Using IVIM Parameters to Differentiate Prostate Cancer and Contralateral Normal Tissue through Fusion of MRI Images with Whole-Mount Pathology Specimen Images by Control Point Registration Method

The intravoxel incoherent motion (IVIM) model may enhance the clinical value of multiparametric magnetic resonance imaging (mpMRI) in the detection of prostate cancer (PCa). However, while past IVIM modeling studies have shown promise, they have also reported inconsistent results and limitations, underscoring the need to further enhance the accuracy of IVIM modeling for PCa detection. Therefore, this study utilized the control point registration toolbox function in MATLAB to fuse T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) MRI images with whole-mount pathology specimen images in order to eliminate potential bias in IVIM calculations. Sixteen PCa patients underwent prostate MRI scans before undergoing radical prostatectomies. The image fusion method was then applied in calculating the patients’ IVIM parameters. Furthermore, MRI scans were also performed on 22 healthy young volunteers in order to evaluate the changes in IVIM parameters with aging. Among the full study cohort, the f parameter was significantly increased with age, while the D* parameter was significantly decreased. Among the PCa patients, the D and ADC parameters could differentiate PCa tissue from contralateral normal tissue, while the f and D* parameters could not. The presented image fusion method also provided improved precision when comparing regions of interest side by side. However, further studies with more standardized methods are needed to further clarify the benefits of the presented approach and the different IVIM parameters in PCa characterization.

Challenges in Pathology Specimen Processing in the New Era of Precision Medicine

Context.— Precision therapies for patients with driver mutations can offer deep and durable responses that correlate with diagnosis, metastasis prognosis, and improvement in survival. Such targeted therapies will continue to increase, pushing us to change our traditional approaches. We needed to search for new tools to effectively integrate technological advancements into our practices because of their capability to improve the efficiency and accuracy of our diagnostic and treatment approaches. Perhaps nothing is as relevant as identifying and implementing new workflows for processing pathologic specimens and for improving communication of critical laboratory information to and from clinicians for appropriate care of patients in an efficient and timely manner. Objectives.— To define the gold standard in delivering the best care for patients, to identify gaps in the process, and to identify potential solutions that would improve our process, including gaps related to knowledge, skills, attitudes, and practices. Design.— We assembled a team across disciplines to systematically perform a gap analysis study to clarify the discrepancy between the current reality in pathology specimen processing and the desired optimal situation to deliver the results intended for patient care. Results.— A practical collaborative workflow for specimen management seeking the cooperation of the stakeholders in each medical discipline to provide guidelines in specimen collection, delivery, processing, and reporting of results with the ultimate goal of improving patients' outcomes is provided. Conclusions.— New tools are required to effectively integrate data-driven approaches in specimen processing to meet the new demands.

Burkitt Lymphoma Presenting as Perforated Appendicitis

Appendicitis is the most common indication for an emergent abdominal operation in the pediatric population. Fewer than .015% of patients who undergo appendectomy for presumed appendicitis are diagnosed with primary lymphoma after evaluation of pathology specimen. 1 Of these primary lymphomas, 29.5% are Burkitt lymphoma. Burkitt lymphoma is an aggressive B-cell lymphoma characterized by translocation and dysregulation of the c-Myc gene. Intraabdominal extranodal Burkitt lymphoma has a polymorphic presentation that includes bowel obstruction, intussusception, and appendicitis. Here we report a case of an adolescent patient who was initially admitted for medical management of perforated appendicitis but was diagnosed with Burkitt lymphoma during his hospital course.

Case report of isolated cardiac sarcoidosis presenting as hypertrophic obstructive cardiomyopathy—a clinical picture printed on lenticular paper

Background Cardiac sarcoidosis (CS) is an inflammatory granulomatous process of the myocardium that can be asymptomatic or have several different clinical phenotypes. One of its rarely described presentations consists of hypertrophy of the septal myocardium, similar to hypertrophic cardiomyopathy (HCM). Isolated cardiac sarcoidosis that haemodynamically mimics hypertrophic obstructive cardiomyopathy (HOCM) has been rarely described in the literature. Case summary A 64-year-old Caucasian female previously diagnosed with non-critical aortic stenosis presented with pre-syncope, and echocardiography showed significant obstruction based on left ventricular outflow tract gradients, confirmed by cardiac magnetic resonance (CMR), concerning for a phenocopy of HCM. Septal myectomy was performed and pathology specimen revealed non-caseating granulomata consistent with cardiac sarcoidosis. She was started on oral corticosteroids and initial cardiac fluorodeoxyglucose positron emission tomography (FDG-PET) done after 1 month of treatment was negative. Repeat FDG-PET 15 months later, in the setting of haemodynamic decompensation, demonstrated diffuse FDG uptake in the myocardium without extra-cardiac involvement. Discussion Our case brings together two entities: isolated cardiac sarcoidosis and its presentation mimicking HOCM, which has been very rarely described in the literature. And it also shows the scenario of surgical pathology diagnosis of sarcoidosis that was not suspected by initial CMR or FDG-PET, despite adequate preparation, only appearing on repeat FDG-PET done 15 months later. Isolated cardiac sarcoidosis should remain a differential diagnosis for any non-ischaemic cardiomyopathy without a clear cause, despite imaging evidence of HCM.

Assessment Criteria and Clinical Implications of Extranodal Extension in Head and Neck Cancer

Tumor breaching the capsule of a lymph node is termed extranodal extension (ENE). It reflects aggressiveness of a tumor, creates anatomic challenges for disease clearance, and increases the risk of distant metastasis. Extranodal extension can be assessed on a pathology specimen, by radiology studies, and by clinical examination. Presence of ENE in a pathology specimen has long been considered a high-risk feature of disease progression and would ordinarily benefit from the addition of chemotherapy to adjuvant radiotherapy. Although the eighth edition of the Union for International Cancer Control/American Joint Committee on Cancer stage classification dichotomizes pathologic ENE according to its presence or absence, emerging evidence suggests that the extent of a pathologic ENE may provide additional value for risk stratification to guide adjuvant therapy. Recent data suggest that the prognostic importance of pathologic ENE is also applicable for HPV-associated head and neck squamous cell carcinoma. In addition, compelling data demonstrate that indisputable radiologic ENE is a powerful risk stratification tool to identify patients at high risk for treatment failure, especially distant metastasis, applicable for both HPV-positive and HPV-negative head and neck squamous cell carcinoma. However, the definition and taxonomy of radiologic ENE requires standardization. The goal of this review is to clarify the contemporary understanding of the prognostic implications of ENE in head and neck squamous cell carcinoma, present the nuances of what is presently known and unknown, and elucidate how to classify ENE pathologically and radiologically with an understanding of the strengths and weaknesses of each approach. Finally, with the development of several risk stratification methods, the relative role of ENE and other prognostic schema will be explored.

An Analysis of the Effect of the COVID-19 Pandemic on Case Volumes in an Academic Subspecialty-Based Anatomic Pathology Practice

The recent COVID pandemic has had a major effect on anatomic pathology specimen volumes across the country. The effect of this pandemic on a subspecialty academic practice is presented. We used a data-driven approach to monitor the changing workloads in a granular fashion and dynamically adjust the scheduling of faculty and histology staff accordingly to minimize the number of people present on-site. At the peak of the pandemic locally, the main hospital in our health system had 450 COVID-positive inpatients. The surgical pathology specimen volume dropped to 13% of the pre-pandemic levels, and this occurred about 2 weeks before the peak of the inpatient census; cytology specimens (the majority of which are outreach gynecological) dropped to approximately 5% of the pre-pandemic volume, 4 weeks before the peak inpatient census. All of the surgical subspecialty services showed a significant decrease in volume, with hematopathology being the least affected (dropped to 30% of the pre-pandemic level). The genitourinary surgical subspecialty service (predominantly prostate and bladder biopsies) was the most affected (dropped to 1% of the pre-pandemic level) but was fastest to return as clinical operations began to return to normal. The only specimen type which showed a significant increase in turnaround time during the pandemic was our gynecologic cytology specimens and that occurred as the specimen volume returned. This was due to stay-at-home directives for the cytotechnologists and the fact that some of them were retasked to participate in our SARS-CoV-2 testing.

Is Surgical Treatment an Option for Locally Advanced Cervical Cancer in the Presence of Central Residual Tumor after Chemoradiotherapy?

Objective To evaluate the outcomes of surgical treatment in patients with chemoradiotherapy (CRT)-resistant and locally advanced cervical cancer (LACC). Methods Patients with LACC who underwent surgery due to resistance to CRT between 2005 and 2015 were reviewed retrospectively. Disease-free survival (DFS) and overall survival (OS) related factors were analyzed. Results A total of 23 patients were included in the study and the median age was 51 years old. A total of 14 patients (60.8%) experienced recurrence; among these recurrences, 8 of them were local, 5 were distant, 1 was both distant and local. A total of 9 patients (39%) died. The Median DFS and OS durations were 15 and 32 months, respectively. A total of 17 patients (74%) had undergone simple hysterectomy, 4 (17%) radical hysterectomy, and 2 (9%) total pelvic exenteration. Postoperative grade 3 and 4 complications were seen in 12 patients (52%). Macroscopic tumor presence in the pathology specimen was associated with distant recurrence and positive surgical margins with local recurrence (Log-Rank test p = 0.029 and p = 0.048, respectively). The only factor associated with OS was surgical margin positivity (Log-Rank test p = 0.008). The type of surgery, grades 3 and 4 postoperative complications, brachytherapy, and tumor histology were not associated with recurrence. Conclusion In patients with LACC, hysterectomy is an option in the presence of a central residual tumor after CRT. However, the risk of grades 3 and 4 complications of performed surgery is high. The presence of macroscopic tumor in the pathology specimen and positive surgical margins are poor prognostic factors. The goal of the surgeon should be to achieve a negative surgical margin. It does not seem important if the surgery is simple or radical.

Plasma Cell-Free DNA Testing of Patients With EGFR Mutant Non–Small-Cell Lung Cancer: Droplet Digital PCR Versus Next-Generation Sequencing Compared With Tissue-Based Results

PURPOSE To compare the results of plasma cell-free DNA (cfDNA) droplet digital PCR (ddPCR) and next-generation sequencing (NGS) on detection of epidermal growth factor receptor ( EGFR) primary activating mutations and p.T790M with results of tissue analysis in patients with EGFR mutated non–small-cell lung cancer. METHODS All patients with EGFR mutated non–small cell lung cancer for which a pathology and a plasma specimen were available upon progression between November 2016 and July 2018 were selected. Concordance, Cohen’s κ, and intraclass correlation coefficients were calculated. RESULTS Plasma cfDNA and pathology specimens of 36 patients were analyzed. Agreement between ddPCR and NGS was 86% (κ = 0.63) for the primary activating mutation and 94% (κ = 0.89) for the p.T790M detection. Allele ratios were comparable, with an intraclass correlation coefficient of 0.992 and 0.997, respectively. Discrepancies of some degree were found in 15 patients (41.7%). In six patients (16.7%), no mutations were detected in cfDNA. In three patients (8.3%), p.T790M was detected in plasma but not in the pathology specimen, whereas in three other patients (8.3%), p.T790M was demonstrated in the pathology specimen but not in plasma. Concordance of cfDNA and pathology for the primary activating mutation was 69% for ddPCR and 83% for NGS. For the detection of p.T790M, this was 75% (κ = 0.49) for ddPCR as well as for NGS. CONCLUSION Mutual agreement is high between NGS and ddPCR in cfDNA on the level of a specific mutation, with comparable ratio results. Plasma testing of EGFR primary activating mutations and p.T790M shows high concordance with pathology results, for NGS as well as for ddPCR, depending on the extent of the panel used. In NGS, more genetic aberrations can be investigated at once.