Prostate Mass in an Older Male

Deloar Hossain, M.D.

Specimen Type:



68 years old male with serum PSA of 5.8 ng/ml.

Pathologic Features:

Gross Features: Submitted in formalin were 12 cores of prostate needle biopsies.

Microscopic Features: The biopsy from the left base (one of 12 cores) showed a distended duct with large crowded glands (fig: 1) exhibiting complex papillary architecture lined by pseudostratified tall columnar cells with mild cytologic atypia (fig: 2). Few nucleoli were seen (fig: 3).

Immunohistochemical Features: Focal, weak and patchy immunoreactivity for basal cell specific high molecular weight cytokeratin 34BE-12 and p63 was noted (fig: 4). The bulk of the lesion was negative for basal cells. Immunohistochemical stain for alpha-methyl-coA-racemase is positive.

Differential Diagnosis:

  • High grade prostatic intraepithelial neoplasia
  • Atypical acinar proliferation highly suspicious for adenocarcinoma
  • Adenocarcinoma of the prostate (Gleason 3+3=6), ductal subtype

High grade prostatic intraepithelial neoplasia (HGPIN)
High grade prostatic intraepithelial neoplasia is oftentimes is a focal lesion characterized by tufting, micropapillary, cribriform, solid, flat or inverted architectural patterns (fig: 5). The lining epithelium is usually proliferative with hyperchromatic enlarged nuclei and prominent nucleoli. The latter distinguishes this lesion from low-grade prostatic intraepithelial neoplasia. The number of basal cells is reduced or is seen as a discontinuous layer using immunostain(s) for cytokeratin 34BE-12 and/or p63.

Atypical acinar proliferation highly suspicious for adenocarcinoma (ASAPH)
As the term implies, the observer deems there is insufficient criteria to make a definitive diagnosis of adenocarcinoma. The reasons may either be quantitative (few atypical glands present) or qualitative (the cells lining the atypical glands lack appreciable nuclear atypia such as hyperchromasia, enlargement and/or macronucleoli) (fig: 6). Immunostains using antibodies directed against cytokeratin 34BE-12 and/or p63 usually show complete absence of basal cell layer in these cases, or basal cells present in a patchy, focal distribution. Occasionally, a continuous layer of basal cells may be present (ref. 1). The diagnosis of adenocarcinoma in the latter instance needs to be made with caution.

Ductal subtype adenocarcinoma of the prostate
Ductal adenocarcinoma is the most common histologic variant of prostate cancer. The incidence is about 3% of all prostatic adenocarcinomas. It is characterized by complex papillary and/or cribriform glands expanding involved ducts. The neoplasm involves both primary and secondary prostatic ducts and may be seen in peripheral prostate needle biopsies. Cytologically, the lining epithelium is distinctively pseudostratified and tall columnar (fig:6). Cytologic atypia range from mildly atypical without prominent nucleoli to severely atypical with true macronucleoli. Basal cells may be present on immunostain.

Table 1. Comparative features of -
  HGPIN ASAPH Ductal Adenocarcinoma
Architecture Focal; non-infiltrative
Absent or mild ductal distention
Tufting, papillary, solid, cribriform, or flat patterns

Variably sized acini
Infiltrative or duct-confined
Distends affected ducts
Complex papillary and cribriform patterns
More diffuse than HGPIN
Lining Cells Pseudostratified columnar with macronucleoli Usually simple cuboidal with prominent nucleoli Pseudostratified columnar with or without macronucleoli
Immunostain +; often discontinuous
Negative; rarely +
Negative; or + in patchy distribution


Ductal adenocarcinoma, Gleason 3+3=6

Key Features

  • Acini with complex branching papillae
  • Ductal distention
  • Basal cells mostly absent or present focally
  • Pseudostratified tall columnar lining epithelium. A few cells show prominent nucleoli

This case study illustrates the dilemma that sometimes confront a Pathologist looking at prostate needle biopsies. Two experts disagree on the diagnosis. One expert favored adenocarcinoma while another favored ASAPH. The follow-up biopsies, seen and diagnosed by an outside (third) Pathologist, reportedly showed “HGPIN” in 2 cores, from the right and left bases. We did not have the opportunity to review the last set of biopsies. Awareness of the difficult differential diagnosis between ASAPH, high grade prostatic intraepithelial neoplasia and ductal adenocarcinoma of the prostate should prompt Pathologists to seek a second opinion on these cases. Although high grade prostatic intraepithelial neoplasia may have a papillary pattern, it usually does not show the complex branching architecture seen in ductal adenocarcinoma. Differentiation between the two entities should depend on the complex architectural characteristics, duct distention and extent of involvement rather than the presence of a basal cell layer.


  1. Oliai BR, Kahane H, Epstein JI. Can basal cells be seen in adenocarcinoma of the prostate?: An immunohistochemical study using high molecular weight cytokeratin 34BE-12 antibody. Am J Surg Pathol 26(9): 1151-1160, Sept. 2002.
  2. Humphrey PA. Prostate Pathology. ASCP press, 2003.