremely rare (<1%) in ET-naïve patients. This suggests that ESR1 mutations arise almost exclusively under the pressure of ET. Therefore, we designed a breast cancer-specific hybrid capture-based NGS liquid biopsy assay covering 12 breast cancer-related genes, including ESR1, PIK3CA, AKT1, ERBB2, BRCA1/2, and TP53. We validated the HS2-Mamma-LIQ assay extensively using reference material to detect mutations to 0.1% variant allele frequency (VAF) and compared the performance to a commercially available ESR1 ddPCR assay. Results: We show the results of routine diagnostic analysis of the first consecutive 354 patients with activating ESR1 mutations rate of 43%, with 20% of patients harboring co-mutations in PIK3CA and other genes underlining the relevance of tumor heterogeneity. Our study highlights liquid biopsy as a preferred approach for monitoring ESR1 mutations in breast cancer patients by showing cases where NGS analysis suggests complex tumor heterogeneity with multiple ESR1 as well as PIK3CA mutations at different VAFs. Conclusions: Our findings not only corroborate prior research concerning the rarity of these mutations in unselected patients but also emphasize the importance of robust and broad molecular assays rather than single gene assays in their detection and characterization in the diagnostic setting. Advantages of different approaches are discussed to address the current clinical need.

We present a case of diffuse large B-cell lymphoma characterized by areas exhibiting unexpectedly low Ki67 staining in a 47-year-old man. No histologic or cytologic differences are observed between the areas with low and high proliferation index. With an alternative Ki67 clone, the proliferation index was significantly higher, revealing an additional Ki67 weakly positive population. Our findings suggest a potential partial false-negative staining of tumor cells for Ki67. The phenomenon of false-negative immunohistochemical staining has been described in the literature, especially for MYC protein and Bcl2. In the studies, the phenomenon of false negativity was explained by MYC gene polymorphism leading to disruption of the commercial antibodies-binding epitope. To our knowledge, false-negative Ki67 staining has not been described in the medical literature. While Ki67 is regarded as a reliable proliferation marker, it is important to be aware of this rare potential pitfall to avoid a diagnostic misinterpretation of such tumors as indolent B-cell lymphomas, especially in small limited biopsies.

Introduction Homologous recombination deficiency (HRD) is a key biomarker in the management of high-grade serous ovarian cancer (HGSOC), guiding treatment decisions, particularly regarding the use of poly(ADP-ribose) polymerase inhibitors (PARPi). As multiple HRD assays are available, each with distinct methodologies and cutoff values, the interpretation and clinical application of HRD testing remain complex. This intergroup statement, endorsed by the German Ovarian Cancer Commission, NOGGO, AGO Austria, and AGO Swiss, aims to provide guidance on the indications, appropriate use, and limitations of HRD testing in ovarian cancer. Materials and methods The statement is based on an interdisciplinary review of available literature, clinical trial data, and expert consensus. The recommendations focus on the current landscape of HRD assays, their clinical applicability, and practical considerations regarding the optimal timing and indications for testing. Results and discussion Various HRD assays, including established commercial tests and emerging academic-clinical approaches, are reviewed in this statement. The document outlines key eligibility criteria for HRD testing in ovarian cancer, emphasizing its relevance in specific histological subtypes and clinical scenarios. Additionally, exclusion criteria are defined, highlighting cases where HRD testing may not be appropriate due to insufficient clinical validation or lack of therapeutic implications. Finally, the statement discusses the pathological minimum requirements for tissue samples used in HRD testing, ensuring adequate sample quality and tumor content for reliable results. Conclusion HRD testing is a valuable tool for personalizing ovarian cancer treatment, particularly in identifying patients who may benefit from PARPi therapy. However, assay selection, timing, and result interpretation require careful consideration. This statement provides a structured approach to optimize HRD testing, aiming to improve clinical decision-making and patient outcomes.

Large shallow-marine foraminifera tests occur in deep-sea carbonate sediments of the northern Red Sea as a minor but recurring component among the remains of otherwise pelagic and deep-marine benthic biogenic assemblages. In this study of sediments recovered along the northern shore of Saudi Arabia, the symbiont-bearing taxa Sorites variabilis, S. orbiculus, Amphisorus hemprichii, Amphistegina lobifera, A. lessonii and A. radiata were identified in samples from between 430 to 1,000 m depth. These foraminifera are dwelling in shallow-water environments, associated with coral reefs and seagrass habitats. The seemingly erratic occurrence of photosymbiotic benthic organisms in deep-sea sediments was explained by the finding of such foraminifera tests along with seagrass (e.g., Halophila leaves) and macroalgae remains in pristine preservational states in the sediment of the Umluj brine pool below ~ 638 m depth. This indicates a passive transport process by rafting attached to floating macrophytes to these off-platform settings. The abundant seagrass and oceanographic conditions along the Arabian Peninsula may facilitate the transport of epiphytes and associated taxa offshore. Such long-distance transport mechanisms could further contribute to the rapid (co-)dispersal of some of these organisms into new habitats. Passive rafting should thus be considered in interpretation of sedimentary records and biogeographic patterns.

The deep Southern Ocean (SO) circulation plays a key role in the storage and release of CO2 in Earth’s climate system. The uptake and release of CO2 strongly depend on the redistribution of well and poorly ventilated deep ocean water masses. Recently, evidence was found for possible stronger Pacific deep water overturning and subsequent intrusion into the SO during periods of reduced AMOC. Here, we present new authigenic neodymium isotope data (ɛNd) from two sites within the Atlantic sector of the SO to assess the distribution of water masses during the past 150 ka. PS 1768-8 (3299 m) and ODP 1093 (3624 m) feature unradiogenic interglacial ɛNd-signatures, which are typical for present-day Weddell Sea sourced Antarctic Bottom Water (AABW) (ɛNd ~ − 8.6). During peak glacial periods, radiogenic ɛNd-values ranging from ~ − 2.5 to − 3.5 are recorded. This may be the result of either a strong Pacific or benthic flux influence on the Nd budget in the Atlantic sector of the SO. However, an ocean circulation model indicates no stronger Pacific influence during glacials. Thus, we suggest that an increase in benthic flux influences the SO Nd budget, which is modulated by ACC strength. The more stratified and more sluggish deep water supports decreased vertical mixing and increased glacial carbon storage without the intrusion of poorly ventilated Pacific waters. The occurrence of highly radiogenic glacial bottom water or porewater signatures requires reassessment of the glacial Southern Hemisphere ɛNd-endmember for water mass sourcing reconstructions in the glacial Atlantic.