RENAL PATHOLOGY

TUMOURS OF THE URINARY TRACT

Assoc. Prof. Dr. Manjit Singh Saren

HOD Pathology
MAHSA University
2019
TUMOURS OF RENAL SYSTEM

Desired Learning Outcome:

On completion of this topic, you should be able to:

1. List the common tumours of the urinary tract.

2. Classify and discuss renal cell carcinoma in terms of aetiopathogenesis, morphology, clinical
manifestations, complications and laboratory investigations.
3. Discuss nephroblastoma in terms of aetiology, associated genetic factors, morphology,
complications.
4. Discuss the bladder carcinomas in terms of aetiology, pathogenesis, morphology, clinical
manifestations, complications and laboratory diagnosis.

Contents.
1. Renal Cell carcinoma.
i. Aetiopathogenesis.
ii. Morphology
iii. Clinical manifestations.
iv. Laboratory investigations.
2. Nephroblastoma
i. Aetiology.
ii. Morphology
iii. Clinical manifestations.
iv. Laboratory investigations

3. Urinary Bladder Tumours.

i. Aetiopathogenesis.
ii. Morphology
iii. Clinical manifestations.
iv. Laboratory investigations.
CLASSIFICATION : URINARY TRACT
TUMOURS

1. BENIGN TUMORS
a. Cortical adenoma
b. Renal fibroma
c. Angio-myolipoma
d. Leiomyoma
e. Haemangioma
2. Malignant Tumours

1. Renal cell carcinoma

2. Nephroblastoma

3. Urothelial Carcinoma.
TUMOURS OF THE RENAL SYSTEM

1. Childhood:
Age: 2 yrs-8 yrs.
“Blastoma”
2. Adults:
Age: 60yrs-70 yrs.
Carcinomas:
i. Renal Cell Carcinoma
ii. Transitional Cell Carcinoma.
iii. Squamous Cell Carcinoma.
Hypertension:
i. Renal Parenchymal Disease:
Chronic kidney disease.
ii. Renal artery stenosis.
iii. Renal cell carcinoma.
iv. Wilm’s tumour.
RENAL CELL CARCINOMA

(CLEAR CELL CARCINOMA)

A 64- year -old male presented with hypertension and
microscopic haematuria for 3 months. Urine FEME showed 12-
15rbc/hpf. His haemoglobin was 9.6 g/ml. An ultrasound
confirmed a renal tumour in the upper pole of the left kidney.
Histological features were those of a renal cell carcinoma.
Classification: Subtypes:

1. Clear cell carcinoma.

2. Papillary clear cell carcinoma.
3. Chromophobe renal cell carcinoma
Renal Clear Cell Carcinoma
Origin:
Proximal tubular epithelium.
• Incidence:
2 % of all human cancers
190,000 cases annually.
85% of Renal carcinomas

• Sex: Twice as common in men as in women: 2/1

• Age: Sixth –seventh decade of life
• 2% associated with inherited conditions:
Von Hippel- Lindau gene mutation.
 Genetics:
1. Inactivation of the VHL tumor-suppressor protein.
Von Hippel–Lindau (VHL) Disease:
Familial Renal Cell Cancer Syndrome.
Incidence VHL:
1:36,000 to 1:45,500 population.
VHL Germ line mutation gene: Chromosome 3p-25.

2. Transcription Hypoxia Induced Factor (HIF)

HIF factor induces:
i. Hypoxia
ii.Angiogenesis:
Over expression Vascular Endothelial Growth Factor.
(VEGF)
3. Familial Cancer Syndrome:
Hereditary Non -Polyposis Colorectal Cancer
(Lynch Syndrome- autosomal dominant.)

4. Hereditary Leiomyomatosis and RCC Syndrome:

i. Cutaneous and uterine leimyomatosis.
ii. Aggressive papillary renal cell carcinoma.

5. Hereditary Papillary carcinoma:

Mutation of MET proto-oncogene.
RISK FACTORS:
1. Smoking: Doubles the risk
2. Analgesics:
Phenacetin
Cyclophosphamide
3. Occupational Carcinogens:
i. Coal, Asphalt, Tar
ii. Petrochemicals and Plastics
iii. Asbestos
iv. Heavy metals: Cadmium
4. Radiotherapy:
Pelvis.
5. Obesity: (Female)
6. Additional factors: Hypertension
Acquired cystic kidney disease
Chronic Renal Dialysis
Tuberous sclerosis.
Common Location

Gross:
Upper pole
Cortical
Globular and bossellated
Solitary unilateral mass
Pseudo-encapsulation
Golden brown (Lipids, Cholesterol and Phospholipids)
Variegated appearance
Cystic and haemorrhagic necrosis
Micro:
Tumour cells in alveolar pattern

Solid nests of tumour cells.

Nuclei:
Small and hyperchromatic.
Cytoplasm:
Clear-granular. (Glycogen)
Eosinophilic granular. (Lipids)
Vacuolated
Stroma:
Vasculature: Network of thin blood vessels.
Spread:
Invasion of Renal Vein
Clear Cell Carcinoma (Low magnification)
Blood Vesels

Clear Cells

Clear Cell Carcinoma (High Magnification)

Clear Cell Carcinoma
SYMPTOMS

TRIAD

1. Costo-vertebral pain
2. Haematuria
3. Flank mass.
4. Fever and malaise
5. Weight loss
6. Anaemia.
7. Paraneoplastic Syndromes.
Costo-Vertebral Angle
Paraneoplastic Syndrome: Renal Cell Carcinoma

1. Hypercalcemia.
(Pseudo-hyperparathyroidism)

2. Erythrocytosis: (Polycythaemia).
(Elevated erythropoietin).

3. Hypertension.
(Increased renin levels).

4. Gynaecomastia. (Feminization)
(Increased prolactin and gonadotrophins)

5. Cushing syndrome.
Spread:
1. Renal vein
2. Para-renal veins: Inferior Vena Cava.
Metastases:
Lungs and the bones.

Prognosis:
Nuclear changes

1. Grade 1: Small nuclei with no nucleoli.

2. Grade 2: Open nuclei with inconspicuous nucleoli.

3. Grade 3: Open nuclei with granular chromatin and

nucleoli.
4. Grade 4: Hyperchromatic nuclei with macro-nucleoli.
Staging
Stage 1: <7cm. And confined to kidney.

Stage 2: >7cm and confined to kidney.

Stage 3: Tumour invades renal capsule

Confined to Gerot’s fascia.

Stage 4: Invasion adjacent structures

Metastasis:
Lymph nodes.
Distal organs.
5 Year Survival Rate

Stage 1: 90 %

Stage 2: 85 %

Stage 3: 60 %

Stage 4: 10 %
NEPHROBLASTOMA
WILM’S TUMOUR
a
Age:
37-45 months
98 %: Under 1 year
7th commonest childhood malignancy.
Sex:
Both
Incidence:
1 in 8000
Origin:
Mesoderm
Inherited as an autosomal dominant trait
Ethnicity:
Africans: High.
Asians: Low
Both kidneys equally affected.
Genetics:
a). WT 1: Mutation Tumour Suppressor Gene.

1. WAGR syndrome:
(Wilm Tumour, Anirida, Genito-urinary abnormalities, Mental Retardation)
1 in 3 develop Wilm’s Tumour
2. Denys-Drash Syndrome: 90 % risk.
i. Gonadal dysgenesis
ii. Early nephropathy.
iii. Inactivation of WT1 gene
Both: Associated with abnormalities of the Wilms Tumor 1 gene
(WT-1) located on 11p13.

3). WT-2: Abnormalities locus on WT-2

1. Beckwith-Wiedemann Syndrome (BWS): WT-2

Gross:
Solid unilateral renal mass.
Color:
Grey-tan.
Renal shape:
Distorted.
Calcification
Fibrous pseudo-capsule
Cystic:
With polypoidal protrusions.
 KIDNEY

WILMS TUMOUR

URETER
Micro:
Triphasic:
1. Blastemal Cells: Undifferentiated.
Small blue oval mitotically active cells
Pattern: Rosettes
Papillary
Tubular
2. Epithelial Cells: Differentiated
Abortive renal tubules
Primitive glomeruli.
3. Stromal: Mesenchymal tissue
Fibrocystic or myxoid elements
Muscle
Adipose
Tubules
Blastemal Cells

WILMS TUMOUR
a
 Tubules

Stroma

WILMS TUMOUR
Clinical Features:
i. Abdominal mass
ii. Pain
iii. Fever
iv. Acute abdomen
v. Anaemia
vi. Haematuria
vii. Hypertension (Renin)
viii. Polycythemia (Erythropoietin)
ix. Intestinal obstruction.

Increased risk: Leukemia and lymphoma.

Sarcoma.
Breast cancers.
Grading:
Infiltration into capsule.

Immunoprofile:
WT 1 in epithelial and blastema cells
Metastasis:
Lungs
Bone

Prognosis:
Favourable.
URINARY BLADDER CARCINOMA

1. UROTHELIAL CARCINOMA
(Transitional Cell Carcinoma)

2. SQUAMOUS CELL CARCINOMA

Histopathology Classification: Bladder Tumours.

1. Transitional cell carcinoma 90%

2. Squamous cell carcinoma 7-8%
3. Adenocarcinoma 1-2%
4. Small cell carcinoma.
5. Leiomyosarcoma.
6. Lymphoma.
TRANSITIONAL CELL CARCINOMA
Definition:

Malignant urothelial neoplasm.

Origin: Transitional epithelium:
1. Urinary bladder.
2. Ureters.
3. Renal calyces /pelvis .
Commonly: Papillary in nature
Multifocal.
Superficial: 70 %
Invasive: 30 % (Aggressive)
Recurrence: High
UROTHELIAL TUMOURS

SITES:

 URINARY BLADDER :
94% OF ALL UROEPITHELIAL TUMORS

 RENAL PELVIS:
 5% OF ALL UROTHELIAL TUMORS

 URETER:
 1% OF ALL UROTHELIAL TUMORS
TRANSITIONAL CELL CARCINOMA

Incidence: 7th commonest (3.2 % of all cancers)

Sex: M/F-3.5/1
Aetiology:
Smoking: Chemical carcinogens: DNA damage
Glutathione -S Transferase M1: Null status.
Occupational:
i. Aniline dye workers (Aromatic amines)
ii. Benzidine
iii. Leather works
Tryptophan metabolites

Drugs:
Analgesic abuse
Cyclophosamide.
Infections: Chronic urinary tract Infections.
Common sites:

Posterior and lateral walls: 70 %

Trigone and neck: 20 %
Vault: 10 %

Grades: Nuclear Anaplasia.

Grade 0 (Papilloma)
Grade 1.Well differentiated: Mild anaplasia
Grade 2. Moderately differentiated: Moderate anaplasia
Grade 3. Poorly differentiated: Marked anaplasia
Papillary Carcinoma versus Invasive Carcinoma
PAPILLARY (FLAT) CARCINOMA
INVASIVE VERSUS NONINVASIVE
Squamous Cell Carcinoma
Predisposing factors
 Chronic irritation (bladder stone)
 Schistosoma haematobium infection - the ova are
deposited in bladder wall lead to chronic
inflammation  progressive squamous metaplasia 
dysplasia (mild-moderate-severe)  Anaplasia.
 Squamous cell carcinoma
 SIGNS AND SYMPTOMS:
Depends on site
Extent of tumour invasion.

1. Painless gross haematuria. (Blood Clots)

2. Dysuria
3. Frequent micturition.
4. Palpable pelvic mass
5. Lower leg oedema
6. Weight loss
7. Anaemia
8. Bone pains.
 
Bladder Urothelial Carcinoma

Complications:
Obstructive uropathy.
Hydronephrosis.

Spread:
Direct extension: Prostate, Uterus, Seminal vesicles.
Retroperitoneal, Colon and vagina.
Lymphatic: Pelvic nodes
Blood: Bones and lungs.
Implantation:
Wounds and prostate
Denuded urothelium.
ANGIOMYOLIPOMA
Age: Adults 1 %
Benign Tumour: A hamartomata.

Comprises: Vessels, Smooth Muscle and Adipose tisue

Origin:
Perivascular Epithelial Cells
Associated with Tuberous Sclerosis: 25-50%.
Usual symptoms:
Abdominal pain, haematuria, chills and fever.
 Aetiology:
Due to loss of: TSC1 or TSC2 tumour suppression gene.
Complication:
Haemorrhage.
Hypertension
ANGIOMYOLIPOMA
 DIAGNOSIS:

1. Urine cytology.
2. Ultra-sonography
3. CT scan
4. MRI
5. Cystoscopy
6. Bladder Biopsy.
7. Radionuclide bone scan.
Recommended Reading

1. Robbin’s: Basic Pathology 9th Ed.

Pgs: 549-262

2. Cotran and Robbins: Pathology Basis of Disease 9th Ed.

Pgs: 479-481
964-968