|Year : 2001 | Volume
| Issue : 1 | Page : 1-9
Renal angiomyolipoma in Indian population - a single center experience and review of literature
Sanjay Gogoi, Anant Kumar, Bhavna Mehta, Aneesh Srivastava, Anil Mandhani
Department of Urology & Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow., India
Department of Urology, SGPGIMS, Rae Bareilly Road, Lucknow - 226 014
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Introduction: Angiomyolipoma is an under-reported entity from the Indian subcontinent. This study was undertaken to analyze our decade long experience in the management of renal angiomyolipoma (AML).
Material and Methods: A total of 12 patients with 20 AML attended our center between July 1989 & December 1999. The mean age at presentation was 46.6 years with a female to male ratio of 2:1. Majority had solitary unilateral disease and bilateral lesions were seen in 2 patients. 25% of patients had associated tuberous sclerosis. A review of all imaging studies and repeat histopathological analysis was undertaken to evaluate the diagnostic pitfalls and tumor characteristics.
Results: 83.3% of our patients were symptomatic with loin pain being the predominant symptom (33.3%). 3 cases presented with large palpable lumps. I patient presented with a hemorrhagic shock (Wunderlich's syndrome). 2 of our patients were asymptonnatic (one detected during obstetrical USG and other during live donor nephrectomy).
Renal USG and CT scan were highly suggestive of AML in 66.7% and 80% of patients respectively. The mean tumor attenuation value on CT scan was -53.4 H. U. Histopathologically multicentricity was a predominant finding in tuberous sclerosis.
Mean tumor size was 7.4 cm with an equal number of patients in group I (< 4 cnn) and group II (> 4 cm). Of the group I patients treated conservatively; 75% could be managed for a mean duration of 33.3 months without aggravation of symptoms or any major complications. 50% of group II patients elected, for conservative management. All of these patients required surgical intervention at a mean duration of 7 months, one on account of major complication (spontaneous bleeding).
Conclusion: Our experience validates the presently accepted recommendation of conservative management in renal AML less than 4 cm in size with regard to probability of complications. However we found a poor correlation between tumor size and severity of symptoms and early intervention may be judiciously offered for relief of symptoms.
Keywords: Angiomyolipoma; Kidney; Tuberous Sclerosis.
|How to cite this article:|
Gogoi S, Kumar A, Mehta B, Srivastava A, Mandhani A. Renal angiomyolipoma in Indian population - a single center experience and review of literature. Indian J Urol 2001;18:1-9
|How to cite this URL:|
Gogoi S, Kumar A, Mehta B, Srivastava A, Mandhani A. Renal angiomyolipoma in Indian population - a single center experience and review of literature. Indian J Urol [serial online] 2001 [cited 2019 Jul 22];18:1-9. Available from: http://www.indianjurol.com/text.asp?2001/18/1/1/37371
Renal angiomyolipoma is an uncommon benign tumor accounting for less than 1% of surgically excised renal tumors. Although considered benign their presentation may span from an incidentally detected innocuous lesion on one hand to a hurricane course with hypotension & shock as seen in spontaneous bleeding.
| Introduction|| |
While the English literature has numerous reports and articles on angiomyolipomas, it is yet an under-reported entity from the Indian subcontinent. Medline search revealed only four case reports and no long-term series.
This study was undertaken to review the biological behavior of this tumor in the Indian population as well as to review the opinion in the world literature.
| Materials and Methods|| |
All cases of renal angiomyolipoma that attended our center between July 1989 and December 1999 were retrospectively analyzed with an aim to study their natural history, diagnostic dilemma and treatment outcome. A repeat analysis of all biopsy specimens was done to confirm the diagnosis and to evaluate the ultrastructural character of the lesion. All patients who were alive were re-evaluated either by clinical examination and radiological imaging or through their response to objective questionnaires.
Patients were considered to have associated tuberous sclerosis based on the Gomez criteria [Table - 1] and rest were labelled as sporadic angiomyolipoma. For comparative assessment patients were classified into group I (< 4 cm) and group II (> 4 cm) based on the size of the largest lesion.
| Results|| |
A total of 12 patients with 20 angiomyolipomas attended our center between July 1989 and Dec. 1999. The mean age at presentation was 46.6 years (range 24 to 63 years). Majority of our patients were females, with the female to male ratio of 2:1 (8 females and 4 males). Bilateral lesions were present in 2 patients and rest all had solitary unilateral lesions. 3 of our patients could be categorized as suffering from tuberous sclerosis, I on the basis of cutaneous signs and 2 by virtue of having bilateral renal angiomyolipomas.
The presenting features are tabulated in [Table - 2]. All except two of our patients were symptomatic (83.3%). In these 2 patients, the lesions were incidentally detected while undergoing radiological assessment for some other pathology. Mild to moderate loin pain was the commonest complaint (33.3%).
Pain associated with hematuria occurred in 16.7% of cases. Both of these patients had intermittent gross hematuria associated with vermiform clots and clot colic. Isolated painless hematuria was the presenting complaint in one case (8.3%).
3 cases presented with palpable lumps (25%). One was asymptomatic, the second one had a painful lump & the third patient presented to emergency with acutely painful, rapidly increasing loin lump along with hemorrhagic shock (Wunderlich's syndrome).
Size of lesions and correlation with symptoms
Size of the lesions ranged from 1.5 to 19 cm with a mean of 7.4 cm. Both group 1 (< 4 cm) & group II (> 4 cm) had equal number of patients (6 each). [Table - 3]
Out of the 6 group I patients, 2 were asymptornatic & were incidentally detected (one during live donor nephrectomy and the other during obstetrical ultrasound) & the rest had mild to moderate symptoms. 4 out of group I patients including one diagnosed during pregnancy were treated conservatively until they became overtly symptomatic or lesion size increased to greater than 4 cm. The mean duration of conservative management was 33.3 months (range 12-48 months). Tumor growth was evident in 3 out of these 4 patients (75%). One patient did not have growth in the tumor size, however he opted for surgical treatment due to intractable pain.
Of the group II patients, 4 had long-standing symptoms, one was asymptomatic and one presented with spontaneous bleeding and shock. The mean size of tumor in this group was 10.2 cm (5-19 cm). All of these patients were advised surgical treatment, however 3 of these patients with minimal symptoms decided for conservative treatment. 2 of these became overtly symptomatic within a mean period of 8.5 months and the initially asymptomatic patient presented with spontaneous bleeding at 4 months. Thus all the three group II patients treated conservatively required intervention at a mean duration of 7 months.
Number of lesions
Majority of our patients including 1 with associated tuberous sclerosis had unilateral solitary tumors (80%). In only 2 patients tumors were present bilaterally and both had multiple lesions.
Presenting symptoms in patients with bilateral tumors were similar to those with unilateral tumors. However they were more accurately diagnosed radiologically and presented earlier for treatment.
Sporadic angiomyolipoma versus tuberous sclerosis
Amongst sporadic angiomyolipoma the mean age of presentation was 52.6 years compared to the younger age (28.6 years) of presentation in cases with tuberous sclerosis. In both subtypes female preponderance was seen. The right kidney was more commonly involved (66.6%) in sporadic angiomyolipoma compared to bilateral involvement in the latter. There was no significant difference in the tumor size between two subtypes. [Table - 4]
Association with tuberous sclerosis
Of the three cases with tuberous sclerosis two had bilateral angiomyolipomas. One had unilateral solitary lesion along with adenoma cebaceum [Figure - 1], shagreen patches, periungual fibromas & associated history of seizures. The largest lesion in two of these patients measured more than 8 cm, and was electively treated surgically. The third patient had lesions smaller than 4 cm and could be managed conservatively for 4 years, during which period the largest lesion grew to 5.3 cm and symptoms aggravated.
Ultrasound findings were highly suggestive of renal angiomyolipoma in 8 of our patients (66.7%). All of these had characteristic hyperechoic lesions [Figure - 2]. Of the four patients in which the diagnosis was missed two had large mixed echogenic lesions thought to be renal adenocarcinoma. The other two patients had less than 4 cm tumor, however one had a small medially located tumor and was misdiagnosed as renal pelvic transitional cell carcinoma & the other patient was an asymptomatic voluntary kidney donor whose radiological evaluation during the donor workup had failed to detect the lesion.
CT demonstration of fat densities within the masses clinched the diagnosis in 8 of our 10 patients (80%) in whom CT was done [Figure - 3]. The CT Houndsfield units (H.U) of these tumors varied between -26 to -65 (mean -53.4 H.U). Of the two cases where CT was non-diagnostic, one had a suspicious patchily enhancing large lesion and the other had a medially located tumor with pelvic indentation suggesting renal pelvic transitional cell cancer. Lymphadenopathy was evident on CT in 2 patients (18.2%). In both cases the lymph nodes were less than 2 cm and were uncharacteristic.
Angiography was performed in three cases of which digital substraction angiography (DSA) was performed in two. Angiographic findings of hypervascularity, enlarged interlobar and interlobular feeding arteries, tortuous ectatic vessels & multiple peripheral microaneurysms corroborated the CT findings of angiomyolipoma in the first two patients [Figure - 4]. The third patient with normal USG findings underwent angiography as a part of donor workup. Angiographic findings were not diagnostic in this patient.
Tumor size of the largest resected lesion ranged from 1.5 to 19 cm. The gross appearance of the tumor in all cases was yellowish brown with areas of hemorrhage and necrosis. The tumor had sharp borders in all cases except in three with multicentricity.
Histologically all cases showed proliferation of mature red cells, smooth muscle cells and abnormal thick-walled blood vessels in varying proportions. Other features included nuclear atypic of smooth muscle cells in one and ring of ossification and entrapped tubules around the tumor in one case. The origin of smooth muscles from the vessel wall could be appreciated in two cases. No lesion was of the epitheliod variant. Resected lymph nodes in two cases showed only reactive changes.
The patient of tuberous sclerosis with cutaneous stigma had a macroscopic solitary lesion. However on thorough sampling multicentricity was found. None of the other patients with solitary lesion had multicentricity.
Conservative treatment was offered to patients with lesion less than 4 cm in size and minimal symptoms. Patients with larger tumors and symptomatic small tumors were offered surgical management.
Conservative management was carried out in 4 out of 6 group I patients in whom radiological diagnosis was convincing. 3 out of these 4 patients could be managed conservatively for a mean duration of 33.3 months; during this period all had tumor growth despite no aggravation of symptoms. The fourth patient became overtly symptomatic after 6 months, despite a minimal tumour growth (3.5 to 4 cm). While 2 of these patients underwent nephrectomy, the other 2 underwent tumor enucleation including the patient with bilateral tumors who underwent initial angioembolization.
Two group I patients were treated surgically at presentation; one underwent nephroureterectomy with the erroneous diagnosis of renal pelvic transitional cell carcinoma and the other underwent donor nephrectomy.
One of the group 11 patients presented in shock and underwent emergency nephrectomy successfully. The others were advised surgical intervention. However only two patients agreed for nephrectomy and the rest including one with tuberous sclerosis decided to postpone surgery. All of these three patients returned for surgical management after a mean period of 7 months (4 - 11 months). While one came with spontaneous bleeding [Figure - 5], the other two returned with intractable pain. Two of these patients underwent nephrectomy, while one with tuberous sclerosis underwent tumor enucleation.
| Follow-up|| |
Of our 12 patients 11 are alive at a median follow-up of 36.9 months (12-60 months). One patient died in the perioperative period due to respiratory arrest secondary to overdose of narcotics. All the rest, except one of our patients had been in regular follow-up. This patient responded to an objective questionnaire that was mailed to her.
Out of the two living tuberous sclerosis patients one had a 4 x 4 cm residual tumor in the un-operated side. After a follow-up of 6 years, patient continues to be asymptomatic despite an increase in the size of the lesion to 6 x 5 cm. In spite of advice, patient has refused surgery. The other patient as yet has not developed any recurrence and is asymptomatic. None of our patients with unilateral tumour developed recurrence and all of them continue to be symptomatic.
| Discussion|| |
Renal angiomyolipoma has been known to occur in two different clinical settings: in association with tuberous sclerosis and sporadically. Of our 12 patients 9 (75%) had sporadic angiomyolipoma and the other 3 (25%) had associated tuberous sclerosis. [Table - 4]
Amongst those presenting with sporadic angiomyolipomas, the mean age at presentation was 52.6 years and the female to male ratio 1.25:1. Of the female patients all were post-menopausal with a mean age of 56.8 years. The right kidney was twice more frequently involved than the left. All of these sporadic patients had solitary lesion and no multifocality was evident microscopically.
Of those presenting with tuberous sclerosis, one had cutaneous & ocular stigmata and the rest had bilateral renal angiomyolipoma. All three were female patients with a mean age of 28.6 years. While two of these (66%) had bilateral multiple lesions, one had solitary macroscopic lesion. However microscopically multicentricity was present in all.
Of the group I patients treated conservatively, 75% could be managed for a mean duration of 33.3 months. None of these patients had aggravation of symptoms or spontaneous bleeding and indication for intervention was tumor growth. 50% of group II patients declined surgery and were managed conservatively. All of these patients required surgical intervention at a mean duration of 7 months, two on account of symptoms and one because of spontaneous bleeding.
Grawitz coined the term angio-myo-lipoma der niere in 1900 to accurately describe this tumor for the first time. Until recently, most have considered renal angiomyolipomas to be hamartoma but presently strong evidence supports the concept that it is a neoplasm and more precisely termed as choristomas. A common progenitor cell theory was suggested by Green et al after they noticed non-random inactivation of the X chromosome in angiomyolipoma associated with tuberous sclerosis. Bonetti et al proposed that perivascular epitheloid cells is the precursor to all the three cell types seen in angiomyolipoma, and it is demonstrated by immunoreactivity of each of these to HMB-45.
The incidence of angiomyolipoma is usually quoted as less than 1 % of surgically excised renal tumours. However in an unselected population of asymptomatic adults screened ultrasonographically, Fuji et al found incidence of angiomyolipoma to be more common than renal cell carcinoma.
Renal angiomyolipoma presents in two varied clinical spectrums: in association with tuberous sclerosis and sporadically. Stilwell et al reviewed a series of 95 patients with tuberous sclerosis and found that 47% of the patients had angiomyolipomas and of these 71% had bilateral angiomyolipoma and 87% had multiple lesions. Similarly an incidence of 49% was reported by Cook et al amongst their 139 patients with tuberous sclerosis. Different authors have used different criteria for the diagnosis of tuberous sclerosis, accounting for the variability in the reported association with angiomyolipoma. However the revised diagnostic criteria suggested by Gomez et al considers multiple angiomyolipoma to be diagnostic of tuberous sclerosis. [Table - 1]
Approximately 50% of patients with the diagnosis of angiomyolipoma have some or all of the other stigmata of tuberous sclerosis. These patients require more stringent evaluation as angiomyolipoma may also be found in the brain, eye, heart, lung and the bone. These patients tend to be younger, more likely to have multifocal and bilateral disease, more symptomatic and to have larger tumors that are more likely to grow and require surgery.
Sporadic angiomyolipoma present in three varied clinical settings of which the incidentally detected group comprises the majority. Patients with mild to moderate symptoms in the form of local discomfort and gastrointestinal symptoms secondary to compression on the stomach and duodenum comprise the second predominant group. The third group of patients has acute presentation in the form of sudden pain or hypotension because of massive hemorrhage within the lesion, which may have perirenal extension.
Propensity for a patient to be symptomatic is related to the tumor size. More than 80% of tumors larger than 4 cm are symptomatic. Abdominal or flank pain (>50%), hematuria (>20%) and palpable mass (>10%) are the commonest symptoms., Occasionally they present with hypertension and fever of unknown origin., Spontaneous intrarenal or perirenal hemorrhage extending to the retroperitoneum (Wunderlich's syndrome) is a rare presentation and is seen mainly in larger lesions. Its reported incidence is about 10%.
Radiological imaging permits confident diagnosis of renal angiomyolipoma in majority of cases. CT scan estimation of fat density is almost characteristic of an angiomyolipoma. However lesions composed predominantly of smooth muscles may be impossible to distinguish from renal cell carcinoma preoperatively., On the other hand the occasional occurrence of radiologically detectable fat in other renal tumours, such as Wilms tumour and renal cell carcinoma,, can lead to misdiagnosis.
Risk of spontaneous hemorrhage has been correlated with tumor size. Oesterling concluded that the risk of hemorrhage was minor in tumors less than 4 cm in diameter but rose to more than 50% above that size. Van Baal et al considered 3.5 cm to be the diameter above which the risk of hemorrhage is high. On the other hand Koh found that a size greater than 6 cm was associated with hemorrhage and that radiographic demonstration of pseudoaneurysm was a predictor of major life-threatening hemorrhage.
Another potential serious complication is renal failure. Multiple bilateral lesions cause renal insufficiency in approximately 15% patients with tuberous sclerosis and this contributes significantly to the mortality and morbidity.,
Renal angiomyolipoma very rarely invades into the renal venous ststem. It may involve only the renal veins  or extend into the vena cava., Very rarely it may extend up to the right atrium. Lymphadenopathy associated with angiomyolipoma is rare and is believed to be manifestation of multifocality rather than metastasis. Longitudinal follow-up of up to 20 years of such patients with lymphadenopathy have confirmed its benign nature.
Epithelioid variant of angiomyolipoma is an uncommon variant of angiomyolipoma with characteristic histological and immunohistochemical features., These tumors are associated with large, locally infiltrative lesions with tendency for local recurrence.
Not all patients diagnosed with angiomyolipoma warrant intervention. Current management options consider patient's symptoms or size of the lesion as a determining factor. Asymptomatic lesions smaller than 4 cm size may not require therapy but must be observed. Many of these small tumors do not increase in size even after years of follow-up. In a retrospective analysis Dickinson et al concluded that small asymptomatic lesions (< 4 cm) tend to remain stable but should be periodically evaluated. Medium sized lesions (4-8 cm) have the most variable behavior necessitating serial imaging studies. Large lesions (> 8 cm) are associated with significant morbidity and due to the potential complications should be electively treated.
Current treatment guidelines recommend renal preservation in patients in whom intervention is indicated. Selective arterial embolization, tumor enucleation and partial nephrectomy are the procedures most frequently employed, especially so in bilateral or multiple lesions or in patients with solitary kidney. The nephrectomy rate has continued to decrease due to reliable preoperative diagnosis with CT scan and ultrasound.
| Conclusion|| |
We believe that ours is the largest series of renal angiomyolipoma reported from the Indian subcontinent. The natural history, complications and treatment outcome were found to be similar to those reported in the West. Our experience validates the presently accepted recommendation of conservative management in renal angiomyolipoma less than 4 cm in size in regard to the probability of complications. However we found a poor correlation between tumor size and the severity of symptoms and early intervention may be judiciously offered for the relief of symptoms. Treatment approach in bilateral angiomyolipoma should be as conservative as possible in view of higher recurrence rate and with the aim to preserve renal function.
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[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5]
[Table - 1], [Table - 2], [Table - 3], [Table - 4]