Celebrating the 80th anniversary of hormone ablation for prostate cancer

In this special issue of Endocrine-Related Cancer, we are celebrating the 80th anniversary of hormone ablation as treatment for metastatic prostate cancer. Our understanding has evolved from the observation that androgen withdrawal, either surgical or pharmacological, resulted in prostatic atrophy in animal models, to its application in patients, to investigation of the mysterious way in which prostate cancer escapes androgen dependence. We are now in an era of novel AR pathway inhibitors, combination of androgen ablation with chemotherapy, PARP inhibitors, immunotherapies, guided radiotherapy, and novel drug application based upon genetic testing of individual tumors. In this Anniversary Issue, we bring together a collection of eight reviews that cover not only the history of 80 years of progress after the initial identification of androgen ablation as an effective treatment of prostate cancer, but subsequent improvements in the understanding of the biology of the disease, development of novel treatment paradigms, resistance to those treatments and disease progression following that resistance.

Nuclear morphometric study of prostatic atrophy

The prostatic atrophy is a lesion with small glands that can mimic adenocarcinoma, commonly diagnosed in the elderly and whose preneoplastic role is controversial. Over time several classifications have been developed for this lesions according to its architectural and cellular aspects. Materials and Methods: Aim of the study is morphometrically assessment of epithelial component nuclei in prostatic atrophy. We evaluated parameters represented by nuclear area (NA), nuclear perimeter P (μm) Elongation factor (E), average diameter (DEQ), maximum diameter (Dmax), Minim diameter (Dmin). The control group was represented by adenomatous hyperplasia component of benign hyperplasia of the prostate. Results: Morphometric analysis revealed significantly higher values of nuclear parameters in atrophy compared with adenomatous component in controls (p <0.05) which can signify nucleomegaly and a potential preneoplastic role.

EFFECT OF TESTOSTERONE REPLACEMENT ON EPITHELIAL AND STROMAL TISSUE IN PROSTATIC LOBE IN ORCHIDECTOMIZED WISTAR

Objective: To evaluate the effect of testosterone replacement on epithelial and stromal changes of prostatic lobes in castrated wistar rats. Material & Method: The subjects were 30 wistars equally assigned to castrated + testosterone replacement group (n = 10), castrated group (n = 10), and control group (n = 10). After 60 days, prostatectomy was performed in all rats and prostatic specimens were analyzed by haematoxylin eosin (HE) staining under microscope. Semi–quantitative analysis was performed by evaluating growth of epithelial structure and loss of fibromuscular stroma. Results were analyzed using ANOVA test method for normally distributed data. The statistical analysis was performed using SPSS. Results: There was significant reversibility in castration + testosterone replacement groups in all prostatic lobes compared with castration groups (p = 0,010).There were 5 rats showing normal structure of prostate gland compared to control groups in all prostatic lobes (50%), and 5 showed hyperplasia in all prostatic lobes (50%). Conclusion: Testosterone deprivation can cause prostatic atrophy. Dominant atrophy was found in ventral and lateral lobes. Testosterone replacement can prevent atrophy in all prostatic lobes regardless of specific prostatic lobes.Keywords: Testosterone deprivation, testosterone replacement, prostatic lobes.

Nonneoplastic Lesions of the Prostate and Bladder

Context.—Specimens from the prostate and bladder are commonly encountered by the general surgical pathologist. Emphasis is usually placed on neoplasms of the bladder and prostate, particularly if malignant, owing to their therapeutic consequences. A good command of benign lesions occurring in the bladder and prostate, and knowledge of their preneoplastic potential will help pathologists confidently diagnose malignancy versus its benign mimickers and guide the urologists in choosing the appropriate therapy and follow-up for the patient. Objective.—To present a mixture of benign entities, and discuss their histologic and clinical characteristics, hoping to provide a practical review for the general surgical pathologist. Data Sources.—An extensive review of the literature on the entities discussed was performed. Conclusions.—A wide variety of benign entities are present in the prostate and bladder. Benign lesions in the prostate can be age related, such as prostatic atrophy and benign prostatic hyperplasia; transition zone associated, such as basal cell hyperplasia, adenosis, and sclerosing adenosis; or prostatic urethra associated. Benign lesions of the bladder encompass a wide variety of reactive changes that can occur in the urothelium, as well as hyperplastic lesions or reactive proliferations that could be misdiagnosed as malignant. The bladder responds to chronic irritation through several reactive/metaplastic lesions such as cystitis cystica/glandularis, keratinizing squamous metaplasia, or nephrogenic metaplasia. The urothelium can also give rise to hyperplastic/proliferative lesions, in particular von Brunn nest hyperplasia, papillary polypoid cystitis, and pseudocarcinomatous proliferation, which should be distinguished from malignant processes. Ectopic tissue, such as prostatic or mullerian, can also be seen.