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; Shaomin Hu, MD, PhD, staff pathologist, Cleveland Clinic; S. Emily Bachert, MD, breast pathology fellow, Brigham and Women’s Hospital, Boston; and Amarpreet Bhalla, MD, assistant professor of pathology, Albert Einstein College of Medicine, Montefiore Medical Center.
Insights into fatal COVID-19 pneumonia using NGS and immunohistochemistry
January 2021—The authors conducted a review of postmortem pulmonary histopathologic findings of COVID-19 pneumonia in patients who had a spectrum of disease course that ranged from rapid demise to prolonged hospitalization. They analyzed histopathologic findings in postmortem lung tissue from eight patients who died from COVID-19 pneumonia. Immunohistochemistry and next-generation sequencing (NGS) were used to detect the virus. Diffuse alveolar damage (DAD) was seen in all cases with a spectrum of acute phase or organizing phase, or both. IHC with monoclonal antibodies against SARS-CoV-2 viral nucleoprotein and spike protein detected virus in areas of acute but not organizing DAD. Intracellular viral antigen and RNA expression were seen predominantly in patients whose illness lasted less than 10 days. Major vascular findings included thrombi in medium- and large-caliber vessels, platelet microthrombi detected by CD61 IHC, and fibrin microthrombi. The detection of SARS-CoV-2 viral RNA by NGS early in the disease course and finding of viral antigen by IHC exclusively in the acute phase of DAD suggests that the virus may play a major role in initiating the acute lung injury in DAD. However, after the first 10 days of illness or when DAD progresses to the organizing phase, the virus may have been cleared from the lungs through the patient’s immune response. These findings suggest the possibility of a major change during the disease course of COVID-19 pneumonia that may have therapeutic implications. Frequent thrombi and microthrombi may present potential targets for therapeutic intervention.
Sauter JL, Baine MK, Butnor KJ, et al. Insights into pathogenesis of fatal COVID-19 pneumonia from histopathology with immunohistochemical and viral RNA studies. Histopathology. 2020;77:915–925. doi:10.1111/his.14201
Correspondence: Dr. W. D. Travis at travisw@mskcc.org
Urothelial proliferation of unknown malignant potential involving the bladder
Urothelial proliferation of unknown malignant potential (UPUMP) is a 2016 World Health Organization classifier that encompasses prior categories of flat and papillary urothelial hyperplasia. It also occurs in de novo and prior bladder neoplasia. The authors conducted a study on a cohort of 68 patients to identify UPUMP features associated with subsequent neoplastic development. The cohort included 26 patients with de novo and 42 patients with prior bladder neoplasia. Three urologic pathologists reviewed patient slides. Patients with de novo UPUMP were identified through clinical findings (26 of 26, 100 percent), whereas surveillance cystoscopy primarily detected UPUMP in patients with prior neoplasia (29 of 42, 69 percent). The histopathologic criteria evaluated included urothelial hyperplasia, urothelial cytology, vascular ingrowth, denudation, inflammation, edema, and fibrosis. The mean clinical follow-up was 68.9 months for patients with de novo neoplasia and 69.5 months for patients with prior neoplasia. Subsequent neoplasia developed in four of 26 (15.4 percent) patients with de novo UPUMP and was associated with cystoscopic papillary appearance (P = .02) or microscopic thin papillary ingrowths or papillations (P = .02; median time to progression, 4.1 months). Of 42 patients with prior neoplasia, 17 (40.5 percent) had subsequent neoplasia significantly associated with an absence of prominent lamina propria edema (P <.001; median time to progression, 11 months). A higher rate of progression to high-grade disease was present in patients with a prior neoplasia versus those with de novo disease (58.9 percent versus 25 percent). The authors concluded that urothelial proliferation of unknown malignant potential showed a subsequent risk of neoplastic development of 17 percent in patients with de novo disease and 40 percent in patients with prior neoplasia. The greatest risk of progression was associated with early papillary formation.
Lowenthal BM, Sahoo D, Amin MB, Hansel DE. Urothelial proliferation of unknown malignant potential involving the bladder: Histopathologic features and risk of progression in de novo cases and cases with prior neoplasia. Arch Pathol Lab Med. 2020;144(7):853–862.
Correspondence: Dr. Donna E. Hansel at hansel@ohsu.edu
TIL status as a predictor of prognosis in mucinous colorectal adenocarcinoma
Mucinous colorectal adenocarcinoma is defined by extracellular mucin comprising more than 50 percent of the tumor area, while tumors with less than 50 percent mucin are designated as having a mucinous component. However, these definitions are largely arbitrary, and comparisons of clinico-molecular features and outcomes by proportion of mucinous component are limited. The authors conducted a study in which they examined a cohort of 1,643 patients with stage II/III cancer for tumor mucinous component, DNA mismatch repair (MMR) status, BRAF mutation, and tumor-infiltrating lymphocytes (TILs). They found that tumors with 50 percent or less mucinous component exhibited characteristics that were similar to those of mucinous tumors, including association with female gender, proximal location, high grade, TIL high, defective MMR (dMMR), and BRAF mutation. Proportion of mucinous component did not stratify disease-free survival. In univariate analysis, dMMR status, but not histological grade, stratified survival for mucinous and mucinous component tumors. However, dMMR status was not an independent predictor in multivariate analysis. The prognostic value of BRAF mutation depended on mucinous differentiation and MMR status, and poor prognosis was limited to nonmucinous pMMR tumors (hazard ratio [HR], 2.61; 95 percent confidence interval [CI], 1.69–4.03; p < .001). TIL status was a strong independent predictor of disease-free survival in mucinous and mucinous component tumors (HR, 0.40; 95 percent CI, 0.23–0.67; p < .001) and a superior predictor of prognosis compared with histological grade, MMR, and BRAF mutation. Mucinous component and mucinous stage II/III colorectal carcinomas exhibit clinico-molecular resemblances, with histological grade and BRAF mutation lacking prognostic value. Prognosis for these tumors was strongly associated with TIL status, with the most favorable outcomes in TIL-high dMMR tumors. TIL-low tumors had poor outcomes irrespective of MMR status.
Williams DS, Mouradov D, Newman MR, et al. Tumour infiltrating lymphocyte status is superior to histological grade, DNA mismatch repair and BRAF mutation for prognosis of colorectal adenocarcinomas with mucinous differentiation. Mod Pathol. 2020;33(7):1420–1432.
Correspondence: Dr. Oliver M. Sieber at sieber.o@wehi.edu.au