Prostate gland & seminal vesicles

Acinar / ductal adenocarcinomas

Adenocarcinoma with aberrant p63


Editorial Board Member: Bonnie Choy, M.D.
Deputy Editor-in-Chief: Maria Tretiakova, M.D., Ph.D.
Kenneth A. Iczkowski, M.D.

Last author update: 26 January 2023
Last staff update: 26 January 2023

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PubMed Search: Adenocarcinoma with aberrant p63

Kenneth A. Iczkowski, M.D.
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Cite this page: Iczkowski KA. Adenocarcinoma with aberrant p63. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/prostateadenoaberrantp63.html. Accessed February 6th, 2023.
Definition / general
  • A small subset of prostatic acinar carcinoma is characterized by strong p63 nuclear immunoexpression; distinctive morphologic and molecular phenotypes have been described in these cases
Essential features
  • p63 protein is normally present in basal cells of benign acini but is absent in usual type acinar or ductal cancers
  • However, starting in 2008, a rare subset of cancers with diffuse p63 positivity has been described
  • Atrophic and basaloid phenotype has been noted on H&E slides
  • Immunostains for cytokeratin 34 beta E12 (negative) and AMACR / P504s (positive) can help resolve problematic foci
  • References: Am J Surg Pathol 2008;32:461, Am J Surg Pathol 2013;37:1401
ICD coding
  • ICD-O: 8140/3 - acinar adenocarcinoma
  • ICD-10: C61 - malignant neoplasm of prostate
  • ICD-11: 2C82.0 & XH4PB1 - adenocarcinoma of prostate & acinar adenocarcinoma of prostate
Epidemiology
Diagnosis
  • Immunostaining is performed with either the triple immunostain (high molecular weight cytokeratin, p63 and p504S) or with p63 alone
Laboratory
Prognostic factors
  • The first description of this entity was comprised of all organ confined cases (Am J Surg Pathol 2008;32:461)
  • A subsequent report described 76% as organ confined, with relatively low Gleason scores, although 38% were 3 + 5 = 8 (Am J Surg Pathol 2013;37:1401)
  • However, one case with metastasis has been reported (Cureus 2022;14:e22753)
    • Thus, most but not all cases seem to have favorable pathology
    • Long term outcome has not been studied yet
  • Parenthetically, p63 staining can assume predominant cytoplasmic reactivity in prostate cancer (unlike its strong nuclear staining in basal cells) but this is a separate matter
Case reports
Microscopic (histologic) description
  • The first series in 2008 by Osunkoya et al. described 21 cases on needle biopsy, including 8 with matched prostatectomy in which > 70% of cancer cells were p63 positive (Am J Surg Pathol 2008;32:461)
    • Distinctive, atrophic-like morphology was noted
  • 21 matched biopsy / prostatectomy cases were characterized (Am J Surg Pathol 2013;37:1401)
    • Besides atrophic-like change, salient features that have been described include a basaloid appearance and high N:C ratio, with multilayered and sometimes spindled nuclei
    • Notably, at prostatectomy, 86% of cases had coexisting usual type p63 negative adenocarcinoma while 14% were pure
Microscopic (histologic) images

Contributed by Kenneth A. Iczkowski, M.D.
Atrophic-like dilated cancer acini

Atrophic-like dilated cancer acini

Basaloid appearance

Basaloid appearance

Atrophic, mucinous cancer

Atrophic, mucinous cancer


Strong diffuse nuclear p63 expression Strong diffuse nuclear p63 expression

Strong diffuse nuclear p63 expression

Few p63 positive acini

Few p63 positive acini

Cytoplasmic p63

Cytoplasmic p63

Positive stains
Negative stains
Molecular / cytogenetics description
  • 37 p63 positive cancer cases were compiled to investigate the molecular phenotype (Mod Pathol 2015;28:446)
    • These tumors were almost all positive for ΔNp63 isoform by immunofluorescence and p63 mRNA by in situ hybridization
    • 100% of these tumors lacked ERG rearrangement at the molecular level by FISH and the protein level by immunostaining; moreover, 100% lacked PTEN loss
      • These 2 features are found in ~50% and 33% of usual acinar carcinomas, respectively
    • Tumors frequently express GSTP1 (14/19; higher than usual)
  • In one case report, 5 tumor foci in a prostatectomy were present, of which one was p63 positive; this focus did not show a TMPRSS::ERG translocation by FISH, while the other foci did (Int J Surg Pathol 2011;19:131)
  • ETS2 tumor suppressor gene is highly expressed in 95% (18/19) of p63 expressing prostatic carcinomas and benign prostate basal cells, with lower to undetectable expression in luminal cells and primary usual type adenocarcinomas (Prostate 2018;78:896)
Sample pathology report
  • Prostate, right mid, biopsy:
    • Prostatic adenocarcinoma, Gleason 3 + 4 (grade group 2) (see comment)
    • Comment: The tumor demonstrates a basaloid appearance with aberrant p63 nuclear reactivity. This is a rare subtype of prostatic adenocarcinoma and cancer is confirmed by lack of immunoreactivity for cytokeratin 34 beta E12.
Differential diagnosis
Board review style question #1

Which of the following are features of the rare type of prostatic carcinoma pictured above?

  1. Basaloid H&E appearance and negative for all luminal and basal markers
  2. Basaloid H&E appearance and positive for basal markers such as cytokeratin 34 beta E12, CK5/6, CK14 and CK15
  3. Basaloid H&E appearance and positive for luminal markers such as CK8, CK18, androgen receptor, NKX3.1, prostein and P504S
  4. Luminal H&E appearance and positive for basal markers such as cytokeratin 34 beta E12, CK5/6, CK14 and CK15
  5. Luminal H&E appearance and positive for luminal markers such as CK8, CK18, androgen receptor, NKX3.1, prostein and P504S
Board review style answer #1
C. Basaloid H&E appearance and positive for luminal markers such as CK8, CK18, androgen receptor, NKX3.1, prostein and P504S. The H&E appearance of these rare tumors is basaloid and atrophic but paradoxically they retain luminal marker expression and are negative for basal cell markers such as cytokeratin 34 beta E12.

Comment Here

Reference: Adenocarcinoma with aberrant p63
Board review style question #2

What is the p63 stain morphology shown above expected to display?

  1. Aberrant diffuse nuclear p63 positivity
  2. Lack of ERG rearrangement
  3. Lack of PTEN loss
  4. Positive reactivity for cytokeratin 34 beta E12
  5. Reduced cancer specific survival and high grade
Board review style answer #2
E. Reduced cancer specific survival and high grade. This cytoplasmic staining is not to be confused with diffuse nuclear p63, which is the topic of this section. The cytoplasmic staining is associated with a worse outcome. B, C and D are incorrect because usual type tumors (without nuclear p63) do not necessarily show lack of ERG rearrangement or lack of PTEN loss and should have loss of basal markers such as cytokeratin 34 beta E12.

Comment Here

Reference: Adenocarcinoma with aberrant p63
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