Metastatic prostate cancer diagnosed by fine‐needle aspiration: Contemporary cytopathologic and biomarker assessment with clinical correlates

Abstract

Introduction The diagnosis of metastatic prostatic cancer (MPC) by fine needle aspiration (FNA) can usually be rendered by typical cytomorphologic and immunohistochemical (IHC) features. However, MPC diagnosis may be complicated by transformation to atypical phenotypes such as small cell carcinoma, typically under pressure from androgen deprivation therapy (ADT). Predictive and prognostic biomarkers can also be assessed by IHC. This study illustrates how careful assessment of cytologic and biomarker features may provide therapeutic and prognostic information in MPC. Design We reviewed our anatomic pathology archives for MPC diagnosed by FNA from January 2014 to June 2021. Clinical histories, cytology slides, and cell blocks were reviewed. Extensive IHC biomarker workup was performed, including markers of prostate lineage, cell‐cycle dysfunction, Ki‐67, neuroendocrine markers, PDL1, and androgen receptor splice variant 7. Cases were reclassified into three categories: conventional type, intermediary type, and high‐grade neuroendocrine carcinoma (HGNC). Results Eighteen patients were identified. Twelve had conventional MPC, including six of six ADT‐naive patients. Six of twelve (50%) with prior ADT were reclassified as intermediary or HGNC. Four intermediary cases included two with squamous differentiation and two with pro‐proliferative features. Two HGNC cases had typical small cell carcinoma cytomorphology. Expression of PDL1 was identified in two cases and ARv7 in three cases. Five of five intermediary and HGNC patients died of disease versus six of eleven with with conventional type. Conclusions Aggressive cytomorphologic variants were commonly identified in patients with prior ADT. Identification of nonconventional cytomorphology and increased proliferation can provide important prognostic information. Recognition of these changes is important for an accurate diagnosis, and the identification of high‐grade variants can affect therapeutic decision‐making. Clinically actionable biomarkers such as PDL1 and ARv7 can be assessed by IHC.

Experience and Lessons Learned in the Treatment of Transforming Small Cell Neuroendocrine Carcinoma of the Prostate: A Case Report and Literature Review

“…However, the transformation from CPAC to SCNECP is a dynamic process, and the patient may still have adenocarcinoma components after the transformation. Therefore, the patient may have two tumor cells simultaneously during the course of the disease [ 9 ].…”

“…IHC is the most important diagnostic tool for SCNECP. Almost all SCNECP may be positive for one or more NE markers (synaptophysin, chromogranin, and neuron-specific enolase) [ 9 ]. Therefore, it is not difficult to diagnose SCNEC.…”

Therapeutic Approaches to Targeting Androgen Receptor Splice Variants

“…Despite significant advancements in the targeting of this pathway, the emergence of castration-resistant prostate cancer (CRPC) and its inherent resistance to conventional anti-androgen therapies have underscored the complexity of the disease. Metastatic CRPC (mCRPC), under pressure from regimens targeting the AR pathway, can undergo molecular changes driving resistance to these treatment regimens [ 2 ]. A pivotal facet of this resistance arises from alternative splicing of AR mRNA, generating AR splice variants (AR-Vs) [ 3 ].…”