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; Rachel Stewart, DO, PhD, assistant professor, Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington; Nicole Panarelli, MD, associate professor of pathology, Albert Einstein College of Medicine, Montefiore Medical Center; and Shaomin Hu, MD, PhD, gastrointestinal/liver pathology fellow, University of Chicago.
Validation of 2016 ITBCC recommendations for tumor budding in stages I–IV colorectal cancer
September 2019—Tumor budding is a robust prognostic parameter in colorectal cancer and can be used as an additional factor to guide patient management. Although backed by large bodies of data, a standardized scoring method is essential for integrating tumor budding into reporting protocols. Such a scoring system was proposed at the 2016 International Tumor Budding Consensus Conference (ITBCC). The authors conducted a study to validate the ITBCC method of tumor budding assessment on a well-characterized colorectal cancer cohort of 379 patients with resected stages I–IV colorectal cancer. Tumor budding was scored by two pathologists according to the ITBCC recommendations for hematoxylin-and-eosin–stained slides, using BD1 (low grade), BD2 (intermediate grade), and BD3 (high grade). Analysis was performed using a three-tier approach, two-tier approach (BD1 plus BD2 versus BD3), and budding as a continuous variable. High-grade tumor budding was associated with adverse clinicopathological features, including higher pT and higher pN stages, higher tumor-node-metastasis stage (all P < .001), and poorer overall survival on univariate analysis (P = .0251 for BD1/BD2/BD3; P = .0106 for BD1 plus BD2 versus BD3; and P = .0195 for continuous scores; hazard ratio, 1.023 [95 percent confidence interval, 1.004 –1.043 per bud]). In stage II cancers, BD3 was associated with poorer disease-free survival (P < .01). Tumor budding assessed using the method proposed by the ITBCC is applicable to colorectal cancer resection specimens and can be used for widespread reporting.
Dawson H, Galuppini F, Träger P, et al. Validation of the International Tumor Budding Consensus Conference (ITBCC 2016) recommendations on tumor budding in stage I-IV colorectal cancer. Hum Pathol. 2019;85:145–151.
Correspondence: Dr. Heather Dawson at heather.dawson@pathology.unibe.ch
Immune-related adverse events in the GI tract: utility of upper GI biopsies
Immune checkpoint inhibitors improve survival across a range of malignancies but are also associated with a spectrum of gastrointestinal immune-related adverse events (GI-irAE). The authors conducted a study to explore the diagnostic value of gastric and duodenal biopsies and address considerations in the differential diagnosis. They identified 39 patients who were treated with immune checkpoint inhibitors and had a subsequent upper GI biopsy. They recorded clinical data and endoscopic findings and reviewed patients’ gastric, duodenal, and colonic biopsies. Twenty-one (54 percent) patients were treated with an anti-PD-1/anti-PD-L1 antibody alone and 17 (44 percent) with a combination of anti-CTLA-4 and anti-PD-1 antibodies. Thirty-two (82 percent) patients presented with diarrhea. Gastric alterations included peri-gland inflammation and granulomas, and the duodenal changes included villous blunting, intraepithelial lymphocytosis, granulomas, and neutrophilic activity. The authors recognized four patterns of colonic injury—acute self-limiting colitis, lymphocytic colitis, collagenous colitis, and apoptosis only. Twenty-nine (74 percent) and 10 (26 percent) patients were diagnosed clinically as positive and negative for GI-irAE, respectively. Gastric peri-gland inflammation (P = .004) and increased colonic lamina propria mononuclear cells (P = .04) correlated with the clinical diagnosis of GI-irAE. Histologic alterations associated with immune checkpoint inhibitor injury were more often identified in upper GI (71 percent) than colonic (65 percent) biopsies. The authors concluded that the morphologic spectrum of immune checkpoint inhibitor-related GI disease is broad and mimics a range of infectious and inflammatory diseases. Gastric peri-gland inflammation represents one of the more characteristic histologic features of GI-irAE. The study underscores the importance of a comprehensive review of upper and lower GI biopsies for diagnosing immune-related adverse events.
Zhang ML, Neyaz A, Patil D, et al. Immune-related adverse events in the gastrointestinal tract: diagnostic utility of upper gastrointestinal biopsies [published online ahead of print July 30, 2019]. Histopathol. doi:10.1111/his.13963.
Correspondence: Dr. Vikram Deshpande at vikramdirdeshpande@gmail.com
Plasmacytoid/diffuse urothelial carcinoma: a single-institution study
Accurate diagnosis of plasmacytoid urothelial carcinoma is important given its poor prognosis and frequent presentation at a higher stage. The authors conducted a study to assess the clinicopathologic features, molecular aberrations, and follow-up data in a series of plasmacytoid urothelial carcinoma (PUC) cases from a single tertiary cancer center. They identified 72 urinary bladder, ureteral, and renal pelvic specimens with urothelial carcinoma with plasmacytoid differentiation. IHC stains were performed on 48 cases. Among the urinary bladder origin markers, GATA3 was most sensitive (96 percent). The breast carcinoma markers (estrogen receptor and mammaglobin) were usually negative, but progesterone receptor stained one (four percent) case. The neuroendocrine markers CD56 and TTF-1 were each positive in one (four percent for each) case. The gastrointestinal adenocarcinoma marker CDX2 was positive in four (15 percent) cases, but nuclear β-catenin was negative in all cases. CD138 was positive in 83 percent of cases and e-cadherin expression was lost in 57 percent. FISH using the UroVysion bladder cancer kit and FGFR3 mutation analysis using polymerase chain reaction were performed on 15 cases. Deletion of chromosome 9p21 was common (60 percent), and FGFR3 mutations were detected in 60 percent of cases. (Five cases had both deletion 9p21 and FGFR3 mutations.) Cases were divided into three morphologic groups: classic (29 percent), desmoplastic (35 percent), and pleomorphic (36 percent). The three morphologic subtypes had distinct survival outcomes (P = .083), with the median survival for all patients being 18 months versus 10 months for the desmoplastic group.
Perrino CM, Eble J, Kao CS, et al. Plasmacytoid/diffuse urothelial carcinoma: a single-institution immunohistochemical and molecular study of 69 patients. Hum Pathol. 2019;90:27–36.
Correspondence: Dr. Carmen Perrino at cperrino@lifespan.org
Risk of malignancy in the categories of the PSC system for reporting pancreaticobiliary cytology
Management of pancreatic lesions depends on the risk of malignancy, which is primarily determined from cytologic and radiologic evaluation findings. The Papanicolaou Society of Cytopathology (PSC) published a classification system for reporting pancreaticobiliary cytology. However, the “neoplastic: other” category can be further stratified by high-grade atypia (HGA). Studies on the risk of malignancy, using the PSC system, have been limited. Recognizing this, the authors of this study prospectively classified all patients who had undergone endoscopic ultrasound-guided fine-needle aspiration (FNA) for a pancreatic lesion at Massachusetts General Hospital from January 2016 to December 2016. They reviewed the clinical, radiographic, and endoscopic findings, cytologic and histologic diagnoses, and follow-up data from 334 FNA biopsies from 322 patients. The neoplastic: other category was subclassified as low-grade atypia or HGA. The absolute risk of malignancy was determined by the histologic outcome or follow-up of six months or more. The absolute risk of malignancy was 7.7 percent for the nondiagnostic category; one percent for negative, 28 percent for atypical, zero for neoplastic: benign, 30.3 percent for neoplastic: other, 90 percent for neoplastic: other with HGA, 100 percent for suspicious, and 100 percent for positive. When the neoplastic: other with HGA, suspicious, and positive cytologic diagnoses were considered positive, the sensitivity, specificity, positive predictive value, and negative predictive value for pancreatic FNA biopsy was 92.2, 98.8, 98.3, and 94.3 percent, respectively. Categories of the PSC system carry an implied absolute risk of malignancy, increasing from the negative to positive categories. The presence of HGA identifies lesions at greatest risk of malignancy in the neoplastic: other category, and its inclusion with suspicious and positive as positive diagnoses optimizes the ability to identify high-risk lesions that warrant surgical excision.