Nephroblastoma Final

Nephroblastoma

Paediatric Surgery

Case A 3 yr old female presents with

Abdominal distension and discomfort Abdominal mass “red’ urine

Examination reveal a palpable mass in the Rt flank extending to umbilical region and elevated blood pressure

Introduction

Wilms' tumor (WT) or nephroblastoma,

is an embryonal tumor of renal origin.

Wilms tumor, is the most common

childhood abdominal malignancy.

Approximately 500 cases of WT are

diagnosed in the USA each yr.

Epidemiology

It arises in approximately 10 children per

million under age 15 years and is usually

diagnosed between ages 2 and 5 years.

Bodkyn et al in 2010 found and incidence of

Wilms tumour : 2.7 per 100,000 pyrs for

females in Trinidad and Tobago which was

also less in males.

Pathophysiology

Wilms' tumor (WT) is attributed to an altered residual WT1 gene that is required for the maturation of blastemal and epithelial cells but not for the maturation of stromal and heterologous elements

Pathophysiology

Associated with 3 groups of congenital malformations WAGR syndrome – characterized by aniridia, genital

anomalies and mental retardation WT1 suppressor gene and 11 p13 deletion

Denys-Drash syndrome- characterised by male puedohermaphroditism , progressive nephropathy WT1 suppressor gene and 11 p13 mutation

Beckwith-Wiedemann syndrome -an overgrowth syndrome characterized by visceromegaly, macroglossia, hypoglycemia & omphalocele.

WT1 at 11p15 chromosome

Morphology

Gross- large, solitary, well-

circumscribed mass On cut section, the

tumor is soft, homogeneous, and tan to gray with occasional foci of hemorrhage, cyst formation, and necrosis

Histology Favorable -The classic

triphasic combination of : Blastemal cell types-small blue

cells, with little distinctive features

Stromal cells type- fibrocytic or myxoid in nature, skeletal muscle differentiation is not uncommon

Epithelial cell types-abortive tubules or glomeruli.

Unfavoarable - Anaplasia ( 5%) - cells with large, hyperchromatic, pleomorphic nuclei and abnormal mitoses.

Presentation Most common presentation 60 % :

Palpable abdominal mass With/ without pain Abdominal distension

Hematuria ( 15%) Hypertension ( 25%) Weight loss Fever

Presentation

In association with other syndromes

WAGR – WT with anirdia , genitourinary

anomalies mental retardation

Beckwith- Wiedemann syndrome – WT present

later into adult hood

Denys –Drashy – WT with intersex disorder,

and progressive nephropathy

Presentation Examination

A palpable abdominal mass

Investigations

The following lab investigations are used CBC count Chemistry profile- Renal function Test

and electrolytes and calcium Urinalysis Coagulation studies Cytogenetic studies for WT1 gene

and concomitant chromosomal abnormalities 11p 15, 11p 13

Imaging Studies

Renal ultrasonography detects : If mass originated from kidney is cystic or solid Presence of potential tumor thrombus within

the renal vein and inferior vena cava

Ultrasound demonstrates a large heterogenousmass ( Wilms' tumour) arising from the left kidney containing multiple areas of haemorrhage or necrosis.

Imaging Studies

CT scanning of abdomen origin of the tumor, involvement of the lymph

nodes, bilateral kidney involvement, invasion into major vessels (eg, inferior vena cava), and liver metastases.

CT scan of a Wilms' tumor involving the right kidney. Arrows show remnants of the remaining functional kidney

CT showing bilateral Wilms' tumors

Imaging Studies

MRI scanning of abdomen Caval patency the IVC is directly invaded by tumor

and tumor thrombus in IVC . Metastasis to liver or lung

Both CT and MRI are important in differentiating Wilms tumor from neuroblastoma

Chest radiography Images may depict lung metastases.

Urinary catecholamine levels To distinguish btw neuroblastoma ( elevated) and

Wilms tumour (normal)

Differentials Neuroblastoma Polycystic Kidney Disease Rhabdomysarcoma

Management

Treatment is determined via Stage of tumour

This is done via Surgical exploration Preoperative imaging studies and

Histology

Staging- National Wilms Tumour Study

Stage I Encapsulated tumor, completely excised

Stage 2 Extends beyond the kidney, completely excised

Stage 3 Residual tumor confined to the abdomen or nodes

Stage 4 Haematogenous metastases (lung metastases on CXR or on CT

Stage 5 Bilateral tumours at diagnosis

Treatment

In Stage 1 tumors - nephrectomy and adjuvant chemotherapy for 3 months.

In Stage 2 tumors, nephrectomy and two-agent chemotherapy for 12–15 months

Stage 3 tumors, nephrectomy with a three-agent chemotherapy for 12–15 months, with radiotherapy as an occasional adjunct. If the tumor is large, chemotherapy may be

used to ‘shrink’ the tumor before surgical removal.

Treatment

In Stage 4 tumors, nephrectomy with

chemotherapy is the mainstay of

treatment.

Stage 5 – not well established but preservation of renal parenchyma following initial preoperative chemotherapy.

Surgery

Exploratory laparotomy to confirm diagnosis asses the opposite

kidney Completely resect the

primary tumour, ureter and adjacent lymph nodes

Partial nephrectomy is perform if tumour is bilateral for sparing of renal parenchyma.

Intra operative picture of large Wilms' tumor within the left kidney outlined by arrows

Prognosis (U.S.A.)

Patient with stage V disease have 70-80% survival rate if synchronous and 45-50% if metachronous .

Stage Overall survival

Favourable histology

(4 yr )Unfavourable histology

I 98 % 95%

II 96% 70%

III 95% 56%

IV 90% 14%

References www.emedicine.com – Paediatric Wilms tumor Sabiston Textbook of Surgery, 18th ed.

Chapter 71 Anatomical Pathology Museum Case

studies – Wilms’ tumor Bodykyn et al 2010 Common childhood

caners in Trinidad and Tobago.WIMJ. Vol 65

Thank you