OBJECTIVE:Diffusion-weighted imaging and the quantified apparent diffusion coefficient (ADC) correlate with cell density and histopathological features in tumors. Radiomics analysis may provide more insight into the underlying microstructure and may better correlate with histopathology. The present study used cross-sectional guided biopsy specimens to exploit the precise spatial localization of the performed biopsy to correlate radiomics features of the ADC map with immunohistochemical features in hepatocellular carcinoma (HCC). MATERIALS AND METHODS:A total of 51 patients (11 female patients, 21.6 %) were included in the present study. The mean age was 71.9 ± 9.9 years, ranging from 42 to 91 years. Prebioptic liver MRI with diffusion-weighted imaging was used to correlate the radiomics features of the ADC maps with the immunohistochemical features quantified in liver biopsy. Proliferation potential Ki 67, leukocyte count and tumor-stroma ratio were evaluated as histopathological parameters. RESULTS:The following ADC texture features were correlated with the Ki 67 index _MinNorm (r = -0.307, p = 0.03), Vertl_RLNonUni (r = - 0.309, p = 0.03), 135dr_RLNonUni (r = -0.346, p = 0.01). The texture feature _MinNorm achieved the best diagnostic accuracy with an area under the curve of 0.76 (95 % CI 0.60-0.91, p < 0.01) to discriminate between low and high proliferative HCC. Multiple statistically significant correlations were found between ADC texture features and tumor-stroma-ratio, the highest for S(0,1)Contrast (r = 0.460, p = 0.001). No statistically significant correlations were found between the ADC texture features with the CD45+ leukocyte count and grading. CONCLUSION:Radiomics features of the ADC maps can reflect the underlying histopathology in HCC patients including the proliferation potential and tumor-stroma ratio but not CD45 positive cells and tumor grading. The complex interactions between quantitative imaging and histopathology need to be further investigated in a validation cohort.

Abstract Objective Investigate the association between the relative tumor enhancement (RTE) of gadoxetic acid across various MRI phases and immunohistochemical (IHC) features in patients with liver metastases (LM) from colorectal cancer (CRC), breast cancer (BC), and pancreatic cancer (PC). Methods A retrospective analysis was conducted on 68 patients with LM who underwent 1.5-T MRI scans. Non-contrast and contrast-enhanced T1-weighted (T1-w) gradient echo (GRE) sequences were acquired before LM biopsy. RTE values among LM groups were compared by cancer type using analysis of variance. The relationships between RTE and IHC features tumor stroma ratio, cell count, Ki67 proliferation index, and CD45 expression were evaluated using Spearman’s rank correlation coefficients. Results Significant differences in RTE were observed across different MRI phases among patients with BCLM, CRCLM, and PCLM: arterial phase (0.75 ± 0.42, 0.37 ± 0.36, and 0.44 ± 0.19), portal venous phase (1.09 ± 0.41, 0.59 ± 0.44, and 0.53 ± 0.24), and venous phase (1.11 ± 0.45, 0.65 ± 0.61, and 0.50 ± 0.20). In CRCLM, RTE inversely correlated with mean Ki67 (r = −0.50, p = 0.01) in the hepatobiliary phase. Negative correlations between RTE and CD45 expression were found in PCLM and CRCLM in the portal venous phase (r = −0.69, p = 0.01 and r = −0.41, p = 0.04) and the venous phase (r = −0.65, p = 0.01 and r = −0.44, p = 0.02). Conclusion Significant variations in RTE were identified among different types of LM, with correlations between RTE values and IHC markers such as CD45 and Ki67 suggesting that RTE may serve as a non-invasive biomarker for predicting IHC features in LM. Critical relevance statement RTE values serve as a predictive biomarker for IHC features in liver metastasis, potentially enhancing non-invasive patient assessment, disease monitoring, and treatment planning. Key Points Few studies link gadoxetic acid-enhanced MRI with immunohistochemistry in LM. RTE varies by liver metastasis type and correlates with CD45 and Ki67. RTE reflects IHC features in LM, aiding non-invasive assessment. Graphical Abstract

Abstract While few studies on miRNA profiling in primary chordomas have been published, there is no data on the miRNA landscape of long-term recurrences. Therefore, we performed a miRNA analysis and whole exome sequencing (WES) investigating four patients with multiple recurrences over seven to 16 years and eight patients with non-recurrent tumors (NRTs), conventional, sacral chordomas in order to compare both groups as well as the recurrence cases (RCs) to each other. Our aim was to find typical miRNA patterns distinguishing the recurrences from the NRTs. After histopathological classification, immunohistochemical and morphometric analysis, DNA and miRNA were extracted from formalin-fixed-paraffin-embedded tissue samples and analyzed by WES and Nanostring. The microRNA regulation patterns showed similarities within RCs differing from NRTs. In unsupervised clustering there is a tendency of recurrences clustering apart from the NRTs. The differential expression between cases developing recurrences and NRTs showed highly significant differences between both groups with 32 miRNAs upregulated in the RCs being downregulated in NRTs. The miRNA expression of long-term recurrences of each patient are quite homogenous differing only from their primary tumor. Comparing NRTs with primary tumors that would later develop long-term recurrences showed significant up-regulation of 5 miRNAs in the RCs. This suggests a pivotal molecular difference between singular and long-term recurring chordomas. Our WES analysis confirmed known and revealed possible new driver genes. Recurring tumors had a higher number of mutations classified as pathogenic as well as increased proliferation rates and pleomorphic changes. Recurrences displayed a change in mutational distribution, showing considerably more disturbances in embryonic signaling and our proposed driver genes. Intriguingly, our study found a progress in number of alterations throughout the recurrences most of all affecting chromatin regulation and the new drivers. Less disruption of these pathways in primary cases than in recurrences implies their pivotal role not only in chordoma formation, but also in recurrence evolution. The miRNA alterations were correlated with the genomic differences. Validated affected genes of miRNAs deregulated primarily in the recurrences are involved in those pathways as well. As current targeted therapy options are only sporadically altered in few patients, the progress in number of pathogenic mutations throughout the recurrences as well as the drastic change in miRNA expression could present new research approaches for chordomas with long-term recurrences. Combined clinical and molecular studies of miRNA patterns and genetic alterations could expand the understanding of recurrence development leading to new therapeutic targets inhibiting or delaying recurrence formation. Citation Format: Sarah R. Ullmann, Franziska Karras, Julian Schreier, Kerstin Körber-Ferl, David A. Ullmann, Sabine Franke, Albert Roessner, Dörthe Jechorek. microRNA profiling in combination with whole exome sequencing reveals insights into long-term recurrence patterns in chordoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5057.

TFF3 is a typical secretory poplypeptide of mucous epithelia belonging to the trefoil factor family (TFF) of lectins. In the intestine, respiratory tract, and saliva, TFF3 mainly exists as a high-molecular-mass complex with IgG Fc binding protein (FCGBP), which is indicative of a role in mucosal innate immunity. For the first time, we identified different forms of TFF3 in the endocervix, i.e., monomeric and homodimeric TFF3, as well as a high-molecular-mass TFF3-FCGBP complex; the latter also exists in a hardly soluble form. Immunohistochemistry co-localized TFF3 and FCGBP. Expression analyses of endocervical and post-menopausal vaginal specimens revealed a lack of mucin and TFF3 transcripts in the vaginal specimens. In contrast, genes encoding other typical components of the innate immune defense were expressed in both the endocervix and vagina. Of note, FCGBP is possibly fucosylated. Endocervical specimens from transgender individuals after hormonal therapy showed diminished expression, particularly of FCGBP. Furthermore, mucus swabs from the endocervix and vagina were analyzed concerning TFF3, FCGBP, and lysozyme. It was the aim of this study to illuminate several aspects of the cervico-vaginal innate immune barrier, which is clinically relevant as bacterial and viral infections are also linked to infertility, pre-term birth and cervical cancer.

Introduction: Patients with chronic pancreatitis (CP) as well as with pancreatic head carcinoma (CA) undergo the surgical intervention named “pylorus-preserving pancreatoduodenectomy according to Traverso–Longmire (PPPD)”, which allowed a comparative analysis of the postoperative courses. The hypothesis was that patients with CA would have worse general as well as immune status than patients with CP due to the severity of the tumor disease and that this would be reflected in the more disadvantageous early postoperative outcome after PPPD. Methods: With the aim of eliciting the influence of the different diagnoses, the surgical outcome of all consecutive patients who underwent surgery at the Dept. of General, Abdominal, Vascular and Transplant Surgery at the University Hospital at Magdeburg between 2002 and 2015 (inclusion criterion) was recorded and comparatively evaluated. Early postoperative outcome was characterized by general and specific complication rate indicating morbidity, mortality, and microbial colonization rate, in particular surgical site infection (SSI, according to CDC criteria). In addition, microbiological findings of swabs and cultures from all compartments as well as preoperative and perioperative parameters from patient records were retrospectively documented and used for statistical comparison in this systematic retrospective unicenter observational study (design). Results: In total, 192 cases with CA (68.1%) and 90 cases with CP (31.9%) met the inclusion criteria of this study. Surprisingly, there were similar specific complication rates of 45.3% (CA) vs. 45.6% (CP; p = 0.97) and in-hospital mortality, which differed only slightly at 3.65% (CA) vs. 3.3% (CP; p = 0.591); the overall complication rate tended to be higher for CA at 23.4% vs. 14.4% (CP; p = 0.082). Overall, potentially pathogenic germs were detected in 28.9% of all patients in CP compared to 32.8% in CA (p = 0.509), and the rate of SSI was 29.7% (CA) and 24.4% (CP; p = 0.361). In multivariate analysis, CA was found to be a significant risk factor for the development of SSI (OR: 2.025; p = 0.048); the underlying disease had otherwise no significant effect on early postoperative outcome. Significant risk factors in the multivariate analysis were also male sex for SSI and microbial colonization, and intraoperatively transfused red cell packs for mortality, general and specific complications, and surgical revisions. Conclusions: Based on these results, a partly significant, partly trending negative influence of the underlying disease CA, compared to CP, on the early postoperative outcome was found, especially with regard to SSI after PPPD. This influence is corroborated by the international literature.

Aim: By means of the scientific description of two uncommon cases who underwent. surgical resection of multinodous goiter and following histopathological investigation revealing isolated extrapulmonary manifestation of sarcoidosis, this uncommon diagnosis including symptomatology, clinical findings, diagnostic and therapeutic management is to be illustrated. Case descriptions: 1) Clinical findings: 61-years old patient with a multinodous goiter for 10 years characterized by an increasing size. Diagnostics: Scintigraphy of the thyroid gland with a left-thyroid cold node; ultrasound-guided puncture (cytological investigation, non-suspicious). Therapy: Elective thyroidectomy with no macroscopic anomalies und no abnormal aspects with regard to surgical tactic and technique. Histopathological investigation: Complete resection specimen of the thyroid gland with granulomatous inflammation consistent with sarcoidosis. Clinical course: Uneventful with no further manifestations of sarcoidosis in the following diagnostics. 2) Clinical finding: 30-years old female patient with soft swelling of increasing size at the right neck. Diagnostics: Ultrasound, inhomogeneous node (37x30x35 x30 x35 mm) of the right thyroideal gland with echo-poor parts and peripheral vascularization; scintigraphy showing marginally compensated unifocal autonomy of the thyroid gland (laboratory parameters, increased serum level of thyroglobulin [632 ng/mL]). Therapy: Planned right hemithyroidectomy with confirmed nodous structure of thyroid parenchyma, without suspicious lymph nodes. Histopathological investigation: 33-mm follicular, nodular, encapsulated structure of thyroid parenchyma (diagnosed as follicular adenoma); 2nd opinion: low-grade differentiated carcinoma of thyroid gland with angioinfiltrating growth and granulomatous inflammation of sarcoidosis type. Procedural intent: After tumor-board consultation, completing thyroidectomy was performed within a 5-weeks interval (pT2 pN0[0/1] V1 L0 G3 R0) with subsequent ablating radio'active iodine therapy; 18 F-FDG-PET-CT (several atypical infiltrates within the right upper lobe of the lung) and bronchoscopy with no detection of further manifestation of sarcoidosis. Conclusion: Sarcoidosis is considered a rare granulomatous multi-locular, systemic disease of not completely known etiopathogenesis with substantial heterogeneity. In most cases, it is associated with the lung, but which can become manifest in various organs. Frequently, extrapulmonary manifestations are usually detected as histological findings by coincidence, which require further investigation to find out additional manifestations as well as to exclude florid infection or other granulomatous processes (clarifying competently differential diagnosis). Therapy is only indicated in symptomatic organ manifestations, taking into account the high rate of spontaneous healing and possible side effects.

INTRODUCTION:The relationships between histopathology and imaging remain elusive, and investigating the underlying reasons for tumor microstructure leading to an imaging phenotype is of clinical importance. In the present study, a cross-sectional guided biopsy specimen was used to correlate prebioptic magnetic resonance imaging (MRI) with immunohistochemical staining of the histopathologic specimen using precise spatial biopsy localization. METHODS:Twenty-seven patients with mass-forming cholangiocarcinoma (CCA) were included in the present analysis. All patients were imaged with a 1.5 T clinical scanner at least 1 month prior to biopsy. The contrast-enhanced dynamic sequences were analyzed with quantified signal intensities. The bioptic specimens were obtained by cross-sectional guided biopsy and further analyzed for cell density, proliferation index (Ki67), tumor-infiltrating lymphocytes, tumor-stroma ratio (TSR), and collagen. RESULTS:There were no statistically significant correlations between MRI signal intensities and cell count, TSR, Ki67 index, and CD45 count. Only a moderate correlation was observed between relative signal intensities of the venous phase and the collagen-stained area (r = 0.40, p = 0.04). CONCLUSION:DCE-MRI is not associated with histopathological features in CCA. The complex interactions of tumor and tumor microenvironment are not reflected in the MRI phenotype.

Dedifferentiated chondrosarcoma (DDCS) is a rare malignant cartilage tumor arising out of a low-grade chondrosarcoma, whereby the well-differentiated and the dedifferentiated components coexist in the same localization. DDCS has a massively increased metastatic potential in comparison to low-grade chondrosarcoma. So far, the underlying mechanisms of DDCS development and the increased malignancy are widely unknown. Targeted DNA sequencing revealed no genetic differences between both tissue components. Besides genetic events, alterations in epigenetic control may play a role in DDCS development. In this preliminary study, we have analyzed the differential miRNA expression in paired samples of both components of four primary DDCS cases and a rare lung metastasis with both components using the nCounter MAX analysis system from NanoString technologies. We identified 21 upregulated and two downregulated miRNAs in the dedifferentiated components of the primary cases. Moreover, three miRNAs were also significantly deregulated in the dedifferentiated component of the lung metastasis, supporting their possible role in DDCS development. Additionally, validated targets of the 23 deregulated miRNAs are involved in signaling pathways, like PI3K/Akt, Wnt/β-catenin, and TGF-β, as well as in cellular processes, like cell cycle regulation, apoptosis, and dedifferentiation. Further investigations are necessary to confirm and understand the role of the identified miRNAs in DDCS development.