Citations

Abstract BRCA-associated homologous recombination deficiency (HRD) is present in ~ 50% of high-grade serous carcinomas (HGSC) and predicts sensitivity to platinum-based therapy. However, there is little understanding of why some patients with BRCA-deficient tumors experience unexpectedly poor outcomes. We profiled 154 tumors, enriched for patients with BRCA-deficient tumors that experienced short overall survival (≤ 3 years, n = 42), using whole-genome, transcriptome, and methylation analyses. All but one BRCA-deficient tumor exceeded an accepted HRD genomic scarring threshold. However, patients with BRCA1-deficient HGSC with a more elevated HRD score survived significantly longer. Patients with BRCA2-deficient HGSC and loss of NF1 survived twice as long as those without NF1 loss, whereas PIK3CA or RAD21 amplification defined BRCA2-deficient HGSC with exceptionally short survival. BRCA1-deficient tumors in short survivors had evidence of immunosuppressive c-kit signaling and EMT. In a large HGSC cohort (n = 1,389) including 282 individuals with pathogenic germline BRCA variants (gBRCApv), the location of the mutation within functional domains stratified clinical outcomes. Notably, residual disease after primary surgery had limited prognostic effect in gBRCApv-carriers compared to non-carriers. Our findings indicate that tumor HR proficiency in the context of therapy response and survival is not a binary property, and highlight genomic and immune modifiers of outcomes in BRCA-deficient HGSC.

Objectives: To evaluate return-to-sport (RTS) rates and patient reported outcome measures (PROMs) following hip arthroscopy for femoroacetabular impingement (FAI) in active football players with a minimum of 5-years follow-up. Methods: All active football players who underwent hip arthroscopy for FAI from 2010-2019 were identified. Preoperative radiographic measures including lateral center edge angle, Tönnis angle, alpha angle, and acetabular depth were obtained. Patients were evaluated for post-operative RTS and revision surgery data at final follow-up. Modified Harris Hip Score (mHHS), Hip Outcome Score (HOS), HOS Activities of Daily Living (HOS-ADL), HOS Sports Specific Subscale (HOS-Sports), Tegner Activity Scores, Visual Analogue Scale (VAS) for pain, and surgery satisfaction were collected at a minimum 5-year follow-up. Descriptive and comparative statistical analysis was performed using R software (version 4.4.1). Results: Sixty-six hips from 53 male patients were included. The mean age was 20.4 ± 6.4 years and mean BMI was 27.3 ± 6.6 kg/m² (Table 1). Mean follow-up was 8.7 ± 2.8 years. The majority (60%) were high school players and 19% were college players. Figure 1 displays the most commonly affected positions which included wide receiver (32%), defensive lineman (26%), and tight end or offensive lineman (16%). There were 11 bilateral cases and 2 revisions. The mean lateral center edge angle was 31.6º ± 6.4, the mean Tönnis angle was 5.0º ± 5, and the mean alpha angle was 63.2º ± 12.7. There was significant improvement in all PROMs from baseline to a minimum 5-year follow-up (p<0.04). Fifty-four percent of athletes returned to football postoperatively and the average overall surgery satisfaction rating was 8.1/10. Among those who didn’t return, 14% cited hip-related reasons, while 67% cited non-hip related reasons such as priorities changing or graduating (Figure 2). Athletes who returned to football had significantly higher mean HOS-ADL (p=0.049), HOS-Sport (p=0.042), and Tegner level before surgery (p=0.023) compared to those who did not return (Table 2). Conclusions: Football players undergoing hip arthroscopy for FAI demonstrate significant improvements in outcome scores at a minimum 5-year follow-up with a moderate return-to-sport rate. Athletes who are able to return to football report higher patient reported outcomes compared to those who do not. Player position may also influence incidence and outcomes. Although football players demonstrate significant improvements following hip arthroscopy, the moderate RTS rates highlights the demanding nature of the sport and need for improved perioperative counseling.

Abstract The practice of formally documenting radiologic and pathologic concordance after percutaneous breast biopsies was instituted more than 20 years ago. There are several ways in which this can be done, but in many practices the performing radiologist independently compares the imaging findings with the pathology report to determine concordance. However, some studies show that a multidisciplinary review of breast biopsy results can maximize cancer detection, identify discordant cases in a timely manner, decrease imaging follow-up, and avoid unnecessary surgical intervention. This article will propose a practical method to establish a formal radiology-pathology conference in which percutaneous breast biopsies are reviewed with multidisciplinary input to increase efficiency and improve patient care. With the wide implementation of digital radiologic imaging and digital pathology evaluation plus the recent adoption of virtual meeting platforms, a successful radiology-pathology conference can be implemented in nearly any practice setting. Case examples will be presented demonstrating the utility of such a conference.

Abstract Background: Congenital peritoneal encapsulation (cocoon deformity) is a rare variant of intestinal malrotation. Objectives: To characterize the clinical presentation and outcomes in patients undergoing surgery for intestinal malrotation with cocoon deformity. Design: Retrospective review. Settings: A large tertiary care center, from January 2003 to December 2022. Patients and Methods: All patients who underwent surgery for intestinal malrotation with cocoon deformity were included. Sample Size: Nine patients were identified. Main Outcome Measures: Patient demographics and operative outcomes. Results: Most patients were female (88.9%), with a median age of 37 years (interquartile range [IQR], 19–53). Most were symptomatic upon diagnosis (88.9%), with abdominal pain (77.8%) being the most common symptom. One patient presented acutely, requiring immediate surgical intervention. Computed tomography was the most frequently used modality to establish a diagnosis of intestinal malrotation. A laparoscopic Ladd procedure was attempted in all patients, with three requiring conversion to open surgery. The median operative time was 119 min (IQR, 96.5–202), with a median estimated blood loss of 25 mL (IQR, 15–125). The median length of hospital stay was 2 days (IQR, 1.5–7). The most common postoperative complications were ileus ( n = 3, 33.3%) and 30-day readmission ( n = 3, 33.3%). Most patients experienced partial or complete resolution of symptoms ( n = 7, 77.8%) and no patients required reoperation. The median follow-up duration was 71.8 months (IQR, 21.3–138.7). Conclusions: The laparoscopic Ladd procedure with excision of the cocoon deformity can be performed safely and is associated with significant improvement in preoperative symptoms. Limitations: Cocoon deformity was not diagnosed preoperatively, and there is currently no gold standard imaging modality for its detection.

AimsPolymyalgia rheumatica (PMR) is a chronic autoimmune disorder that mainly affects older adults. Pulmonary disease in PMR is rare but may be under‐recognized and pathological descriptions thereof are few. We aimed to characterize diffuse parenchymal lung disease (DPLD) in PMR.Methods and resultsInstitutional archives were searched for patients having PMR and DPLD with lung tissue sampling. After excluding cases with infection, concomitant rheumatoid arthritis, or smoking‐related DPLD only, 11 patients (9 women, median age 75 years) were enrolled. Clinical history and pathology slides were reviewed. One of the 11 patients (9%) had concomitant giant cell arteritis; the remaining patients had no other rheumatological diseases. All had been treated for PMR with immunosuppression, and most presented years later (median 6 years) with non‐specific respiratory symptoms. Radiographically, bilateral ground‐glass opacities and reticulation were typical and were usually lower lobe predominant. Histologically, fibrosis was seen in 8 of 11 (73%) patients and was unclassifiable in four; non‐specific interstitial pneumonia was encountered in three patients, and usual interstitial pneumonia was seen in only one case. Evidence of acute lung injury occurred in 9 (82%) patients, including three with acute lung injury only, usually manifesting as organizing pneumonia. Diffuse alveolar haemorrhage was seen in four cases (29%), including two patients with haemoptysis and capillaritis.ConclusionsOur data corroborate prior reports of clinically significant DPLD in some patients with PMR. Histopathological findings mirror other rheumatological disorders and include diffuse alveolar haemorrhage with capillaritis. Additional studies are warranted to clarify the association between PMR and DPLD.

Introduction. Increased steatosis on preimplant liver frozen section is associated with delayed graft function and primary nonfunction. Efforts to standardize histologic assessment have proven difficult. Frozen section artifact and lipopeliosis complicate the detection of steatosis. We aimed to develop and validate an AI model to recognize large droplet fat and fat induced artifact (FIA)/lipopeliosis on preimplantation frozen section and to correlate the AI results with post-transplant clinical parameters. Methods. The model was applied to 161 consecutive liver transplant specimens with preimplant slides. Results were correlated with traditional and Banff histologic assessment and clinical parameters. Results. By traditional assessment, steatosis ranged from 0%–40%. The AI model identified a range of 0 to 15.9% steatosis. There was no difference in patient survival by any measures of steatosis. AI steatosis correlated with increased risk of early allograft dysfunction (OR = 1.63, P < .001), respiratory failure (OR = 1.21, P = .003), and more advanced fibrosis (OR = 1.18, P = .030), but was not correlated with graft or patient survival. FIA/lipopeliosis were identified in a range of 0 to 6.42%. In univariate analysis the percentage of FIA/lipopeliosis correlated with both graft and patient survival ( P = .044 and P = .009, respectively), but was not associated with increased risk of early allograft dysfunction, respiratory failure, or advanced fibrosis. Conclusions. We developed an AI model that quantitates large droplet fat and FIA/lipopeliosis on frozen section slides and found a correlation with post-transplant outcomes. Further studies on larger, multi-institutional cohorts with higher fat containing donors are necessary to determine the role this model may have in organ acceptance decisions.

ABSTRACT Capillary malformation-arteriovenous type 2 syndrome (CM-AVM2) is a rare, genetic vascular disorder associated with abnormal capillary malformations and arteriovenous malformations. We present a case of CM-AVM2 with refractory diarrhea and failure to thrive due to aberrant, telangiectatic capillaries, and subepithelial collagen deposition found throughout the GI tract on bidirectional endoscopy. The patient was recalcitrant to standard therapies, so bevacizumab was trialed, but the patient expired. This is the first case of CM-AVM2 with diffuse GI mucosal involvement resulting in malabsorption. There is no treatment for this pathology, but treatment with bevacizumab or a mammalian target of rapamycin inhibitor may be efficacious.

Transbronchial cryobiopsies (CB) are increasingly replacing surgical biopsies (video-assisted thoracoscopic/VATS biopsies) for diagnosing diffuse parenchymal lung disease (interstitial lung disease, ILD), but there is very little guidance for pathologists on CB interpretation. Here we propose a fairly simple approach. First, if the diagnosis can be made on a traditional forceps biopsy, it can be made on a cryobiopsy. Many diseases with specific features will fall into this category (eg, sarcoidosis or Langerhans cell histiocytosis). More problematic are patterns such as usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia (NSIP), in which low-power architecture is the key to diagnosis. In this circumstance, an adequate sample is crucial to look for features such as fibroblast foci, because a combination of fibroblast foci plus any patchy old fibrosis, fibrotic architectural remodeling, or honeycombing, allows a diagnosis of a UIP pattern. However, in most instances, CB will not separate the UIP patterns seen in idiopathic pulmonary fibrosis, fibrotic hypersensitivity pneumonitis, or connective tissue disease-interstitial lung disease (CTD-ILD), although giant cells/granulomas (uncommon findings) in this setting favor fibrotic hypersensitivity pneumonitis. Fibroblast foci can be difficult to differentiate from organizing pneumonia (OP), but granulation tissue plugs clearly in airspaces favor OP. Absent fibroblast foci, patchy old fibrosis, architectural distortion, and honeycombing by themselves do not allow a specific diagnosis. NSIP in CB microscopically looks like NSIP in VATS biopsies, and the presence of an NSIP or an NSIP+OP pattern is typical of CTD-ILD. All the above diagnoses require correlation with clinical and radiologic findings.

Abstract Introduction: Endobronchial optical coherence tomography (EB-OCT) imaging has unique potential to diagnose and quantify early, microscopic disease changes and assess therapeutic responsivity in interstitial lung disease (ILD). However, training and time requirements for interpretation and quantitative evaluation of large volumetric EB-OCT datasets need to be optimized to facilitate clinical adoption. We develop and validate a computationally-efficient, rapid EB-OCT quantitative image analysis framework using artificial intelligence (AI) with deep learning architecture for 2D feature segmentation, 3D feature burden and spatial distribution mapping, and computer-aided diagnosis in early ILD subjects. Methods: Volumetric EB-OCT datasets, consisting of 2D cross-sectional images, were acquired from multiple locations in the bilateral lungs of ILD and healthy control subjects. EB-OCT features were manually segmented from cross-sectional images by an expert EB-OCT reader, including fibrosis, microscopic honeycombing, traction bronchiolectasis, normal parenchyma, and emphysema. EB-OCT images with corresponding feature segmentations were used to train and validate a multiclass convolutional neural network. The 2D AI-based segmentation model was subsequently evaluated against manual ‘ground truth’ segmentations for each feature in a de novo ‘test’ dataset of independent subjects using dice similarity score, precision, recall/sensitivity, specificity, and balanced accuracy. To generate 3D AI-based quantitative feature burden and spatial distribution maps, AI-based feature segmentation was performed on each EB-OCT 2D cross-sectional image within a volumetric imaging site. Three external pathologist readers independently interpreted 3D AI-based features maps for each EB-OCT imaging site acquired for a subject (without access to EB-OCT images) and provided a single diagnosis of usual interstitial pneumonia (UIP) or non-UIP ILD. Performance of computer-aided ILD diagnosis was compared against independently evaluated histopathology, clinical diagnosis, and prior EB-OCT image interpretation. Results: EB-OCT was acquired in 51 subjects: 30 in vivo early ILD, 5 in vivo non-ILD controls, and 16 ex vivo end-stage ILD. Overall pixel similarity between 2D manual and AI-based segmentation demonstrated high accuracy for each ILD feature (mean balanced accuracy 0.9). 3D quantitative AI-based feature maps demonstrated strong agreement (Spearman ρ0.87, p&lt;0.001) between manual and AI-based segmentation. AI-based computer-aided diagnosis demonstrated 100% sensitivity/specificity for histologic UIP and clinical IPF for all pathologist readers, with improved diagnostic accuracy and significantly reduced training (45-minute training, 75% reduction) and interpretation time (&lt;1 minute per subject for computer-aided diagnosis, 88% reduction) compared to EB-OCT image interpretation. Conclusion: The AI-based EB-OCT image analysis framework could expedite computer-aided diagnosis of early ILD and robust, quantitative assessment of microscopic disease burden, progression, and therapeutic responsivity.