Systematic Prostate Biopsy Versus Perilesional Sampling: If It Isn't Broke, Why Fix It?

The 2024 EAU-EANM-ESTRO-ESUR-ISUP-SIOG guidelines for prostate cancer recommend a targeted and perilesional biopsy (TPLBx) strategy for primary diagnosis. In comparison to the classical approach of combined targeted and systematic biopsy, TPLBx may reduce overdiagnosis of insignificant cancers and mitigate the grade shift associated with targeted biopsy.

The Value of Protocol Biopsy in Kidney Transplantation on Monitoring Transplant Outcomes: A Systematic Review and Meta-Analysis.

BACKGROUND: There is a great debate about the role of biopsies per protocol in kidney transplant recipients, and the published studies show contradictory results. We aimed to assess the safety and effectiveness of protocol biopsies in kidney transplant recipients in improving short- and long-term outcomes. METHODS: We conducted searches until July of 2023 to identify all randomized clinical trials (RCT). Studies were identified through search strategies for CENTRAL, MEDLINE, EMBASE, and LILACS. Titles and abstracts were screened independently by 2 authors; 2 authors independently assessed retrieved abstracts and the full text. Assessment of risk of bias was carried out using the Cochrane risk of bias tool. The outcomes of interest were: Acute rejection, graft loss, mortality, glomerular filtration rate, and safety outcomes. Meta-analysis was performed for variables of interest when appropriate. Quality of evidence was assessed using GRADE methodology. RESULTS: We screened 5,695 records. Four trials met all eligibility criteria. No benefit of protocol biopsy was found in detecting acute rejection (3 studies RR: 2.0, 95% CI: 0.68-5.85, p = .2) or preventing graft loss at 12 months (2 studies, RR 0.33, 95% CI 0.06-1.72, p = .19). No differences were found between the groups in the glomerular filtration rate at 6 months post-transplantation (2 studies, MD 2.97, 95% CI 1.4-7.3, p = .18). A total of 23 safety events were present in the biopsy group compared to six in the control group. CONCLUSION: No benefit was found in performing protocol biopsy following kidney transplantation.

Meta-analysis: High pooled positive predictive value of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition no-biopsy approach for coeliac disease testing in children.

BACKGROUND: The European Society of Paediatric Gastroenterology, Hepatology and Nutrition established guidelines in 2012 for a no-biopsy approach to diagnose coeliac disease in children. This guideline required symptoms suggestive of coeliac disease, positive human leukocyte antigen (HLA) DQ2/DQ8 haplotypes, tissue transglutaminase type-2 immunoglobulin A antibody titre at levels greater than 10 times the upper limit of normal, and positive endomysial immune-globulin A antibody test. An updated 2020 guideline excluded the need for symptoms and positive HLA. AIMS: To assess the pooled positive predictive value (PPV) of the no-biopsy approach with small bowel biopsy (SBB) data as the reference standard for comparison. METHODS: Database searches (October 2023) provided data that we combined using a random-effects meta-analysis to provide a pooled PPV, representing the probability that a positive test result means that an individual truly has the condition. RESULTS: We included 23 studies. Study sample sizes totalled 23,769 but only 3007 children had comparative SBB. The proportion of coeliac disease confirmed by the no-biopsy approach and SBB ranged from 79.2% to 100%, with an overall pooled PPV of 97.4% (95% confidence interval 96.0, 98.6). Sensitivity analysis showed higher PPV for the criteria that included HLA (98.5% vs. 96.8%; p = 0.017). CONCLUSION: Both no-biopsy criteria exhibit high PPV when compared to the reference standard. These results provide a consistent message of accuracy and feasibility to inform change and improve outcomes.

[The pathological processing of prostate biopsy and resection specimens]. / A prosztatabiopsziák és -reszekátumok patológiai feldolgozása.

Prostate cancer stands as the most prevalent malignant tumor among men; with its incidence increasing with advancing age. The spectrum of patient care options for this disease is broad, encompassing approaches such as "active surveillance," definitive radiation therapy, robot-assisted surgery, among others. These diverse modalities afford opportunities for cure or successful management in the majority of cases. It is paramount to underscore that optimal treatment hinges upon a multidisciplinary framework, wherein the coordinated efforts of allied healthcare professionals yield the highest standard of patient care. Hence, it is imperative for pathologists to keep abreast of contemporary processing and specimen collection protocols, as well as the potential necessity of supplementary investigations and their clinical significance. The latest Hungarian guideline on prostate cancer care features a dedicated chapter delineating the pivotal role and responsibilities of pathologists. Through this discourse, we aim to consolidate and disseminate pertinent insights, thereby fostering the continuing enhancement of pathologists' knowledge and elucidating the intricacies of histological processing to our clinical counterparts.

A nomogram for the preoperative estimation of neuroblastoma risk despite inadequate biopsy information.

BACKGROUND AND PURPOSE: If the preoperative pathological information is inadequate, a risk classification may not be able to be determined for some patients with neuroblastoma. Our objectives were to include imaging factors, serum biomarkers, and demographic factors in a nomogram to distinguish high-risk patients before surgical resection based on the COG classification. METHOD: A total of 106 patients were included in the study. Of these, patients with clinicopathologically confirmed neuroblastoma at Tianjin Children's Hospital from January 2013 to November 2021 formed the training cohort (n = 82) for nomogram development, and those patients from January 2010 to December 2013 formed the validation cohort (n = 24) to confirm the model's performance. RESULT: On multivariate analysis of the primary cohort, independent factors for high risk were the presence of distant metastasis (p = 0.004), lactate dehydrogenase (LDH) (p = 0.009), and tumor volume (p = 0.033), which were all selected into the nomogram. The calibration curve for probability showed good agreement between prediction by nomogram and actual observation. The C-index of the nomogram was 0.95 95% [0.916-0.99]. Application of the nomogram in the validation cohort still gave good discrimination and good calibration. CONCLUSION: Three independent factors including the presence of distant metastasis, lactate dehydrogenase (LDH), and tumor volume are associated with high-risk neuroblastoma and selected into the nomogram. The novel nomogram has the flexibility to apply a clinically suitable cutoff to identify high-risk neuroblastoma patients despite inadequate preoperative pathological information. The nomogram can allow these patients to be offered suitable induction chemotherapy regimens and surgical plans. LEVELS OF EVIDENCE: Level III.

Impact of prostate biopsy secondary pathology review on radiotherapy management.

BACKGROUND: The Gleason scoring system is the most widely used method to assess prostate adenocarcinoma pathology however interobserver variability is significant. Gleason score, PSA level, and clinical stage comprise the NCCN risk stratification that guides treatment decision making. Given the importance of an accurate Gleason score and wide interobserver variability, referral centers routinely review outside pathology at the time of consultation. We sought to address the impact a secondary pathology review had on radiation therapy treatment recommendations in men with prostate cancer at our institution. METHODS: We retrospectively collected patient data on 342 patients seen at our institution from January 2012 to December 2018. Clinicopathologic data were used to subdivide patients into risk groups and available treatment options per NCCN criteria. Cases reviewed by our genitourinary pathologist (GUP) were compared with reports from outside pathologists. Inter-rater reliability between pathologists was assessed with weighted Cohen's kappa statistic and agreement of treatment options was determined by McNemar's exact tests. RESULTS: GUP scored more cores positive in 16.47% of cases on secondary review. Primary Gleason score was changed in 12.28% of patients and secondary score in 26.02% of cases. Total Gleason score was different in 29.24% of cases, 19.01% were downgraded and 10.23% upgraded. The weighted kappa statistic was 0.759 (95% confidence interval [CI]: 0.711, 0.807). 18.77% of patients were assigned to a different NCCN risk group following secondary review. The weighted kappa statistic comparing NCCN risk stratification was 0.802 (95% CI: 0.754, 0.850). Secondary review influenced radiation therapy recommendations pertaining to brachytherapy boost and androgen deprivation therapy in men with high risk disease (χ2 = 5.33, p = 0.0386; χ2 = 8.05, p = 0.0072, respectively). Kappa statistic was found to be highest when GUP assessed high-risk disease versus all other categories (κ = 0.823, 95% CI: 0.750, 0.895). CONCLUSIONS: We found nearly one in five men (18.7%) was assigned a different NCCN risk group and thus offered potentially different treatment options after a secondary pathology review at our institution. Given the inherent nature of prostate cancer and lung disease-specific survival associated with modern therapies, our study demonstrates the importance of a secondary pathology review and its potential impact on radiation therapy recommendations.

Effect of changes in Breslow thickness between the initial punch biopsy results and final pathology reports in acral lentiginous melanoma patients.

Acral lentiginous melanoma (ALM) is the most common subtype of cutaneous melanoma among Asians; punch biopsy is widely performed for its diagnosis. However, the pathologic parameters evaluated via punch biopsy may not be sufficient for predicting disease prognosis compared to the parameters evaluated via excisional biopsy. We investigated whether changes in Breslow thickness (BT) between initial punch biopsy results and final pathology reports can affect the prognosis of ALM. Pathologic parameters were recorded from specimens acquired through the initial punch biopsy and wide excision. Patients were classified into two groups based on a change in Breslow depth: the BT increased or decreased on comparing the samples from the initial punch biopsy and final wide excision. We compared clinical characteristics, and a Cox regression model was used to identify independent prognostic factors influencing melanoma-specific death (MSD). Changes in BT did not affect MSD (hazard ratio [HR]: 0.55, P = 0.447). In multivariate analysis, a higher BT (> 2 mm) (HR: 9.93, P = 0.046) and nodal metastasis (HR: 5.66, P = 0.041) were significantly associated with an increased MSD risk. The use of punch biopsy did not affect MSD despite the inaccuracy of BT measurement as long as ALM was accurately diagnosed.

AGA Clinical Practice Update on Surveillance After Pathologically Curative Endoscopic Submucosal Dissection of Early Gastrointestinal Neoplasia in the United States: Commentary.

The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update was to review the available evidence and provide expert advice regarding surveillance using endoscopy and other relevant modalities after removal of dysplastic lesions and early gastrointestinal cancers with endoscopic submucosal dissection deemed to be pathologically curative. This Clinical Practice Update was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the Clinical Practice Updates Committee and external peer review through standard procedures of Gastroenterology. This expert commentary incorporates important as well as recently published studies in this field, and it reflects the experiences of the authors, who are advanced endoscopists with high-level expertise in performing endoscopic submucosal dissection to treat dysplasia and early cancers in the luminal gastrointestinal tract.

Assessment of the Concordance Rate between Intraoperative Pathological Diagnosis and the Final Pathological Diagnosis of Spinal Cord Tumors.

The intraoperative pathological diagnosis (IPD) plays an important role in determining the optimal surgical treatment for spinal cord tumors. The final pathological diagnosis (FPD) is sometimes different from the IPD. Here, we sought to identify the accuracy of the IPD of spinal cord tumors compared to the FPD. We retrospec-tively analyzed the cases of 108 patients with spinal cord tumors treated surgically in our institute; the IPD, FPD, mismatched cases, and concordance rate between the IPD and FPD were investigated. Five cases involved a mismatch between the IPD and FPD. The overall concordance rate was 95.4%, with 90.9% for extra-dural lesions, 98.5% for intradural extramedullary lesions, 84.2% for intramedullary lesions, and 100% for dumbbell-type tumors. The concordance rate of intramedullary lesions tended to be lower than that of other lesions (p = 0.096). A lower concordance rate was revealed for intramedullary lesions compared to the other lesions. Despite the IPD clearly remaining a valuable tool during operative procedures, surgeons should recog-nize the limitations of IPDs and make comprehensive decisions about surgical treatments.

Effect of training and individual operator's expertise on prostate cancer detection through prostate biopsy: Implications for the current quantitative training evaluation system.

PURPOSE: This study was conducted to evaluate the relevance of training and experience to gaining expertise in prostate biopsy based on an assessment of outcomes from the performance of urology residents. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 10,299 patients who underwent prostate biopsy by 50 operators under a unified urology residency program. The number of prostate biopsies performed by an operator for each patient was used as an indicator of operator experience. Residents were grouped into quartiles according to cancer detection rates in the first 50 and the last 50 procedures. RESULTS: Among 10,299 patients (median age, 67.5 years; median prostate-specific antigen [PSA], 7.04 ng/mL), the overall prostate cancer detection rate and that for patients with PSA <10.0 ng/mL were 37.0% and 25.9%, respectively. Operator experience was a significant predictor for cancer detection in patients with PSA <10.0 ng/mL. Cancer detection rates and the proportion of more advanced prostate cancers were higher in the last 50 cases than in the first 50 cases. Detection rates varied significantly among operator; residents with higher detection rates at training initiation showed even higher detection rates after additional training. CONCLUSIONS: Training that adds to the cumulative experience of a trainee appears to play a meaningful role in improving cancer detection rates. The level of skill required to achieve mastery for independent practice may be assessed from the accuracy results of prostate biopsy procedures, and trainees with poor rates will require more technical training to improve precision.

Comparison of the diagnostic efficacy and complications of transbronchial biopsy in elderly and young patients.

INTRODUCTION: Among bronchoscopic procedures, transbronchial biopsy (TBB) is considered a high-risk procedure. In this study, we aimed to investigate the indications, diagnostic efficacy and complications of TBB in the elderly, which is accepted as a sensitive group. MATERIALS AND METHODS: The study was designed as a multicenter retrospective observational study. Data of 4226 patients who underwent diagnostic bronchoscopy were scanned for this study. 791 patients who underwent transbronchial biopsy were included in this study. All patients were evaluated in terms of lung regions, diagnosis, and complications. RESULT: A total of 791 patients, 329 (41.6%) female patients, who underwent TBB were included in the study. Mean age of the patients was 54.54 ± 14.94 years. The most common indications were ILD (45.6%), malignancy (24.0%) and sarcoidosis (9.9%). Mean age of the elderly patients (n= 263) was 69.89 ± 4.83 years, and mean age of the young patients (n= 528) was 46.90 ± 11.28 years (p<0.001). In both age groups, the most common indication was ILD. Complications developed during and after the procedure in 51 of the young patients (9.7%) and in 21 of the elderly (8.0%) (p= 0.441). The most common complication was pneumothorax with 4.6% in the elderly, and pneumothorax with 5.9% in the young (p= 0.441). The most common diagnosis was malignancy (12.2%) in the elderly, as the most common diagnosis was malignancy (7.2%) in the young (p = 0.020). While anthracosis, ILD and organized pneumonia were the other common diagnoses in the elderly, sarcoidosis, anthracosis and organized pneumonia were the other common diagnoses in the young. The diagnosis of sarcoidosis was achieved more frequently in the young (6.6%) than in the elderly (0.8%) (p<0.001). CONCLUSIONS: Transbronchial biopsy can be performed safely in elderly patients, with similar diagnostic success and complication rates to younger patients.

A combination of fecal calprotectin and human beta-defensin 2 facilitates diagnosis and monitoring of inflammatory bowel disease.

Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) show a large overlap in clinical presentation, which presents diagnostic challenges. As a consequence, invasive and burdensome endoscopies are often used to distinguish between IBD and IBS. Here, we aimed to develop a noninvasive fecal test that can distinguish between IBD and IBS and reduce the number of endoscopies.We used shotgun metagenomic sequencing to analyze the composition and function of gut microbiota of 169 IBS patients, 447 IBD patients and 1044 population controls and measured fecal Calprotectin (FCal), human beta defensin 2 (HBD2), and chromogranin A (CgA) in these samples. These measurements were used to construct training sets (75% of data) for logistic regression and machine learning models to differentiate IBS from IBD and inactive from active IBD. The results were replicated on test sets (remaining 25% of the data) and microbiome data obtained using 16S sequencing.Fecal HBD2 showed high sensitivity and specificity for differentiating between IBD and IBS (sensitivity = 0.89, specificity = 0.76), while the inclusion of microbiome data with biomarkers (HBD2 and FCal) showed a potential for improvement in predictive power (optimal sensitivity = 0.87, specificity = 0.93). Shotgun sequencing-based models produced comparable results using 16S-sequencing data. HBD2 and FCal were found to have predictive power for IBD disease activity (AUC ≈ 0.7).HBD2 is a novel biomarker for IBD in patients with gastro-intestinal complaints, especially when used in combination with FCal and potentially in combination with gut microbiome data.

Archival bone marrow smears are useful in targeted next-generation sequencing for diagnosing myeloid neoplasms.

Gene abnormalities, including mutations and fusions, are important determinants in the molecular diagnosis of myeloid neoplasms. The use of bone marrow (BM) smears as a source of DNA and RNA for next-generation sequencing (NGS) enables molecular diagnosis to be done with small amounts of bone marrow and is especially useful for patients without stocked cells, DNA or RNA. The present study aimed to analyze the quality of DNA and RNA derived from smear samples and the utility of NGS for diagnosing myeloid neoplasms. Targeted DNA sequencing using paired BM cells and smears yielded sequencing data of adequate quality for variant calling. The detected variants were analyzed using the bioinformatics approach to detect mutations reliably and increase sensitivity. Noise deriving from variants with extremely low variant allele frequency (VAF) was detected in smear sample data and removed by filtering. Consequently, various driver gene mutations were detected across a wide range of allele frequencies in patients with myeloid neoplasms. Moreover, targeted RNA sequencing successfully detected fusion genes using smear-derived, very low-quality RNA, even in a patient with a normal karyotype. These findings demonstrated that smear samples can be used for clinical molecular diagnosis with adequate noise-reduction methods even if the DNA and RNA quality is inferior.

Desmoid fibromatosis: is the current picture changing?

Desmoid fibromatosis is a locally aggressive tumor with an unpredictable clinical course. Surgery was once the mainstay of treatment, but the treatment protocol has been constantly evolving and currently active surveillance is the front-line approach. There have been significant insights into the molecular biology with the addition of mutational analysis of CTNNB1 adding to prognostic information. We present a review of the literature with current practice guidelines, also including novel therapeutic targets and ongoing clinical trials, to unravel the next step in the management of sporadic desmoid fibromatosis.

Lay abstract Desmoid fibromatosis is an aggressive local tumor with continuously changing treatment paradigms. It requires MRI with biopsy for diagnosis and follow-up. Usually the tumor responds to a 'wait and watch' approach in most patients with either stable disease or regression on follow-up; a surgical plan is made only after multidisciplinary discussion, as surgery does not provide additional benefit in most patients. After a period of wait and watch, if there is disease progression, patients can be kept on medical management such as chemotherapy. Currently we have novel drugs for medical management like tyrosine kinase inhibitors, which result in disease stabilization in a majority of patients. In order to reduce the morbidity of treatment, it is essential for the patient to be on continuous follow-up and for clinicians to be updated with the continuously changing management of this disease.

Prognostic performance of 7 biomarkers compared to liver biopsy in early alcohol-related liver disease.

BACKGROUND & AIMS: Alcohol is the most common cause of liver-related mortality and morbidity. We therefore aimed to assess and compare the prognostic performance of elastography and blood-based markers to predict time to the first liver-related event, severe infection, and all-cause mortality in patients with a history of excess drinking. METHODS: We performed a prospective cohort study in patients with early, compensated alcohol-related liver disease. At baseline, we obtained a liver biopsy, transient elastography (TE), 2-dimensional shear-wave elastography (2D-SWE), enhanced liver fibrosis test (ELF), FibroTest, fibrosis-4 index (FIB-4), non-alcoholic fatty liver fibrosis score (NFS) and Forns index. We compared C-statistics and time-dependent AUC for prognostication. We used validated cut-off points to create 3 risk groups for each test: low, intermediate and high risk. RESULTS: We followed 462 patients for a median of 49 months (IQR 31-70). Median age was 57 years, 76% were males, 20% had advanced fibrosis. Eighty-four patients (18%) developed a liver-related event after a median of 18 months (7-34). TE had the highest prognostic accuracy, with a C-statistic of 0.876, and time-dependent AUC at 5 years of 0.889, comparable to 2D-SWE and ELF. TE, ELF and 2D-SWE outperformed FibroTest, FIB4, NFS, Forns index and biopsy-verified fibrosis stage. Compared to patients with TE <10 kPa, the hazard ratios for liver-related events for TE 10-15 kPa were 8.1 (3.2-20.4), and 27.9 (13.8-56.8) for TE >15 kPa. Periods of excessive drinking during follow-up increased the risk of progressing to liver-related events, except for patients in the low-risk groups. CONCLUSION: TE, ELF and 2D-SWE are highly accurate prognostic markers in patients with alcohol-related liver disease. Easy-to-use cut-offs can distinguish between substantially different risk profiles. LAY SUMMARY: Alcohol is the leading cause of death and illness due to liver disease. In this study, we assessed the ability of biomarkers to predict the risk of developing symptomatic liver disease in patients with early stages of alcohol-related liver disease. We found that several tests accurately predicted the risk of liver-related events such as ascites, esophageal varices and hepatic encephalopathy during an average follow-up of 4.1 years. Liver stiffness measurements by ultrasound elastography and the enhanced liver fibrosis test performed best. By using them, we were able to stratify patients into 3 groups with significantly different risks.

Development and Validation of a Deep Learning Model to Quantify Interstitial Fibrosis and Tubular Atrophy From Kidney Ultrasonography Images.

Importance: Interstitial fibrosis and tubular atrophy (IFTA) is a strong indicator of decline in kidney function and is measured using histopathological assessment of kidney biopsy core. At present, a noninvasive test to assess IFTA is not available. Objective: To develop and validate a deep learning (DL) algorithm to quantify IFTA from kidney ultrasonography images. Design, Setting, and Participants: This was a single-center diagnostic study of consecutive patients who underwent native kidney biopsy at John H. Stroger Jr. Hospital of Cook County, Chicago, Illinois, between January 1, 2014, and December 31, 2018. A DL algorithm was trained, validated, and tested to classify IFTA from kidney ultrasonography images. Of 6135 Crimmins-filtered ultrasonography images, 5523 were used for training (5122 images) and validation (401 images), and 612 were used to test the accuracy of the DL system. Kidney segmentation was performed using the UNet architecture, and classification was performed using a convolution neural network-based feature extractor and extreme gradient boosting. IFTA scored by a nephropathologist on trichrome stained kidney biopsy slide was used as the reference standard. IFTA was divided into 4 grades (grade 1, 0%-24%; grade 2, 25%-49%; grade 3, 50%-74%; and grade 4, 75%-100%). Data analysis was performed from December 2019 to May 2020. Main Outcomes and Measures: Prediction of IFTA grade was measured using the metrics precision, recall, accuracy, and F1 score. Results: This study included 352 patients (mean [SD] age 47.43 [14.37] years), of whom 193 (54.82%) were women. There were 159 patients with IFTA grade 1 (2701 ultrasonography images), 74 patients with IFTA grade 2 (1239 ultrasonography images), 41 patients with IFTA grade 3 (701 ultrasonography images), and 78 patients with IFTA grade 4 (1494 ultrasonography images). Kidney ultrasonography images were segmented with 91% accuracy. In the independent test set, the point estimates for performance matrices showed precision of 0.8927 (95% CI, 0.8682-0.9172), recall of 0.8037 (95% CI, 0.7722-0.8352), accuracy of 0.8675 (95% CI, 0.8406-0.8944), and an F1 score of 0.8389 (95% CI, 0.8098-0.8680) at the image level. Corresponding estimates at the patient level were precision of 0.9003 (95% CI, 0.8644-0.9362), recall of 0.8421 (95% CI, 0.7984-0.8858), accuracy of 0.8955 (95% CI, 0.8589-0.9321), and an F1 score of 0.8639 (95% CI, 0.8228-0.9049). Accuracy at the patient level was highest for IFTA grade 1 and IFTA grade 4. The accuracy (approximately 90%) remained high irrespective of the timing of ultrasonography studies and the biopsy diagnosis. The predictive performance of the DL system did not show significant improvement when combined with baseline clinical characteristics. Conclusions and Relevance: These findings suggest that a DL algorithm can accurately and independently predict IFTA from kidney ultrasonography images.

Practical application and validation of the 2018 ATS/ERS/JRS/ALAT and Fleischner Society guidelines for the diagnosis of idiopathic pulmonary fibrosis.

BACKGROUND: Accurate diagnosis of idiopathic pulmonary fibrosis (IPF) is essential to inform prognosis and treatment. In 2018, the ATS/ERS/JRS/ALAT and Fleischner Society released new diagnostic guidelines for usual interstitial pneumonitis (UIP)/IPF, adding Probable UIP as a CT category based on prior studies demonstrating this category had relatively high positive predictive value (PPV) for histopathologic UIP/Probable UIP. This study applies the 2018 ATS/ERS/JRS/ALAT and Fleischner Society guidelines to determine test characteristics of CT categories in academic clinical practice. METHODS: CT and histopathology were evaluated by three thoracic radiologists and two thoracic pathologists. Comparison of consensus categorization by the 2018 ATS and Fleischner Society guidelines by CT and histopathology was performed. RESULTS: Of patients with CT UIP, 87% (PPV, 95% CI: 60-98%) had histopathologic UIP with 97% (CI: 90-100%) specificity. Of patients with CT Probable UIP, 38% (PPV, CI: 14-68%) had histopathologic UIP and 46% (PPV, CI: 19-75%) had either histopathologic UIP or Probable UIP, with 88% (CI: 77-95%) specificity. Patients with CT Indeterminate and Alternative Diagnosis had histopathologic UIP in 27% (PPV, CI: 6-61%) and 21% (PPV, CI: 11-33%) of cases with specificities of 90% (CI: 80-96%) and 25% (CI: 16-37%). Interobserver variability (kappa) between radiologists ranged 0.32-0.81. CONCLUSIONS: CT UIP and Probable UIP have high specificity for histopathologic UIP, and CT UIP has high PPV for histopathologic UIP. PPV of CT Probable UIP was 46% for combined histopathologic UIP/Probable UIP. Our results indicate that additional studies are needed to further assess and refine the guideline criteria to improve classification performance.

Update on the Diagnostic Pitfalls of Autopsy and Post-Mortem Genetic Testing in Cardiomyopathies.

Inherited cardiomyopathies are frequent causes of sudden cardiac death (SCD), especially in young patients. Despite at the autopsy they usually have distinctive microscopic and/or macroscopic diagnostic features, their phenotypes may be mild or ambiguous, possibly leading to misdiagnoses or missed diagnoses. In this review, the main differential diagnoses of hypertrophic cardiomyopathy (e.g., athlete's heart, idiopathic left ventricular hypertrophy), arrhythmogenic cardiomyopathy (e.g., adipositas cordis, myocarditis) and dilated cardiomyopathy (e.g., acquired forms of dilated cardiomyopathy, left ventricular noncompaction) are discussed. Moreover, the diagnostic issues in SCD victims affected by phenotype-negative hypertrophic cardiomyopathy and the relationship between myocardial bridging and hypertrophic cardiomyopathy are analyzed. Finally, the applications/limits of virtopsy and post-mortem genetic testing in this field are discussed, with particular attention to the issues related to the assessment of the significance of the genetic variants.