Wilms Tumor

Overview

Epidemiology

• Most common renal malignancy Malignancy Hemothorax in children
• Accounts for 6%–7% of all childhood malignancies
• 500 new cases per year in the United States
• Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency of approximately 7 cases/million children age < 15 years in the United States:
  • ⅔ of cases diagnosed before 5 years of age.
  • 95% of cases diagnosed before 10 years of age.
• Median Median After arranging the data from loWest to highest, the median is the middle value, separating the lower half from the upper half of the data set. Measures of Central Tendency and Dispersion age at diagnosis for:
  • Unilateral disease:
    • Boys: 37 months
    • Girls: 43 months
  • Bilateral disease:
    • Boys: 24 months
    • Girls: 31 months
• Associated congenital Congenital Chorioretinitis anomaly is diagnosed at an earlier age.
• African Americans have a greater risk of developing disease.
• Asians have a significantly lower risk of developing disease.

Etiology

• Generally occurs sporadically
• Approximately 10% have a multiple malformation syndrome:
  • WAGR syndrome: chromosomal deletion of WT1 gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics at 11p13
    • Wilms tumor Tumor Inflammation
    • Aniridia
    • Genitourinary abnormalities
    • Intellectual disability Disability Determination of the degree of a physical, mental, or emotional handicap. The diagnosis is applied to legal qualification for benefits and income under disability insurance and to eligibility for social security and workman’s compensation benefits. ABCDE Assessment (mental Retardation)
  • Beckwith–Wiedemann syndrome (BWS): microduplication mutations at WT2 gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics at 11p15
    • Wilms’ tumor Tumor Inflammation (in 5%–10%)
    • Macrosomia
    • Macroglossia
    • Hemihypertrophy
    • Omphalocele Omphalocele Omphalocele is a congenital anterior abdominal wall defect in which the intestines are covered by peritoneum and amniotic membranes. The condition results from the failure of the midgut to return to the abdominal cavity by 10 weeks’ gestation. Omphalocele
    • Prominent eyes
    • Ear creases
    • Enlarged kidneys Enlarged kidneys Autosomal dominant polycystic kidney disease (ADPKD)
    • Pancreatic hyperplasia Hyperplasia An increase in the number of cells in a tissue or organ without tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. Cellular Adaptation
    • Neonatal hypoglycemia Hypoglycemia Hypoglycemia is an emergency condition defined as a serum glucose level ≤ 70 mg/dL (≤ 3.9 mmol/L) in diabetic patients. In nondiabetic patients, there is no specific or defined limit for normal serum glucose levels, and hypoglycemia is defined mainly by its clinical features. Hypoglycemia
  • Denys–Drash syndrome Denys–Drash Syndrome Nephrotic Syndrome in Children: germline point mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations in the 8th or 9th exon in the WT1 gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics
    • Wilms tumor Tumor Inflammation
    • Male pseudohermaphroditism: may have undescended testes Undescended testes A developmental defect in which a testis or both testes failed to descend from high in the abdomen to the bottom of the scrotum. Testicular descent is essential to normal spermatogenesis which requires temperature lower than the body temperature. Cryptorchidism can be subclassified by the location of the maldescended testis. Familial Juvenile Polyposis owing to gonadal dysgenesis
    • Diffuse mesangial sclerosis in kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy: proteinuria Proteinuria The presence of proteins in the urine, an indicator of kidney diseases. Nephrotic Syndrome in Children in infancy, which progresses to nephrotic syndrome Nephrotic syndrome Nephrotic syndrome is characterized by severe proteinuria, hypoalbuminemia, and peripheral edema. In contrast, the nephritic syndromes present with hematuria, variable loss of renal function, and hypertension, although there is sometimes overlap of > 1 glomerular disease in the same individual. Nephrotic Syndrome and renal failure Renal failure Conditions in which the kidneys perform below the normal level in the ability to remove wastes, concentrate urine, and maintain electrolyte balance; blood pressure; and calcium metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of proteinuria) and reduction in glomerular filtration rate. Crush Syndrome

Pathophysiology

• Associated with aberrant renal development:
  • Abnormal glomerular or tubular development in metanephric blastema proliferation
  • Believed to arise from nephrogenic rests or nephroblastomatosis (which are foci of persistent immature or embryonal cells):
    • Present in 1% of newborn Newborn An infant during the first 28 days after birth. Physical Examination of the Newborn kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy and regress in early childhood
    • Present in 35% of unilateral and almost 100% of bilateral Wilms tumor Tumor Inflammation
• Tumorigenesis:
  •  Thought to be from genetic changes triggering these nephrogenic rests
  • Associated with loss-of-function mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations in a number of tumor Tumor Inflammation suppressor and transcription Transcription Transcription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination. Stages of Transcription genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure:
    • WT1
    • WT2
    • p53
    • FWT1
    • FWT2
• Some tumors do not have any of the above genetic mutations Genetic Mutations Carcinogenesis, suggesting that other, unknown genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure may be involved in Wilms tumor Tumor Inflammation.

Clinical Presentation

Manifestations

• Most present with only a firm, painless smooth mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast that does not cross the midline.
• Other less common symptoms:
  • Abdominal pain Abdominal Pain Acute Abdomen
  • Hematuria Hematuria Presence of blood in the urine. Renal Cell Carcinoma
  • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
  • Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension
• Subset of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship presents with subcapsular hemorrhage:
  • Rapid abdominal enlargement
  • Anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types
  • Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension
  • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever

Physical examination

• General abdominal exam with patient in supine position: 
  • Visually inspect abdomen and flank.
  • Assess for palpable mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast.
  • Careful exam required if Wilms tumor Tumor Inflammation suspected (vigorous palpation Palpation Application of fingers with light pressure to the surface of the body to determine consistency of parts beneath in physical diagnosis; includes palpation for determining the outlines of organs. Dermatologic Examination increases risk of rupture and tumor Tumor Inflammation spillage).
• General genitourinary exam assessing for syndromic conditions
• Eye exam to assess for aniridia
• Assess for hemihypertrophy of limbs.

Diagnosis

Screening Screening Preoperative Care

Serial abdominal ultrasonography for those at risk for Wilms tumor Tumor Inflammation:

• Children with BWS or isolated hemihyperplasia: every 3 months until 7 years old
• Children with WAGR and WT1-associated syndromes: every 3 months until 5 years old
• Siblings of patient with familial Wilms tumor Tumor Inflammation: every 3 months until 8 years old
• Children of survivors of bilateral Wilms tumor Tumor Inflammation: every 3 months until 8 years old

Diagnostic imaging and laboratory studies

• Abdominal (renal) ultrasonography: detects hydronephrosis Hydronephrosis Hydronephrosis is dilation of the renal collecting system as a result of the obstruction of urine outflow. Hydronephrosis can be unilateral or bilateral. Nephrolithiasis is the most common cause of hydronephrosis in young adults, while prostatic hyperplasia and neoplasm are seen in older patients. Hydronephrosis and a multicystic renal mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast
• CT with contrast CT with Contrast Imaging of the Head and Brain or MRI of abdomen: to further evaluate nature or extent of disease
• CT of chest:
  • To determine if there is lung metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis
  • Biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma if there is a suspicious nodule Nodule Chalazion
• Definitive diagnosis is via biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma:
  • Tumor Tumor Inflammation is a mixed pattern of 3 types of cells:
    • Blastemal cells
    • Stromal cells
    • Epithelial cells
  • Proportions vary, leading to multiple appearances.
  • Anaplastic Wilms tumor Tumor Inflammation:
    • Large, distorted nuclei + multipolar Multipolar Single axon on one end of the cell body and many dendrites on the other. Nervous System: Histology polypoid mitotic figures noted
    • More common in older age
    • Indicative of adverse outcome
• Laboratory tests:
  • Urinalysis Urinalysis Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. Urinary Tract Infections (UTIs) in Children:
    • Hematuria Hematuria Presence of blood in the urine. Renal Cell Carcinoma
    • Proteinuria Proteinuria The presence of proteins in the urine, an indicator of kidney diseases. Nephrotic Syndrome in Children in Denys–Drash syndrome Denys–Drash Syndrome Nephrotic Syndrome in Children
  • CMP for baseline creatinine
  • CBC for baseline hemoglobin (may have polycythemia Polycythemia An increase in the total red cell mass of the blood. Renal Cell Carcinoma)
  • Abnormal liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy function tests if there is liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis

Staging Staging Methods which attempt to express in replicable terms the extent of the neoplasm in the patient. Grading, Staging, and Metastasis

From National Wilms Tumor Tumor Inflammation Study (NWTS)/Children’s Oncology Group (COG):

• Stage I:
  • Tumor Tumor Inflammation confined to the kidney and completely excised
  • Renal capsule Renal capsule Pyelonephritis and Perinephric Abscess is intact.
  • No biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma was performed or tumor Tumor Inflammation spillage
  • No renal vessel involvement
  • No positive surgical margins
  • All sampled lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy negative
• Stage II:
  • Tumor Tumor Inflammation has grown beyond the kidney but is completely excised.
  • May have regional extension Extension Examination of the Upper Limbs of tumor Tumor Inflammation ( penetration Penetration X-rays of renal capsule Renal capsule Pyelonephritis and Perinephric Abscess or invasion of renal sinus).
  • Blood vessels outside the renal parenchyma may contain tumor Tumor Inflammation.
  • All lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy sampled are negative.
• Stage III:
  • Residual tumor Tumor Inflammation remains (incomplete surgical excision)
  • Tumor Tumor Inflammation penetrating through the peritoneum Peritoneum The peritoneum is a serous membrane lining the abdominopelvic cavity. This lining is formed by connective tissue and originates from the mesoderm. The membrane lines both the abdominal walls (as parietal peritoneum) and all of the visceral organs (as visceral peritoneum). Peritoneum: Anatomy
  • Positive tumor Tumor Inflammation spillage or biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma
  • Positive regional lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy (not in distant lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy)
• Stage IV:
  • Hematogenous Hematogenous Hepatocellular Carcinoma (HCC) and Liver Metastases metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis
  • Lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs node metastases outside the abdominopelvic region
  • Tumor Tumor Inflammation within the adrenal gland
• Stage V: bilateral renal involvement

Management

Treatment

Recommendations based on the NWTS/COG trials:

• Depends on the stage and histology
• Stages I and II:
  • Primary surgical resection
  • 19 weeks of vincristine Vincristine An antitumor alkaloid isolated from vinca rosea. Microtubule and Topoisomerase Inhibitors and dactinomycin Dactinomycin A compound composed of a two cyclic peptides attached to a phenoxazine that is derived from streptomyces parvulus. It binds to DNA and inhibits RNA synthesis (transcription), with chain elongation more sensitive than initiation, termination, or release. As a result of impaired mRNA production, protein synthesis also declines after dactinomycin therapy. Antitumor Antibiotics after surgery
  • If patient has high-risk molecular markers (loss of heterozygosity at chromosomes Chromosomes In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. DNA Types and Structure 1p and 16q): 
    • Add doxorubicin.
    • Extend chemotherapy Chemotherapy Osteosarcoma regimen to 25 weeks.
  • If patient has stage I anaplasia or stage II focal anaplasia:
    • Add doxorubicin.
    • Extend chemotherapy Chemotherapy Osteosarcoma regimen to 25 weeks.
    • Add radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma therapy.
  • If patient has stage II + diffuse anaplasia: 
    • Add carboplatin Carboplatin An organoplatinum compound that possesses antineoplastic activity. Alkylating Agents and Platinum, cyclophosphamide Cyclophosphamide Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It has been used in the treatment of lymphoma and leukemia. Its side effect, alopecia, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. Immunosuppressants, and etoposide Etoposide A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the g2 and s phases of the cell cycle. Microtubule and Topoisomerase Inhibitors.
    • Remove dactinomycin Dactinomycin A compound composed of a two cyclic peptides attached to a phenoxazine that is derived from streptomyces parvulus. It binds to DNA and inhibits RNA synthesis (transcription), with chain elongation more sensitive than initiation, termination, or release. As a result of impaired mRNA production, protein synthesis also declines after dactinomycin therapy. Antitumor Antibiotics.
    • Add radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma therapy.
    • Extend chemotherapy Chemotherapy Osteosarcoma regimen to 30 weeks.
• Stage III:
  • Primary surgical resection with lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs node sampling
  • 25 weeks of vincristine Vincristine An antitumor alkaloid isolated from vinca rosea. Microtubule and Topoisomerase Inhibitors, dactinomycin Dactinomycin A compound composed of a two cyclic peptides attached to a phenoxazine that is derived from streptomyces parvulus. It binds to DNA and inhibits RNA synthesis (transcription), with chain elongation more sensitive than initiation, termination, or release. As a result of impaired mRNA production, protein synthesis also declines after dactinomycin therapy. Antitumor Antibiotics, and doxorubicin after surgery
  • Radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma therapy
  • If patient has high-risk molecular markers:
    • Add cyclophosphamide Cyclophosphamide Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It has been used in the treatment of lymphoma and leukemia. Its side effect, alopecia, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. Immunosuppressants and etoposide Etoposide A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the g2 and s phases of the cell cycle. Microtubule and Topoisomerase Inhibitors.
    • Extend chemotherapy Chemotherapy Osteosarcoma regimen to 31 weeks.
  • If patient has diffuse anaplasia:
    • Add carboplatin Carboplatin An organoplatinum compound that possesses antineoplastic activity. Alkylating Agents and Platinum, cyclophosphamide Cyclophosphamide Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It has been used in the treatment of lymphoma and leukemia. Its side effect, alopecia, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. Immunosuppressants, and etoposide Etoposide A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the g2 and s phases of the cell cycle. Microtubule and Topoisomerase Inhibitors.
    • Remove dactinomycin Dactinomycin A compound composed of a two cyclic peptides attached to a phenoxazine that is derived from streptomyces parvulus. It binds to DNA and inhibits RNA synthesis (transcription), with chain elongation more sensitive than initiation, termination, or release. As a result of impaired mRNA production, protein synthesis also declines after dactinomycin therapy. Antitumor Antibiotics.
    • Extend chemotherapy Chemotherapy Osteosarcoma regimen to 30 weeks.
• Stage IV:
  • Primary surgical resection with lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs node sampling
  • 25 weeks of vincristine Vincristine An antitumor alkaloid isolated from vinca rosea. Microtubule and Topoisomerase Inhibitors, dactinomycin Dactinomycin A compound composed of a two cyclic peptides attached to a phenoxazine that is derived from streptomyces parvulus. It binds to DNA and inhibits RNA synthesis (transcription), with chain elongation more sensitive than initiation, termination, or release. As a result of impaired mRNA production, protein synthesis also declines after dactinomycin therapy. Antitumor Antibiotics, and doxorubicin after surgery
  • Radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma therapy
  • If patient has high-risk molecular markers and/or lung nodule Nodule Chalazion with incomplete response in 6 weeks:
    • Add cyclophosphamide Cyclophosphamide Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It has been used in the treatment of lymphoma and leukemia. Its side effect, alopecia, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. Immunosuppressants and etoposide Etoposide A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the g2 and s phases of the cell cycle. Microtubule and Topoisomerase Inhibitors.
    • Extend chemotherapy Chemotherapy Osteosarcoma regimen to 31 weeks.
  • If patient has focal anaplasia:
    • Add carboplatin Carboplatin An organoplatinum compound that possesses antineoplastic activity. Alkylating Agents and Platinum, cyclophosphamide Cyclophosphamide Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It has been used in the treatment of lymphoma and leukemia. Its side effect, alopecia, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. Immunosuppressants, and etoposide Etoposide A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the g2 and s phases of the cell cycle. Microtubule and Topoisomerase Inhibitors.
    • Remove dactinomycin Dactinomycin A compound composed of a two cyclic peptides attached to a phenoxazine that is derived from streptomyces parvulus. It binds to DNA and inhibits RNA synthesis (transcription), with chain elongation more sensitive than initiation, termination, or release. As a result of impaired mRNA production, protein synthesis also declines after dactinomycin therapy. Antitumor Antibiotics.
    • Extend chemotherapy Chemotherapy Osteosarcoma regimen to 30 weeks.
  • If patient has diffuse anaplasia:
    • Add carboplatin Carboplatin An organoplatinum compound that possesses antineoplastic activity. Alkylating Agents and Platinum, cyclophosphamide Cyclophosphamide Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It has been used in the treatment of lymphoma and leukemia. Its side effect, alopecia, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. Immunosuppressants, and irinotecan Irinotecan A semisynthetic camptothecin derivative that inhibits DNA topoisomerase I to prevent nucleic acid synthesis during s phase. It is used as an antineoplastic agent for the treatment of colorectal neoplasms and pancreatic neoplasms. Microtubule and Topoisomerase Inhibitors.
    • Remove dactinomycin Dactinomycin A compound composed of a two cyclic peptides attached to a phenoxazine that is derived from streptomyces parvulus. It binds to DNA and inhibits RNA synthesis (transcription), with chain elongation more sensitive than initiation, termination, or release. As a result of impaired mRNA production, protein synthesis also declines after dactinomycin therapy. Antitumor Antibiotics.
    • Extend chemotherapy Chemotherapy Osteosarcoma regimen to 36 weeks.
• Stage V (bilateral):
  • Preoperative vincristine Vincristine An antitumor alkaloid isolated from vinca rosea. Microtubule and Topoisomerase Inhibitors, actinomycin, and doxorubicin for 6 weeks
  • Surgery
  • Postoperative chemotherapy Chemotherapy Osteosarcoma and radiotherapy (decision based on histopathology of the tumor Tumor Inflammation and lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs node involvement)

Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas

• 5-year survival rate > 90%
• Depends on tumor Tumor Inflammation stage at diagnosis
• Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with diffuse anaplasia have the worst prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas.
• Age influences prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas:
  • Older age at diagnosis is associated with a worse prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas.
  • Adults: higher rate of treatment-associated toxicity Toxicity Dosage Calculation
  • < 2 years of age: lower relapse Relapse Relapsing Fever rate
• Cause of death:
  • Tumor-related: 86%
  • Late effects of therapy: 9%
  • Not related to disease or effects of therapy: 5%
  • Unknown: 1%

Differential Diagnosis

• Clear cell sarcoma of the kidney: second most common pediatric malignancy Malignancy Hemothorax of the kidney: This condition has higher relapse Relapse Relapsing Fever and mortality Mortality All deaths reported in a given population. Measures of Health Status rates than Wilms’ tumor Tumor Inflammation. Bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types is a common site of metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis. Pathology shows cords and nests of pale-stained tumor Tumor Inflammation cells with significant extracellular matrix Extracellular matrix A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. Hypertrophic and Keloid Scars that is separated by a network of vascular arcades. Diagnosis is via imaging ultrasonography or CT, and treatment consists of surgery and chemotherapy Chemotherapy Osteosarcoma.
• Rhabdoid tumor Tumor Inflammation of the kidney: highly malignant renal tumor Tumor Inflammation that commonly involves children < 2 years old. At diagnosis, the tumor Tumor Inflammation is often advanced, with metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis to the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy, lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy, abdomen, brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification, liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy, and bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types. Mortality rate Mortality rate Calculated as the ratio of the total number of people who die due to all causes over a specific time period to the total number of people in the selected population. Measures of Health Status is high (> 80%) within a year of diagnosis. Abdominal imaging: ultrasonography versus CT with biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma are utilized for diagnosis, and treatment is with chemotherapy Chemotherapy Osteosarcoma.
• Congenital Congenital Chorioretinitis mesoblastic nephroma: benign Benign Fibroadenoma renal mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast diagnosed during first year of life or via prenatal ultrasonography: Congenital Congenital Chorioretinitis mesoblastic nephroma associated with hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension and elevated renin Renin A highly specific (leu-leu) endopeptidase that generates angiotensin I from its precursor angiotensinogen, leading to a cascade of reactions which elevate blood pressure and increase sodium retention by the kidney in the renin-angiotensin system. Renal Sodium and Water Regulation and calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes. The mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast is usually infiltrative and requires surgical excision.
• Renal cell carcinoma Renal cell carcinoma Renal cell carcinoma (RCC) is a tumor that arises from the lining of the renal tubular system within the renal cortex. Renal cell carcinoma is responsible for 80%-85% of all primary renal neoplasms. Most RCCs arise sporadically, but smoking, hypertension, and obesity are linked to its development. Renal Cell Carcinoma ( RCC RCC Renal cell carcinoma (RCC) is a tumor that arises from the lining of the renal tubular system within the renal cortex. Renal cell carcinoma is responsible for 80%-85% of all primary renal neoplasms. Most RCCs arise sporadically, but smoking, hypertension, and obesity are linked to its development. Renal Cell Carcinoma): Rare in childhood, but at presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor the disease is usually already advanced in children as compared with in adults. Neuroblastoma Neuroblastoma Neuroblastoma is a malignancy that arises from the neural crest cell derivatives along the sympathetic chain (neuroblasts) and is most commonly located in the adrenal medulla. The tumor often presents in childhood with a flank mass that crosses the midline. Neuroblastoma survivors who had renally directed radiotherapy and platinum-based chemotherapy Chemotherapy Osteosarcoma may be at increased risk of RCC RCC Renal cell carcinoma (RCC) is a tumor that arises from the lining of the renal tubular system within the renal cortex. Renal cell carcinoma is responsible for 80%-85% of all primary renal neoplasms. Most RCCs arise sporadically, but smoking, hypertension, and obesity are linked to its development. Renal Cell Carcinoma. Diagnosis is with abdominal imaging, and treatment is surgical excision.
• Renal medullary carcinoma: highly invasive, rare renal malignancy Malignancy Hemothorax: Disease is essentially seen in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with sickle cell hemoglobinopathy, particularly sickle cell trait sickle cell trait The condition of being heterozygous for hemoglobin S. Sickle Cell Disease. Tumor Tumor Inflammation is aggressive and is noted with early metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis. Treatment is with surgical excision and chemotherapy Chemotherapy Osteosarcoma.