Anatomic pathology selected abstracts

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Eldersveld JM, Yi ES, Kunze KL, et al. Usual interstitial pneumonia in contemporary surgical pathology practice: Impact of international consensus guidelines for idiopathic pulmonary fibrosis on pathologists. Arch Pathol Lab Med. 2021;145(6):717–727.

Correspondence: Dr. Brandon T. Larsen at larsen.brandon@mayo.edu

Predicting patterns of residual disease following neoadjuvant chemotherapy for breast cancer

The pattern of residual disease in the breast varies among breast cancer patients treated with neoadjuvant chemotherapy who do not experience a pathologic complete response. Pretreatment clinicopathologic features that predict the pattern of residual tumor are not well established. To investigate this issue, the authors performed a detailed review of histologic sections of the post-treatment surgical specimens for 665 patients with stages I through III breast cancer treated with neoadjuvant chemotherapy (NAC) followed by surgery from 2004 to 2014 and for whom slides of the post-NAC surgical specimen were available for review. The review included 242 (36.4 percent) patients with hormone receptor (HR)+/HER2- cancers, 216 (32.5 percent) with HER2+ tumors, and 207 (31.1 percent) with triple-negative breast cancer (TNBC). Slide review was blinded to pretreatment clinicopathologic features. Pathologic complete response was achieved in 7.9 percent, 37 percent, and 37.7 percent of HR+/HER2-cancers, HER2+ cancers, and TNBC, respectively (p<0.001). Among 389 patients with residual invasive cancer in whom the pattern of residual disease could be assessed, 287 (73.8 percent) had a scattered pattern and 102 (26.2 percent) had a circumscribed pattern. In univariate and multivariate analyses, a significant association between tumor subtype and pattern of response was found. Among patients with HR+/HER2- tumors, 89.4 percent had a scattered pattern and 10.6 percent had a circumscribed pattern. In contrast, 52.8 percent of those with TNBC had a circumscribed pattern and 47.2 percent had a scattered pattern (p<0.001). In addition to subtype, both histologic grade and tumor size at presentation were significantly related to the pattern of residual disease in multivariate analysis, with lower grade and larger size associated with a scattered response pattern (p=0.002 and p=0.01, respectively). A better understanding of the relationship between pretreatment clinicopathologic features of the tumor and pattern of residual disease may help guide postchemotherapy surgical management.

Pastorello RG, Laws A, Grossmith S, et al. Clinico-pathologic predictors of patterns of residual disease following neoadjuvant chemotherapy for breast cancer. Mod Pathol. 2021;34:875–882.

Correspondence: Dr. Stuart J. Schnitt at sschnitt@bwh.harvard.edu

Challenges of Ki67 assessment in pulmonary large-cell neuroendocrine carcinomas

The authors conducted a study to gather evidence regarding Ki67 values in large-cell neuroendocrine carcinoma and to determine whether certain cutoff values could serve as prognostic features of the disease. They used Aperio ScanScope AT Turbo, Aperio eSlide Manager, and Aperio ImageScope software (Leica Biosystems) to measure Ki67 percentages in 77 resected large-cell neuroendocrine carcinomas (LCNEC) diagnosed using World Health Organization (WHO) criteria. Overall (OS) and disease-free survival (DFS) were analyzed using the Kaplan-Meier method and SAS software (SAS Institute). Survival data were also analyzed using American Joint Committee on Cancer (AJCC) eighth edition pathological stage and six discrete Ki67 classes arbitrarily defined by 10 percent increments up to 60 percent. In addition, survival data were assessed using Ki67 classes separated by a cut-point of 20 percent or more or 40 percent or more. Tumors ranged from 0.9 to 11.5 cm, and pathological staging comprised stages I through III. The system measured Ki67 percentage positivity using 4,072 to 44,533 tumor nuclei per case (mean, 16,610 ± 8,039). Ki67 values ranged from one to 64 percent (mean and median, 26 percent). Only 16 (21 percent) tumors had Ki67 values of 40 percent or more. Overall survival ranged from one to 298 months (median follow-up, 25 months). Disease-free survival ranged from one to 276 months (median follow-up, nine months). Overall and disease-free survival differed across AJCC stage (overall log-rank, P=0.038 and P=0.037, respectively). However, neither overall nor disease-free survival significantly correlated with stratification by Ki67 percentage into six or two classes, regardless of whether 20 percent or greater or 40 percent or greater was used as the cut-point. A literature review identified 14 papers meeting the authors’ inclusion criteria by evaluating 10 or more LCNEC without comingling the results for LCNEC and small-cell carcinoma. Reported Ki67 values ranged from two to 100 percent. The authors concluded that their findings caution against a blanket use of 20 percent, 40 percent, or other Ki67 percentage cut-points for LCNEC diagnosis or prognostication.

Walts AE, Mirocha JM, Marchevsky AM. Challenges in Ki-67 assessments in pulmonary large-cell neuroendocrine carcinomas. Histopathology. 2021;78(5):699–709.

Correspondence: Dr. Ann E. Walts at ann.walts@cshs.org