Context.— The Ventana programmed death ligand-1 (PD-L1) SP142 immunohistochemical assay (IHC) is approved by the US Food and Drug Administration as the companion diagnostic assay to identify patients with locally advanced or metastatic triple-negative breast cancer for immunotherapy with atezolizumab, a monoclonal antibody targeting PD-L1. Objective.— To determine interobserver variability in PD-L1 SP142 IHC interpretation in invasive breast carcinoma. Design.— The pathology database was interrogated for all patients diagnosed with primary invasive, locally recurrent, or metastatic breast carcinoma on which PD-L1 SP142 IHC was performed from November 2018 to June 2019 at our institution. A subset of cases was selected using a computerized random-number generator. PD-L1 IHC was evaluated in stromal tumor-infiltrating immune cells using the IMpassion130 trial criteria, with positive cases defined as immunoreactivity in immune cells 1% or more of the tumor area. IHC was interpreted on whole slide images by staff pathologists with breast pathology expertise. Interobserver variability was calculated using unweighted κ. Results.— A total of 79 cases were assessed by 8 pathologists. Interobserver agreement was substantial (κ = 0.727). There was complete agreement among all 8 pathologists in 62% (49 of 79) of cases, 7 pathologists or more in 84% (66 of 79) of cases and 6 pathologists or more in 92% (73 of 79) of cases. In 4% (3 of 79) of cases, all of which were small biopsies, pathologists' interpretations were evenly split between scores of positive and negative. Conclusions.— The findings show substantial agreement in PD-L1 SP142 IHC assessment of breast carcinoma cases among 8 pathologists at a single institution. Further study is warranted to define the basis for discrepant results.
Flat epithelial atypia (FEA) is an alteration of terminal duct-lobular units by a proliferation of ductal epithelium with low grade atypia. No consensus exists on whether the diagnosis of FEA in core needle biopsy (CNB) requires excision (EXC). We retrospectively identified all in-house CNBs obtained between 1/2012-7/2018 with FEA. We reviewed all CNB slides and assessed radiologic-pathologic concordance. An upgrade was defined as invasive carcinoma (IC) and/or ductal carcinoma in situ in the EXC. The EXC slides of all upgraded cases were re-reviewed. Out of ~15,700 consecutive CNBs in the study period, 106 CNBs from 106 patients yielded FEA alone or with classic lobular neoplasia (LN). We excluded 52 CNBs (40 patients with prior/concurrent carcinoma and 12 without EXC). After re-review, we reclassified 14 cases (2 marked nuclear atypia, 10 focal ADH, 2 benign). The final FEA study cohort consisted of 40 CNBs from 40 women. The CNB targeted mammographic calcifications in 36 (90%) cases, MRI non-mass enhancement in 3 (8%), and 1 (2%) sonographic mass. All CNBs were deemed radiologicpathologic concordant. FEA was present alone in 34 CNBs and with LN in 6. EXC yielded 2 low grade IC, each spanning less than 2 mm, identified in tissue sections without biopsy site changes. The remaining 38 cases had no upgrade. Classic LN did not affect the upgrade. The upgrade rate of FEA was 5%; both minute, low-grade "incidental" IC. We conclude that non-surgical management may be considered in patients without prior/concurrent carcinoma and radiologicpathologic concordant CNB diagnosis of FEA.
False-negative (FN) intraoperative frozen section (FS) results of sentinel lymph nodes (SLN) have been reported to be more common after neoadjuvant chemotherapy (NAC) in the primary surgical setting. We evaluated SLN FS assessment in breast cancer patients treated with NAC to determine the FN rate and the histomorphologic factors associated with FN results. Patients who had FS SLN assessment following NAC from July 2008 to July 2017 were identified. Of the 711 SLN FS cases, 522 were negative, 181 positive, and 8 deferred. The FN rate was 5.4% (28/522). There were no false-positive results. Of the 8 deferred cases, 5 were positive on permanent section and 3 were negative. There was a higher frequency of micrometastasis and isolated tumor cells in FN cases (P<0.001). There was a significant increase in tissue surface area present on permanent section slides compared with FS slides (P<0.001), highlighting the inherent technical limitations of FS and histologic under-sampling of tissue which leads to most FN results. The majority (25/28, 89%) of FN cases had metastatic foci identified exclusively on permanent sections and were not due to a true diagnostic interpretation error. FN cases were more frequently estrogen receptor positive (P<0.001), progesterone receptor positive (P=0.001), human epidermal growth factor receptor-2 negative (P=0.009) and histologic grade 1 (P=0.015), which most likely reflects the lower rates of pathologic complete response in these tumors. Despite its limitations, FS is a reliable modality to assess the presence of SLN metastases in NAC treated patients.
Purpose Evaluate the clinical presentation and imaging findings of breast implant‐associated anaplastic large cell lymphoma (BIA ALCL) at a large US cancer center. Materials and Methods HIPAA‐compliant IRB approved retrospective study, for which informed consent was waived. The Hospital Information System was screened for women who underwent implant reconstruction and were diagnosed with BIA ALCL between 2010 and 2016. Two radiologists reviewed images in consensus. Clinical and imaging characteristics were summarized using means and ranges for continuous variables and percentages for categorical variables. Results Patient cohort included 11 women with BIA ALCL (mean age at diagnosis = 54 years, range: 35‐77), including women with (9/11) and without (2/11) history of breast cancer. Mean time from breast implant placement to diagnosis was 10 years (range: 6‐14). BIA ALCL was identified in patients with saline (4/11) and silicone (5/11) implants. Implants were textured in 7/11 (63%) and unknown in 4/11 (36%) cases. All patients presented with a peri‐implant seroma, (9/11 documented on imaging). Two of 11 patients had a mass within this seroma. Ten of 11 patients (91%) presented with symptoms. Conclusions Saline and silicone breast implants may predispose patients to a rare lymphoma subtype, BIA ALCL, which presents on imaging as a peri‐implant fluid collection ± mass.
Background.-Multiple synchronous ipsilateral invasive breast carcinomas (BCs) with similar histology usually have concordant receptor status. It is unknown whether individual foci with similar histology also share molecular and biological similarities or are heterogenous. This study examines the concordance of the 21-gene recurrence score (RS) in multiple synchronous morphologically similar ipsilateral BCs.Methods.-We identified patients with multiple ipsilateral BCs and available RS treated at our institution from 1/2014 to 6/2018. BCs were divided into 3 groups based on RS: 1) RS in same risk category, 2) RS in different risk categories but within 2-unit difference (e.g. RS 17 and RS 19), and 3) RS in different risk categories and a change of >2 units. BCs in groups 1 and 2 were considered concordant (no significant clinical impact) and BCs in group 3 were discordant (variation affects management).Results.-A total of 53 patients met the study criteria. RS was concordant in 46 (87%) cases. Seven (13%) cases were discordant (group 3). Of these, 3 (43%, 3/7) had biopsy cavity changes (BXC) adjacent to the BC with the highest RS. In two cases the focus with higher RS had a lower percentage of PR-positive tumor cells. In two cases extensive DCIS was associated with BC focus with the lower RS.Conclusions.-Morphologically similar multifocal ipsilateral BCs have concordant RS in 87% (46/53) of cases. Our results suggest that in cases of morphologically similar multifocal BC testing of a single focus provides accurate prognostic and predictive information.
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