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| Year : 2010 | Volume
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| Issue : 2 | Page : 314-319 |
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| Giant renal angiomyolipomas and pulmonary lymphangiomyomatosis |
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Kiran Nasir, Aasim Ahmad
Department of Nephrology, The Kidney Centre, Karachi, Pakistan
Click here for correspondence address and email
| Date of Web Publication | 9-Mar-2010 |
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 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 |
| Introduction | |  |
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 | | |
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 | | |
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]
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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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PMID: 20228520 
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10] |
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