- 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
- 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"
- 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
- 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
- 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)
Small focus of 3-5 glands
Higher mag of glands
Insufficient cytologic support
Small focus of atypical glands
Images courtesy of Dr. Kenneth Iczkowski:
Definite nuclear atypia (Fig.1)
Mild nuclear atypia (Fig.2)
Outpouchings of PIN, or invasive cancer (Fig.3)
Racemase (pink) reactivity not increased (Fig.4)
Ambiguity in interpretation of stain (Fig.5)
- P504S (alpha-methylacyl CoA racemase) often positive but reactivity may be weaker than expected for cancer, causing hesitation in diagnosing cancer
- 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
End of Prostate > Prostatic carcinoma > Atypical small acinar proliferation (ASAP), suspicious for but not diagnostic of malignancy
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