Wilms tumor was named after German surgeon Max Wilms, who published the first comprehensive review of the disease in 1899. The National Wilms Tumor Study Group (NWTSG)  established  in 1969.


  • 7.6 cases/million
  • Lower incidence in Asians 
  • Male ratio Female =  0.92:1.00
  • Occurs earlier in boys 


  • Sotos Syndrome
  • Kilppel – Trenaunay – Weber syndrome
  • Genetic instability
  • Blooms
  • Incontinentia pigmenti 
  • Fanconi group D
  • Li-Fraumeni
  • Wilms tumor Aniridia Genitourinary mental Retardation – 11p germline mutations
  • Denys Drash  syndrome – 11p mutation pseudohermaphroditism
  • Degenerative renal disease (GN,NS) Wilms tumor – del 11p
  • Hemihypertrophy 
  • Beckwith Wiedemann syndrome – macroglossia, Omphalocele, visceromegaly 
  • SimpNF


  • Homozygous deletion detected
  • Constitutional deletion in B/L cases
  • Homozygous somatic mutations in nonhereditary forms


  • Homozygous deletion detected
  • Constitutional deletion in B/L cases
  • Homozygous somatic mutations in nonhereditary forms 


  • 11p13 has 10 imprinted genes
  • IGFII 
  • Involved in BWS HH
  • Loss of maternal allele – LOH leads to upregulation


  • Imprinted opposite to IGFII
  • Has tumor suppressor functions
  • Inactivation occurs by loss of maternal allele and loss of imprint


  • Paternally regulated


  • 17q linkage – FWT1 gene
  • 19q linkage – FWT2 gene
  • 9p, 20p, 3q other suspected areas
  • 16q LOH
  • 1p LOH
  • 7p LOH

75% anaplastic histology:restricted to areas of anaplasia – involved in anaplastic progression

β catenin

  •         Involved in Wnt pathway
  •         Cell adhesion molecule

Telomerase, TrkB, VGEF, survivin FAS INK4 involve

Inactivation of WTX—a new tumour suppressor gene identified on the sex-determining X-chromosome—might be associated with the development of Wilms’ tumour. It takes a single genetic event to inactivate WTX in either males or females


  • Solitary lesions
  • Multifocal – unilateral or bilateral
  • metachronous or synchronous
  • Extrarenal –pelvic, inguinal, retroperitoeum thorax


  • Variegated
  • Hemorrhage and necrosis 
  • Polypoid extension into PCS
  • Soft friable, firm if stromal elements ++++
  • Pseudo capsule helps to distinguish Mesoblastic nephroma, CSSK, Rhabdoid tumor, Lymphoma
  • Reach IVC RT atrium 


  • Curable with surgery alone
  • If no anaplasia – favorable Histology
  • If anaplasia – Unfavorable Histology 
  • Blastemal rich present with high stage but good 
  • chemotherapy response
  • Epithelial, rhabdomyomatous –low stage but 
  • less chemo sensitive 
  • If no solid nodular growth but immature nephrogenic elements in septa -  cystic partially differentiated nephroblastoma(CPDN)
  •  If only mature – cystic nephroma(CN)
  • Blastemal – small blue cells – diffuse or organoid pattern
  • Stromal – immature spindeloid cells, skeletal muscle cartilage , osteoid, fat
  • epithelioid elements- glomeruli or tubules
  • Triphasic – monophasic 
  • Can be cystic


  • Metastatize in lung bone brain, soft tissue
  • Clear cells
  • Biphasic
  • No IHC marker 

Rhabdoid tumor

  • Macronucleoli 
  • Hyaline cytoplasmic inclusions
  • Cytokeratin, EMA, Desmin, neurofilament EMA+
  • Del 22q characteristic
  • Associated with brain tumors(ATRT) 
  • In first 2 years
  • Widely metastatic
  • Sheets of monotonous cells
  • Vescicular nuclei

Cong Mesoblastic Nephroma:

  • T(12;15) in cellular subtype 
  • Grows in pelvis and perirenal spaces
  • Metastasis in 20% 
  • Chemo/Radio refractory
  • Surgery should be radical
  • Followup for metastasis
  • Infants
  • Classic
  • Cellular
  • Mixed Types
  • Grows as intersecting band of spindle cells


  • Young adults
  • TFE gene breakpoints at Xp11.2
  • Focal or no immunoreactivity to epithelial 
  • Markers and vimentin


  • Abdominal mass 
  • Hematuria 
  • Abdominal pain
  • Fever
  • Hypertension
  • Varicocele that does not reduce on sleeping
  • Des not cross midline
  • Syndromic features


  • Contrast enhanced CT
  • CT chest 
  • CXR
  • X ray bones – in CSSK
  • Bone scan in RCC
  • MRI / CT brain + contrast if CSSK, Rhabdoid tumor, RCC 
  • Hypertension in about 25% of patients and congenital anomalies
  • (aniridia, genitourinary malformations,hemihypertrophy, or signs of
  • overgrowth) in 13–28% of children
  • USG abdomen
  • Doppler US
  • Contrast enhanced CT
  • CT chest
  • CXR
  • X ray bones – in CSSK
  • Bone scan in RCC
  • MRI / CT brain + contrast if CSSK, Rhabdoid tumor, RCC
  • overgrowth) in 13–28% of children
  • USG abdomen
  • Doppler US
  • CBC
  • RFT
  • LET
  • Urine analysis
  • <10% have coagulopathy (acquired von Willebrand disease)


  • Tumor Stage
  • Histology

             Anaplasia may be diffuse or focal; focal anaplasia intermediate prognosis

            Anaplasia (irregular mitotic figures, large nuclear size, and hyperchromasia) is associated with adverse outcome.

            Clear-cell sarcoma of the kidney and malignant rhabdoid tumor of the kidney are considered distinct tumor types

  • Patient Age

          Patients less than 2 years of

  • Small (<550 g) tumors
  • Biological Prognostic Factors

            loss of heterozygosity (LOH) at chromosomes 1p and 16q.

            Gene expression profiling



The most important role for the surgeon is to ensure complete tumor removal without rupture and perform an assessment of the extent of disease. Radical nephrectomy and lymph node sampling via a transabdominal incision is the procedure of choice.For patients with resectable tumors, preoperative biopsy should not be performed. Partial nephrectomy remains controversial and is notrecommended except for bilateral tumors.


Hilar, periaortic, iliac, and celiac lymph node sampling is mandatory. Patients with massive, nonresectable unilateral tumors, bilateral tumors, or venacaval tumor thrombus above the hepatic veins are candidates for preoperative chemotherapy because of the risk of initial surgical resection Preoperative chemotherapy should follow a biopsy, which may be performed percutaneously through a flank approach. Children treated for Wilms tumor are at increased risk for developing second malignant neoplasms. This risk depends on the intensity of their therapy, including the use of radiation and doxorubicin, and on possible genetic factors.


The renal vein and IVC are palpated to exclude intravascular tumor extension before vessel ligation. Gentle handling of the tumor throughout the procedure is mandatory to avoid tumor spillage, which leads to a sixfold increase in local abdominal relapse.

  • Small bowel obstruction (7%)
  • Hemorrhage (6%)
  • Wound infection, hernia (4%)
  • Vascular complications (2%)
  • Splenic and intestinal injury (1.5%)






  • NWTS-5 recommendation for the management of bilateral Wilms’ tumor includes initial biopsy and local staging followed by chemotherapy (according to abdominal stage and histologic features) and second-look surgery at week 5
  • If needed, additional chemotherapy or radiation therapy is given, but definitive surgery is recommended within 12 weeks of diagnosis to limit the risk of chemoresistant clonal expansion
  • Failure of bilateral Wilms’ tumor to respond to preoperative chemotherapy is often due not to anaplasia but to persistence of mature elements with a skeletal muscle component.
  • In patients with anaplastic tumors, complete surgical excision is warranted, and in such cases the NWTSG favors tumor resection with a margin of renal tissue rather than enucleation.

Metachronous bilateral Wilms’ tumor

  • Lower survival rates for patients with metachronous rather than synchronous bilateral tumors .
  • Second tumor developed at a median interval of 23.1 months.
  • Children in whom a contralateral tumor developed more than 18 months after the initial diagnosis had a better OS rate than did those in whom it developed less than 18 months after diagnosis
  • Children younger than 12 months who have perilobar nephrogenic rests are at markedly increased risk of contralateral disease and require frequent and regular surveillance for several years.

 Treatment of Anaplastic Wilms’ Tumor

  • In NWTS 4 patients with ananplasia with Cyclophos had better outcome
  • NWTS-5 incorporated cyclophosphamide into the treatment plan for patients with stage II, III, or IV diffuse anaplasia.
  • Abdominal irradiation and vincristine, doxorubicin, and cyclophosphamide alternating with cyclophosphamide and etoposide.
  • Stage I diffuse or focal anaplastic Wilms’ tumor were treated with vincristine and dactinomycin because earlier studies had shown good outcomes for this group
  • future COG studies will add doxorubicin and irradiation to the therapeutic regimen for these patients.


  • Mesenchymal cell (skeletal and smooth muscle, fat, fibrous tissue, tumor, bone, cartilage) – Sarcoma.
  • RMS – stem cells commited to skeletal muscle lineage – may arise in tissues not having skeletal muscle.
  • Undifferentiated tumors – no lineage can be identified – multi lineage markers ex ecto mesenchymomas (neural + skeletal muscle markers) malignant triton tumors(schwannomas + skeletal muscle markers)


  • Annual incidence 4.3 / million.
  • Incidence lower in blacks and Asians
  • RMS incidence less than half of Non RMS STS


  • Overall genetic risk 7-33%
  • Neurofibromatosis
  • Li-Fraumeni syndrome germline p53 mutation (STS, Adrenocortical carcinomas, early Ca breast)
  • ? Increased sensitivity to toxins – maternal/ paternal use of marijuana(x3), Cocaine(x5)
  • Costellos syndrome (AD – postnatal Growth retardation, coarse facies, loose skin,dev. Delay, solid tumors)
  • Beckwidth Widemann Synd. (IGF II mutations)


  • Botryoid or spindle cell RMS – good prognosis
  • Embryonal – intermediate
  • Alveolar - poorer
  • Undifferentiated – poor
  • Light microscopy - cross striations
  • IHC – actin myosin desmin myoglobin Z protein, MyoD
  • EM – actin myosin bundles, Z band material




  • Differential diagnosis
  • Trauma – clear history/ hematoma/ skin colour
  • Or BIOPSY in case of doubt/expansion of growth over 1-2 weeks
  • UTI may give imaging and cystoscopic findings of RMS
  • Lipoma, Neurofibroma, rhabdomyoma – complete excision if mutilation not necessary
  • Myositis ossificans- ulcerated, polypoid intraluminal growth – cystitis and dysuria
  • Mass with FTT      

                 Others LCH, HL, NB, EwS


  • Examination of Lymphnodes
  • CBC
  • BUN, Creatinine, LFTs
  • Ser. Electrolytes, Ca++, PO4-3, Mg++
  • Uric acid
  • Bone marrow aspiration biopsy B/L(<2% chances in absence of other Mets)
  • Coagualtion profile – DIC
  • Hypercalcemia
  • X-ray of affected part
  • 99mTc bone scans/ Gallium-67 in bowel
  • PET?
  • CT scans
  • USG esp. abdomen
  • MRI esp Head and neck tumors
  • Use of thin cut abdominal and pelvic CT scans with double contrast to assess regional lymph node involvement for patients with paratesticular primaries




  • Metastasis
  • Age <1yr >10yrs – poor
  • Site
  • Gross residue VS Microscopic residual disease VS total resection
  • LN involvement


  • Surgery
  • Chemotherapy
  • Radiotherapy
  • Combined


  • Primary removal
  • Function and cosmesis not impaired

               Aggressive surgery not warranted

  • Vagina & female genital tract
  • Urinary bladder orbit
  • Head and neck – in v/o major vessels and nerve
  • If MRD re-excision esp. in trunk
  • Debulking
  • Second look surgery if
  • SIOP MMT group – non radical surgery F/B VIE – high recurrence even if Histo path –ve after induction. thus Local therapy must after Complete induction
  • IRS III Clinical group III – chemo + local RT FB  delayed primary resection – second look surgery produces CR by removing tumor and improved clinical and radiologic accuracy
  • St Jude – CR maintained in patients with lower RT

 Special Groups

  • Head & neck – wide excision difficult, good response to chemo, incisional biopsy, orbital tumrs have good prognosis, parameningeal and LN + ve have poor outcome.
  • Paratesticular tumor – Radical inguinal orchidectomy no biopsy, RPLND(?) only if radiologically involved, sampling recommended downgrading – worse outcome
  • Ipsilateral RLND in boys > 10 yrs
  • Vulval/Vaginal/Uterine- no wide resection respond to chemo and operate later. Uterine – operate later, ovaries and distal vagina preserved unless involved
  • Bladder prostate-morbidity after local surgery complete resection only if function preserved . Partial cystectomy if dome bladder
  • Extremities: attempt initial total excision, poor prognosis if tumor left behind, LN biopsy of suspicious LN. Supra claviculat Para aortic, iliac LN = stage 4
  • Others: Difficult surgery. Wide local excision of Chest wall tumors with rob above and below.
  • Metastatectomy


  • Alone insufficient but can eradicate residual tumor cells. Esp. head and neck 150 – 180/200 cgy # daily
  • 41.4-45 Gy for microscopic residual disease
  • 40.4 – 54 for gross residual disease
  • Cone down or shrinking field. 2 cm margins
  • Parameningeal and base skull intracranial erosions – in first several days. No whole-brain irradiation if no overt meningeal involvement Others – 3-12 weeks
  • Clinical Group - > 5 cm, other than GUT, alveolar undifferentiated Lung mets 1440 cgy


  • Erythema loss of growth desqamation
  • The later effects of radiation are loss of function or
  • growth due to fibrosis, which increases with increasing
  • dose and volume and diminishes with increasing age of
  • the patient
  • 70% of patients with orbital RMS have impaired vision
  • abnormal dentofacial development
  • Failure to maintain their initial height velocity

 Active agents

  • Vcr 
  • Etoposide
  • Dacarbazine
  • Cyclophosphamide
  • Ifosamide+Doxorubicin/Dacarbazine
  • MTx topotecan,  topo+cyclo
  • Ifo+ doxo, ifo + etop, melphelan+vcr
  • Irenotecan+VCR
  • Paclitaxel, docetaxel
  • Vinorelbine


  • Tumors removed at onset better outcome
  • Post chemo surgery removes residual tumors


  • Stage I, Clinical Groups I and II (primary sites in head and neck non-parameningeal or genitourinary tract non-bladder/prostate), and Group III (orbit only)
  • Stage II Group I (all sites with maximum tumor diameter <5 cm.)
  • Certain subgroups of low-risk patients have achieved high cure rates of approximately 90% using two-drug chemotherapy with vincristine and actinomycin  with XRT to the local disease site if microscopic or gross residual tumor is present
  • Other subgroups of low-risk patients have achieved high cure rates using three-drug chemotherapy with vincristine, actinomycin D, and cyclophosphamide.
  • Patients found to have alveolar histology or undifferentiated sarcoma will be treated non-randomly with VAC ± radiation therapy (XRT)


  • Survival rates ranging from 55% to 70%]

  • This category includes patients with -Embryonal rhabdomyosarcoma at unfavorable sites who have gross residual disease (i.e., group III)

    • Metastatic embryonal RMS in children  

    • Non-metastatic alveolar RMS at any site
  • (VAC) is the standard chemotherapy treatment
  • VAC = VAI
  • XRT


  • High-risk patients have metastatic disease in one or more sites at diagnosis (stage 4). These patients continue to have a relatively poor prognosis (≤50% 5-year survival rate)


First year off therapy

  • PE every 3 months
  • Chest X-ray every 3 months.
  • Other indicated imaging studies every 3 to 6 months

Second and third years off therapy

  • PE every 4 months
  • Chest X-ray every 4 months.
  • Other studies appropriate to the individual patient

Five to ten years

  • Annual visit for PE and specific studies


Recurrence connotes relative or absolute resistance to the chemotherapy or irradiation used in initial therapy.  Among the various molecular mechanisms that may play a role in the development of drug resistance are : 

Overexpression of P-glycoprotein
Hypermethylation of the tumor cells DNA
Elevated levels of DNA polymerase-alpha and beta,topoisomerase II,
Overexpression of O6-methylguanine-DNA methyltransferase
Constitutive expression of the c-H-ras oncogene
 Rare after 3 or 4 years from diagnosis
Can take place many years after apparently successful treatment


Must be fully evaluated and staged
Documented by biopsy or fine-needle aspiration
Imaging studies (plain films, CT, and/or magnetic resonance

 imaging) should be performed to evaluate the lungs, site of
 primary tumor, and any sites suggested by the history and
physical examination
Bone marrow biopsy

 Factors afecting treatment

Timing of the recurrence relative to the completion of therapy

 The extent of disease at recurrence

  The extent of disease at diagnosis

  Nature of prior therapy


Aggressive multimodality approach should be considered for the patient with an isolated site of recurrent disease Cmplete surgical resection can be accomplished, followed by adjuvant postoperative irradiation and chemotherapy

The choice of a salvage chemotherapeutic regimen depends on the previous chemotherapy and the timing of the relapse. For patients who have not previously received known active agents such as ifosfamide, doxorubicin, or etoposide, or newer agents such as topotecan or irinotecan, these agents should be strongly considered when choosing a regimen


Patients in whom recurrence develops with metastatic disease are essentially incurable. Surgical resection of metastatic lesions is unlikely to be of benefit with regard to curative potential, although low-morbidity procedures may be useful for palliative purposes.
 Chemotherapy is the primary therapeutic modality, with palliative radiotherapy usually reserved to treat painful lesions or to prevent spinal cord compression.