ca prostate presentation by dr Dushyant s

Carcinoma prostate

1. Carcinoma of Prostate

2. Carcinoma prostate is the most common form of visceral cancer (followed by the lung cancer), and second leading cause of death in males.

3. Clinical Features: • Usually affects men over 50 years • About 70 to 80% percent arises in the peripheral zone ; due to its peripheral location, it is less likely to cause urethral obstruction in the early stages. • Most cases are clinically silent • Extensive prostatic disease can produce ‘ prostatism ’ (local discomfort and lower urinary tract obstruction). • May come to attention due to bone metastases (may be lytic , more commonly blastic ).

4. Factors Implicated in the Pathogenesis: • Dietary factors: Increased consumption of fats and reduced consumption of lycopenes , selenium, soya products and vitamin D increase the risk of prostatic cancer. • Family history : Men with a family history of prostatic cancer have a twofold increase in incidence and an earlier age of onset.

5. Genetic factors: • Prostatic carcinoma is initially androgen dependent and relies on the androgen receptor (AR) to mediate the effects of androgens (therapy includes antiandrogens and LHRH analogues). However, all cancers eventually become androgen independent , often referred to as hormone refractory prostate cancer. This transformation is not yet fully understood (AR amplification, overexpression or mutation and alterations in the AR signalling pathway may play a role).

6. • Analyses have revealed that hypermethylation of GSTP1 (glutathione S- transferase P) gene , encoding the carcinogen detoxification enzyme glutathione S- transferase pi, may serve as an initiating genome lesion for prostatic carcinogenesis. Somatic mutation leading to juxtaposition of coding sequence of ETS family transcription factor gene next to androgen-regulated TMPRSS2 promoter induces overexpression of ETS transcription factors which upregulates matrix metalloproteinases to enhance invasiveness of prostatic cancer cells. • Germline mutations of BRCA2 are associated with a twentyfold increase in the risk.

7. Gross Morphology • Prostate is enlarged, normal sized or smaller than normal, hard and fixed. • Cut section is homogeneous, fibrous and may show yellowish irregular areas. • Local invasion into seminal vesicles, adjacent soft tissue and wall of the urinary bladder may be seen. • Invasion of rectum is less common ( Denonvilliers , fascia separating the lower urinary tract structures from the rectum, prevents growth into the rectum).

8. Microscopy: Four histological types: 1. Adenocarcinoma 2. Transitional cell carcinoma 3. Squamous cell carcinoma 4. Undifferentiated carcinoma

9. Adenocarcinoma Prostate • It is the most common histological type (96% cases). • The tumour is composed of closely packed acini arranged in a back-to-back manner with little or no stroma between them. The acini are too many, too small, too crowded. • Glands may be well differentiated to almost undifferentiated and are lined by a single layer of epithelium (basal layer seen in normal or hyperplastic glands is absent). Tumour cells may be clear, hyperchromatic or eosinophilic (granular). • Foci of intraepithelial neoplasia (PIN) may be seen in close association with carcinoma.

10. Invasion of intraprostatic perineural spaces is a common occurrence. Stage, grade, surgical margins, pre operative PSA, angiolymphatic and perineural invasion are important prognosis.

11. 9/30/2024 11 Carcinoma of prostate. (A) Schematic gross; (B) Diagrammatic microscopy; (C) Microphotograph of low-grade prostate cancer consisting of back-to-back uniform-sized malignant glands. Inset shows perineural invasion

12. Grading of Carcinoma Prostate Gleason grading is the most widely used grading system for adenocarcinoma prostate. It is based on the glandular architectural patterns and the relationship of the tumour cells with the stroma

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14. Diagnosis and Staging of Carcinoma Prostate • Digital rectal examination: Most of the prostatic tumours are located in posterior lobe, so are easily palpable on per rectal examination. • Transrectal ultrasonography with guided biopsy for early detection of tumour . • Computed tomography and magnetic resonance imaging scan to evaluate the lymph node status. • Pelvic lymphadenectomy to look for microscopic metastasis as metastasis to regional pelvic lymph nodes can occur. • Skeletal survey or radionuclide scanning for detection of osteoblastic metastasis.

15. Tumour marker assays: 1. Prostatic acid phosphatase (PAP) 2. Prostate-specific antigen (PSA): Uses of PSA • Diagnosis of prostatic diseases • To assess the response to chemotherapy in cancer • To check whether radical prostatectomy is complete or not • To confirm the origin of metastatic deposits as prostate 3. AMACR(alpha methylacyl-CoA racemase ) 4. PCA3: a gene on chromosome 9q