Older Male with Elevated Serum PSA

Specimen Type:



A 66-year-old male with an elevated serum PSA underwent prostate needle biopsies.

Pathologic Features:

The biopsies reveal glandular structures infiltrating the stroma. Some glands are large and branching (Figures 1, 2), some are small glands with a solid appearance (Figures 3, 4). The proliferating epithelial cells show variable appearance, ranging from flattened to cuboidal to columnar and areas with elongate hobnail appearance (Figures 5, 6). The cytoplasm is clear or eosinophilic with mucin production (Figures 6, 7). The nuclei are intermediate to large in size, often with prominent nucleoli. Brisk mitotic activity is present (Figure 6). The tumor is negative for PAP, PSA, CK20, and positive for 34BE12 (Figure 8) and CK7 (Figure 9).

Differential Diagnosis:

  • Prostatic adenocarcinoma (Fig. 10)
  • Nephrogenic metaplasia (Fig. 11)
  • Urothelial carcinoma with glandular differentiation
  • Metastatic clear cell carcinoma

Postatic adenocarcinoma: This is the most common primary malignancy in the prostate (Fig. 10). The diagnosis is based on architecturally infiltrating pattern, atypical cytological features, and absence of basal cells. Tumor cells are positive for PSA.

Nephrogenic metaplasia: Nephrogenic metaplasia most often occurs in adult patients in the bladder (Fig. 11), renal pelvis, ureter and urethra; prostatic uretheral involvement is rare. It usually follows instrumentation, urethral catheterization, infection, or calculi. Although tubular pattern is the most common, polypoid, papillary and cystic patterns are also seen. The tubules, cysts, and papillae are lined by flattened, cuboidal or low columnar cells with scant cytoplasm, and hobnail cells are appreciated in up to 70% of the cases. Nuclear abnormalities are uncommon and, when present, appear reactive or degenerative.

Urothelial carcinoma with glandular differentiation: Typical urothelial carcinoma is usually easily identified, and the “glands” with lumen formation are surrounded by cells with pseudostratified appearance and superficial cell differentiation of urothelium, although typical glands lined by single layer columnar epithelium can be present.


Clear cell adenocarcinoma in the prostate

Key Features:

  • Infiltrating pattern
  • Glandular structures lined by flat, cuboidal, or columnar cells, and characteristic hobnail cells are at least focally present; cytoplasm is clear or eosinophilic
  • Significant cytologic atypia including enlarged nuclei, prominent nucleoli and mitotic figures

Comment: In this case, the major differential consideration is the prostatic adenocarcinoma, which is effectively excluded by negativity for PAP and PSA, and positivity for 34BE12. In addition, extension of colonic adenocarcinoma is excluded by expression of CK 7 and lack of CK20 staining. Negativity for CK20 argues against urethelial carcinoma with glandular differentiation. The combination of histology and immunophynotye is diagnostic of clear cell adenocarcinoma. Regarding the origin, prostate primary is possible, although it is extremely rare (reference), but extension from urethra/bladder primary should be ruled out.


  1. Pan CC, et al. Tubulocystic clear cell adenocarcinoma arising within the prostate. Am J Surg Pathol. 2000 Oct;24(10):1433-6.