Solitary fibrous tumor (SFT) is an uncommon fibroblastic neoplasm with considerable risk of local recurrence. SFT is histologically characterized by bland spindled-to-epithelioid cells in alternating hyper-and hypocellular zones, a "patternless pattern," ectatic "staghorn" vessels with variable edematous perivascular stroma, and thick ropey collagen.Cytologically, smears are variably cellular with spindled-to-epithelioid cells with oval nuclei, wispy cytoplasm, multiple inconspicuous nucleoli, and occasional nuclear pseudoinclusions. Small vessels and bare/stripped nuclei are generally present while mild atypia is not uncommon. STAT6 nuclear expression is the most useful immunohistochemical stain and is the product of a NAB2-STAT6 gene fusion. SFTs with mediastinal involvement may be diagnostically challenging due to proximity to vital structures and anticipated patient risks. Endobronchial and endoscopic ultrasound-guided fineneedle aspiration (EBUS/EUS-FNA) are minimally-invasive tissue sampling methods that provide diagnostic material while minimizing patient risk, and the mediastinum is accessible by both procedures. Small aspirate samples and SFT nonspecific features can compound the diagnostic difficulty, although familiarity with the cytologic, morphologic, immunophenotypic, and genetic features of SFTs assist the pathologist in confirming the diagnosis. Pathologists must also be aware of high-risk SFT features to ensure appropriate therapy and management. Case #1 describes a recurrent mediastinal SFT with high-risk features sampled by EUS-FNA. Case #2 describes a primary diagnosis of mediastinal SFT with malignant behavior made on an EBUS-FNA specimen. K E Y W O R D S endoscopic ultrasound, fine-needle aspiration, mediastinum, solitary fibrous tumor, STAT6
Incorporation of a MYC immunohistochemical stain in the work-up of large B-cell lymphomas has become common in hematopathology practice. Evaluation of this stain can be difficult due to staining heterogeneity and can have inter-observer variability, particularly when performed on entire tumor sections. We identified 87 cases of aggressive B cell lymphoma (34 core needle and 53 excisional biopsies) and compared the following methods of MYC immunohistochemical staining evaluation: the original pathologist's interpretation, a systematic retrospective method of evaluation by manual analysis, and a retrospective method of evaluation by digital image analysis (using scanned slides analyzed via the Aperio Nuclear algorithm). Overall, concordance among these methods was around 80% with kappa statistics showing good agreement. However, nearly one-third of our cases had a percent MYC positivity in the 30% to 50% range and, for these cases, concordance among the various methods was marginal/poor. This suggests limited utility as a prognostic or predictive marker using 40% as a cut-off value. In our series, core biopsy specimens were poor predictors of MYC gene rearrangement and there was no association between MYC immunohistochemical stain and MYC gene gain/amplification. Our retrospective digital image analysis showed strong correlation in MYC percent positivity with our retrospective manual review (correlation coefficient of 0.90) and similar concordance to pathologist interpretation as among pathologists, suggesting digital image analysis is a viable alternative to manual determination of MYC percent positivity. Digital image analysis provides further opportunities for more sophisticated and standardized scoring systems, which may be helpful in future prognostic/predictive studies.
Background: In MA.31, the lapatinib-taxane combination led to shorter PFS than trastuzumab-taxane in HER2+ metastatic breast cancer. We investigated the prognostic and predictive effects of pretreatment serum biomarkers. Methods: MA.31 accrued 652 patients; 537 (82%) were centrally-confirmed HER2+. Biomarkers were categorized for univariate and multivariate predictive investigations with a median cut-point, ULN cut-points (15 ng/ml- HER2; 506 pg/ml- CAIX; 454 pg/ml- TIMP-1; 1940 pg/ml– uPA; 600 pg/ml- activin A), and custom cut-points (30 and 100 ng/ml for HER2). Stratified step-wise forward Cox multivariate analysis used continuous and categorical biomarkers for PFS in the ITT and central HER2+ populations; central HER2+ biomarker results are shown. Results: Serum was banked for 472 (72%) of 652 patients. Higher serum activin A (>median; >ULN; p<0.0001); higher CAIX (>median; >ULN; p=0.02; p=0.001); higher HER2 (>median; >15; >30; or >100 ng/ml; p=0.05-0.002) and higher TIMP-1 (>median; >ULN; p=0.001; p=0.02) had shorter univariate PFS. In multivariate analysis for PFS: higher continuous activin A (HR=6.75 with Box-Cox transformation, P<0.0001) was associated with significantly shorter PFS, along with treatment arm, prior adjuvant anthracyclines, and higher central EGFR status. In multivariate analysis for OS: higher continuous activin A (HR=85.9, with Box-Cox transformation, P<0.0001) was associated with significantly shorter OS, along with treatment arm and higher central EGFR status. The interaction terms of serum biomarkers with treatment were not significant. Elevated serum activin A was also significant at the median cutpoint for PFS (HR 1.79, p=0.0002) and OS (HR 2.39, p=0.006) in multivariate analysis. Conclusions: Higher serum activin A was a significant independent prognostic biomarker of shorter progression-free and overall survival. No serum biomarker was predictive of differential response to lapatinib vs. trastuzumab. Evaluation of activin A and CAIX-targeted therapy in addition to HER2-targeted therapy may be warranted in patients with elevated serum levels of these biomarkers. *AK, MH, DH, & JH contributed equally Grant: PA Breast Cancer Coalition. Citation Format: Kang A, Hupp M, Ho D, Huang J, Leitzel K, Ali S, Shepherd L, Parulekar WR, Ellis CE, Rocco CJ, Zhu L, Virk S, Nomikos D, Aparicio S, Gelmon KA, Truica C, Al-Marrawi Y, Rizvi S, Vasekar M, Nagabhairu V, Polimera H, Marks E, Richardson A, Ali AS, Krecko L, Carney WP, Downs S, Chen BE, Lipton A. Effect of serum biomarkers (activin A, CAIX, HER2, TIMP-1, and uPA) on outcome in HER2+ metastatic breast cancer patients treated in first line with lapatinib or trastuzumab combined with taxane: CCTG MA.31 [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-07-06.
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