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Clear cell papillary renal cell tumor (CCPRCT) is a distinct clinical entity with characteristic pathological features and non-aggressive clinical behavior. Diagnostically challenging cases present when there are immunomorphological findings of CCPRCT associated with heterogeneous morphologies, aggressive histological features, and advanced pathological stages—so-called CCPRCT-like tumors. In this report, we describe a heterogeneous, multifocal renal tumor with immunomorphological characteristics of CCPRCT but with associated aggressive features such as sarcomatoid and necrotic areas, perirenal and sinus fat involvement, and most notably, lymph node metastasis composed entirely of classic CCPRCT morphology and immunophenotype. Immunohistochemical and fluorescence in situ hybridization studies did not support a translocation renal cell carcinoma. Molecular analyses did not identify common mutations or chromosomal abnormalities seen in clear cell renal cell carcinoma or ELOC -mutated renal cell carcinoma. This case highlights that rare renal cell tumors remain difficult to classify and the distinction between CCPRCT and CCPRCT-like tumors remains to be better defined. [ABSTRACT FROM AUTHOR]

Breast implant-associated anaplastic large cell lymphoma (breast implant-associated ALCL) is a recently described, distinct clinicopathological entity associated with macrotextured breast implants. The diagnostic workup of a patient suspected to have breast implant-associated ALCL includes cytological assessment of effusions and tissue biopsies of any masses or enlarged lymph nodes, with morphologic and immunophenotypic evaluation and possible flow cytometric and molecular testing. We report the case of a woman found to have breast implant-associated ALCL on fine needle aspirate and core biopsy, who on surgical resection, had extensive local disease with involvement of the resection margins and lymph nodes, requiring systemic treatment. We focus on the flow cytometric findings that identified a population of large cells on the CD30/side scatter dot plot and whose immunophenotype was consistent with breast implant-associated ALCL, highlighting the value of flow cytometry as an adjunct to morphological and immunophenotypic evaluation. [ABSTRACT FROM AUTHOR]

Background: Little is known about the total patient burden associated with clinical development and where burdens fall most heavily during a drug development program. Our goal was to quantify the total patient burden/benefit in developing a new drug., Methods: We measured risk using drug-related adverse events that were grade 3 or higher, benefit by objective response rate, and trial outcomes by whether studies met their primary endpoint with acceptable safety. The differences in risk (death rate) and benefit (overall response rate) between industry and nonindustry trials were analyzed with an inverse-variance weighted fixed effects meta-analysis implemented as a weighted regression analysis. All statistical tests were two-sided., Results: We identified 103 primary publications of sunitinib monotherapy, representing 9092 patients and 3991 patient-years of involvement over 10 years and 32 different malignancies. In total, 1052 patients receiving sunitinib monotherapy experienced objective tumor response (15.7% of intent-to-treat population, 95% confidence interval [CI] = 15.3% to 16.0%), 98 died from drug-related toxicities (1.08%, 95% CI = 1.02% to 1.14%), and at least 1245 experienced grade 3-4 drug-related toxicities (13.7%, 95% CI = 13.3% to 14.1%). Risk/benefit worsened as the development program matured, with several instances of replicated negative studies and almost no positive trials after the first responding malignancies were discovered., Conclusions: Even for a successful drug, the risk/benefit balance of trials was similar to phase I cancer trials in general. Sunitinib monotherapy development showed worsening risk/benefit, and the testing of new indications responded slowly to evidence that sunitinib monotherapy would not extend to new malignancies. Research decision-making should draw on evidence from whole research programs rather than a narrow band of studies in the same indication., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)