Clear cell adenocarcinoma (CCA) is a rare tumor in the genitourinary tract with female predominance and few reports in men. We identified 15 cases of CCA in men evaluated at our institution. Five arose in the bladder, 7 in the prostate or prostatic urethra, 2 in the membranous urethra (1 multifocal in the prostatic and membranous urethra), 1 periprostatic (likely from an embryologic remnant), and 1 between rectum and bladder (likely in a prostatic utricle cyst). No cases showed associated Müllerian structures. One case showed separate foci of nephrogenic adenoma at diagnosis, and 1 case showed urothelial carcinoma in situ on a later follow-up biopsy. Four tumors extended into other organs (prostate to seminal vesicle and periprostatic soft tissue, periprostatic soft tissue to prostate, prostatic urethra to bladder and rectum, and prostate to bladder neck). One tumor showed extraprostatic extension alone. Four tumors metastasized to lymph nodes, with 3 also metastasizing to other sites (bladder, lung and adrenal, and right flank). Eleven patients underwent resection, including 3 transurethral resections. Seven underwent other treatments, including radiation (5 [1 for recurrence]), chemotherapy (3), hormonal therapy (3), immunotherapy with nivolumab (1), and targeted therapy with gefitinib (1). The mean follow-up was 35 months (range: 1 to 138 mo). At the last follow-up, 7 patients showed no evident disease and 3 were alive with disease. Four died with the cause of death unknown, with 2 cases having confirmed disease at the time of death and the remaining 2 dying less than a year after diagnosis. The mean time to death was 16 months (range: 6 to 39 mo). No follow-up was available on 1 patient. All patients who died in this series had CCA of the prostate or prostatic urethra. Pathologists need to be attuned to CCA occurring in males, given that the literature emphasizes its occurrence in females. In addition to established sites such as bladder and urethra, our series demonstrates that tumor may present in unusual adjacent sites, such as in periprostatic embryologic remnants or prostatic utricle.

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Background: Breast cancer (BC) evolution is influenced by tumor microenvironment. Presence of CD8+ cytotoxic T lymphocytes (TILs) has been proposed as surrogate marker of adaptive immune response, and programmed death ligand-1 (PD-L1) is a negative regulator of the tumor immune microenvironment. However, whether PD-L1 expression adversely affects breast cancer outcome is unknown (Oncotarget 2014; 6:5449). Tumor-associated macrophages (TAMs) in the tumor microenvironment may contribute to BC progression and metastagenicity. We assessed the potential correlations between PD-L1 expression, the presence of TAMs and TILs, and BC outcomes. Methods: 59 primary BCs (16 HR+, 16 HER2+, and 27 TNBC) with known clinical and pathological features and patient (pt) follow-up for a median of 3.9 years were evaluated by immunohistochemistry for expression of CD8, CD68, and PD-L1 within tumor and stroma. The average number of CD8+ cells within 10 high power fields was determined separately for invasive tumor cell nests and for stroma within each sample, and the median number of CD8+ cells within tumor vs stroma was calculated (Breast Cancer Res Treat 2011 128:703–711). Non-lymphocyte mononuclear cells in tumor and stroma were used in counting CD68+ TAMs. BCs were positive for CD8+ TILs (Cell Marque clone #C8144B) or CD68+ TAMs (Cell Marque clone #KP1) if the number of cells positive in the sample was greater than the median. PD-L1 (Dako 28-8 pharmDx) was positive if at least 1% of tumor cells expressed PD-L1. The log-rank was used to compare the survival and progression free survival between groups and Spearman's rank-order correlation tests were conducted to determine associations between CD8, CD68, and PD-L1. Results: 57% of TN, 26% of HER2+ and 13% of HR+ BCs expressed PD-L1 in tumor. TNBC pts received anthracycline/ taxane chemotherapy (62%) or taxane therapy alone (22%). HR+ and HER2+ pts received standard endocrine therapy and trastuzumab-based therapy. Stromal CD8+ TILs were associated with improved OS in the overall population (log rank p=0.026). In TNBC, PD-L1 expression was positively correlated with the presence of TILs (p=0.0002) and TAMs (p=0.0005) as well as with improved 3 year PFS and OS (log rank p=0.04 and p=0.03, respectively). Furthermore, stromal CD8+ TILs and stromal CD68+ TAMs correlated positively with each other in the TNBC group (p=0.0094). Conclusions: PD-L1 expression correlated with TILs and TAMs in TNBC and was associated with a favorable outcome. PD-L1+ TNBCs with high levels of TILs and TAMs may be primed for exceptional response to immunogenic chemotherapy alone. Whether some pts with PD-L1+ TNBCs with high TILs/TAMs will benefit additionally from an anti-PD-L1/PD-1 agent is being investigated currently. Citation Format: Mardones MA, Grosser D, Levin MK, Daoud Y, Palucka K, O'Shaughnessy J, Osborne C. PD-L1 expression in triple negative breast cancer (TNBC) is associated with improved outcomes [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 P2-04-20.

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With the advent of tyrosine kinase inhibitors, the identification of tumors with alterations in tyrosine kinase genes has become important to guide treatment. Lung adenocarcinomas harboring ALK translocations may be targeted with drugs such as crizotinib. We undertook a retrospective review of our institution's pathology records from January 2015 through September 2017 and identified 10 lung adenocarcinomas with ALK rearrangements. We reviewed the histomorphologic features and immunohistochemical results from these 10 cases. Morphologic features included patterns such as acinar, papillary, micropapillary, and solid, as well as features such as cribriform, signet ring, and extracellular mucin. Acinar (including simple and cribriform) was the most common pattern, followed by papillary. Solid and signet ring features were the least common. These findings were consistent with prior histomorphologic studies of ALK-positive lung adenocarcinomas. Certain histomorphologic patterns are associated with ALK positivity. However, histomorphologic features are neither absolutely sensitive nor absolutely specific in suggesting ALK rearrangement. Thus, identification of lung adenocarcinomas that may benefit from treatment with tyrosine kinase inhibitors requires comprehensive molecular testing.