A significantly higher rate (12.4 percent) of significant pathologic findings was identified in this prospective study compared with published literature. None of the lesions was identified on preoperative mammogram. Age was significantly associated with significant pathologic findings. Increased sampling was associated with significant pathologic findings only in patients 40 years or older, indicating the need for thorough sampling of reduction mammaplasty specimens in patients older than 40.
Programmed Death 1 Ligand 1 (PD-L1) Immunohistochemistry (IHC) is the key FDA-approved predictive marker to identify responders to anti-PD1 axis drugs. Multiple PD-L1 IHC assays with various antibodies and cut-points have been used in clinical trials across tumor types. Comparative performance characteristics of these assays have been extensively studied qualitatively but not quantitatively. Here we evaluate the use of a standardized PD-L1 Index TMA to objectively determine agreement between antibody assays for PD-L1 applying quantitative digital image analysis. Using a specially constructed Index Tissue Microarray (TMA) containing a panel of 10 isogenic cell lines in triplicate, we tested identical but independently grown batches of isogenic cells to prove Index TMAs can be produced in large quantities and hence serve as a standardization tool. Then the Index TMAs were evaluated using quantitative immunofluorescence (QIF) to validate the TMA itself and also to compare antibodies including E1L3N, SP142 and SP263. Next, an inter-laboratory and inter-assay comparison of 5 PD-L1 chromogenic IHC assays (US Food and Drug Administration (FDA) approved and lab developed test (LDT)) were performed at 12 sites around the USA. As previously reported, the SP142-FDA assay failed to detect low levels of PD-L1 in cell lines distinguished by the other 4 assays. The assays for 22C3-FDA, 28-8-FDA, SP263-FDA and E1L3N-LDT were highly similar across sites and all laboratories showed a high consistency over time for all assays using this Index TMA. In conclusion, we were able to objectively quantify PD-L1 expression on a standardized Index TMA using digital image analysis and we confirmed previous subjective assessments of these assays, but now in a multi-institutional setting. We envision commercial use of this Index TMA or similar smaller version as a useful standardization mechanism to compare results between institutions and to identify abnormalities while running routine clinical samples.
Metastatic melanoma may simulate a broad spectrum of primary breast malignancies. Although the application of a simple panel of antibodies assists in rendering the correct interpretation, lesions presenting as isolated breast tumors may introduce a significant diagnostic difficulty, especially when there is inadequate patient history and/or limited biopsy material. Further challenges are introduced by the extraordinary phenotypic plasticity of metastatic melanoma. Awareness of this pattern variance is essential to avoid inappropriate treatment, especially in cases simulating a "triple negative," poorly differentiated carcinoma of the breast.
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