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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.
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 later 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.
Acute prostatitis is not common. 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 do not generally cause major symptomatology, but may be associated with some dysuria. Microscopically, the glands are filled with neutrophils, and the intervening stroma may also contain a few neutrophils.
Chronic prostatitis may follow acute prostatitis. In some cases, bacterial organisms can be cultured from urine that indicate the etiology. In other cases, chlamydial organisms may be the cause. In some cases, 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 stroma.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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 over half 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.
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.
The PSA is normally less than 4 µg/L (normal ranges vary depending upon which assay is used). A mildly increased PSA (4 to 10 µg/L) in a patient with a very large prostate can be due to nodular hyperplasia, or to prostatitis, rather than carcinoma. A rising PSA (more than 0.75 µg/L per year) is suspicious for prostatic carcinoma, even if the PSA 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.
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.
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. 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.
| Stage | Definition | 10-year Survival |
|---|---|---|
| A1 | Incidental, <5% of volume | 93-98% |
| A2 | Incidental, >5% of volume, or high grade | 50% |
| B1 | Palpable nodule in one lobe but <1.5 cm in diameter | 70-75% |
| B2 | Larger palpable nodule | 62% |
| C1 | Invades capsule of prostate | 40-50% |
| C2 | Invades seminal vesicle | 33-39% |
| D1 | Metastases to regional lymph nodes, or extensive regional spread | 17-20% |
| D2 | Evident distant metastases | <10% |
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