Kidney Tumours: Benign & Malignant

Introduction

• Renal tubules can be associated with Papillary adenoma and Renal cell carcinoma
• Mesenchymal tissue can be associated with angiomyolipoma and medullary fibroma
• Epithelium of renal pelvis can be associated with urothelial carcinoma
• Embryonic tissue can be associated with mesoblastic nephroma and nephroblastoma

Types of Benign Tumours

• Renal papillary adenoma is a benign tumour.
• Renal oncocytoma is a benign tumour.
• Medullary fibroma is a benign tumour.
• Angiomyolipoma is a benign tumour.
• Mesoblastic nephroma is a benign tumour.

Types of Malignant Tumours

• Renal cell carcinoma (adenocarcinoma of the kidney) is a malignant tumour
• Nephroblastoma (Wilm's Tumour) is a malignant tumour.
• Urothelial tumours of the pelvicalyceal system are malignant.

Renal Cell Carcinoma (RCC)

• The most common renal cancer accounts for 85% of renal cancers in adults
• Approximately 30,000 new cases are diagnosed per year, with around 12,000 deaths
• Usually occurs during the 6th and 7th decades of life
• The male to female ratio is 2:1
• RCC arises from tubular epithelium
• RCC is also known as hypernephroma, Grawitz tumour, or adenocarcinoma of the kidney

Etiology and Pathogenesis of RCC

• Tobacco is the most important risk factor, with smokers having a two-fold higher risk
• Other factors include:
  • Obesity
  • Oestrogen therapy
  • Hypertension
  • Asbestos exposure
  • Petroleum products and heavy metals
  • Analgesic nephropathy
  • Tuberous sclerosis
  • Cystic diseases of the kidney, whether congenital or acquired

Genetic Factors in RCC

• Genetic factors account for about 5% of RCC cases
• A higher incidence is found in first-degree relatives
• Inherited cases are associated with:
  • Von Hippel-Lindau (VHL) disease: an autosomal dominant cancer syndrome characterized by:
    • Haemangioblastoma of the cerebellum
    • Retinal angiomas
    • Clear cell RCC (40% of all cases of VHL disease)
    • Pheochromocytoma and cysts in various organs

Hereditary Clear Cell Carcinoma

• Hereditary (familial) clear cell carcinoma inheritance is autosomal dominant
• It is characterized by clear cell carcinoma without other manifestations of VHL

Hereditary Papillary Carcinoma

• Hereditary papillary carcinoma inheritance is autosomal dominant
• It is characterized by multiple, bilateral, and multifocal tumors with a papillary growth pattern

Characteristics of Hereditary RCC

• All forms of hereditary RCC tend to be multifocal and bilateral
• Hereditary RCC appears at a younger age compared to sporadic versions

Genetic Mutations in Sporadic Clear Cell RCC

• Loss of the allele of the VHL gene (located on 3p) occurs in 90% of sporadic clear cell RCC
• Mutations in the VHL gene are found in > ½ of these tumours

Tumour Suppressive Function of VHL

• Genetic mutations strongly supports that the loss of the tumour suppressive function of the VHL is an important event in the genesis of clear cell RCC
• Hereditary Papillary RCC shows no association with the VHL gene

Morphology of RCC

• Commonly occurs at the poles of the kidney
• Typically has a golden-yellow colour and is circumscribed
• The cut section appears solid or partly cystic with areas of hemorrhage and necrosis
• Grossly visible papillae appear in the papillary type

Histological Classification of RCC

• Clear Cell RCC accounts for 70% of cases
• Papillary type accounts for 15% of cases
• Granular Cell Type accounts for 8% of cases
• Chromophobe RCC accounts for 5% of cases
• Sarcomatoid Type accounts for 1.5% of cases
• Collecting Duct Type accounts for 0.5% of cases

Clinical Features of RCC

• The classic triad includes haematuria, flank pain, and a palpable abdominal mass, but only occurs in 10% of cases
• Haematuria is the single most common presenting sign
• Known as one of the great mimics in clinical medicine
• Symptoms include intermittent fever, weight loss, cachexia, and fatigability
• Paraneoplastic syndromes occur due to ectopic hormone production
  • Hypercalcemia, hypertension, polycythemia, and Cushing's syndrome can appear

Prognosis of RCC

• The overall survival rate is 40% at 5 years
• Prognosis is influenced by tumour size, extent of invasion and metastasis, histological type, and nuclear grade
• Few patients with the sarcomatoid type survive for more than 1 year
• For clear cell RCC, survival after nephrectomy is 50%
• Papillary and chromophobe types have a better prognosis than clear cell type, while the granular cell type has a worse prognosis
• Tumour stage, which is a measure of the invasion and metastasis, is the most important prognostic factor

Metastasis of RCC

• Possible sites of metastasis include:
  • Lungs (>50%)
  • Bones (33%)
  • Regional lymph nodes, liver, adrenal gland, and brain

Nephroblastoma Overview

• Nephroblastoma, also known as Wilm's tumour is defined as the commonest malignant abdominal tumour in children
• It is the 3rd most common malignancy in children under 10 years old, after Leukemia and Neuroblastoma
• It is diagonised between 1 and 6 years (peak 2-5 years), with 95% before age 10
• There is an equal incidence by sex

Key Features of Nephroblastoma

• There can be affectation of both kidneys either synchronously or metachronously
• Bilateral cases account for about 5-10% of cases
• Bilateral cases usually occur about 10 months earlier than the unilateral ones
• Malignant neoplasm of embryonal nephrogenic elements include:
  • Blastemal
  • Stromal (messenchymal)
  • Epithelial

Classification of Nephroblastoma in relation to similar tumour types

• Nephroblastoma is categorised as a small round with blue cell tumours

• Other tumours are classified in this group:

  • Burkitt lymphoma
  • Retinoblastoma
  • Medulloblastoma
  • Neuroblastoma
  • Hepatoblastoma
  • Rhabdomyosarcoma
  • Ewing sarcoma

Pathogenesis of Nephroblastoma

• In 5% of cases, it arises in the context of 3 different congenital syndromes
• All of these syndromes include an increased risk for the development of the cancer at an early age & bilaterality
  • WAGR syndrome
  • Wilms tumour
  • aniridia
  • genitourinary abnormalities
  • mental retardation
• Deny-Drash syndrome (DDS)
  • Wilms tumour
  • intersexual disorders
  • glomerulopathy
• Beckwith-Wiedeman syndrome (BWS)
  • Wilms tumour
  • overgrowth ranging from gigantism to hemi-hypertrophy
  • visceromegaly and macroglossia

Genetic and Familial aspects of Nephroblastoma

• Familial links accounts for around 5% of cases
• It is characterised by Early onset, bilateral but not associated with any other syndrome
• 1/3 of children with WAGR syndrome eventually develop Wilms tumour
• In WAGR, there is constitutional deletion of 11p13
• WT1 is a tumour suppressor gene

Genetic factors and syndromes associated with Nephroblastoma

• All Wilms tumours linked with WAGR syndrome display defects of WT1
• Less than than 10% of sporadic tumours exhibit this abnormality
• Other genes play a more critical role than WT1 in the genesis of sporadic Wilms tumours
• A second gene (WT2) was discovered in sporadic tumours that showed loss of heterozygosity on chromosome 11p15
• This site is distinct but close to WT1
• WT2 is also linked to BWS

Genetic risk factors associated with Nephroblastoma

• Patients with Denys Drash have a higher risk for WT (90%) than WAGR
• Apart from WT, risks also include a developing Gonadoblastoma (a germ cell tumour)
• Patients with BWS also have a potential development of hepatoblastoma, pancreatoblastoma, adrenocortical tumours & rhabdomyosarcoma

Macroscopic Morphology of Nephroblastoma

• Tumors are typically large, replacing most of the kidney
• Cut section shows usually bulging & pale tan surface with occasional foci of hemorrhage, cysts & necrosis

Microscopic Histology of Nephroblastoma

• Microscopically, Nephroblastoma is categorised small round blue cell tumour
• The tumors are composed of 3 types of of elements that resemble normal foetal tissue
• – metanephric blastema
• immature stroma (mesenchymal tissue) include
• immature epithelial element
• Usually components will contain of all 3 types, but sometimes only 2

Components of Nephroblastoma

Blastema components

• Blastema cells microscopucally have Small round to ovoid cells with scanty cytoplasm, growing in nests & trabecules

Epithelial components

• Contains of small tubular structures & sometimes as structures resembling immature glomeruli

Stroma of Nephroblastoma

• Spindle cells which are mostly undifferentiated but occasionally display smooth muscle or fibroblast differentiation
• Skeletal muscle most common heterotopic stromal element, though bone, cartilage, fat or neural tissue may be seen

Clinical features of Nephroblastoma

• Usually presents between 1 & 3 years of age
• 98% of cases occur before 10 years of age
• Spontaneous cases account for 99% of all
• Few familial cases exist as autosomal dominant inheritance
• In only 5% of sporadic cases appears bilateral
• Diagnosis most often happens after recognition of an abdominal mass

Additional symptoms of Nephroblastoma

• Abdominal pain
• Intestinal obstruction
• Hypertension
• Haematuria
• Symptoms of traumatic rupture of the tumour

Prognosis and related factors of Nephroblastoma

• Patients younger than 2 years of age tend to have a better prognosis
• Invasion of the tumour beyond the renal capsule, noted at the time of surgery, is a negative prognostic indicator
• Anaplasia is also a negative indicator, tending to appear more common in older patients
• Combined therapy with chemotherapy, radiotherapy & surgery offers best hope
• Overall long survival rate in many centres is approaching almost 90%