Renal angiomyolipoma in pregnancy

Abstract

Renal angiomyolipomas (RAMLs), the most common mesenchymal neoplasm of the kidney, occur with a significant female preponderance. Most RAMLs are identified as an incidental finding on renal imaging and remain clinically silent. The quality of evidence guiding treatment approach regarding the indications for active intervention in the general population is poor. Reports of high rates of complications of RAML in pregnancy leading to recommendations for active treatment have been based upon case studies and small case series, potentially affected by reporting and publication bias. No clinical studies or large case series have examined the course of RAML during pregnancy. The literature regarding the course, complications and management of RAML in pregnancy is reviewed.

Keywords

Renal angiomyolipoma pregnancy haemorrhage tumour growth

Introduction

Renal angiomyolipomas (RAMLs) are benign mesenchymal tumours composed of a mixture of vessels, smooth muscle and adipose tissue, classified as belonging to the family of perivascular epithelioid cell neoplasms. There is a female predominance, with female-to-male ratios varying from 2:1 to 16:1 in case series.¹ Fifty to eighty percent of RAMLs occur as a sporadic finding, the other 20–50% being syndromic in individuals with tuberous sclerosis complex (TSC), lymphangioleiomyomatosis (LAM), Sturge–Weber and Birt–Hogg–Dube syndromes.² Rates of RAML in sporadic LAM, TSC and TSC-associated LAM are 30%, 60% and 80%, respectively.^3–5 Perivascular epithelioid cell neoplasms have a common molecular pathogenic mechanism of inactivating genes resulting in hyperactivation of the mammalian target of rapamycin (mTOR) pathway. Tuberous sclerosis complex is a heterogenous condition with a spectrum of clinical manifestations. Inheritance of TSC is autosomal dominant with inactivating genes identified as TSC1 and TSC2; however, up to two-thirds of patients have de novo mutations, and 15–20% have no variant identified through standard genetic testing.⁶

Sporadic RAML are typically associated with smaller size, slower growth (1.9 mm/year in non-pregnant) and unilateral disease, whereas syndromic RAML is associated with younger age at diagnosis, larger and multiple / bilateral tumours, a higher growth rate (12.5 mm/year) and increased risk of complications.^7,8

Renal angiomyolipomas are typically identified as an incidental finding on imaging or detected at routine imaging surveillance of individuals with associated syndromes. In a systematic review, 92% of RAML observed in the general population were asymptomatic over an average follow-up period of 37 months.⁹

The major complication of RAML is intratumoral bleeding and rupture that may lead to flank pain, retroperitoneal haemorrhage, haemodynamic instability and shock. Rates of haemorrhage in case series of sporadic RAML under active surveillance in the general population have ranged from 0.4% to 4.5%, equating to an annual risk of rupture of 1 per 164 to 1 per 909 patient-years.^10,11 Mortality related to rupture in the general population occurred in five cases out of 281 RAML haemorrhages (1.9%) electronically available in English-language published literature.^12,13 All deaths occurred in individuals with TSC-associated RAML with no sporadic RAML mortality. Risk factors proposed for RAML haemorrhage include tumour size, vascular complexity, including the number and size of intratumoral blood vessels, aneurysms and pseudoaneurysms, accelerated growth, syndromic disease and pregnancy.

Other complications of RAML include haematuria, tumour growth (9%), vascular invasion and deterioration in renal function.¹⁴ Rarely malignant mesenchymal tumours (sarcomas) may develop with epithelioid subtype RAML, which make up 3.9% of RAML in total.⁹

Historically, a cut-off for tumour size of 40 mm for sporadic RAML has been used to predict likelihood of complications in the general population.¹⁵ A systematic review found that RAML greater than 40 mm in size were more likely to be symptomatic (34% vs. 6%), increase in size (34% vs. 6%) and haemorrhage (16% vs. 1%).^9,11 As a result, the Canadian Urological Association and the European Association of Urology recommend that asymptomatic RAML less than 40 mm in diameter may be observed, while symptomatic or RAML greater than 40 mm require treatment.^9,16 The relationship between RAML and risk of haemorrhage, however, is not consistent, with some studies revealing no difference in the risk of tumour growth or haemorrhage with tumours smaller or larger than 40 mm.^10,17 Other authors have proposed RAML size of greater than between 60 and 80 mm as being better predictors of haemorrhage in the general population.^17–19

The presence of aneurysmal vessels with a diameter greater than 5 mm has been shown to be associated with an increased risk of retroperitoneal bleeding with a sensitivity of 100% and specificity of 86%.¹⁷ A recent review of six cases of tumour haemorrhage in 150 individuals with RAML found that tumour size at diagnosis, rich blood supply and intralesional aneurysms were associated with odds ratios for haemorrhage of 1.03, 12.09 and 8.5, respectively.¹⁴ Other authors have reported relative risks for rupture of 3.5 for highly vascular RAML and 3.0 for intratumoral aneurysms greater than 5 mm in diameter.^17,20,21 Some authors have recommended treatment for RAMLs that grow at a rate of greater than 2.5 mm per year.²² Xu et al. proposed a scoring system to predict RAML haemorrhage based upon symptoms at presentation, tumour size, growth pattern and tumour blood supply.²³

Computerised tomography angiography (CTA) has better spatial resolution than magnetic resonance imaging (MRI) and is probably superior for assessing tumour vascularity in RAML.^22,24 Magnetic resonance imaging avoids radiation with respect to serially following tumour size and is useful in defining RAML with low-fat content. Doppler ultrasound does not consistently detect or define vascularity, and serial measurements of size are limited by poor intra- and inter-observer reproducibility. Multiphasic CTA is the imaging modality in the investigation of acute RAML haemorrhage and in planning for selective trans-arterial embolisation (S-TAE).

Options for management of RAML include active surveillance, the use of mTOR inhibitors in syndromic disease, and treatment with S-TAE, partial / radical nephrectomy, and rarely cryoablation and radiofrequency ablation.

Selective trans-arterial embolisation has become first-line management for RAML in the general population with a technical success rate of rate of 96%, and emergency control in 96–100% of individuals.^25–27 A systematic review and meta-analysis found S-TAE was associated with a mean 43.3% reduction in RAML volume (from mean 87.9 to 64.7 mL).²⁷ Major complications of S-TAE in the general population occur in 6.9% of patients and include non-target embolisation (2.3%), respiratory compromise (2%), renal abscess formation (1.6%), induced RAML rupture (1%), hypersensitivity reaction (0.6%), urinary retention, urinary tract infection (0.3%), insertion site complication (0.3%) and renal artery spasm (0.3%).¹² A review of 1059 embolisations performed for RAML in the general population found that 163 patients (15.4%) required re-embolisation and 16 (1.5%) received subsequent surgical management.²⁷

Nephrectomy (nephron sparing or radical) is now typically reserved for individuals with life-threatening active retroperitoneal haemorrhage despite attempted embolisation, complex renal vascular anatomy unsuitable for embolisation, where embolisation is not available, or in rare cases where the diagnosis is not clear or there is vascular invasion.²⁸

A high index of suspicion is required to consider RAML haemorrhage in pregnancy, given that placental abruption, uterine rupture, other vascular dissection and rupture (including aortic, renal and splenic artery), hepatic haemorrhage / rupture with HELLP syndrome, adrenal haemorrhage and sepsis with acute pyelonephritis may also cause acute flank pain with hypotension and a fall in haemoglobin. The perception that pregnancy is associated with a significantly increased risk of haemorrhage and rapid tumour growth has led to many authors opining women of reproductive potential or those requiring hormonal therapy are poor candidates for active surveillance and should be recommended for prophylactic treatment prior to pregnancy or hormonal therapy, irrespective of tumour size and vascularity.^22,29 Mean absorbed radiation dose at the mother's skin and uterus with S-TAE have been estimated to be 13.37 and 6.2 mGy, respectively.^30,31 The estimated fetal radiation exposure is therefore below the 10 mGy risk at which there is a stochastic increased risk of later childhood malignancy, and well below the 50 mGy limit estimated to cause fetal harm. Radiation exposure during pregnancy may be reduced by a transradial rather than transfemoral approach.

This review was undertaken because of the potential for previous assertions in published literature having been influenced by reporting in case reports and small case series.

Objective

To review the available literature regarding the course, risk of complications including renal haemorrhage, vascular invasion and rapid tumour growth and the management of RAMLs in pregnancy.

Methods

Previous case reports of RAML in pregnancy were identified by a search of Medline, Embase and Google Scholar from its inception to July 2025 using the terms ‘pregnancy’, ‘renal angiomyolipoma’, ‘kidney haemorrhage’, ‘tuberous sclerosis’ and ‘lymphangioleiomyomatosis’. Abstracts were used to filter results. The references from case series, case reports and review articles obtained were manually reviewed to identify additional studies.

Results

A total of 2296 articles were found using the primary search protocol. From these 154 full-text articles were retrieved, with another 38 articles included from review of full-text article references.

Renal haemorrhage

One hundred and eleven cases of haemorrhage complicating RAMLs related to pregnancy were identified in case reports since 1952. Of these 85 cases had adequate information for analysis – 75 cases of haemorrhage occurring during pregnancy, and a further 10 cases within 4 weeks of delivery (Tables 1 and 2). A further 11 cases of renal haemorrhage were reported in two surveys of adult women from national databases of individuals with TSC.^32,33

Table 1.

Cases of antepartum RAML haemorrhage.

Author / year	Age	P	K	Size (mm)	Shock	Management	Outcome	Syndromic
Kiser 1964	26	2	18	55	Yes	Nephrectomy	VD at term
Cohen 1968	27	1	24		Yes	Nephrectomy	Term delivery
Drips 1968	41	2	35	150	No	Conservative; nephrectomy at time CS	ElCS at k = 37
Cohen 1968	35	7	37		No	Nephrectomy	VD at term
Arrighi 1971	27	4	36		Yes	EmCS then nephrectomy	EmCS at k = 36
Gallagher 1978	25	0	40	150	No	EmCS then nephrectomy	EmCS at k = 40
Swift 1980	19		22	80	Yes	Nephrectomy	Term delivery
Jones 1981	21	0	19	110	No	Conservative	Term delivery
Brody 1982	33		10		No	Nephrectomy	VD at term
Sunanta 1983	40		16	120	Yes	Nephrectomy
Rattan 1983	31	4	31	220	No	Nephrectomy	ElCS at k = 35	TSC
Valvo 1983	27	2	32	180	No	Conservative; nephrectomy pp	ElCS at term
Dumas 1984	29		24		Yes	Nephrectomy	ElCS at k = 32
Lewis 1985	16	0	20	210	No	Nephrectomy		TSC
Lewis 1985	23	2	30		Yes	Nephrectomy	VD at term
Lewis 1985	29	2	38		No	EmCS then nephrectomy	EmCS at k = 38	TSC
Petrikovsky 1990	27	0	27		No	EmCS for PET - Conservative	EmCS at k = 27	TSC
Lee 1994	29		27		Yes	Nephrectomy then IUFD	IUFD, ElCS
Ponsot 1994	26		31	120	Yes	EmCS then embolisation then nephrectomy	EmCS at k = 31
Wolff 1995	29		22		Yes	Nephrectomy
Yanai 1996	31		10		No	Conservative; prior embolisation non-pregnant	ElCS at term	MB
Shah 1999	36	1	26	50	No	Embolisation at k = 28 for repeat haem	Term delivery
Kehagias 1999	33		29		No	Conservative		TSC
Molina 2001	28	0	17	240	Yes	IUFD then nephrectomy	IUFD, VD
Author / year	Age	P	K	Size (mm)	Shock	Management	Outcome	Syndromic
Tanaka 2001	23	1	27	70	No	Conservative; embolisation postpartum	VD at term
Khaitan 2001	25		37		No	Embolisation	VD at term
Morales 2005	28		10	100	No	Embolisation	VD at term
Argente 2006	40		33		Yes	EmCS then nephrectomy	EmCS at k = 33
Raft 2006	40	1	35	200	Yes	EmCS then laparotomy	EmCS at k = 35	LAM
Storm 2006	32	0	39	68	No	Conservative	VD at term	MB
Koh 2007	31		12		No	Conservative	ElCS at term
Al-Ateeqi 2007	26	2	12	68	No	Conservative	VD at term
Al-Ateeqi 2007	29	3	32	770	Yes	Conservative	ElCS at k = 36
Molina 2007	28		33		No	Conservative	ElCS at term
Kontos 2008	28	0	33	70	No	EmCS then nephrectomy	EmCS at k = 33
Binkowska 2009	26	0	20	174	Yes	Embolisation	ElCS at term
Komeya 2010	39		38	115	No	EmCS then embolisation	EmCS at term
Gylmadu 2011	21		25	115	No	Conservative	ElCS at term	MB
Zapardial 2011	30	0	35	110	No	EmCS then embolisation	EmCS at k = 35
Flood 2012	36	0	31		No	Conservative	ElCS at k = 37
Al shami 2012	46	9	31	114	Yes	Failed embolisation; EmCS then nephrectomy	EmCS at k = 31
Ferianec 2013	30	0	9	210	Yes	Nephrectomy	TOP	TSC
Davis 2013	35	2	16	130	No	Embolisation	El CS at term	MB
Iruloh 2013	23	0	34	110	No	Conservative; pp embolisation and nephrectomy	ElCS at term	LAM
Pontis 2013	33	0	34	48	No	Delivery then nephrectomy	EmCS at k = 34
Santos 2014	40	2	18	50	No	Conservative	ElCS at k = 35
Preece 2015	45		24	150	Yes	Embolisation then nephrectomy	ElCS at term
Myoen 2015	37		25	80	Yes	Embolisation	ElCS at term
Liu 2015	31	0	37	80		EmCS then nephrectomy	EmCS at k = 37
Rana 2016	24	0	6		Yes	Nephrectomy	ElCS at term
Uqwamba 2016	26	1	16	150	Yes	Nephrectomy	ElCS at term
Author / year	Age	P	K	Size (mm)	Shock	Management	Outcome	Syndromic
Kira 2016	30	0	19	120	No	Conservative until rebleed at k = 34; Embolisation pp	EmCS at k = 34
Patil 2017	24	0	10	79	No	Embolisation
Ao 2017	30	0	20	100	No	Conservative until rebleed at k = 34; Embolisation pp	EmCS at k = 34
Ng 2018	36		9	120	Yes	Embolisation	ElCS at term
Ng 2018	33		32	77	No	EmCS then embolisation	EmCS at k-32
Nath 2018	30	0	32	185	Yes	EmCS then nephrectomy	EmCS at k = 32
Scharf 2019	30	0	6	140	No	Embolisation at k = 19
Kane 2019	29	4	17	70	Yes	Embolisation	VD at k = 38
Gao 2019	31	1	20	210	Yes	Nephrectomy; IUFD	IUFD	MB
Goes 2019	32		34		Yes	EmCS then embolisation D4 pp	EmCS at k = 34	MB
Liu 2020	39	0	16	217	Yes	Embolisation then TOP	TOP	TSC, LAM
Zhang 2020	38	1	19	159	No	TOP then nephrectomy	TOP
Knapp 2022	30	0	15	200	No	Embolisation at k = 28	ElCS at term	TSC
Khor 2024	30	2	11	76	Yes	Embolisation k = 12	Term delivery
Mao 2024	26		16		No	Embolisation	IUFD	TSC, LAM
Khor 2024	37	3	27	44	Yes	EmCS then nephrectomy; NND	EmCS
Sayuti 2024	37		27	43	Yes	EmCS then nephrectomy; NND	EmCS at k = 27
Basri 2024	30	3	28	43	Yes	EmCS then nephrectomy	EmCS at k = 27
Singla 2024	33	2	33		Yes	EmCS then nephrectomy	EmCS at k = 33
Singla 2024	25	1	35	160	No	IUFD in setting preeclampsia; conservative	VD
Singla 2024	24	0	39	110	No	Conservative	ElCS at term
Sharma 2025	31	1	26	125	No	Nephrectomy	Term delivery
Al-falahi 2025	30	3	28	160	Yes	Embolisation at k = 28	ElCS at term
Albarracin 2025	25	1	37	84	Yes	EmCS then embolisation then nephrectomy	EmCS at k = 37

P: parity; K: gestation (weeks); size: maximal diameter; EmCS: emergency caesarean section; ElCS: elective caesarean section; VD: vaginal delivery; IUFD: intrauterine fetal demise; TOP: termination of pregnancy; pp: postpartum; TSC: tuberous sclerosis complex; MB: multiple bilateral tumours with no genetic diagnosis established; LAM: lymphangioleiomyomatosis; blank spaces: not stated; RAML: renal angiomyolipoma.

Table 2.

Cases of postpartum RAML haemorrhage.

Author / year	Age	P	K	Size (mm)	Shock	Management	Outcome	Syndromic
Rusche 1952	23	1	12 h pp	170	Yes	Nephrectomy pp	VD at term
Shinoda 1985	27	0	Day 15 pp	200	No	Nephrectomy pp
Atalla 1987	39	2	Day 5 pp	30	Yes	Nephrectomy pp	VD at term
Martinez-Pecino 1989	29		Day 15 pp	200	Yes	Nephrectomy	VD
Lucky 2009	21	1	5 h pp	120	No	Embolisation pp	VD	TSC
Iruloh 2013	23	0	2 h pp	144		Conservative	ElCS at term	LAM
Sen 2014	24	0	‘early’ pp	200	No	Conservative	ElCS at term	LAM
Idilman 2014	25		Day 14 pp		Yes	Embolisation pp		MB
Orywal 2015	31	3	‘hours’ pp		Yes	Embolisation pp
Shegenov 2024	‘20s’	3	5 h pp	72	Yes	Nephrectomy pp	ElCS at term

P: parity; K: gestation (weeks); size: maximal diameter tumour; pp: postpartum; VD: vaginal delivery; ElCS: elective caesarean section; TSC: tuberous sclerosis complex; MB: multiple bilateral tumours with no genetic diagnosis established; LAM: lymphangioleiomyomatosis; blank spaces: not stated; RAML: renal angiomyolipoma.

The mean age of women with haemorrhage complicating RAML in pregnancy was 30 years. Parity was reported in 58 cases. Twenty-six women were primigravida, and there were 56 previous pregnancies to the remaining 32 women. Timing of initial pregnancy-related RAML haemorrhage was 11 cases in first trimester, 26 in second trimester, 38 in third trimester and 10 in the postpartum period. The size of RAML associated with haemorrhage was stated in 61 cases. The median and mean maximal diameter of RAML associated with haemorrhage were 110 and 122 mm, respectively (range 30–240 mm; Figure 1). Only one tumour with RAML haemorrhage was less than 40 mm in maximal diameter. The presence of aneurysms or pseudoaneurysms was described in only eight cases of RAML haemorrhage.

Figure 1.

Distribution renal angiomyolipoma (RAML) size associated with haemorrhage.

At the time of presentation with haemorrhage, the diagnosis of underlying RAML was not known in 77 of the 85 women (91%). Thirty-nine of the women (47%) with RAML haemorrhage presented with severe haemodynamic instability/shock.

There were no maternal deaths. There were five cases of intrauterine fetal demise, three cases of neonatal death and three pregnancies were terminated following haemorrhage.

Initial and subsequent management of antepartum RAML haemorrhage in case reports are summarised in Figure 2.

Figure 2.

Initial management of antenatal renal angiomyolipoma haemorrhage.

Eighteen women were initially managed conservatively. Only one of these women presented with shock / haemodynamic instability. Fifteen of these women proceeded to delivery at or near term, while two had repeat episodes of RAML haemorrhage at 34 weeks’ gestation, proceeding to emergency caesarean delivery.

Seventeen women, nine of whom presented with shock, underwent primary S-TAE. One proceeded to emergency caesarean section at a result of rebleeding, the remainder delivering at term.

Seventeen women, 12 of whom who presented with shock, underwent radical nephrectomy as primary treatment.

Twenty women, 11 of whom presented with shock, were delivered by emergency caesarean. Seventeen of these women subsequently underwent nephrectomy and/or S-TAE.

Since the first case of antepartum SAE was described in 1999, only five women have initially been managed with primary nephrectomy.

Of the 10 cases of RAML haemorrhage occurring within 4 weeks of delivery, four occurred following vaginal delivery, three following caesarean delivery and the mode of delivery was not stated in three cases.

Twenty-nine cases of RAML observed during pregnancy without complication have been described in the literature. Mean RAML size was 177 mm (range 75–220 mm). Thirteen of these cases occurred in women with TSC and/or LAM, with a further two cases involving multiple and bilateral RAM without a genetic diagnosis. A further 122 pregnancies in women with syndromic RAML without haemorrhage were described in two surveys of National Association databases.^32,33

Increase in RAML size

Seven case reports of sporadic RAML had multiple measurements available during pregnancy. The RAML size increased in three cases, decreased in one case, remained unchanged in one case and fluctuated in two cases.^34–38 One of the cases describing an increase in size during pregnancy compared measurement using ultrasound with a subsequent measurement by MRI.³⁶

Toei et al. performed a retrospective review of changes in size of syndromic RAML (LAM or TSC-LAM) during pregnancy.³⁹ Of seven untreated RAML (volume 15–57 mL, mean 22 mL) in two women, six demonstrated minor increases in volume during pregnancy. One hypervascular tumour grew rapidly with a relative volume increase of 409% during pregnancy, shrinking spontaneously postpartum to pre-pregnancy size. In comparison, none of seven far larger syndromic RAML which had undergone S-TAE a mean of 22 months prior to pregnancy demonstrated an increase in volume during pregnancy. No cases of RAML haemorrhage occurred during pregnancy in treated or untreated patients.

Vascular invasion

Four cases of vascular invasion by RAML during pregnancy were identified.^37,40–42

Discussion

Statements in published literature regarding RAMLs in pregnancy have included the rarity of tumours, increased risk of haemorrhage and rapid tumour growth during pregnancy and the need for prophylactic intervention, rather than consideration of active surveillance, in women of childbearing age and/or requiring hormonal therapy.^22,29,43 These assertions may have been influenced by reporting and publication bias.

Prevalence of RAML

Very small RAML appears to be common in the general population. A series of consecutive unselected autopsies found very small RAMLs in 17 of 81 (21%) adult non-pregnant women, tumours ranging in size from 0.1 to 10 mm (mean 1.5 mm, median 1.9 mm).⁴⁴ Multiple tumours were found at autopsy in 16%. Sporadic RAML were identified as an incidental finding in 0.6% of women in a series of 61,400 ultrasound examinations performed for a variety of diseases or preventive medical examinations.⁴⁵ The size of RAMLs on ultrasound varied from 3 to 38 mm, with a mean tumour size of 10.8 ± 5.8 mm. Multiple RAMLs were identified on ultrasound in only 5.2% of patients. A study finding the prevalence of RAML on ultrasound in the general population to be 0.13% is likely to have been influenced by 72% of the individuals examined being of male gender.⁴⁶ This data suggests RAML may be more common in pregnancy than has been previously understood.

Increased risk of RAML complications during pregnancy

Numerous authors have ascribed increased risk of RAML complications during pregnancy to hormone receptor expression within tumours. Hormone receptor expression has been reported for oestrogen receptor beta, oestrogen receptor alpha, progesterone receptor androgen receptor and aromatase in up to 100%, 28% 38%, 79% and 10% of RAML, respectively.⁴⁷ Despite this proposed mechanism, only single case reports of rapid RAML growth have been described with the initiation of the oral contraceptive pill, and with ovarian stimulation, respectively.^48,49

A review of English language full-text articles available in MEDLINE over a 5-year period from July 2020 until June 2025 revealed seven case reports of RAML haemorrhage in pregnancy. This compares with 64 cases of RAML haemorrhage in non-pregnant individuals during the corresponding 5-year period, consisting of 45 individual case reports, and a further 19 cases in two case series.

Two surveys of adult female members from national databases of women with TSC have suggested pregnancy is not associated with renal complications of RAML. A survey of women with known RAML from the United States National Tuberous Sclerosis Association found no difference in renal complications in 67 women who had a total of 150 pregnancies, and 12 women who had never been pregnant.³² Renal complications were defined as a composite of RAML-related haemorrhage, hypertension, pain, rupture, renal failure or requirement for embolisation, nephrectomy or renal transplantation. In the ever-pregnant group, nine episodes of renal complications occurred during pregnancy, and 38 episodes of complications while not pregnant.³² For all pregnant women with TSC, the percentage of pregnancies with a reported RAML complication was 3.4%. Considering RAML haemorrhage alone, 30% of women (20/67) with a history of pregnancy and known renal involvement experienced RAML haemorrhage, compared with 11% (2/18) of women with known renal involvement in the never-pregnant group. The authors considered this difference may have been because of the significantly younger age of the latter group.

A survey of 39 adult women from the German Tuberous Sclerosis patient organisation database found the use of the combined oral contraceptive (64%) or pregnancy (39%) was not associated with the overall prevalence of RAML, renal haemorrhage, necessity for nephrectomy or the age at first diagnosis of RAML.³³

There is a paucity of information regarding change in RAML size during pregnancy. Of the 14 RAML in pregnancy where data was available only 1 tumour was noted to have a marked increase in volume during pregnancy.

Eighty-two previously published cases of RAML with venous tumour thrombus in the general population have been described, compared with the four cases in pregnant women, suggesting venous tumour thrombus formation does not occur significantly more often in pregnancy.⁵⁰

Potential for mTOR inhibitors in management of syndromic RAML in pregnancy

In non-pregnant individuals with syndromic RAML with rapid growth (>2.5 mm/year), treatment with mTOR inhibitors (everolimus or sirolimus) may reduce RAML size and prevent RAML growth.^51,52

Individual cases of efficacy of mTOR inhibitor therapy in sporadic RAML in resulting in reduction in size of tumour, marked regression of inferior vena caval tumour thrombus, and a complete and sustained response in the setting of metastatic epithelioid RAML, respectively, have been described.^53–55 Kenerson et al. demonstrated increased levels of phosphor-p70S6K, a marker of mTOR activity in 15 of 15 non-TSC RAML.⁵⁶ A phase II randomised controlled trial investigating the effect of everolimus on tumour size in sporadic RAML demonstrated at least 25% reduction in 58% of patients.⁵⁷

Mammalian target of rapamycin inhibitors reduce the size of RAML predominantly by reducing their highly vascularised components (by 75–100%) and fat-poor compartments.⁵⁸

A systematic review identified 12 cases where everolimus was used throughout pregnancy in solid organ transplant recipients, resulting in one miscarriage and 11 live births.⁵⁹ No fetal or neonatal structural anomalies were observed. In addition, the National Transplantation Pregnancy Registry has enrolled six pregnancies during everolimus use, resulting in two miscarriages and five live births, with no congenital malformations observed.⁶⁰ Yamamura et al. described a woman with TSC receiving everolimus for control of RAML who was found to be pregnant at 7 weeks’ gestation.⁶¹ Everolimus was withheld, bilateral S-TAE was performed at 21 and 24 weeks’ gestation, and everolimus therapy was resumed at 25 weeks’ gestation for the remainder of the pregnancy. The woman gave birth to a normally formed infant at 37 weeks’ gestation, although cardiac tumours thought to be rhabdomyomas due to inherited TSC were present. Maternal and umbilical cord blood everolimus concentrations were 1.1 and 1.0 ng/mL, respectively. In two women, everolimus levels were either undetectable or detectable in very small amounts in colostrum, though there is no published information on levels with breastfeeding.^62,63 Krishna et al. reported the use of sirolimus throughout 10 pregnancies in women with LAM, without fetal health concerns.⁶⁴ Seven of these 10 children were breastfed with continued maternal sirolimus therapy. At a median age of 3.5 years, no reported adverse health outcomes were reported in the children.

The use of administration of maternal mTOR inhibitor therapy for transplacental passage in successfully reducing the size of fetal complicated cardiac rhabdomyoma has been described in 22 cases, and neonatal sirolimus has been used in the management of life-threatening upper airway lymphatic malformations and complicated vascular anomalies in 18 neonates.⁶⁵

Syndromic RAML demonstrates increase in volume following discontinuation of everolimus; however, there was no evidence of rapid regrowth.⁶⁶

Major complications of everolimus therapy in non-pregnant individuals include stomatitis (40–90%), convulsions (22%), irregular menses (65%), urinary tract infections (15%) and upper respiratory tract infections (13–15%).^51,67,68 Low-dose everolimus has been shown to be effective for TSC-associated RAML with only mild adverse effects.⁶⁹

Conclusions

Renal angiomyolipoma–related haemorrhage and rupture should be considered in the differential diagnosis of pregnant women who present with flank or abdominal pain, haemodynamic instability and/or abrupt fall in haemoglobin.

It is unclear from the literature whether pregnancy is associated with a significantly increased risk of RAML complications. There is a lack of international consensus or Society guidelines with respect to the prophylactic management of RAML in women of reproductive age, or women who are diagnosed with RAML for the first time in pregnancy.

An international registry would be useful to prospectively study the course of RAML in pregnancy and factors predictive of RAML complications, to accurately define the indications for intervention both prophylactically prior to pregnancy, and in women first diagnosed with RAML in pregnancy. Retrospective datasets of RAML in women of child-bearing age may be able to be identified by radiomic assessment of large databases of renal computerised tomography and MRI. Imaging features predictive of RAML complications may be able to be identified from such retrospective studies.

Pre-pregnancy assessment of RAML vascularity appears to be best performed by CTA. Studies of change in tumour size during pregnancy could be assessed by non-gadolinium MRI during each trimester and in the postpartum period.

Syndromic and sporadic RAML should be studied as two distinct entities.

Further studies regarding the efficacy of mTOR inhibitor therapy in reducing haemorrhage in syndromic RAML, and overall efficacy in sporadic RAML would be useful.

Further research is required to compare the efficacy and outcome of prophylactic S-TAE and any possible effects on long-term renal function.

Peripartum haemorrhage with RAML is rare, and mode of delivery should be as per obstetric indications.

Footnotes

ORCID iD

Adam Morton

Ethics approval

Waived by Mater Health HREC.

Informed consent

Not applicable.

Author Contributions

AM performed a literature review, wrote and reviewed the manuscript.

Funding

The author received no financial support for the research, authorship and/or publication of this article.

Declaration of conflicting interests

The author declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

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Renal angiomyolipoma in pregnancy – A review

Abstract

Keywords

Introduction

Objective

Methods

Results

Renal haemorrhage

Increase in RAML size

Vascular invasion

Discussion

Prevalence of RAML

Increased risk of RAML complications during pregnancy

Potential for mTOR inhibitors in management of syndromic RAML in pregnancy

Conclusions

Footnotes

ORCID iD

Ethics approval

Informed consent

Author Contributions

Funding

Declaration of conflicting interests

References