Prostate
Prostatic carcinoma
Atypical small acinar proliferation (ASAP), suspicious for but not diagnostic of malignancy

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

Revised: 8 August 2016, last major update March 2015

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

PubMed Search: Atypical small acinar proliferation [title] prostate
Definition / General
  • ASAP represents our inability to render an incontrovertible diagnosis of cancer within a focus of concern that invariably has fewer than 2 dozen acini - less than the size of the head of a pin (Am J Surg Pathol 1997;21:1489)
  • Most ASAP foci have ≤ 5 acini (see Fig. 1 in Micro images below)
  • Some ASAP foci have > 5 acini, yet the cytologic features of nuclear enlagement, prominent nucleoli, and basal cell absence are all equivocal, preventing a definite cancer diagnosis (see Fig. 2)
  • The histologic features that most often preclude a definitive diagnosis of malignancy are the small size of the focus (70% of cases), disappearance on step levels (61%), lack of significant cytologic atypia such as nucleolomegaly (55%), and associated inflammation (9%), raising the possibility of one of many mimics of adenocarcinoma (Am J Surg Pathol 1997;21:1489)
  • A subset of ASAP diagnoses occur in conjunction with adjacent high-grade prostatic intraepithelial neoplasia (HGPIN) (Hum Pathol 2001;32:389)
    • This raises the special problem of an inability to separate tangential cutting of medium-sized pre-existing outpouchings of HGPIN from the usually smaller discrete acini of cancer (see Fig. 3)
    • In such cases, we prefer the term ASAP + HGPIN to avoid over-diagnosis of tangentially-cut outpouchings of HGPIN as cancer
    • ASAP is placed first owing to its stronger predictive value for subsequent cancer
Terminology
  • ASAP synonyms include Focal Glandular Atypia (FGA) and Atypical glands suspicious for cancer
  • In the line diagnosis, "Atypical small acinar proliferation" is incomplete without adding the words, "suspicious for but not diagnostic of malignancy"
Epidemiology
Diagnosis
  • In order to diagnose ASAP, ask yourself:
    • "Would you remain absolutely confident of this biopsy diagnosis if it were followed by a negative radical prostatectomy?"
    • "Are you certain there would be diagnostic agreement for cancer if your work got audited by another pathologist?"
    • "Can the findings in this one core alone support an overall confident diagnosis of cancer for the case?"
  • If these questions cannot be answered in the affirmative, ASAP is the suitable diagnosis
Treatment
  • Taking all studies into account, 34% to 60% of repeat biopsies showed cancer following the diagnosis of ASAP, but the vast majority place the predictive value for cancer in the 40%-50% range (Pathol Case Rev 2014;19:147)
  • ASAP is never an indication for radical prostatectomy or definitive therapy
  • Repeat biopsy is strongly recommended
  • One recommendation (regardless of serum PSA) is to sample 3 cores from the site of the initial atypical sextant site, 2 cores from the adjacent atypical sextant sites; and 1 core from other sextant sites (Mod Pathol 2004;17:307)
  • The predictive value of ASAP + HGPIN is about the same as for ASAP alone
Micro Description
  • The histologic features that most often preclude a definitive diagnosis of malignancy are the small size of the focus (70% of cases), disappearance on step levels (61%), lack of significant cytologic atypia such as nucleolomegaly (55%), and associated inflammation-either acute or chronic (9%), raising the possibility of one of many mimics of adenocarcinoma such as atrophy or reactive acini (Am J Surg Pathol 1997;21:1489)
Micro Images

Images hosted on other servers:

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Small focus of 3-5 glands

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Higher mag of glands

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Insufficient cytologic support

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Small focus of atypical glands



Images courtesy of Dr. Kenneth Iczkowski:

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Definite nuclear atypia (Fig.1)

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Mild nuclear atypia (Fig.2)

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Outpouchings of PIN, or invasive cancer (Fig.3)

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Racemase (pink) reactivity not increased (Fig.4)

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Ambiguity in interpretation of stain (Fig.5)

Positive Stains
  • P504S (alpha-methylacyl CoA racemase) often positive but reactivity may be weaker than expected for cancer, causing hesitation in diagnosing cancer
Negative Stains
  • Prostatic basal cell stains (cytokeratin 34βE12-cytoplasmic and p63-nuclear) often negative or retain a stray basal cell, again causing hesitation in diagnosing cancer (see Fig. 5)
  • Staining for these 3 antigens separately or simultaneously using two different colored chromogens can, under ideal conditions, resolve up to 76% of ASAPs per consensus of 3 urologic pathologists studied (Histopathology 2004;45:218)
  • However, quite often immunostains cannot resolve a diagnostic dilemma but will support or reinforce a diagnosis of ASAP