Male Reproductive

• Prostate Histology

  Prostate gland is a retroperitoneal organ encircling neck of bladder and urethra.

  In a healthy male, it weighs about 20g

  4 zones:

  • Peripheral
  • Central
  • Transitional
  • Anterior fibromuscular stroma

  Types of Proliferative Lesions

  1. Inflammation
  2. Benign Prostatic Hyperplasia (Transitional)
  3. Prostatic Carcinoma (Peripheral)
• BPH: benign prostatic hyperplasia (or hypertrophy), an enlargement of the prostate gland common in elderly men.
• BPH is related to action of androgens. Dihydrotestosterone (DHT), a metabolite of testosterone, is the ultimate mediator of prostatic growth.

  • It is synthesised in prostate and located primarily in stromal cells and can diffuse into nearby epithelial cells.
  • In both cells, DHT binds to nuclear androgen receptors and signals the transcription of growth factors that are mitogenic to epithelial and stromal cells
  • Oestrogen also appears to play a role
  • Not all patients benefit from androgen-depriving therapy -> May be other causative factors
• Histology:

  On a cross-section of prostate, the nodules are fairly readily identified.

  • Nodules that are primarily glandular in make-up = soft/yellow-pink
  • Nodules that are primarily stromal in make-up = hard, pale grey and less clearly demarcated from surrounding tissue

  Microscopically, the hallmark of BPH is nodularity due to glandular proliferation and to fibrous or muscular proliferation of the stroma
• BPH Symptoms:

  • compression of urethra with difficulty urinating
  • Retention of urine in bladder
• BPH Treatment:

  • Alpha1-blockers - decrease smooth muscle tone by inhibiting androgenic receptors
  • DHT Inhibitors - physically shrinks prostate
  • TURP (Transurethral Resection of the Prostate) - mod-severe cases that do not respond to therapy. -> shaving of the cells within the prostate
• Prostate Cancer:

  Adenocarcinoma most common in men.

  • second leading cause of cancer death
  • typically >50
  • men of increased risk -> screening at 40
• Cancer Aetiology

  • androgen receptor is polymorphic
  • shortest CAG repeats on average are found in Africans. Caucasians intermediate and Asians longest.
• Risk factors

  • germline inheritance of cancer susceptibility genes(10%)
  • 1 first degree relative have 2fold higher risk
  • 2 first degree relatives have 5 fold risk
  • strong family history = early development
• Histology

  • ~70% arise in Peripheral zone, in a posterior location -> palpable on rectal exams.
  • spread by direct local invasion and through bloodstream and lymphatics. Haematogenous spread in bones.
  • Bony metastases are typically osteoblastic and point to Prostate cancer -> lumbar spine, femur, pelvis and ribs
• Lymphatic spread


  1. Occurs initially to pelvic lymph nodes

  2. Lymph nodes spread occurs frequently and often precedes spread to the bones
• Histological lesions


  • Most are adenocarcinomas
  • Produce well defined gland patterns
  • Neoplastic glands are typically smaller than benign glands
  • Lined by a single uniform layer of cuboidal or low columnar epithelium
• Histological diagnosis


  Difficult due to amount of tissue available for examination
• Benign glands


  • Contain basal myoepithelial cells
  • Absent in cancer
• IHC markers


  Used to label basal myoepithelial cells such as cytokeratins and p63

  • prostate specific antigen (PSA)
  • p63
  • High molecular keratin (HMWK)
  • Alpha-Methylacyl coenzyme A racemase (AMACR)
• Limitations are reduced when IHC labels is used in conjunction with H&E stained sections
• Gleason Scoring System

  Graded on the basis of glandular pattern and degree of differentiation.

  2 scores are given:

  • First no. refers to primary grade (dominant pattern) of tumour
  • Second no. is assigned to next most frequent pattern (secondary grade)

  The most well differentiated tumors have a Gleason of 2 (1+1) and the least have a score of 10 (5+5)

  Gleason scores are combined into 2 groups with similar behaviour:

  • 2-4 represents well differentiated cancers
  • 5-6 intermediate grade cancers
  • 7 moderate to poorly differentiated cancers
  • 8-10 high grade cancers (anaplastic)
• Treatment

  • Surgery, radiotherapy and hormonal manipulation.
  • >90% of patients treated can expect to live 15 years post treatment
  • Most common treatment is radical prostatectomy (removal of prostate, part of the urethra and seminal vesicles)
  • Prognosis is based on pathological stage, margin status and Gleason score
  • Endocrine therapy is mainstay for treatment of advanced, metastatic cancer->cancer cells depend on androgens for their sustenance, the aim of endocrine manipulations is to deprive the tumor of testosterone.
  • Achieved either pharmacologically or surgically
• PSA Stain

  • a serine protease. Almost exclusively produced in prostate ductal and acinar epithelium
  • Found in normal, hyperplastic and malignant prostate tissue
  • Expression by IHC is a specific and sensitive marker of prostatic lineage in with up to 97-4% sensitivity
• p63 IHC

  • p53 homologue, encodes for different isotypes that can either transactivate p53 receptor genes or act a p53-dominant-negatives
  • Expressed in the basal or myoepithelial cells of many epithelial organs. In the prostate, p63 expression is limited to the myoepithelial cells and is absent in secretory and neuroendocrine cells.
  • A nuclear Stain
  • p63 gene is essential for normal stem cell function in the prostate
• HMWK

  Great value in highlighting the presence/absence of a basal layer of prostatic glands in prostate tissue.

  Stains in a membranous/cytoplasmic pattern.

  34betaE12 is most widely used clone. Stains cytokeratins 5, 10 and 11
• AMACR & PIN4 Cocktail

  AMACR:

  • AMACR or racemase enzyme mainly localised to peroxisomal structures
  • Prostate carcinomas consistenly revealed a significantly higher expression of racemase than that in normal prostate
  • Both untreated and hormonally treated prostate cancer metastases have strong reactivity to racemase
• HMWK + p63 + RACEMASE (PIN4 Cocktail)

  Cytoplasmic racemase staining, combined with absence of myoepithelial staining with p63 and HMWK has proven to be of great assistance in establishing the diagnosis of prostate cancer, especially in needle biopsies

  A cocktail of these 3 may be extremely useful for studying prostatic neoplasia, especially in difficult cases and in cases with limited tissue