A 69-year old man with a clinical diagnosis of nodular hyperplasia underwent transurethral resection of the prostate. His serum PSA was 3.5 ng/ml. Ten grams of prostatic chips were removed, which were totally submitted for review. The majority of the chips revealed nodular hyperplasia. About 5% of the specimen showed areas of papillary proliferation.

The sections revealed nodular hyperplasia in the majority of the prostatic chips. However, approximately 5% of the overall specimen was involved by a complex papillary proliferation lined by pseudostratified columnar epithelium (Fig. 4.1). The papillary areas enclosed delicate fibrovascular cores (Fig. 4.2). The lining epithelial cells had abundant eosinophilic cytoplasm and enlarged oval or round uniform nuclei with minimal pleomorphism Prominent nucleoli and mitotic figures were rare (Fig. 4.3).

The differential diagnostic considerations include high-grade prostatic intraepithelial neoplasia (HGPIN) (Fig. 4.4), ductal adenocarcinoma (Fig. 4.5A, Fig. 4.5B), large gland variant of Gleason pattern 3 adenocarcinoma, urothelial carcinoma involving the prostate (Fig. 4.6), metastases such as colonic adenocarcinoma involving the prostate, ectopic prostatic tissue (prostatic urethral polyp) (Fig. 4.7A, Fig. 4.7B), proliferative papillary urethritis, and nephrogenic metaplasia.

Ductal Adenocarcinoma of the Prostate

Key Features:

• Originally considered to be a distinct pathologic and clinical entity since its first description more than 30 years ago; however, its current status as a unique neoplasm is controversial
• The terms "endometrioid" and "endometrial" have been discarded in favor of "ductal" to describe this tumor
• Accounts for about 0.8% of all prostate cancers and arises in prostatic urethra and large periurethral prostatic ducts. About 5% of radical prostatectomy specimens may show "ductal" pattern in the peripheral zone without the involvement of periurethral region
• Serum PSA and PAP may not be elevated
• Histologically, it consists of complex papillae, acini or cribriform structures lined by pseudo-stratified columnar epithelium. Many cases lack nuclear pleomorphism (such as in this case), prominent nucleoli, or increased mitotic activity
• Immunohistochemical profile includes strong immunoreactivity for PSA (Fig. 4.8), PAP, and occasionally CEA
• Differential diagnosis includes high-grade prostatic intraepithelial neoplasia, large gland variant of Gleason pattern 3 adenocarcinoma, urothelial carcinoma of the prostate, metastases (e.g. colonic adenocarcinoma), ectopic prostatic tissue, benign polyp, and nephrogenic metaplasia
• Clinical Significance: There is a lot of controversy regarding its biological behavior. Many studies have suggested that it pursues a more aggressive than conventional acinar adenocarcinoma with a shorter time to progression. Others show no difference or even better prognosis. Our opinion is ductal adenocarcinoma is not a unique entity and this pattern arises by the spread of typical acinar adenocarcinoma into the large accomodating spaces of periurethral or peripheral prostatic ducts. Its natural history is probably similar to that of acinar adencarcinoma, with similar patterns of metastases and response to hormonal manipulation. We and others believe that there are no consistent differences in clinical behavior between ductal and acinar adenocarcinoma and recommend that ductal adenocarcinoma should be treated in the same manner as acinar adenocarcinoma. We assign it a Gleason score of 3 in the absence of necrosis and Gleason 5 if necrosis is present

Comment:

The most challenging task is its distinction from cribriform or micropapillary forms of high-grade prostatic intraepithelial neoplasia. Ductal adenocarcinoma contains well-formed papillary structures with fibrovascular cores. Micropapillary HGPIN shows tall columnar cells lining delicate micropapillary fronds without fibrovascular cores. Stromal fibrosis, hemosiderin deposition, and perineural invasion are features often associated with ductal adenocarcinoma; they are not seen in prostatic intraepithelial neoplasia. Ductal adenocarcinoma often involves large areas containing numerous back-to-back glands. Prostatic intraepithelial neoplasia usually involves isolated or small clusters of glands; however, in a limited sample such as a needle biopsy, this distinction may be extremely difficult.

The presence of acinar differentiation allows its separation from urothelial carcinoma. In difficult cases, immunostains for PSA and PAP are useful (positive in ductal carcinoma, Fig. 4.8; negative in urothelial carcinoma). The presence of urothelial abnormalities in the adjacent urethral mucosa also favors urothelial cancer.

Benign lesions such as ectopic prostatic tissue (prostatic urethral polyp), proliferative papillary urethritis, and nephrogenic metaplasia can usually be distinguished more readily from ductal adenocarcinoma by the lack of dysplasia.

Follow-up

The patient underwent radical prostatectomy which revealed extensive involvement of the gland by cancer. Approximately 70% of the tumor had typical acinar pattern; the remaining 30% showed papillary and cribriform architecture. Such areas were seen both in the transition and the peripheral zone. The overall Gleason score was 3+4=7.

1. Bock BJ, Bostwick DG. Does prostatic ductal adenocarcinoma exist? Am J Surg Pathol 23(7):781-85, 1999. 2.
2. Brinker DA, Potter SR, Epstein JI. Ductal adenocarcinoma of the prostate diagnosed on needle biopsy. Am J Surg Pathol 23(12):1471-79, 1999.