Pj McIntire

Folate Receptor Alpha Expression Is Associated With Increased Risk of Recurrence in Triple-negative Breast Cancer

Background: Folate receptor alpha (FOLR1) has been identified as a potential prognostic and therapeutic target in breast cancer. The limited studies evaluating the role of FOLR1 in breast cancer have shown that FOLR1 protein expression is enriched in triple‐negative breast cancer (TNBC) and associated with poor prognosis in all breast cancer types. Newly developed anti‐FOLR1 therapy could potentially be used in patients with TNBC for whom few therapeutic options exist. We sought to evaluate FOLR1 protein expression in a cohort of patients with TNBC to determine its prevalence and prognostic value. Materials: Immunohistochemistry was performed for FOLR1 in 76 cases of primary TNBC. Membranous staining in ≥ 5% of cells was deemed positive in a given case. Statistical analyses correlating FOLR1 protein expression with clinicopathologic parameters and clinical outcome (disease‐free survival and overall survival) were performed. Results: A total of 76 cases of primary TNBC were studied. Most cases were negative for FOLR1 (80.3%; 61/76). FOLR1 expression did not correlate with any clinicopathologic parameters. FOLR1 expression was significantly correlated with decreased disease‐free survival (hazard ratio, 2.61; 95% confidence interval, 0.96–7.09; P = .0497 log‐rank test). Although FOLR1 expression trended towards decreased overall survival, it was not statistically significant (hazard ratio, 1.99; 95% confidence interval, 0.62–6.36; P > .05 log‐rank test). Conclusion: We found a lower incidence of FOLR1 expression in TNBC compared with other studies; however, these patients may benefit from anti‐folate therapy as other targeted therapies are not available. Although no correlation between FOLR1 expression and standard clinicopathologic parameters was identified, our findings suggest that FOLR1 expression is prognostically significant in TNBC. Micro‐Abstract: Treatment options for patients with triple‐negative breast cancer (TNBC) are limited. Folate Receptor Alpha (FOLR1) is a potential target, whereas overexpression has been associated with poor prognosis in all breast cancer subtypes. In 76 TNBCs, 20% demonstrated FOLR1 overexpression, which was significantly associated with decreased disease‐free survival. Although eligible for anti‐FOLR1 therapy, patients with FOLR1‐positive TNBC were found to have an increased risk of recurrence.

Vascular tumours of the breast: a comprehensive review with focus on diagnostic challenges encountered in the core biopsy setting

Vascular proliferations of the breast comprise a spectrum of benign and malignant lesions. In limited samples, such as core needle biopsies (CNB), these lesions may be difficult to distinguish due to significant overlap in morphological features. As the treatment and prognosis of these entities vary widely, it is important for pathologists to consider a complete differential diagnosis and correctly synthesise histological features, results of adjunctive immunohistochemical studies, and pertinent clinical and imaging information, to render an accurate diagnosis in such limited samples. The diagnostic pitfalls of under- or overdiagnosis of vascular lesions sampled in CNB will also be discussed.

Hotspot enumeration of CD8+ tumor infiltrating lymphocyte using digital image analysis in triple negative breast Cancer yields consistent results

Tumor-infiltrating lymphocytes (TILs) have emerged as prognostic in triple-negative breast cancer (TNBC). We aimed to assess the consistency of hotspot placement and TIL enumeration among multiple pathologists. Additionally, we assessed hotspot TIL count consistency by comparing hotspot counts in 3 separate locations within a single whole-tissue section. Anti-CD8 immunohistochemistry was performed on a representative section from 66 cases of primary TNBC, which were then scanned as whole-slide images. Quantification of the tissue area and combined stromal and intratumoral CD8+ TILs was performed using digital image analysis (DIA) within 2.2 mm-diameter circle hotspots. TIL counts were quantified as absolute counts and densities (absolute count/tissue area in micrometers2). For each case, 6 pathologists placed a single hotspot, defined as an area with the subjectively highest CD8+ immunoreactivity, within the tumor bed. Separately for each case, a single pathologist placed hotspots in 3 different locations within a single tumor section. Intraclass correlation coefficients (ICCs) were generated following TIL enumeration via DIA. ICCs for single hotspot placement by 6 pathologists were 0.96 for density and 0.97 for absolute counts, respectively. In 32% of cases (21/66), all the hotspots placed by the 6 pathologists were in the same location. When evaluating hotspots in 3 different locations within a tumor, the ICC was 0.95 for both density and absolute counts. Hotspot evaluation by DIA is a reproducible method for CD8+ TIL quantification, and the use of hotspots may reduce TIL count variation caused by intratumoral TIL heterogeneity.

Hot Spot and Whole-Tumor Enumeration of CD8+ Tumor-Infiltrating Lymphocytes Utilizing Digital Image Analysis Is Prognostic in Triple-Negative Breast Cancer

Background: CD8+ tumor‐infiltrating lymphocytes (TILs) have emerged as a prognostic indicator in triple‐negative breast cancer (TNBC). There is debate surrounding the prognostic value of hot spots for CD8+ TIL enumeration. Methods: We compared hot spot versus whole‐tumor CD8+ TIL enumeration in prognosticating TNBC using immunohistochemistry on whole tissue sections and quantification by digital image analysis (Halo imaging analysis software; Indica Labs, Corrales, NM). A wide range of clinically relevant hot spot sizes was evaluated. Results: CD8+ TIL enumeration was independently statistically significant for all hot spot sizes and whole‐tumor annotations for disease‐free survival by multivariate analysis. A 10× objective (2.2 mm diameter) hot spot was found to correlate significantly with overall survival (P = .04), while the remaining hot spots and whole‐tumor CD8+ TIL enumeration did not (P > .05). Statistical significance was not demonstrated when comparing between hot spots and whole‐tumor annotations, as the groups had overlapping confidence intervals. Conclusion: CD8+ TIL hot spot enumeration is equivalent to whole‐tumor enumeration for prognostication in TNBC and may serve as a good alternative methodology in future studies and clinical practice.

Myofibroblastic, Fibroblastic and Myoid lesions of the Breast

Myofibroblastic, fibroblastic and/or myoid lesions are rare in the breast but comprise the majority of mammary mesenchymal spindle cell lesions. Whereas most have similar features to their counterparts at extramammary sites, pseudoangiomatous stromal hyperplasia is considered a breast-specific myofibroblastic proliferation on the same spectrum as myofibroblastoma. Other lesions with myofibroblastic/fibroblastic differentiation include fibromatosis and nodular fasciitis, as well as more aggressive tumors such as the rarely reported myofibrosarcoma, inflammatory myofibroblastic tumor and fibrosarcoma. Lesions with myoid differentiation include benign leiomyoma, myoid hamartoma and leiomyomatous myofibroblastoma, but primary leiomyosarcoma and rhabdomyosarcoma may also rarely arise in the breast. Furthermore, fibroepithelial lesions and metaplastic carcinomas can demonstrate myoid metaplasia. Diagnosis can be challenging, particularly on core biopsy, but benign lesions with or without recurrence potential must be distinguished from more aggressive tumors, especially metaplastic carcinoma and phyllodes tumors. This article will review lesions with myofibroblastic, fibroblastic and myoid differentiation in the breast, with special emphasis on differential diagnosis.