Wilms tumor, also known as nephroblastoma, is a rare kidney cancer that primarily affects children, typically before the age of five. While most Wilms tumors have a favorable prognosis with standard treatment, anaplastic Wilms tumor represents a more aggressive subtype. Understanding the distinct characteristics of this specific form is important for effective diagnosis and treatment.
Defining Anaplastic Wilms Tumor
Wilms tumor originates from immature kidney cells, leading to uncontrolled growth. Anaplastic Wilms tumor is distinguished by the presence of anaplasia, a term describing significant cellular abnormalities under microscopic examination. These abnormal cells show marked changes, including nuclei that are at least three times larger than adjacent normal cells, distorted shapes, increased darkness (hyperchromasia), and atypical cell division (mitotic figures).
This anaplastic histology, often referred to as “unfavorable histology,” indicates a more aggressive disease course compared to favorable histology Wilms tumors, which account for about 90% of cases. Anaplastic tumors are rarer, occurring in 5% to 10% of all Wilms tumor diagnoses. The presence of anaplasia suggests increased resistance to standard chemotherapy and a higher likelihood of recurrence.
Anaplasia can be focal, meaning it is confined to one or a few localized regions within the tumor, or diffuse, indicating widespread anaplasia throughout the tumor. Diffuse anaplasia carries a poorer prognosis than focal anaplasia. Genetic changes, such as mutations in the TP53 gene, are often associated with anaplasia, contributing to its aggressive behavior and treatment resistance.
Identifying the Tumor: Diagnosis and Staging
The diagnostic process for anaplastic Wilms tumor typically begins with recognizing initial symptoms. The most common sign is an asymptomatic abdominal mass, often discovered by a caregiver, though children may also experience abdominal pain, swelling, fever, or blood in the urine. Once a kidney tumor is suspected, imaging techniques are employed.
Ultrasound, computed tomography (CT) scans, and magnetic resonance imaging (MRI) of the abdomen and chest are commonly used to visualize the tumor, assess its size, and check for spread to other organs like the lungs or liver. While imaging can identify a mass, the definitive diagnosis of anaplasia relies on pathological examination of tumor tissue. A biopsy, or more commonly, surgical removal of the tumor (nephrectomy), provides the tissue for microscopic analysis to confirm the presence and type of anaplasia.
Staging determines the extent of the disease and guides treatment decisions. The Children’s Oncology Group (COG) staging system, widely used in North America, classifies Wilms tumors into five stages (I-V). The presence of anaplasia, particularly diffuse anaplasia, significantly impacts the prognosis at each stage, often necessitating more aggressive treatment regardless of the stage.
- Stage I: Tumor completely confined to the kidney and fully removable by surgery.
- Stage II: Tumor has grown outside the kidney but is still completely resected.
- Stage III: Tumor spread to nearby lymph nodes or structures, or incomplete surgical removal.
- Stage IV: Distant spread to organs like the lungs or liver.
- Stage V: Tumors in both kidneys at diagnosis.
Treatment Strategies
Treatment for anaplastic Wilms tumor is aggressive and multi-modal, involving a combination of surgery, chemotherapy, and radiation therapy. The specific approach is tailored based on the tumor’s stage and the extent of anaplasia (focal or diffuse). Initial treatment often involves surgery to remove the affected kidney (nephrectomy), followed by chemotherapy and, in many cases, radiation.
Chemotherapy regimens for anaplastic Wilms tumor are more intensive than those for favorable histology tumors, reflecting the anaplastic cells’ increased resistance to treatment. Common chemotherapy drugs include vincristine, dactinomycin, and doxorubicin, often administered over several months. For higher-risk cases, such as those with diffuse anaplasia or advanced stages, additional agents like cyclophosphamide, etoposide, and carboplatin may be included.
Radiation therapy plays a significant role in local control, particularly for higher stages or when anaplasia is present, and is often delivered to the area of the tumor shortly after surgery. The timing of radiation therapy is important, with guidelines recommending initiation within 14 days of nephrectomy to improve outcomes. This comprehensive care involves a collaborative team of pediatric oncologists, surgeons, and radiation oncologists to manage the complexities of this disease effectively.
Outlook and Long-Term Management
The prognosis for anaplastic Wilms tumor is more challenging than for favorable histology Wilms tumor due to its aggressive nature and resistance to therapy. However, advancements in treatment protocols have improved outcomes, with survival rates varying based on factors such as tumor stage, the distribution of anaplasia (focal versus diffuse), and the patient’s age. While diffuse anaplasia carries a poorer outlook, focal anaplasia may have an intermediate prognosis.
Long-term management for survivors of anaplastic Wilms tumor is important. This includes regular follow-up appointments with imaging scans to monitor for recurrence, which is most likely to occur within the first two years after treatment. Patients also undergo monitoring for potential late effects of treatment, such as secondary malignancies, cardiac issues, or kidney problems, which can arise from chemotherapy and radiation. Supportive care programs address these long-term health needs, aiming to ensure the best possible quality of life for survivors.