Abstracts from USCAP 2020: Genitourinary Pathology (860-1046)

Background: Blocking androgen receptor is the main therapeutic target in advanced and metastatic prostate cancer (PCa).However, a subset of patients relapse and develop androgen-independent and aggressive forms of PCa.Androgen deprivation therapy (ADT) may induce transdifferentiation of PCa cells to neuroendocrine-like tumor cells resulting in resistance to therapy, disease progression and poor outcomes.While PCa neuroendocrine transdifferentiation(NETD) after ADT has been well described, NETD occurring in a de novo setting is understudied.Herein, we report a series of de novo NETD in untreated high-grade PCa.Design: Treatment naïve patients with primary PCa with NETD between 2013-2019 were identified.H&E slides were reviewed by 2 GU pathologists to evaluate morphologic features.Cases with lack of conventional small cell carcinoma(SCC) features were included.IHC stains for PSA, NKX3.1, Chromogranin, Synaptophysin, Cyclin D1, RB1 and Ki67 were performed.Radiology, treatment and follow-up data were reviewed.Results: Fourteen patients were included(9 biopsies, 3 transurethral resection, 2 prostatectomy).High-grade PCa with focal acinar features was identified, reminiscent of Gleason scores 9 or 10.Additionally, areas showed sheets of tumor cells with deep amphophilic/basophilic cytoplasm, enlarged hyperchromatic nuclei with granular chromatin and inconspicuous nucleoli with high mitotic activity.IHC showed the neoplastic cells to express patchy NKX3.1(8/14),Synaptophysin(7/14),Chromogranin(8/14) with negative PSA(10/14).RB1 showed loss of expression(8/14), cyclin D1 showed reduced expression(13/14) and Ki67 showed high-proliferative index(14/14).Adverse radiologic findings(extraprostatic extension and seminal vesicle invasion) were identified in most cases.Metastasis was documented in 5 patients.Two patients died of the disease.Treatment included ADT alone, ADT followed by docetaxel, carboplatin-based chemotherapy and radiation therapy.Both patients on ADT and 3 of 4 who received ADT followed by docetaxol showed undetectable PSA, while those who received carboplatin and etoposide showed progression.Conclusions: PCa with NETD exhibit high-grade nuclei, lack of prominent nucleoli, high mitotic activity, reduced PSA expression with high Ki67 and functional inactivation of RB1 pathway, suggesting transdifferentiation from androgen-driven to more proliferative-driven phenotype.While the majority of these tumors are seen in patients with history of PCa post ADT, de novo cases can occur.

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