A rare case of malignant epithelioid angiomyolipoma: involvement of the lumbar vein pathway with downward extension to the iliac veins

Abstract

Introduction and Importance:

Epithelioid angiomyolipoma (EAML) is a rare renal perivascular epithelioid cell tumor (PEComa) with malignant potential in up to one-third of cases. Venous invasion usually involves the renal vein or inferior vena cava, while extension through the lumbar venous pathway is exceedingly uncommon.

Case Presentation:

We describe a 51-year-old woman with malignant EAML presenting with a left renal mass and extensive tumor thrombus extending via the lumbar venous complex into the bilateral iliac veins. Preoperative CT angiography demonstrated collateral venous drainage, and MRI venography was omitted due to adequate CT detail. The patient underwent radical nephrectomy and thrombectomy following preoperative embolization. Histopathology confirmed malignant EAML with negative margins and intraluminal tumor thrombus without venous wall invasion. Postoperative recovery was uneventful, and no recurrence was observed at 12 months. Next-generation sequencing revealed TP53, TSC, and MTOR mutations.

Clinical Discussion:

This case illustrates a unique venous invasion route of EAML via the lumbar vein, an anatomic pathway not previously reported. Recognition of this pattern is essential for preoperative planning and surgical decision-making. The findings also highlight the molecular underpinnings of EAML and potential therapeutic implications of mTOR and PD-1 pathways.

Conclusion:

Malignant EAML can invade atypical venous routes such as the lumbar vein. Comprehensive imaging, multidisciplinary evaluation, and long-term follow-up are crucial for successful management.

Introduction

Epithelioid angiomyolipoma (EAML) is an uncommon variant of angiomyolipoma (AML), first described by Mai et al in 1996[1]. AML represents the most frequent mesenchymal tumor of the kidney and belongs to the family of perivascular epithelioid cell tumors (PEComas)^[2,3^]. EAML is characterized by a proliferation of epithelioid smooth-muscle-like cells with abundant eosinophilic cytoplasm and minimal adipose tissue, which often makes its radiologic appearance difficult to distinguish from renal cell carcinoma (RCC)^[4,5^].

HIGHLIGHTS

• Rare malignant epithelioid angiomyolipoma (EAML) with lumbar vein involvement.

• Tumor showed downward extension into the iliac veins, extremely uncommon.

• Case emphasizes surgical management of venous tumor thrombus extension.

• Provides clinical reference for rare aggressive renal EAML.

Although most AMLs behave in a benign manner, approximately one-third of EAMLs exhibit malignant potential, presenting with local recurrence, lymph-node metastasis, or venous invasion[6]. According to Folpe et al, histologic malignancy in EAML is defined by a mitotic rate exceeding 1 per 50 high-power fields, the presence of necrosis, and significant nuclear atypia[7]. Venous extension is a recognized but uncommon feature, typically involving the renal vein and inferior vena cava (IVC); however, invasion through the lumbar vein or extension into the iliac veins is exceedingly rare.

Here, we report a rare case of malignant EAML extending from the renal vein through the lumbar venous pathway to the bilateral iliac veins. To our knowledge, this venous invasion route has not been previously documented. The case is presented in accordance with the SCARE 2025 guidelines[8], aiming to enhance awareness of this unique vascular involvement pattern and its implications for surgical management and postoperative follow-up.

Case report

A 51-year-old woman presented in March 2024 with a 6-week history of lower back pain and numbness of the lower limbs. She had uterine fibroids for 5 years but no features of tuberous sclerosis. Physical examination revealed a large palpable mass in the left abdomen. Contrast-enhanced CT showed a 10.5 × 8.0 × 8.7 cm heterogeneous mass in the left kidney, extending via the lumbar venous complex toward the iliac veins. The IVC, bilateral iliac veins, and left ovarian vein were markedly dilated. CT angiography clearly outlined the venous thrombus and collateral circulation (Fig. 1A–E); MRI venography was omitted as CT provided sufficient information and the patient had borderline renal function. No distant metastasis was detected.

Figure 1.

Contrast-enhanced CT findings.

(A) Axial venous-phase image showing tumor invasion of the lumbar vein (red arrow). (B) Axial view showing extension of the tumor thrombus into the inferior vena cava (IVC). (C) Left renal vein without direct involvement (red arrow). (D) Arterial-phase image showing heterogeneous enhancement of the left renal tumor. (E) Coronal reconstruction demonstrating tumor extension from the lumbar vein into the IVC and bilateral iliac veins, along with coexisting uterine leiomyomas.

Following transcatheter renal artery embolization, radical nephrectomy and thrombectomy were performed through a midline incision. Intraoperatively, the tumor extended from the lumbar vein into the IVC and iliac veins, with firm thrombus in the left lumbar and iliac veins (Fig. 2A). These veins were ligated and transected; vascular bypass was not performed because collateral drainage was adequate. Despite stapler transection, no tumor spillage occurred (Fig. 2B–C).

Figure 2.

Intraoperative and gross specimen photographs.

(A) Intraoperative view showing tumor extension from the lumbar vein into the IVC. (B) Excised left kidney with adherent venous thrombus. (C) Resected segment of lumbar vein, IVC, and iliac veins containing tumor thrombus.

Histopathology confirmed malignant EAML with negative margins and intraluminal thrombus without venous wall invasion. Immunohistochemistry was positive for HMB-45, Melan-A, SMA, and Cathepsin K, and negative for PAX8 (Figs 3 and 4).

Figure 3.

Representative hematoxylin–eosin-stained sections.

(A) Epithelioid tumor cells arranged in nests separated by slender vessels (×10). (B) Cells with abundant eosinophilic cytoplasm, prominent nucleoli, and frequent mitoses (×40). (C) Areas of necrosis with clear-cytoplasmic tumor cells. (D) Nests of epithelioid cells with granular cytoplasm and delicate vasculature. (E) Multinucleated giant cells with eosinophilic cytoplasm and large nucleoli. (F) Metastatic focus in regional lymph node.

Figure 4.

Immunohistochemical staining.

(A) Ki-67 (×10). (B) Cytokeratin partial positive. (C) HMB-45 positive. (D) PAX8 negative. (E) SMA positive. (F) TFE3 moderate positive. (G) Vimentin positive. (H) Melan-A positive. (I) SMA diffuse positive.

Postoperatively, transient lower-limb edema and orthostatic hypotension resolved within weeks. The patient recovered uneventfully and resumed ambulation on day 7. At 12 months, she remained recurrence-free, with preserved limb function. Next-generation sequencing identified TP53, TSC, and MTOR mutations consistent with malignant EAML (Table 1).

Table 1.

Targeted next-generation sequencing results showing multiple missense mutations in TP53, TSC, and MTOR genes associated with tumor progression and vascular invasion.

Mutant genes	Mutant position	Function
TP53	c.524 G>A (p.R175H)	Inducing the loss of TP53 tumor suppressor function in promoting tumorigenesis and tumor progression
TSC	c.2713C>T (p.R905W)	A germline mutation in tuberous sclerosis complex (TSC) involved in tumorigenesis and tumor progression increasing the sensitivity of tumor cells to mTOR inhibitors.
ATRX	c.5939del (p.S1980Ffs*2)	Inactivation of ATRX protein function.
KEAPI	c.1006C>T(p.R336*)	Disruption of the association between KEAP1 and NRF2
MTOR	C.5395G>A (p.E1799K)

Discussion

Classic AML is a benign mesenchymal tumor composed of dysplastic vessels, smooth muscle, and adipose tissue. EAML, however, may exhibit malignant behavior and often mimics RCC radiologically due to its low fat content^[4,9^]. Preoperative diagnosis is therefore challenging, and most patients are initially suspected of having RCC. In our case, intravascular leiomyomatosis was also considered given the patient’s history of uterine fibroids.

The typical venous invasion route for renal tumors involves the renal vein and IVC. In this case, tumor thrombus propagated via an atypical lumbar venous pathway, with minimal renal vein involvement^[3,6,10^]. CT angiography clearly delineated the thrombus and collateral veins, and MRI venography was omitted because of adequate CT detail and marginal renal function. Preoperative embolization was performed to reduce blood loss. During surgery, multiple lumbar and iliac veins were transected, and vascular bypass was not attempted because collateral circulation provided adequate drainage. Despite stapler transection, no tumor spillage occurred[11], and follow-up imaging showed no recurrence at 12 months. Histopathology confirmed thrombus within the vessel lumen without wall invasion, explaining preserved limb function.

The mechanism of venous invasion in EAML remains unclear. It may result from perivascular spread or mechanical compression, allowing tumor migration into venous channels. The distinct lumbar venous route in this case suggests a collateral-dependent invasion pattern not previously reported^[5,7^].

Molecularly, EAML is characterized by TSC1/TSC2 mutations and activation of the mTOR pathway. Everolimus, an mTOR inhibitor, was used postoperatively and maintained disease stability. Previous studies have reported mTOR resistance in advanced cases, with PD-1 immunotherapy showing potential as an alternative^[8,12,13^].

This case highlights a unique venous invasion route through the lumbar veins and emphasizes the importance of thorough vascular evaluation, multidisciplinary surgical planning, and long-term follow-up for malignant EAML.

Conclusion

In conclusion, we have reported an exceedingly rare case of malignant EAML with concurrent TT in the IVC and bilateral iliac veins. Simultaneously, the patient underwent radical nephrectomy and resection of the IVC and bilateral iliac veins. We hope that this case can provide valuable insights and considerations for similar cases in the future.

Ethical approval

This case report was conducted in accordance with the Declaration of Helsinki.

Ethical approval was waived for this single case report, as per the policy of our institutional review board, because it describes routine clinical practice.

Consent

Written informed consent was obtained from the patient for publication and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Sources of funding

This study was supported by two research grants. Full details of the funding source are withheld for double-blind peer review and will be disclosed upon acceptance.

Author contributions

D.W.: drafted and revised the manuscript, performed literature review, and contributed to data interpretation. H.C.: performed the surgery, contributed to clinical management of the patient, and revised the manuscript critically for important intellectual content. M.L.: performed immunohistochemical analysis and contributed to pathological interpretation. Y.Y.: performed immunohistochemical analysis and contributed to pathological interpretation. W.H.: was involved in study conception and surgical management. Z.N.: was involved in study conception and surgical management.

Conflicts of interest disclosure

The authors declare no conflict of interest.

Research registration unique identifying number (UIN)

Not applicable.

Guarantor

Zhihong Niu. The guarantor accepts full responsibility for the integrity of the work, had access to the data, and controlled the decision to publish.

Animal studies

Not applicable.

Provenance and peer review

Not commissioned, externally peer-reviewed.

Data availability statement

The data supporting the findings of this study are available from the corresponding author upon reasonable request.