COW-2020-20

CASE OF THE WEEK

2020-20 / May 18
(Contributors: Daniel H. Russell and Salvatore E. Mignano)

A 64 year-old-male presented with hematuria and a mass in the fossa navicularis of the anterior urethra. Past history was notable for Grade Group 5 (Gleason score 4+5=9) pT3b pN0 acinar adenocarcinoma of the prostate. His PSA had an interval increase to 0.569 ng/mL. PSA immunohistochemistry on the tumor showed scattered patchy expression.

Quiz

1. What is the diagnosis?

a. Invasive high grade urothelial carcinoma

b. Metastatic prostatic adenocarcinoma (acinar adenocarcinoma; usual-type)

c. Metastatic prostatic adenocarcinoma with neuroendocrine features

d. Metastatic large cell neuroendocrine carcinoma of prostatic origin

e. Primary urothelial large cell neuroendocrine carcinoma

1. Metastatic prostatic adenocarcinoma with neuroendocrine features

The histology shows a poorly-differentiated tumor with prominent nucleoli and moderate amphophilic cytoplasm growing in sheets, with focal acinar formation. The tumor co-expresses synaptophysin and PSA. In conjunction with the patient’s history, the findings are compatible with prostatic adenocarcinoma with neuroendocrine features (PCANF). Current primary prostatic neuroendocrine tumors recognized by the WHO include PCANF, prostatic adenocarcinoma with Paneth cell-like change, well differentiated neuroendocrine tumor (carcinoid tumor), small cell carcinoma, and large cell neuroendocrine carcinoma (LCNEC). By definition, PCANF is a morphologically typical usual-type (acinar) adenocarcinoma (usually high grade), which co-expresses both acinar and neuroendocrine markers via immunohistochemistry (IHC). The utility of identifying PCANF with the use of IHC is of unconvincing clinical benefit, and as such, the routine use of IHC to evaluate neuroendocrine phenotype is not recommended, and scattered tumor cells expressing a neuroendocrine phenotype in usual prostate cancer is normal. In light of this, the presence of neuroendocrine cells in usual-type prostate cancer often increases with castration resistance, and thus it is unsurprising that a majority of prostatic neuroendocrine cancers arise in previously treated patients, a process termed “transdifferentiation”. The value in recognition of PCANF is its distinction from neuroendocrine carcinomas, usually LCNEC, given that men with PCANF remain eligible for androgen deprivation therapy, whereas the diagnosis of “neuroendocrine carcinoma” may exclude patients from this potential benefit. The diagnosis of LCNEC of the prostate is contentious. To be considered, all of the classic morphologic findings must be present, including peripheral palisading and expansile nests of high grade classic tumor cells with central comedonecrosis and expression of at least 1 neuroendocrine marker without co-expression of acinar markers. There have been a handful of reported cases of morphologically pure LCNEC that co-express acinar markers, typically in a reduced fashion, which have arisen both de novo and post-therapy. The significance of these observations is currently unsettled, while some data, albeit sparse, indicates that clinical benefit may still be derived from traditional androgen deprivation therapy in these patients.

1. Humphrey PA, Amin MB, Berney DM. In: Molch H, Humphrey PA, Ulbright TM, Reuter VM eds. WHO Classification of Tumours of the Urinary System and Male Genital Organs. 4th ed. Geneva, Switzerland. WHO Press/World Health Organization; 2016.

2. Epstein JI, Amin MB, Beltran H, Lotan TL, Mosquera JM, Reuter VE, Robinson BD, Tronosco P, Rubin MA. Proposed morphologic classification of prostate cancer with neuroendocrine differentiation. Am J Surg Pathol. 2014 Jun;38(6):756-767.

3. Bellur S, Van der Kwast T, Mete O. Evolving concepts in prostatic neuroendocrine manifestations: from focal divergent differentiation to amphicrine carcinoma. Hum Pathol. 2019 Mar;85:313-327.

Daniel H. Russell and Salvatore E. Mignano
Tripler Army Medical Center

russdanny22@gmail.com

Urethra

Prostatic Adenocarcinoma with Neuroendocrine Features; Castration Resistance; Transdifferentiation of Prostate Cancer;