Prostate Pathology

Objectives:

  1. Disorders of the prostate
    1. Inflammation
    2. Hyperplasia
    3. Adenocarcinoma
      1. Clinical Features, Diagnosis, Staging, Prognosis

 

Axial specimen of prostate; urethra runs through it

 

Inflammation of the Prostate

  1. Acute prostatitis: usually associated with urinary tract infection
    1. Fever, perineal pain, dysuria
  1. Chronic prostatitis – may be bacterial or abacterial – chronic inflammatory cells
  1. Granulomatous prostatitis – rare.
    1. May be ass. with BCG therapy for urothelial carcinoma

Hyperplasia

Benign Prostatic Hyperplasia(BPH)
  • 70% by age 60 years
  • Up to 90% by 70 years +
  • Age dependent process
  • African-Americans
  • Dihydrotestosterone (DHT) is synthesized in the prostate from testosterone: androgen receptors increased with age
  • Post-castration: Does not occur
  • *Not premalignant
  • LUTS: Lower Urinary Tract Symptoms

 

Pathogenesis

 

(assume production of DHT is constant)

  1. Increase in Androgen receptors in cells
  2. Stimulates production of growth factors (prostate)
  3. Prostate cells proliferate
  4. Tumor cell formed

 

Histology (of Benign Prostate Hyperplasia)

Location:

Periurethral glands:

– (L) & (R) sides (“lateral lobes”)

– Behind urethra (“median lobe”)

Anatomically the central zone is involved

 Features:

  • Firm, white, nodular
  • +/- inflammation, abscess, infarction
  • Glands/stroma/mixed

Prostate tumour:                                    Histology Gross:

             

 

Clinical Presentation (of Benign Prostate Hyperplasia)

  1. Chronic partial obstruction
  2. Urinary obstruction + Infection
  3. Acute retention
  4. Infection
  1. Bladder hypertrophy/dilatation
  2. Hydroureter/hydronephrosis (obstruction of ureter/nephrons)
  3. Chronic renal failure
  4. Pyelonephritis (kidney inflammation)

Prostatic Carcinoma

 

  1. Acinar adenocarcinoma (>95%)
  2. Prostatic ductal carcinoma
  3. Small cell carcinoma
  4. Adenoid cystic carcinoma
  5. Stromal sarcoma
 Commonest malignancy in men

Age dependent;

– (uncommon <40, 10% in 50s, 70% in 70s)

Race: Common in African Americans, African Caribbeans; “Western” populations in general

Rare in Asian poplns

 

Risk Factors:

  1. Family history – 5-11 fold increase in risk when 2 or more 1st degree relatives are affected
  1. Diet: fat and animal products
  2. Antioxidants protect
  4. Environmental (pesticides, cadmium)
  5. Age
 Others:

  • Posterior/Peripheral – majority of tumours
  • DRE – digital rectal exam may detect
  • Multifocal disease, typically
  • Yellow-white grossly, though difficult to evaluate grossly esp if low grade
Prognosis:

  • Stage: TNM

Confined to prostate: 10 years~95%

Lymph node +: 10 years=40%

 Staging

T1: clinically inapparent tumour – not detected by palpation or imaging

T2: tumour confined to prostate

T3: extraprostatic extension +/- SV invasion

T4: invades adjacent structure other than SV

eg rectum or bladder neck

 

 

Metastatic Prostatic Adenocarcinoma: spread (TNM)

  1. Direct
  2. Perineural (cancer spreading to the space surrounding a nerve)
  3. Lymphatic
  4. Haematogenous
  5. Bone:Osteosclerotic
Absence of Basal Cells in PCA

 Perineural Invasion

 Malignant

 

Grading (Prostatic Adenocarcinoma)

Donald Gleason: 1966 Minneapolis VA Hospital

  • Prostatic adenocarcinoma tends to be multifocal and heterogenous
  • More than 1 architectural pattern is usually observed
  • Gleason score is the sum of the 2 most common architectural patterns
GLEASON GRADE AND SCORE The Gleason grading system has stood the test of time

Gleason grade is based only on the architectural pattern (grades 1 to 5)

  • The most common grade is the primary grade
  • The next most common is the secondary grade
  • These grades are added to give the score (eg Grade 3 + grade 4 = Gleason score 7)

Remains one of the most important predictors of outcome in multivariate and univariate analyses

 

Prostate cancer.PNG

Immunohistochemistry

  • High MW Cytokeratins (CK 903, p63, 34BE12)
    • marker for basal cells: invasive carcinoma lacks basal cells
  • AMACR (p504s): alpha methylacyl coenzyme A racemase (a serine protease)
  • Prostate Specific Antigen (PSA): only if there is doubt about the diagnosis
  • Ki67 – not helpful

    

Prognosis

Three factors are important in predicting prognosis and are combined in clinical nomograms to predict outcome:

  1. Gleason score
  2. Clinical stage (based on DRE and/or imaging
    1. Serum PSA at diagnosis (Prostate Specific Antigen)
      1. Screening (somewhat controversial)
      2. Monitoring response to therapy
      3. Prediction of outcome
      4. Detection of recurrences
    2. PSA screening has led to an increase in the detection of small volume, early cancers
    3. The incidence of prostatic cancer may therefore be “higher” in countries where serum PSA testing is widely available
      • Caution must be used in interpreting serum PSA values
    4. A level above 4ng/ml is considered “abnormal” in many centres
    5. However, this is not specific for cancer – elevation of PSA can occur in infection, inflammation, following surgical procedures, even ejaculation
      • It increases with age and with BPH
      • 4-10 ng/ml is a “grey-zone”

 

PSA   (determining significance)

Consider:

      1. PSA velocity – rate of rise on repeat testing
      2. PSA density – ratio of serum PSA to gland volume by imaging
      1. Free and bound PSA – lower free PSA ass. with higher risk of cancer
      2. Age-specific reference ranges

 

 

Prostatic Intraepithelial Neoplasia (PIN)

“In situ neoplasia”

Cellular atypia within pre-existing prostatic ducts & glands with cytologic features mimicking adenocarcinoma, but without stromal invasion

Because PIN satisfies almost all the requirements for a premalignant condition, high-grade PIN (HGPIN) is widely accepted as a precursor to prostate cancer. (Adenocarcinoma)

→ Cancer on follow-up biopsy: 16 – 20%

      • High Grade PIN (HGPIN) is reproducible
      • Low grade PIN lacks inter-observer agreement
Atypical Small Acinar Proliferation (ASAP)

  1. Needle biopsy: small focus of glands that have some but not all of the features of malignancy
  1. Immunohistochemistry does not clarify: A diagnosis of uncertainty
    1. Up to 40% of such cases will have carcinoma on repeat biopsy
  2. Therefore close follow-up is warranted
“Insignificant tumour”

  • Biopsy positive for Carcinoma, PSA<10ng/ml,
  • Clinically confined to prostate
  • Microscopic focus of tumour, not more than Gleason score 6, on only 1 core

50% chance of tumour volume <0.5cc at time of diagnosis
“Insignificant tumour”

  • Active surveillence – i.e
    • Follow PSA
    • Repeat biopsy
    • Intervene promptly if progression occurs
  • Significant risk of complications with radical prostatectomy
    • urinary incontinence and erectile dysfunction
  • Active surveillance now being considered for Gleason 7 (3+4); originally only for Gleason 6(3+3)
Prostatic adenocarcinoma

Tumour Grade Groups based on prognosis

  1. Gleason score 6(3+3) – Grade group 1
  2. Gleason score 7(3+4) – Grade group 2
  3. Gleason score 7(4+3) – Grade group 3
  4. Gleason score 8(4+4) – Grade group 4
  5. Gleason score 9 &10 – Grade group 5