Anatomic pathology selected abstracts

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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.

Association of PD-L1 expression by IHC and gene microarray with molecular subtypes of ovarian tumors

September 2020—Identifying patients who respond to immune checkpoint blockade is a significant challenge in oncology. PD-L1 expression by immunohistochemistry is the diagnostic gold standard for patient selection, but it does not capture all patients who may respond to immune checkpoint blockade (ICB). Recent gene-expression studies of high-grade serous ovarian carcinoma have defined an immunoreactive molecular subtype that shows a measurable favorable difference in patient survival compared with nonimmunoreactive subtypes, but no studies have demonstrated its impact on predicting response to ICB. As a step toward establishing the predictive value of gene-expression classifiers in ICB, the authors assessed the relationship between PD-L1 IHC and molecular subtypes of ovarian epithelial cancer. They analyzed 93 tissue specimens from patients with stages III and IV disease and compared PD-L1 IHC with gene expression by Agilent microarrays using The Cancer Genome Atlas-defined subtypes. The analysis showed that ovarian tumors with elevated IHC PD-L1 expression are more strongly associated with the immunoreactive subtype as compared with other molecular subtypes, reaching statistical significance against differentiated (Dunn’s test, 33.39, p = .0003) and mesenchymal (39.63, p < .0001) subtypes. Comparing PD-L1 scoring with combined positive score (CPS) versus tumor proportion score (TPS) showed similar trends but with stronger correlation strength when using CPS (Kruskal-Wallis, H = 27.52, p < .0001) versus TPS (H = 25.04, p < .0001). Interestingly, while PD-L1 gene expression by microarray was significantly increased in the immunoreactive subtype (H = 20.25, p = .0002), it showed a positive but relatively poor correlation to IHC. Overall, the results demonstrate potential value in using the molecular classifier to select patients for ICB pending further studies that assess its ability to predict treatment outcomes. In the future, integration of cellular, protein, and genomic biomarkers related to the tumor and tumor microenvironment may improve the ability to predict treatment response.

Chin CD, Fares CM, Campos M, et al. Association of PD-L1 expression by immunohistochemistry and gene microarray with molecular subtypes of ovarian tumors [published online ahead of print May 13, 2020]. Mod Pathol. doi:10.1038/s41379-020-0567-3.

Correspondence: Dr. Gottfried Konecny at gkonecny@mednet.ucla.edu or Dr. Jianyu Rao at jrao@mednet.ucla.edu

Clinical implications of amyloidosis in surgically resected atrial appendages

Histomorphologic parameters of atrial appendages removed during the Cox-Maze procedure have been shown to correlate with recurrence of atrial fibrillation. While amyloid deposition has been noted within atrial appendages, the incidence and significance are not completely understood. More accurate amyloid typing methodologies and targeted pharmacotherapeutics have been developed, prompting pathologists to provide more detailed information about the type of amyloid identified in such samples. The authors conducted a study to characterize the morphologic characteristics of atrial amyloidosis, as well as its incidence and clinical significance. They queried tissue registry archives at the Mayo Clinic for atrial appendages removed during cardiac surgeries between 2010 and 2014 and abstracted from the medical record patient demographics and salient clinical findings. Typing of the amyloid protein was performed on a subset of cases by laser-capture microdissection with mass spectrometry-based proteomic analysis. The study included 383 atrial appendages from 345 consecutive patients (mean age, 69 years; range, 26–92 years). Amyloidosis was present in 46 percent of patients. A linear relationship was observed between age and presence of atrial amyloidosis. Women were more likely to have atrial amyloidosis. Two distinct morphologies of amyloidosis were observed: filamentous and nonfilamentous. They correlated perfectly with amyloid type (filamentous = AANF-type amyloid; nonfilamentous = ATTR-type amyloid). Filamentous deposits were observed in 91 percent of those with amyloidosis. The disorder was more likely to be found in the left atrial appendage than the right. Patients with atrial amyloidosis, irrespective of type, were more likely to have had stroke or transient ischemic attack and more likely to have atrial arrhythmia preoperatively. In addition, those with atrial amyloidosis were more likely to have arrhythmia recur postoperatively than those who did not have atrial amyloidosis. The authors concluded that understanding the morphologic characteristics of AANF-type amyloid will allow for identification by light microscopy and obviate the need to use expensive ancillary typing techniques. A finding of nonfilamentous amyloidosis should still prompt confirmation of amyloid type so that targeted therapy may be employed.

Fayyaz AU, Bois MC, Dasari S, et al. Amyloidosis in surgically resected atrial appendages: a study of 345 consecutive cases with clinical implications. Mod Pathol. 2020;33(5):764–774.