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Difficulty: MediumPathology and Biopsy Interpretation

A 68-year-old man presents to the clinic for a follow-up evaluation of an elevated prostate-specific antigen (PSA) level of 6.8 ng/mL6.8 \text{ ng/mL}. His digital rectal examination reveals a firm, non-tender nodule in the right peripheral zone of the prostate. He undergoes a transrectal ultrasound-guided core needle biopsy. The pathologist reviews the tissue cores from the right peripheral zone and reports a proliferation of small, crowded, irregularly spaced glands with scant intervening stroma. High-power magnification demonstrates cells with enlarged nuclei and prominent nucleoli. To differentiate between neoplastic and non-neoplastic processes, immunohistochemical analysis is performed. The atypical glands demonstrate a complete absence of staining for p63 and high-molecular-weight cytokeratin (HMWCK). Furthermore, the glands show strong, diffuse cytoplasmic staining for alpha-methylacyl-CoA racemase (AMACR). Based on these histopathologic and immunohistochemical findings, which of the following is the most definitive diagnosis?

  1. Invasive prostatic adenocarcinomaAnswer
  2. B
    High-grade prostatic intraepithelial neoplasia
  3. C
    Benign prostatic hyperplasia
  4. D
    Atypical adenomatous hyperplasia
  5. E
    Granulomatous prostatitis

Answer

Invasive prostatic adenocarcinoma
The correct diagnosis is invasive prostatic adenocarcinoma. The histopathologic finding of small, crowded glands with prominent nucleoli is characteristic. To definitively separate adenocarcinoma from benign mimics, immunohistochemistry is utilized. Normal prostate glands have a dual-cell layer: an inner secretory layer and an outer basal layer. Invasive prostatic adenocarcinoma is defined by the complete loss of this basal cell layer, proven by negative immunohistochemical staining for basal markers such as p63 and high-molecular-weight cytokeratin (HMWCK). Concurrently, alpha-methylacyl-CoA racemase (AMACR, also known as P504S) is highly overexpressed in prostate carcinoma cells. A profile showing p63(-)/HMWCK(-) and AMACR(+) definitively establishes the diagnosis.

Step-by-Step Solution

1
Analyze the architectural and cytologic features on the H&E stain.
The presence of small, crowded glands with scant stroma, enlarged nuclei, and prominent nucleoli raises high suspicion for malignancy.
These are the classic morphological hallmarks of prostatic adenocarcinoma.
2
Interpret the immunohistochemical stains for basal cell markers (p63 and HMWCK).
There is a complete absence of staining for p63 and high-molecular-weight cytokeratin.
Normal prostate glands and benign mimics (like BPH or adenosis) possess an intact or patchy basal cell layer. The complete loss of basal cells is the defining feature of invasive prostatic adenocarcinoma.
3
Interpret the immunohistochemical stain for AMACR (P504S).
The glands show strong, diffuse cytoplasmic staining for AMACR.
AMACR is upregulated in prostate cancer. The combination of absent basal cell markers and positive AMACR confirms the diagnosis of invasive adenocarcinoma.

Key Concept

Immunohistochemical diagnosis of prostate cancer relies on the demonstration of absent basal cells (negative p63/HMWCK) and positive expression of AMACR.
Estimated Time:1m 15s
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Topics

Pathology and Biopsy Interpretation

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