My Clinical Notes

Adenocarcinoma

• Most common form of cancer in men and the second leading cause of cancer death

 

Incidence

• Occurs in men over 50
• More prevalent on black than asian populations

 

Aetiology

• Risk factors which play a role;
  • Age
  • Race
  • Family history
  • Hormonal levels – androgens, possibly related to polymorphisms in the androgen receptors
  • Environmental factors – incidence among Japanese rises when they emigrate to USA
    • May be due to increased intake of fats or deceased dietary intake of protective foods e.g. lycopenes, vitamin A, vitamin E, selenium and soy product
• In 1/3 of familial cases, a susceptibility gene has been mapped to chromosome 1q24-25
• P53 mutations are late event in prostatic carcinogenesis
• Other TSG genes thought to play a role are PTEN and KAI1
• Prostatic cancers frequently display a loss of E-cadherin and CD44
• One of the most common genetic alteration is hypermethylation of glutathione-S-transferase gene promoter. This turns off the gene which plays a role in preventing damage to a wide range of carcinogens
• Types are divided into 3 groups based on their behaviour;
  • Latent – small foci of well differentiated carcinoma, frequently an incidental finding. Remain confined to the prostate for a long period
  • Invasive – invade locally and metastasise
  • Occult – not clinically apparent at the primary site but present as metastatic disease

 

Morphology

• 70% arise from the posterior peripheral zone
• Spread of prostate cancer occurs by direct local invasion and through the blood stream and lymph
• Local extension commonly affects the seminal vesicles and the base of the urinary bladder
• Haematogenous spread occurs mostly to bones, particularly the axial skeleton – producing osteoblastic (sclerotic) lesions. Can also go to liver and lungd
• Lymph node spread, which occurs most commonly, occurs to the obturator nodes, perivesical, hypogastric, iliac, presacral and para-aortic nodes
• One feature that distinguishes benign and malignant prostates is that benign glands contain basal cells that are absent in cancer
• In approximately 80% of cases, prostatic tissue removed for carcinoma also harbours the precursor lesion – high grade prostatic intraepithelial neoplasia (PIN)
• These lesions consist of benign glands  with intra-acinar proliferation of cells that demonstrate nuclear anaplasia
• High-grade PIN consists of more widely separated, branching glands with papillary infolding, in contrast to invasive cancer which is typically characterised by small, crowded glands with straight luminal borders. Cytologically the two processes might be identical

 

 

Grading and staging

• The Gleason system has 5 grades of prostate cancer
  • Grade 1 – well differentiated
  • Grade 5 – no glandular differentiation
• Most tumours display more than one pattern so you grade the dominant pattern and the secondary grade and add the two together
• A tumour of one pattern is graded and the grade doubled for its total Gleason score
• 2-4 represent well differentiated cancers
• 5-6 intermediate grade
• 7 is a moderately to poorly differentiated tumour
• 8-10 is high grade and unlikely to be curable
• Grading helps predict prognosis

 

• TNM is the most common staging system
  • T1 refers to cancers found incidentally
  • T2 is organ confined cancer
  • T3a shows extraprostatic extension without involvement of the seminal vesicle (b there is involvement of the seminal vesicles)
  • T4 direct invasion of contiguous organs
• Any spread to lymph nodes generally has a fatal outcome

 

Clinical course

• In 70% of men over the age of 80 asymptomatic, microscopic cancers are found at post mortem or in tissue removed for prostatic hyperplasia
• Urinary symptoms occur late as most cancers develop in the posterior of the gland
• Therefore detection is generally via rectal examination (firm, craggy mass) or an elevated PSA
• Some patients with advanced disease and bony mets present with back pain
• Osteoblastic metastases in bone are virtually diagnostic of prostate cancer
• PSA is a product of prostatic epithelium and is normally secreted into the semen. It is a serine protease which cleaves and liquefies the seminal coagulum formed after ejaculation
• PSA is also produced in benign prostatic hyperplasia, although generally to a lesser extent
• PSA also rises with prostatitis, infarct and instrumentation of the prostate
• Also 20-40% of patients with organ confined prostatic cancer do not have a raised PSA
• PSA can be free or bound. The lower the free portion the greater the risk of cancer

 

• Treatment is with surgery, radiotherapy and hormone therapy
• Endocrine therapy is used for advanced metastatic disease – synthetic agonists of luteinising hormone-releasing hormone are used
• Antiandrogen therapy does induce remissions but tumour progression can lead to the emergence of testosterone-resistant clones
• Orchidectomy can also benefit
• 75% of patients benefit from treatment which reduces androgen levels

 

• Diagnosis is by;
  • Imaging – ultrasound, X-ray and isotope bone scan
  • Biopsy – immunohistochemical detection of PSA and prostate –specific acid phosphatase (PSAP)
  • PSA and PSAP may be used as markers of disease, levels being raised when there is metastatic disease

 

 

Miscellaneous Tumours and Tumour-like conditions

• Although acinar adenocarcinoma of the prostate is the most common, prostatic adenocarcinomas can also arise from the prostatic ducts
• Those arising from the peripheral ducts present similarly to acinar adenocarcinoma
• Those coming from the larger peri-urethral ducts present with urinary obstruction and haematuria
• Prostatic duct adenocarcinoma is associated with a relatively poor prognosis
• Prostatic carcinoma can also show squamous differentiation
• The most aggressive type is small cell carcinoma which is rapidly fatal

 

This entry was posted on Friday, December 21st, 2007 at 4:48 pm and is filed under Male genital tract. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.