Elsevier

Human Pathology

Volume 64, June 2017, Pages 186-190
Human Pathology

Case study
Transformation of prostatic adenocarcinoma to well-differentiated neuroendocrine tumor after hormonal treatment

https://doi.org/10.1016/j.humpath.2017.01.006Get rights and content

Highlights

  • Report a unique case of prostate cancer transforming to a carcinoid-like carcinoma.

  • Highlight neuroendocrine transdifferentiation in posttreatment prostate cancer.

  • Help pathologists to evaluate prostate cancer with neuroendocrine differentiation.

  • Discuss clinical significance of neuroendocrine differentiation in prostate cancer.

Summary

Carcinoid tumor of the prostate is extremely rare. Here we report a unique case of prostate cancer that underwent complete transformation from conventional adenocarcinoma to carcinoid-like tumor shortly after androgen-deprivation treatment (ADT). The patient was a 59-year-old man who presented with lower urinary tract symptoms. His biopsy specimen demonstrated a high-grade prostatic adenocarcinoma with mixed acinar and ductal features. After ADT for 6 months, the patient underwent radical prostatectomy. The post-ADT tumor showed monotonous neoplastic cells with fine granular chromatin forming rosette-like structures, resembling a carcinoid tumor. No residual conventional adenocarcinoma was present. On immunostain, the tumor cells were diffusely positive for synaptophysin and chromogranin and negative for prostate-specific antigen and prostein. Thus, the carcinoid-like tumor represented complete transformation from prostatic adenocarcinoma to well-differentiated neuroendocrine tumor after ADT. This unique case highlights the important role of ADT in neuroendocrine differentiation of prostate cancer.

Introduction

Neuroendocrine (NE) cells are a minute subset of specialized cells in the prostate glands that account for less than 0.5% of all epithelial cells; however, they produce a variety of peptide hormones and regulate cell proliferation, apoptosis, metabolism, angiogenesis, and other biological functions in the prostate [1], [2], [3]. On routine hematoxylin and eosin (H&E) examination, NE cells are difficult to distinguish from other epithelial cells in the prostate except for those with Paneth-like features or granular eosinophilic cytoplasm. NE cells are usually recognized by immunoreactivity for NE markers, such as synaptophysin, chromogranin, and CD56 [3]. Although most prostate cancers are composed of adenocarcinoma, pure or de novo NE tumors are extremely rare in the prostate [4], [5]. However, on immunohistochemical analysis, most prostate cancers show rare NE cells that are scattered in the adenocarcinoma [1], [2], [3]. Several studies have found that NE differentiation is enhanced in prostate cancer when patients undergo androgen-deprivation treatment (ADT) [6], [7]. Herein we report a unique case of prostate cancer that underwent a complete transformation from conventional adenocarcinoma to carcinoid-like, well-differentiated NE tumor shortly after ADT.

Section snippets

Case report

A 59-year-old man initially presented with gross hematuria, but the clinical evaluation, including cystoscopy and computed tomographic urogram, was unremarkable. Four years later, he developed lower urinary tract symptoms with urinary retention, which required the placement of a Foley catheter. Cystoscopic examination revealed a small papillary tumor in the prostatic urethra, which was resected. Microscopically, the lesion was composed of large cribriform atypical glands with focal papillary

Discussion

Although NE cells can be demonstrated in most prostate cancers by immunohistochemistry, the origin of NE cells in prostate cancer remains uncertain. It has been hypothesized that they may originate from the pluripotent stem cells similar to the NE cells in the normal prostate [2], but other researchers proposed separate origins of NE cells in benign and neoplastic prostate glands based on the different gene expression [1], [3]. For instance, NE cells in prostate cancer express α-methyl-

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    These NE cells, therefore do not derive from normal NE cells, and should be defined as ‘NE-like PC cells’ (Yuan et al., 2007; Cerasuolo et al., 2015; Noble et al., 2018). To date, a growing body of evidence in the literature supports the idea that the onset of NED from conventional prostate cancer is associated with systemic treatments (Miyoshi et al., 2001; Tanaka et al., 2001; Beltran et al., 2012; Gilani et al., 2017; Wang et al., 2018; Nouri et al., 2017). This transformation arises because of lineage plasticity.

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    Recently, a case report of a tumor fulfilling the criteria of a well-differentiated NE tumor (carcinoid tumor) was reported in a patient with conventional adenocarcinoma treated with androgen-deprivation therapy [54]. It is not clear whether this tumor would represent a second primary tumor or transdifferentiation from the original prostatic adenocarcinoma [54]. Data on the molecular pathogenesis of well-differentiated NE tumors are scarce.

  • Genitourinary neuroendocrine neoplasms

    2020, The Spectrum of Neuroendocrine Neoplasia: A Practical Approach to Diagnosis, Classification and Therapy
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Disclosures: None.

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