Difficulties in interpreting specimens after neoadjuvant hormonal therapy and radiation with illustration of neuroendocrine differentiation

Pattern and cellular changes attributable to neoadjuvant hormonal therapy (NHT) might cause the unwary pathologist to overgrade or fail to recognize a treated prostatic cancer. Overdiagnosis and overgrading of surgical resections and biopsies can be avoided if an appropriate history of therapy is conveyed with the surgical specimen and if the pathologist is aware of the altered morphology of prostatic cancer treated by NHT alone or NHT plus radiation. Study of three prostatectomy specimens with post-NHT predominance of neuroendocrine cells showed positive staining for prostate specific antigen (PSA) and prostatic acid phospbatase (PAP), as well as staining for chromogranin and synaptophysin in Paneth-like and small neuroendocrine cells. Difficult-to-interpret needle biopsies and transnrethral resection (TUR) biopsies of prostate, where the urologic pathologist's suspicion of a radiation effect was confirmed by additional history, showed absence of the basal cell layer with 34βE12 keratin immunostaining in prostatic cancer glands, while basal cells were present in the nonneoplastic glands with radiation-induced atypia. Postradiation salvage prostatectomy specimens showed greater apoptosis after combined NHT and radiation than after radiation without NHT. Changes attributable to radiation and radiation plus NHT are illustrated.