Renal angiomyolipoma (AML) is an unusual benign tumour with no malignant potential in the kidney. We present two cases of unusual Giant Renal Angiomyolipoma (Renal Hamartoma).

Keywords: angiomyolipoma, AML, renal neoplasm, benign renal tumour, arterial embolisation, partial nephrectomy.
Authors: D W CRANSTON, MB ChB, DPhil, FRCSConsultant UrologistChurchill Hospital, Oxford OX3 7LJ, UK Department of Urology, The Churchill Hospital, Oxford OX3 7LJ, UK
Corresponding Author: MAITHAM MOSLIMĀ  Elective Medical Student, Medical School, Oxford University, UKFifth year Medical Student, Faculty of Medicine, Damascus University, Syria Email: maitham.moslim@gmail.com, guyton7391@yahoo.com

Abstract 

Renal angiomyolipoma (AML) is an unusual benign tumour with no malignant potential in the kidney. It is composed of adipose tissue, smooth muscle and abnormal blood vessels. It can occur sporadically, or it can be associated with tuberous sclerosis. The classic presentation of AML is Lenk's triad. The two major morbidities associated with renal angiomyolipomas are retroperitoneal hemorrhage and impingement of the angiomyolipoma on the kidneys and other vital organs.
Case presentation 1: A case of a unusual giant AML underwent arterial embolisation and then partial nephrectomy. The underlying diagnosis of renal angiomyolipoma was made based on contrast enhanced multi-detector computed tomography urography (CTU) findings.
Case presentation 2: Another case of asymptomatic giant AML detected incidentally during investigations for microcytic anaemia. The diagnosis was confirmed based on CTU and abdominal magnetic resonance imaging (MRI) findings. Partial nephrectomy was performed leaving 80 percent of the kidney behind.
             
Introduction

Definition and Epidemiology
Renal angiomyolipoma (AML) is a benign tumour in the kidney. It has an incidence of 0.3–3% and it is estimated that ten million people worldwide have such lesions. It is identified increasingly due to increased use of medical imaging and advances in imaging technology.  It arises from the mesenchymal elements of the kidney [1]. It is composed of varying proportions of mature adipose tissue, smooth muscle and abnormal thick-walled blood vessels. For that reason AML is also known as renal Hamartoma. The adipose component is characteristic of AML and if fat is identified, its benign nature can be established.
A marked female predominance was observed with AML. The overall female:male ratio is approximately 4:1 which suggesting a hormonal component to tumour growth [2].
It can occur sporadically, or it can be part of the tuberous sclerosis complex (TSC). 
Sporadic angiomyolipomas account for 80 percent of AML, are usually solitary and occur almost exclusively in women in the fourth to fifth decade of life (mean age 43 [3]).
Angiomyolipomas are found in approximately 45–80 percent of patients with tuberous sclerosis and tend to occur in adolescents and young adults (third decade). It has also been identified in a child as young as 5 years old [4,5]. Tuberous sclerosis is a familial inherited disorder comprising adenoma sebaceum, mental retardation, and epilepsy.
In sporadic AML, the number of AML is scanty and unilateral. Its size usually remains constant for a long time or it may grow slowly. In tuberous sclerosis associated angiomyolipomas, it may grow faster; they are typically bilateral and asymptomatic and the female:male prevalence is nearly equal.

Clinical Manifestations
Most small angiomyolipomas are asymptomatic and found incidentally on radiological studies.
Research has shown that 25-50 percent of patients have some or all of the features and stigmata of TSC.
The classical presentation of AML is a palpable tender mass (47%), flank pain (53%) and gross haematuria (23%); this is known as 'Lenk's triad' [6]. However, it is rare to have a diagnosed AML with this triad. Less frequently associated  
symptoms include nausea or vomiting, fever, anaemia and blood pressure alteration [7]. 
The two major morbidities associated with renal AML are retroperitoneal hemorrhage and impingement of the AML on normal tissue, which can impair renal function [2,8]. Enlarging angiomyolipomas can develop micro- and macro-aneurysms that can rupture. This can be sudden and painful, and occasionally life-threatening. 
Several studies have demonstrated that the frequency of symptoms and risk of bleeding (rupture) increases with the size of the AML. The reported risk of hemorrhage varies markedly, ranging from 3 to 50 percent. 
In a review of angiomyolipomas ≥ 4 cm, 82 to 94 percent were symptomatic and 50 to 60 percent bled spontaneously [9]. In another report that utilized CT scanning and angiography, lesion size of ≥ 4 cm and aneurysm size of ≥ 5 mm were associated with a sensitivity and specificity for rupture of 100 and 38 percent and 100 and 86 percent, respectively. This report also indicated that aneurysm size was the most important factor linked to rupture [10]. The rupture can occur spontaneously, in patients on anticoagulants, or in patients with trauma to the kidney. Rupture has also been reported during pregnancy or in the post-partum period [11,12]. The slow growth of angiomyolipomas may eventually encroach upon normal tissue and lead to progressive renal insufficiency, as mentioned before, but how often this occurs is still unclear. 
Patients with a rare condition termed lymphangioleiomyomatosis may have multiple renal and hepatic angiomyolipomas, multiple pulmonary cysts, enlarged abdominal lymph nodes, and lymphangiomyomas [13].

Diagnosis
There are two imaging characteristics that are highly suggestive of an angiomyolipoma: they are echogenic on ultrasound; and, on CT scanning, they have the density of fat, which is less than that of water (negative i.e. -10 to -100 Hounsfield units) [14]. MRI can be used to identify the fatty tissue; however, because the presence of bleeding in any renal tumour can mimic the typical pattern of angiomyolipoma, MRI should not be considered the diagnostic method of choice.
The images generally show a highly or mixed echogenic renal tumour without calcification that is difficult to distinguish from renal cell carcinoma on US and thus requires further imaging with CT. On CT, angiomyolipomas have well defined margins, with a variable proportion of fat and soft tissue. 
AML can vary in size from a few millimeters to larger than 20 cm [15]. It is unusual to see an AML over 10 cm, therefore many studies have demonstrated that any AML measuring over that number is considered “giant”.
These CT findings usually help to differentiate angiomyolipomas from other tumours, such as perinephric liposarcomas [16].
Arterial angiography can reveal neovascularity similar to that of renal cancer and therefore is not helpful in differential diagnosis.

Treatment
The management of angiomyolipomas historically has been correlated with symptoms. 
Most patients with small tumours (less than 4 cm) that tend to be asymptomatic are managed conservatively, with periodic ultrasonography [17]; however patients with tumours over than 8 cm generally tend to be asymptomatic. It is these larger tumours that are at greater risk of spontaneous or traumatic rupture resulting in haemorrhagic complications. These patients are therefore treated with angiography and selective arterial embolisation as a first line. Partial or radical nephrectomy is indicated if there is persistent haemorrhage, suspicion of malignancy, or failed embolisation [15]. 
Prophylactic embolisation of asymptomatic lesions 4 cm or larger is recommended in select high risk patients, including younger women who intend future pregnancy or in patients in whom regular follow-up is difficult [2].
Renal sparing approaches are preferred when intervention is necessary [2,8,18]. These include partial or nephron-sparing surgeries (which are associated with a risk of significant hemorrhage) and interventional radiological (IR) treatment like arterial embolisation, Radiofrequency ablation and cryoablation [19]. Embolisation reduces the risk of hemorrhage by blocking the blood supply to the angiomyolipoma. Urgent arterial embolisation is indicated if tumour rupture is suspected as it may save the life of patients.
After embolisation, the tumour does not disappear. The tumour size usually decreases by two-thirds to 40 percent. Recurrence of the tumour has been reported and repeated embolisations are occasionally needed, especially in patients with TSC [20,21].
Radiofrequency ablation (RFA) of renal tumours has been proven as a useful treatment for small, incidentally found, renal cortical lesions in elderly patients or patients with a solitary kidney at high risk of renal dysfunction following partial nephrectomy. However, RFA is not suitable for tumours over 4cm. A radiofrequency probe or needle is inserted into the tumour and thermal energy is used to ablate the tumour [22,23]. The most worrisome complication is thermal injury to the pelvicalyceal system and ureter [23].
More revolutionary, cryoablation has been used for ablation of renal tumours [24]. The needles are small and they can be inserted safely into the tumour. Compressed helium and argon gas are used to perform deep cooling surrounding the needle. The cells die when the temperature is below -40ºXC. The merit of this treatment is that it is less painful and can be monitored under CT or even MRI. The size of ablation can be maintained accurately with lower risk to injure to the collecting system [23].
Indications for a radical nephrectomy include a nonfunctioning kidney or deterioration of renal function causing uncontrolled hypertension, local surrounding tissue invasion, tumour in the renal vein, and very strong evidence of malignancy [2].
Given the difference in the natural history of angiomyolipomas in patients with tuberous sclerosis, prophylactic intervention in patients with lesions greater than 4 cm irrespective of symptoms is recommended, with close follow-up of smaller lesions [13].
The importance of this follow-up has been demonstrated with documented evidence that 27 percent of lesions smaller than 4 cm and 46 percent of lesions greater than 4 cm have been shown to grow up to 4 cm per year over a mean follow-up period of 4 years [1]. 
In all cases of AML, the aim of treatment is to preserve renal function and to prevent haemorrhage or rupture [15].

Case presentation 1

A 37-year-old gentleman, a lecturer in a university, presented to the urology clinic with one month history of blunt bilateral groin pain and scrotal fullness prompting a scrotal ultrasound that showed the presence of bilateral varicocele. Right flank pain with some paraesthesia had noted over the past few days. Due to that, the patient underwent subsequent bladder and kidney US scans which revealed the presence of a right renal mass. The ultrasound of the retroperitoneum illustrated a normal left kidney and a mass in the right kidney that measures 11.1 cm on US in greatest diameter. There was no right renal collecting system dilation. There were innumerable subcentimeter hpoechoic masses within the right renal cortex. In addition, there were discontinuity of the upper pole cortex and an echogenic mass extending from the upper pole into the hepatorenal space with associated acoustic shadowing.
As renal cell carcinoma (RCC) was suspected clinically, the patient underwent further investigation with contrast (omnipaque) enhanced multi-detector computed tomography Urography (CTU) scan. 
Findings on CTU included an approximately 16.7 * 8.8 * 6.8 cm mass arising from the right kidney (Figure 1). 
Fig. 1. (a) Non-enhanced multi-detector computed tomography urogram (CTU) scan demonstrates the presence of angiomyolipoma arising from the anterior surface of the right kidney; axial section. (b,c) Post-contrast MDCTU scan demonstrates a hypodense mass arising from the anterior superior aspect of the right kidney and displacing surrounding structures. No pelvicaliectasis was appreciated. No frank involvement of the inferior vena cava; axial and coronal sections. This CTU was done before arterial embolisation.



It contained large areas with fat density, areas of enhancing soft tissue, as well as irregular large vessels. This mass arose from the anterior superior aspect of the right kidney and displaced surrounding structures, including the right adrenal gland, liver and pancreas. This mass contained no calcification. It was most compatible with a large angiomyolipoma. There were numerous cortical subcentimeter hypodensities within the right kidney that were too small to characterize. No pelvicaliectasis was appreciated. The liver contained a sub-5 mm hypodensity too small to characterize. No frank involvement of the inferior vena cava on that side. Magnetic resonance imaging (MRI) wasn’t performed.
The patient had good appetite and his weight was stable. He had a history of asthma and gastro-oesophageal reflux disease (GORD) but there was no history of tuberous sclerosis and his presentation wasn’t preceded with HTN or anaemia. No known drug allergies (NKDA). He was ex-smoker 4-5 cigarettes/day (gave up five years ago).
After ten days of the diagnosis, the patient underwent arterial embolisation of the right AML in USA (Figure 2). He had some fevers and severe episodes of right loin pain immediately post the procedure and these settled afterwards. 
Fig. 2. (a,b) Arterial angiography of the right kidney demonstrates the vasculature of angiomyolipoma arising from the upper pole. (c) The catheter is in the main artery supplying the tumour in order to perform embolisation.



Then after five months, he was readmitted to the hospital with ongoing right loin pain, which wasn’t improving. On examination, he seemed to be relatively well although his abdomen was tender but soft on the right side. He was opening his bowels and passing urine normally. His CT was repeated and reported as there was a large right AML persists with max diameter of 12 cm (Figure 3). It was predominantly exophytic but extending into the right kidney hilum. After embolisation, some areas of the tumour remained vascular.
Fig. 3. (a,b,c) Non-enhanced multi-detector computed tomography urogram (CTU) scan, after arterial embolisation of the right AML, reveals that the tumour is persisting  but becomes smaller than before; axial, coronal and sagittal sections. (d,e,f) Post-contrast CTU scan after arterial embolisation demonstrates that some areas of the tumour remain vascular; axial, coronal and sagittal sections.



Routine biochemical blood tests including platelet count, blood clotting profile, and renal function were all normal. Urinalysis was also normal.
The decision was made to perform right partial nephrectomy aiming at removing the whole tumour with clear margins and preserving the rest anatomy and function of the kidney under general anaesthesia. The partial nephrectomy was quite difficult as it was a large vascular mass arising from the upper part of the right kidney. We managed to preserve about half to two thirds of the kidney which looked viable at the end of the procedure. The estimated blood loss was 500 ml.
After the operation, the patient was transfused two blood units as his hemoglobin dropped. Pain settled with Patient-controlled analgesia (PCA) 5 ml/hr. Drain was taken out after two days and catheter was removed once the pain was under control. Blood tests and renal function were normal. He was sent back home after 5 days.
The histological examination reported a 354 g weighing mass which measures 13,5 * 9,8 * 5.0 cm. The anterior surface was covered by peritoneum. The surgical resection margin was present at posterior surface. Bivalving reveals that most of the tissue was composed of a well circumscribed, lobulated tumour. There were widespread areas of fat necrosis with foreign body type giant cells. In other areas thick walled blood vessels and radiating epithelioid smooth muscle cells were seen. There was no increased mitotic activity. The adrenal gland was present and normal. The definitive diagnosis was angiomyolipoma (AML) in the right kidney with no evidence of any malignancy.
After 6 weeks, abdominal examination in urology clinic revealed a well healed subcostal incision but with a tender drain wound in the periumbilical region. The rest of his abdomen was soft and non-tender. After 6 weeks the pain settled.

Case presentation 2

A 63-year-old female presented to the gastroenterology clinic as a part of her investigation for microcytic anaemia with low hemoglobin concentration (6.6 g/dL). She had a history of miscarriage, benign skin tumour on her right thigh (papilloma), hypertension, endoscopic bilateral occlusion of fallopian tubes (sterilization), motor vehicle accident (RTA), ischemic heart disease (IHD) and fainting attacks. She had a family history of mental disorders; however there was no history of tuberous sclerosis. After she had oesophagogastroduodenoscopy (OGD) which revealed the presence of acute haemorrhagic gastritis, she underwent a computed tomography (CT) scan.
Abdominal CT scan assured the presence of erosive gastritis and a moderate hiatus hernia was noted. The liver was normal with no focal lesions. Both lungs were normal. Gallbladder was contracted and contained a gallstone with peripheral curvilinear calcification. There was minimal intrahepatic duct dilation. There was a low-density lesion in the spleen measuring 2.8 cm consistent with a simple cyst. The bowel was well demonstrated and showed an evidence of diverticular disease in the sigmoid and descending colon. The surprising radiological manifestation was a large mass arising from the left kidney measuring 12 * 13 cm. The bladder was moderately distended. According to the result of the previous CT, our patient underwent ultrasound test which revealed that there was a mass arising from her left kidney.
She was admitted to our urology unit to evaluate her renal mass with no urological symptoms. Her abdomen was soft and non-tender.
In order to ascertain the diagnosis, she underwent multi-detector computed tomography urography (CTU) which reported a 15 cm left lower pole fatty mass and mesenteric vessels were splayed over its surface, however the majority of the left kidney was normal (Figure 4).
Fig. 4. (a) Enhanced multi-detector computed tomography urogram (CTU) scan demonstrates the presence of AML; axial section. (b,c) Enhanced CTU scan demonstrates a hypodense mass arising from the lower pole of the left kidney and impinging on surrounding structures; coronal and sagittal sections.



No renal vein invasion was detected. Abdominal magnetic resonance imaging (MRI) was also performed and revealed that there  was  a  large  heterogeneous  fatty  mass centered  in  the  left  retroperitoneum,  involving  the  lower pole  of  the  left  kidney,  with  displacement  of  the small bowel and descending colon (Figure 5). 

Fig. 5. (a,b) Abdominal magnetic resonance imaging (MRI) demonstrates a large heterogeneous fatty mass (AML) in the left retroperitoneum. (c) MRI demonstrates AML involving the lower pole of the left kidney with displacement of the duodenum, small bowel and descending colon.



The diagnosis of AML arising from the lower pole of the left kidney was confirmed. However, the decision was made to perform partial nephrectomy as liposarcoma was slightly suspected. After three months, left partial nephrectomy was performed under general anaesthesia leaving 80 percent of the left kidney behind. The estimated blood loss was 750 ml. On the next day her pain settled with Patient-controlled epidural analgesia (PCEA). After two days drain was taken out and she was passing good volume of clear urine. She was sent back home after 5 days.
The histological examination was consistent with angiomyolipoma in the left kidney with no evidence of any malignancy.

References

1- Steiner MS, Goldman SM, Fishman EK, Marshall FF: The natural history of renal angiomyolipoma. J Urol 1993, 150:1782-1786.
2- Nelson CP, Sanda MG: Contemporary diagnosis and management of renal angiomyolipoma. J Urol 2002, 168(1):1315-1325.
3- Blute ML, Malek RS, and Segura JW: Angiomyolipoma: clinical metamorphosis and concerns. Urol 1988, 139(1):20-24.
4- Seyam RM, Bissada NK, Kattan SA, et al. Changing trends in presentation, diagnosis and management of renal angiomyolipoma: comparison of sporadic and tuberous sclerosis complex-associated forms. Urology. 2008; 72:1077-82.
5- Winterkorn EB, Daouk GH, Anupindi S, et al. Tuberous sclerosis complex and renal angiomyolipoma: case report and review of the literature. Pediatr Nephrol. 2006; 21:1189-93.
6- Simmons JL, Hussain SA, Riley P, Wallace DM: Management of renal angimyolipoma in poatients with tuberous sclerosis complex. Oncol Reports 2003, 10:237-241.
7- Oesterling JE, Fishman EK, Goldman SM, Marshall FF: The management of renal angiolipomas. J Urol 1986, 135:1121-1124.
8- Bissler, JJ, Kingswood, JC. Renal angiomyolipomata. Kidney Int 2004; 66:924.
9- Soulen, MC, Faykus, MH Jr, Shlansky-Goldberg, RD, et al. Elective embolization for prevention of hemorrhage from renal angiomyolipomas. J Vasc Interv Radiol 1994; 5:587.
10- Yamakado, K, Tanaka, N, Nakagawa, T, et al. Renal angiomyolipoma: Relationships between tumor size, aneurysm formation, and rupture. Radiology 2002; 225:78.
11- Lucky MA, Shingler SN, Stephenson RN. A case report of spontaneous rupture of a renal angiomyolipoma in a post-partum 21-year-old patient. Arch Gynecol Obstet. 2009 280:643-5.
12- Morales JP, Georganas M, Khan MS, et al. Embolization of a bleeding renal angiomyolipoma in pregnancy: case report and review. Cardiovasc Intervent Radiol. 2005; 28:265-8.
13- Smith's General Urology 16th ed 2003.
14- Curry, NS. Small renal masses (lesions smaller than 3 cm): Imaging evaluation and management. AJR Am J Roentgenol 1995; 164:355.
15- Wright T and Sooriakumaran P. Renal angiomyolipoma presenting with massive retroperitoneal haemorrhage due to deranged clotting factors: a case report. Cases Journal 2008, 1:213.
16- Wang, LJ, Wong, YC, Chen, CJ, See, LC. Computerized tomography characteristics that differentiate angiomyolipomas from liposarcomas in the perinephric space. J Urol 2002; 167:490.
17- Dickinson M, Ruckle H, Beaghler M: Renal angiomyolipoma: optimal treatment based on size and symptoms. Clin Nephrol 1998, 49(5):281-286.
18- Byrd, GF, Lawatsch, EJ, Mesrobian, HG, et al. Laparoscopic cryoablation of renal angiomyolipoma. J Urol 2006; 176:1512.
19- Ewalt, DH, Diamond, N, Rees, C, et al. Long-term outcome of transcatheter embolization of renal angiomyolipomas due to tuberous sclerosis complex. J Urol 2005; 174:1764.
20- Kothary N, Soulen MC, Clark TW, et al. Renal angiomyolipoma: long-term results after arterial embolization. J Vasc Interv Radiol. 2005;16:45-50.
21- Sooriakumaran P, Gibbs P, Coughlin G, et al. Angiomyolipomata: challenges, solutions, and future prospects based on over 100 cases treated. BJU Int. 2010; 105:101-6.
22- Prevoo W, van den Bosch MA, Horenblas S. Radiofrequency ablation for treatment of sporadic angiomyolipoma. Urology. 2008; 72:188-91.
23- Ch Kwok P, Interventional Radiological Treatment of Renal Angiomyolipoma. The Hong Kong Medical Diary Vol.15 No.7 July 2010; 15-16.
24- Silverman SG, Tuncali K, vanSonnenberg E, et al. Renal tumors: MR imaging guided percutaneous cryotherapy--initial experience in 23 patients. Radiology. 2005; 236(2):716-24.
 


Date added to bjui.org: 17/11/2010 (publication information)
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CASE REPORTS: Unusual Giant Renal Angiomyolipoma (Renal Hamartoma): Clinical manifestation, Radiology, Pathology and Treatment

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