Encyclopedia of Pathology

Living Edition
| Editors: J.H.J.M. van Krieken

Atypical Small Acinar Proliferation

  • Alessia Cimadamore
  • Silvia Gasparrini
  • Rodolfo MontironiEmail author
Living reference work entry
DOI: https://doi.org/10.1007/978-3-319-28845-1_4782-1



Atypical Small Acinar Proliferation (ASAP) suspicious for, but not diagnostic of, adenocarcinoma (Epstein and Herawi 2006; Montironi et al. 2006).

Clinical Features

  • Incidence

    5% of prostate biopsies

  • Age

    The same age as prostate cancer (mean 65.8 years (Range 44–80)).

  • Sex


  • Sit

    All prostate zones.

  • Treatment

    Definitive therapy (either surgical or nonsurgical) discouraged. Repeat biopsy and follow-up (Borboroglu et al. 2001).

  • Outcome

    Risk of detection of carcinoma on needle core re-biopsy: 40%.


  • Focus of small size.

  • Small acinar proliferation.

  • Small number of cells with enlarged nucleoli.

  • No basal cells in the initial H&E-stained sections (Egevad et al. 2006; Epstein 1998; Epstein and Herawi 2006; Montironi et al. 2006).


Basal cell markers and racemase: The former are absent in prostate cancer and the latter is expressed in 80% of cancers (See differential diagnosis and specific items) (Fig. 1).
Fig. 1

(a, b) Prostate tissue with small focus of atypical glands

Molecular Features

See prostate cancer

Differential Diagnosis

Common Differential Diagnosis

  • Prostatic adenocarcinoma. The presence of ASAP in a biopsy is a strong predictor for subsequent cancer. Immunostains such as p63 and high molecular weight cytokeratin that is detected by antibody 34βE12 can aid in the investigation of ASAP by staining basal cells. Cancer lacks a basal cell layer. Therefore, the presence of basal cells in ASAP excludes cancer. Conversely, the absence of a basal cell layer supports the diagnosis of cancer. Using immunohistochemical staining, racemase is strongly and diffusely positive in 97–100% of prostate cancers.

  • Atrophy, especially post-atrophic hyperplasia. Simple atrophy appears as a well-circumscribed area of around a central dilated duct. Immunohistochemical stains for basal cell markers (See above) show staining of the basal cells in the glands of simple atrophy and post-atrophic hyperplasia, ruling out cancer. Alpha-methylacyl coenzyme A racemase (AMACR) is negative in simple atrophy and uncommonly expressed in post-atrophic hyperplasia

  • Basal cell hyperplasia. A spectrum of benign basal cell proliferations ranging from hyperplasia to carcinoma exists. These are usually located in the transition zone. Demonstration of strong immunoreactivity for basal cell markers and lack of AMACR can be useful to confirm the diagnosis of basal cell hyperplasia.

  • Seminal vesicles/ejaculatory ducts. Both are characterized by branching glandular structures, often with numerous small glands. The presence of nuclear hyperchromasia, with smudged chromatin and scattered pleomorphic cells beyond what is seen in acinar PCa, as well as the presence of lipofuscins, occasional intranuclear inclusions, and, in the case of the seminal vesicle, a muscular wall, are all helpful clues leading toward the correct final diagnosis. Difficult cases can be resolved by immunohistochemistry, because seminal vesicle and ejaculatory duct epithelium are usually PSA negative and the epithelial structures are surrounded by basal cells.

Less Common Differential Diagnosis

  • Adenosis. It is characterized by a nodular proliferation of closely packed, small glands that often merge with larger glands. The glands of adenosis exhibit strong positivity for PSA. Up to 18% of cases express AMACR. Immunohistochemical staining demonstrates absence of basal cells in about one-half of all glands.

  • Cowper’s glands. The duct-acinar architecture, cytoplasmic mucin, and lack of cellular atypia distinguish Cowper’s glands from ASAP. In difficult cases, special stains for mucin (mucicarmine, PAS-D) may be used. Cowper’s glands show variable staining results for PSA; however, they are negative for PAP.

  • Nephrogenic adenoma. Papillary structures, small tubules, or cystically dilated tubules lined by cuboidal, low columnar, or hobnail-shaped eosinophilic cells are present. Lesions predominantly composed of small tubules are those most likely to be confused with ASAP and with urothelial carcinoma with small tubules. This is confounded by nephrogenic adenoma being negative for basal cell markers and not infrequently positive for AMACR, PSA by IHC. The characteristic histomorphological and immunohistochemical features, possibly supplemented by positive PAX2 and/or PAX8 immunostains, both described specific markers for NA, can be used to arrive at the correct diagnosis.

  • Verumontanum mucosal gland hyperplasia. It is characterized by a proliferation of uniform, well-circumscribed, closely packed, rounded glands that usually contain eosinophilic secretions. These glands are cytologically bland, and basal cells are usually identified with ease.

References and Further Reading

  1. Borboroglu, P. G., Sur, R. L., Roberts, J. L., & Amling, C. L. (2001). Repeat biopsy strategy in patients with atypical small acinar proliferation or high grade prostatic intraepithelial neoplasia on initial prostate needle biopsy. The Journal of Urology, 166, 866–870.CrossRefGoogle Scholar
  2. Egevad, L., Allsbrook, W. C., & Epstein, J. I. (2006). Current practice of diagnosis and reporting of prostatic intraepithelial neoplasia and glandular atypia among genitourinary pathologists. Modern Pathology, 19, 180–185.CrossRefGoogle Scholar
  3. Epstein, J. I. (1998). Atypical small acinar proliferation of the prostate gland. American Journal of Surgical Pathology, 22, 1430–1431.CrossRefGoogle Scholar
  4. Epstein, J. I., & Herawi, M. (2006). Prostate needle biopsies containing prostatic intraepithelial neoplasia or atypical foci suspicious for carcinoma: Implications for patient care. Journal of Urology, 175, 820–834.CrossRefGoogle Scholar
  5. Montironi, R., Scattoni, V., Mazzucchelli, R., Lopez-Beltran, A., Bostwick, D. G., & Montorsi, F. (2006). Atypical foci suspicious but not diagnostic of malignancy in prostate needle biopsies (also referred to as “atypical small acinar proliferation suspicious for but not diagnostic of malignancy”). European Urology, 50, 666–674.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Alessia Cimadamore
    • 1
  • Silvia Gasparrini
    • 1
  • Rodolfo Montironi
    • 1
    Email author
  1. 1.Institute of Pathological Anatomy and HistopathologyPolytechnic University of the Marche Region (Ancona)AnconaItaly