prostatic adenocarcinoma

See also: prostate cancer

Synopsis

Prostatic adenocarcinoma shows prominent nucleoli and an increased nuclear size and N/C ratio. There is an absent basal cell layer, and glands tend to be rounded rather than tufted. Definitive features of prostatic adenocarcinoma include perineural invasion, collagenous micronodules / mucinous fibroplasia, and glomerular forms. It is negative for p63 (usually) and CK903, and positive for AMACR / racemase.

Epidemiology

Prostate cancer (CaP) is the most commonly diagnosed malignancy and the second leading cause of cancer mortality in males in the United States. The high rate of mortality is associated with widespread metastatic disease.

In 2006, about 234,460 men in the U.S. will be diagnosed with prostate cancer and nearly 27,500 deaths can be attributed to the disease each year.

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

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)

Microscopy

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 carnomas have fucised 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.

Variants

 Variants of usual acinar adenocarcinoma of the prostate (2004 World Health Organization classification)

• atrophic prostatic adenocarcinoma
• pseudohyperplastic prostatic adenocarcinoma
• foamy prostatic adenocarcinoma
• colloid prostatic adenocarcinoma (mucinous prostatic adenocarcinoma)
• signet ring prostatic adenocarcinoma
• oncocytic prostatic adenocarcinoma
• lymphoepithelioma-like prostatic adenocarcinoma

 Variants of non-acinar carcinoma of the prostate (2004 World Health Organization classification Sarcomatoid carcinoma)

• prostatic ductal adenocarcinoma
• prostatic squamous cell carcinoma and adenosquamous carcinoma
• prostatic urothelial carcinoma
• prostatic small-cell carcinoma
• prostatic basal cell carcinoma
• prostatic clear cell adenocarcinoma

 Variants of prostatic carcinoma described since the 2004 World Health Organization classification

• prostatic microcystic adenocarcinoma
• prostatic PIN-like adenocarcinoma
• prostatic large-cell neuroendocrine carcinoma
• prostatic pleomorphic giant cell adenocarcinoma
• PIN (prostatic intraepithelial neoplasia)

American Urological Society Clinical Staging

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%

Prognosis

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)

Classification

 prostatic adenocarcinomas

• classical prostatic adenocarcinomas
• prostatic adenoid cystic carcinoma / prostatic basal cell carcinoma

 prostate carcinoma with squamous differentiation (15105655)

According to androgen dependance

 androgen-dependent prostate cancer
 androgen-independent prostate cancer

Differential diagnosis

Features against the diagnosis of adenocarcinorna :
 atrophic cytoplasm
 merging in with benign glands (r/o adenosis )
 corpora amylacea
 inflammation
 adjacent PIN (r/o PINATYP )

Abnormal protein expression

 aberrant diffuse expression of p63 (18300803)

Molecular biology

 DNA microarrays: 12084220
 Proteomics: 11721637

By genes

 PTEN

• PTEN loss is associated with upgrading of prostate cancer from biopsy to radical prostatectomy. (24993522)

Genetics

 see "prostate cancer genetics"

Links

 WebPathology

Open references

 PTEN loss is associated with upgrading of prostate cancer from biopsy to radical prostatectomy. Lotan TL, Carvalho FL, Peskoe SB, Hicks JL, Good J, Fedor HL, Humphreys E, Han M, Platz EA, Squire JA, De Marzo AM, Berman DM. Mod Pathol. 2015 Jan;28(1):128-37. doi : 10.1038/modpathol.2014.85 PMID: 24993522

References

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 Anatomy of the prostate revisited: implications for prostate biopsy and zonal origins of prostate cancer. Fine SW, Reuter VE. Histopathology. 2012 Jan;60(1):142-52. PMID: 22212083

 Staging of prostate cancer. Cheng L, Montironi R, Bostwick DG, Lopez-Beltran A, Berney DM. Histopathology. 2012 Jan;60(1):87-117. PMID: 22212080

 Histological variants of prostatic carcinoma and their significance. Humphrey PA. Histopathology. 2012 Jan;60(1):59-74. PMID: 22212078

 Diagnosis of limited adenocarcinoma of the prostate. Epstein JI. Histopathology. 2012 Jan;60(1):28-40. PMID: 22212076

 The impact of the 2005 International Society of Urological Pathology (ISUP) consensus on Gleason grading in contemporary practice. Zareba P, Zhang J, Yilmaz A, Trpkov K. Histopathology. 2009 Oct;55(4):384-91. PMID: 19817888

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 Pre-neoplastic lesions of the prostate. Parkinson MC. Histopathology. 1995 Oct;27(4):301-11. PMID: 8847060

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