Prostate gland & seminal vesicles

• There is some overlap of histologic alterations and some divergence, caused by androgen deprivation therapy and by radiation, to both prostate cancer and benign epithelium

• Adjuvant androgen deprivation with radiotherapy has benefits for progression free survival (J Clin Oncol 2021 Jan;39:136)
  • Neoadjuvant use prior to prostatectomy was given in about 2% of cases in 2004 - 2014 and correlated with lower odds of positive margins and in a minority of cases, pathologic downstaging; it caused elimination of the adverse risk factor of presence of intraductal carcinoma in some cases (Ann Surg Oncol 2019;26:297, Prostate Cancer Prostatic Dis 2018;21:364, Prostate 2020;80:284)
  • However, some studies do not show a survival benefit (J Clin Oncol 2020;38:3042)
• Grading of radiation effect on a 0 - 6 scale is highly predictive of local failure (Cancer 1997;79:81)
  • A system proposed in 1997 takes the sum of cytoplasmic changes (0 - 3) and nuclear changes (0 - 3):
    • Cytoplasmic change grades are (1) swelling and microvesicles, (2) extensive vacuolation and voluminous cytoplasm and (3) dilated glands plus single cells without lumens
    • Nuclear change grades are (1) some swelling or smudging but nucleoli identified, (2) large bizarre nuclei and (3) pyknotic condensed nuclei
  • In the above study, local failure was 55% for 0 - 2 grade effect, 30% for grade 3 - 4 and 0% for grade 5 - 6
• There is no evidence for tumor dedifferentiation after radiotherapy (Cancer 1997;79:81)

Contributed by Kenneth Iczkowski, M.D. and Debra L. Zynger, M.D.

• After androgen deprivation
  • PSA, pancytokeratin helps confirm cancer cells
  • Post therapy, PSA and PSAP may decrease (Prostate 1985;7:195, J Urol 1983;130:95)
• After radiation treatment
  • High molecular weight keratin identifies basal cells in benign radiated glands (Semin Diagn Pathol 2005;22:88)
  • AMACR helps to differentiate prostatic adenocarcinoma from radiation induced atypia in benign prostatic epithelium (Hum Pathol 2006;19:287)
  • PSA and PSAP is usually retained by radiated prostate glands (Cancer 1997;79:81, Semin Diagn Pathol 2005;22:88)
  • Caveat about GATA3: expression is positive in 100% of both secretory cells and benign cells in benign prostate with radiation atypia, whereas reactivity is limited to basal cells in the absence of radiation atypia; this finding, along with the cytologic atypia of radiation, can mimic urothelial carcinoma (Histopathology 2017;71:150)

• Atrophy (without therapeutic cause):
  • Exceedingly common finding in prostatic biopsies but there usually are some admixed nonatrophic glands
  • In the presence of 100% of glands being atrophic, history of treatment effect should be sought, particularly androgen deprivation
  • If atrophy is accompanied by basal cell hyperplasia, seek a history of radiotherapy
• Xanthoma:
  • Contains cells with foamy cytoplasm but atypia would be absent and immunostain would reveal positivity for CD68 and negativity for cytokeratins
• Foamy gland adenocarcinoma:
  • Has abundant foamy cytoplasm and less cytologic atypia than other cancers; this may mimic radiation effect but radiation effect creates vacuoles with both nuclear and cytoplasmic enlargement, which are different findings

Which immunostain may be falsely positive in benign glands after radiotherapy?

1. Basal cell cytokeratin
2. GATA3
3. P504S
4. p63
5. PSA

B. GATA3 may be falsely positive and mimic urothelial carcinoma in benign glands after radiotherapy. P504S should be positive in cancer and negative in benign glands. Basal cell cytokeratin and p63 should be negative in cancer after therapy. PSA reactivity is usually retained so expected to be positive.

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Reference: Treatment effect - prostate

A 65 year old man with a history of prostate cancer diagnosed 8 years ago has a prostatectomy. Carcinoma from his prostatectomy specimen is shown. Which of the following is the best diagnosis?

1. Prostatic adenocarcinoma 3+3=6
2. Prostatic adenocarcinoma 3+4=7
3. Prostatic adenocarcinoma 4+4=8
4. Prostatic adenocarcinoma 4+5=9
5. Prostatic adenocarcinoma with treatment effect

E. Prostatic adenocarcinoma with treatment effect. In this case the patient was treated with brachytherapy. Radiation change is seen consisting of atrophic glands with nuclei that touch the cell membrane and gland retraction. A Gleason score is not rendered for tumors with marked therapy effect such as this case.

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Reference: Treatment effect - prostate