CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
Editors: Rouzan Karabakhtsian, MD, PhD, professor of pathology and director of the Women’s Health Pathology Fellowship, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY; Nicole Panarelli, MD, associate professor of pathology, Albert Einstein College of Medicine, Montefiore Medical Center; Shaomin Hu, MD, PhD, gastrointestinal/liver pathology fellow, University of Chicago; and S. Emily Bachert, MD, pathology resident, Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington.
Evaluation of tumor quantitation as an aid in predicting biochemical recurrence in organ-confined prostate cancer
December 2019—In the eighth edition of the AJCC Cancer Staging Manual, all organ-confined disease is assigned pathologic stage T2, without subclassification. The authors investigated whether total tumor volume (TTV) or maximum tumor diameter (MTD) of the index lesion, or both, enhance the ability to predict biochemical recurrence in pT2 patients. They identified 1,657 patients using digital tumor maps and quantification of TTV/MTD who had pT2 disease on radical prostatectomy. Multivariable Cox regression models were used to assess whether TTV or MTD, or both, are independent predictors of biochemical recurrence when adjusting for a base model incorporating age, preoperative prostate-specific antigen, radical prostatectomy grade group, and surgical margin status. If either tumor quantification added significantly to the base model, the authors calculated and reported the c-index. Ninety-five patients experienced biochemical recurrence after radical prostatectomy. The median follow-up for patients without biochemical recurrence was 5.7 years. The c-index was 0.737 for the base model. Although there was some evidence of an association between TTV and biochemical recurrence (P = .088), this did not meet conventional levels of statistical significance and only provided a limited increase in discrimination (0.743; c-index improvement, 0.006). MTD was not associated with biochemical recurrence (P > .9). In analyses excluding patients with grade group one disease on biopsy, who would be less likely to undergo radical prostatectomy in contemporary practice (622 patients; 59 with biochemical recurrence), neither TTV nor MTD added significantly to the base model (P = .4 and P = .8, respectively). Without evidence that tumor quantitation, in the form of TTV or MTD of the index lesion, is useful for predicting biochemical recurrence in pT2 prostate cancer, the authors do not recommend routinely reporting it.
Ito Y, Vertosick EA, Sjoberg DD, et al. In organ-confined prostate cancer, tumor quantitation not found to aid in prediction of biochemical recurrence. Am J Surg Pathol. 2019;43(8):1061–1065.
Correspondence: Dr. Samson W. Fine at fines@mskcc.org
Cytomegalovirus reactivation in IBD: an uncommon occurrence related to corticosteroid dependence
Cytomegalovirus promotes mucosal injury in patients with inflammatory bowel disease, historically affecting 10 to 25 percent of ulcerative colitis patients with refractory disease. Viral reactivation is likely related to long-term corticosteroid therapy, which is no longer central to the maintenance of patients with inflammatory bowel disease. The authors hypothesized that viral detection rates have decreased in the modern era, reflecting widespread use of immunomodulatory agents to control inflammation. They performed a study to evaluate the relationships between medical regimens and cytomegalovirus detection rates among patients with inflammatory bowel disease. The authors searched their database for all patients with established inflammatory bowel disease and severe flares diagnosed from 2002 to 2017. Patients maintained with corticosteroid therapy were considered to be corticosteroid dependent, and those treated with other agents were classified as corticosteroid independent provided they had not received corticosteroids within six months of colonoscopy. Biopsy samples were reviewed for viral inclusions and subjected to cytomegalovirus immunohistochemistry, and rates of viral detection were compared between groups. There were 135 corticosteroid-dependent patients, and most had ulcerative colitis flares between 2002 and 2009. Patients with ulcerative colitis and Crohn disease were equally represented in the corticosteroid-independent group (n = 133), and most were evaluated for disease flares during the 2010–2017 interval. Cytomegalovirus was detected in 13 cases, nine of which were diagnosed from 2002 to 2009, and all involved corticosteroid-dependent patients (P = < .001). The authors concluded that rates of cytomegalovirus-related enterocolitis are declining among inflammatory bowel disease patients, reflecting a shift away from corticosteroid-based maintenance therapy in lieu of more effective agents that do not promote viral reactivation.
Hissong E, Chen Z, Yantiss RK. Cytomegalovirus reactivation in inflammatory bowel disease: an uncommon occurrence related to corticosteroid dependence. Mod Pathol. 2019;32(8):1210–1216.
Correspondence: Dr. Erika Hissong at emh9016@med.cornell.edu
DNA methylation profiling to distinguish pulmonary enteric adenocarcinoma from metastatic colorectal cancer
Pulmonary enteric adenocarcinoma is a rare nonsmall cell lung cancer subtype. It is poorly characterized and cannot be distinguished from metastatic colorectal or upper gastrointestinal adenocarcinomas using routine pathological methods. Because DNA methylation patterns are known to be highly tissue specific, the authors aimed to develop a methylation-based algorithm to differentiate these entities. To this end, they developed a reference cohort from genome-wide methylation profiles of 600 primary pulmonary, colorectal, and upper gastrointestinal adenocarcinomas obtained from The Cancer Genome Atlas and the Gene Expression Omnibus database to train a machine-learning algorithm. The resulting classifier correctly classified all samples from a validation cohort of 680 primary pulmonary, colorectal, and upper gastrointestinal adenocarcinomas, demonstrating the ability of the algorithm to reliably distinguish these three entities. The authors then used the algorithm to analyze methylation data from 15 pulmonary enteric adenocarcinomas, four pulmonary metastases, and four primary colorectal adenocarcinomas. The 15 pulmonary enteric adenocarcinomas were reliably classified as primary pulmonary tumors, and the four metastases and four primary colorectal cancer samples were identified as colorectal adenocarcinomas. In a t-distributed stochastic neighbor-embedding analysis, the pulmonary enteric adenocarcinoma samples did not form a separate methylation subclass but rather diffusely intermixed with other pulmonary cancers. Additional characterization of the pulmonary enteric adenocarcinoma series using FISH, next-generation sequencing, and copy number analysis revealed KRAS mutations in nine of 15 (60 percent) samples and a high number of structural chromosomal changes. Except for an unusually high rate (67 percent) of chromosome 20 gain, the molecular data were mostly reminiscent of standard pulmonary adenocarcinomas. The authors provided sound evidence of the pulmonary origin of pulmonary enteric adenocarcinomas and a publicly available machine-learning–based algorithm to reliably distinguish these tumors from metastatic colorectal cancer.