Neoplasms - MedPath

What does this refer to

• Present at or before birth due to developmental anomalies

• Etiologies: Genetic mutations, teratogenic exposures, in utero obstruction

• May affect kidneys, ureters, bladder, or external genitalia

• Detected through prenatal imaging or postnatal symptoms like UTIs, incontinence, or renal dysfunction

Overview of Congenital Conditions

What does this refer to

• Urethral meatus opens on the ventral side of the penis

• Pathophysiology: Failure of urethral folds to fuse during fetal development

• Clinical: Abnormal stream, chordee (curvature), cosmetic concerns

• Managed with surgical repair between 6–18 months of age

Hypospadias

What does this refer to

• Urethral opening on the dorsal surface of penis or clitoris

• Often associated with bladder exstrophy complex

• Pathogenesis: Malposition of genital tubercle

• Surgical reconstruction is required for continence and function

Epispadias

What does this refer to

• One or both testes fail to descend into the scrotum

• Pathogenesis: Hormonal or mechanical disruptions in testicular descent

• Increased risk of infertility and testicular cancer

• Managed by orchiopexy, ideally before 1 year of age

Cryptorchidism

What does this refer to

• Congenital membranous obstruction in male posterior urethra

• Leads to bladder outlet obstruction and progressive hydronephrosis

• May cause oligohydramnios and Potter sequence deformities prenatally

• Requires catheterization and surgical ablation

Posterior Urethral Valves

What does this refer to

• Retrograde flow of urine from bladder to ureters/kidneys

• Due to congenital incompetence of vesicoureteral junction

• May result in recurrent pyelonephritis and renal scarring

• Diagnosed via voiding cystourethrogram (VCUG)

Vesicoureteral Reflux (VUR)

What does this refer to

• Genetic disorder causing multiple renal cysts

• ADPKD: presents in adulthood; PKD1/PKD2 mutations

• ARPKD: presents in infancy; associated with hepatic fibrosis

• Leads to progressive renal failure, HTN, and cyst rupture

Polycystic Kidney Disease (PKD)

What does this refer to

• Dilation of renal pelvis/calyces due to outflow obstruction

• Can be congenital or acquired

• Chronic backpressure leads to ischemia and atrophy

• Imaging: ultrasound shows fluid-filled renal pelvis

Hydronephrosis

What does this refer to

• Seen in patients on long-term dialysis

• Pathophysiology: hyperplasia of renal tubules with cyst formation

• Increased risk of renal cell carcinoma

• Regular imaging recommended for surveillance

Acquired Renal Cystic Disease

What does this refer to

• Obstruction → Pressure buildup → Ischemia → Atrophy

• Reflux → Infections → Inflammation → Scarring

• Genetic mutations → Abnormal morphogenesis → Functional impairment

Pathophysiologic Themes

What does this refer to

• Prenatal US: detects hydronephrosis, oligohydramnios

• Postnatal US: structural evaluation

• VCUG: reflux and urethral abnormalities

• CT/MRI: stone, abscess, masses

Diagnosis and Imaging

What does this refer to

• Surgical: hypospadias repair, valve ablation, orchiopexy

• Medical: antibiotics, anticholinergics, dialysis

• Long-term: monitor renal function, manage complications

Treatment Approaches

What does this refer to

• Arise from diverse tissues: epithelium, muscle, germ cells

• Include both benign (e.g., oncocytoma) and malignant types

• High morbidity and mortality if not detected early

• Risk factors: genetics, toxins, infections, hormones

GU Neoplasms

What does this refer to

• Originates in renal tubular epithelial cells (usually proximal tubule)

• Clear cell RCC: most common, VHL gene inactivation → ↑HIF → ↑VEGF

• Papillary RCC: MET gene mutations

• Symptoms: hematuria, flank pain, palpable mass (classic triad, but rare)

Renal Cell Carcinoma (RCC)

What does this refer to

• Pediatric malignancy of nephrogenic blastemal origin

• WT1 gene (regulates kidney and gonad development) often mutated

• Associated syndromes:

  • WAGR (Wilm’s tumor, aniridia, GU abnormalities, and developmental delays),

  • Beckwith-Wiedemann ( increased birth weight and height, macroglossia, and an increased risk of childhood cancers like Wilms tumor and hepatoblastoma )

• Histology: triphasic pattern—blastemal, epithelial, stromal components

Wilms Tumor (Nephroblastoma)

What does this refer to

• Most common in bladder but can arise in renal pelvis/ureters

• Initiated by chronic exposure to carcinogens (e.g., tobacco, dyes)

• Papillary (low grade) vs. Flat (high grade/CIS) pathways

• Genetic alterations: TP53, FGFR3, RAS

• High recurrence due to field cancerization

Urothelial Carcinoma

What does this refer to

• 90% are transitional cell carcinomas

• Multifocal origin: entire urothelium at risk

• Clinical signs: painless gross hematuria, irritative voiding symptoms

• Pathophysiology: dysplasia → carcinoma in situ → invasive carcinoma

• Muscle-invasive disease has worse prognosis

Bladder Cancer

What does this refer to

• Adenocarcinoma from peripheral prostate glands

• Hormone-driven (androgen receptor signaling)

• TMPRSS2-ERG fusion gene in ~50%

• Graded using Gleason score (pattern-based histologic grading)

• Metastasizes to bone: osteoblastic lesions (elevated alkaline phosphatase)

Prostate Cancer

What does this refer to

• Peak incidence: ages 15–35

• Seminoma: radiosensitive, slow-growing, ↑placental ALP

• Non-seminomas: aggressive, elevated AFP/β-hCG

• Cryptorchidism is a major risk factor

• Histology and serum markers guide diagnosis and treatment

Testicular Germ Cell Tumors

What does this refer to

• Less than 5% of testicular tumors

• Leydig cell tumors: androgen excess → virilization, precocious puberty

• Sertoli cell tumors: rarely hormonally active

• Usually benign but may rarely become malignant

• Diagnosis based on hormonal profile and pathology

Testicular Sex Cord-Stromal Tumors

What does this refer to

• Squamous cell carcinoma linked to high-risk HPV (16, 18)

• Often preceded by penile intraepithelial neoplasia (PeIN)

• Risk factors: poor hygiene, phimosis, smoking

• Lymphatic spread to inguinal nodes is common

• Treatment: surgery, chemo, and/or radiation based on stage

Penile Cancer

What does this refer to

• Key Pathways:

  • renal cell carcinoma in

    • Von Hippel-Lindau disease-congenital disease of GU tumors

    • Hypoxia-inducible Factor-protein involved in bladder/kidney CAs

    • VEGF

  • Androgen receptor signaling in prostate cancer

  • FGFR3 and TP53 mutations in bladder cancer

• Epigenetic silencing (e.g., hypermethylation of tumor suppressor genes)

• Immune evasion via PD-L1 (programmed death-ligand 1) overexpression in RCC and urothelial cancers

Molecular Mechanisms in GU Cancer

What does this refer to

• Grading: assesses differentiation

- RCC: Fuhrman nuclear grade

- Prostate: Gleason score (sum of 2 most common patterns)

• TNM Staging: guides prognosis and treatment

- T: local invasion

- N: nodal involvement

- M: distant metastasis

Tumor Grading and Staging

What does this refer to

• RCC:

  • EPO → polycythemia

  • PTHrP → hypercalcemia

  • Renin → hypertension

• Prostate:

  • Bone pain, high ALP due to osteoblastic metastases

• Bladder:

  • Rare systemic symptoms like fever, weight loss

Paraneoplastic Syndromes

What does this refer to

• Renal tumors: US → CT abdomen w/contrast

• Bladder cancer: cystoscopy with biopsy

• Testicular tumors: scrotal US → tumor markers (AFP, β-hCG, LDH)

• Prostate: PSA + digital rectal exam → TRUS biopsy

• MRI, PET for metastasis workup

Diagnosis and Imaging

What does this refer to

• Prostate: PSA and DRE (individualized, start age 50 or 40 with risk factors)

• Bladder: screening not routine unless high risk (e.g., chemical exposure)

• Testicular: self-exam education in young men

• Preventive measures: quit smoking, HPV vaccination, avoid toxins

Screening and Prevention

What does this refer to

• RCC: partial or radical nephrectomy

• Bladder: TURBT (early), cystectomy (muscle-invasive)

• Prostate: prostatectomy, sometimes nerve-sparing

• Testis: radical inguinal orchiectomy

• Penile: partial or total penectomy, lymph node dissection

Surgical Treatment Options

What does this refer to

• RCC: resistant to chemo → use immunotherapy or TKIs

• Testicular: platinum-based chemotherapy (cisplatin)

• Bladder: BCG intravesical therapy for CIS

• Prostate: external beam radiation or brachytherapy + ADT

• Penile: chemoradiation in advanced cases

Medical & Radiation Therapies

What does this refer to

• RCC: TKIs (sunitinib, pazopanib), mTOR inhibitors, checkpoint inhibitors

• Prostate: PARP inhibitors (BRCA mutations), androgen receptor blockers (enzalutamide)

• Bladder: anti-PD-1/PD-L1 agents for advanced/metastatic disease

• Precision oncology is evolving in all GU cancers

Targeted and Immunotherapies