1. Introduction
Renal angiomyolipoma (AML) is a benign mesenchymal neoplasm composed of variable amounts of adipose tissue, spindled smooth muscle cells, and dysmorphic thick-walled blood vessels. Although most AMLs arise sporadically, they are also a common manifestation of tuberous sclerosis complex (TSC; OMIM 191100). AMLs are associated with biallelic loss of
TSC1 (9q34; encoding hamartin) or
TSC2 (16p13.3; encoding tuberin) genes.
[1] Relative to sporadic AMLs, TSC-associated tumors present at a younger age and are more often multifocal, bilateral, and larger in size. In most cases, classic AMLs have an indolent clinical course; however, selected tumors may cause clinically significant morbidity, especially when associated with spontaneous subcapsular hemorrhage (Wunderlich syndrome) into the retroperitoneum. Accordingly, treatment is guided by clinical context and may include surveillance, embolization, surgery, or mTOR inhibitor therapy.
[2, 3]Aggressive behavior in AML is most often linked to epithelioid angiomyolipoma (eAML), a rare malignant variant.
[1] Lymph node involvement in classic AML is exceedingly rare and, despite its worrisome appearance, has not generally been associated with adverse clinical outcomes.
[4, 5] The biologic basis of this phenomenon remains uncertain, with prior authors proposing multifocality or benign dissemination rather than true metastasis. We report a sporadic classic renal AML with extensive regional lymph node involvement. Although the tumor also showed renal sinus and venous branch involvement, these findings should be interpreted cautiously and, in isolation, do not establish malignant behavior. The patient remains alive and disease-free 30 months after nephrectomy. This case broadens awareness of an uncommon manifestation of classic AML and emphasizes the need to avoid overdiagnosis and overtreatment.
2. Case report
A 43-year-old woman with a medical history of hypertension presented with early satiety, poor appetite, and fifteen-pound weight loss over the last several months. Computed tomography and magnetic resonance imaging demonstrated a 23 cm fat-containing mass involving the lower pole of the right kidney, crossing the midline, and exerting mass effect on surrounding structures (see
Figure 1). She had previously undergone right renal artery embolization with plans for staged embolization procedures.
[1, 2] Due to persistent fever and malaise, she was referred for surgical resection. The imaging appearance favored angiomyolipoma, although the size and extent of the lesion also raised consideration of eAML and retroperitoneal liposarcoma. Biopsy of the mass was deferred pre-operatively due to the risk of bleeding.
At surgery, several retroperitoneal lymph nodes were noticeably enlarged and were concerning for disease involvement. A frozen section diagnosis of an enlarged lymph node was requested, with the planning for extensive retroperitoneal lymph node dissection if there was any concern for eAML or malignancy. An intraoperative frozen section revealed only classical AML component without any epithelioid elements, providing reassurance to minimize the extent of dissection to only paracaval and interaortocaval lymph nodes, rather than proceeding with a more extensive retroperitoneal lymphadenectomy.
Gross examination showed a 20 cm × 18 cm × 7.8 cm exophytic, ill-defined mass arising from the renal hilum and extending beyond the renal parenchyma. The tumor involved the hilar and perinephric adipose tissue and abutted Gerota’s fascia. The cut surface was golden yellow with hemorrhagic foci (see
Figure 1). All surgical margins were negative.
Microscopic examination confirmed a classic AML composed of haphazardly arranged spindled smooth muscle cells, adipose tissue, and dysmorphic vessels (see
Figure 2). Prior embolization material was present. Immunohistochemical stains were performed, and the tumor cells demonstrated positive expression of HMB45, Melan-A, smooth muscle actin (SMA), and cathepsin K, with negative inhibin expression. The Ki-67 proliferative index was low (1%-5%). AML involved the renal sinus and extended into the branches of the renal vein (see
Figure 2). In addition, all 19 sampled interaortocaval and paracaval lymph nodes were involved by AML (see
Figure 3). Germline testing for
TSC1 and
TSC2 did not reveal any pathogenic alterations, and no clinical stigmata of tuberous sclerosis complex were identified. The postoperative course was uneventful. After 30 months of follow-up, the patient remains alive and without evidence of recurrence.
3. Discussion
Classic renal AML is a benign PEComa that occurs sporadically or in association with TSC. Most lesions are discovered incidentally, although large tumors may present with pain, hemorrhage, or other mass-effect symptoms. Contemporary management is risk-stratified rather than based on size alone. Active surveillance is appropriate for many asymptomatic lesions, whereas selective arterial embolization, nephron-sparing surgery, thermal ablation in selected cases, and mTOR inhibition (particularly in TSC-associated disease) may be considered for symptomatic tumors or those with features associated with bleeding risk.
[6, 7] Surgical intervention is preferred in sporadic cases, owing to a lower rate of recurrence and secondary procedures.
The epithelioid variant of AML is associated with aggressive disease and metastasis. True metastasis has not been recognized in classic AML, but regional lymph node involvement has been described. A targeted review of the English-language literature identified approximately 53 previously reported patients with classic renal AML involving regional lymph nodes (see
Table 1). In 1964, Wilson and Lo reported the first case of triphasic AML with lymph node involvement in an autopsy.
[8] Collectively, 53 other patients, including the present case, have been reported in 27 other manuscripts although overlap across pooled series cannot be completely excluded.
[4, 9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34] Reported patients are predominantly female (male-to-female ratio is 7:20) and span a wide age range (mean 40.9 years; range 9-73 years). Only 16 patients had a known history of TSC (38%, excluding patients whose TSC history was unknown). The tumors in a non-TSC setting are reported to be solitary, except for one case.
[24] In the available follow-up data, no convincing distant metastases and no clear disease-related mortality have been documented for classic AML with nodal involvement after resection. These observations support the concept that nodal involvement in classic AML does not necessarily imply malignant behavior.
The biologic basis of nodal involvement in classic AML remains unsettled. Proposed explanations include multifocal tumor development and benign dissemination from the renal lesion. Using microsatellite marker analysis on 12 patients, Tan et al. showed that lineage relationships between tumors in the kidney and corresponding lymph nodes though unlikely could not be definitively excluded, as one patient had a clonal relationship suggesting that the lymph node lesion could have originated from the tumor in the kidney.
[19] However, similar relationships could not be found in the other patients. Similar observations have been reported in lymphangiomyomatosis.
[35] Furthermore, other benign tumors such as pleomorphic adenoma and leiomyoma can also involve regional lymph nodes.
[36, 37] Importantly, long-term follow-up in previously reported cases has favored an indolent process rather than behavior analogous to malignant renal neoplasia. In the present case, renal sinus and venous branch involvement is a noteworthy morphologic finding, but we have deliberately avoided using it as proof of malignant metastatic biology. Instead, we interpret the overall clinicopathologic picture as most consistent with a benign tumor showing regional nodal involvement. This is in keeping with the current WHO consensus, which recommends reporting such cases as multifocal tumors rather than true metastatic deposits.
From a practical standpoint, recognition of this phenomenon has implications for intraoperative and postoperative management. When frozen section and permanent histology confirm classic AML without epithelioid or sarcomatoid features, the presence of suspicious regional nodes should not be taken as evidence of aggressive malignancy. Rather, pathologic confirmation may help limit the extent of nodal dissection and avoid unnecessary overtreatment. Our patient remains disease-free at 30 months; however, this follow-up interval is still relatively short, and longer surveillance will be useful to further document long-term behavior.
4. Conclusions
Classic renal AML can rarely involve regional lymph nodes in both sporadic and TSC-associated settings. Based on the available literature and the present case, this finding does not by itself indicate aggressive metastatic behavior. Knowledge of this phenomenon can help prevent overtreatment in these patients.
Authors contributions
NR collected data, performed literature review, and drafted the manuscript. IT, DS, and UN contributed to the clinical and pathologic interpretation. PK conceived the study, supervised the project, and critically revised the manuscript. All authors approved the final manuscript.
Funding
Not applicable.
Conflicts of Interest Disclosure
The authors declare no conflicts of interest.
Informed consent
Obtained.
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The journal’s policies adhere to the Core Practices established by the Committee on Publication Ethics (COPE).
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Not commissioned; externally double-blind peer reviewed.
Data availability statement
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
Data sharing statement
No additional data are available.
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