Measuring cancer burden in prostatic needle core biopsies: simplified assessments outperform complex measurements in assessing outcome: evidence to assist pathologist efficiency and minimize datasets.

AIMS: The optimal method of measuring cancer extent in prostate cancer (PCa) biopsies is unknown. METHODS AND RESULTS: Nine hundred eighty-one men with clinically localised PCa managed conservatively were reviewed with follow up. The number of positive cores (NPC), the Maximum Cancer Length in a core (MCL), Total Cancer Length (TCL), and percentage of positive cores (%+cores) was calculated and univariate and multivariate analysis performed using prostate-specific antigen (PSA), T-stage, and Gleason score. The presence of stromal gaps (SG) was recorded. Univariate models were run where SG made a difference to the MCL. All variables showed significant association with PCa death in univariate models. In multivariate models, incorporating PSA, T-stage, and Gleason score, only %+cores was a significant predictor of outcome, with a 10% increase in %+cores resulting in a hazard ratio (HR) of 1.07 (likelihood-ratio test P > Χ2  = 0.01). There were 120 patients where SG made a difference to the MCL and a total of 20 events in this group. Including SG, on univariate analysis the median MCL was 10 mm and HR was 1.16 (P = 0.007), not including SG, the median MCL was 6 mm and HR was 1.23 (P = 6.3 × 10-4 ). Inclusion or exclusion of SG made no significant difference to TCL as a predictor of outcome. CONCLUSION: Cancer extent is a strong predictor of PCa death but only %+cores added to the multivariate model. Expressed as a fraction of NPC/total number of cores, this is the simplest method of assessment, which we favour over more complicated methods in nontargeted biopsies.

Efficacy and safety of ultrasound-guided core needle biopsies (US-CNBs) in cervical lymphadenopathy in patients with suspected head and neck cancer during the COVID-19 pandemic.

BACKGROUND: Cervical lymphadenopathy can be benign or malignant. Its accurate diagnosis is necessary to determine appropriate treatment. Ultrasound-guided core needle biopsies (US-CNBs) are frequently used as a percutaneous sampling approach. OBJECTIVES: Our aim was to identify the efficacy and safety of US-CNBs in 125 patients with cervical lymphadenopathy and clinically suspected head and neck cancer during the COVID-19 pandemic with limited surgical resources. METHODS: US-CNBs of pathological lymph nodes were performed in 146 lymph nodes on 125 patients. Biopsies were performed ultrasound-guided with a reusable gun core biopsy system and a 10-cm-long 16-G needle. Standard of reference for the histological findings were panendoscopy, clinical and sonographic follow-up, surgical biopsy or a repeat US-CNB. RESULTS: Adequate material for histologic diagnosis was obtained in 111 patients (89%), of these 83 patients (75%) were diagnosed as malignant, whereas benign lymphadenopathy accounted for 28 patients (25%). Therefore, US-CNB was able to identify malignant or benign lymphadenopathy with an overall accuracy of 88% and 90%, respectively. CONCLUSIONS: Percutaneous US-CNB is a safe and effective alternative to surgical biopsy in the management of cervical lymphadenopathy in patients with clinically suspected head and neck cancer in a setting with limited resources.

The effect of delay of excisional biopsy on upstage rate for atypical ductal hyperplasia, flat epithelial atypia, intraductal papilloma, and radial scar.

PURPOSE: When Core Needle Biopsy (CNB) demonstrates Atypical Ductal Hyperplasia (ADH), Flat Epithelial Atypia (FEA), Intraductal Papilloma (IDP), or Radial Scar/Complex Sclerosing Lesion (RS), excisional biopsy (EB) is often performed to rule out underlying malignancy with upstage rates (UR) ranging between 1 and 20%. The COVID-19 pandemic led to delayed EB for many patients. We sought to evaluate whether this delay was associated with higher UR. METHODS: We performed a retrospective analysis of women who underwent CNB and then EB for ADH, FEA, IDP, or RS between 2017 and 2021 using an IRB-approved repository. UR was evaluated by days between CNB and EB. RESULTS: 473 patients met inclusion. 55 were upstaged to cancer (11.6%). 178 patients had pure ADH on CNB and 37 were upstaged (20.8%). 50 patients had pure FEA and 3 were upstaged (6%). 132 had pure IDP and 7 were upstaged (5.3%). 98 had pure RS and 1 was upstaged (1%). 7/15 (46.7%) had a combination of diagnoses or diagnosis with palpable mass and were upstaged. Days between CNB and EB were < 60 for 275 patients (58.1%), 60-90 for 108 (22.8%), 91-120 for 43 (9.1%), and > 120 for 47 (9.9%). There was no significant difference in UR (10.9% for < 60, 14.8% for 60-90, 7% for 90-120, and 12.8% for > 120, p = 0.54). UR for ADH was clinically increased after 60 days (27.8 vs. 17.5%), but this did not reach statistical significance (p = 0.1). CONCLUSION: Surgical delay was not associated with an increased UR.

Clinical characteristics and histopathology of COVID-19 related deaths in South African adults.

Comparisons of histopathological features and microbiological findings between decedents with respiratory symptoms due to SARS-CoV-2 infection or other causes, in settings with high prevalence of HIV and Mycobacterium tuberculosis (MTB) infections have not been reported. Deaths associated with a positive ante-mortem SARS-CoV-2 PCR test and/or respiratory disease symptoms at Chris Hani Baragwanath Academic Hospital in Soweto, South Africa from 15th April to 2nd November 2020, during the first wave of the South African COVID-19 epidemic, were investigated. Deceased adult patients had post-mortem minimally-invasive tissue sampling (MITS) performed to investigate for SARS-CoV-2 infection and molecular detection of putative pathogens on blood and lung samples, and histopathology examination of lung, liver and heart tissue. During the study period MITS were done in patients displaying symptoms of respiratory disease including 75 COVID-19-related deaths (COVID+) and 42 non-COVID-19-related deaths (COVID-). The prevalence of HIV-infection was lower in COVID+ (27%) than in the COVID- (64%), MTB detection was also less common among COVID+ (3% vs 13%). Lung histopathology findings showed differences between COVID+ and COVID- in the severity of the morphological appearance of Type-II pneumocytes, alveolar injury and repair initiated by SARS-CoV-2 infection. In the liver necrotising granulomatous inflammation was more common among COVID+. No differences were found in heart analyses. The prevalence of bacterial co-infections was higher in COVID+. Most indicators of respiratory distress syndrome were undifferentiated between COVID+ and COVID- except for Type-II pneumocytes. HIV or MTB infection does not appear in these data to have a meaningful correspondence with COVID-related deaths.

High concordance of 70-gene recurrence risk signature and 80-gene molecular subtyping signature between core needle biopsy and surgical resection specimens in early-stage breast cancer.

BACKGROUND AND OBJECTIVES: With increased neoadjuvant therapy recommendations for early-stage breast cancer patients due to the COVID-19 pandemic, it is imperative that molecular diagnostic assays provide reliable results from preoperative core needle biopsies (CNB). The study objective was to determine the concordance of MammaPrint and BluePrint results between matched CNB and surgical resection (SR) specimens. METHODS: Matched tumor specimens (n = 121) were prospectively collected from women enrolled in the FLEX trial (NCT03053193). Concordance is reported using overall percentage agreement and Cohen's kappa coefficient. Correlation is reported using Pearson correlation coefficient. RESULTS: We found good concordance for MammaPrint results between matched tumor samples (90.9%, κ = 0.817), and a very strong correlation of MammaPrint indices (r = 0.94). The concordance of BluePrint subtyping in matched samples was also excellent (98.3%). CONCLUSIONS: CNB samples demonstrated high concordance with paired SR samples for MammaPrint risk classification and BluePrint molecular subtyping, suggesting that physicians are provided with accurate prognostic information that can be used to guide therapy decisions.

How Does Invasive Breast Cancer Oncotype Dx Recurrence Score on Core Needle Biopsies Influence Neoadjuvant Treatment Decision? A Descriptive Study.

BACKGROUND: Oncotype Dx (ODx) is a genomic assay which estimates the risk of distant recurrence and predicts adjuvant chemotherapy benefit in early stage breast cancer patients. Most ODx data is derived from excisional specimens. AIM: We assess the utility of ODx on core needle biopsies (CNB) and measure its impact on neoadjuvant treatment decisions, particularly in patients with clinically complicated situations. METHODS: Consecutive ODx results on breast CNBs with invasive carcinoma from 2012-2020 at 3 tertiary care hospitals with dedicated Breast Health Centers were reviewed. Clinical indications to perform ODx on CNB were recorded through a review of patients' electronic medical records. Clinicopathologic features, surgical or oncologic modalities and follow-up data were recorded. RESULTS: Three distinct clinical indications for performing ODx on CNB in 85 ER+ invasive breast carcinomas were identified: 1) Excisions with insufficient tissue to perform ODx, 2) adjudicate neoadjuvant therapy versus primary surgical resection, and 3) select neoadjuvant chemotherapy (NAC) versus neoadjuvant endocrine therapy (NET). Primary surgery was selected in patients with low score RS (<18), and NET was preferred in patients with intermediate or high RS (>18). NET was preferred over NAC in patients with low RS (<18). CONCLUSION: This study shows that CNB ODx RS helps guide treatment decisions in a neoadjuvant setting along with other contributing factors such as the presence of pathogenic mutations, node positivity, patient age, and comorbidities. The use of ODx on CNB is furthermore valuable in the midst of the COVID-19 pandemic for early breast cancer patients to administer effective therapy in a timely manner.

The PROCEM study protocol: Added value of preoperative contrast-enhanced mammography in staging of malignant breast lesions - a prospective randomized multicenter study.

BACKGROUND: Correct preoperative estimation of the malignant extent is crucial for optimal planning of breast cancer surgery. The sensitivity of mammography is lower in dense breasts, and additional imaging techniques are sometimes warranted. Contrast-enhanced mammography (CEM) has shown similar sensitivity and in some cases better specificity, than magnetic resonance imaging (MRI) in small, observational studies. CEM may be more cost-effective than MRI, and may provide better identification of the tumor extent, however, no randomized trials have been performed to date to investigate the added value of CEM. In a feasibility study, we found that the treatment was changed in 10/47 (21%) cases after additional CEM. The purpose of the present study is to evaluate the added value of CEM in preoperative staging of breast cancer in a randomized study. METHOD: This prospective randomized study will include 440 patients with strongly suspected or established diagnosis of breast malignancy, based on assessment with mammography, ultrasound and core biopsy/cytology, and for whom primary surgery is planned. Patients will be randomized 1:1 using a web-based randomization tool to additional investigation with CEM or no further imaging. The CEM findings will be taken into consideration, which may lead to changes in primary treatment, which is the primary endpoint of this study. Secondary endpoints include rate of reoperation and number of avoidable mastectomies, as well as a cost-benefit analysis of additional CEM. Patient-reported health-related quality of life will be investigated at 1 year with the validated Breast-Q™ questionnaire. The rate of local recurrence or new cancer ipsi- or contralaterally within 5 years will be assessed from medical records and pathology reports. DISCUSSION: The aim of this trial is to explore the added value of CEM in preoperative staging of breast cancer. The results obtained from this study will contribute to our knowledge on CEM as an additional imaging method to standard investigation with digital mammography and ultrasound. The findings may also provide additional information on which patient groups would benefit from CEM, and on the economic aspects of CEM in standard preoperative practice. TRIAL REGISTRATION: This trial is registered at clinicaltrials.gov , registration no: NCT04437602 , date of registration: June 18, 2020.

Percutaneous Lung Biopsy with Pleural and Parenchymal Blood Patching: Results and Complications from 1,112 Core Biopsies.

PURPOSE: To evaluate the outcomes of computed tomography (CT) fluoroscopy-guided core lung biopsies with emphasis on diagnostic yield, complications, and efficacy of parenchymal and pleural blood patching to avoid chest tube placement. METHODS: This is a single-center retrospective analysis of CT fluoroscopy-guided percutaneous core lung biopsies between 2006 and 2020. Parenchymal blood patching during introducer needle withdrawal was performed in 74% of cases as a preventive measure, and pleural blood patching was the primary salvage maneuver for symptomatic or growing pneumothorax in 60 of 83 (72.2%) applicable cases. RESULTS: A total of 1,029 patients underwent 1,112 biopsies (532 men; mean age, 66 years; 38.6%, history of emphysema; lesion size, 16.7 mm). The diagnostic yield was 93.6% (1,032/1,103). Fewer complications requiring intervention were observed in patients who underwent parenchymal blood patching (5.7% vs 14.2%, P < .001). Further intervention was required in 83 of 182 pneumothorax cases, which included the following: (a) pleural blood patch (5.4%, 60/1,112), (b) chest tube placement without a pleural blood patch attempt (1.5%, 17/1,112), and (c) simple aspiration (0.5%, 6/1,112). Pleural blood patch as monotherapy was successful in 83.3% (50/60) of cases without need for further intervention. The overall chest tube rate was 2.6% (29/1,112). Emphysema was the only significant risk factor for complications requiring intervention (P ≤ .001). CONCLUSIONS: Parenchymal blood patching during introducer needle withdrawal decreased complications requiring intervention. Salvage pleural blood patching reduced the frequency of chest tube placement for pneumothorax.

[Post mortem core needle biopsy of Covid-19 fatalities]. / Punción post mortem con aguja gruesa a cadáveres fallecidos por COVID-19.

The difficulties involved in performing autopsies of patients who had died due to COVID-19 required the use of alternative methods in order to obtain tissue samples of affected organs. We describe the technique of core needle aspiration, without ultrasonographic guidance, which we used in 19 cadavers and which produced a high yield in lungs, heart (>94%) and liver (>89%), thus enabling the study of the morphological changes produced by SARS-CoV-2.

Multi-organ pathological findings associated with COVID-19 in postmortem needle core biopsies in four patients and a review of the current literature.

Coronavirus disease 2019 (COVID-19) has spread worldwide, resulting in significant morbidity and mortality. Histopathological findings are essential in understanding its pathogenesis and we present our findings from postmortem core needle biopsies in an attempt to share information that may shed some light on this severe pandemic. Different organ samples from four patients with PCR-confirmed COVID-19 at the Infanta Sofía Hospital (Madrid) were studied during the months of April and May, 2020 by six pathologists using routine stains, histochemistry and immunohistochemistry. Results were compared with other reported cases. All patients had a clinical diagnosis of pneumonia and biopsies revealed lung damage in the majority. Heart, liver, spleen and kidney were also studied and abnormalities were found in all cases and are extensively described. The histopathology of organs affected by COVID-19 is vital to the understanding of this disease and its sequelae.

Histopathological features of multiorgan percutaneous tissue core biopsy in patients with COVID-19.

AIMS: The global outbreak of COVID-19 has resulted in an increased mortality. However, whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect multiple organs is still unclear. In this study, postmortem percutaneous biopsies of multiple organs from deceased patients were performed to understand the histopathological changes caused by COVID-19. METHODS: Biopsy specimens of pulmonary, cardiac, hepatic and lymphoid tissues were obtained from three patients, who died due to COVID-19 pneumonia. H&E stain, Masson trichrome stain, immunohistochemistry stain and in-situ hybridisation were used. RESULTS: Pulmonary damages caused by SARS-CoV-2 infection was diffuse alveolar damage (DAD). In the early phase, the histological findings were mainly those of exudative features of DAD. The later phase was characterised by organisation of DAD combined with bacterial pneumonia. No serious damage was found in the bronchiolar epithelium and submucosal glands. The hepatic tissue revealed features of ischaemic necrosis, but findings suggestive of mild lobular hepatitis were also observed. The lymphoid tissue revealed features of non-specific acute lymphadenitis. The cardiac tissue revealed changes of underlying disease. SARS-CoV-2 RNAs were not detected in hepatocytes, cholangiocytes and lymphocytes of lymph nodes. CONCLUSIONS: COVID-19 predominantly involves the pulmonary tissue, causes DAD and aggravates the cardiovascular disease. However, other extrapulmonary tissues did not reveal any virus-specific findings, but were affected by multiple factors. The findings in this report caution the pathologists that they should not mistakenly attribute all the histological features to CoV infection. Moreover, the clinicians should pay attention to the potentially injurious and correctable causes.

Late histopathologic characteristics of critically ill COVID-19 patients: Different phenotypes without evidence of invasive aspergillosis, a case series.

PURPOSE: Pathological data of critical ill COVID-19 patients is essential in the search for optimal treatment options. MATERIAL AND METHODS: We performed postmortem needle core lung biopsies in seven patients with COVID-19 related ARDS. Clinical, radiological and microbiological characteristics are reported together with histopathological findings. MEASUREMENT AND MAIN RESULTS: Patients age ranged from 58 to 83 years, five males and two females were included. Time from hospital admission to death ranged from 12 to 36 days, with a mean of 20 ventilated days. ICU stay was complicated by pulmonary embolism in five patients and positive galactomannan on bronchoalveolar lavage fluid in six patients, suggesting COVID-19 associated pulmonary aspergillosis. Chest CT in all patients showed ground glass opacities, commonly progressing to nondependent consolidations. We observed four distinct histopathological patterns: acute fibrinous and organizing pneumonia, diffuse alveolar damage, fibrosis and, in four out of seven patients an organizing pneumonia. None of the biopsy specimens showed any signs of invasive aspergillosis. CONCLUSIONS: In this case series common late histopathology in critically ill COVID patients is not classic DAD but heterogeneous with predominant pattern of organizing pneumonia. Postmortem biopsy investigations in critically COVID-19 patients with probable COVID-19 associated pulmonary aspergillosis obtained no evidence for invasive aspergillosis.

Pathological Findings of Postmortem Biopsies From Lung, Heart, and Liver of 7 Deceased COVID-19 Patients.

Background. A novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been affecting almost all nations around the world. Most infected patients who have been admitted to intensive care units show SARS signs. In this study, we aimed to achieve a better understanding of pathological alterations that take place during the novel coronavirus infection in most presumed affected organs. Methods. We performed postmortem core needle biopsies from lung, heart, and liver on 7 deceased patients who had died of coronavirus disease 2019. Prepared tissue sections were observed by 2 expert pathologists. Results. Diffuse alveolar damage was the main pathologic finding in the lung tissue samples. Patients with hospitalization durations of more than 10 days showed evidence of organization. Multinucleated cells in alveolar spaces and alveolar walls, atypical enlarged cells, accumulation of macrophages in alveolar spaces, and congestion of vascular channels were the other histopathologic alteration of the lung. None of our heart biopsy samples met the criteria for myocarditis. Liver biopsies showed congestion, micro- and macro-vesicular changes, and minimal to mild portal inflammation, in the majority of cases. Conclusions. Similar to the previous coronavirus infection in 2003, the main pathologic finding in the lung was diffuse alveolar damage with a pattern of organization in prolonged cases. The SARS-CoV-2 infection does not cause myocarditis, and the ischemia of myocardium is the most probable justification of the observed pathologic changes in the heart. Liver tissue sections mostly showed nonspecific findings; however, ischemia of the liver can be identified in some cases.

Breast Cancer and COVID-19: The Effect of Fear on Patients' Decision-making Process.

BACKGROUND/AIM: Coronavirus-19 (COVID-19) pandemic outbreak is currently having a huge impact on medical resource allocation. Breast Cancer (BC) patients are concerned both with BC treatment and COVID-19. This study aimed to estimate the impact of anxiety among patients, caused by the spreading of COVID-19. PATIENTS AND METHODS: Between the 16th of January and the 20th of March 2020, we retrospectively enrolled 160 patients. Eighty-two patients with a suspected breast lesion (SBL) were divided into two groups: PRE-COVID-19-SBL and POST-COVID-19-SBL. Seventy-eight BC patients were divided into PRE-COVID-19-BC and POST-COVID-19-BC. Patient characteristics including age, marital status, SBL/BC diameter, personal and family history of BC, clinical stage and molecular subtype were recorded. Procedure Refusal (PR) and Surgical Refusal (SR) were also recorded with their reason. RESULTS: BC and SBL analysis showed no difference in pre-treatment characteristics (p>0.05). Both POST-COVID-19-SBL and POST-COVID-19-BC groups showed higher rates of PR and SR (p=0.0208, p=0.0065 respectively). Infection risk represented primary reason for refusal among POST-COVID-19 patients. CONCLUSION: COVID-19-related anxiety could affect patients' decision-making process.

Pathological study of the 2019 novel coronavirus disease (COVID-19) through postmortem core biopsies.

Data on pathologic changes of the 2019 novel coronavirus disease (COVID-19) are scarce. To gain knowledge about the pathology that may contribute to disease progression and fatality, we performed postmortem needle core biopsies of lung, liver, and heart in four patients who died of COVID-19 pneumonia. The patients' ages ranged from 59 to 81, including three males and one female. Each patient had at least one underlying disease, including immunocompromised status (chronic lymphocytic leukemia and renal transplantation) or other conditions (cirrhosis, hypertension, and diabetes). Time from disease onset to death ranged from 15 to 52 days. All patients had elevated white blood cell counts, with significant rise toward the end, and all had lymphocytopenia except for the patient with leukemia. Histologically, the main findings are in the lungs, including injury to the alveolar epithelial cells, hyaline membrane formation, and hyperplasia of type II pneumocytes, all components of diffuse alveolar damage. Consolidation by fibroblastic proliferation with extracellular matrix and fibrin forming clusters in airspaces is evident. In one patient, the consolidation consists of abundant intra-alveolar neutrophilic infiltration, consistent with superimposed bacterial bronchopneumonia. The liver exhibits mild lobular infiltration by small lymphocytes, and centrilobular sinusoidal dilation. Patchy necrosis is also seen. The heart shows only focal mild fibrosis and mild myocardial hypertrophy, changes likely related to the underlying conditions. In conclusion, the postmortem examinations show advanced diffuse alveolar damage, as well as superimposed bacterial pneumonia in some patients. Changes in the liver and heart are likely secondary or related to the underlying diseases.