Successful management approach for Wilms tumor metastatic to the skull treated with regimen I chemotherapy in 10th week: A case report

Abstract

Wilms tumor is the most common pediatric renal malignancy, while skull metastasis is rare, occurring in fewer than 2% of cases. We report a five-year-old girl with stage II anaplastic nephroblastoma who developed skull metastasis two months after radical nephrectomy. She received 24 weeks of regimen I chemotherapy. The skull mass regressed by week six and completely resolved by week ten, with full closure of the exposed area by week eighteen. Adverse effects included alopecia, nausea, anemia, and leukopenia. Post-treatment imaging showed no residual skull lesion. Regimen I demonstrated an effective therapeutic response in this rare presentation.

Highlights

• •Skull metastasis in Wilms tumor is extremely rare.
• •Stage II anaplastic nephroblastoma with skull lesion.
• •Regimen I chemotherapy for 24 weeks.
• •Complete skull mass resolution by week 10.
• •No residual skull lesion on post-treatment MRI.

1. Introduction

Nearly 6–7% of pediatric cancers consist of renal tumors, and 90% of these are Wilms tumors. The annual incidence in Europe is approximately 1 per 100,000 children (around 100 new cases each year), while in the United States the incidence is 8.1 per 1,000,000 (approximately 500 new cases annually). Wilms tumor is the fourth leading cause of childhood malignancy and accounts for 5% of all pediatric cancers and 95% of renal cancers in children.^1,2 It is most commonly diagnosed in children aged 2–3 years, with a relatively equal male-to-female distribution and a slight female predominance outside Eastern Asia.²

Treatment of Wilms tumor typically consists of multimodal therapy, including surgery, chemotherapy, and radiotherapy. The choice of chemotherapy regimen depends on histology (favorable versus unfavorable), disease stage, and specific molecular characteristics. Advances in outcomes are attributed to the systematic refinement of treatment protocols and a multidisciplinary approach to care.² Currently, two major protocols are used: the Société Internationale d’Oncologie Pediatrique (SIOP) protocol and the North American protocol developed by the National Wilms Tumor Study Group/Children's Oncology Group (NWTSG/COG).¹

Wilms tumor typically spreads to regional lymph nodes, with distant metastases most commonly involving the lungs and liver. In contrast to neuroblastoma, bone metastasis in classical Wilms tumor is extremely rare. Among 375 patients diagnosed with Wilms tumor between 1962 and 1992, only three cases (0.8%) developed bone metastases.³

2. Case presentation

A six-year-old girl presented with a chief complaint of a right abdominal mass that had been present for one year and had progressively enlarged over the past six months (Fig. 1). She also reported radiating abdominal pain and nausea without vomiting. Additionally, she experienced a weight loss of 3 kg over two months and hematuria for the past two months. There was no significant family or surgical history. The patient had previously received treatment at the pediatric polyclinic of a secondary referral hospital and was subsequently referred to a tertiary referral hospital. On physical examination, a palpable mass was found in the right abdomen.

Fig. 1.

Clinical manifestation abdomen of abdominal mass in a 6-year-old female patient.

Abdominal ultrasonography (Fig. 2a and b) revealed a solid, heterogeneous right renal mass measuring 9.9 × 8.8 × 10.6 cm with well-defined borders. Contrast-enhanced abdominal CT scan (Fig. 2c and d) demonstrated a solid right renal mass with a claw sign, measuring 22 × 15 × 13 cm, showing contrast enhancement, crossing the midline, adherent to the inferior vena cava, and associated with multiple lymphadenopathies. Chest X-ray (Fig. 2e) showed no evidence of metastatic disease.

Fig. 2.

Imaging Studies. (a) Abdominal Ultrasonography; (b) Abdominal Ultrasonography; (c) Abdominal CT-Scan with Contrast; (d) Abdominal CT-Scan with Contrast; (e) AP/Lateral Chest x-ray.

The patient underwent right radical nephrectomy on June 4, 2021, at a tertiary referral hospital (Fig. 3a). Histopathological examination confirmed anaplastic nephroblastoma, stage IV. Two months after surgery, the patient developed a mass on the left side of her head (Fig. 3b).

Fig. 3.

(a) Abdominal Mass (Wilms tumor); (b) Skull metastasis in a 6-year-old female patient with Wilms tumor; (e) Head CT-Scan with Contrast.

A contrast-enhanced head CT scan (Fig. 3c) revealed an extra-axial isodense lesion in the left frontal region with heterogeneous enhancement, measuring approximately 3.8 × 4.8 × 5.7 cm, associated with destruction of the left frontal bone.

The patient subsequently underwent 24 weeks of regimen I chemotherapy consisting of vincristine, doxorubicin, cyclophosphamide, and etoposide from June 2021 to December 2021. She was also evaluated by the neurosurgery department for the cranial mass and was advised to continue chemotherapy and monitor treatment response.

The cranial mass decreased in size after six weeks of chemotherapy and completely resolved by the tenth week. The previously exposed skull area was fully covered by the eighteenth week of treatment (Fig. 4a–d).

Fig. 4.

(a) Evaluation Clinical Manifestation at: 6th week; (b) Evaluation Clinical Manifestation at: 10th week; (c) Evaluation Clinical Manifestation at: 18th week; (d) Evaluation Clinical Manifestation at: 24th week; (e) Evaluation Skull MRI with Contrast.

After completion of 24 weeks of chemotherapy, a contrast-enhanced skull MRI (Fig. 4e) and abdominal CT scan (Fig. 5) were performed. The skull MRI demonstrated no pathological lesions, indicating complete resolution of the cranial mass.

Fig. 5.

Evaluation abdominal CT-Scan with contrast.

3. Discussion

Wilms tumor is the second most common intra-abdominal malignancy in childhood and the fifth most common pediatric cancer overall. It accounts for approximately 6% of all pediatric cancers and more than 95% of renal tumors in children. Approximately 75% of cases occur in children younger than five years, with a peak incidence at 2–3 years of age. Survival outcomes have improved significantly, with more than 85% of patients with localized disease and over 70% with metastatic disease achieving long-term survival.⁴

The lungs are the most common site of distant metastasis, whereas hepatic metastases are less frequent. Approximately 12% of patients present with hematogenous metastases at diagnosis, with pulmonary involvement in 80%, liver in 15%, and other sites in 4%.⁵ Wilms tumor typically spreads to regional lymph nodes, with distant metastases involving the lungs and liver. In contrast to neuroblastoma, bone metastasis in Wilms tumor, as observed in this case, is extremely rare. Among 375 patients diagnosed between 1962 and 1992, only three cases (0.8%) developed bone metastases.³

Some pediatric renal tumors may be asymptomatic and detected incidentally by parents or during routine health examinations. Most patients present with abdominal swelling or a palpable abdominal mass (83%), with or without abdominal pain (37%), fever (23%), hematuria (21–25%), and hypertension (20–25%).⁶ In this case, the patient presented with a right abdominal mass that had been present for one year and progressively enlarged over the preceding six months. The patient also experienced radiating abdominal pain, nausea without vomiting, a weight loss of 3 kg over two months, and hematuria for two months. Physical examination confirmed a palpable mass in the right abdomen.

Management of Wilms tumor is based on two major approaches: the upfront surgery-based protocol developed by the National Wilms Tumor Study (NWTS) and the preoperative chemotherapy-based protocol developed by the International Society of Pediatric Oncology (SIOP).⁷ In this case, the NWTS protocol was selected because pre-nephrectomy chemotherapy carries potential risks, including treatment of a benign lesion without histological confirmation (as pre-chemotherapy biopsy is not mandatory in SIOP trials), alteration of tumor histology, misclassification of tumor type, and loss of accurate staging information. However, the NWTS approach also carries disadvantages, including intraoperative tumor spillage and inadequate lymph node sampling, which may lead to under-staging and suboptimal treatment.⁴

According to the National Wilms Tumor Study (NWTS), chemotherapy regimens include: (1) EE4A (vincristine and dactinomycin), (2) DD4A (vincristine, dactinomycin, and doxorubicin), (3) VAD (vincristine, dactinomycin, and doxorubicin), (4) regimen M (vincristine, dactinomycin, doxorubicin, cyclophosphamide, and etoposide), and (5) regimen I (vincristine, doxorubicin, cyclophosphamide, and etoposide). A primary objective of NWTS-5 was to improve outcomes in patients with stage II–IV diffuse anaplastic histology using regimen I. Outcomes with regimen I compared favorably with historical controls.⁶

In the study by Jeffrey et al., patients with diffuse anaplastic histology treated in NWTS-3 and NWTS-4 with nephrectomy followed by regimen J demonstrated 4-year overall survival rates of 70.1% for stage II, 56.3% for stage III, and 16.7% for stage IV disease.⁷ In comparison, patients treated in NWTS-5 with immediate nephrectomy followed by regimen I achieved 4-year overall survival rates of 81.5% for stage II, 66.7% for stage III, and 33.3% for stage IV disease.⁸

In our case, the patient received systemic therapy with regimen I for 24 weeks. The cranial mass decreased in size after six weeks and completely resolved by the tenth week of chemotherapy. The previously exposed skull area was fully covered by the eighteenth week of treatment. After completing 24 weeks of therapy, contrast-enhanced skull magnetic resonance imaging demonstrated no residual pathological lesions. However, contrast-enhanced abdominal computed tomography revealed multiple nodules in the right and left hepatic lobes.

Although regimen I likely contributed to improved outcomes observed in NWTS-5 compared with NWTS-4, shifts in patient characteristics may also have influenced results. A higher proportion of patients with unilateral tumors received pre-nephrectomy chemotherapy in NWTS-5 (14%) compared with NWTS-4 (9%).⁶

In the study by Jeffrey et al., among 91 patients treated with regimen I as initial therapy, common grade 3–4 toxicities included neutropenia, leukopenia, anemia, thrombocytopenia, and infection. Two patients developed second malignant neoplasms. One patient with stage IV diffuse anaplastic histology developed acute myeloid leukemia 14 months after diagnosis. Another patient with stage II diffuse anaplastic histology had a focus of rhabdomyosarcoma within the primary tumor and later developed orbital rhabdomyosarcoma, an unusual site for Wilms tumor.⁶

In our case, the patient experienced anemia and leukopenia during chemotherapy but showed no evidence of secondary malignancy, acute myeloid leukemia, or rhabdomyosarcoma.

4. Conclusion

Wilms tumor with skull metastasis is extremely rare. Among 375 patients diagnosed with Wilms tumor between 1962 and 1992, only three cases (0.8%) were reported to have bone metastases. This case demonstrates that regimen I chemotherapy may provide an effective therapeutic approach in managing Wilms tumor with skull metastasis.

CRediT authorship contribution statement

Buyung Prasetyawan: Conceptualization, Data curation, Investigation, Writing – original draft. Kurnia Penta Seputra: Investigation, Supervision, Writing – review & editing. Pradana Nurhadi: Supervision, Validation, Writing – review & editing.

Informed consent

Written informed consent was obtained from the patient's parents for publication of this case report and accompanying images.

Data availability statement

The data supporting this study are not publicly available due to patient confidentiality but are available from the corresponding author upon reasonable request.

Funding statement

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Conflicts of interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.