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Saudi Journal of Kidney Diseases and Transplantation
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CASE REPORT Table of Contents   
Year : 2010  |  Volume : 21  |  Issue : 2  |  Page : 314-319
Giant renal angiomyolipomas and pulmonary lymphangiomyomatosis


Department of Nephrology, The Kidney Centre, Karachi, Pakistan

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Date of Web Publication9-Mar-2010
 

   Abstract 

Renal Angiomyolipomas (AML) are benign tumors, which can acquire huge size and when bilateral, they are diagnostic of tuberous sclerosis (TS). Pulmonary Lymphangiomyo­matosis (LAM) is more common in female patients with TS and mostly diagnosed in patients with renal AMLs. We report a case of giant bilateral AMLs and pulmonary LAM in a 48-year-old female patient, who required nephrectomy for life-threatening hemorrhage.

How to cite this article:
Nasir K, Ahmad A. Giant renal angiomyolipomas and pulmonary lymphangiomyomatosis. Saudi J Kidney Dis Transpl 2010;21:314-9

How to cite this URL:
Nasir K, Ahmad A. Giant renal angiomyolipomas and pulmonary lymphangiomyomatosis. Saudi J Kidney Dis Transpl [serial online] 2010 [cited 2019 Nov 18];21:314-9. Available from: http://www.sjkdt.org/text.asp?2010/21/2/314/60202

   Introduction Top


The Tuberous Sclerosis Complex (TSC) is a multisystem, autosomal dominant disorder affec­ting children and adults and results from mu­tations in one of two genes, TSC1 (encoding hamartin) or TSC2 (encoding tuberin). First des­cribed in depth by Bourneville in 1880, [1] TSC often causes disabling neurological disorders, including epilepsy, mental retardation, and au­tism. Additional major features of the disease include dermatologic manifestations such as facial angiofibromas, renal angiomyolipomas (AML), and pulmonary lymphangiomyomato­sis (LAM). TSC has a wide clinical spectrum of disease. AML is a benign renal neoplasm composed of fat, vascular, and smooth muscle elements. It has an incidence of about 0.3-3% and two types are described: isolated angio­myolipoma and angiomyolipoma that is asso­ciated with tuberous sclerosis (TS). [1] AMLs that are associated with TS account for 20% of these tumors; [2] the lesions are typically larger than isolated angiomyolipomas, and they are often bilateral and multiple. Angiomyolipomas occur in 80% patients with TS. [2],[3] AMLs may be detected by ultrasonography, computed tomo­graphy (CT), or magnetic resonance imaging (MRI). Because these tumors have abnormal vasculature and often contain aneurysms, spon­taneous life-threatening bleeding is an impor­tant complication, especially when angiomyo­lipomas are three cm or greater in diameter. The rate of growth of AMLs varies among pa­tients and lesions. [4]

As many as 40% of AMLs are symptomatic; [5] they can present as a palpable abdominal mass or with hematuria, or flank pain. The solitary sporadic tumors may cause acute abdomen and shock as a result of spontaneous hemorrhage in the tumor. Most of the AMLs have a benign course. If the diagnosis is certain, patients can be treated conservatively. If the patients have recurrent episodes of hemorrhage or massive bleeding, the tumor can be resected. Renal ar­terial embolization may also be used to control hemorrhage. [6]

Lymphangiomyomatosis (LAM), also called lymphangioleiomyomatosis, affects women al­most exclusively, and is characterized by wide­spread pulmonary proliferation of abnormal smooth-muscle cells and cystic changes within the lung parenchyma. [7] LAM is usually diag­nosed during early adulthood and is initially manifested by dyspnea or pneumothorax. Radio­graphic evidence indicates that the incidence of LAM among women with TSC is 26 to 39%. [8],[9] In a series of 49 TSC-related deaths reported by the Mayo Clinic, LAM was cited as the cause of four deaths, making it the third most frequent cause of death after renal and brain lesions. [10]


   Case Report Top


A 48-year-old female patient came to the outpatient department of our tertiary care renal unit with abdominal distension and pain. Phy­sical examination showed bilateral palpable kidneys. Ultrasound abdomen showed bilateral enlarged and distorted kidneys with huge echo­genic masses, measuring 10.2 × 7 cm on the right side and 14.3 × 7.2 cm on the left side. The serum creatinine at the time of scan was 1.3 mg/dL. A CT scan of the abdomen done at that time showed bilateral giant AMLs; right measured 16 × 8 × 7 cm while left measured 22 × 14 × 8 cm [Figure 1],[Figure 2] and [Figure 3]. A diagno­sis of TS with bilateral huge AMLs was made. As the patient was asymptomatic, she was ma­naged conservatively. One month after the diagnosis, the patient presented with a drop in hemoglobin of two grams without evidence of gross hemorrhage. The patient was initially managed conservatively. After one week, bila­teral angio-embolizaion was successfully done. After angio-embolization, her serum creatinine raised to 2.0 mg/dL. Follow-up CT scan showed a reduction in size of both tumors. The size of the AML on the right side reduced to 14 × 6 × 6 cm and on the left side, it reduced to 18 × 12 × 8 cm [Figure 4],[Figure 5],[Figure 6] and [Figure 7]. Four months after angio-embolization, the patient presented to the emergency room with severe left flank pain and an increasing swelling in the left iliac fo­ssa after mild exertion at home. Physical exa­mination revealed a pale looking, thin built woman with obvious swelling of left side of the abdomen. Her blood pressure was 100/70 mmHg, pulse rate was 92 beats/min; respi­ratory rate of 20/min and temperature was 37.4°C. Left side of the abdomen was disten­ded with a tender palpable lump involving left flank and extending down the left iliac fossa to left groin. Her hemoglobin dropped to 8 gm/L from 11 gm/L and serum creatinine was 2.2 mg/dL. Diagnosis of massive hemorrhage from left AML was made, which was confirmed with ultrasound. For this, she required emer­gency nephrectomy and 11 pints of blood trans­fusion. Histopathology grossly showed a bla­ckish - brown, friable, soft, multilobulated mass measuring 19.8 × 13 × 8 cm. Microscopically, it showed a tumor displaying an intimate admix­ture of thick walled blood vessels, smooth mu­scle and fat. The tumor showed moderate nuc­lear hyperchromatism and pleomorphism focally, consistent with AML. Arteriovenous fistula was made for future hemodialysis. Patient was ad­vised to undergo elective right nephrectomy to avoid life threatening hemorrhage. Serum creatinine at the time of discharge was 2.8 mg/dL. Six months later, elective right nephrectomy was performed. She was started on thrice­weekly hemodialysis. Two months after star­ting hemodialysis, she complained of blood in the sputum for which CT scan of the chest was performed, which showed evidence of multiple cystic air spaces in both lungs in scattered distribution with predominant involvement of lower lobes [Figure 8],[Figure 9] and [Figure 10]. They mea­sured 1.5 cms or less in size. Findings were consistent with lymphangiomyomatosis. Pul­monary function tests showed FEV1 of 1.68 and FEV1/FVC ratio of 80% suggestive of mild irreversible obstructive airway disease.

Currently, she is on hemodialysis three times per week. Her pulmonary condition is stable. She is advised to undergo CT scan of the chest as well as pulmonary function tests every three monthly. She is planned for a renal transplan­tation in future.


   Discussion Top


Tuberous sclerosis, a rare autosomal domi­nant disorder with variable penetrance, affects approximately 1 in 10,000 people with a point prevalence of 10 per 100,000. [11] Classically, the disease is described as a clinical triad of ade­noma sebaceum, mental retardation, and sei­zures. However, due to incomplete penetrance, symptomatology may range from isolated or­gan involvement, present in mild incomplete disease, or forme fruste, to involvement of mul­tiple organs. The pathophysiology of TS can include glial tumors of the brain, adenoma se­baceum of the skin, rhabdomyoma of the heart, and hamartomatous tumors of the thyroid, re­tina, liver, pancreas, lung, kidney, adrenals and ovaries. [12],[13]

Renal manifestations of TS comprise angio­myolipomas, cysts and, rarely, renal cell car­cinomas. The most common renal lesions seen in TS are AML. They are bilateral in most pa­tients with TSC. The estimated incidence of AML in TSC ranges from 55 to 75%. [2],[3] These tumors are composed of vascular tissue (angio), smooth muscle (myo), and fat (lipoma). Al-though benign, an AML larger than four cm is at risk for a potentially catastrophic hemo­rrhage, either spontaneously or with minimal trauma. An enlarging AML can distort the re­nal architecture, causing renal failure and even death. [14] In general, surgical resection is avoi­ded whenever possible in order to preserve renal function; AMLs that are more than three to four cm in diameter can usually be treated successfully by embolization. [15],[16] An enlarging AML can distort the renal architecture, causing renal failure and even death. [17] Dysmorphic blood vessels in the AML often form micro­aneurysms, which may rupture and result in renal hemorrhage. Ruptured AMLs are most commonly seen in lesions > 4 cm in diame­ter. [15] The exact mechanism by which AMLs and renal cystic disease cause renal failure is not known. Okada et al noted the rarity of renal failure in patients with TS and associated renal cystic disease and hypothesized that the cysts, and not the AMLs, were the cause of renal failure. [12]

Pulmonary lymphangiomyomatosis (LAM) is a rare disease, which results from benign proliferation of smooth muscle in lung and other organs. Patients with advanced disease may demonstrate cystic changes and honey­combing in their lungs, leading to a mixed picture of interstitial and obstructive disease. Common complications include pneumotho­rax, chylothorax, and hemoptysis. Due to the fact that women of reproductive age are pre­dominantly affected by LAM, it was suggested that there might be a hormonal influence, and in fact estrogen receptors have been found in these lesions. [18]

Furthermore, the anti-estrogen drug tamoxi­fen has proven beneficial in slowing the di­sease process. The disease is characterized by widespread pulmonary proliferation of abnor­mal smooth-muscle cells and cystic changes within the lung parenchyma. [7] Radiographic evidence indicates that the incidence of lym­phangiomyomatosis among women with TSC is 26 to 39%; many of these women are a­symptomatic. [8],[9] The first case report of con­comitant renal AMLs and pulmonary LAM was published in 1994. [19] Recent genetic ana­lysis has shown that the proliferative bron­chiolar smooth muscle in TS-related LAM is monoclonal metastasis from a co-existing re­nal AML. There have been cases of TSC­ related LAM recurring following lung trans­plant. [20]

The prognosis for individuals with TSC de­pends on the severity of symptoms, which range from mild skin abnormalities to varying degrees of learning disabilities and epilepsy to severe mental retardation, uncontrollable sei­zures, and kidney failure. Those individuals with mild symptoms generally do well and live long productive lives, while individuals with the more severe form may have serious dis­abilities. However, with appropriate medical care, most individuals with the disorder can have normal life expectancy. [17] Kidney complications such as angiomyolipoma (AML) and cysts are common, and more frequent in fe­males than males and in TSC2 than TSC1. Re­nal cell carcinoma is uncommon. Pulmonary lymphangioleiomyomatosis is only a risk for females with AMLs. [21] Leading causes of death include renal disease, brain tumor, lymphan­giomyomatosis of the lung, and status epilep­ticus or bronchopneumonia in those with se­vere mental handicap. [22]

 
   References Top

1.Bourneville DM. Scleroses tubereuse des circonvolutions cerebrales: idiotie et epilepsie hemiplegique. Arch Neurol (Paris) 1880;1:81-91.  Back to cited text no. 1      
2.Debora SL, Jozwiak S, Franz DN, et al. Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2, compared with TSC1, disease in multiple organs. Am J Hum Genet 2001;68:64­-80.  Back to cited text no. 2      
3.Ewalt DH, Sheffield E, Sparagana SP, Delgado MR, Roach ES. Renal lesion growth in children with tuberous sclerosis complex. J Urol 1998;160:141-5.  Back to cited text no. 3  [PUBMED]    
4.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.  Back to cited text no. 4      
5.Cohen MD. Genitourinary tumours. In: Cohen MD, ed. Imaging of Children With Cancer. St Louis, Mo: Mosby Year Book; 1992:552-88.  Back to cited text no. 5      
6.Earthman WJ, Mazer MJ, Winfield AC. Angio­myolipomas in tuberous sclerosis: sub selec­tive embolotherapy with alcohol, with long­term follow-up study. Radiology 1986;160(2): 437-41.  Back to cited text no. 6      
7.Ryu JH, Moss J, Beck GJ, et al. The NHLBI lymphangioleiomyomatosis registry: Characte­ristics of 230 patients at enrolment. Am J Respir Crit Care Med 2006;173:105-11.  Back to cited text no. 7  [PUBMED]    
8.Franz DN, Brody A, Meyer C, et al. Muta­ional and radiographic analysis of pulmonary disease consistent with lymphangioleiomyo­matosis and micro nodular pneumocyte hyper­plasia in women with tuberous sclerosis. Am J Respir Crit Care Med 2001;164:661-8.  Back to cited text no. 8  [PUBMED]    
9.Costello LC, Hartman TE, Ryu JH. High fre­quency of pulmonary lymphangioleiomyoma­tosis in women with tuberous sclerosis complex. Mayo Clin Proc 2000;75:591-4.  Back to cited text no. 9  [PUBMED]    
10.Shepherd CW, Gomez MR, Lie JT, Crowson CS. Causes of death in patients with tuberous sclerosis. Mayo Clin Proc 1991;66:792-6.  Back to cited text no. 10  [PUBMED]    
11.Stillwell TJ, Gomez M, Kelalis PP. Renal le­sions in tuberous sclerosis. J Urol 1987;138: 477.  Back to cited text no. 11      
12.Okada R, Platt M, Fleishman J. Chronic renal failure in patients with tuberous sclerosis: Asso­ciation with renal cysts. Nephron 1982;30:85­8.  Back to cited text no. 12      
13.Roach IS, Smith M, Huttenlocher P. Diagnostic criteria: Tuberous sclerosis complex. J Child Neurol 1992;7:221-4.  Back to cited text no. 13      
14.Dickinson M, Ruckle H, Beaghler M, Hadley HR. Renal angiomyolipoma: Optimal treatment based on size and symptoms. Clin Nephrol 1998;49:281-6.  Back to cited text no. 14  [PUBMED]    
15.Ewalt DH, Diamond N, Rees C, et al. Long­term outcome of transcatheter embolization of renal angiomyolipomas due to tuberous scle­rosis complex. J Urol 2005;174:1764-6.  Back to cited text no. 15  [PUBMED]    
16.Kothary N, Soulen MC, Clark TW, et al. Renal angiomyolipoma: Long-term results after arte­rial embolization. J Vasc Interv Radiol 2005; 16:45-50.  Back to cited text no. 16  [PUBMED]    
17.Tuberous Sclerosis Fact Sheet. National Insti­tute of Neurological Disorders and Stroke (2006-04-11). Retrieved on 2006-10-03.  Back to cited text no. 17      
18.Luna C, Gene R. Pulmonary lymphangiomyo­matosis associated with tuberous sclerosis. Chest 1985;88:473-5.  Back to cited text no. 18      
19.Brisman JL, Kirsch AJ, Taylor JA, et al. Pul­monary lymphangiomyomatosis in tuberous sclerosis: Association with chronic renal fai­lure. P&S Med Rev 1994;2(1).  Back to cited text no. 19      
20.Henske EP. Metastasis of benign tumor cells in tuberous sclerosis complex. Genes Chromosomes Cancer 2003;38(4):376-81.  Back to cited text no. 20      
21.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.  Back to cited text no. 21      
22.Shepherd C, Gomez M, Lie J, Crowson C. Causes of death in patients with tuberous sclerosis. Mayo Clin Proc 1991;66(8):792-6.  Back to cited text no. 22      

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Correspondence Address:
Kiran Nasir
Consultant Nephrologist, The Kidney Centre, 197/9, Rafique Shaheed Road, Karachi 75530
Pakistan
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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10]

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