Primary Intrarenal Neuroblastoma in an Infant Mimicking Wilms Tumor: A Rare Case Report and Diagnostic Dilemma

Abstract

Background

Primary intrarenal neuroblastoma (IRNB) is an exceptionally rare pediatric malignancy that can closely resemble Wilms tumor on clinical and radiologic evaluation, posing significant diagnostic and therapeutic challenges. Accurate differentiation between these two entities is critical, as their management strategies and prognostic profiles differ considerably.

Case Presentation

We report the case of an 8-month-old male infant who presented with a progressively enlarging right-sided abdominal mass. Contrast-enhanced computed tomography revealed a large heterogeneously enhancing right renal mass with vascular encasement and intratumoral calcifications, findings that initially favored a diagnosis of Wilms tumor. The patient received preoperative chemotherapy in accordance with the SIOP protocol, followed by radical nephrectomy. Histopathologic examination of the resected specimen demonstrated a poorly differentiated neuroblastoma characterized by Homer–Wright rosettes, neuropil formation, and salt-and-pepper nuclear chromatin. Immunohistochemical analysis showed diffuse synaptophysin positivity and absence of WT1 expression, confirming the diagnosis of primary intrarenal neuroblastoma. The patient subsequently received neuroblastoma-directed chemotherapy and achieved complete remission.

Conclusion

Primary intrarenal neuroblastoma is a rare but important differential diagnosis of renal masses in infancy, particularly when imaging reveals atypical features, such as vascular encasement and intratumoral calcifications, or when there is a suboptimal response to Wilms tumor–directed chemotherapy. Because of its significant clinical and radiologic overlap with Wilms tumor, preoperative diagnosis remains challenging. In patients with atypical findings, tissue diagnosis by core needle or open surgical biopsy, followed by histopathologic and immunohistochemical evaluation, should be considered before initiating empiric chemotherapy. Early multidisciplinary assessment is essential for accurate diagnosis and appropriate management.

Introduction

Neuroblastoma (NB) is the most common extracranial solid malignancy of childhood, accounting for approximately 8–10% of all pediatric cancers and contributing disproportionately to childhood cancer-related mortality. ¹ It arises from primitive sympathoadrenal neural crest progenitor cells and most frequently originates in the adrenal medulla or paravertebral sympathetic ganglia. Approximately 65% of all neuroblastoma cases arise within the adrenal gland, while the remainder develop along the paraspinal sympathetic chain, with occasional ectopic foci reported. ¹ Renal involvement is rare and may occur due to ectopic adrenal rests, intrarenal sympathetic tissue, or secondary invasion by adjacent neuroblastoma.^2,3

Primary intrarenal neuroblastoma (IRNB) is an exceedingly rare clinicopathologic entity, representing approximately 1–2% of all neuroblastoma cases.^4,5 By definition, IRNB arises exclusively within the renal parenchyma without an identifiable extrarenal primary tumor, distinguishing it from cases of direct adrenal or retroperitoneal neuroblastoma with secondary renal invasion. Its clinical, biochemical, and radiologic presentation frequently overlaps with that of Wilms tumor, thereby creating a challenging and consequential diagnostic dilemma. Neuroblastoma has accordingly been designated a “great masquerader” in the setting of pediatric renal masses. ⁶

Despite overlapping clinical and imaging features, IRNB and Wilms tumor arise from fundamentally distinct embryologic lineages, the neural crest and intermediate mesoderm, respectively, and differ markedly in their biological behavior, risk stratification frameworks, chemotherapeutic regimens, and prognostic outcomes.^6,7 IRNB is frequently associated with more aggressive local behavior and mandates neuroblastoma-specific risk-adapted therapy rather than the nephroblastoma-directed protocols that are standard for Wilms tumor. ⁷ Consequently, misclassification carries serious clinical ramifications, including administration of inappropriate initial chemotherapy, delayed surgical planning, and suboptimal disease control.

Preoperative radiologic differentiation between IRNB and Wilms tumor is further complicated by significant imaging overlap, particularly in the setting of large renal masses with heterogeneous enhancement and internal complexity.^8,9 In resource-limited environments, this diagnostic challenge is compounded by restricted access to confirmatory biochemical assays such as urinary catecholamine measurements, which serve as an important noninvasive discriminating tool in better-resourced settings. This report describes a case of primary IRNB in an 8-month-old male infant who was initially managed as a Wilms tumor under the SIOP neoadjuvant chemotherapy protocol. The case illustrates the key clinicopathologic, radiologic, and histopathologic features that ultimately led to a definitive diagnosis and underscores the indispensability of integrated multidisciplinary assessment in the evaluation of pediatric renal masses.

Case Presentation

An 8-month-old male infant presented with a one-month history of progressive right-sided abdominal swelling associated with intermittent low-grade fever, poor appetite, and occasional non-bilious vomiting. There was no history of hematuria, urinary complaints, constipation, neurologic symptoms, or weight loss. Antenatal, perinatal, developmental, and immunization histories were unremarkable. On physical examination, the infant appeared pale but was hemodynamically stable. Abdominal examination revealed a firm, non-tender right flank mass measuring approximately 14 × 10 cm with extension across the midline and an indistinct superior border. No hepatosplenomegaly, ascites, or peripheral lymphadenopathy was identified.

Laboratory investigations revealed severe microcytic anemia (hemoglobin 6.3 g/dL; mean corpuscular volume 59.6 fL), markedly elevated serum lactate dehydrogenase (LDH 1445 U/L), and hyperuricemia (uric acid 10.36 mg/dL). Renal and hepatic function tests were within normal limits. Measurement of urinary catecholamines (vanillylmandelic acid and homovanillic acid) was not performed due to the unavailability of the assay at the treating institution. This limitation, characteristic of resource-constrained clinical environments in low-resource settings, precluded an important noninvasive biochemical discriminator and necessitated reliance on clinical, radiologic, and ultimately histopathologic evaluation for definitive diagnosis.

An ultrasound of the abdomen revealed a large heterogeneous mass in the right flank, with non-visualization of the right kidney. Contrast-enhanced CT (CECT) demonstrated a well-defined, heterogeneously enhancing mass measuring approximately 11 × 10 × 10 cm arising from the right kidney. The lesion crossed the midline and showed encasement of the right renal artery, right renal vein, and inferior vena cava (IVC), with associated compression and leftward displacement of the IVC and iliac vessels. No intralesional calcifications or cystic components were identified. Both adrenal glands appeared normal, and there was no evidence of pulmonary metastasis. Based on the initial radiologic impression, the lesion was diagnosed as Wilms tumor (Figure 1).

Figure 1.

Contrast-enhanced computed tomography (CECT) of the abdomen. Axial, coronal, and sagittal images (A-C) demonstrate a large, heterogeneously enhancing hypodense retroperitoneal mass arising from the right kidney. The mass crosses the midline and shows encasement of the inferior vena cava, right renal vessels, and abdominal aorta

Following six weeks of neoadjuvant chemotherapy according to the SIOP Wilms tumor protocol, a follow-up CECT demonstrated an interval reduction in tumor dimensions to 6.5 × 7.1 × 9.2 cm. The lesion remained heterogeneously enhancing and exhibited newly apparent punctate intralesional calcifications. Persistent encasement of the right renal vessels and inferior vena cava was noted, without significant interval change (Figure 2). These imaging features, particularly the presence of calcifications and ongoing vascular encasement despite chemotherapy, raised concern for an alternative diagnosis.

Figure 2.

Follow-up CECT of the abdomen in axial (A) and coronal (B) planes shows a large (6.5 × 7.1 × 9.2 cm), heterogeneously enhancing right renal fossa mass arising from the right kidney (large white arrow) with punctate intralesional calcifications. The mass encases the right renal vessels and IVC, displacing the IVC and iliac vessels to the left (small black arrow in b). CECT, contrast-enhanced computed tomography; IVC, inferior vena cava

The patient subsequently underwent a right radical nephrectomy. Intraoperatively, the tumor was locally advanced with adherence to the posterior diaphragm and paraspinal musculature, proximal ureteric invasion, encasement of the inferior vena cava, and multiple enlarged paracaval lymph nodes. The resected specimen was submitted for histopathological and immunohistochemical evaluation. Microscopic examination demonstrated a malignant small round blue cell tumor composed of poorly differentiated neuroblasts arranged in Homer-Wright rosettes with abundant eosinophilic neuropil. Tumor cells exhibited hyperchromatic nuclei with characteristic salt-and-pepper chromatin and scant cytoplasm. Focal calcifications and areas of Schwannian stroma were present. The mitotic-karyorrhectic index was low (<100/5000 neuroblasts) (Figure 3). Two regional lymph nodes showed metastatic involvement. Immunohistochemical analysis demonstrated diffuse cytoplasmic positivity for synaptophysin and absence of WT1 expression, confirming the diagnosis of primary intrarenal neuroblastoma (Figure 4A-B). Bone marrow examination showed no evidence of metastatic disease.

Figure 3.

Histopathologic section showing tumor fragments composed of Homer Wright rosettes with small-to medium-sized cells having scant cytoplasm, salt-and-pepper chromatin, and conspicuous single nucleoli. The rosettes contain central eosinophilic neuropil material, with associated focal calcifications and small areas of Schwannian stroma

Figure 4.

Immunohistochemical analysis demonstrating diffuse cytoplasmic positivity for synaptophysin in tumor cells (B), while WT1 immunostaining is negative (A)

Assessment of molecular prognostic markers, including MYCN amplification and segmental chromosomal aberrations (e.g., 11q deletion), was not performed due to limited diagnostic resources. Tumor staging was based on the International Neuroblastoma Staging System (INSS), a surgically oriented classification, and the disease was classified as Stage III, reflecting a locally advanced tumor with midline extension and regional lymph node involvement. Despite the absence of molecular risk stratification, the patient was considered low risk based on favorable histopathological features, including favorable histology according to the International Neuroblastoma Pathology Classification and a low mitotic-karyorrhectic index (MKI). These features are associated with a more favorable prognosis. In the absence of clinically evident high-risk characteristics, a low-risk neuroblastoma treatment protocol was initiated. This approach represents a pragmatic, resource-adapted strategy in which treatment decisions are guided primarily by clinical stage and histopathological findings when advanced molecular diagnostics are unavailable.

The postoperative course was uneventful. The patient completed four cycles of chemotherapy and achieved complete remission. At six months after completion of therapy, he remained asymptomatic, with no clinical or radiologic evidence of disease recurrence on follow-up evaluation. However, the duration of follow-up is relatively short to allow definitive conclusions regarding long-term disease control and survival. Given the potential for late relapse and treatment-related complications in neuroblastoma, prolonged surveillance is warranted. The patient is therefore planned for ongoing periodic clinical and radiologic follow-up to enable early detection of recurrence and assessment of long-term outcomes.

Discussion

Primary intrarenal neuroblastoma (IRNB) is an exceptionally rare entity, representing approximately 1–2% of all neuroblastoma cases, and remains a well-recognized diagnostic pitfall in pediatric oncology due to its close clinical and radiologic resemblance to Wilms tumor. ⁵ The present case highlights this diagnostic challenge, as the infant presented with a classic, painless abdominal flank mass, an archetypal presentation of a Wilms tumor, leading to initial misclassification and Wilms tumor–directed therapy. Similar to previously reported cases, the definitive diagnosis of IRNB in this patient was only established following surgical excision and detailed histopathologic and immunohistochemical evaluation, underscoring the inherent limitations of imaging-based diagnosis alone. ⁵

Radiologic differentiation between IRNB and Wilms tumor remains particularly challenging. In this case, contrast-enhanced CT demonstrated a large renal-region mass with a “claw sign,” traditionally considered highly suggestive of renal origin and commonly used to support a diagnosis of a Wilms tumor. However, as demonstrated here and supported by prior reports, a large intrarenal neuroblastoma arising from ectopic adrenal rests or intrarenal sympathetic tissue may distort surrounding renal parenchyma, producing a misleading claw sign and reinforcing an incorrect presumptive diagnosis. ¹⁰ This observation emphasizes that the claw sign, while useful, is not pathognomonic and should be interpreted cautiously in the context of other radiologic features. Several imaging characteristics may favor neuroblastoma over Wilms tumor and were partially evident in this patient. Punctate or coarse calcifications, present in up to 90% of neuroblastoma cases but seen in only 10–15% of Wilms tumors, are a key discriminating feature.^11,12 In the current case, calcifications became apparent only on follow-up imaging after neoadjuvant chemotherapy, highlighting that their absence on initial imaging does not exclude neuroblastoma. Additionally, vascular encasement, particularly of the renal vessels and inferior vena cava, is more characteristic of neuroblastoma, whereas Wilms tumor typically displaces rather than encases major vessels. ⁹ The persistent encasement of the renal artery, vein, and IVC in this patient, despite chemotherapy, was a critical radiologic clue consistent with IRNB and aligns with previously reported cases.

Clinically, the absence of hypertension in this patient is noteworthy. IRNB has been reported to have a significantly higher incidence of hypertension at presentation, ranging from 66% to 100%, compared with approximately 27% in extrarenal neuroblastoma and around 20% in Wilms tumor.^6,13,14 This heightened hypertensive tendency in IRNB is thought to result from direct compression of renal vasculature and stimulation of renin and catecholamine release. ¹³ The lack of hypertension in this case illustrates the clinical heterogeneity of IRNB and reinforces that its absence does not exclude the diagnosis. Furthermore, the unavailability of urinary catecholamine measurements in this resource-limited setting removed an important noninvasive diagnostic discriminator, contributing to delayed recognition and reflecting challenges frequently encountered in low- and middle-income countries.

This case also underscores the diagnostic implications of treatment protocols that rely heavily on imaging-based presumptive diagnoses. Under the SIOP approach, neoadjuvant chemotherapy is administered prior to nephrectomy, in contrast to the Children’s Oncology Group (COG) strategy of upfront surgery. ¹⁵ While preoperative chemotherapy reduces tumor rupture and facilitates surgical resection in true Wilms tumor cases, it may delay definitive diagnosis when Wilms tumor mimickers such as IRNB are present. In this patient, the suboptimal response after six weeks of Wilms-directed chemotherapy served as a pivotal clinical indicator that the initial diagnosis was incorrect, a scenario echoed in prior reports of IRNB managed under the SIOP framework. ¹⁵

Histopathologic examination remains the cornerstone of definitive diagnosis. The identification of Homer Wright rosettes, eosinophilic neuropil, and “salt-and-pepper” chromatin strongly supported neuroblastoma in this case. ¹⁶ However, given the morphologic overlap with other small round blue cell tumors, immunohistochemistry is indispensable for diagnostic confirmation. ¹⁷ The diffuse positivity for synaptophysin and negativity for WT1 conclusively distinguished IRNB from Wilms tumor and allowed appropriate risk-adapted neuroblastoma therapy to be instituted. Despite the lack of molecular prognostic markers such as MYCN amplification due to resource constraints, the favorable histology and low mitotic-karyorrhectic index permitted classification as low-risk disease, consistent with favorable short-term outcomes reported in similar cases.

Taken together, this case reinforces the importance of maintaining a high index of suspicion for IRNB when a presumed Wilms tumor exhibits atypical features, including vascular encasement, calcifications, hypertension, or inadequate response to neoadjuvant chemotherapy. While the SIOP protocol offers clear benefits, its reliance on radiologic diagnosis necessitates vigilance for diagnostic mimickers. Early reconsideration of the diagnosis, timely surgical intervention, and comprehensive histopathologic and immunohistochemical assessment are essential to avoid inappropriate therapy and ensure optimal outcomes. Integrated clinical, radiologic, and pathologic correlation remains the most reliable strategy for navigating this rare but clinically significant diagnostic dilemma.

Conclusion

Primary intrarenal neuroblastoma is an exceptionally rare but important differential diagnosis in infants presenting with renal masses, particularly when imaging reveals atypical features such as vascular encasement, intratumoral calcifications, or a suboptimal response to Wilms tumor–directed chemotherapy. Given its substantial clinical and radiologic overlap with Wilms tumor, preoperative diagnosis remains challenging and requires a high index of suspicion. In cases with atypical clinical or imaging findings, tissue diagnosis by core needle or open surgical biopsy, followed by comprehensive histopathologic and immunohistochemical evaluation, should be considered before initiating empiric chemotherapy to ensure accurate tumor classification and appropriate treatment. This case underscores the importance of close multidisciplinary collaboration among pediatric surgeons, radiologists, pathologists, and pediatric oncologists to achieve timely diagnosis, guide appropriate risk-adapted therapy, and improve clinical outcomes in this rare entity.