Multiple Angiomyolipomas Research Articles

Perivascular Epithelioid Cell-Family Tumors in Children, Adolescents, and Young Adults: Clinicopathologic Features in 70 Cases.

Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors of uncertain histogenesis expressing smooth muscle and melanocytic markers. The clinicopathologic spectrum in young patients is not well documented. To describe a multi-institutional series of PEComas in children, adolescents, and young adults. PEComas, not otherwise specified (NOS); angiomyolipomas (AMLs); lymphangioleiomyomatosis; and clear cell sugar tumors were retrospectively identified from 6 institutions and the authors' files. Seventy PEComas in 64 patients (median age, 15 years) were identified. They were more common in females (45 of 64 patients), occurring predominantly in the kidney (53 of 70), followed by the liver (6 of 70). Thirty-four patients had confirmed tuberous sclerosis complex (TSC), 3 suspected TSC mosaicism, 2 Li-Fraumeni syndrome (LFS) and 1 neurofibromatosis type 1. Most common variants were classic (49 of 70) and epithelioid (8 of 70) AML. Among patients with AMLs, most (34 of 47) had TSC, and more TSC patients had multiple AMLs (15 of 36) than non-TSC patients (2 of 13). Two TSC patients developed malignant transformation of classic AMLs: 1 angiosarcomatous and 1 malignant epithelioid. Lymphangioleiomyomatosis (5 of 70) occurred in females only, usually in the TSC context (4 of 5). PEComas-NOS (6 of 70) occurred exclusively in non-TSC patients, 2 of whom had LFS (2 of 6). Three were malignant, 1 had uncertain malignant potential, and 2 were benign. All 4 PEComas-NOS in non-LFS patients had TFE3 rearrangements. Compared to the general population, TSC was more prevalent in our cohort; PEComas-NOS showed more frequent TFE3 rearrangements and possible association with LFS. This series expands the spectrum of PEComas in young patients and demonstrates molecular features and germline contexts that set them apart from older patients.

68 Ga-FAPI-04 PET/MRI in a Case of Tuberous Sclerosis Complex With Extrarenal Retroperitoneal Angiomyolipoma.

Extrarenal retroperitoneal angiomyolipomas are rare benign tumors that may mimic other benign or malignant retroperitoneal tumors. We describe 68 Ga-FAPI-04 PET/MRI findings in a case of tuberous sclerosis complex with an extrarenal retroperitoneal angiomyolipoma and multiple angiomyolipomas involving bilateral kidneys. The extrarenal retroperitoneal angiomyolipoma and most of the renal angiomyolipomas were 68 Ga-FAPI-04-avid. One left renal angiomyolipoma with extensive hemorrhage and fibrosis had no significant 68 Ga-FAPI-04 uptake. Angiomyolipoma should be included in the differential diagnosis of FAPI-avid renal or extrarenal retroperitoneal lesions.

A rare association of phakomatosis

Simultaneous occurrence of neurofibromatosis and tuberous sclerosis is very rare. A 55-year-old hypertensive man was referred for ophthalmic evaluation. On examination, Lisch nodules were seen over the iris in both the eyes with fundus showing bilateral temporal pallor. Magnetic resonance imaging (MRI) brain was done to rule out optic pathway gliomas. MRI brain was negative for gliomas but showed subependymal nodules in the ventricles, a feature of Tuberous sclerosis. A screening computed tomography (CT) abdomen showed multiple angiomyolipoma in the kidney, which confirmed the diagnosis. It is important to be aware of this rare co-existence so that a devastating consequence can be prevented.

The effect of sirolimus on angiomyolipoma is determined by decrease of fat-poor compartments and includes striking reduction of vascular structures

Renal angiomyolipomas hemorrhage is associated with their size and vascular constitution. The effects of sirolimus on different components of angiomyolipomas was analyzed in patients with tuberous sclerosis complex, sporadic lymphangioleiomyomatosis and multiple sporadic angiomyolipomas. Thirty angiomyolipomas from 14 patients treated with sirolimus were retrospectively evaluated. A Hounsfield-unit threshold was used to classify angiomyolipomas in fat-rich, fat-poor and intermediate-fat tumors, and to categorize tumor compartments in fat rich, fat poor, intermediate fat and highly vascularized. Diameter variations were measured to assess the effects on aneurysmatic/ectatic vascular formations. Volume reduction following treatment with sirolimus was higher in fat-poor than fat-rich angiomyolipomas. Tumor reduction was mainly determined by decrease of the fat-poor and highly-vascularized compartments while the volume of the fat-rich compartment increased. Broad liposubstitution was observed in some tumors. A median reduction of 100% (75 to 100) in the diameter of aneurysmatic/ectatic vascular structures was observed. Our study showed that sirolimus reduces the size of angiomyolipomas by decreasing primarily their highly-vascularized and fat-poor compartments. This effect is associated with a remarkable reduction of tumoral aneurysms/ectatic vessels, revealing the likely mechanism responsible for the risk-decreasing effect of mTOR inhibitors on angiomyolipoma bleeding. These findings support the role of mTOR in the development of angiomyolipoma blood vessels.

Enhancing disease awareness for tuberous sclerosis complex in patients with radiologic diagnosis of renal angiomyolipoma: an observational study

BackgroundTuberous Sclerosis Complex (TSC) is a genetic disorder, with renal manifestations like angiomyolipoma (AML) occurring in 70–80% of patients. AML usually cause more complications in TCS patients than in non-TSC patients. However, AML patients are not routinely investigated for TSC. Our aim was to retrospectively assess the correlation between radiologically diagnosed AML and TSC.MethodsAll patients were stratified into AML related vs. unrelated to TSC. Correlations were calculated to determine the association between age, AML, and TSC.ResultsComplete data were available for 521 patients with renal AML, in 7 of which the concurrent diagnosis of TSC was found. Younger age significantly positively correlated with the prevalence of TSC in AML patients (p < 0.01). 37 (7%) of the 521 patients were within the age-range of 18–40 years, in which TSC occurred in 6 cases, 4 (66.7%) of which presented with multiple, bilateral renal AML (p < 0.05), and 2 (33.3%) of which with a single, unilateral AML (p < 0.05). In patients with AML but without TSC, unilateral AML was found in 83.9% and bilateral AML in 16.1% (p < 0.05). Simple binary logistic regression analysis revealed bilateral AML (OR 33.0; 95% CI 3.2–344.0; p = 0.003) (but not unilateral AML (OR 0.09; 95% CI 0.01–0.88; p = 0.04)) to be a risk factor for TSC.ConclusionsThe presence of bilateral AML in patients within the age-range of 18–40 years should raise suspicion for TSC as the underlying cause. Therefore, our advice is to refer patients with multiple bilateral renal AML for further investigations regarding TSC.

Dissecting TSC2-mutated renal and hepatic angiomyolipomas in an individual with ARID1B-associated intellectual disability

BackgroundSeveral subunits of the SWI/SNF chromatin remodeling complex are implicated in both cancer and neurodevelopmental disorders (NDD). Though there is no clinical evidence for an increased tumor risk in individuals with NDDs due to germline mutations in most of these genes so far, this has been repeatedly proposed and discussed. A young woman with NDD due to a de novo mutation in ARID1B now presented with a large renal (> 19 cm in diameter) and multiple hepatic angiomyolipomas (AMLs) but no other signs of tuberous sclerosis complex.MethodsWe analyzed tumor and healthy tissue samples with exome and panel sequencing.ResultsAdditionally to the previously known, germline ARID1B variant we identified a post-zygotic truncating TSC2 variant in both renal and hepatic AMLs but not in any of the healthy tissues. We did not detect any further, obvious tumor driver events. The identification of a passenger variant in SIPA1L3 in both AMLs points to a common clonal origin. Metastasis of the renal AML into the liver is unlikely on the basis of discordant histopathological features. Our findings therefore point to very low-grade mosaicism for the TSC2 variant, possibly in a yet unknown mesenchymal precursor cell that expanded clonally during tumor development. A possible contribution of the germline ARID1B variant to the tumorigenesis remains unclear but cannot be excluded given the absence of any other evident tumor drivers in the AMLs.ConclusionThis unique case highlights the blurred line between tumor genetics and post-zygotic events that can complicate exact molecular diagnoses in patients with rare manifestations. It also demonstrates the relevance of multiple disorders in a single individual, the challenges of detecting low-grade mosaicisms, and the importance of proper diagnosis for treatment and surveillance.

Retinal astrocytic hamartoma in tuberous sclerosis complex in an elderly person: a case report

BackgroundSpectral domain optical coherence tomography (SD-OCT) is proposed as a way of predicting the development and likelihood of retinal astrocytic hamartoma (RAH) in tuberous sclerosis complex (TSC) in elderly patients.Case presentationThis report describes a case of RAH in TSC in an elderly patient. The patient was a 62-year-old woman and experienced pain in the lower left abdomen for two years. Bilateral renal angiomyolipoma, multiple hepatic angiomyolipoma and multiple pulmonary nodules were demonstrated using computed tomography (CT). Brain CT showed bilateral multiple calcification near by the cella lateralis. A clinical diagnosis of TSC was made. Visual acuity (decimal) in the right and left eye was determined to be 0.6 and 0.8, respectively. SD-OCT revealed a retinal tumour in the inner layer of the retina in the right fundus and a pre-retinal membrane which may have evolved later.ConclusionsA routine ophthalmic examination is advised for patients suspected of having TSC to prevent this condition from being overlooked. In addition, an OCT examination can be used to predict the development and likelihood of RAH.

Atypical tuberous sclerosis complex presenting as familial renal cell carcinoma with leiomyomatous stroma

We report an atypical tuberous sclerosis complex (TSC) phenotype presenting as familial multiple renal cell carcinomas (RCCs) with (angio)leiomyomatous stroma (RCCLS) (5/7 familial RCCs) on a background of multiple angiomyolipomas, hypopigmented skin macules, and absence of neurological anomalies. In the index case and three relatives, germline genetic testing identified a heterozygous TSC2 missense pathogenic variant [c.2714 G > A, (p.Arg905Gln)], a rare TSC‐associated alteration which has previously been associated with a milder TSC phenotype. Whole‐exome sequencing of five RCCs from the index case and one RCC from his mother demonstrated either unique tumour‐specific deleterious second hits in TSC2 or significant allelic imbalance at the TSC2 gene locus (5/6 RCCs). This study confirms the key tumourigenic role of tumour‐specific TSC2 second hits in TSC‐associated RCCs and supports the notion that RCCLS may be strongly related to abnormalities of the mTOR pathway.

IMPORTANCE OF SCREENING FOR LUNG LYMPHANGIOLEIOMYOMATOSIS AMONG RENAL ANGIOMYOLIPOMA CASES

(Background) Multiple renal angiomyolipoma (AML) may develop concurrently with tuberous sclerosis complex (TSC) and lung lymphangioleiomyomatosis (LAM). In recent years, an increase in subjects undergoing chest computed tomography examinations, including medical examinations, has been accompanied by an increase in LAM cases that are diagnosed while still asymptomatic. Surgical treatment may also be performed for renal AML to prevent bleeding. We clarified the clinical features of AML that is complicated by LAM, and discussed the significance of screening for LAM. (Methods) Between January 1, 2006 and April 30, 2014 two groups, comprising 7 patients with LAM (LAM-AML group) and another 26 patients without LAM (sporadic AML group), were compared with regard to findings for renal AML such as imaging examinations, pathological features, and treatment course. Screening for LAM was chest CT scanning. (Results) In the LAM-AML group, there were younger and more female cases and tumors tended to be multiple, large and bilateral. 85.7% of cases underwent surgery. On the other hand, in the sporadic group 73.1% of cases were followed up without treatment. There was no preoperative lung screening except the one TSC case and all 5 LAM cases were diagnosed postoperatively. One LAM patient was symptomatic and eventually required lung transplantation, while all other LAM cases were handled by monitoring the course, without treatment. (Conclusion) Many cases of asymptomatic LAM are untreated. However, the poor prognosis, risk of a need for general anesthesia, and potential for renal sparing by selection of pharmacotherapy must be taken into account. In that light-especially in the case of young women-patients with multiple renal AML should undergo preoperative screening for LAM.

Tuberous sclerosis complex: Hamartin and tuberin expression in renal cysts and its discordant expression in renal neoplasms

Tuberous sclerosis complex (TSC) results from mutation of TSC1 or TSC2 that encode for hamartin and tuberin. It affects the kidneys often in advance of extra-renal stigmata. We studied 14 TSC cases, and 4 possible TSC cases with multiple angiomyolipomas (AMLs) for hamartin and tuberin protein expression to determine if the staining profile could predict mutation status or likelihood of TSC with renal-limited disease. The 18 cases included 15 nephrectomies and 1 section of 6 TSC-associated renal cell carcinomas (RCC). Controls included the non-neoplastic kidney in 5 tumor nephrectomies, 4 sporadic cases of AML and 6 clear cell RCCs. In the 14 TSC cases, 9 had AMLs, 9 had RCCs, 5 had polycystic kidney disease and 8 had eosinophilic cysts (EC) lined by large eosinophilic cells. The controls and study cases showed luminal staining of proximal tubules (PT) and peripheral membrane staining in distal tubules/collecting ducts for hamartin and cytoplasmic staining for tuberin. Eosinophilic cysts had a luminal PT-like stain with hamartin and a cytoplasmic reaction for tuberin. Hamartin stained myoid cells in all AMLs. Tuberin was negative in all but 1AML, an epithelioid AML. All but 1 RCC were positive for tuberin; 13 RCCs (7 TSC/6 non-TSC) were negative for hamartin and 4 showed a weak reaction. We conclude that the ECs of TSC are proximal tubule-derived. The hamartin and tuberin staining profiles of AMLs and most RCCs are reciprocal precluding prediction of the mutation in TSC, and fail to predict if a patient with multifocal AML has TSC.

Combination of Superselective Arterial Embolization and Radiofrequency Ablation for the Treatment of a Giant Renal Angiomyolipoma Complicated with Caval Thrombus.

This is a case of a 78-year-old male patient with multiple angiomyolipomas of a solitary right kidney. The largest of these tumors (maximum diameter: 13.4 cm) caused significant extrinsic compression of the inferior vena cava complicated by thrombosis of this vessel. Treatment of thrombosis with anticoagulants had been ineffective and the patient had experienced a bleeding episode from the largest right renal angiomyolipoma, which had been treated by transarterial embolization in another institution, 4 months prior to our intervention. Our approach included superselective transarterial embolization of the dominant, right kidney angiomyolipoma with hydrogel microspheres, which was combined, 20 days later, with ultrasonographically guided radiofrequency ablation. Both interventions were uneventful. Computed tomography 2 months after ablation showed a 53% reduction in tumor volume, reduced space-occupying effect on inferior vena cava, and resolution of caval thrombus. Nine months after intervention the patient has had no recurrence of thrombosis or hemorrhage and no tumor regrowth has been observed. The combination of superselective transarterial embolization and radiofrequency ablation seems to be a feasible, safe, and efficient treatment of large renal angiomyolipomas.

Renal involvement in tuberous sclerosis complex.

Dear Editor, I think that the research article published in Volume 50, issue 1, 2015 in your journal between the pages of 51 and 60 titled “Tuberous sclerosis complex; a single center experience” written by Erol et al. (1) is an important article in terms of emphasizing awareness of this clinical condition. Tuberous sclerosis is a rare disease with genetic inheritance which may involve any organ system. As stated in the international diagnostic criteria, the importance of physical examination can not be denied in the diagnosis of tuberous sclerosis complex. Recognition of specific lesions including hypomelanotic macules (>3), Shagreen patch, forehead plaque, non-traumatic fibromas around nails and adenoma sabaceum (angiofibromas on the face) which can be identified on examination of the skin should suggest tuberous sclerosis (2, 3). Renal or lung involvement is observed more commonly in the adult patient group. Renal involvement is present in 50–80% of all patients (4). Renal involvement is most commonly manifested by angiomyolipomas. Presence of bilateral and multiple angiomyolipoma especially in the kidney on imaging is a significant clue. Massive hemorrhage which develops suddenly may require an urgent approach. Nephrectomy may be needed or hemorrhage may result in exitus. Patients may present with end stage renal disease in the adulthood. There is a risk of development of renal cell carcinoma (∼%1) and oncocytoma, albeit low. Presence of rapid growth in renal lesions, calcifications and central necrosis should raise suspicion in terms of malign transformation (5). The finding that there was no malignancy in the study of Erol et al. (1) may be related with the fact that the study was conducted with children. Signs including bloody urine and side pain should be absolutely evaluated in this patient group. In conclusion, recognition of skin lesions by good inspection will allow physicians to make a diagnosis of tuberous sclerosis and enable nephrologic follow-up of these cases. Renal function tests should be monitored, hypertension should be controlled and renal lesions should be monitored by radiological imaging regularly. Renal involvement is the second cause of death after central nervous system disorders in the childhood and the first cause of death in the adulthood (6). This retrospective study of Erol et al. (1) is important in terms of raising awareness and clinical suspicion. I thank the authors and you for this nice article.

術前診断に難渋した若年女性の多発性肝血管筋脂肪腫の1例

症例は22歳女性．胃腸炎症状で腹部超音波検査施行した際，肝左葉外側区域に10 cm大の肝腫瘍を指摘され，精査目的で入院．肝機能は正常，HBV，HCVの肝炎ウイルスマーカー，腫瘍マーカーは陰性で，各種画像検査から肝細胞腺腫，血管腫，限局性結節性過形成などの良性多血性肝腫瘍が疑われたが，大きさや出血のリスクを考慮して拡大肝左葉切除術を施行した．病理組織学的検査では腫瘍内に短紡錘性細胞が索状に増生し，血管周囲性の配列やわずかに脂肪成分も見られた．免疫染色ではHMB-45陽性であり，主腫瘍周囲にも同様の結節が散見されたことから多発性の肝血管筋脂肪腫と診断した．肝血管筋脂肪腫は血管，筋，脂肪から成る肝良性腫瘍で，脂肪成分を含む割合が様々であり，画像診断が困難なことがある．多発性の肝血管筋脂肪腫は稀であり，若干の文献的考察を加えて報告する．

Tuberous sclerosis-associated renal cell carcinoma: a clinicopathologic study of 57 separate carcinomas in 18 patients.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder with characteristic tumors involving multiple organ systems. Whereas renal angiomyolipoma (AML) is common in TSC, renal cell carcinoma (RCC) is rarely reported. Fifty-seven RCCs from 13 female and 5 male TSC patients were reviewed. Age at surgery ranged from 7 to 65 years (mean: 42 y). Nine patients (50%) had multiple synchronous and/or metachronous RCCs (range of 2 to 20 RCCs) and 5 had bilateral RCCs (28%). Seventeen patients (94%) had histologically confirmed concurrent renal AMLs, including 15 with multiple AMLs (88%) and 9 (50%) with AMLs with epithelial cysts. None of the 15 patients with available clinical follow-up information had evidence of distant metastatic disease from 6 to 198 months after their initial surgery (mean: 52 mo). The 57 RCCs exhibited 3 major distinct morphologies: (1) 17 RCCs (30%) had features similar to tumors previously described as "renal angiomyoadenomatous tumor" or "RCC with smooth muscle stroma"; (2) 34 RCCs (59%) showed features similar to chromophobe RCC; and (3) 6 RCCs (11%) showed a granular eosinophilic-macrocystic morphology. Distinct histologic changes were also commonly present in the background kidney parenchyma and included cysts or renal tubules lined by epithelial cells with prominent eosinophilic cytoplasm, nucleomegaly, and nucleoli. Immunohistochemically, all RCCs tested showed strong nuclear reactivity for PAX8 and HMB45 negativity. Compared with sporadic RCCs, TSC-associated RCCs have unique clinicopathologic features including female predominance, younger age at diagnosis, multiplicity, association with AMLs, 3 recurring histologic patterns, and an indolent clinical course. Awareness of the morphologic and clinicopathologic spectrum of RCC in this setting will allow surgical pathologists to better recognize clinically unsuspected TSC patients.

Is the follow-up of small renal angiomyolipomas a necessary precaution?

To investigate the natural history and rationalize follow-up of renal angiomyolipomas (AMLs). A prospectively gathered radiology database was scrutinized to identify patients with renal AMLs over a 3 year period (January 2006 to December 2008). Radiological investigations were examined to identify those AMLs exhibiting change during surveillance. A total of 135 patients were identified. Mean age at first detection was 49.6 years and patients were followed up for a median 21.8 months (6-85.3 months). Small AMLs (≤20 mm) were less likely to grow than their larger counterparts [odds ratio 13.3, confidence interval (95% CI) 1.4-123.9, p = 0.02] and exhibited a slower growth rate (0.7 versus 9.2 mm/year). Patients with AMLs that increased in size were significantly younger (median age 43 versus 52 years, p < 0.001). Multiple AMLs or those associated with genetic conditions grew at a significantly greater rate (3 versus 0.1 mm/year, p < 0.001). AMLs with a large extra-renal component are less reliably measured on ultrasound (median error 7 versus 1 mm, p < 0.001). This is the first study with the primary purpose to investigate growth of small AMLs (≤20 mm). Small, solitary AMLs (≤20 mm) do not require follow-up due to their low probability of growth. Patients with multiple AMLs and younger patients require closer monitoring due to their comparatively greater AML growth rate. Ultrasound-detected AMLs with an extra-renal component may require computed tomography (CT) to confirm their size.

Prevalence of sporadic renal angiomyolipoma: a retrospective analysis of 61,389 in- and out-patients

To calculate the prevalence, localization, and growth of sporadic angiomyolipomas and to identify the predominant sex in the largest patient population reviewed to date. Abdominal ultrasound analyses of 61,389 patients (49.7% women; 50.3% men) were consecutively collected using a PC-based, standardized documentation system from September 1999 to December 2012. The present study evaluates and presents this data. The population studied includes 270 cases of sporadic angiomyolipoma (184 females; 86 males). This represents an overall prevalence of 0.44%, with 0.60% in the female and 0.28% in the male subpopulations. Mean tumor size was 10.8±5.8mm. Fifty-seven percent of cases involved the right kidney and 43.0% the left kidney. Only 14 of the 270 patients presented with multiple angiomyolipomas, four of which were bilateral. Sixty-one cases were followed over a mean period of 25months (range: 1-105months) and showed no significant increase in tumor size during the period of observation. The analysis of 61,389 patients revealed a higher prevalence of sporadic angiomyolipoma than previously observed in smaller studies. There was a significantly higher prevalence in females than in males. Multiple and bilateral angiomyolipomas were rare, and tumor growth was marginal.

Angiomyolipomas, renal cell carcinomas and pulmonary lymphangioleiomyomatosis.

A 46-year-old female presented with worsening bilateral flank and abdominal pain. Abdominal CT revealed bilateral enlarged kidneys containing lesions suggestive of multiple angiomyolipomas (AML) and bilateral enhancing solid renal masses suggestive of multifocal renal cell carcinoma (RCC) [Table/Fig-1a–b]. A chest CT disclosed multiple random pulmonary cysts and small nodules in both lungs compatible with lymphangioleiomyomatosis (LAM) and multiple micronodular pneumatosis hyperplasia [Table/Fig-1c]. Overall findings were consistent with tuberous sclerosis (TS). The patient underwent bilateral renal artery branches embolization [Table/Fig-1d,e] with resolution of symptoms. Patient had another two admissions with same symptoms and signs, during which she underwent repeat embolizations for renal artery aneurysms. Patient was lost to follow up before initiation of any further therapy. [Table/Fig-1]: Axial (a) and coronal (b) views of contrast-enhanced CT scan of abdomen showing bilateral enlarged kidneys with multiple fat-containing lesions suggestive of angiomyolipomas (white arrows) and multiple enhancing solid renal lesions suspicious of multifocal ... TS should be suspected when common manifestations are found, including renal AML (55-75%) and LAM (26-39%) [1]. AML is one of the leading causes of death in TS patients. Patients are at risk of serious complications such as life-threatening hemorrhage (25%–50%). As the disease progresses, end-stage renal disease leading to dialysis develops secondary to encroachment of AML on normal renal parenchyma [2]. Historically, treatment of TS has focused on watchful waiting and surgical procedures to reduce tumor burden. Embolization is preferred in the setting of recent or active hemorrhage, or when large or multiple aneurysms are present. At the molecular level, loss of the TS complex 1 (TSC1) or TSC2 gene has been associated with increased production of vascular endothelial growth factor (VEGF), and inhibitors of mTOR have been shown to have an inhibitory effect on production of VEGF, tumor growth, and angiogenesis, both in vitro and in vivo. Everolimus is such an mTOR inhibitor approved for the treatment of adults with renal AML and TSC not requiring immediate surgery, based on favorable results from multicenter, international, randomized, double-blind, placebo-controlled trials EXIST-1 and EXIST-2 [2]. In 2–5% of patients with TS, RCC may develop within dysplastic epithelial cysts. Intriguingly, the course of RCC in TS differs from that in the general population. The mean age of TS-associated RCC is 25 years lower than in those without TSC mutations. In addition, TS-related RCC is usually bilateral and is more often found in women. However, RCC may be over-diagnosed in this patient population given the difficulty in differentiating from fat-poor AML with imaging studies alone. Immunostaining is helpful in such cases, with human melanoma black 45 (HMB-45) stain being characteristic for TSC-associated AML and lymphangioleiomyomatosis (LAM), while cytokeratin immunopositivity is typical for RCC [3]. LAM is characterized by cystic destruction of the lung caused by infiltration of smooth muscle cells and affects predominantly women, occurring more rarely in patients without TS (sporadic LAM). Symptomatic relief of air flow obstruction with bronchodilators and oxygen support can be used, as effective treatment options for this condition are lacking [2]. However, clinical evidence suggests that mTOR targeting can benefit other TSC-associated disease manifestations, including pulmonary LAM, thus rendering it a potential systemic treatment option for this genetic multifaceted disorder [4].

Liver transplantation for multiple angiomyolipomas complicating tuberous sclerosis complex

Tuberous sclerosis complex is a genetic multisystem disorder characterised by widespread hamartomas in several organs, including the brain, heart, skin, eyes, kidney, lung, and liver. Hepatic multiple, bilateral angiomyolipomas are a rare and usually asymptomatic complication in patients with tuberous sclerosis. We report here the case of a patient who needed liver transplantation because of debilitating manifestations and mechanical complications of massive liver involvement by multiple angiomyolipomas (severe malnutrition, anorexia and abdominal pain). Seventeen tumors, from 2 to 16 cm in diameter, were identified at examination of the liver explant. No feature suggestive of malignant behaviour was identified at histological examination. In conclusion, this unusual indication of liver transplantation underlines the interest of this therapeutic approach for benign tumors for which the multiplicity of the lesions and their huge volume prevent any attempt at surgical resection.

Laparoscopic Nephron-Sparing Surgery in the Management of Angiomyolipoma: A Single Center Experience

Angioembolization is often the first-line treatment for patients with renal angiomyolipoma (AML). Regrowth and repeated hemorrhage after embolization, however, remain a concern. Laparoscopic partial nephrectomy (LPN) is the definitive, minimally invasive treatment alternative. We compared the outcomes of LPN in patients who had a diagnosis of AML with patients with other renal tumors. From a prospective LPN database, we identified patients with a final pathologic diagnosis of AML (group 1). The ability of preoperative imaging to predict AML final pathology results was studied. Surgical and postoperative outcomes in group 1 were compared with the outcomes of the rest of our LPN cohort (group 2). Of 184 LPNs that were performed between 2002 and 2008, 14 (7.6%) patients and 15 renal units had a diagnosis of AML. Two patients underwent concomitant LPN and radiofrequency ablation (RFA) for multiple AML lesions. In group 1, only 33% of the patients had a preoperative diagnosis of AML. There were no significant differences in tumor size, age, preoperative estimated creatinine clearance, body mass index, and comorbidities between the groups. The mean estimated blood loss in groups 1 and 2 was 214 mL and 178 mL, respectively (P = 0.5). The complication rates were similar between the groups. With a median follow-up of 15 months, no AML recurrences or bleeding was observed in group 1. The results of LPN or RFA, when appropriate, in AML patients are comparable to the results of LPN for other renal tumors. The preoperative imaging studies were a poor predictor of AML in patients who were undergoing LPN.

Two Different Renal Cell Carcinomas and Multiple Angiomyolipomas in a Patient with Tuberous Sclerosis

We report a case of tuberous sclerosis associated with two histologically different renal cell carcinomas (RCCs) and multiple angiomyolipomas (AMLs) in the same kidney. A 43-year-old female was admitted to our hospital with left flank pain and a huge palpable mass in the left flank area. Abdominal computed tomography revealed two concurrent RCCs and multiple AMLs in the left kidney. Because of the clinical suspicion of RCC, the patient underwent left radical nephrectomy. On gross examination, the total size of the resected left kidney was 30.5×17×8 cm. Microscopically, the upper pole tumor features were consistent with chromophobe RCC and the midpole tumor was a clear-cell RCC. The multifocal masses in the remaining remnant parenchyma were AMLs. Six months after surgery, the patient is healthy without signs of tumor recurrence.