Male Genito-Urinary Tract Pathology

• Focus is on the pathology of the male genito-urinary tract for Year 2 Pathology course taught by Dr. Odharnaith O’Brien on March 5th, 2024.

Learning Outcomes

• Discussing congenital abnormalities of the male GU tract is part of the course
• Explaining phimosis is a learning outcome
• The course includes a discussion on genital warts
• The course includes a discussion on tumours of the penis and testis
• The course includes a discussion on infection of the testis and epididymis
• Discussing benign prostatic enlargement is a learning outcome
• Prostatic carcinoma's epidemiology, aetiology, and histology will be covered.

Overview of Lecture

• Prostate pathology (BPH and cancer) is part of the lecture
• Testis pathology (germ cell tumours) is part of the lecture
• Penis and scrotum pathology will be explored.

Prostatitis

• Primarily a clinical concern, not a histopathological query, but PSA can increase raising cancer worries
• Acute bacterial prostatitis is usually seen in UTIs, commonly in adult men with systemic and local symptoms
• Chronic bacterial prostatitis presents as acute, but is relapsing with lesser symptoms
• Granulomatous prostatitis is uncommon, infectious or unknown, shares prostatitis symptoms, has a high PSA, and a hard prostate on DRE

Basic Prostate Anatomy

• BPH is found in the transitional zone
• 20-25% of cancers are in the transitional zone
• 70-75% of cancers are in the peripheral zone

BPH (Benign Prostatic Hyperplasia)

• Common disorder with high urologist referral rates
• Aetiology is hormonal, age-related, and possibly due to genetic predisposition
• Symptoms of BPH are referred to as Prostatism

Symptoms of Prostatism

• Symptoms include poor flow, hesitancy, incomplete bladder emptying and dribbling
• Other symptoms include urgency and nocturia

Malignant Prostate Tumours

• Adenocarcinoma (microacinar and ductal variants) is a primary tumour type
• Rare tumours include squamous and small cell carcinoma, sarcoma and lymphoma
• Secondary tumours are rare and occur through direct extension from bladder or rectal cancer

Epidemiology of Prostate Cancer

• Approximately 3,400 new cases in Ireland annually
• Prostate cancer leads to under 550 deaths in Ireland each year.
• The lifetime risk of being diagnosed with prostate cancer is 16%, but the risk of dying from it is 2.9%
• Up to 50% of men over the age of 60 have prostate cancer
• If detected at an early stage there is a 5 year survival of >95%
• Most prostate cancers are indolent

Symptoms of Prostate Cancer

• Discovered incidentally through PSA tests, digital rectal exams, or during BPH resection
• Late stage symptoms mimic BPH
• Local affects mimic BPH
• Metastatic symptoms could include bone issues

PSA (Prostate Specific Antigen)

• Present in low quantities in normal men (<4 ng/mL)
• The PSA can be increased for other reasons
• PSA is a glycoprotein secreted by prostatic epithelial cells to liquefy semen
• Largely used as a screening test for prostate cancer

Screening

• Prostate cancer incidence was stabilised since 2010 (3300-3500/annually)
• PSA was FDA approved as a screening tool in 1994

PCa Diagnosis

• A high S-PSA result typically leads to a biopsy
• This then will leads to either treatment or another biopsy depending on the test result

Traditional Prostatic Biopsy

• Transrectal, extended sextant: 12 cores

Pathological Features of PCa

• Prostate cancer is subtle
• Macroscopic features are multifocal, and infiltrative
• Microscopic features have minimal pleomorphism, infrequent mitoses and small foci

Histological Features of Prostatic Adenocarcinoma

• Features include small, crowded glands, nuclear enlargement, large nucleoli, and a lack of basal myoepithelial cells
• There is no singular defining feature to diagnose

Limitations of Traditional Biopsy

• Primary limitation is lack of targeting
• A negative biopsy doesn't exclude the possibility of prostate cancer
• Biopsy results may not accurately reflect actual cancer extent and grade in the prostate

TNM Staging

• T1: incidentally detected cancer
• T1a and T1b on TURP
• T1c on needle core
• T2: confined to prostate
• T3: extraprostatic
• T4: into adjacent organ
• N0/N1 refers to regional nodes
• M0/M1 refers to distant sites
• Iliac lymph nodes are impacted before bone metastases
• Pathological (p)T and clinical (c)T-staging varies slightly

Gleason Scoring

• Based purely on gland pattern
• Patterns 1-2 are rarely used now
• Pattern 3 has single well formed glands
• Pattern 4 has poorly formed / fused glands
• Pattern 5 has no glands (single cells, sheets, rows)
• Gleason Score calculates adding predominant pattern + second pattern
• Predominant pattern + second pattern is Gleason score

Grade Groups

• Gleason score in reality is measured from 6 to 10
• Group 1: Gleason score 6
• Group 2: Gleason score 3+4=7
• Group 3: Gleason score 4+3=7
• Group 4: Gleason score 8
• Group 5: Gleason score 9-10

High-Risk Prostate Cancer

• 15% of diagnosed cancers
• Clinical stage T3
• Gleason score >8
• PSA >10

New Solutions for PCa

• Early imaging using MRI
• Better biopsy
• Targeted biopsy for MRI detected lesions or template biopsy

Radiology of Prostate Cancer I

• For evaluation, MRI is useful in identifying 'high risk' PCa
• This involves a mix of T2W, diffusion, and dynamic studies
• Use PI-RADS (Prostate Imaging Reporting and Data System) for standardisation
• Scoring is from 1-5 with these parameters:
  • 1=‘most probably benign’
  • 5=‘most probably malignant’
  • 3 is indeterminate

Newer Prostatic Biopsies

• Template (transperineal/ TP) biopsies - better access
• More biopsies and better access to the apex
• Targeted prostate biopsies exist Persistent concern despite negative biopsies leads to main indication

Testis Anatomy

• These are all components of testies anatomy
• Vas deferens
• Epididymis
• Rete testis
• Seminiferous tubules
• Tunica vaginalis
• Tunica albuginea

Cryptorchidism

• It is caused by failure of testis to descend into scrotum
• Cause is usually unknown
• Mechanical issues and congenital syndromes could cause the failure (eg Prader-Willi)
• Atrophy and infertility occur, causing an increase risk of germ cell tumour
• Orchidopexy occurs before puberty to reduce risk

Benign Cysts and 'Celes'

• Varicocele is caused by dilated veins in spermatic cord and leads to fertility problems
• Hydrocele is caused by fluid collection in tunica vaginalis, it could be caused by infection
• Relating to the epididymis
• Epididymal cyst and spermatocele cause dilation of duct

Inflammation and Torsion

• Orchitis / epididymo-orchitis can be caused by mumps, STD's, or are idiopathic
• Torsion of the testis occurs by twisting of spermatic cord and testis
• Severe pain occurs during twisting of spermatic cord and testis, this is a surgical emergency
• The average age of being affected is at birth or around puberty

Testicular Tumours

• Consists of germ cell (~90%), sex cord/stromal tumours, with GCTs being divided into seminomas and non-seminomas
• Germ cell accounts for 90% of tumors
• Other rare tumors include lymphomas and metastases (older men)
• Not all testis lumps are tumours, infections/cysts, etc can be the cause

Basic Facts About GCT

• These tumours are malignant
• Rare tumors occurs roughly 175 cases a year
• Most common is solid tumour in young men
• Chemo and radiation yields survival
• Risk factors are categorized by the following:
  • Racial: white > black
  • Cryptorchidism
  • Others (rare) include e.g. Klinefelter syndrome
  • Incidence is increasing from environmental factors

Spread and Staging of GCT

• Staging by TNM:
  • T1 limited to testis
  • T2 limited to testis, invades tunica albuginea, vascular invasion
  • T3 invades cord
  • T4 invades scrotum
• Spread occurs via lymph nodes to the paraaortic nodes, upwards to chest with no inguinal nodes; can be haematogenous, affecting lungs/brain
• In Non seminoma the haematogenous is more common

Seminoma vs ‘Non-seminoma’

• Seminoma has peak at age 40s and adjuvant radiation
• Non-seminoma has peak at age 30s and adjuvant chemotherapy
• Seminoma has no specific ‘tumour marker’ in blood but LDH is often increased
• Non-seminoma has substances ('tumour markers') such as hCG and AFP, LDH is also raised

Early Change of Germ cells

• Germ cell neoplasia in situ is an In-situ malignant, it cannot metastasise

Non-Seminoma Types

• Types: Embryonal carcinoma, teratoma, yolk sac tumour
• For yolk sac, the tumour marker is Alpha fetoprotein (AFP)
• For Choriocarcinoma(uncommon), the tumour marker is human chorionic gonadotropin (hCG)

Summary of Testicular Tumours

• Overall are rare in young men but one the most common malignancies
• Tumours metastasise first to paraaortic nodes, not inguinal nodes
• Survival rate is very good cause chemo and radiation
• Not all lumps in scrotum/testis are tumours

Penis/Scrotal Pathology - Congenital

• Hypospadia is where the opening in urethra is not normal, vs epispadia
• Phimosis occurs where it is impossible to retract the foreskin
• Normal for boys to have have 'phimosis' as a default

Penis/Scrotal Pathology - Inflammatory

• STDs : Herpes simplex, Syphilis
• Gonorrhoea and chlamydia cause urethral inflammation instead of with other external inflammation
• HPV causes genital warts , and increases the risk of penile cancer

Penile Cancer

• Rare, fewer than 20 cases/year in Ireland
• Squamous cell carcinoma
• Seen in males > 55 y/o.
• Linked to HPV infection, history of genital warts, and HIV
• Poor hygiene, lichen sclerosus

Penile Cancer - Staging

• pTis is carcinoma in situ
• pT1 involves the subepithelial tissues
• pT2 means invasion of corpus spongiosum
• pT3 means Invasion of corpus cavernosum
• pT4 means Invasion of adjacent structures
• Can occur with urethra
• Usually spreads to lymph nodes in predictable fashion with the inguinal nodes first affected