Wilms Tumor Flashcards
What percentage of childhood cancers are Wilms Tumor?
What are the most common syndromes associated with it?
Syndromes with an increased risk of WT associated with somatic overgrowth include
- Isolated hemihypertrophy
- Beckwith-Wiedemann syndrome (BWS)
- Perlman syndrome
- Sotos syndrome
- Simpson-Golabi-Behmel Syndrome.
- BWS (macroglossia, macrosomia, midline defects, ear creases, neonatal hypoglycemia) is associated with chromosome 11p15 imprinting abnormalities.
Syndromes with an increased risk of WT without somatic overgrowth are almost invariably related to abnormalities of the WT1 gene on chromosome 11p13 and include
- Denys-Drash syndrome (DDS – under-virilization, renal mesangial sclerosis, and WT)
- WAGR (WT, aniridia, genital anomalies, and mental retardation)
What is the single most important histologic predictor of response and survival in patients with WT?
Tumors harboring anaplasia (cellular features characterized by large nuclei, abnormal mitotic figures, and hyperchromasia) identify patients at higher risk for relapse or death. This feature defines patients with “unfavorable histology.”
Anaplasia is found in ~10% of patients and is the single most important histologic predictor of response and survival in patients with WT.
Focal anaplasia is differentiated from diffuse anaplasia, which carries a worse prognosis.
What embryologic component does Wilms Tumor originate from?
Nephrogenic rests are abnormally retained embryonic kidney precursor cells arranged in clusters, and they are recognized as potential precursor lesions of WT that may also involute spontaneously.
It is estimated that rests are harbored in 35% of unilateral WT patients, 100% of bilateral WT patients, and in 1% of unselected infants identified on post-mortem exam. It is believed that only 1% of rests will go on to become WT.
What are the symptoms of Wilms Tumor?
The most common presentation is that of an asymptomatic abdominal mass noted by the parents or other caregivers.
Less commonly, children will present with abdominal pain or gross hematuria.
Hypertension related to high plasma renin levels may be present.
Physical examination should evaluate for syndromic features such as aniridia, hemihypertrophy, and genitourinary abnormalities. A palpable mass in the flank is the norm.
What should the workup for Wilms Tumor be?
Laboratory evaluation should include
- complete blood count
- liver function tests
- renal function panel
- urinalysis.
It is also advisable to obtain a coagulation panel to determine the potential for acquired von Willebrand disease (4%-8% of patients with WT).
While ultrasonography is frequently the first-line imaging study, cross-sectional imaging is necessary to define location, size, and local extension of the tumor, to evaluate the contralateral kidney and the presence of metastatic disease, with the lungs being the most common site.
Computerized tomography (CT) is used in most centers but magnetic resonance imaging (MRI) is also acceptable. CT of the abdomen is sufficient to evaluate for the presence of IVC extension.
What upstages the tumor during surgery?
Surgeons should be cognizant of the propensity for tumor rupture in WT, as intraoperative tumor spillage results in upstaging and requires treatment with abdominal radiation.
A recent study using data from the current COG biology study (AREN03B2 – biology and banking study open to all newly diagnosed pediatric renal tumors) described a 10% intraoperative spill rate in patients with unilateral WT; spillage was more common in tumors > 12 cm and located on the right side.
Stage I Wilms Tumor
43% of patients
The tumor is limited to the kidney and was completely excised.
The renal capsule has an intact outer surface.
The tumor was not ruptured or biopsied prior to removal.
The vessels of the renal sinus are not involved.
There is no evidence of tumor at or beyond the margins of resection.
All lymph nodes sampled are negative.
Stage II Wilms Tumor
20% of patients
The tumor extends beyond the kidney, but was completely excised.
There must be no evidence of tumor at or beyond the margins of resection.
There may be regional extension of tumor (penetration of the renal capsule or extensive invasion of the renal sinus or invasion into adrenal gland).
The blood vessels outside the renal parenchyma, including those of the renal sinus, may contain tumor.
Vascular extension of tumor is considered stage II only if it is completely removed en bloc in the nephrectomy specimen.
All lymph nodes sampled are negative.
Stage III Wilms Tumor
21% of patients
Residual non-hematogenous tumor is present, and confined to the abdomen. Any one of the following may occur:
Lymph nodes within the abdomen or pelvis are found to be involved by tumor - renal hilar, para-aortic, or beyond. (Lymph node involvement in the thorax or other extra-abdominal sites would be a criterion for stage IV.)
The tumor has penetrated through the peritoneal surface.
Tumor implants are found on the peritoneal surface.
Gross or microscopic tumor remains postoperatively. (e.g. tumor cells are found at the margin of surgical resection on microscopic examination)
The tumor is not completely resectable because of local infiltration into vital structures.
Tumor spillage occurs either before or during surgery.
Any biopsy is performed, regardless of type- Tru-cut biopsy, open biopsy, or fine-needle aspiration- before the tumor is removed.
The tumor is resected in more than one piece. For example, if the adrenal gland is involved with tumor but resected separately from the kidney it would be considered stage III.
Extension of the primary tumor in the vena cava into the thoracic vena cava and heart is considered stage III, rather than stage IV, even though outside the abdomen. Of note, lower levels of IVC thrombus extention can be stage II if completely resected en bloc with the nephrectomy specimen.
Stage IV Wilms Tumor
11% of patients Hematogenous metastases (lung, liver, bone, brain), or lymph node metastases outside the abdominopelvic region are present. Tumor thrombi which embolize to the pulmonary vasculature are considered stage IV and specifically a site of extra-pulmonary metastatic disease. Presence of tumor within the adrenal gland is not interpreted as metastasis.
Stage V Wilms Tumor
5% of patients
Bilateral renal involvement is present at diagnosis.
Since patients with bilateral WT, predisposition syndromes and solitary kidneys are at higher risk for long-term renal dysfunction, they are treated with upfront chemotherapy in an attempt to reduce tumor burden and facilitate partial nephrectomy. Biopsy before treatment is not required.
What do you do for Stage I through IV Wilms Tumor?
Patients with unilateral WT, stages I-IV, proceed to nephrectomy through a generous transverse abdominal or thoracoabdominal incision in order to avoid intraoperative tumor rupture and to facilitate intra-abdominal inspection and renal hilar, periaortic, pericaval and inter-aorto-caval lymph node assessment.
Extraperitoneal flank incisions are not recommended. In rare cases, patients with large tumors may be deemed “inoperable.”
Intraoperative tumor rupture or initial biopsy requires abdominal radiotherapy for treatment.
The adrenal gland can be left in place unless an upper pole or abutting tumor exists (or venous thrombus), and the ureter should be taken as low as conveniently possible.
Intra-operative assessment of the contralateral kidney is not necessary if appropriate preoperative imaging has been obtained.
Palpation of the renal vein and IVC should be performed to exclude tumor thrombus. Pathologic and radiologic staging will determine risk group assignment and chemoradiation protocols.
Criteria for Inoperability for Wilms Tumor
Extension of tumor thrombus at or above the level of the hepatic veins
Tumor involves contiguous structures whereby the only means of removing the tumor requires removal of the other structure (spleen, pancreas, colon but excluding the adrenal gland)
Unnecessary morbidity/mortality, diffuse tumor spill or residual tumor
Pulmonary compromise due to extensive pulmonary metastases
Tumor biopsy in Wilms Tumor
In COG protocols, tumor biopsy is considered a “tumor spill” and mandates stage III designation and the administration of radiotherapy.
Chemotherapy for Wilms Tumor
The duration of treatment is variable based on risk stratification, which in turn considers, histology (favorable vs. anaplastic), molecular features (presence of loss of heterozygosity 1p and 16q) and staging.
Regimen Name Regimen Description
Regimen EE-4A Vincristine, dactinomycin
Regimen DD-4A Vincristine, dactinomycin, doxorubicin
Regimen M Vincristine, dactinomycin, doxorubicin, cyclophosphamide, etoposide
Regimen UH-1 Vincristine, doxorubicin, cyclophosphamide, carboplatin, etoposide
Regimen UH-2 UH-1 + vincristine / irinotecan (VI) window
