Publications

Small cell-like glandular proliferation of prostate: A rare lesion not related to small cell prostate cancer

Virchows Arch. 2017 Jan;470(1):47-54

Kryvenko ON, Williamson SR, Trpkov K, Gupta NS, Athanazio D, Selig MK, Smith PT, Magi-Galluzzi C, Jorda M

Abstract

Small cell-like change (SCLC) is a rare prostate lesion which has been described in only two previous studies (total of eight cases). Its relation to possible neuroendocrine differentiation remained unclear. We evaluated 11 SCLC cases with immunohistochemistry and electron microscopy. SCLC was characterized by crowded hyperchromatic small nuclei with scant cytoplasm, rosette-like structures, finely granular chromatin with indistinct nucleoli, and lack of mitoses, apoptoses, and necroses. In nine cases, SCLC was admixed with high-grade cancer, and in two cases, it represented a separate intraductal process, spatially remote from a low-volume Gleason score 6 (grade group 1) cancer. Only 2/11 SCLC labeled for synaptophysin, chromogranin, and serotonin, although 6/11 were at least focally positive for TTF1. Staining for NKX3.1 and pancytokeratin was typically weak, focal, and markedly reduced compared to the adjacent cancer. SCLC was positive for ERG in 1/8 and for racemase in 6/10 cases, again typically in a focal and weak fashion. There was no immunoreactivity with CD56, p63, or HMWCK. Ki-67 highlighted only rare nuclei (<1 %). No neuroendocrine granules were demonstrated by electron microscopy in four cases that showed no immunoreactivity for neuroendocrine markers. In summary, SCLC is more frequently found in high-grade prostate cancer, but it may also be encountered as a noninvasive lesion in Gleason score 6 (grade group 1) cancer. Importantly, it does not appear to indicate neuroendocrine differentiation. The low-grade cytology, the lack of mitoses and apoptoses, and the minimal Ki-67 reactivity are findings to support its discrimination from a small cell carcinoma.

PubMed

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Dr. Nawaid Usmani and team receive funding for their PRIME study!

The PRIME Study – Prevention and Intervention for MEtabolic syndrome:

Androgen deprivation therapy (ADT), and newer manipulations of androgen receptor signaling have improved outcomes for advanced prostate cancer (PCa) patients.  The toxicities of ADT are many, including an increased risk of developing metabolic syndrome (MS; defined as at least 3 of: hyperglycemia; abdominal obesity; hypertriglyceridemia; reduced HDL cholesterol; and/or hypertension). MS is associated with an increased risk of diabetes, cardiovascular disease mortality, stroke mortality, and all-cause mortality.  The prevalence of MS in men receiving ADT is at least 50% and contributes to decreased quality of life and increased non-cancer-related mortality.  Metformin holds promise as a countermeasure to MS development, and also has been shown to suppress PCa growth in pre-clinical models.

We hypothesize that the addition of metformin to ADT will reduce the rates of MS in men with advanced PCa, diminishing important toxicities of a therapy universally used in advanced disease.

We propose a double-blind, randomized phase III study of metformin or placebo in men with PCa starting intermittent ADT. The primary endpoint is the difference in MS rates at 1 year.  Other aims include evaluation of the influence of metformin on: individual MS components at additional time points; mean serum insulin levels and measures of insulin resistance; weight and quality of life.

A finding that metformin reduces MS incidence and/or has other benefits would change practice, as it would provide a practical and inexpensive strategy to reduce toxicity of an intervention employed in most men with advanced PCa.

- Catalina Vasquez