Renal Tumors Flashcards
An asymptomatic 3-year-old boy is found to have a large palpable abdominal mass on routine examination. Imaging demonstrates a large mass originating from the kidney with a “claw sign.” Which of the following is true regarding the most likely diagnosis in this child?
A. The current overall survival rate of these patients is about 50%.
B. The hereditary form of this tumor is more aggressive and more common.
C. Common metastatic foci are in the lungs and liver.
D. There is no role for preoperative chemotherapy in the treatment of this childhood tumor.
E. Measurement of serotonin metabolites in the urine aids in the diagnosis and in monitoring the course of the disease.
ANSWER:
C
COMMENTS: The differential diagnosis for this mass is Wilms tumor and neuroblastoma.
The most common solid tumor in children younger than 2 years is neuroblastoma, which accounts for 6%–10% of all childhood cancers.
In children older than 2 years, the most common solid tumor is Wilms tumor.
This patient has a Wilms tumor that is an embryonal tumor of renal origin. It commonly presents as an asymptomatic abdominal mass.
Abdominal and thoracic CT, magnetic resonance imaging (MRI), or both are used preoperatively to distinguish Wilms tumor from neuroblastoma and to stage the tumor.
Wilms tumors may be bilateral and may metastasize to the liver or lungs.
The “claw sign” is useful in determining whether a mass arises from a solid structure or if it is located adjacent to it. With Wilms tumor, the affected kidney is concave, splayed out, and appears to be cupping or grasping the tumor mass.
Vascular extension with tumor thrombus within the inferior vena cava is not uncommon.
Urine examination for VMA also helps distinguish Wilms tumor from neuroblastoma since it is produced by neuroblastomas and not by Wilms tumor.
The most common germline mutation is the Wilms tumor gene-1. Hereditary Wilms tumor is uncommon.
Wilms tumor is associated with the Denys-Drash syndrome, WAGR syndrome, and Beckwith-Wiedemann syndrome.
Denys-Drash syndrome is gonadal dysgenesis, nephropathy, and Wilms tumor.
WAGR syndrome is Wilms tumor, aniridia, genitourinary abnormalities, and mental retardation.
Beckwith-Wiedemann syndrome is a combination of some of these: macroglossia, macrosomia (giantism), abdominal wall defects (omphalocele, umbilical hernia, diastasis recti), ear creases or ear pits, neonatal hypoglycemia, and childhood solid tumors (Wilms tumor, hepatoblastoma, others).
Patients with these syndromes need to be screened for Wilms tumor.
Treatment is neoadjuvant chemotherapy followed by surgical resection. The overall survival rate after resection exceeds 85%.
Overview of renal cystic diseases?
Renal cystic diseases may be inherited or acquired. The most common renal cystic disease is multicystic dysplastic kidney, which is essentially a nonfunctioning kidney.
Most renal cysts and cystic diseases do not require intervention, with the exception of multilocular cystic nephroma. Cases of multilocular cystic nephroma cannot be differentiated from malignant tumors (ex: cystic Wilm’s tumor) and therefore must undergo nephrectomy.
Autosomal dominant polycystic kidney disease and autosomal recessive polycystic kidney disease are both inherited renal cystic diseases, with the latter more commonly presenting in the neonatal period. These inherited renal cystic diseases should be managed in conjunction with nephrology given their sequelae of renal dysfunction.
What is the most common renal cystic disease diagnosed in childhood?
• Multicystic dysplastic kidney (MCDK) is the most common renal cystic disease diagnosed in childhood, with an incidence of approximately 1 in 2,500.
MCDKs occur sporadically and are more common in males than females. They are usually unilateral (left more common than right) and asymptomatic. Most cases are diagnosed on prenatal ultrasound.
Does a MCDK have any function?
• Multicystic dysplastic kidneys are non-functional and associated with ureteral atresia. There are two main theories as to why MCKDs form. One theory is that renal pelvic ureteral atresia results in severe hydronephrosis and MCKD.
The other theory is that there is a disruption in the interaction between the metanephric blastema and the ureteric bud during development, which results in failure of the kidney and ureter to develop normally.
How can you differentiate between multicystic dysplastic kidney and a severely hydronephrotic kidney?
- Appearance on renal ultrasound:
The MCDKs have multiple small cysts among larger cysts, the cysts do not communicate, and there is no large central cyst.
In kidneys with severe hydronephrosis the dilated calyces appear as cysts, and are organized around the periphery.
In hydronephrosis there appears to be a central cyst, which is the dilated renal pelvis.
Normal reni-form shape is preserved in hydronephrosis but not in MCDKs.
- Radionuclide scan:
Nuclear imaging studies to look at the function of the cystic kidney are helpful in differentiating between MCDK and hydronephrosis.
Using either dimercaptosuccinic acid (DMSA) or technetium-99 m mercaptoacetyltriglycine (MAG3), there will be no radiotracer uptake in a MCDK, while a kidney with hydronephrosis will usually show some uptake.
Do patients with MCDKs need a voiding cystourethrogram (VCUG)?
• No.
It is known that vesicoureteral reflux to the contralateral kidney occurs in 17–43% of patients with MCDKs.
However, studies have shown that VCUG results do not impact management and that the use of VCUG does not prevent febrile urinary tract infections.
Do MCDKs need to be removed?
The natural history of MCDKs is that they will involute over time, and therefore the current standard is non-operative management of these kidneys.
Follow up renal ultrasound can confirm involution and compensatory hypertrophy of the contralateral kidney.
Nephrectomy is performed in the setting of enlarging MCDKs, especially if symptomatic.
For children with MCDKs who develop hypertension, some studies have shown that hypertension can be cured by nephrectomy.
What cystic renal lesions require nephrectomy?
Patients with a benign multilocular cyst, or multilocular cystic nephroma, must undergo nephrectomy.
Although it is a benign lesion, multilocular cystic nephroma cannot be differentiated on imaging from malignant cystic renal tumors (for example: cystic Wilms tumor, mesoblastic nephroma, clear cell sarcoma).
How can you tell the difference between MCDK and multilocular cystic nephroma?
• While MCDK is a dysplastic kidney, a multilocular cystic nephroma is a complex multicystic mass with uniformly thin septa between the cysts that arises from the kidney.
How do you manage a simple renal cyst?
- A simple renal cyst is a solitary thin walled cyst with no septations or nod- ules. They occur in less than 0.3% of children, and are more common in adults. The most common location is the right upper pole, which can make it hard to distinguish from upper pole hydronephrosis related to an obstructed ureterocele or ectopic ureter. If needed, the cyst can be aspirated to aid with diagnosis (cyst fluid has the same BUN and creatinine as the patient). Simple renal cysts are usually discovered incidentally and are asymptomatic. It is important to obtain a family history, as patients with autosomal dominant pol- ycystic kidney disease may only have a single cyst in childhood.
- If the cyst is large and symptomatic, treatment options include percuta- neous drainage with a sclerosing agent (or they will recur) or surgical marsupialization.
Is autosomal dominant polycystic kidney disease (ADPKD) diagnosed in childhood?
• Not typically. In contrast to autosomal recessive polycystic kidney disease (ARPKD), patients with ADPKD most commonly present in adulthood, between 30 and 50 years old. However, there have been a few reported cases of early-onset ADPKD.
How do you differentiate between ARPKD and early-onset ADPKD?
• While early-onset ADPKD is rare, it can be challenging to differentiate it from ARPKD.
Obtaining a family history aids in differentiating the two.
A history of oligohydramnios supports ARPKD.
A liver biopsy can be obtained, which will always show congenital hepatic fibrosis in ARPKD, and almost never in ADPKD.
A biopsy of the kidney in ARPKD would show cysts arising from the collecting ducts only that remain connected to the nephron of origin.
Meanwhile, a biopsy of the kidney in ADPKD would show cysts arising from all segments of the tubule that are not connected to the nephron of origin.
There are commercially available tests for the ARPKD mutation, but these are unreliable. Commercially available tests also exist for the ADPKD mutation, but there are false negatives.
What are the key differences between ADPKD and ARPKD?
ADPKD
- 1:400 - 1:1,000
- Autosomal dominant
- Chromosome 16 (PKD1 gene), Chromosome 4 (PKD2 gene)
- Adult
- Enlarged kidneys with random cysts
ARPKD
- 1:6,000 - 1:55,000
- Autosomal recessive
- Chromosome 6 (PKHD1 gene)
- Perinatal
- Enlarged hyperechoic kidneys with no discrete cysts
What are the clinical features of ARPKD?
• ARPKD is diagnosed by bilaterally enlarged kidneys in infants, due to numerous microscopic collecting duct cysts. It can be detected as early as 24 weeks gestation on ultrasound, which will demonstrate bilateral enlarged echogenic kidneys with poor corticomedullary differentiation. There may be oligohydramnios due to poor renal function.
ARPKD has a spectrum of severity, with the most severe forms appearing at birth. The most common presentation is respiratory failure due to pulmonary hypoplasia, volume overload, or poor diaphragm function due to the enlarged kidneys.
It is always associated with congenital hepatic fibrosis, which causes portal hypertension.
Clinical features of portal hypertension include esophageal varices, splenomegaly and dilated biliary ducts which can predispose to cholangitis.
When do patients with ARPKD require nephrectomy?
Patients with significant respiratory distress can benefit from unilateral or bilateral nephrectomies.
If unilateral nephrectomy is performed, renal function should first be assessed to determine which kidney provides greater function and should therefore be left in situ.
If bilateral nephrectomy is performed, peritoneal dialysis (PD) catheter should be placed simultaneously.
If a PD catheter is to be placed, it is recommended that nephrectomy be approached extraperitoneally.
The size of these kidneys not only compromises the respiratory system, but can also have a significant impact on feeding tolerance and therefore nephrectomy is sometimes indicated in these cases.
How do you treat an infected renal cyst?
In the setting of an infected cyst, the urine culture may be negative.
Thus patients with signs and symptoms of infection should be treated accordingly.
Patients should be treated with lipid soluble antibiotics that can penetrate the cysts, such as trimethoprim-sulfamethoxazole or ciprofloxacin.
Rarely, infected cysts will need to be percutaneously aspirated.
Which of the following is false with regard to Wilms’s tumour?
A. Wilms’s tumour accounts for 6%–7% of all paediatric malignancies.
B. Wilms’s tumour is the fourth most common intra-abdominal solid organ tumour in children.
C. The annual incidence of Wilms’s tumour in North America is 8 per million children.
D. 650 new cases are diagnosed a year in North America.
E. The 3- to 5-year survival is 85%.
B
Wilms’s tumour represents 6%–7% of all paediatric malignancies and is the second most common intra-abdominal solid organ tumour found in children.
The annual incidence in North America is 8.1 per million children representing about 650 new cases each year.
The 3- to 5-year survival is approaching 85%–90%.
Which of the following is not characteristic of WAGR syndrome?
A. 30% risk of developing Wilms’s tumour
B. absence of the iris
C. malformations of the genitourinary tract
D. mental retardation
E. WT2 gene implicated
E
WAGR syndrome comprises Wilms’s tumour, aniridia, genitourinary malformation and mental retardation.
The risk of developing Wilms’s tumour is more than 30%.
Cytogenetic analysis of individuals with this syndrome showed deletions at chromosome 11p13, which has been found to be the locus of the contiguous set of genes including PAX6 (the gene causing aniridia), and WT1 (one of the Wilms’s tumour genes), rather than WT2.
WT1 gene encodes a transcription factor that is crucial for normal kidney and gonadal development.
Which of the following syndromes is not associated with Wilms’s tumour?
A. Beckwith–Wiedemann’s syndrome
B. Denys–Drash’s syndrome
C. Perlman’s syndrome
D. Li–Fraumeni’s syndrome
E. Down’s syndrome
E
Down’s syndrome (trisomy 21) is not associated with Wilms’s tumour.
Beckwith–Wiedemann’s syndrome is an overgrowth disorder manifested by large birthweight, macroglossia, organomegaly, hemihypertrophy, neonatal hypoglycaemia, abdominal wall defects, ear abnormalities and a predisposition to Wilms’s tumour.
About 5% of individuals with this syndrome will develop Wilms’s tumour.
Beckwith–Wiedemann’s syndrome maps to chromosome 11p15, a locus also known as WT2, because loss of heterozygosity at this locus has been detected in Wilms’s tumour.
Denys–Drash’s syndrome is characterised by pseudohermaphroditism, glomerulopathy, renal failure and a 95% chance of developing Wilms’s tumour.
Perlman’s syndrome and li–Fraumeni’s syndrome are both associated with Wilms’s tumour.
Which of the following is not related to Beckwith–Wiedemann’s syndrome?
A. high birthweight B. macroglossia C. risk of multiple tumours D. hyperglycaemia E. omphalocele
D
Beckwith–Wiedemann’s syndrome is associated with hypoglycaemia.
Of the following statements, which one is true?
A. 10% of Wilms’s tumours present with stage V disease.
B. Mean age at diagnosis for Wilms’s tumour is 7 years.
C. Renal sparing procedures for patients with Wilms’s are only suitable for those with a solitary kidney.
D. Chemotherapy agents used in Wilms’s include dactinomycin, vincristine and doxorubicin.
E. A skeletal survey and bone scan are required for all patients with Wilms’s tumour.
D
The mean age at diagnosis for Wilms’s tumour is 3 years.
Six per cent of patients with Wilms’s tumour present with stage V (bilateral) disease.
Partial nephrectomy is indicated in those with a solitary kidney but also in those with bilateral Wilms’s tumour.
Partial nephrectomy for small polar tumours with no evidence of spread, is practised in some centres, especially in Italy.
Chemotherapy agents used include dactinomycin, vincristine and doxorubicin.
A skeletal survey and bone scan are not required in all patients with Wilms’s tumour but should be routine investigations in those with clear cell sarcoma because of the high metastatic potential of this tumour.
Which of the following is false?
A All patients over 6 months of age in the Société International d’Oncologie Pédiatrique (SIOP) trials undergo prenephrectomy chemotherapy.
B In North America, patients with Wilms’s tumour thrombus extending into the right atrium undergo prenephrectomy chemotherapy.
C In North America, children with stage II tumours (favourable histology), treated with vincristine and dactinomycin, also receive radiotherapy.
D In North America, patients with stage V Wilms’s tumour should undergo bilateral renal biopsy with staging of each kidney followed by chemotherapy to facilitate renal sparing procedures.
E In North America, all patients with stage V (bilateral) disease undergo prenephrectomy chemotherapy.
C
In the SIOP studies the therapeutic approach has focused on developing stage specific strategies after prenephrectomy therapy.
Stage classification and histopathological diagnosis are delayed until after surgery. It is thought that the use of prenephrectomy chemotherapy facilitates surgical resection and minimises complications.
Children under 6 months of age undergo primary nephrectomy unless there is evidence of metastases at presentation.
Therefore, patients in the SIOP trial with chemotherapy-induced tumour shrinkage result in a different stage distribution to those patients in the North American National Wilms’ Tumour Study Group (NWTSG).
The staging system for the NWTSG is as follows.
● Stage I ― Tumour confined to the kidney and completely resected; no penetration of the renal capsule or involvement of renal sinus vessels.
● Stage II ― Tumour extends beyond the kidney but is completely resected (negative margins and lymph nodes); at least of the following has occurred:
(i) penetration of the renal capsule
(ii) invasion of the renal sinus vessels
(iii) biopsy of the tumour before removal
(iv) spillage of the tumour locally during removal.
● Stage III ― Gross or microscopic residual tumour remains postoperatively including; inoperable tumour, positive surgical margins, tumour spillage involving peritoneal surfaces, regional lymph node metastases, or transected tumour thrombus.
● Stage IV ― Haematogenous metastases or lymph node metastases outside the abdomen (e.g. liver, lungs, bone, brain).
● Stage V ― Bilateral renal Wilms’s tumour.
most Wilms’s tumours that appear to involve neighbouring structures usually simply compress rather than invade. This therefore reduces the need for radical en bloc dissection and its associated complications. Tumour extending into the renal vein and proximal IVC can, in most cases, be removed en bloc with the kidney. Tumour extending into the inferior vena cava (IVC) (hepatic level) or into the right atrium should be treated with prenephrectomy chemotherapy to facilitate surgical resection.
At diagnosis, about 6% of children present with bilateral Wilms’s tumour. Survival is more than 70%; however, these children are at high risk of renal failure. This risk has led to the recommendation that such children undergo bilateral renal biopsy with staging of each kidney followed by chemotherapy to shrink the tumour and aid renal sparing procedures. Primary excision of the tumour masses is not recommended.
Radiotherapy is an important treatment modality in children with Wilms’s tumour. Successive NWTSG trials have refined the indications for radiotherapy. NWTS-2 showed that radiotherapy could be avoided in stage I disease if they received vincristine and dactinomycin. The NWTS-3 study proved that children with stage II disease treated with vincristine and dactinomycin could also avoid radiotherapy.
Concerning patients with renal cell carcinoma (RCC), which of the following is false?
A. Between 2% and 5% of paediatric renal tumours are RCCs.
B. M = F.
C. It may be associated with von Hippel–Lindau’s disease.
D. Papillary and clear cell subgroups are described.
E. 50% present with lung, liver or brain metastases.
E
RCC accounts for 2%–5% of all paediatric renal tumours and 0.5%–2% of all RCCs occur in those under 21 years of age. Patients classically present with frank haematuria, loin pain and a palpable mass.
Twenty-five per cent, however, are asymptomatic and are detected on imaging.
Twenty per cent of patients will present with metastatic disease (bone, liver, brain).
Bilateral presentation can be associated with conditions such as von Hippel–lindau’s disease.
Two main morphological subgroups can be identified – namely, papillary and clear cell tumours.
Survival of children with renal call carcinoma is largely affected by stage at presentation and completeness of resection at radical nephrectomy, with overall survival at 64%–87%.
Five year survival
Stage I: higher than 90%
Stages II–III: 50%–80%
Stage IV: 9%
Nephrectomy is adequate for stage I–II disease.
Regarding clear cell sarcoma of the kidney (CCSK), which of the following is incorrect?
A. Abdominal mass is a common presenting feature.
B. Bilateral cases are well recognised.
C. No familial or syndromic association exists.
D. Peak incidence at 1–4 years.
E. It is more common in boys.
B Clear cell carcinoma occurs with a peak incidence at 1–4 years, boys being more commonly affected (ratio 2 : 1).
Classically patients present with an abdominal mass. No patients have been reported with bilateral disease and there is no known syndrome or familial association.
Clear cell carcinoma has a high malignant potential; hence it is also known as bone-metastasing renal tumour of childhood.
Bone metastases occur in 15%–60% of patients with CCSK and metastases to other organs can also occur.
Four per cent will present with distant metastases at presentation.
Regarding mesoblastic nephroma, which of the following is false?
A Between 3% and 10% of all paediatric renal tumours are mesoblastic nephromas.
B Mesoblastic nephroma is the most common renal tumour in those under 3 months.
C 90% are diagnosed within the first year of life.
D Mesoblastic nephroma can be divided into classic and papillary types.
E Mesoblastic nephroma is associated with maternal polyhydramnios.
D
Mesoblastic nephroma gives rise to 3%–10% of all paediatric renal tumours, and is the most common renal tumour in those under 3 months of age.
Ninety per cent are diagnosed within the first year of life and it is twice as common in boys as girls. Two morphological types are recognised and include classic and cellular types and the latter accounts for 42%–63% of cases.
mesoblastic nephroma classically presents with an abdominal mass and occasional haematuria. many cases are diagnosed on prenatal ultrasound and give rise to polyhydramnios, hydrops and premature delivery.
Mesoblastic nephroma is treated with radical rather than partial nephrectomy to reduce the risk of local recurrence.
Nephrectomy is usually sufficient as the tumour generally follows a benign course. Ninety-five per cent of patients do not relapse, and the 5% who do have the cellular variant of the disease.
Regarding malignant renal rhabdoid tumour, which of the following is false?
A It accounts for 2% of all paediatric renal tumours.
B It can present with hypercalcaemia.
C It is more common in females.
D 80% present with metastases.
E 60% occur in those under 1 year of age.
C
malignant renal rhabdoid tumour is a rare but aggressive renal tumour accounting for 2% of all paediatric renal tumours and 80% occur in those under 2 years of age (60% in those under 1 year of age).
male predominance is 1.5 : 1.
Haematuria is a common presenting feature, as are symptoms from metastatic spread as metastatic spread occurs in 80% of patients. Patients have also been reported as presenting with hypercalcaemia due to increased parathormone concentrations.
Malignant renal rhabdoid tumour has an 80% overall mortality at 12–18 months follow-up, due to advanced stage at presentation and poor response to traditional chemotherapy and radiotherapy. Completely resected tumours with negative lymph nodes also have a poor prognosis with only 50% survival.
NWTS-5 study is using a protocol whereby radical nephrectomy is followed by carboplatin and etoposide alternating with cyclophosphamide for 24 weeks and radiotherapy.
What three elements comprise classic Wilms Tumor?
WTs are currently divided into those with favorable histology and those with unfavorable histology.
Unfavorable histology proved to be the most important factor in patient outcome in NWTS-1, a finding that has remained consistent through the current trials.
Fortunately, favorable histology accounts for 90% of the tumors.
These tumors are the “classic WT” consisting of three elements: blastemal, stromal, and epithelial tubules.
Tumors contain various proportions of each of these elements. Triphasic are the most characteristic, but biphasic and monophasic lesions also occur.
The proportion of these three elements in WTs have been studied but have not been shown to predict outcomes. Under the current COG treatment protocols, they are not utilized to determine therapy.
This is in contrast to SIOP, which uses a postchemotherapy staging system.
Abnormal mucinous or squamous epithelium, skeletal muscle, cartilage, osteoid, and fat are less frequent elements found in WT.
What are unfavorable tumors?
Unfavorable tumors are those with focal or diffuse anaplasia.
Anaplasia is defined by:
multipolar polyploid mitotic figures,
marked nuclear enlargement (giant nuclei with diameters at least three times those of adjacent cells), and
hyperchromasia.
Determining whether a tumor has diffuse or focal anaplasia is important for prognosis and therapy.
Focal anaplasia is defined as the presence of one or a few sharply localized regions of anaplasia within a primary tumor, the majority of which contains no nuclear atypia.
Tumor designated as diffuse anaplasia must have at least one of the following four criteria:
anaplastic cells outside of the kidney,
presence of anaplasia in a random
kidney biopsy,
anaplasia in more than one region of the kidney, or
anaplasia in one region with extreme nuclear pleomorphism in another site.
Anaplasia occurs primarily in children older than 2 years.
In NWTS-1, 66.7% of patients with anaplasia experienced relapse and 58.3% died of their tumor.
Also, there was a higher frequency of relapse and death in the “diffuse” subgroup.
Additionally, anaplasia in extrarenal tumor sites and a predominantly blastemal tumor pattern were both adverse prognostic factors.
TP53 deletion on chromosome 17 has been associated with anaplasia. However, a recent study demonstrated recurrent anaplasia-specific genomic loss and underexpression in several additional regions, most strikingly 4q and 14q, suggesting anaplasia is not linked solely to deletions of chromosome 17, but is associated with loss at multiple loci.
H&A
What is clear cell sarcoma of the kidney?
CCSK and malignant RTK were grouped in the initial NWTSG studies with the unfavorable-histology WT. They are now considered distinct entities from WT based on their pathologic appearance, biologic behavior, and response to different therapies.
CCSK is a highly malignant tumor with an unusual proclivity for bony metastasis.
Generally, it appears as a large unifocal and unilateral tumor with a homogeneous mucoid, tan, or gray/tan cut surface, often with foci of necrosis or prominent cysts.
This tumor invades and surrounds the renal parenchyma rather than compressing the margin into a pseudocapsule as is seen in WT.
Its classic appearance is that of a deceptively bland tumor with uniform oval nuclei with a delicate chromatin pattern, a prominent nuclear membrane, and sparse, poorly stained vacuolated “water-clear” cytoplasm with indistinct cell membranes.
Although the cells generally appear in cords or nests divided by an arborizing network of vessels and supporting spindle cell septa, there are variations and nine major histologic patterns have been identified.
Recently, a translocation t(10;17) and deletion (14q) also have been described in CCSK, suggesting that they may play a role in its pathogenesis.
The cell of origin of this tumor is not known.
In addition to osseous metastases, CCSKs also have a significant incidence of metastases to the brain.
Long-term follow-up is important as one report found 30% of the relapses occur more than 2 years after diagnosis.
H&A
What is malignant rhabdoid tumor of the kidney?
CCSK and malignant RTK were grouped in the initial NWTSG studies with the unfavorable-histology WT. They are now considered distinct entities from WT based on their pathologic appearance, biologic behavior, and response to different therapies.
Malignant RTK occurs in young infants with a median age of 11 months.
Most (85%) cases occur within the first 2 years of life.
It is the most aggressive and lethal of all pediatric renal tumors, and fortunately only accounts for 2% of renal tumors.
Grossly these tumors are unencapsulated and invasive with characteristic involvement of the perihilar renal parenchyma.
Histologically, RTKs are characterized by monomorphous, discohesive, rounded to polygonal cells with acidophilic cytoplasm and eccentric nuclei containing prominent large “owl eye” nucleoli reminiscent of skeletal muscle, but lacking its cytoplasmic striations, ultrastructural features, and immunochemical markers.
A large periodic acid–Schiff (PAS)positive hyaline cytoplasmic inclusion occurs in a variable population of tumor cells and is a hallmark of this tumor.
Ultrastructural examination reveals parallel cytoplasmic filamentous inclusions packed in concentric whorled arrays, a distinctive feature of this tumor, which suggests a neuroectodermal origin. The tumor tends to infiltrate the adjacent renal parenchyma rather than to compress it.
These tumors are notable for the occurrence of a second primary tumor in the midline of the brain, resembling medulloblastoma.
A consistent deletion (22q11-12) has been described in both renal and extrarenal rhabdoid tumors. These deletions delineate an area of overlap at the site of the hSNF5/INI1 gene, and tumors have biallelic alterations or deletions of this gene.
For all renal tumors except RTK, immunohistochemical staining for the wildtype INI-1 protein shows nuclear positivity. In renal and extrarenal rhabdoid tumors, this is absent.
H&A
What are the two principal staging systems used for children with Wilms tumor?
Two principal staging systems are used for children with WT.
Children’s Oncology Group (COG)
The COG system is based on pretreatment findings prior to administration of chemotherapy or radiotherapy.
Patients are given a local stage and a disease stage.
The local stage defines the extent of abdominal disease, and the disease stage considers both the local extent of disease and distant metastasis.
Both factors determine therapy with the use of local RT to the tumor bed based on the local stage and the intensity of chemotherapy based on the disease stage.
Société Internationale D’Oncologie Pédiatrique (SIOP)
SIOP protocols generally recommend chemotherapy followed by nephrectomy, with surgicopathologic staging occurring at the time of nephrectomy.
The SIOP classification was revised in 2010 based on a review of the histologic appearance of the tumors at resection (post neoadjuvant chemotherapy) and the corresponding outcomes.
Tumors are now classified on SIOP protocols as completely necrotic (low-risk tumor), blastemal (high-risk tumor), and other histology (intermediate-risk tumors).
H&A
What are the types of renal tumors?
Renal tumors are the second most common abdominal tumor seen in infants and children behind neuroblastoma.
They represent a wide spectrum from benign to extremely malignant tumors (Box 64.1).
These tumors include Wilms tumor (WT) (also referred to as nephroblastoma or renal embryoma), renal cell carcinoma (RCC), clear cell sarcoma of the kidney (CCSK), rhabdoid tumor of the kidney (RTK), congenital mesoblastic nephroma (CMN), cystic renal tumor, and angiomyolipoma.
H&A
Which of the following is not related to Beckwith–Wiedemann’s syndrome?
A high birthweight
B macroglossia
C risk of multiple tumours
D hyperglycaemia
E omphalocele
D
Beckwith–Wiedemann’s syndrome is associated with hypoglycaemia.
SPSE 1
Regarding mesoblastic nephroma, which of the following is false?
A Between 3% and 10% of all paediatric renal tumours are mesoblastic nephromas.
B Mesoblastic nephroma is the most common renal tumour in those under 3 months.
C 90% are diagnosed within the first year of life.
D Mesoblastic nephroma can be divided into classic and papillary types.
E Mesoblastic nephroma is associated with maternal polyhydramnios.
D
Mesoblastic nephroma gives rise to 3%–10% of all paediatric renal tumours, and is the most common renal tumour in those under 3 months of age.
Ninety percent are diagnosed within the first year of life and it is twice as common in boys as girls.
Two morphological types are recognised and include classic and cellular types and the latter accounts for 42%–63% of cases.
Mesoblastic nephroma classically presents with an abdominal mass and occasional haematuria.
many cases are diagnosed on prenatal ultrasound and give rise to polyhydramnios, hydrops and premature delivery.
mesoblastic nephroma is treated with radical rather than partial nephrectomy to reduce the risk of local recurrence.
Nephrectomy is usually sufficient as the tumour generally follows a benign course.
Ninety-five per cent of patients do not relapse, and the 5% who do have the cellular variant of the disease.
SPSE 1
- Mesoblastic nephroma: (a) classical type, showing infiltrative growth with entrapped renal parenchyma; and (b) cellular type.
https://www.researchgate.net/figure/Mesoblastic-nephroma-a-classical-type-showing-infiltrative-growth-with-entrapped_fig3_239312854
How is risk stratification done for Wilms patients?
In addition to staging, Wilms tumors are risk-stratified in a manner similar to many other pediatric malignancies.
This risk stratification takes into account stage, histopathology, response to treatment, and biologic markers.
The presence of anaplasia renders the tumor one with unfavorable histology.
Anaplasia is strictly defined by two criteria.
The first is the presence of giant tumor cells with markedly enlarged and hyperchromatic nuclei (at least three times the size of other adjacent tumor cells).
The second is the presence of abnormal mitotic figures (multipolar or other forms of frankly abnormal mitoses). Both criteria must be present for diagnosing anaplastic Wilms tumor, with the exception of small biopsies where one of the two criteria is sufficient.
Once anaplasia is identified, the pathologist must determine if it is focal or diffuse, again using rigorous criteria. A diagnosis of focal anaplasia is warranted only when present in limited foci, not within renal vessels or outside the kidney, and completely surrounded by non-neoplastic tissue. Focal anaplasia is of indeterminate clinical significance at the current time.
Diffuse anaplasia is associated with worse outcomes and chemoresistance.
In addition to histology, 1p and/or 16q loss of heterozygosity (LOH) are independently associated with a worse prognosis.
1q gain has emerged as another negative biologic marker, which will be further investigated in future COG studies.
These features place patients in a higher risk category. In these patients, cyclophosphamide and etoposide are often added to the standard three-agent chemotherapy.
On the other end of the spectrum, a very low-risk category of Wilms tumor has been defined. These are children less than 2 years of age with abdominal and disease stage I Wilms tumors weighing less than 550 g with favorable histology. The risk of recurrence in these patients with surgery alone is about 10%. Therefore, 90% of patients can avoid chemotherapy with vincristine and dactinomycin.
The remainder will be salvaged with three-agent chemotherapy if recurrence ensues.
The tradeoff therefore is the need to add doxorubicin to the chemotherapy regimen if recurrence occurs.
Overall survival in these children is 100%.
Criteria for surgery only treatment may be broadened in the future, with increasing use of biologic markers in selecting patients for this modality.
Sherif
