Материал: Advanced Imaging of the Abdomen - Jovitas Skucas

Ultrasonography detects hyperechoic prostatic foci. Seminal vesiculography outlines the dilated lumen and irregular border. After therapy the prostate decreases in size and the hyperechoic foci become less evident. Some investigators believe that calcifications also diminish.

In endemic regions the presence of typical calcifications is presumptive evidence for schistosomiasis.

Prostatic aspergillosis is rare in a immunocompetent patient. It is associated with recurrent urinary tract infections.

Brucellar prostatitis is rare even in brucel- losis-endemic regions, such as certain provinces of Spain. Ultrasonography is useful to follow therapy.

Malacoplakia

Prostatic malacoplakia is a granulomatous inflammatory disorder, presumably being a variant of chronic granulomatous prostatitis. Prostatic malacoplakia can form fistulas to adjacent structures. It often mimics a malignancy and some affected men have undergone a radical prostatectomy for suspected carcinoma.

Past urinary tract infections are a common precedent.

Ultrasonography revealed a hypoechoic peripheral zone tumor in three men with prostatic malacoplakia (15).

A biopsy should provide the diagnosis by detecting Michaelis-Gutmann bodies, although even a biopsy can be misdiagnosed as a carcinoma.

Tumors

Sclerosing Adenosis

Sclerosing adenosis usually develops in a setting of prostatic gland hyperplasia. Even histologically, this entity is difficult to differentiate from a well-differentiated adenocarcinoma.

ADVANCED IMAGING OF THE ABDOMEN

cysts. Müllerian duct cysts tend to project somewhat lateral to the midline, while utricle cysts are midline structures; müllerian duct cysts tend to be larger and extend further superiorly, while utricle cysts tend to be small. However, considerable overlap exists and these cysts cannot be readily differentiated from each other. A rare müllerian duct cyst is associated with prostatitis.

A dilated utricle is associated with hypospadias and testicular abnormalities. Some utricle cysts lead to dysuria. They vary in size. Urography and US simply detect a retrovesical cyst.

An occasional midline prostatic cyst is a cystadenoma or a simple cyst, but not all prostatic cysts are benign. A rare one is a prostatic cystic adenocarcinoma, often in a young man.

Clinically most prostatic cysts are asymptomatic,although an occasional larger one leads to bladder outlet obstruction or becomes infected.

Magnetic resonance reveals prostatic cysts similar to other fluid-filled structures; namely, they are hypointense on T1and hyperintense on T2-weighted images. Blood and other fluid modify these findings.

Prostatic cysts are amenable to transrectal puncture and drainage under US guidance. A müllerian duct cyst causing ejaculatory duct obstruction was drained transurethrally using US guidance (16).

Benign Neoplasm

Benign prostatic neoplasms are almost nonexistent, and most reported ones are anecdotal. No imaging features differentiate them from malignancies.

A schwannoma within the prostate ranges from a focal tumor to an enlarged prostate. Transrectal US identified one as a hypoechoic nodule in the periphery (17); specific diagnosis could be established only by biopsy.

Prostate involvement in neurofibromatosis is rare. Endorectal coil MR localizes and provides guidance for biopsy of suspicious tumors.

Prostatic and Müllerian Cysts

Prostatic cysts are uncommon. Embryologically, many of these cysts represent either an enlarged prostatic utricle or a cystic müllerian duct; both tend to be located close to the midline, which helps differentiate them from the more laterally located seminal vesicle and ejaculatory duct

Prostate Carcinoma

Primary

Clinical Aspects

General: In the West, prostatic cancer is the most commonly diagnosed cancer in men. For

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unknown reasons, the relative incidence appears to be increasing in both Europe and North America. Only part of this increase is explained by improved diagnosis. One factor influencing results is that the number of prostate T1a–b cancers has declined considerably, with the decline probably due to less frequent use of surgical prostatectomy for treating BPH. At least in the United States a rise and fall in prostate cancer detection rates occurred in the 1990s, believed by some to represent primarily a removal of previously undetected T2 cancers from the prostate cancer pool due to improved screening, leaving behind mostly undetected T1c cancers as a residual reservoir (18). Among men treated with a radical prostatectomy for clinical stages T1c to T2c from 1988 to 1996, T1c cancers increased from 10% in 1988 to 73% in 1996, cancers confined to the prostate increased from 40% to 75%, and transition zone cancers increased from 10% to 21% (18); on the other hand, seminal vesicle invasion decreased from 18% to 5%, positive surgical margins decreased from 30% to 14%, and the mean patient age decreased from 65 to 62 years.

Unlike many other cancers, prostate cancer has a wide spectrum of activity, and a number of these cancers do not result in serious morbidity and mortality. Especially welldifferentiated ones tend to be quiescent for considerable time, although the current concept is that prostatic cancers progress. Some investigators assume a simplistic division of prostatic cancers into indolent ones that are unlikely to progress and those that result in extensive morbidity and mortality. Probably a more realistic assumption is a continuous spectrum containing two peaks. Thus although prostate cancer is quite common in elderly men, it is difficult to predict in any one individual whether the cancer will progress or not. Extrapolating findings from an autopsy study of prostates containing a clinically undetected carcinoma, carcinomas remaining clinically insignificant throughout life tend to have long doubling time, while those that become clinically significant are likely to have doubling times of several years or less; thus knowledge of a tumor doubling time in an elderly patient could provide clinical guidance.

In men at a mean age of 64 years, the Association Française d’Urologie estimates a 43% histologic prevalence of prostate cancer and that it

takes about 12 years for a 0.5-cc cancer to reach a volume of 4cc, a size associated with the risk of distant metastases (19); without therapy, a localized cancer diagnosed before age of 65 years results in a survival of less than 30%. Complicating matters, even with therapy prostate cancer diagnosed before the age of 50 years is associated with <50% survival at 5 years; many of these men already have metastases at initial diagnosis.

Most prostatic carcinomas originate in the prostatic gland periphery. With growth, the tumor invades the surrounding structures, including the rectum. Thus occasionally an invasive prostatic carcinoma presents with rectal bleeding.

One patient with prostate cancer developed disseminated intravascular coagulopathy (20); the authors postulated the release of procoagulation substances during diagnostic or therapeutic procedures.

Etiology: A study combining data from several French urologic centers concluded that clusters in families (familial) account for 15% to 25% of prostate cancers and hereditary forms were evident in 5% to 10% (21). In addition to such an inherited trait, having an autosomal-dominant mode with variable penetrance, environmental factors also have a role,and in some of these men a purely environmental influence is evident.Carriers of a germline mutations in the BRCA1 gene on chromosome 17q appear at increased risk for prostate cancer. In general, a hereditary influence is more evident in those who develop prostate cancer at a younger age. No major pathologic differences exist between the hereditary and sporadic forms of cancer.

Applying familial cancer data to clinical practice, the Association Française d’Urologie estimates that, compared to the general population, a family history (first-degree relative) of prostate cancer is associated with a twoto threefold increased risk of prostatic cancer (19); such a familial association thus defines a highrisk group for screening.

Schistosomiasis is associated with bladder, rectal, and renal cancers. No definite association with prostate cancer is established, although prostate cancer is occasionally reported in young men with schistosomiasis.

Although adenomatous hyperplasia appears intermediate between BPH and a welldifferentiated carcinoma, suggesting that it is a

possible precursor for carcinomas arising in the transition zone, BPH is not considered to be a precursor to prostatic cancer. Likewise, in spite of some earlier reports, no definite association exists between prior vasectomy and prostate cancer.

Screening: Screening for prostatic cancer is controversial. In the United States and some European countries routine physical examination of men at risk (generally considered to be those over age 50 years) include a digital rectal examination and determination of serum prostate-specific antigen (PSA) level. In some countries PSA testing is not routinely performed, the reasoning being that its use in screening results in overdiagnosis and overtreatment. Also, some believe that no firm evidence exists that early diagnosis decreases mortality. In addition, because of the prolonged time course of prostatic cancer growth in some men, whether cure in the higher surgical risk group really represents the best option is also questioned. Some physicians believe that PSA testing is not usually indicated in men over about 70 years unless digital examination suggests prostatic disease; another viewpoint is that in those with a life expectancy greater than of 10 to 15 years an elevated PSA level is an indication for US and biopsy. Nevertheless, in countries with extensive screening, evidence suggests that an earlier diagnosis has an impact on this cancer, and the number of men seen with advanced disease decreases.

In the United States, the recommended frequency for PSA screening for prostate cancer is every year, although an optimal interval has not been established. A Rotterdam study, in which 4133 men, aged 55 to 75 years, underwent PSA screening initially, again 4 years later in over half the subjects, and, when indicated, a needle biopsy was performed, found that initially 36% of the cancers detected had a Gleason score of 7 or higher but only 16% of those detected 4 years later had such an elevated score (22); initially 25% of the cancers detected had adverse prognostic features, but only 6% of those detected 4 years later did, and the authors concluded that most large prostate cancers are detected by PSA screening and, among these men, a screening interval of 4 years appears to be short enough to prevent large tumors from developing.

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A serum PSA level of up to 4 nanograms per milliliter is commonly assumed to be within the normal range, although this level is arbitrary, and a number of men with a lower PSA level have developed prostatic cancer. Of interest is that many of these tumors are also not detected by endorectal US and digital rectal examination.

The production of PSA is influenced by androgen levels, and those taking drugs for androgen suppression have low PSA levels even in the presence of a prostatic carcinoma. False serum positive PSA levels are uncommon when using a monoclonal assay. The PSA levels are elevated in some men with urinary tract infection but decline as infection clears; this marker thus appears useful in following infection progression. The PSA level is also increased with some nonprostatic neoplasms, including some lymphomas.

A digital rectal screening examination detects two thirds to three quarters of prostatic cancers. In general, the sensitivity of the PSA assay is higher than either digital rectal examination or endorectal US. When combining serum PSA levels and digital rectal examinations for screening, some cancers are detected because of an elevated PSA level only. A high proportion of these men will have a nonpalpable prostate cancer, and endorectal US is appropriate in this population.

About 40% to 50% of hypoechoic foci identified by endorectal US are cancerous. These percentages can be improved; thus a majority of hypoechoic foci in men with a PSA >10ng/mL are positive for cancer, but in those with a PSA £4ng/mL only a small minority are positive.

What is the effect of instituting PSA screening and sextant biopsies on prostate cancer detection? From serum stored in Göteborg, Sweden, in 1980, PSA was analyzed for 658 men born in 1913 with no previously known prostate cancer (23); among those found to have a PSA level of >3ng/mL, the mean time from increased PSA to an eventual clinical diagnosis of prostate cancer was 7 years. Thus screening 67-year-old men should lead to cancer detection and treatment a mean of 7 years before clinical symptoms develop.

In summary, in asymptomatic men a screening digital rectal examination together with a

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serum PSA level detects more prostate cancer and at an earlier stage than a digital rectal examination alone. Currently endorectal US is not sufficiently sensitive and specific to be used for routine screening for prostate cancer. Nevertheless, a basic question remains: Are the additional cancers detected with a screening program mostly latent ones of limited future significance or do they represent those that will progress and, if untreated, metastasize?

A number of PSA-related tests have been investigated: serum PSA level, age-adjusted PSA level, PSA density, PSA velocity and a ratio of free-to-total PSA. In blood, PSA is either free or bound to proteins. PSA associated with prostate cancer tends to be more protein-bound and thus the ratio of free-to-bound PSA appears of some value in estimating cancer risk. A PSA agecorrected level is often used in screening programs. The rationale is that it will detect younger patients with potentially curable prostate cancer and identify those older patients not requiring additional tests.

The ratio of free to total PSA varies with prostate volume, but this ratio is of limited use in differentiating benign from malignant disease. It appears to have a role with a serum total PSA level between 4 and 10ng/mL, and some authors suggest the use of this ratio in men with a total PSA level between these levels as an indicator of whether to biopsy or not, yet the cutoff ratio used influences the resultant sensitivity and specificity. The specificity can be improved, but at decreased sensitivity (i.e., fewer cancers detected). Currently this ratio is not commonly employed as an initial guide about whether to biopsy.

Serum PSA levels increase with prostate volume. Thus rather than relying on an absolute serum value, a PSA density value appears useful, defined as serum PSA level divided by prostatic gland volume as measured by rectal US and expressed in nanograms per milliliter per milliliter of tissue. Theoretically, PSA density compensates for the gradual increase in PSA level due to gland growth with age. A PSA density value is most useful in men with a normal digital rectal examination and a PSA level between 4 and 10ng/mL, although some authors deem such density measurements unreliable. In men with a PSA level >10ng/mL, the PSA density is of even less significance.

A variant of the above is to use the PSA value adjusted for prostate transitional zone volume. This PSA transition zone density is obtained by dividing the PSA value by the transition zone volume. A change in PSA blood level over time is known as PSA velocity and is expressed as a PSA increase per year. Although men with BPH also have an increase in PSA level with age, those with cancer have a more logarithmic increase. The PSA velocity is of less use in patients with an elevated PSA level and negative biopsy.

Pathologic Study

Adenocarcinoma accounts for about 95% of all prostatic malignancies. Mucinous adenocarcinomas of the prostate are uncommon, and their prognosis is worse than that of a more typical adenocarcinoma. A rare papillary cystadenocarcinoma has been reported; cyst aspiration yields a very high PSA level. An adenoid cystic carcinoma is a variant of a prostatic adenocarcinoma; some of these are associated with a normal PSA level even in the face of spread.

Of the rest, transitional cell carcinoma predominates, followed by an occasional squamous cell carcinoma, small cell carcinoma, sarcoma, and metastasis to the prostate. Primary squamous cell carcinomas and sarcomatoid carcinoma have developed in previously treated adenocarcinomas, although a sarcomatoid carcinoma can originate de novo (24). A rare prostatic carcinoma contains endometrioid features; both PSA and CEA levels tend to be elevated. These are rather aggressive cancers. A curiosity is one malignancy metastasizing to another malignancy. Thus prostate carcinomas have metastasized to renal cell carcinomas.

Occasionally a biopsy reveals prostatic intraepithelial neoplasia without an adenocarcinoma. This neoplasia, considered a precursor of prostate cancer, is subdivided into high grade and low grade; high-grade intraepithelial neoplasia is believed to be premalignant and a strong predictor of later cancer, while the lowgrade variety tends to behave like BPH and is associated with a low risk of carcinoma. Abnormal growth factor receptors and general genetic instability are associated findings with prostatic intraepithelial neoplasia. A biopsy finding of

high-grade intraepithelial neoplasia without evidence of a carcinoma generally should be followed by additional biopsies. One should also keep in mind that some prostatic intraepithelial neoplasias are difficult to differentiate from cancers based on cytologic material.

A finding of neuroendocrine tumor cells is not uncommon in prostate cancers and presumably reflects different stem cell evolution. In distinction to androgen-responsive prostate cancer cells, these neuroendocrine tumor cells lack androgen receptors and are androgen insensitive.

Prostate carcinomas are graded using either the Gleason or World Health Organization (WHO) grading systems (with nucleolar subgrading). In the United States the Gleason grading system is more widely used. At least for relatively advanced primary tumors the Gleason grading system appears superior in predicting prognosis than the WHO grading system (25).

In the Gleason system the tumor glandular pattern is evaluated and the two most common patterns graded from 1 to 5. These primary and secondary patterns are then combined to obtain a Gleason score. A score of 2 signifies a well-differentiated tumor and 10 is a highly malignant one. In general, a biopsy Gleason score correlates with resected prostate specimen Gleason score. Paired biopsies and prostatectomy specimens from clinically localized prostate cancers revealed exact score agreement in 57% and a difference of ±1 unit in 92% of the paired samples and predicted tumor stage (26); with minimal tumor size on a biopsy, however, the Gleason score does not predict tumor stage.

A less often used grading system is based on an estimate of mean nuclear volume, developed by Gunderson and Jensen. In some hands this system is prognostically superior to the Gleason system.

Cytometry of the DNA is useful in some patients. Thus a finding of a constant diploid and tetraploid pattern with DNA cytometry identifies those who are at little or no significant risk of tumor progression even without therapy (27); men with a DNA tetraploid histogram may deteriorate with hormonal therapy. A DNA aneuploid pattern suggests that a cancer may not respond to hormonal therapy.

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A xanthoma is a localized collection of cholesterol-filled histiocytes. Most are idiopathic, although some develop in a setting of hyperlipidemia. Their importance is that occasionally a xanthoma biopsy suggests a carcinoma; confusing the issue, xanthomas have been reported adjacent to foci of adenocarcinoma. A foamy gland carcinoma contains xanthomatous cytoplasm but lacks the nuclear enlargement and prominent nucleoli associated with a carcinoma.

Detection

Currently the most common initiator for a search for prostate carcinoma is a screening finding of an elevated PSA level. Examinations used in prostate cancer detection include digital rectal examination, endorectal US, MRI, and US-guided transrectal biopsy. Each of these procedures has its limitations. In general, the detection rate for prostate carcinoma increases when these procedures are used in combination.

Computed Tomography: Nonhelical CT detects an enlarged gland but cannot distinguish between BPH and a neoplasm. Carcinoma is suggested only by an irregular contour outline. Helical CT, on the other hand, identified cancer in 88% of patients as peripheral zone regions of contrast enhancement (28); transitional zone cancers, on the other hand, appear similar to benign nodules.

Ultrasonography: Most peripheral zone carcinomas are hypoechoic, a nonspecific finding because a number of benign conditions are also hypoechoic. If a tumor is hypoechoic and also palpable, the probability of carcinoma is about 75%. Hyperechoic prostatic cancers are less common. They tend to be large when first detected. The least common are isoechoic ones. Common US criteria used to suggest a prostate cancer are the presence of a peripheral zone hypoechoic nodule, peripheral zone inhomogeneity, and loss of zonal architecture.

Adenocarcinomas originating in the transition zone are usually not detected with US.

Endorectal US provides more information than a transabdominal approach. Nevertheless, to put US in perspective, based on data from sextant biopsies, in one study overall agreement