Dr Perner 2024 Renal Lecture 4 Neoplasms MGT & Prostate PDF

Neoplasms of the male genital tract & pathology of the prostate gland Lecture 4 Division of Anatomical Pathology Wits Medical School Learning objectives MGT neoplasms 1. Common neoplasms of the penis including precursor lesions 2. Aetiology and pathogenes...

Neoplasms of the male genital tract & pathology of the prostate gland Lecture 4 Division of Anatomical Pathology Wits Medical School Learning objectives MGT neoplasms 1. Common neoplasms of the penis including precursor lesions 2. Aetiology and pathogenesis of carcinoma of the penis 3. Neoplasms of the urinary tract (ie ureter, bladder and urethra) 4. Tumours of the testis, differences between the seminomatous and non-seminomatous germ cell tumours 5. Spread and staging of testicular tumours, prognosis and treatment Learning objectives - prostate gland 1. Define and describe the pathogenesis, pathology and clinical manifestations of prostatitis. 2. Define benign prostatic enlargement (BPE) and describe the aetiology, pathogenesis, pathology, sequelae and clinical manifestations of this condition. 3. Define and describe the pathogenesis, pathology, spread and staging of prostatic carcinoma. Common neoplasms of penis Benign Pre-malignant 1. Condyloma accuminatum 1. HPV & Penile intra- epithelial neoplasia & “Giant condyloma” 2. Bowenoid Papulosis 3. Bowen Disease 4. Paget disease Malignant 1. Squamous cell carcinoma Condyloma accuminatum Benign tx, related to the common wart (verruca vulgaris) Caused by “low risk” HPV subtypes – esp type 6 and 11 Penis - coronal sulcus and inner surface of prepuce most common sites Single or multiple sessile or pedunculated red papillary excrescences 1 – several mm size This circumcision specimen shows a warty cauliflower-like lesion with papillary or polypoid fronds in a foreskin. A low power scan of the glass slide shows warty cauliflower-like lesion with numerous papillary or polypoid fronds. The usual location for genital condylomas is corona of glans penis or penile meatus. This image shows hyperkeratosis, parakeratosis, and koilocytosis. Cytologic atypia is minimal. Condylomas that have been treated with podophyllin may show significant reactive atypia that may be mistaken for malignant changes. Pre-malignant lesions of the penis Bowenoid papulosis Young sexually active males 16- 35yr Small 2-10mm multicentric smooth velvety lesions esp on glans Oncogenic HPV esp 16, also 18 &/or 33-35 often found Histo: Penile IEN grade III – In situ Ca -same histo picture as Bowen disease Predom transient & clinically benign in young people – spontan regression reported in immunocompetent male < 30 yrs  Pre-malignant lesions of the penis Bowen Disease See Seefull fullsize sizeimage image Older male - av age 61 yrs HPV strains 16, 18, 34, and 48 Untreated, transformation to SCC 5-33% Single well demarcated red papule/plaque Pre-malignant lesions of the penis HPV & penile intra-epithelial neoplasia (IEN) “High risk’ HPV subtypes- esp 16 and 18 Penile IEN – graded I – III Grade depends on proportion of epithelial thickness replaced by atypical cells Carcinoma Penis Squamous cell carcinoma 1% cancer USA Not circumcised (smegma) HPV (16/18) 40-70 yrs Pathology: Glans / inner surface prepuce Indurated white plaque →Ulcerating / fungating tumour Squamous cell ca of Penis = sexually transmitted disease Clinically Slow growing Metastases: Inguinal & Iliac LN If limited to shaft:→ Penectomy: 95-100%, 5yr survival Regional LN →30-50% survival Here is a squamous cell carcinoma of the head of the penis. Note the uncircumcised state, which increases the risk for such carcinomas. The neoplasm has an ulcerated surface. This is an example of moderately-differentiated squamous cell carcinoma arising in an uncircumcised elderly male with phimosis. Lack of circumcision with poor hygiene leading to smegma retention appears to be a major risk factor for penile cancer. Tumours of the urinary tract Ureter, bladder and urethra  Ureter, bladder and urethra Obstructive symptoms or haematuria Common in 6-7th decade of life Most commonly transitional cell carcinoma Urinary bladder: risk factors Cigarette smoking, prolonged exposure to cyclophosphamide, analgesic use, bladder irradiation unusual SCC - bilharzia Ureter, bladder and urethra Pathology: Macro: Papillary, polypoid, sessile or ulcerated Subtle; granular or velvety mucosa Micro: Majority: invasive irregular aggregates / small clusters and single neoplastic transitional cells Urothelial carcinoma of the ureter. The papillary fronds have obstructed the flow of urine, causing hydroureter and hydronephrosis.  Papillary urothelial carcinoma. An opened cystectomy specimen shows a large papillary neoplasm at the left and several smaller papillary neoplasms at the top and right. Urothelial carcinoma. The invasive carcinoma is separating fibres of the muscularis propria. Tumours of the Testis  Classification Testicular Tumours WHO CLASSIFICATION (Modified) 1) Germ cell tumours 1) Pure – Seminoma, Embyronal Ca, Yolk sac tumor, trophoblastic tumors, teratomas 2) Mixed – any combination of above 2) Sex-cord stromal tumours 1) Leydig cell tumour 2) Sertoli cell tumour 3) Granulosa cell tumour 3) Mixed sex-cord – germ cell tumours 4) Mesenchymal tumours 5) “Passenger” cell tumours 1) Lymphoma 2) Leukaemia Germ cell tumours Clinical features Two broad categories Seminoma GCT Non-seminomatous GCT Different clinical presentation and behaviour Both present with painless mass ALL PAINLESS TESTICULAR MASSES –TUMOUR UNTIL PROVEN OTHERWISE Comparison seminoma & non- seminomatous germ cell tumours SEMINOMA NSGCT Remain localised for long Metastases occur earlier time Haematogenous → less Lymphatic spread → predictable predictable Less sensitive to DXT / Radio / chemosensitive Chemo Less aggressive Aggressive Better prognosis Poorer prognosis  Spread and Staging of Testicular Tumors Lymphatic spread: retroperitoneal LN (int iliac & para-aortic) → mediastinal → supraclavicular Haematogenous → lung, liver Staging: TNM classification Stage 1: Confined to testes Stage 2: Retroperitoneal LN, below diaphragm Stage 3: Mets beyond retroperitoneal LN / above diaphragm Stage 4: Visceral mets Pathology of the Prostate Gland PROSTATITIS 3 types: Acute suppurative (bacterial) prostatitis Chronic bacterial prostatitis Granulomatous prostatitis Acute suppurative prostatitis Secondary to urethritis or cystitis – coliforms (E.coli etc), staphylococci, gonococci After urethral catheterisation or endoscopy Rarely, blood borne infection Acute suppurative prostatitis Symptoms: difficulty in micturition, perineal or rectal pain, gen malaise, pyrexia Palpably enlarged, soft & tender prostate on PR Histology: Acute inflammation with acini distended by neutrophils, macrophages and damaged epi cells +/- necrosis with abscess formation with discharge into urethra There is marked neutrophilic infiltrate within and around glands. Some glands are partially destroyed. Chronic bacterial prostatitis Secondary to acute prostatitis Sexually active, STD: Chlamydia trachomatis Numerous small dark blue lymphocytes are seen in the stroma between the glands. The serum prostate specific antigen may be slightly elevated. Granulomatous prostatitis Heterogeneous grp Enlargement of gland, urethral obstruction Enlarged, firm indurated gland on PR d/t fibrosis & inflam component – can mimic Ca Aetiology: Idiopathic (assoc with leakage of material from distended ducts in gland enlarged by BPH) TB Following transurethral resection for BPH Allergic (eosinophilic) prostatitis- rare , in men with bronchial asthma Other – following BCG therapy  Non-specific Granulomatous Inflammation The inflammatory infiltrate is largely composed of plasma cells, lymphocytes, and macrophages. Rare neutrophils are also seen.  Post-biopsy granuloma An area of fibrinoid necrosis walled off by a cuff of histiocytes is seen in this prostate biopsy.  Benign Prostatic Enlargement (BPE) Definition: Benign proliferation of all elements (hypertrophy and hyperplasia) Incidence: Common 20% by age 40yrs 70% by age 60yrs 90% by age 90yrs Only 5-10% require intervention Decade earlier in Black Aetiology Hormonal imbalance 1) Aging →↑expression of testosterone receptors → sensitivity to testosterone, although testosterone levels decrease with age 2) DHT accumulates in prostate, more potent than testosterone Pathology Enlarged 60-100gm Nodular Yellowish – pink → fibrous white nodules TRANSITION ZONE Compresses urethra to slit-like space Complications Hypertrophy of bladder → trabeculations →diverticula UTI Hydronephrosis NOT PRE-MALIGNANT, but assoc with cancer as both occur in same age group Tumours of the prostate  Ca Prostate Incidence Most common ca in 69 / 100 000 ↑ incidence with ↑ age 45-49 yrs: 4,8 / 100 000 70-75 yrs: 513 / 100 000 Aetiology Risk factors Age Race: blacks > whites Family history Environmental factors Consumption of fats ? Influences levels of testosterone Vitamin A / β-carotene Endocrine factors: Androgens → permissive role Not in eunuchs Castration / Oestrogen = treatment Tumour cells = androgen receptors Prostatic intra-epithelial neoplasia (PIN) 80% of cases of adenocarcinoma have coexistent PIN 33% PIN → cancer, within ~ 10 yrs PIN = same molecular changes of carcinoma Malignancy follows cumulative molecular changes Prognosis 1. Histological Grading (Gleason’s score / WHO Grade) 2. Clinical Staging A) Incidental / unsuspected clinically A1: < 5% resected tissue; A2: > 5% B) Palpable PR, confined to prostate B1: 1 Lobe; B2: Both lobes C) Beyond prostate, no metastases C1: Not involving seminal vesicles; C2: SV Involved D) Distant metastases Diagnosis Symptoms of urinary obstruction PR: Craggy, firm gland Transrectal ultrasound (TRUS) Serum PSA (> 4ng/µl) Biopsy Treatment Surgery A,B stage → Radical prostatectomy Survival ~ 15 years C,D stage → Palliative Radiotherapy Disseminated disease → palliation Orchidectomy Oestrogen administration The End