Prostate
Prostatic carcinoma
Treatment effect

Author: Kenneth Iczkowski, M.D. (see Authors page)

Revised: 8 August 2016, last major update June 2015

Copyright: (c) 2003-2016, PathologyOutlines.com, Inc.

PubMed Search: Treatment effect [title] prostate
Definition / General
  • The histologic alterations caused by androgen deprivation therapy and by radiation have some overlapping features and some divergent ones

    5-alpha Reductase Inhibitors (Dutasteride, Finasteride):
    • Currently the most common type of androgen deprivation
    • Benign epithelium acquires distinctive changes from treatment, including atrophy and a decrease in epithelial height (Fig 1)
      • The peripheral zone shows the most marked response to treatment
      • Stroma may be fibrotic (Urology 2005;65:76)
    • In cancer tissue (Urology 2005;65:76):
      • Glands show nuclear pyknosis, urothelial or squamous metaplasia, and atrophy with prominence and hyperplasia of basal cell layer
      • Tumor volume is significantly lower in dutasteride treated men than in placebo-treated men
      • The percentage of atrophic cancer epithelium is increased, and the stroma/gland ratio is consequently doubled compared to placebo treated men
    • Atrophy consists of three types of changes:
      1. Atrophic: similar to benign atrophic glands
      2. Atrophic glands with pyknotic nuclei and clear or xanthomatous cytoplasm (Figs 2-3)
      3. Tumor cells resembling inflammatory cells
    • The Gleason score is not altered

    LHRH agonists and flutamide:
    Estrogen therapy:
    • Causes cytoplasmic vacuolization, nuclear pyknosis, naked nuclei
    • Also squamous metaplasia of normal and malignant glands

    Brachytherapy:
    • Radioactive seed implantation produces changes identical to external beam therapy
    • Clinician may NOT be aware of treatment history
    • Causes effects on vascular, stromal and epithelial compartments
    • Vascular: arterial luminal narrowing due to myointimal proliferation (thickened vascular walls) and thrombi, foam cells in vessel walls, vascular hyalinization
    • Stroma: stromal fibrosis, atypical fibroblasts
    • Benign epithelium:
      • The most striking change is marked basal cell hyperplasia (Fig 4)
        • These basal cells have cytologic atypia (nuclear enlargement, bizarre nuclei, prominent nucleoli) but glands still retain their lobular architecture: several glands in a cluster without infiltration (Am J Surg Pathol 1999;23:1173)
      • May see glandular atrophy with scant eosinophilic cytoplasm and small pyknotic nuclei, basal cell prominence, variable squamous metaplasia, Paneth cell-like change, mucinous metaplasia, luminal blue-tinged mucinous secretions (Am J Surg Pathol 1999;23:1021)
      • Fibrosis and atrophy of seminal vesicles (Am J Surg Pathol 1982;6:541)
      • Changes may persist for a long time after treatment (Am J Surg Pathol 2003;27:206)
      • Persistent tumor usually retains pretreatment architectural pattern with fewer tumor cells
      • Benign tissue shows cytologic atypia so diagnose residual tumor based on architecture, not cytology
    • Cancer epithelium: Similar changes to benign epithelium, but with:
      • Infiltrative growth, perineural invasion, intraluminal crystalloids, blue mucin secretions, but no corpora amylacea
      • Also high grade PIN
Diagnosis
  • After Androgen Deprivation:
    • Normal prostate shows atrophy, basal cell hyperplasia and prominence
    • Adenocarcinoma shows reduced cytoplasmic quantity, cytoplasmic vacuolation, nuclear pyknosis, reduced gland diameter, mucinous breakdown
    • PSA, pancytokeratin immunoreactivity helps confirm cancer cells
    • Tumor cells lack high molecular weight cytokeratin expression, similar to untreated cancer cells
    • Post-therapy PSA, PSAP reactivity may decrease (Prostate 1985;7:195, J Urol 1983;130:95)
    • High grade PIN persists after endocrine treatment
    • Tufted PIN may be replaced by flat high grade PIN (Hum Pathol 1999;30:1503)
    • Difficult to evaluate margin status after androgen deprivation
    • Current recommendations are to NOT assign a Gleason grade to androgen deprivation treatment specimens (Clin Prostate Cancer 2004;2:228)

  • After Radiation Treatment:
Prognostic Factors
  • The grading of radiation effect on a 0-6 scale is highly predictive of local failure
  • There is no evidence for tumor dedifferentiation after radiotherapy (Cancer 1997;79:81)
Micro Images

Images hosted on other servers:

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Brachytherapy change

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Radiation changes: benign prostate



Images courtesy of Dr. Kenneth Iczkowski:

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After androgen deprivation

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Cancer acini

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Close-up of cancer acini

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After radiation therapy