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, associate pathologist, Brigham and Women’s Hospital, Boston; and Amarpreet Bhalla, MD, assistant professor of pathology, Albert Einstein College of Medicine, Montefiore Medical Center.
Prognostic significance of tumor-associated stroma in nasopharyngeal carcinoma
September 2024—Research has shown assessment of tumor-associated stroma to be of reliable prognostic value. The authors conducted a study in which they evaluated the prognostic value of tumor-stroma ratio in a large multicenter cohort of nasopharyngeal carcinoma. They used the conventional H&E-stained slides of 115 cases of nasopharyngeal carcinoma to assess tumor-stroma ratio as described in recent guidelines. The amount of tumor-associated stroma was assessed as a percentage and then tumors were classified as stroma high (more than 50 percent) or stroma low (50 percent or less). Kaplan-Meier curves, a χ2 test, and Cox regression univariable and multivariable analyses were conducted. Forty-eight (41.7 percent) tumors were stroma high and 67 (58.3 percent) were stroma low. In the Cox regression multivariable analysis, the tumors categorized as stroma high were associated with worse overall survival, with a hazard ratio of 2.30 (95 percent confidence interval [CI], 1.27–4.15; P=.006), and poor disease-specific survival (hazard ratio, 1.87; 95 percent CI, 1.07–3.28; P=.029). The authors concluded that the assessment of tumor-stroma ratio in nasopharyngeal carcinoma is simple and cost-effective and has significant prognostic value. Tumor-stroma ratio can aid in risk stratification and clinical decision-making in nasopharyngeal carcinoma.
Almangush A, Ruuskanen M, Hagström J, et al. Prognostic significance of tumor-associated stroma in nasopharyngeal carcinoma: A multicenter study. Am J Surg Pathol. 2024;48(1):54–58.
Correspondence: Dr. Alhadi Almangush at alhadi.almangush@helsinki.fi
Impact of tissue sampling on detection of venous invasion in colorectal cancer
Venous invasion is a powerful yet under-reported prognostic factor in colorectal cancer. Efforts to improve detection have largely focused on histological assessment, with less attention given to tissue-sampling strategies. The authors conducted a study to prospectively determine the number of tumor blocks required to optimize detection of venous invasion in colorectal cancer resections. They also investigated the relationship between linear spiculation (LS) and extramural venous invasion (EMVI). A standardized tissue-sampling protocol was developed and applied prospectively to 217 CRC resections (AJCC cancer staging manual eighth edition: stage I [n=32], stage II [n=84], stage III [n=87], and stage IV [n=14]). Forty-six patients received post-neoadjuvant therapy. Elastin stains were performed on all tumor blocks. Venous invasion was identified in 55 percent of cases (EMVI, 37 percent; intramural venous invasion alone, 18 percent). The sensitivity for detecting venous invasion increased with increasing numbers of tumor blocks submitted (one block, 35 percent; three blocks, 66 percent; five blocks, 84 percent; six blocks, 95 percent; and seven blocks, 97 percent). Similar findings were observed for EMVI (one block, 35 percent; three blocks, 73 percent; five blocks, 89 percent; six blocks, 96 percent; and seven blocks, 96 percent). Linear spiculation was identified macroscopically in 22 percent of specimens. In cases where no neoadjuvant therapy had been given, EMVI was significantly associated with LS (71 percent in LS+ cases versus 29 percent in LS - cases; P<.001). In addition, tumor blocks targeting LS were associated with a fivefold higher rate of EMVI compared with blocks that did not target LS (P<.001). The findings demonstrate the impact of tissue sampling and quality of gross examination on detecting venous invasion and may inform sampling practices in future colorectal cancer protocols.
Duan K, Chow B, Tsui W, et al. Impact of tissue sampling on detection of venous invasion in colorectal cancer: a prospective analysis. Histopathology. 2023;83(6):891–902.
Correspondence: Dr. James Conner at james.conner@sinaihealth.ca
Comparison of IHC, NGS, and FISH for detecting loss of MTAP in pleural mesothelioma
The 9p21 deletions involving MTAP and CDKN2A genes are detected in diffuse pleural mesotheliomas but not in benign mesothelial proliferations. Loss of MTAP expression by IHC is well accepted as a surrogate marker for 9p21 deletion to support a diagnosis of diffuse pleural mesothelioma (DPM). Accurate antibody interpretation can be critical in diagnosing DPM, but variations in antibody performance may impact interpretation. The authors conducted a study in which they compared the performance of the MTAP monoclonal antibodies (mAbs) EPR6893 and 1813 and MTAP expression by IHC with 9p21 copy number status in DPM. Cytoplasmic expression of MTAP IHC with mAbs EPR6893 (ab126770, Abcam) and 1813 (NBP2-75730, Novus Biologicals) was evaluated in 56 DPM (47 epithelioid, seven biphasic, and two sarcomatoid) profiled by targeted next-generation sequencing. The 9p21 copy number status was assessed by fraction and allele-specific copy number estimates from tumor sequencing (FACETS) analysis and by CDKN2A FISH in discrepant cases when material was available. MTAP mAb 1813 showed stronger immunoreactivity, more specific staining, and no equivocal interpretations compared with mAb EPR6893, which showed equivocal staining in 19 (34 percent) cases due to weak or heterogenous immunoreactivity, lack of definitive internal positive control, or nonspecific background staining. MTAP expression with mAb 1813 showed near perfect agreement with 9p21 copy number by combined FACETS/FISH calls (κ = 0.85; 95 percent confidence interval, 0.71–0.99; P< .001). MTAP IHC with mAb 1813 was 96 percent sensitive, 86 percent specific, and 93 percent accurate for 9p21 homozygous deletion. The findings of this study suggest that interpretation of MTAP IHC is improved with mAb 1813 because mAb EPR6893 was often limited by equivocal interpretations. The authors concluded that their findings suggest that MTAP IHC and molecular assays are complementary in detecting 9p21 homozygous deletion. MTAP IHC may be particularly useful for low tumor purity samples and in low-resource settings.
Febres-Aldana CA, Chang JC, Jungbluth AA, et al. Comparison of immunohistochemistry, next-generation sequencing and fluorescence in situ hybridization for detection of MTAP loss in pleural mesothelioma. Mod Pathol. 2024;37(3). doi:10.1016/j.modpat.2023.100420
Correspondence: Dr. Jennifer L. Sauter at sauterj@mskcc.org
Inflammatory patterns in follow-up biopsies in gastrointestinal immune checkpoint inhibitor toxicity
Colitis is a common manifestation of immune checkpoint inhibitor toxicity and can present with varied histologic patterns of inflammation, some of which have been associated with specific immune checkpoint inhibitor (ICI) drug types. Although the histologic features of ICI colitis seen at the time of diagnosis have been described previously, few reports have followed these patients over time. The authors evaluated initial and follow-up biopsies in 30 patients with ICI colitis and found that 11 (37 percent) patients showed a different inflammatory pattern on follow-up biopsy than on initial biopsy. Patients with differing inflammatory patterns were more likely to have restarted ICI therapy before their follow-up biopsy (64 percent) compared with those whose inflammatory pattern did not change (11 percent; P<.01). The majority of these patients had frequently changed ICI drug types (86 percent). Thirty-six percent of the 11 patients with differing patterns of injury demonstrated an inflammatory bowel disease (IBD)-like pattern, raising the possibility of de novo IBD. However, the symptoms of all patients with an IBD-like pattern resolved without steroids or other immunosuppressive medications after discontinuing ICI therapy, consistent with a diagnosis of ICI toxicity. The authors’ findings suggest that follow-up biopsies in patients with ICI colitis may show a different histology and that this does not necessarily warrant changing the histologic diagnosis.
Tomm NK, Szczepanski JM, Fang JM, et al. Follow-up biopsies in gastrointestinal immune checkpoint inhibitor toxicity may show markedly different inflammatory patterns than initial injury. Hum Pathol. 2024;148:60–65.
Correspondence: Dr. Nicole K. Tomm at tommn@med.umich.edu