Soft Tissue Biopsies Research Articles

Cryo-X-Ray Phase Contrast Imaging Enables Combined 3D Structural Quantification and Nucleic Acid Analysis of Myocardial Biopsies.

Snap-frozen biopsies serve as a valuable clinical resource of archival material for disease research, as they enable a comprehensive array of downstream analyses to be performed, including extraction and sequencing of nucleic acids. Obtaining three-dimensional (3D) structural information before multi-omics is more challenging but can potentially allow for better characterization of tissues and targeting of clinically relevant cells. Conventional histological techniques are limited in this regard due to their destructive nature and the reconstruction artifacts produced by sectioning, dehydration, and chemical processing. These limitations are particularly notable in soft tissues such as the heart. In this study, the feasibility of using synchrotron-based cryo-X-ray phase contrast imaging (cryo-X-PCI) of snap-frozen myocardial biopsies is assessed and 3D structure tensor analysis of aggregated myocytes, followed by nucleic acid (DNA and RNA) extraction and analysis. It is shown that optimal sample preparation is the key driver for successful structural and nucleic acid preservation which is unaffected by the process of cryo-X-PCI. It is proposed that cryo-X-PCI has clinical value for 3D tissue analysis of cardiac and potentially non-cardiac soft tissue biopsies before nucleic acid investigation.

Streptokinase reduces Streptococcus dysgalactiae subsp. equisimilis biofilm formation

BackgroundStreptococcus dysgalactiae subspecies equisimilis (SDSE) is increasingly recognized as an emerging cause of invasive diseases including necrotizing soft tissue infections (NSTIs). In contrast to the closely related Streptococcus pyogenes, SDSE infections mainly affect older and comorbid patients. Biofilm formation has been demonstrated in soft tissue biopsies of S. pyogenes NSTI cases.ResultsHere, we show that bacterial aggregations indicative of biofilms are also present in SDSE NSTI. Although streptokinase (Ska) activity and biofilm formation did not correlate in a diverse set of clinical SDSE isolates, addition of exogenous Ska at an early time point prevented biofilm formation for selected strains. Deletion of ska in SDSE S118 strain resulted in increased biofilm forming capacity. Ska-deficient mutant strain was characterized by a higher metabolic activity and consequent metabolome profiling of biofilms identified higher deposition of a wide range of metabolites as compared to the wild-type.ConclusionsOur results argue that Ska suppresses biofilm formation in SDSE independent of its original plasminogen converting activity. However, the impact of biofilms and its consequences for patient outcomes in streptococcal NSTIs remain to be elucidated.

Challenges in diagnosis of Erdheim-chester disease: a case report

Background: Erdheim-Chester disease is a rare non-Langerhans cell histiocytosis characterized by the infiltration of lipid-laden macrophages into various tissues, leading to diverse clinical manifestations. Case Presentation: A 53-year-old male presented with a history of recurrent flank pain and obstructive uropathy over seven years, which led to multiple imaging studies and treatments for bilateral renal stones. Recent imaging, including a CT scan of the abdomen and pelvis, revealed bilateral perirenal soft tissue thickening extending into the renal sinus and pelvicalyceal systems, moderate hydronephrosis, and bilateral renal stones, suggestive of ECD. A CT-guided biopsy of the perinephric soft tissue confirmed the diagnosis. Histopathological analysis showed fibrofatty tissue with histiocytes exhibiting foamy cytoplasm, lymphocytes, plasma cells, and Touton cells. Immunohistochemistry stains were positive for Factor 13A and CD68 in histiocytes, confirming ECD. Conclusion: This case underscores the importance of considering ECD in patients with unexplained recurrent flank pain and renal abnormalities. Early recognition and biopsy are crucial for accurate diagnosis and management of this rare disease. The successful identification of ECD in this patient illustrates the critical role of advanced imaging and histopathological evaluation in diagnosing rare conditions.

Erdheim-chester disease with bilateral proptosis, coated aorta and hairy kidney

Erdheim-Chester disease (ECD) is a rare histiocytic disorder with a spectrum of clinical manifestations, ranging from asymptomatic single-organ involvement to multisystem disease. We present a classic case of ECD with detailed radiographic and histopathologic findings. A 63-year-old Thai female with a history of triple vessel disease post-PCI presented with bilateral proptosis and blurred vision for one year. On admission, she exhibited marked proptosis epiblepharon, lagophthalmos, conjunctival injection, chemosis, limited extraocular movement and cranial nerve II palsy. Imaging showed increased bilateral retro-orbital infiltrative lesions, osteosclerotic changes, and soft tissue thickening along the great vessels and retroperitoneum. A retro-orbital soft tissue biopsy showed foamy histiocytic proliferation with Touton giant cells. EDC was confirmed by next-generation sequencing revealing a BRAF V600E mutation. This patient received pegylated interferon-alpha. At 1-year follow-up visit, the disease remained stable. In this report, we present a classic case of EDC. The rarity of this disease makes it challenging to diagnose. The typical presentation characteristics raise awareness for the diagnosis of EDC, which is based on features such as osteosclerotic lesions in the long bones, soft tissue infiltration in medium to large vessels (coated aorta) and the bilateral pelvicalyceal systems (hairy kidney). These findings were confirmed through tissue pathology and molecular diagnostics.

Molecular characterization of Pseudomonas aeruginosa from diabetic foot infections in Tunisia.

Background. Pseudomonas aeruginosa is an invasive organism that frequently causes severe tissue damage in diabetic foot ulcers.Gap statement. The characterisation of P. aeruginosa strains isolated from diabetic foot infections has not been carried out in Tunisia.Purpose. The aim was to determine the prevalence of P. aeruginosa isolated from patients with diabetic foot infections (DFIs) in Tunisia and to characterize their resistance, virulence and molecular typing.Methods. Patients with DFIs admitted to the diabetes department of the International Hospital Centre of Tunisia, from September 2019 to April 2021, were included in this prospective study. P. aeruginosa were obtained from the wound swabs, aspiration and soft tissue biopsies during routine clinical care and were confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Antimicrobial susceptibility testing, serotyping, integron and OprD characterization, virulence, biofilm production, pigment quantification, elastase activity and molecular typing were analysed in all recovered P. aeruginosa isolates by phenotypic tests, specific PCRs, sequencing, pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing.Results. Sixteen P. aeruginosa isolates (16.3 %) were recovered from 98 samples of 78 diabetic patients and were classified into 6 serotypes (O:11 the most frequent), 11 different PFGE patterns and 10 sequence types (three of them new ones). The high-risk clone ST235 was found in two isolates. The highest resistance percentages were observed to netilmicin (69 %) and cefepime (43.8 %). Four multidrug-resistant (MDR) isolates (25 %) were detected, three of them being carbapenem-resistant. The ST235-MDR strain harboured the In51 class 1 integron (intI1 +aadA6+orfD+qacED1-sul1). According to the detection of 14 genes involved in virulence or quorum sensing, 5 virulotypes were observed, including 5 exoU-positive, 9 exoS-positive and 2 exoU/exoS-positive strains. The lasR gene was truncated by ISPpu21 insertion sequence in one isolate, and a deletion of 64 bp in the rhlR gene was detected in the ST235-MDR strain. Low biofilm, pyoverdine and elastase production were detected in all P. aeruginosa; however, the lasR-truncated strain showed a chronic infection phenotype characterized by loss of serotype-specific antigenicity, high production of phenazines and high biofilm formation.Conclusions. Our study demonstrated for the first time the prevalence and the molecular characterization of P. aeruginosa strains from DFIs in Tunisia, showing a high genetic diversity, moderate antimicrobial resistance, but a high number of virulence-related traits, highlighting their pathological importance.

A RARE RETROPERITONEAL SOFT TISSUE NEOPLASM IN A 27-YEAR-OLD FEMALE: A CLINICAL CASE

Relevance: Myopericytoma is a soft tissue tumor characterized by the proliferation of myopericytes. The tumor originates from myoid cells localized in the skin and soft tissues. Usually, this tumor is benign, but in rare cases, it can be malignant. Myopericytoma is a rare neoplasm, so specific data on its prevalence around the world are limited. The article presents a clinical case of retroperitoneal myopericytoma and a review of the cases described in the literature to analyze the epidemiology and clinical characteristics. Accurate data on the global prevalence of myopericytoma are not available due to the rarity of the disease and the difficulties of diagnosis. Thus, the study of myopericytoma has significant relevance, as it contributes to a better understanding and management of this rare soft tissue tumor and improves patients’ quality of life. The study aimed to describe a clinical case of retroperitoneal soft tissue myopericytoma in a 27-year-old patient. Methods: The authors present a clinical case of retroperitoneal soft tissue myopericytoma. The descriptions of the other 50 clinical cases of myopericytoma were found in the PubMed, Cochrane Library, eLibrary, CyberLeninka, and Google Scholar electronic databases, including the results of clinical examination, computed tomography (CT) and magnetic resonance imaging (MRI), and histopathological examination of biopsy material. Results: A 27-year-old girl went to the clinic complaining of pressure pains in the lower abdomen. A formation in the retroperitoneal space was revealed after a comprehensive examination, including CT and MRI. Further, soft tissue biopsies of the retroperitoneal space were performed, and the diagnosis of myopericytoma was confirmed. The patient was successfully surgically removed from the tumor. Conclusion: Myopericytomas, although classified as benign tumors, pose a serious problem due to their tendency to relapse. Despite their slow growth, they can reach significant sizes and grow into surrounding structures and organs. Consequently, the experience and skill of surgeons play an important role in the vastness of surgical intervention for radical tumor removal, which is important for the patient’s prognosis and quality of life. Radical surgical treatment for myopericytoma is especially important because it allows the complete removal of the neoplasm and minimizes the risk of recurrence, thereby improving long-term results and reducing the need for additional therapeutic interventions.

Immune cell composition and inflammatory profile of human peri-implantitis and periodontitis lesions.

Peri-implantitis (PI) and periodontitis (PD) are common oral inflammatory diseases, which seem to exhibit critical differences in some of their molecular features. Thus, we assessed the immune cell composition of PI and PD lesions and the corresponding inflammatory profile in soft tissues and crevicular fluid. PI, PD, and control patients were recruited (n = 62), and soft tissue biopsies were collected during surgery. Crevicular fluid around implant or tooth was collected. The proportions of major immune cell populations in tissues were analyzed by flow cytometry, and the inflammatory profile in tissue and crevicular fluid by a multiplex immunoassay. No significant difference was seen between PI and PD lesions in the proportions of immune cells. PI tissues showed an increased frequency of B cells in comparison with control tissues, along with higher levels of IL-1β, TNF-α, IL-4, and BAFF in tissue and crevicular fluid. Moreover, TNF-α, IL-17A, and BAFF were higher in PI tissues, but not in PD, than in control tissues. The immune cell composition did not differ significantly between PI and PD, but an enhanced inflammatory profile was seen in PI tissue. PI lesions were enriched in B cells, and displayed increased levels of IL-1β, TNF-α, IL-4, and BAFF in both tissue and crevicular fluid.

Microbiome Dysbiosis Is Associated with Castration Resistance and Cancer Stemness in Metastatic Prostate Cancer.

Prostate cancer is the second leading cause of death in males in America, with advanced prostate cancers exhibiting a 5-year survival rate of only 32%. Castration resistance often develops during the course of treatment, but its pathogenesis is poorly understood. This study explores the human microbiome for its implications in castration resistance and metastasis in prostate cancer. RNA sequencing data were downloaded for the bone and soft tissue biopsies of patients with metastatic castration-resistant prostate cancer. These included both metastatic and adjacent normal biopsies. These sequences were mapped to bacterial sequences, yielding species-level counts. A vast majority of species were found to be significantly underabundant in the CRPC samples. Of these, numerous were found to correlate with the expression of known markers of castration resistance, including AR, PI3K, and AKT. Castration resistance-associated signaling pathways were also enriched with these species, including PI3K-AKT signaling and endocrine resistance. For their implications in cancer aggression and metastasis, cancer stem cell markers were further explored for a relation to these species. EGFR and SLC3A2 were widely downregulated, with a greater abundance of most species. Our results suggest that the microbiome is heavily associated with castration resistance and stemness in prostate cancer. By considering the microbiome's importance in these factors, we may better understand the highly aggressive and highly invasive nature of castration-resistant prostate cancer, allowing for the needed improvements in the treatment of this disease.

Myeloid sarcoma with RBM15::MRTFA (MKL1) mimicking vascular neoplasm.

Extramedullary involvement of acute myeloid leukemia (AML), aka myeloid sarcoma, is a rare phenomenon in acute megakaryoblastic leukemia with RBM15:: MRTFA(MKL1) fusion, which might mimic non-hematologic malignancies. A 7-month-old infant presented with leukocytosis, hepatosplenomegaly, multiple lymphadenopathies, and a solid mass in the right thigh. Initially, the patient was diagnosed with a malignant vascular tumor regarding the expression of vascular markers from the biopsy of the right thigh lesion that was performed after the inconclusive bone marrow biopsy. The second bone marrow biopsy, which was performed due to the partial response to sarcoma treatment, showed hypercellular bone marrow with CD34 and CD61-positive spindle cell infiltration and > 20% basophilic blasts with cytoplasmic blebs. RNA sequencing of soft tissue biopsy revealed the presence of RBM15::MRTFA(MKL1) fusion. Based on these findings, myeloid sarcoma/AML with RBM15::MRTFA(MKL1) fusion diagnosis was made. AML with RBM15::MRTFA(MKL1) fusion can initially present as extramedullary lesions and might cause misdiagnosis of non-hematologic malignancies.

Left ventricular speckle-tracking-derived mechanical dispersion in patients with transthyretin amyloidosis and their first-degree relatives

Abstract Background Mechanical dispersion has shown to predict ventricular (LV) arrhythmias and sudden cardiac death in populations with established cardiac diseases, such as cardiomyopathies and heart failure. Transthyretin amyloid (ATTR) cardiomyopathy arises from deposition of misfolded, insoluble transthyretin (TTR) in extracellular matrix. The disease impacts profoundly cardiac tissue architecture and its mechanical properties. Purpose The aim of this prospective study was assessment of LV speckle-tracking-derived mechanical dispersion in patients with ATTR cardiomyopathy and their first-degree relatives. Methods We present data based on evaluation of 85 patients, including 34 (group 1) index patients with ATTR and 51 (group 2) first-degree relatives who were studied between June 2020 and January 2023. Study protocol included clinical data, free light chain blood immunoglobulins and urine immunofixation, transthoracic echocardiography (TTE) with global longitudinal strain (GLS) analysis, hybrid technique single-photon emission computed tomography and computed tomography (SPECT/CT) with [99mTc] Tc 3,3-disphono-1,2-propanodicarboxylic acid (DPD), genetic testing by an amplicon-based next-generation TTR sequencing approach, and in selected cases cardiac or soft tissue biopsy. Mechanical dispersion was calculated manually from GLS measurements and defined as the standard deviation (SD) of contraction duration from R on the electrocardiogram (ECG) to peak negative longitudinal strain of all LV segments. Results In group 1 patients were older (66.6±11 vs. 50.7±14) and presented with higher New York Heart Association (NYHA) class (2.4± 1 vs. 1.1± 0.6) (p<0.05). Overall, there were detected following types of TTR variants - Phe53Leu, Ala101Val, Glu112Lys, Glu109Lys, Glu122Lys, Glu82Lys. Compared to group 2, group 1 presented with higher N-terminal (NT)-pro hormone BNP (NT-proBNP) value (5859±7320 vs. 281±990 pg/ml), greater intraventricular septum thickness (19±4 vs. 12±3 mm) and LV mass index values (199±69 vs.111±42 g/m2), impaired LV ejection fraction (44±13 vs. 59±10 %) and GLS (-12.7±6 vs. -18.7±4 %) (p<0.05). Moreover, patients with ATTR cardiomyopathy had significantly higher value of LV speckle-tracking-derived mechanical dispersion compared to their first-degree relatives (96.2±22.3 vs. 77.9±23.3 ms, p=0.0007). Conclusions Patients with ATTR cardiomyopathy present with significantly higher LV mass index value, impaired GLS and higher value of LV speckle-tracking-derived mechanical dispersion compared to their first-degree relatives (p<0.05). Assessment of LV speckle-tracking-derived mechanical dispersion may in future translate into further enhancement of disease evaluation and improving prognosis in the group of patients.

Extramedullary plasmacytoma presenting as a rapidly growing lateral neck mass: A case report

Introduction: We detail the rare clinical presentation of an extramedullary plasmacytoma as a rapidly growing lateral neck mass. The pathology and its management are discussed. A rapidly growing extramedullary plasmacytoma infiltrating the cervical spine. Case Report: A 53-year-old male presented to our emergency room with a one-month history of worsening left-sided neck pain and an enlarging lateral neck mass. Evaluation with cervical imaging and laboratory analysis were performed. The patient underwent a soft tissue biopsy with subsequent spinal cord decompression and an occipital-cervical fusion. Pathology revealed the diagnosis of plasmacytoma. The patient was referred to oncology and radiation therapy for adjuvant treatment. Conclusion: This case represents the unusual presentation of a rapidly growing extramedullary plasmacytoma to the soft tissues of the neck with subsequent erosion of the base of the skull and upper cervical vertebral spine. It was treated effectively with posterior cervical decompression, arthrodesis, and adjuvant radiation and chemotherapy.

Right ventricle involvement in cardiac transthyretin amyloidosis in SPECT/CT with [99mTc]Tc-DPD

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): Pfizer Research Grant (ID#57165999). Background Transthyretin amyloid (ATTR) cardiomyopathy continues to be considered a rare disease; however, it is now more frequently diagnosed, partly due to advances in imaging techniques. Application of hybrid technique single-photon emission computed tomography and computed tomography (SPECT/CT) provides greater anatomic resolution, enabling the assessment of regional cardiac involvement. Purpose The aim of this prospective study was assessment of right ventricle involvement in patients with ATTR in SPECT/CT with [99mTc]Tc 3,3-disphono-1,2-propanodicarboxylic acid (DPD). Methods We present data based on evaluation of 100 patients, including 28 (group 1) index patients with ATTR and 72 (group 2) first-degree relatives who were studied between June 2020 and January 2023. Study protocol included clinical data, free light chain blood immunoglobulins and urine immunofixation, transthoracic echocardiography (TTE) with global longitudinal strain (GLS) analysis, SPECT/CT with [99mTc]Tc-DPD, genetic testing by an amplicon-based next-generation TTR sequencing approach, and in selected cases cardiac or soft tissue biopsy. Results In group 1 there were 39% patients diagnosed with hereditary ATTR (ATTRm) and 61% with ATTR wild type (ATTRwt). There were detected following types of TTR variants - Phe53Leu, Ala101Val, Glu112Lys, Glu109Lys, Glu122Lys, Glu82Lys. Overall, 26% first-degree relatives were diagnosed with pathogenic TTR variant and 7% had positive SPECT/CT with [99mTc]Tc-DPD. In group 2 there was a significant predominance of Phe53Leu variant among carriers. Importantly, among patients with positive SPECT/CT with [99mTc]Tc-DPD 78% presented also right ventricle uptake. Overall, right ventricle involvement was present in 80% of patients with ATTRm and 76% of patients with ATTRwt who presented left ventricle uptake (p>0.05). Conclusions Right ventricle involvement in cardiac transthyretin amyloidosis can be assessed in SPECT/CT with [99mTc]Tc-DPD. In presented group 78% of patients who had cardiac tracer uptake presented as well right ventricle involvement. There were no statistically significant differences in rates between the ATTRwt and ATTRm groups (p>0.05). Assessment of right ventricle involvement in cardiac transthyretin amyloidosis in SPECT/CT may in future translate into further enhancement of disease evaluation and improving prognosis in the group of patients.

Personalized precision combination therapies based on potential actionability and coalterations and therapeutic opportunities for CDK12-mutated prostate cancer.

e17068 Background: Translational studies have reported that CDK12 aberrations in metastatic castration-resistant prostate cancer (mCRPC) are related to homologous recombination (HR) deficiency and focal tandem duplications(FTDs), characterized by gene fusions and fusion-induced neoantigens (FINAs). In prostate cancer,CDK12 aberrations as a biomarker have been reported associated with poor prognosis, whether hormonal and taxane therapies as well as to PARP inhibitors. Herein, we aimed to molecularly, pathologically, and clinically characterize CDK12-aberrant mCRPC. Methods: Clinical data and molecular analyses are collected from the mCRPC patients treated in our center. Thirty-two patients with prostate cancer underwent soft tissue biopsy or sufficient ctDNA(Circulating Tumor DNA) for NGS and confirmed the CDK12 aberrations. Twenty-eight patients had advanced to the stage of mCRPC, and twenty-seven of them had exhausted standard treatment.All of the twenty-seven patients consented to the individualized therapiees based on NGS.PSA50 response rate and progression-free survival(PFS) are used to describe clinical features and outcomes to various individualized therapies, including sensitivity to poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis) and PD-1/PD-L1 inhibitors monotherapy or combined with other off-label drugs. Results: Of the 32 patients with CDK12-aberrant prostate cancer, 19(59.4%) had detected biallelic CDK12 alterations. At diagnosis,17 (68%) patients' PSA≥100ng (only 26 patients retained the PSA data), 27 (93.1%) had Gleason grade group 4-5(only 29 patients retained the pathology),16(51.6%) had lymph node metastasis, 16(51.6%) had bone metastasis.13 patients received PARPi combine NHT(Novel hormone therapy) or not after NHT therapy resistance,only 1 patient PSA response reached PSA50.9 patients received PARPi combine temozolomide,2 reached PSA50,1 patient's liver metastases were significantly reduced ang reached PR.In that five patients,4 of 5 were monotherapied by PARPi.21 patients accepted PD-1/PD-L1 combined with PARPi or other off-label drugs based on the NGS or not.Four patients accepted immune monotherapy,only 1 reached PSA50. In the remaining 17 combined treatment patients, PSA50 responses were noted in 23.5%. What is noteworthy is that,4 of 16 happened HPD(hyperprogressive disease) with clinical manifestations such as rapid increase of PSA and significant decrease of ECOG score. Conclusions: CDK12-aberrant mCRPC is an aggressive subtype and have worse prognosis to PARPi. PARPi combine with temozolomide may be a effective therapeutic schedule. Along with NGS development,more therapeutic drugs are available to us to benefits for patients.But immunotherapy is questionable to CDK12-aberrant mCRPC because of the lower response rate and higher risk of HPD.

Incidence of Chronic Pain following Oral Soft Tissue Biopsies: A Retrospective Study

Soft tissue oral biopsies (STOB) are commonly performed in the medical field to obtain tissue samples for diagnostic purposes. However, like all invasive procedures, these biopsies may carry risks, such as the development of chronic long-lasting neuropathic pain. This study aims to examine the occurrence of chronic pain following STOBs. A retrospective study was conducted on the medical records of 695 patients who underwent STOBs at the Maxillofacial Surgery Department of Hadassah Medical Center between the years 2013 and 2022. Demographic information, details of the procedure, histopathological diagnosis, and data related to post-procedure pain in the biopsy area were collected and analyzed. Out of the 695 patients, only 4 reports of chronic pain with mild intensity lasting more than three months following oral biopsy were documented, with incidence rate of 0.57%; all were females with a median age of 59 ± 2.0 years. The biopsies were taken from various sites and the common diagnoses were lichen planus, venous malformation, and fibromas. In conclusion, chronic pain after oral soft-tissue biopsies is rare, generally mild, and typically does not require extra therapy. These insights can aid clinicians and patients in making informed decisions about these procedures.

Myalgia in a Patient with Adult-Onset Asthma with Periocular Xanthogranuloma (AAPOX) due to Myotonic Dystrophy type 2 (P6-8.013)

<h3>Objective:</h3> To report a patient with myotonic dystrophy type 2 (DM2) and an adult-onset asthma with periocular xanthogranuloma (AAPOX). <h3>Background:</h3> AAPOX is a rare systemic non-Langerhans histiocytosis, clinically characterized by periocular yellowish plaques, adult-onset asthma, and lymphadenopathy, and pathologically characterized by non-caseating granulomas consisting of foamy histiocytes and Touton giant cells. The etiology of AAPOX is unknown, but recent studies suggested a possible link to IgG4-related disease. Autoimmune diseases occur in up to 30% of myotonic dystrophy type 2 (DM2) patients but concomitant AAPOX and DM2 have never been reported. <h3>Design/Methods:</h3> Case report. <h3>Results:</h3> A 38-year-old man with hyperlipidemia presented with 1.5-year history of progressive bilateral periorbital swelling and periocular yellowish plaques, 1-year history of asthma and exercise intolerance, and 4-month history of rosuvastatin-associated myalgias and difficulty climbing stairs. Periorbital soft tissue biopsy revealed characteristic pathological features of AAPOX. Neurologic examination revealed neither weakness nor clinical myotonia. Family history was significant for bradyarrhythmia requiring pacemaker in his mother and maternal grandfather. The patient’s creatine kinase was elevated at 606 U/L (normal &lt; 308 U/L). HMGCR-IgG was negative. IgG4 level was normal. Electromyography revealed diffuse myotonic discharges and a mild proximal myopathy without fibrillation potentials. A triceps brachii biopsy showed a marked increase of fibers harboring internal nuclei, scattered pyknotic nuclear clumps, and type 1 fiber smallness without granulomas. Genetic testing revealed a heterozygous CCTG repeat expansion &gt; 15,600 base pairs in intron 1 of <i>CNBP</i>, consistent with a diagnosis of DM2. His cardiac evaluation was unrevealing. The patient was treated with prednisone and methotrexate with improvement of his periocular disease. Myalgias persisted despite discontinuation of rosuvastati <h3>Conclusions:</h3> We first report the cooccurrence of AAPOX and DM2. Our finding supports the increased risk of autoimmune diseases in DM2 patients. <b>Disclosure:</b> Dr. Skolka has nothing to disclose. The institution of Shreyasee Amin has received research support from NIH. Dr. Liewluck has nothing to disclose.

Computed Tomography-based Radiomics Evaluation of Postoperative Local Recurrence of Pancreatic Ductal Adenocarcinoma.

To develop and validate an effective model for identifying patients with postoperative local disease recurrence of pancreatic ductal adenocarcinoma (PDAC). A total of 153 patients who had undergone surgical resection of PDAC with regular postoperative follow-up were consecutively enrolled and randomly divided into training (n=108) and validation (n=45) cohorts. The postoperative soft-tissue biopsy results or clinical follow-up results served as the reference diagnostic criteria. Radiomics analysis of the postoperative soft-tissue was performed on a commercially available prototype software using portal vein phase image. Three models were built to characterize postoperative soft tissue: computed tomography (CT)-based radiomics, clinicoradiological, and their combination. The area under the receiver operating characteristic curves (AUC) was used to evaluate the differential diagnostic performance. A nomogram was used to select the final model with best performance. One radiologist's diagnostic choices that were made with and without the nomogram's assistance were evaluated. A seven-feature-combined radiomics signature was constructed as a predictor of postoperative local recurrence. The nomogram model combining the radiomics signature with postoperative CA 19-9 elevation showed the best performance (training cohort, AUC=0.791 [95%CI: 0.707, 0.876]; validation cohort, AUC=0.742 [95%CI: 0.590, 0.894]). In the validation cohort, the AUC for differential diagnosis was significantly improved for the combined model relative to that for postoperative CA 19-9 elevation (AUC=0.742 vs. 0.533, p < 0.001). The calibration curve and decision curve analysis demonstrated the clinical usefulness of the proposed nomogram. The diagnostic performance of the radiologist was not significantly improve by using the proposed nomogram (AUC=0.742 vs. 0.670, p=0.17). The combined model using CT radiomic features and CA 19-9 elevation effectively characterized postoperative soft tissue and potentially may improve treatment strategies and facilitate personalized treatment for PDAC after surgical resection.

A phase II study of rucaparib monotherapy in nonmetastatic, hormone-sensitive prostate cancer (nmHSPC) with “BCRAness” genotype (ROAR).

364 Background: Prostate cancer (PCa) patients (pts) with DNA repair defects (aka “BRCAness”) generally have more aggressive disease and a worse overall prognosis compared to men without BRCAness (PMID: 33781305). Biochemical recurrence (BCR) develops in almost one-third of men with PCa after treatment with local therapy. We hypothesized that treatment with rucaparib monotherapy in men with systemic treatment naïve high-risk nmHSPC would result in acceptable disease control, allow a delay of androgen deprivation therapy (ADT) and the onset of metastasis. Methods: This is a single-arm, open-label, phase II trial; eligibility criteria: (1) Histologically proven prostate adenocarcinoma, presence of one of the following alterations in (by soft tissue or liquid biopsy): BRCA1, BRCA2, ATM, BARD1, BRIP1, CHEK1, CHEK2, FANCA, NBN, PALB2, RAD51C, RAD51D, RAD51, RAD51B, (2) No radiographic evidence of metastatic disease by conventional scans (3) PSA doubling time of ≤10 months. The primary endpoint: PSA progression-free survival (PSA-PFS). Secondary endpoints: safety, the proportion of pts with a PSA 50% response (PSA50), and an undetectable PSA. Results: Seven pts were enrolled in the study with the following pathogenic alterations: ATM (n=3), BRCA2 (n=2), BRCA1 (n=1), BRIP1 (n=1), RAD51(n=1), and received treatment with rucaparib at 600 mg twice daily. A 4-week treatment duration comprised one cycle. The median duration of follow-up was 18 months. A median of 20 cycles (range 4-42) was completed, median PSA-PFS was 35.37 months (95% CI: 0 - 85.11 months). 2/7 patients achieved PSA50; both had nadir PSA as undetectable. Grade ≥ 3 adverse events (AEs) were anemia and rash (in 1 pt each). No dose-limiting toxicities or severe AEs were seen. The study was prematurely terminated in June 2022 after the accrual of 7 pts because next-generation scans (e.g., PSMA-PET) became the standard of care for pts with BCR. Conclusions: Rucaparib demonstrated acceptable toxicity and preliminary efficacy in pts with PCa with BCR. Gene alteration-specific efficacy will be presented in the meeting. Limitations: Small cohort, no comparison arm. Hence results should be interpreted cautiously but generally consistent with larger prospective trials of PARP inhibitors. Clinical trial information: NCT03533946 . [Table: see text]

The management of non-diagnostic soft tissue tumour biopsies using a multi-disciplinary team approach: A 10-year retrospective review at a specialist sarcoma unit

Non-Diagnostic (ND) biopsies are occasionally encountered during the investigation of soft tissue sarcoma. We performed a retrospective review of all ND soft tissue biopsies discussed at our regional Multi-Disciplinary Team (MDT) meeting between 2004 & 2014 with the aim of establishing the incidence of ND biopsies, identifying predictive factors for repeat biopsies and evaluating the effectiveness of MDT decisions. We identified 80 ND out of 3233 biopsies. Diagnostic Yield (DY) was 97.5%, 76.0% and 77.8% for the first, second and third successive biopsy respectively. With an MDT approach utilising radiological and clinical information, the diagnostic success rate achieved was 98.5%, 82.0% and 77.8% for the first, second and third biopsies respectively. Malignant tumours (sarcoma & carcinoma) were 19 times more likely to undergo an increasing number of biopsies compared to benign lesions (p < 0.01), while repeat biopsies were less useful for suspected benign lesion. Although a repeat biopsy was only performed in 63% of cases, there were no patients originally diagnosed with a benign lesion that re-presented with the same lesion subsequently being malignant throughout the study period. Our study shows that a specialist MDT approach leads to high diagnostic rates and is a safe and effective method of preventing unnecessary, repeat biopsies where the initial biopsy is ND.

Plastination - A method for preservation of oral hard and soft tissue biopsy specimen v/s the conventional method of preservation with formalin.

Plastination is one of the most advanced method for preserving perishable biological specimen as well as tissue samples as for a longer period of time using polymers. To evaluate the changes in dimension of hard and soft tissue specimens after plastination procedure and compare it with the conventional method of preservation in formalin. Institution-based retrospective study. The study included 20 formalin-fixed soft tissue and 10 formalin-fixed hard tissue specimens. All the specimens were plastinated which involved four basic steps of fixation, dehydration and defatting, impregnation with polymer and curing of polymer followed by finishing and storage. The specimens were analysed for shrinkage and dimensional changes and changes in colour and consistency between formalin-fixed specimen and plastinated soft tissue and hard tissue specimen. Descriptive statistics were used. After plastination, soft tissues showed average shrinkage of 3.49%with a range of 0.80-7.90% in comparison to the original size. In case of teeth and hard tissue specimen, there was no evidence of dimensional changes or shrinkage before and after plastination. Changes in colour and consistency of the soft tissue specimens were also noted before plastination and after plastination. Although the plastinated specimens in the current study showed minimal shrinkage rate, they have proved to be an excellent alternative to formalin-fixed specimens as they are easy to handle and maintain, non-infectious, non-toxic, user-friendly.

Image-Guided Biopsy in Acute Diskitis-Osteomyelitis: A Systematic Review and Meta-Analysis.

BACKGROUND. The reported sensitivity and yield of image-guided biopsies for diskitis-osteomyelitis vary widely. OBJECTIVE. The purpose of this study was to perform a systematic review of the literature and meta-analysis of pooled sensitivity data to elucidate strategies for optimal image-guided biopsies among patients suspected to have diskitis-osteomyelitis. EVIDENCE ACQUISITION. A comprehensive literature search was performed for studies of patient populations with proven or suspected diskitis-osteomyelitis that included percutaneous image-guided biopsy as part of the workup algorithm. Type of pathogens, imaging modality used for biopsy guidance, tissue targeted, antibiotic administration at the time of biopsy, true microbiology positives, true microbiology negatives, false microbiology positives, false microbiology negatives, disease (i.e., diskitis-osteomyelitis) positives as determined by reference standard, true infection positives (i.e., positive microbiology or pathology results), and total number of biopsies performed were extracted from the studies. Microbiology sensitivity, microbiology biopsy yield, and infection sensitivity were calculated from the pooled data. These terms and the data required to calculate them were also defined in detail. EVIDENCE SYNTHESIS. Thirty-six articles satisfied inclusion criteria and were used for analysis. The pooled microbiology sensitivity, infection sensitivity, and microbiology biopsy yields were 46.6%, 70.0%, and 26.7%, respectively. Mycobacterium tuberculosis-only microbiology sensitivity was significantly higher than both pyogenic bacteria and mixed-organism microbiology sensitivity (p < .001). Staphylococcus aureus was the most common causative organism (28.6%). Pooled microbiology sensitivity was not significantly different for CT guidance and fluoroscopy guidance (p = .16). There was a statistically significant difference between pooled microbiology sensitivity of bone/end plate (45.5%) and disk/paravertebral soft-tissue (64.8%) image-guided biopsies (p < .001). There was no statistically significant difference in pooled microbiology sensitivities for patients who received antibiotics before the procedure (46.2%) and those who did not (44.6%) (p = .70). CONCLUSION. Image guidance by CT or fluoroscopy does not affect microbiology yield, disk and paravertebral soft-tissue biopsies should be considered over bone and end plate biopsies, and preprocedural antibiotic administration does not appear to impact biopsy results. CLINICAL IMPACT. Understanding and correctly applying reported statistics contribute to appropriate interpretation of the abundant literature on this topic and optimization of care for patients with diskitis-osteomyelitis.