Week 3 - STI, Scotum, Testes & Penis Disorders

Question 1

Outline syphilis.

Answer 1

• Treponema pallidum (spirochete), global, endemic, incidence increasing.
• Body fluids → skin/mucosa or placenta to new born.
- Transmitted by body fluids directly to skin/mucosa or mother to foetus via placenta.
- Bacteria cannot survive outside the body so direct contact is important.
• Widespread dissemination through lymphatics.
- Occurs early in the disease.
• Proliferative endarteritis - chronic inflam. plasma cells*
- Characteristic lesions of syphilis is proliferative endarteritis - vascular damage. Chronic inflammation with plenty of plasma cells.
- Microscopy - plenty of plasma cells around blood vessel. Endarteritis with plasma cells.
• Congenital - abortion → rash, liver and lung fibrosis, 8th nerve deafness, interstitial keratitis, hutchison teeth (notching of the incisors).
- When baby acquires syphilis. Ranges from intrauterine death (abortion) to mild rash with above features.
*See diagram.

Question 2

Describe the 3 stages of syphilis.

Answer 2

• Primary (3wk) - chancre: ulcerated papule, resolve* spontaneously. Highly infectious*

• Clinically, it occurs in 3 stages.
• Primary - first 3 weeks. Phase where person is highly infectious. Chancre - ulcerated papule that resolves spontaneously.
• Although syphilis produces lots of antibodies, they are not protective.

• Secondary (months) - recurrent lymphadenopathy, palmar rash, Condyloma lata (painless, moist, plaques). Highly infectious etc. Resolve*

• Following healing of chancre, present months later with above features.
• Highly infectious and usually resolve without any treatment.

• Tertiary (years) - Gumma-Necrotising granuloma CVS, CNS. Tabes dorsalis, general paresis, aneurysms 80%.

• Most damage - usually after 5-20 years.
• Known as Gumma - necrotising granulomas in the cardiovascular system mainly but also in the CNS and other organs.
• Aortic aneurysms 80% of cases.

Question 3

Describe the diagnosis of syphilis.

Answer 3

Non Treponemal Ab (to cardiolipin):
• Only early phase, non specific, false positive. Common tests:
- VDRL (Venereal Disease Research Lab).
- RPR (Rapid plasma regain).
• Cardiolipin present on bacteria and in the body.
• Usually in the early phase, not the tertiary phase.
• False positive - not specific to bacteria, can be positive in other diseases.
• Good for screening only, need to confirm. Confirmed with specific antibodies to Treponema.

Treponemal Ab:
• Usually positive in all stages. False positive*
• FTA-ABS (fluorescent Trepo. Ab)
- Fluorescent Treponema antibody absorption test.
• TP-PA (TP particle agglutination)
- Particle agglutination test.
• MHA-TP (Microhaemagglutinin Assay).
- Microhaemagglutinin test.

• Direct detection: darkfield microscopy, PCR, culture?

Question 4

Outline gonorrhoea.

Answer 4

• Common, second to Chlamydia, incidence increasing, resistant to many drugs. Suppurative, only humans. Person to person and to fetus on birth (passage).
- Common pyogenic infection (pus forming).
- Direct contact or mother to foetus.
• Produces dysuria, mucupurulent discharge → PID.
- Ascending infection leading to pelvic inflammatory disease.
• Neisseria gonorrhoeae, gram neg. diplococci.
• Stick to epithelia, 1-14 day incubation.
- Penetrate through epithelia and disseminate through body.
• Fever, pain, inflammation, dysuria, discharge - white pus.
• Urethra, cx, rectum, pharynx, or eyes.
- Causes all itis - urethritis, cervicitis, proctitis, pharyngitis.
• Intracellular, gram neg diplococci.
- Organisms within cytoplasm of neutrophils.
• Complications: stricture, PID, spread.
- PID with fibrosis - frozen pelvis.
• Ocular, neonatal conjunctivitis.

Question 5

Outline nongonococcal urethritis (NGU).

Answer 5

• Most common STI. Chlamydia*, trichomonas vaginalis (protozoa), ureaplasma, Mycoplasma genitalium etc.
- Commonly due to Chlamydia but also other organisms.

Question 6

Outline chlamydia.

Answer 6

• Chlamydia trachomatis (pathology similar to gonococci - less pus in chlamydia infections).
• Gram -ve, elementary body → reticulate body in cell.
- Gram negative bacteria. 2 forms - elementary body outside, reticulate body within cells.
• ~50% are asymptomatic.
• Major cause of infertility in men and women.
- Causes extensive fibrosis → infertility.
- Can be asymptomatic and infecting other people through sexual activity.
• 40% PID, 20% infertility, 9% ectopic pregnancy.
- 40% of cases present with PID.
• In men - urethritis, epididymo-orchitis, prostatitis.
• In patients with HLAB27 → reactive arthritis (Reiter’s syndrome).
• Children - seasonal purulent conjunctivitis. Repeated, untreated → scarring of cornea and eyelids → visual impairment/blindness.
- Children present with seasonal purulent conjunctivitis. Repeated/untreated cases can lead to scarring of cornea and eyelids.

Question 7

Describe the diagnosis of chlamydia.

Answer 7

• Nucleic acid amplification Test (NAAT). Sensitive test.
• In combination with tests for Neisseria gonorrhoeae (also HIV).
- Patients usually tested for chlamydia, gonorrhea and HIV.

Question 8

Outline Reiter’s syndrome.

Answer 8

• Common inflammatory polyarthritis in young men.
- Reactive immune polyarthritis secondary to Chlamydia.
• Chlamydia trachomatis (rarely salmonella and shigella).
• HLA-B27 - risk factor in 70%.
- Patients with HLAB27 more at risk.
• Fever, malaise, myalgia.
• Reactive asymmetric arthritis.
• Conjunctivitis.
• Knee, ankle and feet common e.g. sausage toe, inflammed ankle.
• Chronic, recurrent.
• Disability in ~20% cases.

Question 9

Differentiate GU and Non-GU.

Answer 9

• Major difference is in gonococcal - intracellular diplococci present.
• In non-GU - may not be any organisms present, just neutrophils.
• More pus in gonococcal than non-GU.

Question 10

Outline lymphogranuloma venereum.

Answer 10

• LGV - Chlamydia trachomatis, serotypes L1-L3.
- Also caused by Chlamydia trachomatis but different serotypes (L1-L3).
- Produce ulcerative lesions of the penis and lymph nodes. Initially lymphadenitis then ulcerates.
• Chronic ulcerative, lymphedema, procto-colitis.
• Genital painless papule 2-5 days.
• 1-4 wk suppurative necrotic inguinal lymphadenitis.
• Suppurative granuloma (neutrophil abscess) and chlamydial inclusions in microscopy.
- Also causes extensive granulomas and fibrosis → PID.

Complications:
• Rectal strictures. Pelvic inflammatory disease, frozen pelvis - extensive fibrosis.

Question 11

Outline chancroid.

Answer 11

Chancroid (soft chancre):
• AKA third venereal disease (Syphilis, Gonorrhoea).
- Also produces ulcers similar to LGV but caused by different organism.
• Haemophilus ducreyi.
• Gram -ve coccobacillus.
• Tropical. HIV common, prostitution risk factor*
- Common in prostitution and HIV infected people.
• Erythematous papule → painful ulcer, yellow pus.
- Characteristic feature is painful ulcer and yellowish pus, both male/female genitalia.
• Inguinal lymphadenopathy → buboes → pus draining ulcers.
- Marked lymphadenopathy known as buboes with pus discharging ulcers - typical in chancroid.

Question 12

Outline granuloma inguinale.

Answer 12

• Chronic fibrosing STD by Klebsiella granulomatis. AKA Granuloma venereum/donovansis.
- Not very common, also produces ulcer.
- Klebsiella granulomatis within macrophage bacilli.
• The initial papules on genitalia → ulcers → urethral, vulvar or anal strictures.
• Granulation tissue and intense epithelial hyperplasia that can mimic squamous cell carcinoma.
• Intracellular coccobacilli within vacuolated macrophages (known as Donovan bodies).
• Note: Leishmania donovani (protozoa) - Donovan bodies* is different.

Question 13

Outline genital herpes.

Answer 13

• STD - Herpes Simplex Virus HSV1 and HSV2*
- HSV2 most common.
• 95% of HIV +ve are also positive for HSV.
• Direct contact only - not fomites.
- Mucosa to mucosa.
• 4 day incubation, produces itchy, painful, closely grouped vesicles surrounded by erythema.
• Vesicles burst to form painful ulcers.
• Multinucleate giant cells with viral inclusion.
- Viral inclusions are characteristic on microscopy. Positive by anti herpes virus antibodies.
• Painful inguinal lymphadenopathy.
• Self limited mild in normal.
• Severe infection in immunocompromised.
• Neonatal herpes encephalitis - severe and fatal.

Question 14

Identify the structure, origin and lymphatics of the testes.

Answer 14

• The testes develop in the abdomen (para-aortic region) - testicular lymphatics is para-aortic lymph nodes. Penis and scrotum - inguinal lymph nodes.
• Testes are packed with seminiferous tubules. Each of these tubules are lined by germ cells which gradually mature towards the centre to form sperm. (spermatogonia → primary spermatocyte → secondary spermatocyte → spermatid → sperm cell).

Question 15

Outline epididymo-orchitis.

Answer 15

Aetiology:
• Gonococcal - Neisseria gonorrhoeae
• Non Gonococcal - chlamydia, mycoplasma
- Commonest - NG chlamydia.

Clinical features:
• Testicular pain - unilateral
• Erythema/oedema of the scrotum.
• Uretheritis, dysuria/urethral discharge.

Morphology:
• Gross - swollen, hot, acute inflammation, oedema.
• Microscopy - oedema, neutrophils (acute inflammation), necrosis.

Investigations:
• Exclude torsion/trauma in <30 years.
• Serology, microbiology: C/S, PCR.

Question 16

Describe gonococcal epididymo-orchitis.

Answer 16

• Formation of pus, huge abscess in epididymis and pus in the testes.
• Microscopy - gram negative diplocci.
• Investigations - first pass urine and NAAT. Culture - urethral swab.

Question 17

Outline mumps orchitis.

Answer 17

• Paramyxovirus, respiratory tract spread.
- Commonly epidemics in school children.
• Acute, febrile, bilateral parotitis - children and orchitis in adults (25%) and viral meningitis (15%).
- Bilateral parotitis typical in children.
- Orchitis in 25% patients particularly teenagers.
- Rarely meningitis.
• Orchitis - unilateral, enlarged, painful and tender.
• Patchy inflammation, neutrophils and lymphocytes.
• Increasing pressure → ischaemia, necrosis.
- Increasing pressure due to tough capsule causes ischaemia and necrosis.
• If mild → complete resolution.
• If severe → patchy atrophy → infertility.
- Severe - infertility due to atrophy.

• Microscopy - gradually there is oedema formation and plenty of inflammatory cells filling the tubule damaging the spermatogonia. Patchy areas of inflammation within tubule.

Question 18

Outline cryptorchidism.

Answer 18

Cryptorchidism: “undescended testes”
• Normal descent: 3m to pelvis, 9m to scrotum.
- Usually descends by time of delivery to scrotum (9 months) from the para-aortic region.
• Non descent 5% at birth, 1% at 1y (10% bilateral).
- 5% don’t descend before birth. 1% remain after 1 year. If left undescended in inguinal canal → testes undergo atrophy.
• Cause: Hormonal, intrinsic and mechanical.
• Common in Patau, Prader willi syndrome etc.
• Atrophy - sertoli and Leydig cell hyperplasia.
- Complication = atrophy. Due to temperature increase, spermatogonia undergo atrophy leaving behind only sertoli and Leydig cell hyperplasia.
• 3-5 fold increase in Germ cell malignancy - even in the other testes.
- Increased incidence of germ cell malignancy.
• Orchiopexy - surgical fixing (of testes back into scrotum), reduces risk of sterility and cancer (when done early).

Question 19

Describe the morphology of testicular atrophy.

Answer 19

• When there is atrophy, initially there are only sertoli and Leydig cells remaining within the tubules. All the spermatogonia disappear, testes shrink in size.
• Later, in case of mumps, there will be total atrophy. Patchy atrophy, some normal tubules and totally atrophic tubules.

Question 20

Outline torsion of the testes.

Answer 20

• Twisting of spermatic cord on its axis.
• 1y or 13-16y, swollen, hard, painful.
- Common in infants and teenagers.
- Very painful, sudden, swollen.
• Precipitated by exertion/contraction of cremaster muscle.

Risk factors:
• Maldescent (of testes), long spermatic cord/mesorchium.

2 types:
• Within tunica vaginalis - common, testis and epididymis involvement only.
- Most common, testes turn within tunica vaginalis. Only testes and epididymis involved.
• Above tunica - all structures in that side of the scrotum (includes tunica vaginalis).
- All structures are involved.

Pathogenesis:
• Venous stasis → venous infarction.
- Due to twisting, there is obstruction to venous outflow. However, the thick walled arteries still continue to supply. Results in obstruction to venous outflow → causing venous infarction.

• Surgical emergency → correction/orchidectomy.
- If not performed within a few hours, undergoes total infarction.

Question 21

Describe inflammatory accumulations of the testes.

Answer 21

1. Hydrocele: common, clear fluid in tunica vaginalis. Congenital/acquired (inflammation).
   • Collection of clear fluid in tunica vaginalis. Can be congenital or acquired due to inflammation.
2. Varicocele: engorged spermatic cord veins (pampiniform plexus). Common cause of infertility oligospermia. Primary/secondary.
   • Engorged spermatic cord veins.
3. Spermatocele: epididymis dilatation, trauma/infection, multilocular, sperms.
   • Trauma to epididymis (one of the tubules) causing dilated cysts containing semen.
4. Haematocele: blood in tunica vaginalis. Trauma, tumours.
   • Blood accumulating in tunica vaginalis. Trauma or tumours. Accumulation of blood results in atrophy of the testes due to compression and increased temperature.

Question 22

Outline hydrocele.

Answer 22

• Marked swelling of the scrotum.
• Transilluminant due to the clear fluid (no inflammation).
• Can be non-communicating, communicating (communicates with abdominal cavity) or hydrocele of spermatic cord (rare).

Question 23

Outline disorders of sexual development.

Answer 23

• Ambiguous genitalia → transgender.
• By default all are female.
- All female unless someone has a SRY gene functioning on short arm of Y chromosome → produce androgens → give male characteristic.
- If no gene or mutated gene or testes not functioning, phenotypically will be female (even if have XY genes).
• SRY gene on short arm of Y androgens → male.
• Congenital Adrenal Hyperplasia (CAH) is the most common cause.
- Most common cause of transgender sex. AKA female pseudohermaphrodite. Rarely caused by drugs and hormone therapy during pregnancy (excess androgenic hormones).
- Opposite is male pseudohermaphrodite - genetically male but with female sexual characteristics due to gonadal dysgenesis.
- True hermaphrodite rare - both ova and testes in single person.
• Mixed gonadal dysgenesis (MGD) is the second common cause of DSD.
• Sex chromosome DSD: Turner’s, Klinefelters etc.

1. Female pseudohermaphrodite*** - XX male - CAH.
2. Male pseudohermaphrodite** - XY female - gonadal dysgenesis.
3. True hermaphrodite (rare) - XX/XY - both gonads.
4. Mixed gonadal dysgenesis* - Male Turner - streak and testes.

Question 24

Outline tumours of the testes.

Answer 24

• Commonest tumour of young males, painless swelling.

Aetiology:
• Idiopathic, undescended testes (10%, 10 times).
- Idiopathic most common, 10% related to undescended testes (10x more chance of developing tumour).

Classification:
95% Germ cell tumours
• Seminoma 45% - good prognosis (more local). Most common.
• Non seminoma (NSGT) 45% - poor prognosis. Embryonal ca, Teratoma, Chriocarcinoma, mixed - common.
- 60% of cases, microscopically will find more then one type of germ cell tumour - multipotent nature, can differentiate into any type of cell. Mixed patterns common.

5% Sertoli/Leydig cell tumours.

Clinical features:
• Adults 20-40y - Seminoma.
• Children <10y - NSGT - Yolksac tumour.
• Painless, dragging, unilateral, solid.
- Sensation of dragging, solid swelling.
• Metastases - para aortic LN*
- Metastases goes to the para aortic nodes because of its embryologic origin.

Question 25

Outline seminoma.

Answer 25

• Commonest germ cell tumour, 20-40y.
• Firm, grey, smooth, painless (swelling).
- Not much haemorrhage, well demarcated, looks like a benign tumour.
• Many subtypes - classical*, spermatocytic etc.
- Many subtypes microscopically.
• Microscopy - uniform clear cells + lymphocytes (classical type).
- Look very regular, not pleomorphic.
• Mixed seminoma → seminoma + teratoma, embryonic carcinoma or choriocarcinoma (βhCG 10%) etc.
- βhCG positive. Otherwise seminoma’s don’t produce hormones.

Question 26

Outline embryonic carcinoma (NSGT).

Answer 26

• Second common.
• Clinical: painless swelling, haemorrhagic, malignant, poor prognosis, metastases.
- Also painless but on cut section, very haemorrhagic tumours. Poor prognosis - spread quicker, metastases by the time it is diagnosed.
• Germ cell tumour - embryonic cells.
- Germ cell tumour forming embryonic cells.
• Gross - Haemorrhagic, necrotic tumour.
• Adults - Embryonal Ca.
- Known as embryonal carcinoma.
• Children - Yolksac tumour.
- Commonest in children.
• Tumour marker - AFP (alpha feto protein).
• Microscopy - Pleomorphic cells, embryoid structure. Pink AFP globules in cells.
- Very irregular pleomorphic cells forming embryo like structures (cluster of cells with a space - embryoid bodies).
- Alpha feto protein can be stained as globules.

Question 27

Outline teratoma/teratocarcinoma (NSGT).

Answer 27

• Occur in all gonads, ovaries, midline tumours, in the CNS.
• >1 tissue type (mature/immature).
- Teratoma - when there is more than one tissue type.
- When normal mature looking cells - known as mature teratoma - benign.
- When malignant immature looking cells - known as immature teratoma - malignant.
• Teratoma + other germ cell tumour (Embryonal ca)
- Also can occur with other germ cell tumours, most common with embryonal carcinoma - known as teratocarcinoma.
• Common, 10-30y, aggressive, poor prognosis.
• Both βhCG & AFP +ve - if mixed.
- When both βhCG & AFP +ve → mixed type (with embryonal carcinoma).
• Microscopy - cartilage, fibrous tissue and glandular structures. Both epithelial and connective tissue teratoma.

Question 28

Tumours of the testes summary.

Answer 28

• Germ cell tumours (95%)
- Gonadal - seminoma.

• Non Seminoma Germ cell tumour (NSGT)

• Embryonic - Embryonal ca
• Extraembryonic - Yolk sac tum, Choriocarcinoma.
• Somatic - Teratoma.
• Mixed (40%).

Question 29

Describe the normal penis.

Answer 29

• Shaft (body or corpus), glans, root.
• Corona - neck sulcus.
• Erectile tissues - 3 cylindrical bodies.
• Fibrospongy, vascular tissue fibrous capsule - tunica albigunea.
• Dorsal firm pair corpora cavernosa.
• Ventral soft corpus spongiosum central urethra, extends as glans.
• External urethral meatus.

Lymphatic damage:
• Skin - sup inguinal.
- Skin drains to superior inguinal lymph node.
• Deeper - int. iliac.
- Deeper tissues drain to internal iliac lymph nodes.

Question 30

Describe congenital malformations of the penis.

Answer 30

1. Phimosis (also acquired) - narrow opening of the prepuce (foreskin). Congenital/acquired (due to infections).
2. Paraphimosis - when the glans escape the narrow opening to strangulate → surgical emergency.
3. Hypospadias - when urethra opens on the ventral surface.
4. Epispadias - when urethra opens on the dorsal surface.
5. Atrophy/agenesis - atrophy of male genitals.

Question 31

Outline inflammations of the penis.

Answer 31

• Balanitis, Posthitis and Balanoposthitis.
• Inflammation of the inner surface of the prepuce (posthitis) and inflammation of the glans (balanitis) or occur together.
• Often associated with phimosis or lead to phimosis.
- Due to lack of clearance of secretions - smegma.

Aetiology:
• Poor hygiene, accumulation of smegma (secondary infection).
• Non STI (more common) - Candida (most common), Staph/Strep, gardnerella.
• STI - syphilis, gonorrhea, herpes etc.

Question 32

Outline balanitis xerotica obliterans.

Answer 32

• Similar to Lichen sclerosis of vulva or elsewhere.
• Not common, adults, >30y.
• White plaque and fissures - glans/prepuce.
- White hard plaques with fissures over the glans or prepuce.
• Microscopy - epidermal atrophy, hyperkeratosis with basal layer degeneration, dermal hyalinisation.

Question 33

Outline Peyronie’s disease.

Answer 33

• Penile Fibromatosis, focal, fibrosis with deformity.
- Localised fibrosis with a deformity. Similar to a scar.
- Fibrous plaque leads to deformity similar to Dupuytren’s contracture.
• Unknown cause (idiopathic). Associated with Dupuytren’s contracture (palmar fibromatosis), in ~25% cases.

Question 34

Outline Condyloma Accuminatum.

Answer 34

• Due to Human Papilloma Virus.
- Causes growth tumours.
• HPV serotypes 6 and 11 (Benign wart).
- Benign wart viruses.
• Fleshy (glans)/warty (skin)
- Cause either fleshy growths on the glans or warty growths on the skin.
• Papillary epithelial benign growth.
• Acanthosis and Koilocytes (clear cells).
- Koilocytes loaded with HPV.

Question 35

Outline Bowen’s disease and Erythroplasia of Queyrat.

Answer 35

• Both dysplasias → pre-cancerous conditions.
• Epithelial hyperplasia and dysplasia.
• HPV type 16, 18.
• On Glans: Erythroplasia of Queyrat.
- On glans of penis known as Erythroplasia of Queyrat.
• On Shaft: Bowens Disease.
- On shaft of penis known as Bowens Disease.
• Premalignant → sq. cell ca.
- May lead to squamous cell carcinoma.
• Microscopy - pleomorphic cells with intact basement membrane. Just dysplasia, not infiltrating.

Question 36

Outline carcinoma of the penis.

Answer 36

• 99% are sq. cell carcinoma.
• Hygiene, smegma irritation? Carcinogen.
- Carcinogens in smegma causing cancer.
• Smoking is a risk factor* HPV 16, 18*
- Smoking and HPV malignant strains (cause cervical cancer) are risk factors.
• Circumcision known to prevent.
- Supporting the fact it may be due to infection.
• Starts as erythroplakia/leukoplakia: dysplasia, Ca-in-situ.
- Starts as Bowen’s disease → leads on to well differentiated squamous cell carcinomas with keratin pearls.
• Well diff. sq. ca - epithelial pearls.
• Slow growth, good prognosis.
• 70% 5 year survival.

Question 37

Outline verrucous carcinoma.

Answer 37

• Variant of squamous carcinoma.
• Gross - large, irregular, papillary/warty.
- Cauliflower like growth.
• Microscopy - no pleomorphism.
- Looks very benign.
• Locally invasive - no metastasis.
• Cut section shows just warty growths.