Prostate gland & seminal vesicles

• Atypical small acinar proliferation suspicious (ASAP) was devised to represent our inability to render an incontrovertible diagnosis of cancer within a focus of concern that generally has fewer than 2 dozen acini, less than 1 mm (Am J Surg Pathol 1997;21:1489, Urology 1998;51:749)
• A fallacy among nonpathologists is that it is an early neoplastic lesion or precancerous along with high grade prostatic intraepithelial neoplasia (HGPIN) or a precursor lesion to cancer; rather, it is already cancer or already benign - we cannot tell (Arch Ital Urol Androl 2019;91:153, Curr Urol 2017;10:199, Prostate 2019;79:195)

• In the line diagnosis, "Atypical small acinar proliferation" should be followed by words such as "suspicious for but not diagnostic of cancer"
• Atypical small acinar proliferation suspicious synonyms include focal glandular atypia (FGA) and atypical glands suspicious for cancer

• Age group overlaps with the prostate cancer population; no difference in predictive value for cancer between African Americans and non African Americans (Clin Genitourin Cancer 2017;15:e995)
• 2 - 5% of sets of needle biopsies (more rarely in transurethral resection specimens) (Pathol Case Rev 2014;19:147)

• Serum PSA, PSA density and PSA velocity in the setting of atypical small acinar proliferation suspicious was not found to be predictive of adenocarcinoma (Curr Urol 2017;10:199, Can J Urol 2017;24:8714, World J Urol 2017;35:1009)
• Low serum testosterone, present in 20% of an atypical small acinar proliferation study population, predicted benign repeat biopsy; cancer was detected in 24% of low testosterone men and 40% of eugonadal men (Asian J Androl 2018;20:15)

• Atypical small acinar proliferation is never an indication for definitive therapy
• The standard recommendation is repeat biopsy within 3 - 6 months, however, in recent studies, failure to get a repeat biopsy was noted in up to 63% (see table below); 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)
• A review of all studies through 2014 revealed, 34 - 60% of repeat biopsies show cancer following the diagnosis of atypical small acinar proliferation but the vast majority place the predictive value for cancer in the 40 - 50% range; this exceeds the approximate 25 - 30% predictive value for high grade prostatic intraepithelial neoplasia (Pathol Case Rev 2014;19:147)
• Findings in more recent studies have been largely similar:
  
  

  Study	Frequency of ASAP as worst diagnosis	Repeat biopsy rate of ASAP	Cancer rate on repeat biopsy	Rate of Gleason ≥ 7 cancer	Rate of clinically significant* cancer
  Hum Pathol 2018;79:116	5.8%	11% (included HGPIN)	42%	14%	26%
  Prostate 2019;79:195	n/a	n/a	38%
  Curr Urol 2017;10:199	n/a	37%	43%
  Int Urol Nephrol 2018;50:1	4.6%	41%	36%	9%
  Res Rep Urol 2017;9:187	1.6%	71%	83%	20%
  Urology 2017;110:161	4.4%	47%	34%	14%	8%
  Asian J Androl 2018;20:15	n/a	25%	36%
  Clin Genitourin Cancer 2017;15:e995	n/a	n/a	40%		24%
  Can J Urol 2017;24:8714	5%	20%	31%	20%
  World J Urol 2017;35:1009	n/a	n/a	65% (with 24 region bx)	36%
  Prostate Cancer Prostatic Dis 2016;19:68			34%	8%
  Prostate 2015;75:673	5.3%	50%	36%	19%	51%

  *≤ 2 cores, ≤ 50% of a tissue site with cancer and unilateral cancer only
  
  
• The predictive value of atypical small acinar proliferation plus high grade prostatic intraepithelial neoplasia is about the same as that of atypical small acinar proliferation alone or slightly higher (Pathol Case Rev 2014;19:147, Hum Pathol 2018;79:116)

• Certain histologic features that most often preclude a definitive diagnosis of malignancy:
  • Small size of the focus (70% of cases)
  • Disappearance on step levels (61%)
  • Lack of significant cytologic atypia such as nucleolomegaly (55%)
  • Associated acute / chronic inflammation (9%)
• Lack of sufficient findings for a diagnosis of cancer raises the possibility of one of many benign mimics including:
  • Atrophy, atypical basal cell hyperplasia and reactive change (Am J Surg Pathol 1997;21:1489)

Contributed by Kenneth Iczkowski, M.D.

Quantitative ASAP


Qualitative ASAP


ASAP + HGPIN



Contributed by Debra Zynger, M.D.

• AMACR (alpha-methylacyl CoA racemase, P504S) often positive but reactivity may be weaker than expected for cancer, causing hesitation in diagnosing cancer

• Prostatic basal cell stains (HMWK/cytokeratin 34βE12/CK5 cytoplasmic and p63 nuclear) often negative or retain a stray basal cell, again causing hesitation in diagnosing cancer

Atypical small acinar proliferation, suspicious for malignancy, shown in the image

1. Carries a predictive value for cancer on repeat biopsy of 15 - 25%
2. Is a precursor to invasive carcinoma
3. Usually should be diagnosed only after basal cell and AMACR immunostaining if the worst finding in a prostate needle biopsy case
4. When followed by repeat biopsy that shows cancer, the cancer grade distribution is the same as for all newly detected cancers

C. Usually should be diagnosed only after basal cell and AMACR immunostaining, unless there is definitive cancer in other sites and the additional diagnosis of carcinoma would not impact patient management. Choice A is wrong because the predictive value is closer to > 40%. Choice B is wrong because ASAP is not a precursor lesion but rather an indeterminate diagnosis. Choice D is wrong because cancer following an ASAP diagnosis is skewed toward mostly low grade cancer on repeat biopsy.

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Reference: Atypical small acinar proliferation (ASAP), suspicious for but not diagnostic of malignancy