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Wilms Tumor

Updated : February 5, 2024





Background

Nephroblastoma, also known as Wilms tumor, is the most prevalent kind of kidney cancer in children. Additionally, it is the 4th most frequent form of pediatric cancer overall and the most frequent pediatric abdominal malignancy.

Children under the age of five are most frequently diagnosed with a Wilms tumor. The tumor bears the name of Dr. Max Wilms, a German doctor who originally characterized it in 1899.

Epidemiology

The most typical childhood stomach cancer, Wilms cancer, often manifests between the ages of 3 and 5. In the U.s, there are roughly 650 new infections each year. Wilms is slightly more common in girls than in boys. While East Asians are least likely to get Wilms, Africans & African Americans are more likely to do so.

Additionally, Asian individuals had fewer tumors with poor histology, tended to have less advanced-stage diseases, and had better survival rates. The rates in North America and Europe are comparable. 90% of Wilms tumors are discovered before the age of six, with a mean diagnosis age of 3.5 years.

Chemotherapy has significantly improved, and the vast majority of affected youngsters now recover. In the US, the 5-year survival rate is 92 percent overall, but it is only 78 percent in underdeveloped regions of the world with fewer resources.

Wilms cancer is linked to several distinct disorders, including:

  • WAGR syndrome
  • Denys-Drash disease
  • Beckwith-Wiedemann syndrome
  • Sotos syndrome
  • Perlman syndrome
  • Edward’s syndrome
  • Bloom syndrome
  • Li-Fraumeni syndrome, and
  • Simpson-Golabi-Behmel syndrome

Anatomy

Pathophysiology

Grossly, Wilms cancers typically contain a pseudo-capsule and are well-circumscribed. Wilms is split into ” unfavorable” & “favorable” histology. “Favorable” Histology: An arrangement of epithelial, stromal cells, and blastema in a triphasic form is one of the traditional histological characteristics of a “favorable” type of cancer. The most undifferentiated and conceivably most cancerous component is the blastema.

It is made up of clusters of tiny, spherical blue cells with intense mitotic index and overlapped nuclei. Wide variations in the differentiation of the epithelial component, indicating nephrogenesis at various developmental stages, can be seen from an early tubular formation with rudimentary epithelium rosette-like formations to developing glomeruli or tubule-like formations.

Undifferentiated mesenchyme that is tightly packed together or unstructured cellular myxoid regions could make up the stromal component. It could be challenging to tell these areas apart from non-cancerous stromal linked to chemo-induced alteration. Reduction of heterozygosity at the 1p & 16q loci tends to result in a poorer prognosis, even in cases with “Favorable” histopathology. For this reason, 1p & 16q mutations should be examined cytogenetically in Wilms malignant cells when it is available.

“Unfavorable” Histopathology: The percentage of anaplasia in Wilms cancers with “unfavorable” histopathology will be substantially higher, and these cancers have a worse prognosis & survival rate. Histologically speaking, anaplasia is characterized by pleomorphic hyperchromatic nuclei that are 3 times larger than neighboring cells and exhibit aberrant mitotic patterns. Anaplasia is linked to a subpar response to therapy.

Etiology

Although the exact cause of Wilm’s tumor is unknown, genetic changes related to the regular embryo development of the urogenital tract are thought to be to blame. WT1, WTX, and CTNNB1 gene abnormalities, which have been discovered in around one-third of all Wilms tumors, are also some of the biological traits that have been linked to the disease. MYNC and TP53 are additional genes linked to Wilms cancer.

TP53 and the deletion of heterozygosity at chromosomal 1q, 1p, 11p15, & 16q have both been associated with a worse prognosis. Just 1% of people with Wilms have a relation who is affected, who is usually not a parent. Wilms is hypothesized to be caused by nephrogenic reserves or persisting metanephric cells. 1% of infants’ kidneys may have them, but they normally regress in childhood.

Up to 100% of bilateral Wilms cancers include these aberrant metanephric elements, although only 35 percent of unilateral cancers do. Although it is doubtful that aniridia and hemihypertrophy, as well as a number of urological conditions such as cryptorchidism, hypospadias, and horseshoe kidney, are involved in real carcinogenesis, they are linked to the malignancy. Only 5% of Wilms tumor patients have bilateral cancer, and girls are more likely to have it.

Genetics

Prognostic Factors

The histology and tumor phase affect the prognosis. Depending on the phase, the survival rates for good histology range from 99 percent to 86 percent, whereas those for poor histology range from 84 percent to 38 percent.

About 1% of individuals have final-stage kidney failure, which is typically brought on by metachronous contralateral tumors. Women who have the Wilms tumor-aniridia (WAGR) condition are more likely to get gonadoblastomas and may get ovaries that are streaked.

The following qualities are linked to a worse prognosis:

  • The more severe kind is diffuse anaplasia
  • In stage two to four cancers with anaplastic histopathology
  • TP53 and the deletion of heterozygosity at chromosomal 1q, 1p, 11p15, & 16q
  • Greater than 2 years of age
  • Greater density of positive lymph nodes
  • Enormous tumor mass
  • Due to treatment resistance, even tiny tumor foci may be associated with a worse prognosis.

Clinical History

Physical Examination

Age group

Associated comorbidity

Associated activity

Acuity of presentation

Differential Diagnoses

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

Medication

 

dactinomycin

45

mcg/kg

Intravenous (IV)

every 3-6 weeks for 26 weeks in combination with vincristine and doxorubicin.



 
 

Media Gallary

References

https://www.ncbi.nlm.nih.gov/books/NBK442004/

Wilms Tumor

Updated : February 5, 2024




Nephroblastoma, also known as Wilms tumor, is the most prevalent kind of kidney cancer in children. Additionally, it is the 4th most frequent form of pediatric cancer overall and the most frequent pediatric abdominal malignancy.

Children under the age of five are most frequently diagnosed with a Wilms tumor. The tumor bears the name of Dr. Max Wilms, a German doctor who originally characterized it in 1899.

The most typical childhood stomach cancer, Wilms cancer, often manifests between the ages of 3 and 5. In the U.s, there are roughly 650 new infections each year. Wilms is slightly more common in girls than in boys. While East Asians are least likely to get Wilms, Africans & African Americans are more likely to do so.

Additionally, Asian individuals had fewer tumors with poor histology, tended to have less advanced-stage diseases, and had better survival rates. The rates in North America and Europe are comparable. 90% of Wilms tumors are discovered before the age of six, with a mean diagnosis age of 3.5 years.

Chemotherapy has significantly improved, and the vast majority of affected youngsters now recover. In the US, the 5-year survival rate is 92 percent overall, but it is only 78 percent in underdeveloped regions of the world with fewer resources.

Wilms cancer is linked to several distinct disorders, including:

  • WAGR syndrome
  • Denys-Drash disease
  • Beckwith-Wiedemann syndrome
  • Sotos syndrome
  • Perlman syndrome
  • Edward’s syndrome
  • Bloom syndrome
  • Li-Fraumeni syndrome, and
  • Simpson-Golabi-Behmel syndrome

Grossly, Wilms cancers typically contain a pseudo-capsule and are well-circumscribed. Wilms is split into ” unfavorable” & “favorable” histology. “Favorable” Histology: An arrangement of epithelial, stromal cells, and blastema in a triphasic form is one of the traditional histological characteristics of a “favorable” type of cancer. The most undifferentiated and conceivably most cancerous component is the blastema.

It is made up of clusters of tiny, spherical blue cells with intense mitotic index and overlapped nuclei. Wide variations in the differentiation of the epithelial component, indicating nephrogenesis at various developmental stages, can be seen from an early tubular formation with rudimentary epithelium rosette-like formations to developing glomeruli or tubule-like formations.

Undifferentiated mesenchyme that is tightly packed together or unstructured cellular myxoid regions could make up the stromal component. It could be challenging to tell these areas apart from non-cancerous stromal linked to chemo-induced alteration. Reduction of heterozygosity at the 1p & 16q loci tends to result in a poorer prognosis, even in cases with “Favorable” histopathology. For this reason, 1p & 16q mutations should be examined cytogenetically in Wilms malignant cells when it is available.

“Unfavorable” Histopathology: The percentage of anaplasia in Wilms cancers with “unfavorable” histopathology will be substantially higher, and these cancers have a worse prognosis & survival rate. Histologically speaking, anaplasia is characterized by pleomorphic hyperchromatic nuclei that are 3 times larger than neighboring cells and exhibit aberrant mitotic patterns. Anaplasia is linked to a subpar response to therapy.

Although the exact cause of Wilm’s tumor is unknown, genetic changes related to the regular embryo development of the urogenital tract are thought to be to blame. WT1, WTX, and CTNNB1 gene abnormalities, which have been discovered in around one-third of all Wilms tumors, are also some of the biological traits that have been linked to the disease. MYNC and TP53 are additional genes linked to Wilms cancer.

TP53 and the deletion of heterozygosity at chromosomal 1q, 1p, 11p15, & 16q have both been associated with a worse prognosis. Just 1% of people with Wilms have a relation who is affected, who is usually not a parent. Wilms is hypothesized to be caused by nephrogenic reserves or persisting metanephric cells. 1% of infants’ kidneys may have them, but they normally regress in childhood.

Up to 100% of bilateral Wilms cancers include these aberrant metanephric elements, although only 35 percent of unilateral cancers do. Although it is doubtful that aniridia and hemihypertrophy, as well as a number of urological conditions such as cryptorchidism, hypospadias, and horseshoe kidney, are involved in real carcinogenesis, they are linked to the malignancy. Only 5% of Wilms tumor patients have bilateral cancer, and girls are more likely to have it.

The histology and tumor phase affect the prognosis. Depending on the phase, the survival rates for good histology range from 99 percent to 86 percent, whereas those for poor histology range from 84 percent to 38 percent.

About 1% of individuals have final-stage kidney failure, which is typically brought on by metachronous contralateral tumors. Women who have the Wilms tumor-aniridia (WAGR) condition are more likely to get gonadoblastomas and may get ovaries that are streaked.

The following qualities are linked to a worse prognosis:

  • The more severe kind is diffuse anaplasia
  • In stage two to four cancers with anaplastic histopathology
  • TP53 and the deletion of heterozygosity at chromosomal 1q, 1p, 11p15, & 16q
  • Greater than 2 years of age
  • Greater density of positive lymph nodes
  • Enormous tumor mass
  • Due to treatment resistance, even tiny tumor foci may be associated with a worse prognosis.

dactinomycin

45

mcg/kg

Intravenous (IV)

every 3-6 weeks for 26 weeks in combination with vincristine and doxorubicin.



https://www.ncbi.nlm.nih.gov/books/NBK442004/