Prostate - treatment effect

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Prostate

Prostatic carcinoma

Treatment effect

Reviewers: Komal Arora, M.D. (see Reviewers page)
Revised: 28 July 2012, last major update January 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

Brachytherapy
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● Radioactive seed implantation produces changes similar to external beam therapy (see below)

Brachytherapy change

Cyproterone acetate
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● An anti-androgen

Micro:
● Normal prostate shows atrophy, basal cell hyperplasia and prominence
● Adenocarcinoma shows reduced cytoplasmic quantity, cytoplasmic vacuolation, nuclear pyknosis, reduced gland diameter, mucinous breakdown
● Often collagenous stroma obscuring malignant glands
● Recommended to NOT give a Gleason grade to these specimens
● References: Am J Surg Pathol 2002;26:1400

Estrogen therapy
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● Causes cytoplasmic vacuolization, nuclear pyknosis, naked nuclei
● Also squamous metaplasia of normal and malignant glands

External beam therapy (radiation therapy)
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● 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

Epithelium:
● Variable cytologic atypia (nuclear enlargement, bizarre nuclei, prominent nucleoli) but retention of lobular architecture (Am J Surg Pathol 1999;23:1173)
● 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)
● 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
● High molecular weight keratin stain identifies basal cells in benign radiated glands (Cancer 1989;63:454)
● AMACR immunostaining helps to differentiate prostatic adenocarcinoma from radiation-induced atypia in benign prostatic epithelium (Hum Pathol 2006;19:287)
● PSA and PSAP positivity is usually retained by radiated prostate glands (J Urol 1980;124:488)
● Post-treatment tumor not graded if treatment effect is present
● Less treatment effect in radical prostatectomy specimens than needle biopsies (Am J Surg Pathol 1999;23:1173)

Malignant features:
● Infiltrative growth
● Perineural invasion
● Intraluminal crystalloids
● Blue mucin secretions
● High grade PIN
● No corpora amylacea

Benign glands:
● Nuclear enlargement (86%), prominent nucleoli (50%)

Radiation changes: benign prostate

Finasteride
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● An anti-androgen
● No consistent hormonal therapy effects with finasteride treatment observed morphologically compared with LHRH agonists (Urology 2005;66:930)

LHRH agonists and flutamide
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● Cause striking vacuolization of tumor cells and benign cells
● Nuclear pyknosis, urothelial or squamous metaplasia, atrophy with prominence and hyperplasia of basal cell layer, stromal fibrosis
● May cause pseudomyxoma ovarii type changes of minute to large pools of extravasated basophilic acid mucin dissecting through prostatic stroma with an infiltrative appearance on low power
● Secretions positive for mucicarmine, Alcian blue (pH 2.5), PAS after diastase
● No basal cells present (Am J Surg Path 1998;22:347, Am J Surg Pathol 1996;20:86, Am J Surg Pathol 1994;18:979, Am J Surg Pathol 1991;15:111)
● Histologically three patterns of treatment effect seen in cancer cells:
    1. Atrophic: similar to benign atrophic glands
    2. Atrophic glands with pyknotic nuclei and abundant xanthomatous cytoplasm
    3. Tumor cells resembling inflammatory cells
● To aid in diagnosis, individual tumor cells shoul be searched for at high magnification
● PSA, pancytokeratin immunoreactivity helps confirm cancer cells
● Tumor cells lack HMCK 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

Differential diagnosis
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● Prostatic adenocarcinoma: infiltrative growth, perineural invasion, intraluminal crystalloids, high grade PIN

End of Prostate > Prostatic carcinoma > Treatment effect

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