Prostate Pathology

Return to the tutorial menu.

The Prostate Gland

The male prostate gland is located below the bladder. The seminal vesicles are located posterior to the prostate. The urethra exits from the bladder and traverses the prostate before exiting to the penile urethra.

Normal Prostate

The normal prostate is composed of glands and stroma. The glands are seen in cross section to be rounded to irregularly branching. These glands represent the terminal tubular portions of long tubuloalveolar glands that radiate from the urethra. The glands are lined by two cell layers: an outer low cuboidal layer and an inner layer of tall columnar mucin-secreting epithelium. These cells project inward as papillary projections. The fibromuscular stroma between the glands accounts for about half of the volume of the prostate.

As a male ages, there are more likely to be small concretions within the glandular lumina, called corpora amylacea, that represent laminated concretions of prostatic secretions. The glands are normally separated by stroma. The prostate is surrounded by a thin layer of connective tissue that merges with surrounding soft tissues, including nerves. There is no distinct capsule.

  1. Normal prostate gland, high power microscopic.


Acute prostatitis is not common, but is most likely to occur in young men. Causative agents include bacterial organisms similar to those causing urinary tract infections, as well as Neisseria gonorrheae. A related complication of prostatic abscess is uncommon. The edema and slight enlargement of the prostate with acute inflammation may cause acute rectal, lower back, or perineal pain along with fever. There can be dysuria. The prostate is enlarged and tender. Urine culture may be done, but prostatic massage is contraindicated. Microscopically, the glands are filled with neutrophils, and the intervening stroma may also contain a few neutrophils, explaining the presence of neutrophils on urine microscopic examination..

Chronic prostatitis may follow acute prostatitis, but is more likely to occur without prior history in older men, and may suggest an underlying obstructive urinary tract abnormality. There can be intermittent urinary frequency and dysuria. The prostate may not be enlarged. Prostatic massage may increase the yield of urine culture. Routine cultures, however, do not identify one common organism: Ureaplasma urealyticum.

Chronic abacterial prostatitis is the most common cause for prostatitis, but is difficult to diagnose from lack of specific findings. No organism can be identified as a causative agent. Symptoms of dysuria along with low grade pelvic pain or low back pain may be present. Microscopically, lymphocytes, plasma cells, and macrophages appear in the prostatic stroma.

Prostatitis can elevate the serum prostate specific antigen (PSA), but generally not more than double normal, and generally not increasing significantly over time. (Potts, 2001)

  1. Prostate, chronic prostatitis, high power microscopic.

Prostatic Hyperplasia

Nodular prostatic hyperplasia (also termed benign prostatic hyperplasia, or BPH) is a common condition as men age. Perhaps a fourth of men have some degree of hyperplasia by the fifth decade of life. By the eighth decade, over 90% of males will have prostatic hyperplasia. However, in only a minority of cases (about 10%) will this hyperplasia be symptomatic and severe enough to require surgical or medical therapy. (Bushman, 2009)

The mechanism for hyperplasia may be related to accumulation of dihydrotestosterone in the prostate, which then binds to nuclear hormone receptors which then trigger growth. The effect of drugs which act to inhibit the enzyme 5-alpha reductase, which converts testosterone to dihydrotestosterone within cells. This blocks the growth-promoting androgenic effect and diminishes prostatic enlargement. Such drugs include finasteride and episteride. Drug therapy must be continued to remain effective. (Andríole et al, 2004)

Another class of drugs used to treat BPH are the alpha 1-adrenoreceptors, including prazosin, alfuzosin, indoramin, terazosin, doxazosin, and tamsulosin. These alpha adrenergic blockers lead to relaxation of smooth muscle in prostate and help to relieve obstruction. Drug therapy must be continued to remain effective. (Auffenberg et al, 2009)

The normal prostate weighs 20 to 30 gm, but most prostates with nodular hyperplasia can weigh from 50 to 100 gm. Hyperplasia begins in the region of the veru-montanum, in the inner zone of the prostate, and extends to involve lateral lobes. This enlargement impinges upon the prostatic urethra, leading to the difficulty on urination with hesitency that is typical for this condition. Dysuria, dribbling, and nocturia are also frequent. The urinary tract obstruction leads to urinary retention and risk for infection. In severe, prolonged cases, hydroureter with hydronephrosis and renal failure can ensue. (Wasserman, 2006)

Microscopically, nodular prostatic hyperplasia consists of nodules of glands and intervening stroma. Most of the hyperplasia is contributed by glandular proliferation, but the stroma is also increased, and in rare cases may predominate. The glands may be more variably sized, with larger glands have more prominent papillary infoldings. Nodular hyperplasia is NOT a precursor to carcinoma. (Homma et al, 1996)

  1. Prostate, nodular hyperplasia, gross.
  2. Prostate, nodular hyperplasia, gross.
  3. Prostate, "chips" from transurethral resection, gross.
  4. Prostate, nodular hyperplasia, low power microscopic.
  5. Prostate, nodular hyperplasia, medium power microscopic.

Atypical Adenomatous Hyperplasia

Atypical adenomatous hyperplasia (AAH) is a term that has been utilized to describe changes histologically seen in prostatic glands in the apex, periurethral region, and/or transition zone of the prostate. AAH is a localized proliferation of small acini within the prostate. Such proliferations may be confused with carcinoma, but the glands with AAH still have a fragmented basal layer. AAH can be difficult to distinguish from hyperplasia. There is no clear association between the presence of AAH and the development of prostatic adenocarcinoma. (Helpap et al, 1995)

Prostatic Intraepithelial Neoplasia

Prostatic intraepithelial neoplasia (PIN), which is dysplasia of the epithelium lining prostate glands, is a probable precursor of prostatic carcinoma. The appearance of PIN may precede carcinoma by 10 or more years. It can be divided into low grade and high grade PIN. Low grade PIN may be found even in men in middle age. PIN does not routinely increase the serum prostate specific antigen (PSA).

PIN usually involves an acinus or a small cluster of acini, but it can be more extensive on occasion. The acini are usually medium-sized to large, with rounded borders. The partial involvement of an acinus is a helpful feature to distinguish PIN from adenocarcinoma. PIN is characterized histologically by progressive basal cell alyer disruption, loss of markers of secretory differentiation, nuclear and nucleolar abnormalities, increasing proliferative potential, increasing microvessel density, variation in DNA content, and allelic loss. Unlike adenocarcinoma, with which it may coexist, glands with PIN retain an intact or fragmented basal cell layer. (Ayala and Ro, 2007)

Low grade PIN has epithelial cells that are crowded and irregularly spaced, with nuclei that are hyperchromatic and pleomorphic, with small nucleoli. High grade PIN has even more hyperchromatism and pleomorphism, the cells are more crowded and heaped up, and nucleoli can be prominent. Immunohistochemical staining with antibody to low molecular weight keratin can help to identify the fragmented basal cell layer. Anti-androgenic drug therapy may cause regression of PIN. (Ayala and Ro, 2007)

The appearance of PIN warrants increased surveillance of the prostate for development of an invasive carcinoma because the presence of PIN that is high grade suggests an increased risk for subsequent appearance of adenocarcinoma. PIN itself is not an indication for aggressive treatment. (Lipski et al, 1996)

  1. Prostatic intraepithelial neoplasia (PIN), medium power microscopic.
  2. Prostatic intraepithelial neoplasia (PIN), high power microscopic.

Prostatic Adenocarcinoma

Adenocarcinoma of the prostate is common. It is the most common non-skin malignancy in elderly men. It is rare before the age of 50, but autopsy studies have found prostatic adenocarcinoma in 80% of men more than 80 years old. Many of these carcinomas are small and clinically insignificant. However, some are not, and prostatic adenocarcinoma is second only to lung carcinoma as a cause for tumor-related deaths among males. (Bostwick et al, 2004)

Men with a higher likelihood of developing a prostate cancer (in the U.S.) include those of older age, black race, and family history. Those with an affected first-degree relative have a much greater risk. (Bostwick et al, 2004)

Prostate cancers may be detected by digital examination, by ultrasonography (transrectal ultrasound), or by screening with a blood test for prostate specific antigen (PSA). None of these methods can reliably detect all prostate cancers, particularly the small cancers. Widespread PSA screening is not cost-effective. Men whose life expectancy is less than 10 years not pursue prostate cancer early detection because the likelihood of benefitis outweighed by the risk of harms from treatment. Men at higher risk for prostate cancer at earlier ages, including men of African American ancestry or a family history of prostate cancer in nonelderly relatives, should be provided the opportunity for informed decision making at an earlier age than average-risk men. (Wolf et al, 2010)

PSA is a glycoprotein produced almost exclusively in the epithelium of the prostate gland. In the circulation PSA may be complexed to serum proteins (complexed PSA, or cPSA) or may be free (fPSA). The cPSA and fPSA together comprise total PSA (tPSA). The tPSA is normally less than 4 ng/mL (normal ranges vary depending upon which assay is used). A mildly increased tPSA in a patient with a very large prostate can be due to nodular hyperplasia, or to prostatitis, rather than carcinoma. The fPSA correlates more closely with benign prostatic conditions than the tPSA. The cPSA has a greater sensitivity for prostatic adenocarcinomas at the low ranges of elevation. A rising tPSA is suspicious for prostatic carcinoma, even if the tPSA is in the normal range. Transrectal needle biopsy, often guided by ultrasound, is useful to confirm the diagnosis, although incidental carcinomas can be found in transurethral resections for nodular hyperplasia. (Jung et al, 2006)

Men who have findings suspicious for carcinoma on digital rectal examination and a tPSA of <4 ng/mL have a probability of cancer of at least 10%, while those with tPSA levels from 4 to 10 ng/mL have a 25% probability. Men with tPSA's above 10 ng/mL have a >50% likelihood of having a prostate cancer. (Demura et al, 1996)

Prostatic adenocarcinomas are composed of small glands that are back-to-back, with little or no intervening stroma. Cytologic features of adenocarcinoma include enlarged round, hyperchromatic nuclei that have a single prominent nucleolus. Mitotic figures suggest carcinoma. Less differentiated carcinomas have fused glands called cribriform glands, as well as solid nests or sheets of tumor cells, and many tumors have two or more of these patterns. Prostatic adenocarcinomas almost always arise in the posterior outer zone of the prostate and are often multifocal. (Pearson et al, 1996)

Prostatic adenocarcinomas are usually graded according to the Gleason grading system based on the pattern of growth. There are 5 grades (from 1 to 5) based upon the architectural patterns. Adenocarcinomas of the prostate are given two grade based on the most common and second most common architectural patterns. These two grades are added to get a final grade of 2 to 10. The stage is determined by the size and location of the cancer, whether it has invaded the prostatic capsule or seminal vesicle, and whether it has metastasized.

The grade and the stage correlate well with each other and with the prognosis. The prognosis of prostatic adenocarcinoma varies widely with tumor stage and grade. Cancers with a Gleason score of <6 are generally low grade and not aggressive. Advanced prostatic adenocarcinomas typically cause urinary obstruction, metastasize to regional (pelvic) lymph nodes and to the bones, causing blastic metastases in most cases. Metastases to the lungs and liver are seen in a minority of cases. (Gleason, 1992) (Bostwick, 1996) (Epstein, 2010)

American Urological Society Clinical Staging
StageDefinition10-year Survival
A1Incidental, <5% of volume93-98%
A2Incidental, >5% of volume, or high grade50%
B1Palpable nodule in one lobe but <1.5 cm in diameter70-75%
B2Larger palpable nodule62%
C1Invades capsule of prostate40-50%
C2Invades seminal vesicle33-39%
D1Metastases to regional lymph nodes, or extensive regional spread17-20%
D2Evident distant metastases<10%


  1. Prostate, adenocarcinoma, gross.
  2. Prostate, needle biopsy with adenocarcinoma, low power microscopic.
  3. Prostate, adenocarcinoma, low power microscopic.
  4. Prostate, adenocarcinoma, medium power microscopic.
  5. Prostate, adenocarcinoma, high power microscopic.
  6. Prostate, adenocarcinoma, with nucleoli, medium power microscopic.
  7. Prostate, adenocarcinoma, with nucleoli, high power microscopic.
  8. Prostate, adenocarcinoma, medium power microscopic.
  9. Prostate, adenocarcinoma, medium power microscopic.
  10. Prostate, adenocarcinoma, high power microscopic.
  11. Prostate, adenocarcinoma, immunoperoxidase stain with antibody to prostate specific antigen,high power microscopic.


Andríole G, Bruchovsky N, Chung LW, et al. Dihydrotestosterone and the prostate: the scientific rationale for 5alpha-reductase inhibitors in the treatment of benign prostatic hyperplasia. J Urol. 2004;172(4 Pt 1):1399-403.

Auffenberg GB, Helfand BT, McVary KT. Established medical therapy for benign prostatic hyperplasia. Urol Clin North Am. 2009;36:443-459.

Ayala AG, Ro JY. Prostatic intraepithelial neoplasia: recent advances. Arch Pathol Lab Med. 2007;131:1257-1266.

Bostwick DG. Prospective origins of prostate carcinoma. Prostatic intraepithelial neoplasia and atypical adenomatous hyperplasia. Cancer. 1996;78:330-336.

Bostwick DG, Burke HB, Djakiew D, et al. Human prostate cancer risk factors. Cancer. 2004;101(10 Suppl):2371-2490.

Bushman W. Etiology, epidemiology, and natural history of benign prostatic hyperplasia. Urol Clin North Am. 2009;36:403-415.

Demura T, Shinohara N, Tanaka M, et al. The proportion of free to total prostate specific antigen: a method of detecting prostate carcinoma. Cancer. 1996;77:1137-1143.

Epstein JI. An update of the Gleason grading system. J Urol. 2010;183:433-40.

Gleason DF. Histologic grading of prostate cancer: a perspective. Hum Pathol. 1992;23:273-279.

Helpap BG, Bostwick DG, Montironi R. The significance of atypical adenomatous hyperplasia and prostatic intraepithelial neoplasia for the development of prostate carcinoma. An update. Virchows Arch. 1995;426:425-434.

Homma Y, Kawabe K, Tsukamoto T, et al. Estimate criteria for diagnosis and severity in benign prostatic hyperplasia. Int J Urol. 1996;3:261-266.

Jung K, Lein M, Butz H, Stephan C, Loening SA, Keller T. New insights into the diagnostic accuracy of complexed and total prostate specific antigen using discordance analysis characteristics. J Urol. 2006;175:1275-1280.

Lipski BA, Garcia RL, Brawer MK. Prostatic intraepithelial neoplasia: significance and management. Semin Urol Oncol. 1996;14:149-155.

Pearson JD, Luderer, Metter EJ, et al. Longitudinal analysis of serial measurements of free and total PSA among men with and without prostatic cancer. Urology. 1996;48(6A Suppl):4-9.

Potts JM. The four categories of prostatitis: a practical approach to treatment. Cleve Clin J Med. 2001;68:389-90, 392-3, 397.

Wasserman NF. Benign prostatic hyperplasia: a review and ultrasound classification. Radiol Clin North Am. 2006;44:689-710.

Wolf AM, Wender RC, Etzioni RB, et al. American cancer society guideline for the early detection of prostate cancer: update 2010. CA Cancer J Clin. 2010;60(2):70-98.

Return to the tutorial menu.