Prostate adenocarcinoma

Prostatic adenocarcinoma

Role of serum PSA testing in the clinical diagnosis

•    Used in diagnosis and management of prostate cancer

•    Produced by prostatic epithelium and secreted in semen

•    A serine protease used to cleave and liquefy the seminal coagulum produced after ejaculation

•    Only minute amounts of circulating PSA are found normally

•    Elevated levels of PSA are seen in both localized and advanced cancer

•    Serum level of 4ng/ml is considered the cut-off between a normal and abnormal value, often leading to a biopsy

•    Although PSA is organ-specific, it isn’t disease-specific and can be elevated in BPH, prostatitis, infarct, instrumentation of the prostate, or after ejaculation

•    Refinements in measurement and interpretation of PSA testing have been suggested (eg. PSA density, PSA velocity, the use of age-specific ranges, and the ratio of free to bound PSA)

•    Serial measurements of PSA have a great value in assessing response to therapy, with rising PSA values suggesting recurrent or disseminated disease

Gleason grading criteria

•    According to the Gleason grading system, prostate cancer is stratified into five grades based on glandular pattern and degree of differentiation as seen under low magnification

•    Grade1: most well-differentiated tumours; neoplastic glands are uniform and round in appearance and packed into well-circumscribed nodules

•    Grade 5: show no glandular differentiation; tumour cells infiltrate stroma in the form of cords, sheets and nests

•    Other grades fall in between (Grade 2: glands are less uniform, demonstrate infiltrating edges, nodules less circumscribed; Grade 3: complete glands that infiltrate the stroma; Grade 4: glands demonstrate fusion)

•    Tumours tend to demonstrate two predominant patterns; a primary grade is assigned to the dominant pattern and a secondary grade is assigned to the second-dominant pattern and the two scores are added to give a total score out of 10.

•    Tumours with only one pattern are given the same primary and secondary grade (ie. the grade for the pattern is doubled to give the overall score)

•    Scores range from 2 (Gleason grade 1+1), being the most well-differentiated tumours to 10 (Gleason grade 5+5), being the least differentiated tumours

•    Scores are combined into groups with similar biologic behaviours: 2-4 considered well-differentiated cancer, 5-6 considered intermediate-grade cancer, 7 considered moderate to poorly differentiated cancer, and 8-10 representing high-grade cancer

•    Gleason grade is important, since it, along with stage is the best marker to determine prognosis

Prostate cancer precursor lesions

•    Low grade PIN

-    Architecturally benign prostatic acini or ducts lined by cytologically atypical cells; basophilic appearance on low power

-    Lack of prominent nucleoli (visualized at 20x) or nuclear pleomorphism

-    Slight enlargement of nuclei and stratification
•    High grade PIN

-    Glands have a basophilic appearance due to enlarged nuclei, hyperchromatism, overlapping nuclei, amphophilic cytoplasm and epithelial hyperplasia

-    Tufting of epithelium (consisting of slight mounds of hyperplastic cytologically atypical epithelium) in a pre-existing benign gland is common

-    Nuclei project into lumen as micropapillary PIN (tall epithelial buds lacking fibrovascular cores) or as cribriform PIN

-    Nuclei toward centre of gland are more bland compared to nuclei located apposed to basement membrane (presence of nucleoli in the nuclei apposed to basement membrane qualifies the lesion as high grade PIN)
•    High grade PIN is associated with a 23-35% risk of cancer on subsequent biopsy

•    Thought that high grade PIN is a precursor to prostatic carcinoma:

-    Prostates with carcinoma (compared to those without), have an increase in the size and number of foci of HGPIN, as well as an increased incidence of HGPIN

-    With increasing amounts of HGPIN, there are a greater number of multifocal carcinomas

-    HGPIN is seen in the peripheral zone of the prostate corresponding to the site of origin of most prostatic adenocarcinomas

-    Molecular markers are shared between HGPIN and adenocarcinoma

-    HGPIN is more closely related to intermediate and high grade peripheral adenocarcinomas rather than low grade transition zone carcinomas

•    However, natural history of HGPIN is unknown; when PIN is diagnosed, there is no method to determine whether there is not already infiltrating carcinoma at that site; or when carcinoma evolves, it is unknown whether or not it has done so at the site of PIN, therefore the term CIS is not warranted at this time

•    The clinical significance of LGPIN is unclear at this time

•    Diagnosis of HGPIN warrants a sampling of the entire prostate (sextant biopsy or greater) to rule out synchronous prostatic cancer; not just at original biopsy site

Prostate precursor lesions immunohistochemistry

•    CK34βE12/p63 stain the basal cells present in PIN lesions which differentiate it from prostate cancer

•    AMACR stains the epithelial cells in PIN which distinguish it from normal prostate glands