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; 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.
Morphology of tumor and nontumor liver tissue in hepatocellular carcinoma patients treated with nivolumab
September 2021—Nivolumab is an immune checkpoint inhibitor approved for treating many types of cancer, including hepatocellular carcinoma (HCC). Liver injury is a known complication in patients treated with nivolumab for nonliver tumors. The morphologic changes to tumor and nontumor liver have not been well-characterized in HCC patients. Therefore, the authors conducted a study to characterize morphologic changes in tumor and nontumor liver tissue from patients who underwent partial or total hepatectomy following nivolumab therapy for HCC. They identified 20 patients who underwent partial hepatectomy or liver transplantation after receiving nivolumab for the disease. The authors obtained demographics, laboratory values, and imaging results from patients’ medical records. They evaluated all available slides from resection specimens for tumor necrosis, tumor-infiltrating lymphocytes, and features of liver injury. The study included 16 male and four female patients, who were a median age of 56 years. The underlying liver disease was hepatitis B virus in 10, hepatitis C virus in six, and unknown/other in four. Twelve patients were treated with nivolumab in the neoadjuvant setting, and eight were treated with nivolumab, usually with other therapies, before undergoing liver transplantation. On review of resection specimens, three patients, all of whom were from the neoadjuvant group, demonstrated marked treatment response attributable to nivolumab. Tumor-infiltrating lymphocytes were present in 17 of 20 cases. One case that showed treatment response in the neoadjuvant group demonstrated non-necrotizing granulomas and prominent bile duct intraepithelial lymphocytes in the nontumor liver. One case from the transplant group showed bile duct damage and prominent ductular reaction after long-term nivolumab therapy (32 doses). The authors’ findings indicate that nivolumab is effective in a subset of patients, including in the neoadjuvant setting. Granulomas and bile duct intraepithelial lymphocytes are rare findings in patients treated with nivolumab, but they may indicate potential response to therapy. Bile duct damage and ductular reaction may be manifestations of long-term nivolumab therapy. Future prospective and longitudinal studies with pretreatment tumor biopsies may help identify patients likely to respond to immune checkpoint inhibitor therapy and further characterize patterns of ICI-related liver injury.
Simoes CC, Thun SW, Fiel MI, et al. Morphology of tumor and nontumor tissue in liver resection specimens for hepatocellular carcinoma following nivolumab therapy. Mod Pathol. 2021;34:823–833.
Correspondence: Dr. Stephen C. Ward at stephen.ward@mountsinai.org
Diagnostic value of cell blocks in urine cytopathology: a pilot study
The utility of cell block preparation is well established in cytopathology. Yet even though 23.3 percent of College of American Pathologists-accredited laboratories use cell blocks with liquid-based preparations on urine cytology cases, few studies addressing their performance have been conducted. To determine the usefulness of cell blocks, the authors conducted a retrospective review of urine cytology specimens that underwent cell block preparation. They identified 27 urine cytology cases at their institution involving ThinPrep and cell block preparation between 2016 and 2020 and compiled clinical history and follow-up data on patients. Two pathologists and two cytotechnologists performed a blinded review of ThinPrep alone and ThinPrep with cell blocks. Diagnoses were rendered in accordance with The Paris System for Reporting Urine Cytology. Blood and acute inflammation were common in patients who underwent cell block preparation. The authors found that cell block preparation upgraded the diagnosis in 26 percent (seven of 27) of cases. The maximum utility of cell block preparation was seen in indeterminate cases in which 60 percent (six of 10) were upgraded, including 71 percent (five of seven) of atypical urothelial cells and 30 percent (one of three) of suspicious for high-grade urothelial carcinomas (HGUC). One (one of 12; eight percent) case diagnosed as negative for HGUC with ThinPrep was diagnosed as low-grade urothelial neoplasia via cell block. The authors concluded that their results demonstrate that adjunct use of cell block preparation aids in a definitive diagnosis in the atypical urothelial cell category and may be helpful in cases with cell clusters or tissue fragments and cases suspicious for HGUC. Additional correlation studies are warranted to further understand the utility of cell blocks in urine cytology.
Wilson BL, Russel D, Evans SK, et al. Cell blocks in urine cytopathology: Do they add value to the diagnosis? A pilot study. J Am Soc Cytopathol. 2021;10(1):47–55.
Correspondence: Dr. Tanupriya Agrawal at tanupriya_agrawal@urmc.rochester.edu
Screening for AIN in women with a history of CIN or cancer
High-risk human papillomavirus has been identified in the pathogenesis of anal cancer. The authors conducted a study to assess the prevalence of abnormal anal cytology and human papillomavirus (HPV) in women 40 years and older who had a history of high-grade cervical squamous intraepithelial lesion (SIL) or cancer and to estimate the prevalence of anal intraepithelial neoplasia (AIN) using cytology as the primary screening modality. Anal cytology with HPV-DNA testing was performed. All patients with abnormal anal cytology were referred for high-resolution anoscopy (HRA), and abnormal lesions were biopsied and treated if confirmed pathologically. Abnormal anal cytology correlated with HPV status, HRA findings, and clinical and demographic characteristics. Of 317 women who completed the study, 96 (30.3 percent) had abnormal anal cytology (high-grade SIL, 12.5 percent; low-grade SIL, 19.8 percent; atypical squamous cells, cannot exclude high-grade SIL, 6.3 percent; atypical squamous cells of undetermined significance, 61.5 percent) and 101 (31.9 percent) were HPV-DNA positive. A significant association between abnormal cytology results and presence of high-risk HPV was found. Of the 96 patients with abnormal cytology, 30 (31.3 percent) had biopsy-proven AIN on HRA, representing 9.5 percent of the total patient cohort. Ten (33.3 percent) patients in the latter group had low-grade AIN and 20 (66.7 percent) had high-grade AIN. Older age and smoking were significant risk factors for abnormal anal cytology. The authors concluded that women 40 years and older who have a history of high-grade cervical SIL or cancer have a high rate of AIN. Therefore, screening for anal cancer should be considered in this patient population. The optimal screening approach should be addressed in future studies.
Wohlmuth C, Ghorab Z, Shier M, et al. Cytology-based screening for anal intraepithelial neoplasia in women with a history of cervical intraepithelial neoplasia or cancer. Cancer Cytopathol. 2021;129(2):140–147.