Page 514 - Concise Pathology for Exam Preparation ( PDFDrive )

17 Male Genital Tract 499

Glands
• There is proliferation and cystic dilatation of glands, which are lined by two layers: inner
layer of columnar cells and outer layer of cuboidal or flattened epithelium. Basement
membrane is intact. Multilayering and crowding of epithelium leads to the formation of
papillary infoldings.

Stroma
• Glandular proliferation is accompanied by the fibrous and muscular proliferation.
• Squamous metaplasia and small foci of infarction may be present.

Q. Describe the aetiopathogenesis, clinical features and morphology
of the carcinoma prostrate.

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

Clinical Features

• Usually affects men over 50 years
• Seventy to eighty 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; a few are discovered accidentally in prostatic tissue
removed for NHP.
• 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).

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.
• Genetic factors:
• Prostatic carcinoma is initially androgen dependent and relies on the androgen recep-
tor (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).
• 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.
• Mutations and deletions which activate PI3K/AKT signalling pathway are commonly
involved. There is amplification of 8q24 locus containing the MYC oncogene as well
as deletions affecting the PTEN, P53 and RB tumour suppressor genes.

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.

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