Coexistence of pulmonary lymphangioleiomyomatosis and pulmonary angiomyolipoma

Pulmonary LAM is a rare lung disease that mainly affects young women of childbearing age [3]. Pathologically, LAM is characterized by the appearance of interstitial collections of atypical smooth muscle cells and cyst formation in the lungs. LAM can be sporadic or associated with TSC. Diffuse, small, symmetrical, thin-walled cysts are characteristic hallmarks of LAM on chest CTs, as was seen in this patient. Occasionally, multifocal micronodular pneumocyte hyperplasia (MMPH) is seen in patients with TSC or LAM on chest CT as random small pulmonary nodules with ground-glass opacity, ranging in size from 1 mm to 1 cm [4, 5]. MMPH nodules are composed of thickened fibrotic alveolar septa lined by pleomorphic type II pneumocytes. In our case, pulmonary nodules were initially thought to be an unusual manifestation of MMPH. However, these nodules were consolidated and much larger than those described in the literature, which motivated the decision to perform a biopsy.

Angiomyolipoma is a rare mesenchymal tumor composed of adipose tissue, smooth muscle cells and thick-walled vessels. It is the most common benign tumor of the kidney. Both LAM and angiomyolipoma belong to a family of tumors collectively termed neoplasms with perivascular epithelioid differentiation, which are now referred to as perivascular epithelial cell tumors (PEComas) [2]. HMB-45 and melan-A are present in angiomyolipoma, differentiating it from other primary and secondary mesenchymal or primary epithelial tumors [6]. In our case, HMB-45 and melan-A were both expressed in both renal and pulmonary tumors, confirming the diagnosis of angiomyolipoma. Most angiomyolipomas occur in the kidney; in rare cases, extrarenal angiomyolipoma may arise from the liver, mediastinum, uterus, spermatic cord, retroperitoneum, spleen, skin and lung [7]. Renal angiomyolipomas may occur in association with TSC, pulmonary LAM or occur as a sporadic finding. TSC has been estimated to be present in approximately 10 % of cases of clinically diagnosed renal angiomyolipomas [8].

Both LAM and angiomyolipoma are closely related to TSC, and appear to arise from a common source [9]. Furthermore, pulmonary LAM and renal angiomyolipoma are also closely related. Renal angiomyolipomas have been reported to occur in up to 100 % of patients with TSC-LAM, and in up to 50 % of those with sporadic LAM [10‐13].

Angiomyolipoma is usually benign, but occasionally metastasizes distally. Both sporadic pulmonary angiomyolipoma, and pulmonary metastases originating from renal angiomyolipoma have been described since 1995 [14]; and in a few cases pulmonary metastasis occurred years after the nephrectomy for renal angiomyolipoma [7, 15]. In this case, pulmonary and left renal angiomyolipomas occurred simultaneously 17 years after nephrectomy for right renal angiomyolipoma, and pulmonary and renal angiomyolipoma histopathology was consistent. Therefore, distal metastases seem the most likely explanation. Regrettably, molecular analysis (e.g. p53 gene mutation) [16, 17], which could better chatacterize the homology of renal and pulmonary angiomyolipomas, was not performed in this patient.

Both pulmonary LAM and renal angiomyolipoma are rare diseases; and pulmonary angiomyolipoma has been described in only a few cases. Although the coexistence of LAM and renal angiomyolipoma is noted in about 50 % of sporadic LAM patients, to the best of our knowledge, coexistence of pulmonary LAM and pulmonary angiomyolipoma has not previously been described. Genetic analysis suggested that LAM cells could originate from the smooth muscle cells of renal angiomyolipoma, and be transported through the circulation [18]. Therefore, one explanation for the pulmonary coexistence is that the renal angiomyolipoma released tumor cells to the lung through the blood flow during resection [15], allowing both metastatic pulmonary angiomyolipomas and LAM to form over a long period of time. Another explanation is that the patient might already have had LAM when she underwent nephrectomy since the patient’s pulmonary evaluation 17 years ago was performed via chest X-ray, and this technique is not sufficiently sensitive to detect an early LAM. In this case pulmonary angiomyolipomas may have metastasized from the kidney later. Whichever hypothesis is correct, LAM and angiomyolipoma appear to be related.

The mTOR inhibitor, sirolimus, stabilizes lung function and improves some measures of quality of life in patients with LAM [19, 20]. Sirolimus has been approved by the US Food and Drug Administration for the treatment of moderate-to-severe pulmonary LAM. Sirolimus is also efficacious in controlling tumor volume in patients with renal angiomyolipomas [21]. Everolimus, a derivative of sirolimus, also represents a promising treatment for LAM and renal angiomyolipoma [22, 23]. Surgery or embolism is an alternative choice when an intervention is indicated in patients with renal angiomyolipomas [24]. Sirolimus therapy was chosen in this patient in consideration of the coexistence of pulmonary LAM, pulmonary angiomyolipomas and renal angiomyolipoma. The outcome in this case demonstrated that sirolimus was effective not only for renal angiomyolipoma, but also for metastasized pulmonary angiomyolipomas.