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Abstract

Background:

Renal angiomyolipomas (AMLs) are benign renal tumors arising from perivascular epithelioid cells and are often associated with tuberous sclerosis complex. Renal epithelioid angiomyolipoma (EAML) is a rare variant of AML, characterized by the predominance of epithelioid cells with malignant potential. Although EAML is typically seen in adults, especially females, its occurrence in children is extremely rare and can be difficult to distinguish from other renal tumors.

Case Presentation:

We report a case of an 8-year-old girl with a right renal mass that initially was suspected to be a Wilms tumor based on imaging results and was treated with Wilms-directed chemotherapy without response. Histopathological investigations after a radical nephrectomy revealed an EAML composed primarily of epithelioid cells. Immunohistochemistry confirmed the diagnosis with positive results for HMB45 and Melan-A, highlighting the importance of histopathological and immunohistochemical evaluation in pediatric renal masses with atypical clinical behavior.

Conclusion:

Renal epithelioid angiomyolipoma should be considered in pediatric renal masses with atypical imaging features or poor response to Wilms tumor chemotherapy. Accurate diagnosis relies on histopathological and immunohistochemical evaluation, which helps guide appropriate surgical management and postoperative surveillance due to the tumor’s variable malignant potential.

Keywords

epithelioid angiomyolipoma oncology Wilms tumor pediatric renal mass nephrectomy case report

Introduction

Renal angiomyolipoma (AML) is a benign mesenchymal tumor composed of varying proportions of smooth muscle, thick-walled blood vessels, and adipose tissue. It is a member of the perivascular epithelioid cell tumor family (PEComas) that are characterized by distinctive histological and immunohistochemical features expressing both melanocytic and smooth muscle markers.¹ The epithelioid variant, also known as epithelioid angiomyolipoma (EAML), is rare and potentially malignant. It is characterized by the predominance of epithelioid cells with clear to eosinophilic cytoplasm, and is known for its aggressive behavior, exhibiting both distant metastasis and local recurrence.²

According to the World Health Organization (WHO) classification, epithelioid angiomyolipoma is defined by the presence of ⩾80% epithelioid cells.³ These cells are characterized by round to polygonal morphology with abundant eosinophilic to amphophilic or focally clear cytoplasm. When composed almost entirely of epithelioid elements, the tumor may also be referred to as a “pure epithelioid PEComa of the kidney,” reflecting its classification within the PEComa family.

Less than 10% of all renal AML cases are EAML, which primarily affects middle-aged women and is frequently associated with tuberous sclerosis complex (TSC). Nevertheless, a few cases were classified as sporadic. Its occurrence in the pediatric population is exceedingly uncommon, with only a limited number of cases described in the literature. In children, Wilms tumors are the most common cause of renal masses, which could confuse diagnosis. Radiological findings of EAML can closely resemble those of Wilms tumor, especially when the lesion contains minimal or no adipose tissue, leading to potential diagnostic misinterpretation.

We present a rare case of sporadic renal epithelioid angiomyolipoma in an 8-year-old girl initially diagnosed and treated as Wilms tumor based on radiologic findings. This case is notable for its young age at presentation, absence of tuberous sclerosis complex, radiologic mimicry of Wilms tumor, and exposure to ineffective Wilms-directed chemotherapy prior to definitive histopathologic diagnosis. By highlighting these features, we aim to emphasize the diagnostic challenges and clinical implications of misclassification in pediatric renal masses.⁴

Case Presentation

An 8-year-old female was admitted on March 11th, 2018, after her mother incidentally noticed a mass in the right abdominal area while bathing her 1 month prior. The patient was in her usual state of health and had no complaints other than the incidental mass. She was asymptomatic, and there was no history of fever, weight loss, hematuria, or any other systemic symptoms. Her vitals were stable on the day of admission (BP 104/55, HR 104, RR 20, Temp 36.6°C). Physical examination revealed a palpable mass in the epigastrium extending above the umbilicus; the remainder of the examination was normal. Review of systems was otherwise negative, and there was no family history of malignancy. Laboratory investigations (serum creatinine, urinalysis, and CBC) were in their normal ranges (0.4 mg/dL and unremarkable, respectively).

The patient underwent ultrasound imaging which showed a right renal mass. The patient was then referred to a tertiary-care center, King Hussein Cancer Center (KHCC) in Amman, Jordan for further workup, where she underwent a CT Chest/Abdomen/Pelvis imaging. The CT revealed a large, well-defined vascular tumor in the right kidney, measuring 8.4 × 8.0 cm in axial dimensions and 12.7 cm in length (Figure 1), with no evidence of renal vein or IVC thrombosis, retroperitoneal lymphadenopathy, or distant metastases. Based on the radiologic findings of a large, well-defined renal mass in a child within the typical age range for Wilms tumor, and in accordance with standard pediatric oncology protocols that allow initiation of preoperative chemotherapy without biopsy in radiologically typical cases (SIOP-based approach), the overall clinical impression favored Wilms tumor. The patient and her caregiver were advised to undergo 4 cycles of Wilms-directed chemotherapy (vincristine and actinomycin-D) on April 3rd, 2018, which they completed as recommended.

Figure 1.

Contrast-enhanced CT of the abdomen at presentation (March 11th, 2018): axial (A), zoomed axial (B), and coronal (C) sections demonstrate a large, vascular mass arising from the right kidney.

A follow-up CT scan was performed on April 3rd, 2018 to re-evaluate the case and assess response to the administered chemotherapy cycles. The imaging showed the right renal tumor measuring about 8.3 cm in longest diameter (Figure 2), representing no significant change compared to the baseline CT scan from March 11th, 2018. The poor response to the treatment urged the re-assessment of the case since it is atypical for a standard Wilms tumor to respond poorly to chemotherapy.

Figure 2.

Contrast-enhanced CT of the abdomen after 4 cycles of chemotherapy (April 3rd, 2018): axial (A) and coronal (B and C) sections show the mass measuring 8.3 cm, indicating stable disease with no significant interval change.

Due to the lack of tumor regression, the patient was admitted for a right radical nephrectomy on April 11th, 2018. The tumor was removed completely intact with the kidney. Retroperitoneal lymph nodes were sampled. The tumor specimen underwent pathological testing.

On macroscopic examination, the right kidney and ureter measured about 16 × 10 × 9 cm, with a unifocal tumor occupying the whole right kidney, measuring about 13 × 8.5 × 8 cm. The tumor did not breach the renal capsule, and there was no necrosis identified on the specimen.

On microscopic examination, the specimen showed histological characteristics that are most compatible with an Epithelioid Angiomyolipoma (PEComa family), with no sarcomatoid features or necrosis. Mitotic activity was <1/10 HPF. Renal vein, ureter, and Gerota’s fascia were free of tumor. In addition, para-aortic and caval lymph nodes were negative for malignancy (0/5).

The definitive diagnosis was confirmed with immunohistochemistry (IHC). The staining profile was positive for: Melan-A, HMB45, TEF3 (Nuclear), and Smooth Muscle Actin (SMA). The Pan-CK (AE1/AE3), CK7, CD10, EMA, AMACR, and PAX8 stains showed negative results.

The case was reviewed by a multidisciplinary tumor board on April 24th, 2018, which recommended observation only, along with serial abdominal ultrasound imaging every 3 months for 1 year, given the complete surgical removal and absence of metastasis. No further adjuvant therapy was required and the patient was discharged home in stable condition. At the 1-year follow-up, no recurrence or new lesions were detected and the patient remains clinically well.

Discussion

Angiomyolipoma (AML) is a benign tumor of mesenchymal origin most commonly found in the kidney, composed of blood vessels, smooth muscles, and adipose tissue.⁵ It accounts for approximately 0.3% to 3% of all renal neoplasms.⁶ Renal AML can be histologically classified as either classical AML (typical) or epithelioid AML (EAML; atypical). The classic form is typically triphasic, richer in fat, and commonly associated with tuberous sclerosis complex (TSC).^6,7 In contrast, EAML as the name implies, is characterized by predominance of epithelioid cells with eosinophilic cytoplasm, paucity of adipose tissue, and higher malignant potential.^8,9 In recent years, EAML has been further classified to be included in the perivascular epithelioid cell tumor family (PEComa), which is a group of neoplasms characterized by immunoreactivity for both myogenic and melanocytic markers.^7,10

In children, cases of EAML are exceedingly uncommon, with just a few pediatric specific cases recorded to date.⁷ The current case of an 8-year-old girl with a large EAML initially mistaken for Wilms tumor contributes to the scant literature, broadening the age range for diagnosis and underscoring the diagnostic challenges this tumor poses in the pediatric population.

Radiologically, classical AMLs are often found incidentally and are relatively easy to identify on imaging studies because of the presence of fat in them.⁷ In contrast, EAML lacks macroscopic fat making it harder to distinguish it from other tumors like renal cell carcinoma, or in pediatric population, for Wilms tumor which considered the most common renal malignancy in children.¹¹ On computed tomography (CT), EAML typically appears as an irregular mixed-density mass, often demonstrating attenuation values greater than 45 Hounsfield units (HU) on non-contrast imaging due to its hypercellular nature.^8,9 Contrast-enhanced CT may reveal heterogeneous enhancement with a characteristic “fast-in and fast-out” pattern reflecting its vascularity. On magnetic resonance imaging (MRI), EAML may demonstrate T2 hypointense reticular enhancement patterns and similarly exhibit rapid contrast wash-in and wash-out characteristics.⁴ The presumptive diagnosis of Wilms tumor was maintained until histopathologic and immunohistochemical evaluation established the definitive diagnosis.

The age of presentation in this case is notable, whereas pediatric EAML is most often described in older children or adolescents, there are only a handful of pediatric EAML cases reported in the literature.⁷

Furthermore, several factors have been associated with more aggressive behavior in EAML, including tumor size > 7 cm, intralesional necrosis, higher mitotic count, lymph-vascular invasion, renal vein or IVC involvement, extra-renal dissemination or metastases, and tuberous sclerosis complex (TSC).^6,7 Established risk stratification models for pure epithelioid PEComa also identify ⩾70% atypical epithelioid cells, mitotic count ⩾ 2 per 10 high-power fields, presence of atypical mitoses, and tumor necrosis as predictors of malignant potential.⁸ In our patient, despite the large tumor size (13 × 8.5 × 8.0 cm) which grossly occupied half of the kidney, the lesion did not extend beyond the renal capsule, exhibited no necrosis, demonstrated a mitotic rate < 1 per 10 high-power fields, had negative lymph nodes (0/5), and showed no vascular invasion at the time of surgery, which are favorable features indicating lower risk of recurrence. Based on established risk stratification criteria, this case demonstrates low-risk histologic features despite its large size, supporting the decision for surveillance without adjuvant therapy.

Mutations in the TSC1 gene (chromosome 9q34) and TSC2 gene (chromosome 16p13) have been identified in both TSC-associated and sporadic EAML cases. Dysfunctional hamartin (TSC1) and tuberin (TSC2) complexes result in increased RHEB-GTP activity, leading to activation of the mTORC1 pathway, which promotes cellular growth, proliferation, and vascular smooth muscle differentiation. This molecular pathway underlies the rationale for mTOR inhibitor therapy in selected cases.¹ EAML with TFE3 gene rearrangement is considered a unique molecular subtype within the PEComa family and may demonstrate distinct clinicopathologic features.¹²

Reported rates of aggressive behavior in EAML vary in the literature, with approximately one-third of cases demonstrating malignant potential, including recurrence or metastasis, as reported by Li et al.¹³

Additionally, as a sporadic case (non-TSC-associated) of pediatric EAML, our case became noteworthy as the majority of EAML cases occur in the setting of TSC.¹⁴ The absence of clinical signs and genetic confirmation of TSC in this case suggests a truly sporadic origin.

Pediatric cases of sporadic EAML are exceedingly rare, especially those initially misdiagnosed as Wilms tumor. In addition to Wilms tumor, AML may be confused with other mesenchymal tumors of the kidney including leiomyoma, leiomyosarcoma, liposarcoma, and sarcomatoid renal cell carcinoma (RCC), so careful evaluation of these cases is essential.¹⁵ Table 1 compares key features of these published sporadic cases. For example, Rasalkar et al¹⁶ described a 15-year-old boy initially presumed to have a renal malignancy, whose final diagnosis of pigmented clear cell PEComa was confirmed histologically; the tumor demonstrated aggressive behavior with nodal and hepatic metastases. Similarly, Xi et al¹⁷ reported a 7-year-old boy initially treated for presumed neuroblastoma who failed to respond to chemotherapy; subsequent resection and immunohistochemical analysis established the diagnosis of malignant EAML with early metastasis. Likewise, Dhua et al¹⁸ documented a 12-year-old male with recurrent and metastatic EAML despite radical nephrectomy and targeted therapies, ultimately resulting in a fatal outcome. Other reports describe cases initially suspected to be Wilms tumor based on imaging, including Dhua et al,¹⁸ where definitive diagnosis was achieved only after surgical resection and histopathologic evaluation. Uddin et al¹⁹ also reported a 12-year-old boy in whom differential diagnoses included sarcomatoid RCC and rhabdoid tumor before immunohistochemistry confirmed PEComa. Across these cases, patient ages overlapped with the typical demographic for Wilms tumor, and radiologic findings frequently suggested primary renal malignancy. Final diagnosis in all instances relied on histopathologic assessment and positivity for melanocytic markers such as HMB45 and Melan-A. Clinical outcomes varied, with some patients remaining disease-free following complete resection, whereas others developed recurrence or metastases despite aggressive management.

Table 1.

Reported Pediatric Cases of Renal Tumors with Their Clinical Characteristics.

Case	Age/gender	Tumor size (cm)	Initial diagnosis	Final diagnosis	Positive histochemical markers	Treatment	Outcome
Rasalkar et al.	15/M	7 × 10 × 10	Renal cell carcinoma, primitive neuroectodermal tumor of kidney	Pigmented clear cell PEComa	Various melanocytic markers (non-specified)	Parents declined treatment	Enlargement of primary neoplasm with metastatic deposits, gross pleural effusion and ascites at 3 mo
Xi et al.	7/M	12 × 8 × 7	Neuroblastoma	Malignant EAML	HMB45, Melan-A, SMA, S-100	Partial resection	Metastasis then died 1 y later
Citak et al.	12/M	-	-	Malignant EAML	HMB45, Melan-A, cathepsin K, EMA, PAX8, Cam5.2	Radical nephrectomy, sunitinib maleat, everolimus, axitinib	Metastasis then died 1 y and 4 mo later
Dhua et al.	12/F	27 × 22 × 18	Wilms tumor	Sporadic AML	HMB45, vimentin (trace)	Nephroureterectomy	Followed up annually
Tchaprassian et al.	11/F	20	Wilms tumor	Sporadic AML	-	Nephrectomy	Negative findings at 33 mo
Uddin et al.	12/M	4.6 × 4 × 4	Sarcomatoid renal cell carcinoma, renal rhabdoid tumor, and rhabdomyosarcoma	PEComa	HMB45, Melan-A, vimentin, ASMA, S-100	Nephrectomy	-
Our case	8/F	12.7 × 8.4 × 8	Wilms tumor	EAML	HMB45, Melan-A, TEF-3, SMA	Radical nephrectomy	Stable on annual follow-up

Surgery remains the mainstay of therapy for pediatric EAML. In all reported pediatric cases, including ours, definitive management has primarily involved surgical removal, most commonly radical nephrectomy when EAML was initially misdiagnosed as Wilms tumor, or nephron-sparing surgery when diagnosis was established preoperatively. However, Yang et al⁴ stated that tumors greater than 4 cm should undergo radical nephrectomy and partial nephrectomy for those less than 4 cm. Nevertheless, the presence of a ⩾5 mm intra-tumoral aneurysm poses an increased risk of rupture,²⁰ so transarterial embolization becomes the first choice for treatment despite the size of the tumor.²¹ Our patient initially received 4 cycles of Wilms-directed chemotherapy (vincristine/actinomycin-based); however, repeat radiologic imaging revealed no response, reflecting the known chemoresistance of EAML. mTOR inhibitors such as everolimus are primarily used in both adult and tuberous sclerosis-associated AML, yet are not required in sporadic pediatric cases such as our case.²²

Limitations

This case report has several limitations. First, the follow-up duration of 1 year is relatively short. Given the variable and occasionally delayed aggressive behavior reported in EAML, longer-term surveillance is warranted in pediatric patients to monitor for late recurrence or metastasis. Additionally, molecular genetic testing for TSC1/TSC2 mutations or TFE3 rearrangement was not performed, limiting further biological and molecular characterization of the tumor.

Conclusion

In conclusion, renal epithelioid angiomyolipoma is a rare but important diagnostic consideration in pediatric renal masses with atypical imaging features or poor response to Wilms tumor chemotherapy. Histopathological and immunohistochemical investigations remain the cornerstone of accurate diagnosis, rather than imaging alone. Early diagnostic consideration can prevent unnecessary exposure to ineffective chemotherapy, enable timely surgical management, and should be followed by tailored postoperative surveillance due to the tumor’s variable malignant potential.

Footnotes

Acknowledgements

We express our deep gratitude to the medical ward staff for their invaluable support in completing this report.

ORCID iDs

Somaya Al Kiswani

Azza Gharaibeh

Wael Hashem

Hasan Khalili

Radwan Shayeb

Hasan Shalabi

Ethical Considerations

All procedures involving human participants were conducted in accordance with the ethical standards of the institutional and national research committees and in compliance with the principles of the Declaration of Helsinki (1964) and its later amendments or comparable ethical guidelines.

Consent to Participate

Written and verbal informed consent was obtained from the patient and the patient’s legal guardian for the publication of this case report and accompanying images.

Author Contributions

Somaya Al Kiswani: Conceptualization, Validation, Visualization, Writing – original draft, Writing – review & editing. Azza Gharaibeh: Conceptualization, Validation, Visualization, Writing – review & editing. Wael Hashem: Conceptualization, Validation, Visualization, Writing – original draft, Writing – review & editing. Hasan Khalili: Conceptualization, Validation, Visualization, Writing – original draft, Writing – review & editing. Radwan Shayeb: Conceptualization, Validation, Visualization, Writing – original draft, Writing – review & editing. Hasan Shalabi: Conceptualization, Validation, Writing – original draft. Abdullah Nofal: Project administration, Resources, Validation.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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Sporadic Pediatric Renal Epithelioid Angiomyolipoma Mimicking Wilms Tumor: A Case Report and Literature Review

Abstract

Background:

Case Presentation:

Conclusion:

Keywords

Introduction

Case Presentation

Discussion

Limitations

Conclusion

Footnotes

Acknowledgements

ORCID iDs

Ethical Considerations

Consent to Participate

Author Contributions

Funding

Declaration of Conflicting Interests

References