Renal tumours

Classification according to ICCC : VI.

Definition

Renal tumours account for 4 to 6 percent of all cancers in children under the age of 15. Nephroblastoma (or Wilms’ tumour) is a typical tumour made of embryonic tissue, and the most common renal tumour in children. Non-Wilms’ tumours (mainly renal cell carcinoma, clear-cell sarcoma of the kidney, and rhabdoid tumour) account for 10 to 15 percent of renal tumours. The WHO classification from 2004 describes almost 50 different types of renal tumours, which are defined by their morphology (histology), immunohistochemistry, clinical and genetic characteristics. Only about 4% of all renal tumours are of benign character (angiomyolipoma, cystic tumours, mesoblastic nephroma, …).

Epidemiology

Wilms’ tumour

  • incidence rate of 1 per 10,000, accounting for up to 87% of renal tumours
  • its incidence peaks in children under the age of 5 (median age of 3.5); the tumour is rare in children aged over 10
  • it is slightly more common in girls
  • it is unilateral in most cases, but a bilateral occurrence is reported in 5 to 10 percent of cases

Non-Wilms’ tumours

  • non-Wilms’ tumours are rare cancers
  • renal cell carcinoma accounts for 2 to 6 percent of all renal tumours in children and adolescents, and is slightly more common in girls; its incidence rate is 0.1 to 0.2 per 100,000 children
  • clear-cell sarcoma accounts for 2 to 3 percent of all renal tumours in children, its incidence peaks at the ages of 2.5–4; it is more common in boys, and often metastasises into the bones
  • rhabdoid tumour accounts for about 1 percent of all renal tumours in children

Clinical symptoms

Symptoms are practically the same for all renal tumours.

  • asymptomatic palpable (often even visible) tumour mass is the most common symptom
  • the tumour is often found while giving the child a bath, or during a preventive examination
  • the general patient’s condition is usually very good
  • less than one third of patients have non-specific symptoms: subfebrile temperature, fatigue, pallor, obstipation, abdominal pain; these symptoms are more common in clear-cell sarcoma of the kidney
  • macroscopic haematuria (sometimes only temporary) is present in 10 to 30 of patients, which is the sign of the tumour growing through the hollow system of the kidney.
  • hypertension can occur in 25% of patients

Aetiology

Wilms’ tumour

  • aetiology is usually unknown, the tumour develops sporadically
  • higher risk and predisposition to the development of Wilms’ tumour has been described in hereditary anomalies and syndromes (in about 1% of nephroblastomas)
    • Beckwith-Wiedemann syndrome
    • Denys-Drash syndrome
    • WAGR syndrome (Wilms’ tumour, aniridia, genitourinary anomalies, retardation)
    • Frasier syndrome
    • hemihypertrophy

Non-Wilms’ tumours

  • aetiology is usually unknown, the tumour develops sporadically
  • familial occurrence of renal cell carcinoma has been reported in several predisposition syndromes:
    • von Hippel-Lindau syndrome
    • tuberous sclerosis
    • Birt-Hogg-Dubé syndrome
  • aetiology of clear-cell sarcoma and of rhabdoid tumour is unknown

Diagnosis

  • medical history and family history
  • clinical examination (gentle superficial palpation – risk of rupturing the tumour capsule!)
  • imaging examination:
    • abdominal ultrasound (+doppler, ruling out a tumour thrombus in the vena cava inferior)
    • abdominal CT scan, chest x-ray and CT scan
    • optionally: CT scan of the brain and bone scintigrafy (according to the histological subtype)
    • 18F-FDG PET is not routinely recommended
  • kidney function tests:
    • DTPA kidney scan
  • laboratory examination:
    • haematological (blood count, possibly coagulatin)
    • biochemical (ionogram, renal tests, cystatin C, LDH)
    • urinalysis
    • there is no specific marker for renal tumours
  • histological examination + immunohistochemistry of the tumour
  • cytogenetic and molecular genetic examination of the tumour

Differential diagnosis

In the differential diagnostic procedure, the following should be ruled out:

  1. congenital anomalies imitating the tumour (cysts, horseshoe kidney and other shape anomalies, caliectasis)
  2. inflammatory lesions (abscesses, mycotic foci in the kidney)
  3. benign tumours (mesoblastic nephroma, fibroma, angiomyolipoma, adenoma, teratoma)
  4. other non-Wilms’ malignant primary tumours (renal cell carcinoma, PNET, fibrosarcoma, clear-cell sarcome, rhabdoid tumour of the kidney)
  5. malignant secondary tumours (metastases – rare, rather occuring in systemic malignancies – lymphomas, leukaemias)
  6. nephroblastoma

Treatment

A combination of surgical treatment, chemotherapy and radiotherapy predominates in the treatment of renal tumours.

Wilms’ tumour

Classification into risk groups is performed according to the following factors:

  • histology (exact histological subtype)
  • response to neoadjuvant chemotherapy
  • patients’ age
  • size of the tumour
  • biological characteristics of the tumour

Treatment modalities: in combination

  1. chemotherapy:
    • SIOP (Europe) - 4 weeks of neoadjuvant pre-operative chemotherapy, adjuvant (post-operative) chemotherapy according to the risk group
    • COG (US) - adjuvant chemotherapy after the primary surgery, according to the risk group
  2. surgical treatment:
    • nephrectomy (abdominal approach)
    • heminephrectomy (excision of part of the kidney) in strictly indicated cases
  3. radiotherapy: indications have been reduced significantly; radiotherapy is only used in the following cases:
    • non-radical surgery, perforation (rupture) of the tumour capsule
    • infiltration into abdominal lymph nodes
    • residual lung metastases after chemotherapy

Bilateral tumour:

  • the duration of neoadjuvant therapy is personalised with the objective of maintaining as much functioning renal parenchyma as possible,
  • adjuvant therapy is indicated according to the histological type, response to neoadjuvant chemotherapy, and the local stage

Renal cell carcinoma

Renal cell carcinoma is a chemoresistant tumour. Radical surgical removal of the tumour is crucial in the treatment, providing the only real chance of a long-term survival. The tumour is mostly localised in children and adolescents. Biological therapy (tyrosin kinase inhibitors, mTOR inhibitors, antiangiogenic therapy) is indicated in cases where postoperative (adjuvant) therapy is necessary.

Clear-cell sarcoma

Clear-cell sarcoma is a very agressive tumour, and requires a comprehensive cancer treatment (if possible, a radical surgery followed by an intensive chemotherapy and radiotherapy).

Rhabdoid tumour

Rhabdoid tumour requires an aggressive comprehensive cancer treatment, including a high-dose chemotherapy and an autologous transplantation of haematopoietic cells. Despite an aggressive therapy, the prognosis remains rather poor, and new drugs and treatment procedures must be sought.

Prognosis

Wilms’ tumour

Wilms’ tumour is a curable cancer. The prognosis depends on:

  • histological type of tumour
  • response to neoadjuvant chemotherapy
  • extent (clinical stage) of the disease
  • cytogenetic and biological characteristics of the tumour

The five-year survival rate is about 90% for patients with localised disease, and more than 70% for patients with metastatic disease.

Renal cell carcinoma

The prognosis of renal cell carcinoma depends on the tumour size, and particularly on its stage. More than 60% of paediatric patients survive in the long term. The prognosis is much worse in patients with metastatic disease, and long-term survival has not been described yet.

Clear-cell sarcoma

Clear-cell sarcoma has a rather poor prognosis: after radical surgery and undergoing cancer treatment, up to 70% of patients are still alive 5 years after diagnosis. The prognosis is practically fatal in metastatic, advanced and recurrent tumours.

Rhabdoid tumour

Rhabdoid tumour is one of the most aggressive tumours; up to a quarter of patients have a tumour of stage IV at the time of diagnosis. Less than 25% of patients survive 5 years after diagnosis. There is no effective treatment for metastatic and recurrent tumours, and the prognosis is fatal.

Literature

  1. Bajčiová, V.: Nádory ledvin u dětí, adolescentů a mladých dospělých. Rozdíly v biologii napříč věkovým spektrem. Onkologie 2011; 5(6): 355–358.
  2. Bajčiová, V.: Přehled současných úspěchů i problémů v diagnostice a léčbě nádorů ledvin v dětském věku. Urológia 2007; 13(1): 6–11.
  3. Bajčiová, V.: Wilmsův nádor a nádory ledvin u dětí a adolescentů. In: Adam, Z. a kol.: Speciální onkologie: Příznaky, diagnostika a léčba maligních chorob, Galen 2010. pp. 369–370. ISBN 978-80-7262-648-9.

 

This chapter was authored by:
Viera Bajčiová, M.D., Ph.D.
Department of Paediatric Oncology
University Hospital Brno