Late recurrence of a hepatic angiomyolipoma

Angiomyolipomas are benign mesenchymal tumours, mostly of renal origin. Hepatic angiomyolipomas are rare, and radiological and pathological diagnoses may be difficult We report on the first case of hepatic angiomyolipoma recurrence known to us, 6 years after surgical treatment of the initial tumour. Moreover, this hepatic recurrence was associated with renal angiomyolipoma without any stigmata of tuberous sclerosis.     

Renal involvement in tuberous sclerosis

Three patients are described with renal angiomyolipoma without accompaning central nervous system involvement. Each patient presented in a different manner; the first with signs and symptoms of renal insufficiency, the second with gross hematuria, and the third with flank pain. All patients had replacement of renal parenchyma by hamartomatous tumors composed of blood vessels, adipose tissue and smooth muscle cells. The first case is the fifth report of the development of renal failure in tuberous sclerosis. In the latter two cases, intravenous pyelograms suggested polycystic kidney disease but renal arteriography was diagnostic of diffuse angiomyolipomas. Malignant transformation of these tumors is rare, but hemorrhagic complications following renal biopsy is a major problem in these patients.     

Renal manifestations in tuberous sclerosis

BACKGROUND: Tuberous sclerosis is a rare inherited disease which can involve several organs. Renal involvement is one of the most severe manifestations of the disease. We analysed in this study renal involvement of tuberous sclerosis. METHODS: We studied retrospectively nine cases of tuberous sclerosis with renal involvement diagnosed between 1994 and 2005. The diagnosis was based on the presence of typical extra-renal manifestations and familial history of tuberous sclerosis. RESULTS: There were eight females and one male. Their mean age was 40.8+/-16.4 years (range: 15-62). At first presentation, we noted hypertension in three cases, proteinuria in seven cases, hematuria in eight cases and renal failure in five cases (end stage renal failure in four cases). By ultrasonography, we found angiomyolipoma in one case, cysts in four cases and angiomyolipoma associated to cysts in four cases. Nephrectomy was performed in two patients, in one case for hydronephrosis secondary to urolithiasis and in the other for hemorrhagic complication. In the later, pathological examination revealed renal carcinoma. At last evaluation, two patients were lost to follow-up, one had normal serum creatinine, five were on renal replacement therapy and the latter died from sepsis following kidney removal. CONCLUSIONS: In our patients, renal disease was diagnosed late at chronic renal failure stage. Patients with end-stage renal failure require dialysis and renal transplantation, but we recommend binephrectomy after starting dialysis and before transplantation due to the risk of cancer and bleeding related to angiomyolipomas.     

Hepatic angiomyelolipoma and tuberous sclerosis

A patient with angiomyelolipoma of the liver, together with radiological evidence of pancreatic, renal and bony lesions characteristic of tuberous sclerosis, is described. Although the patient had no other clinical features of tuberous sclerosis, her daughter was found to suffer from the classical triad of this syndrome and also has had hepatic lipomatous lesions and bony involvement. This is the first histologically proven case of hepatic angiomyelolipoma associated with tuberous sclerosis.     

Coincidence of hepatocelluar carcinoma and hepatic angiomyolipomas in tuberous sclerosis complex： A case report

Tuberous sclerosis complex （TSC） is a dominantly inherited disorder which characterized by the growth of harmatomatous in multiple organs. Unlike the common development of renal angiomyolipoma, hepatic angiomyolipoma rarely occur in patients with TSC. We report here a patient with hepatic angiomyolipomas and concurrent hepatocellular carcinoma in TSC. This represents the first reported case in English literature. In this patient, multiple hepatic angiomyolipomas were diagnosed with recognition of their fat components and typical clinical settings. Hepatocellular carcinoma in the left liver lobe was definitely diagnosed by US guided biopsy. In such clinical settings, fat containing lesions in liver can be reasonably treated as angiomyolipomas, but non fat containing lesions must be differentiated from hepatocellular carcinoma, imaging guided biopsy can be adopted to confirm the diagnosis.     

Massive hepatic angiomyolipoma in a young woman with tuberous sclerosis complex: significant clinical improvement during tamoxifen treatment

BACKGROUND/AIMS: Isolated liver angiomyolipomas (AMLs) occur in about 40% of TSC patients. Because of their slow growth, these tumors are often asymptomatic. Since AMLs express estrogen and progesteron receptors we suggest the possible benefits of tamoxifen for the treatment of liver AMLs. METHODS: We report the case of a 26-year-old female affected by tuberous sclerosis (TSC2) with cerebral, renal and hepatic involvement admitted to the Liver Unit for severe malnutrition, anorexia and abdominal pain. MRI showed a grossly enlarged liver, causing severe gastric compression. The liver was entirely filled with multiple nodular lesions of different sizes. Liver biopsy showed tumoral tissue with microscopic and ultrastructural features of angiomyolipoma. All liver function tests were repeatedly normal. Prior to considering the patient for partial hepatectomy, she was administered tamoxifen (20mg b.i.d). RESULTS: After 6 months of tamoxifen treatment a greatly improved quality of life and a significant weight gain were observed. After 12 months the clinical conditions further improved and the MRI showed a significant reduction of the largest lesion with a liquid central area and a diminished compression of the stomach. CONCLUSIONS: This is to our knowledge the first report in which tamoxifen has been successfully used in a TSC patient with multiple liver angiomyolipomas.     

Aktuelle Therapiestudien für die Indikation zystischer Nierenerkrankungen

Inherited cystic kidney diseases are a heterogeneous group of rare diseases. Based on molecular biological findings approved drugs have already been recently tested for the new indications for autosomal dominant polycystic kidney disease (ADPKD) and tuberous sclerosis complex. For ADPKD it is important to note that renal function remains stable for decades so the effectiveness of treatment is determined by renal size as a surrogate marker of disease burden. In a 3-year study of 1,445 ADPKD patients tolvaptan, an aquaretic agent, decreased the growth of kidneys, renal function loss and kidney pain. The long-acting somatostatins octreotide and lanreotide moderately decreased liver and kidney size in patients with ADPKD and polycystic liver disease. The mTOR inhibitors sirolimus and everolimus were ineffective for the indications of ADPKD while these drugs shrunk the renal angiomyolipomas associated with tuberous sclerosis. Health authorities will decide this year on the approval of tolvaptan for ADPKD and of everolimus for the indications for tuberous sclerosis complex.     

Mutations in the tuberous sclerosis complex gene TSC2 are a cause of sporadic pulmonary lymphangioleiomyomatosis

Lymphangioleiomyomatosis (LAM) is a progressive and often fatal interstitial lung disease characterized by a diffuse proliferation of abnormal smooth muscle cells in the lungs. LAM is of unusual interest biologically because it affects almost exclusively young women. LAM can occur as an isolated disorder (sporadic LAM) or in association with tuberous sclerosis complex. Renal angiomyolipomas, which are found in most tuberous sclerosis patients, also occur in 60% of sporadic LAM patients. We previously found TSC2 loss of heterozygosity in 7 of 13 (54%) of angiomyolipomas from sporadic LAM patients, suggesting that LAM and TSC could have a common genetic basis. In this study, we report the identification of somatic TSC2 mutations in five of seven angiomyolipomas from sporadic LAM patients. In all four patients from whom lung tissue was available, the same mutation found in the angiomyolipoma was present in the abnormal pulmonary smooth muscle cells. In no case was the mutation present in normal kidney, morphologically normal lung, or lymphoblastoid cells. Our data demonstrate that somatic mutations in the TSC2 gene occur in the angiomyolipomas and pulmonary LAM cells of women with sporadic LAM, strongly supporting a direct role of TSC2 in the pathogenesis of this disease.     

Leiomyomatosis-like lymphangioleiomyomatosis: A case report of the colonic manifestation of tuberous sclerosis

Introduction:Tuberous sclerosis complex is an inherited multisystemic disorder with manifestations in various organ systems as a result of a mutation of 1 of 2 tumor suppressor genes, tuberous sclerosis complex-1 or tuberous sclerosis complex-2. Perivascular epithelioid cell tumors have been shown to be associated with these gene mutations and include a variety of tumors such as angiomyolipomas and lymphangioleiomyomatosis.Patient concerns:In this report, we present a case of a 28-year-old woman presenting with symptoms of severe abdominal pain and nausea with a medical history of cardiac rhabdomyoma, adenoma sebaceum, Ash leaf spots, bilateral renal angiomyolipomas, and retinal hamartoma, which are manifestations of tuberous sclerosis complex. The patient was operated twice for colonic perforations in the rectosigmoid and ileocecal regions where the pathologic examination revealed multiple tumoral lesions in both specimens.Diagnosis:The tumor consisted of a myomatous component where the nodules were composed of spindle cells with fascicular array, and a lymphangiomatous component where epithelioid cells could be observed. Immunohistochemically, smooth muscle markers (desmin and SMA) were positive and the epithelioid component showed HMB-45 positivity. A diagnosis of leiomyomatosis-like lymphangioleiomyomatosis was established due to its morphological and immunohistochemical features, the presence of the tumor in multiple foci, and widespread lymphovascular invasion.Interventions:The patient had a perforation in her bowel twice during the hospital stay and underwent Hartmann operation and ileocecal resection in 2 different surgical operations.Outcomes:After the second operation the patient developed fever and was diagnosed with SARS-CoV-2 infection. No other complication was observed during her stay and the patient''s follow-up was unremarkable.Conclusion:Perivascular epithelioid cell tumors are associated with tuberous sclerosis and can rarely appear in the colon. Therefore, lymphangioleiomyomatosis should be in the differential diagnosis in a tuberous sclerosis patient presenting with a colonic tumor.     

Initial presentation with dilated cardiomyopathy in a patient of tuberous sclerosis: A rare case report

A 35-year-old man presented with dilated cardiomyopathy, an unusual association with tuberous sclerosis. Clinical history and examination were consistent with tuberous sclerosis including major features of tuberous sclerosis complex (TSC) like facial angiofibroma, shagreen patch, subependymal nodules, and angiomyolipoma of kidney. The clinical manifestations, pathogenesis and evaluation of tuberous sclerosis are discussed.     

TUBEROUS SCLEROSIS MIMICKING ADULT POLYCYSTIC KIDNEY DISEASE

Tuberous sclerosis is a recognised cause of renal disease, usually angiomyolipomas but also cysts; it usually presents in childhood. A father and son are reported with familial tuberous sclerosis presenting in adulthood and mimicking polycystic kidney disease.     

Colonic Angiomyolipoma

Abstract: Angiomyolipoma is a rare benign tumor which usually occurs in the kidney with tuberous sclerosis. We encountered a case of angiomyolipoma of the cecum not associated with tuberous sclerosis. To our knowledge, this is only the third case reported in the international literature.     

Pneumothorax in a female with renal angiomyolipoma

Spontaneous pneumothorax occurs less in females than in males, in contrast to the relatively more commonly and incidentally found renal angiomyolipoma (AML). We report a renal AML in a 23-year-old female patient, which presented as right palpable abdominal mass. This renal tumor was removed owing to enlargement and internal hemorrhage and AML was proved by pathological examination. Three years later, she experienced a life-threatening spontaneous tension pneumothorax and pulmonary lymphangioleiomyomatosis (LAM), which was diagnosed by chest computed tomography. Clinically, she did not have tuberous sclerosis. Pulmonary LAM and renal AML are related lesions and both of these proliferative lesions occur in sporadic patients without family history and at much higher frequency in patients with tuberous sclerosis. Because of the nonspecific symptoms and high rate of complications, we should consider the possibility of LAM in patients diagnosed with AML. The association between renal AML and pulmonary LAM is reviewed.     

The management strategy of renal angiomyolipoma

The purpose of this study is to analyze the management strategy of renal angiomyolipoma. From 1990 to 2002, a total of 62 patients with renal angiomyolipoma were treated at our medical center. Angiomyolipomas were found in 44 female patients (71.0%) and 18 male patients. Of these patients the age ranged from 18 to 87 y/o (mean: 46.9 y/o). Four of 8 patients with bilateral angiomyolipomas were associated with tuberous sclerosis (TS). Nine (14.5%) of 62 patients had got spontaneous rupture. However, 54.8 per cent of patients were asymptomatic. The mean tumor size was 4.83 cm. Tumors larger than 4 cm had a greater incidence of symptoms (60.7%) and a higher nephrectomy rate (43%). Clinical management was based on tumor size and clinical presentation. Treatment consisted of conservative observation in 30 patients (group 1, 48.4%), selective embolization therapy in 2 patients with hemorrhage (group 2, 3.2%), partial nephrectomy and other surgical procedures in 14 patients (group 3, 22.6%), and total nephrectomy in 16 patients (group 4, 25.8%). Nine of 62 patients were associated with spontaneous angiomyolipoma rupture under conservative treatment in 3, TAE in 1, partial nephrectomy in 1, total nephrectomy in 3 and laparotomy to check bleeding in 1. Neither mortality no major complication was noted. Generally the outcomes were smooth and acceptable. Beyond the total nephrectomy for patients with highly suspected malignancy, we suggest conservative treatment with observation strategy for small asymptomatic tumors, selective arterial embolization as the first choice for hemorrhage or rupture and partial nephrectomy for renal sparing strategy.     

Common and epithelioid variants of hepatic angiomyolipoma exhibit clonal growth and share a distinctive immunophenotype

Angiomyolipoma represents a rare liver tumor of uncertain histogenesis that is commonly considered a hamartoma. A series of 12 hepatic angiomyolipomas, including 3 samples of the epithelioid subtype, was analyzed for clonality using the human androgen receptor gene locus (HUMARA). Four of 6 informative cases revealed monoclonality. The polyclonal pattern in the 2 remaining cases was most probably caused by excessive infiltration of inflammatory cells. Monoclonality with an identical X-chromosomal inactivation pattern in all nodules was found in a multifocal recurrent tumor indicating a metastatic process. Despite the morphologic heterogeneity, all tumors displayed an identical immunohistochemical labeling pattern. It is concluded that different subtypes of hepatic angiomyolipoma exhibit a monoclonal and hence probably neoplastic growth and share an identical immunophenotype suitable for their identification even in small biopsy specimens. The epithelioid subtype may give rise to intrahepatic metastasis.     

Juxta-caval hepatic angiomyolipoma masquerading as hepatocellular carcinoma

Hepatic angiomyolipoma is an uncommon primary benign epithelial liver neoplasm. Most patients with angiomyolipomas are middle-aged women who commonly present with epigastric fullness or pain. Angiomyolipomas are tumors consisting of three tissue types: blood vessels, smooth muscle, and fat. Hepatic angiomyolipomas may be difficult to differentiate from other liver neoplasms by noninvasive imaging. We report a 58-year-old asymptomatic woman with a mass in the right lobe of the liver, found incidentally on routine abdominal sonography. Preoperative radiographic evaluation revealed a 6.5-cm hypervascular lesion abutting the inferior vena cava. Preoperative histologic study demonstrated an epithelial neoplasm suspicious for hepatocellular carcinoma. Metastatic workup was negative. At resection, the tumor was found to be an angiomyolipoma composed of lipoid, vascular and smooth muscle cells. Further staining was positive for HMB-45. Resection margins were negative. The woman had an uneventful recovery and was discharged on postoperative day seven. She currently remains well several months after her right hepatectomy.     

Mutation in TSC2 and activation of mammalian target of rapamycin signalling pathway in renal angiomyolipoma

Mutations that inactivate either TSC1 or TSC2 cause tuberous sclerosis. We have used immunoblotting and immunohistochemical analysis to see whether there is phosphorylation of p70 S6 kinase, and the ribosomal S6 protein in angiomyolipomas occurring in tuberous scierosis. Hamartin (encoded by TSC1) and S6K was expressed in all samples. Tuberin (TSC2) was weak or absent in angiomyolipomas, but present in healthy kidney, whereas, phosphorylated p70 S6 kinase and p56 were present only in angiomyolipomas. Our results indicate activation of a mammalian target of rapamycin metabolic pathway in tuberous sclerosis lesions, which contributes to their growth. We suggest that treatment with rapamycin and its analogues could benefit such patients.     

Hepatic angiomyolipoma associated with splenic hamartoma

A 52-year-old woman was admitted to our hospital with thrombophlebitis of the internal jugular vein. Abdominal ultrasonography demonstrated a high echogenic mass measuring 4.5 cm in diameter in the liver, and abdominal CT revealed another liver tumor and an isodensity mass in the spleen. Abdominal MRI and angiography were performed and we presumed the tumors to be two hepatic angiomyolipoma and a splenic hamartoma. As an abdominal CT 21 months later revealed that all tumors were growing, these tomors were surgically resected. The histological diagnoses were hepatic angiomyolipoma and splenic hamartoma.     

Angiomyolipoma of the colon - case report and review of the literature

Angiomyolipoma is one of the benign hamartomas that is found sporadically or associated with tuberous sclerosis. It is a rare soft tissue tumor involving mostly the kidneys, sometimes other visceral organs. The tumor is composed of smooth muscle cells, adipocytes and small sized hyalinized vessels. We present the case of a 74-year-old man with a bifocal angiomyolipoma of the colon. This diagnosis was confirmed at surgery, where a partial colectomy was performed. Histologic examination disclosed the tumor. The patient had no signs of family history of tuberous sclerosis. Extrarenal angiomyolipoma is rare and this may be the first report of bifocal colonic angiomyolipoma.     

Clinical characteristics and outcomes of patients with hepatic angiomyolipoma: A literature review

First reported in 1976, hepatic angiomyolipoma (HAML) is a rare mesenchymal liver tumor occurring mostly in middle-aged women. Diagnosis of the liver mass is often incidental on abdominal imaging due to the frequent absence of specific symptoms. Nearly 10% of HAMLs are associated with tuberous sclerosis complex. HAML contains variable proportions of blood vessels, smooth muscle cells and adipose tissue, which renders radiological diagnosis hazardous. Cells express positivity for HMB-45 and actin, thus these tumors are integrated into the group of perivascular epithelioid cell tumors. Typically, a HAML appears on magnetic resonance imaging (or computed tomography scan) as a hypervascular solid tumor with fatty areas and with washout, and can easily be misdiagnosed as other liver tumors, particularly hepatocellular carcinoma. The therapeutic strategy is not clearly defined, but surgical resection is indicated for symptomatic patients, for tumors showing an aggressive pattern (i.e., changes in size on imaging or high proliferation activity and atypical epithelioid pattern on liver biopsy), for large (> 5 cm) biopsy-proven HAML, and if doubts remain on imaging or histology. Conservative management may be justified in other conditions, since most cases follow a benign clinical course. In summary, the correct diagnosis of HAML is challenging on imaging and relies mainly on pathological findings.