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Coexistence of pulmonary lymphangioleiomyomatosis and pulmonary angiomyolipoma



Lymphangioleiomyomatosis (LAM) and angiomyolipoma are two different, but related rare diseases. To the best of our knowledge, pulmonary LAM and pulmonary angiomyolipoma have not previously been observed in the same patient.

Case presentation

A 38-year-old woman presented with a dry cough and left flank pain. She had a right nephrectomy for renal angiomyolipoma 17 years ago. A magnetic resonance imaging scan demonstrated a round mass in the left kidney. A chest computed tomography scan demonstrated scattered small thin-walled cysts and multifocal round nodules in both lungs. A lung biopsy via video-assisted thoracoscopic surgery revealed that the cysts and nodules were manifestations of LAM and angiomyolipomas, respectively. After sirolimus therapy, the renal angiomyolipoma and metastasized pulmonary angiomyolipomas shrank, but pulmonary cysts were unchanged.


LAM and angiomyolipoma are significantly associated, and may coexist in the lungs in rare cases. Sirolimus is effective for both renal angiomyolipoma and metastasized pulmonary angiomyolipomas.

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Lymphangioleiomyomatosis (LAM) is a rare, progressive disease that typically results in cystic lung destruction and predominantly affects women [1]. Angiomyolipoma is a mesenchymal tumor and is the most common benign tumor of the kidney. LAM and angiomyolipoma are different, but substantially related conditions. Both are perivascular epithelial cell tumors and can arise from a common source [2]. Renal angiomyolipoma is present in almost all cases of tuberous sclerosis complex (TSC)-LAM and about half of cases of sporadic LAM. However, to our knowledge, pulmonary LAM and pulmonary angiomyolipoma have not previously been observed simultaneously in the same patient. Here we present the first case of coexisting pulmonary LAM and pulmonary angiomyolipomas.

Case presentation

A 38-year-old woman presented with a dry cough and left flank pain. Her medical history revealed a right nephrectomy for renal tumor at the age of 21, but she recovered from surgery without complications.

During physical examination, the patient had normal vital signs, with a temperature of 36 °C, pulse of 80 beats/min, BP of 135/80 mmHg, respiratory rate of 18 breaths/min, and oxygen saturation of 98 % on ambient air. She was conscious, with normal cognition. Physical examinations were unremarkable, except for a surgical cicatrix at the right lumber region. Both lungs were clear to auscultation. The abdominal examination was normal, and no percussion tenderness in the region of the kidney was noted.

Complete blood count, urinalysis, renal and hepatic functions were all in normal ranges. Serum VEGF-D was 615 ug/mL (<800 pg/mL). A chest computed tomography (CT) scan demonstrated scattered small thin-walled cysts and 15 round nodules ranging in size from 5 mm to 24 mm in both lungs (Fig. 1a, b). Pulmonary function tests revealed normal ventilation, lung volume and diffusion capacity (FEV1 3.15 L/106.2 %, FEV1/FVC 77.6 %, TLC 112.9 %, and DLCO 91.9 %). Abdominal magnetic resonance imaging scan and CT scan demonstrated a round mass with a diameter of 4 cm on the upper pole of the left kidney (Fig. 2a, b). Histopathological review of the tumor in the right kidney, resected 17 years ago, revealed it to be an angiomyolipoma. Video-assisted thoracoscopic surgery was undertaken, during which cysts and yellowish nodules were seen on the surface of the lung (Fig. 3). Histopathologic analysis of the lung specimen revealed that the cysts coincided with LAM, while the nodules were angiomyolipomas, consistent with that in the right kidney (Fig. 4).

Fig. 1

a Chest computed tomography scan shows scattered thin-walled cysts (arrowheads) and round nodules (arrows) in the lungs. The largest nodule (2.4 cm in diameter) was located in left upper lobe (white arrow). b The pulmonary nodule (white arrow) appears heterogeneous with fatty components on the mediastinal window. c A repeat CT 8 months after sirolimus therapy reveals that the diameter of the largest nodule (white arrow) has shrunk to 1.4 cm in diameter. A surgical scar (black arrow) is seen in the right upper lobe

Fig. 2

a An abdominal magnetic resonance imaging scan and b an abdominal CT scan showing a round heterogeneous mass of 4 cm in diameter (arrow) on the upper pole of the left kidney. c Eight months after sirolimus therapy, the CT reveals that the mass has shrunk to 2.1 cm in diameter

Fig. 3

A yellowish nodule (arrow) and two cysts (arrowheads) are seen on the surface of the lung during video-assisted thoracoscopic surgery

Fig. 4

Biopsy specimen of the lung. a and b The cystic lesion’s walls exhibit the accumulation of some spindle-shaped cells which are positive for HMB45 staining. HE × 10 (a), HMB45 × 60 (b). c and d The nodular lesion is a mixture of adipose tissue, smooth muscle, and small blood vessels. HE × 10 (c), HE × 60 (d)

Germinal TSC gene mutation was not detected in this patient; therefore, the pulmonary LAM was considered to be sporadic. Angiomyolipomas in the lungs and the left kidney were predicted to have metastasized from the resected right kidney. After the patient was prescribed 2 mg/d sirolimus, the cough and left flank pain were gradually relieved. A CT scan 8 months later revealed that the mass in the left kidney and some pulmonary nodules had shrunk, but the cysts in both lungs were unchanged (Figs. 1c and 2c).


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 [1013].

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.


LAM and angiomyolipoma are substantially related, and may coexist in the lungs in rare cases. Sirolimus can effectively resolve both renal angiomyolipoma and metastasized pulmonary angiomyolipomas.





Multifocal Micronodular Pneumocyte Hyperplasia


Perivascular Epithelial Cell Tumors


Tuberous Sclerosis Complex


  1. 1.

    McCormack FX. Lymphangioleiomyomatosis: a clinical update. Chest. 2008;133(2):507–16.

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Martignoni G, Pea M, Reghellin D, Zamboni G, Bonetti F. PEComas: the past, the present and the future. Virchows Arch. 2008;452(2):119–32.

    Article  PubMed  Google Scholar 

  3. 3.

    Sullivan EJ. Lymphangioleiomyomatosis: a review. Chest. 1998;114(6):1689–703.

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Muir TE, Leslie KO, Popper H, Kitaichi M, Gagne E, Emelin JK, Vinters HV, Colby TV. Micronodular pneumocyte hyperplasia. Am J Surg Pathol. 1998;22(4):465–72.

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Kobashi Y, Sugiu T, Mouri K, Irei T, Nakata M, Oka M. Clinicopathological analysis of multifocal micronodular pneumocyte hyperplasia associated with tuberous sclerosis in Japan. Respirology. 2008;13(7):1076–81.

    PubMed  Google Scholar 

  6. 6.

    Tuna EB, Lebe B, Yorukoglu K. HMB45 and melan-A expression in renal angiomyolipoma and their significance for the diagnosis. Tumori. 2003;89(1):46–8.

    PubMed  Google Scholar 

  7. 7.

    Kasuno K, Ueda S, Tanaka A, Tanaka-Kasuno Y, Kuwahara T. Pulmonary angiomyolipoma recurring 26 years after nephrectomy for angiomyolipoma: benign clinical course. Clin Nephrol. 2004;62(6):469–72.

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Bissler JJ, Kingswood JC. Renal angiomyolipomata. Kidney Int. 2004;66(3):924–34.

    Article  PubMed  Google Scholar 

  9. 9.

    Karbowniczek M, Astrinidis A, Balsara BR, Testa JR, Lium JH, Colby TV, McCormack FX, Henske EP. Recurrent lymphangiomyomatosis after transplantation: genetic analyses reveal a metastatic mechanism. Am J Respir Crit Care Med. 2003;167(7):976–82.

    Article  PubMed  Google Scholar 

  10. 10.

    Ryu JH, Moss J, Beck GJ, Lee JC, Brown KK, Chapman JT, Finlay GA, Olson EJ, Ruoss SJ, Maurer JR, et al. The NHLBI lymphangioleiomyomatosis registry: characteristics of 230 patients at enrollment. Am J Respir Crit Care Med. 2006;173(1):105–11.

    Article  PubMed  Google Scholar 

  11. 11.

    Rakowski SK, Winterkorn EB, Paul E, Steele DJ, Halpern EF, Thiele EA. Renal manifestations of tuberous sclerosis complex: Incidence, prognosis, and predictive factors. Kidney Int. 2006;70(10):1777–82.

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    Cudzilo CJ, Szczesniak RD, Brody AS, Rattan MS, Krueger DA, Bissler JJ, Franz DN, McCormack FX, Young LR. Lymphangioleiomyomatosis screening in women with tuberous sclerosis. Chest. 2013;144(2):578–85.

    Article  PubMed  Google Scholar 

  13. 13.

    Yeoh ZW, Navaratnam V, Bhatt R, McCafferty I, Hubbard RB, Johnson SR. Natural history of angiomyolipoma in lymphangioleiomyomatosis: implications for screening and surveillance. Orphanet J Rare Dis. 2014;9:151.

    Article  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Guinee Jr DG, Thornberry DS, Azumi N, Przygodzki RM, Koss MN, Travis WD. Unique pulmonary presentation of an angiomyolipoma. Analysis of clinical, radiographic, and histopathologic features. Am J Surg Pathol. 1995;19(4):476–80.

    Article  PubMed  Google Scholar 

  15. 15.

    Hino H, Ikeda S, Kawano R, Sato F, Tagawa K, Hoshino T, Yokota T, Hata E, Fujii A, Mori M. Angiomyolipoma in the lung detected 15 years after a nephrectomy for renal angiomyolipoma. Ann Thorac Surg. 2010;89(1):298–300.

    Article  PubMed  Google Scholar 

  16. 16.

    Li J, Zhu M, Wang YL. Malignant epithelioid angiomyolipoma of the kidney with pulmonary metastases and p53 gene mutation. World J Surg Oncol. 2012;10:213.

    Article  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Li W, Guo L, Bi X, Ma J, Zheng S. Immunohistochemistry of p53 and Ki-67 and p53 mutation analysis in renal epithelioid angiomyolipoma. Int J Clin Exp Pathol. 2015;8(8):9446–51.

    PubMed  PubMed Central  Google Scholar 

  18. 18.

    Henske EP. Metastasis of benign tumor cells in tuberous sclerosis complex. Genes Chromosomes Cancer. 2003;38(4):376–81.

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Bissler JJ, McCormack FX, Young LR, Elwing JM, Chuck G, Leonard JM, Schmithorst VJ, Laor T, Brody AS, Bean J, et al. Sirolimus for angiomyolipoma in tuberous sclerosis complex or lymphangioleiomyomatosis. N Engl J Med. 2008;358(2):140–51.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  20. 20.

    McCormack FX, Inoue Y, Moss J, Singer LG, Strange C, Nakata K, Barker AF, Chapman JT, Brantly ML, Stocks JM, et al. Efficacy and safety of sirolimus in lymphangioleiomyomatosis. N Engl J Med. 2011;364(17):1595–606.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  21. 21.

    Peng ZF, Yang L, Wang TT, Han P, Liu ZH, Wei Q. Efficacy and safety of sirolimus for renal angiomyolipoma in patients with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis: a systematic review. J Urol. 2014;192(5):1424–30.

    CAS  Article  PubMed  Google Scholar 

  22. 22.

    Bissler JJ, Kingswood JC, Radzikowska E, Zonnenberg BA, Frost M, Belousova E, Sauter M, Nonomura N, Brakemeier S, de Vries PJ, et al. Everolimus for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis (EXIST-2): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2013;381(9869):817–24.

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    Goldberg HJ, Harari S, Cottin V, Rosas IO, Peters E, Biswal S, Cheng Y, Khindri S, Kovarik JM, Ma S, et al. Everolimus for the treatment of lymphangioleiomyomatosis: a phase II study. Eur Respir J. 2015;46(3):783–94.

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Flum AS, Hamoui N, Said MA, Yang XJ, Casalino DD, McGuire BB, Perry KT, Nadler RB. Update on the Diagnosis and Management of Renal Angiomyolipoma. J Urol. 2016;195:834–46.

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All the data supporting our findings is contained within the manuscript.

Authors’ contributions

XS, YZ and RF collected data and drafted the manuscript; JS and KX analyzed data and revised the manuscript. All authors read and approved the final manuscript.

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The authors declare that they have no competing interests.

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Correspondence to Kai-Feng Xu.

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Sun, X., Feng, R., Zhang, Y. et al. Coexistence of pulmonary lymphangioleiomyomatosis and pulmonary angiomyolipoma. BMC Pulm Med 16, 120 (2016).

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  • Case report
  • Lymphangioleiomyomatosis
  • Angiomyolipoma
  • Lung