今日の臨床サポート

腎血管筋脂肪腫

著者: 井川掌 久留米大学医学部 泌尿器科

監修: 中川昌之 公益財団法人 慈愛会 今村総合病院 泌尿器科顧問

著者校正/監修レビュー済:2021/09/29
参考ガイドライン:
  1. 日本泌尿器科学会日本結節性硬化症学会:結節性硬化症に伴う腎血管筋脂肪腫診療ガイドライン 2016年版
  1. 日本皮膚科学会:結節性硬化症の診断基準及び治療ガイドライン
患者向け説明資料

概要・推奨   

  1. 腎血管筋脂肪腫(AML)とは、血管周囲類上皮細胞に由来する腫瘍(PEComa)として分類され、血管、平滑筋、脂肪組織よりなる多くが良性腫瘍である。
  1. 結節性硬化症(TS)を伴う場合とこれを伴わない散発性のものがある。
  1. 腫瘍径4㎝を超える場合は破裂のリスクを考慮し、血管塞栓術の適応を検討することが推奨される。
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
井川掌 : 特に申告事項無し[2021年]
監修:中川昌之 : 研究費・助成金など(武田薬品工業株式会社)[2021年]

改訂のポイント:
  1. 定期レビューを行い、疾患情報等について加筆を行った。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 腎血管筋脂肪腫(AML)とは、血管周囲類上皮細胞(perivascular epithelioid cell: PEC)に由来する腫瘍(PEComa)として分類され、血管、平滑筋、脂肪組織よりなるほとんどが良性腫瘍であり、腎腫瘍全体の約0.3~2%を占める。男女比 1:3 で女性に多い。年齢は20~80歳代と幅があるが、平均年齢は40~50歳代。比較的まれな疾患で人口10万人当たり0.4~0.5人/年の発生率。
  1. 結節性硬化症(TS)を伴う場合とこれを伴わない散発性のものがある。
  1. TSを伴うものは約20~30%とされており、男女比は1:2と女性の頻度がやや低下し、発見年齢も30歳代とより若年傾向にある。逆にTSの約70%に何らかの腎病変を伴い、そのうちAMLは約6割を占めるという報告がある。
  1. 肺を中心とする全身性病変であるリンパ脈管筋腫症(lymphangioleiomyomatosis、LAM)の胸郭外病変として腎LAMを認める場合がある。
  1. 鑑別診断には腎細胞癌、脂肪肉腫、平滑筋腫、多発性嚢胞腎、副腎骨髄脂肪腫などがある。
  1. ときに脂肪成分に乏しい腫瘍(fat poor AML)や類上皮型AMLが存在し、診断が困難な場合がある。また一般に悪性はまれとされる。
  1. 近年は画像診断で偶発的に発見される無症状例の頻度が増加している。
  1. 多くは無症状であるが、症状を認める場合は、側腹部痛、血尿、腹部腫瘤触知が一般的である。まれな病態で著明な後腹膜出血により、血圧低下を認めるWunderlich’s syndromeを呈することがある。
  1. 治療法として腎摘除術、腎部分切除術、選択的動脈塞栓術および薬物療法が挙げられるが、適応は腫瘍のサイズや症状の有無などにより総合的に判断される。
 
  1. AMLのhigh volume 疫学データ(日本)(参考文献:[1]
  1. 日本の九州地区の泌尿器科関連61施設より集積された1998~2002年の間に受診した初診のAML患者計267例に関する疫学・臨床情報
  1. 男性67例(25.1%)、女性200例(74.9%)、男女比1:3
  1. 平均年齢 男性:53.3歳、女性:52.1歳
  1. 腫瘍部位 左側のみ:123例(46.1%)、右側のみ:121例(45.3%)、両側23例(8.6%)
  1. 腫瘍径 0.5-25㎝(中央値2cm)、4㎝未満:191例(72.9%)、8㎝以上:22例(8.4%)
  1. TS合併例:22例(8.4%) 非合併例に比較して有意に年齢が低く、腫瘍が多発し、有症状例が多く、破裂の頻度が高い(22.7% vs 4.5%)。
  1. 自覚症状:なし(73.8%)、疼痛(12.7%)、血尿(9.4%)
  1. 治療選択 非破裂例:経過観察(75.5%)、腎摘(10.2%)、腎部分切除(3.7%)、腫瘍核出(2.6%)、動脈塞栓術(8.0%)
  1. 破裂例:動脈塞栓術(43.8%)、腎摘(37.5%)、経過観察(18.8%)
  1. 手術治療の選択理由(55症例) 腎癌との鑑別困難(60.0%)、腫瘍径4㎝以上(12.7%)、破裂(10.9%)、腫瘍径4㎝以上かつ症状あり(7.3%)、その他(9.1%)
問診・診察のポイント  
  1. 腫瘍による自覚症状としては血尿、腫瘍が大きくなると腫瘤触知や圧迫による腹部症状や血圧上昇などがみられるが、小さなものでは無症状のことが多い。ただし、腫瘍径が平均4cmを超えてくると自然破裂のリスクが上昇するという報告が多く、破裂した場合、腹痛、貧血、ショックなどを起こしてくる。

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文献 

著者: Raouf M Seyam, Nabil K Bissada, Said A Kattan, Alaa A Mokhtar, Muhammad Aslam, Wahib E Fahmy, Walid A Mourad, Ali A Binmahfouz, Hassan M Alzahrani, Kamal A Hanash
雑誌名: Urology. 2008 Nov;72(5):1077-82. doi: 10.1016/j.urology.2008.07.049. Epub 2008 Sep 21.
Abstract/Text OBJECTIVES: To evaluate the changing management of sporadic renal angiomyolipoma and renal angiomyolipoma associated with the tuberous sclerosis complex (TSC) during the past 16 years.
METHODS: We retrospectively reviewed the charts of 60 patients with angiomyolipoma seen at our institutions.
RESULTS: The median age at presentation was 45 years (range 7-78). The presentation was pain in 30 patients and hematuria in 13; it was incidentally discovered in 17 patients. Of the 60 patients, 43 were females. TSC was present in 14 patients. The median tumor size was 4 cm (range 0.3-40, mean 6.5 +/- 1.1). Of the 60 patients, 31 were followed up expectantly. Surgery or intervention was needed for 29 patients to control hemorrhage or relieve pain or because of the suspicion of malignancy. Of these 29 patients, 12 underwent nephrectomy, 11 partial nephrectomy, and 6 embolization. The patients treated for hemorrhage had a median tumor diameter of 11 cm (range 2-21). Patients were followed up for a mean of 39.3 +/- 5.4 months. The lesions grew an average of 4.7 +/- 3.4 cm for TSC tumors and 0.6 +/- 0.2 cm for sporadic angiomyolipoma tumors. None of the patients developed renal impairment. Patients with TSC presented at a younger age, had larger and bilateral lesions, and were more symptomatic during follow-up. In the past 6 years, a significant trend was seen toward finding tumors in asymptomatic patients and toward the use of conservative or interventional (embolization) treatment.
CONCLUSIONS: Renal angiomyolipoma has a slow growth rate. The preservation of renal function was noted in all our patients. A recent shift was noted toward finding smaller tumors in asymptomatic patients and the use of conservative and interventional treatment.

PMID 18805573  Urology. 2008 Nov;72(5):1077-82. doi: 10.1016/j.urology・・・
著者: Shen-Yang Lee, Hsiang-Hao Hsu, Yung-Chang Chen, Chen-Chih Huang, Yon-Cheong Wong, Li-Jen Wang, Cheng-Keng Chuang, Chih-Wei Yang
雑誌名: Cardiovasc Intervent Radiol. 2009 Nov;32(6):1171-8. doi: 10.1007/s00270-009-9637-0. Epub 2009 Jul 2.
Abstract/Text This study retrospectively evaluated outcomes, complications, and tumor shrinkage in renal angiomyolipomas after transcatheter arterial embolization (TAE). All renal angiomyolipoma patients who underwent TAE between August 2000 and December 2008 and had short-term (6 months) follow-up images were evaluated. Complications and tumor relapse after TAE were reviewed. The sizes of embolized tumors were measured to calculate size reductions and reduction rates after TAE. Differences in tumor size, size reduction, and reduction rate between different time points (pre-TAE, short-term follow-up, and long-term follow-up) and groups (completely and incompletely embolized) were determined. Eleven renal angiomyolipoma patients who had undergone TAE were included. Seven (63.6%) patients had postembolization syndrome and one had abscess formation following TAE. Two patients had a tumor relapse (18.2%). The mean tumor size was 8.57+/-2.66 cm on pre-TAE images. The mean size reduction was 3.1 cm (33.3%) and 3.8 cm (43.0%) at short-term and long-term follow-up. Tumor sizes differed significantly between pre-TAE and short-term (p=0.004) or long-term images (p=0.022) but not between short-term and long-term images (p=0.059). Results stratified by the completeness of embolization indicate that only the short-term size reduction rate differed significantly (p=0.025), while the long-term reduction rate and short- and long-term follow-up tumor size and size reduction were comparable between the two groups. In conclusion, selective TAE is effective for tumor shrinkage in most renal angiomyolipomas, with acceptable complication and relapse rates. Tumor shrinkage occurring within 6 months after TAE may reflect the long-term effect of TAE.

PMID 19572171  Cardiovasc Intervent Radiol. 2009 Nov;32(6):1171-8. doi・・・
著者: J Lenton, D Kessel, A F Watkinson
雑誌名: Clin Radiol. 2008 Aug;63(8):864-70. doi: 10.1016/j.crad.2008.02.005. Epub 2008 Apr 28.
Abstract/Text AIMS: To report the outcomes of elective and emergency embolization of renal angiomyolipoma and describe an angiographic sign that will help localize the symptomatic aneurysm in emergency cases.
MATERIALS AND METHODS: A retrospective review of all patients undergoing embolization of renal angiomyolipoma at a two centres between 1998-2007. Indications for treatment and angiographic images were reviewed. Incidence of acute rupture during embolization was noted.
RESULTS: Seventeen patients underwent 23 episodes of embolization using polyvinyl alcohol (PVA) particles, bead block, and coils. Thirteen were elective procedures for large or symptomatic angiomyolipoma and 10 were acute procedures for patients presenting with retroperitoneal haemorrhage. Patients presenting acutely with haemorrhage tended to have extensive multifocal renal involvement. Active bleeding on diagnostic angiography was seen in a single patient who presented with retroperitoneal haemorrhage 48h after elective embolization with PVA alone. Seven out of 10 (70%) of the acute cases displayed splaying of adjacent vessels due to peri-aneurysmal haematoma, known locally as the "light bulb sign". This allowed treatment to be focused on the symptomatic aneurysm. The light bulb sign was not present in any patient undergoing elective embolization. Aneurysm rupture with active extravasation occurred following embolization of the distal tumour circulation with PVA in four of 10 (40%) of the patients in the acute group and three of 13 (23%) patients in the elective group. Five patients required a subsequent embolization, three at a different site. Two patients in the elective group required repeat embolization of the target site, one for delayed haemorrhage and the other whose tumour did not shrink following the initial incomplete treatment.
CONCLUSIONS: Embolization of renal angiomyolipoma produces durable results. The presence of the light bulb sign is a strong indicator of the site of haemorrhage within the kidney. We advocate using a combination of particulate material and coils, as embolization with PVA alone may predispose to acute haemorrhage occurring during or after embolization.

PMID 18625350  Clin Radiol. 2008 Aug;63(8):864-70. doi: 10.1016/j.crad・・・
著者: Y M Han, J K Kim, B S Roh, H Y Song, J M Lee, Y H Lee, S Y Lee, G H Chung, C S Kim, M H Sohn, K C Choi
雑誌名: Radiology. 1997 Jul;204(1):65-70. doi: 10.1148/radiology.204.1.9205224.
Abstract/Text PURPOSE: To evaluate the efficacy of selective arterial embolization in symptomatic renal angiomyolipoma (AML) and the change in angiomyogenic components during long-term follow-up after embolization.
MATERIALS AND METHODS: Fourteen adult patients with symptomatic AMLs underwent 16 selective arterial embolizations. The embolic materials used were absolute alcohol with (n = 5) or without (n = 3) iodized oil, Gianturco coils (n = 4), and polyvinyl alcohol foam powder with gelatin sponge (n = 2). Follow-up ultrasonography and computed tomography (CT) were performed in six and 14 patients, respectively. The effectiveness of selective arterial embolization was evaluated on the basis of the area of the angiomyogenic components in the AML on initial and follow-up images and clinical improvement.
RESULTS: All patients showed devascularization of the tumor on the postembolization angiograms. In 13 patients, clinical symptoms disappeared. The follow-up period was 7-72 months (mean, 33 months). One patient underwent nephrectomy at 7 months after embolization because of a large cystic lesion found at 1 month. In long-term CT follow-up (> or =12 months) in 12 patients, nearly all angiomyogenic components disappeared, but fatty components partially shrank with liquefactive necrosis in tumors.
CONCLUSION: Selective arterial embolization is an effective and safe treatment of AML. The angiomyomatous components crucial for the prevention of bleeding were very sensitive to the embolization.

PMID 9205224  Radiology. 1997 Jul;204(1):65-70. doi: 10.1148/radiolog・・・
著者: John J Bissler, Francis X McCormack, Lisa R Young, Jean M Elwing, Gail Chuck, Jennifer M Leonard, Vincent J Schmithorst, Tal Laor, Alan S Brody, Judy Bean, Shelia Salisbury, David N Franz
雑誌名: N Engl J Med. 2008 Jan 10;358(2):140-51. doi: 10.1056/NEJMoa063564.
Abstract/Text BACKGROUND: Angiomyolipomas in patients with the tuberous sclerosis complex or sporadic lymphangioleiomyomatosis are associated with mutations in tuberous sclerosis genes resulting in constitutive activation of the mammalian target of rapamycin (mTOR). The drug sirolimus suppresses mTOR signaling.
METHODS: We conducted a 24-month, nonrandomized, open-label trial to determine whether sirolimus reduces the angiomyolipoma volume in patients with the tuberous sclerosis complex or sporadic lymphangioleiomyomatosis. Sirolimus was administered for the first 12 months only. Serial magnetic resonance imaging of angiomyolipomas and brain lesions, computed tomography of lung cysts, and pulmonary-function tests were performed.
RESULTS: Of the 25 patients enrolled, 20 completed the 12-month evaluation, and 18 completed the 24-month evaluation. The mean (+/-SD) angiomyolipoma volume at 12 months was 53.2+/-26.6% of the baseline value (P<0.001) and at 24 months was 85.9+/-28.5% of the baseline value (P=0.005). At 24 months, five patients had a persistent reduction in the angiomyolipoma volume of 30% or more. During the period of sirolimus therapy, among patients with lymphangioleiomyomatosis, the mean forced expiratory volume in 1 second (FEV1) increased by 118+/-330 ml (P=0.06), the forced vital capacity (FVC) increased by 390+/-570 ml (P<0.001), and the residual volume decreased by 439+/-493 ml (P=0.02), as compared with baseline values. One year after sirolimus was discontinued, the FEV1 was 62+/-411 ml above the baseline value, the FVC was 346+/-712 ml above the baseline value, and the residual volume was 333+/-570 ml below the baseline value; cerebral lesions were unchanged. Five patients had six serious adverse events while receiving sirolimus, including diarrhea, pyelonephritis, stomatitis, and respiratory infections.
CONCLUSIONS: Angiomyolipomas regressed somewhat during sirolimus therapy but tended to increase in volume after the therapy was stopped. Some patients with lymphangioleiomyomatosis had improvement in spirometric measurements and gas trapping that persisted after treatment. Suppression of mTOR signaling might constitute an ameliorative treatment in patients with the tuberous sclerosis complex or sporadic lymphangioleiomyomatosis. (ClinicalTrials.gov number, NCT00457808.)

2008 Massachusetts Medical Society
PMID 18184959  N Engl J Med. 2008 Jan 10;358(2):140-51. doi: 10.1056/N・・・
著者: John J Bissler, J Christopher Kingswood, Elżbieta Radzikowska, Bernard A Zonnenberg, Michael Frost, Elena Belousova, Matthias Sauter, Norio Nonomura, Susanne Brakemeier, Petrus J de Vries, Vicky H Whittemore, David Chen, Tarek Sahmoud, Gaurav Shah, Jeremie Lincy, David Lebwohl, Klemens Budde
雑誌名: Lancet. 2013 Mar 9;381(9869):817-24. doi: 10.1016/S0140-6736(12)61767-X.
Abstract/Text BACKGROUND: Angiomyolipomas are slow-growing tumours associated with constitutive activation of mammalian target of rapamycin (mTOR), and are common in patients with tuberous sclerosis complex and sporadic lymphangioleiomyomatosis. The insidious growth of these tumours predisposes patients to serious complications including retroperitoneal haemorrhage and impaired renal function. Everolimus, a rapamycin derivative, inhibits the mTOR pathway by acting on the mTOR complex 1. We compared the angiomyolipoma response rate on everolimus with placebo in patients with tuberous sclerosis or sporadic lymphanioleiomyomatosis-associated angiomyolipomata.
METHODS: In this double-blind, placebo-controlled, phase 3 trial, patients aged 18 years or older with at least one angiomyolipoma 3 cm or larger in its longest diameter (defined by radiological assessment) and a definite diagnosis of tuberous sclerosis or sporadic lymphangioleiomyomatosis were randomly assigned, in a 2:1 fashion with the use of an interactive web response system, to receive oral everolimus 10 mg per day or placebo. The primary efficacy endpoint was the proportion of patients with confirmed angiomyolipoma response of at least a 50% reduction in total volume of target angiomyolipomas relative to baseline. This study is registered with ClinicalTrials.gov number NCT00790400.
RESULTS: 118 patients (median age 31·0 years; IQR 18·0–61·0) from 24 centres in 11 countries were randomly assigned to receive everolimus (n=79) or placebo (n=39). At the data cutoff, double-blind treatment was ongoing for 98 patients; two main reasons for discontination were disease progression (nine placebo patients) followed by adverse events (two everolimus patients; four placebo patients). The angiomyolipoma response rate was 42% (33 of 79 [95% CI 31–53%]) for everolimus and 0% (0 of 39 [0–9%]) for placebo (response rate difference 42% [24–58%]; one-sided Cochran-Mantel-Haenszel test p<0·0001). The most common adverse events in the everolimus and placebo groups were stomatitis (48% [38 of 79], 8% [3 of 39], respectively), nasopharyngitis (24% [19 of 79] and 31% [12 of 39]), and acne-like skin lesions (22% [17 of 79] and 5% [2 of 39]).
INTERPRETATION: Everolimus reduced angiomyolipoma volume with an acceptable safety profile, suggesting it could be a potential treatment for angiomyolipomas associated with tuberous sclerosis.
FUNDING: Novartis Pharmaceuticals.

PMID 23312829  Lancet. 2013 Mar 9;381(9869):817-24. doi: 10.1016/S0140・・・
著者: D Mark Davies, Petrus J de Vries, Simon R Johnson, Deborah L McCartney, Jane A Cox, Andreas L Serra, Peter C Watson, Christopher J Howe, Tim Doyle, Kate Pointon, Justin J Cross, Anne E Tattersfield, J Chris Kingswood, Julian R Sampson
雑誌名: Clin Cancer Res. 2011 Jun 15;17(12):4071-81. doi: 10.1158/1078-0432.CCR-11-0445. Epub 2011 Apr 27.
Abstract/Text PURPOSE: Renal angiomyolipomas are a frequent manifestation of tuberous sclerosis and sporadic lymphangioleiomyomatosis (LAM). These disorders are associated with mutations of TSC1 or TSC2 that lead to overactivation of mTOR complex 1 (mTORC1), suggesting an opportunity for targeted therapy by using mTORC1 inhibitors. This study investigated the efficacy and safety of the mTORC1 inhibitor sirolimus for treatment of renal angiomyolipomas in patients with these disorders.
EXPERIMENTAL DESIGN: In this multicenter phase 2 nonrandomized open label trial, 16 patients with tuberous sclerosis or sporadic LAM and renal angiomyolipoma(s) were treated with oral sirolimus for up to 2 years. Steady-state blood levels were 3 to 10 ng/mL. The primary outcome was change in size of renal angiomyolipomas measured by MRI and assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Secondary outcomes included safety, neurocognitive function, and pulmonary function.
RESULTS: The response rate, by RECIST criteria, was 50%. Summated angiomyolipoma diameters were reduced in all 16 patients and by 30% or more in eight (all from the per protocol group of 10). Forty-one of 48 angiomyolipomas were smaller at the last measurement than at baseline. Most shrinkage occurred during the first year of treatment. There was little change in pulmonary function. Recall memory improved in seven of eight patients with tuberous sclerosis. Adverse events were consistent with the known toxicities of sirolimus.
CONCLUSIONS: This study showed sustained regression of renal angiomyolipomas in patients with tuberous sclerosis or sporadic LAM receiving 2 years of sirolimus treatment. Possible effects on pulmonary function and neurocognition require further investigation.

©2011 AACR.
PMID 21525172  Clin Cancer Res. 2011 Jun 15;17(12):4071-81. doi: 10.11・・・
著者: John J Bissler, John Christopher Kingswood, Elżbieta Radzikowska, Bernard A Zonnenberg, Michael Frost, Elena Belousova, Matthias Sauter, Norio Nonomura, Susanne Brakemeier, Petrus J de Vries, Noah Berkowitz, Sara Miao, Scott Segal, Severine Peyrard, Klemens Budde
雑誌名: Nephrol Dial Transplant. 2016 Jan;31(1):111-9. doi: 10.1093/ndt/gfv249. Epub 2015 Jul 8.
Abstract/Text BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors are recommended as first-line treatment of renal angiomyolipoma associated with tuberous sclerosis complex (TSC) or sporadic lymphangioleiomyomatosis (sporadic LAM), but follow-up is limited. Longer term efficacy and tolerability data from a Phase 3, double-blind, placebo-controlled trial are presented.
METHODS: Following favorable results from the primary analysis (data cutoff 30 June 2011) of the EXIST-2 trial, patients still receiving study treatment were allowed to enter an open-label extension. Everolimus was initiated at 10 mg once daily and titrated based on tolerability. The primary outcome was angiomyolipoma response rate (≥ 50% reduction from baseline in target lesion volumes). Safety was a secondary endpoint.
RESULTS: As of the cutoff date (1 May 2013), 112 patients had received everolimus, and the response rate in 107 patients with angiomyolipoma (median duration of medication exposure of 28.9 months) was 54%. The proportion of patients achieving angiomyolipoma reductions of ≥ 30% and ≥ 50% increased over time, reaching 81.6% (62/76) and 64.5% (49/76), respectively, by Week 96. No everolimus-treated patients experienced renal bleeding. The long-term safety profile was consistent with previous reports; adverse events (AEs) were mostly Grade 1/2, and there were no new safety issues. The frequency of emerging AEs and severe AEs lessened over time.
CONCLUSIONS: Longer term everolimus treatment appeared safe and effective in patients with TSC- or sporadic LAM-associated renal angiomyolipoma not requiring surgical intervention. Continued reduction in angiomyolipoma volume was demonstrated, and there was no angiomyolipoma-related bleeding; AEs were predictable and generally manageable.
TRIAL REGISTRATION: clinicaltrialsgov identifier: NCT00790400 (http://clinicaltrials.gov/ct2/show/NCT00790400).

© The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
PMID 26156073  Nephrol Dial Transplant. 2016 Jan;31(1):111-9. doi: 10.・・・
著者: Brian J Siroky, Hong Yin, John J Bissler
雑誌名: Pediatr Nephrol. 2011 Jun;26(6):839-52. doi: 10.1007/s00467-010-1689-5. Epub 2010 Dec 9.
Abstract/Text Patients with tuberous sclerosis complex are at great risk of developing renal lesions as part of their disease. These lesions include renal cysts and tumors. Significant advances in understanding the cell biology of these renal lesions has already led to clinical trials demonstrating that pharmacological interventions are likely possible. This review focuses on the pathology of these renal lesions, their underlying cell biology, and the possible therapeutic strategies that may prove to significantly improve care for these patients.

PMID 21152937  Pediatr Nephrol. 2011 Jun;26(6):839-52. doi: 10.1007/s0・・・
著者: S K Rakowski, E B Winterkorn, E Paul, D J R Steele, E F Halpern, E A Thiele
雑誌名: Kidney Int. 2006 Nov;70(10):1777-82. doi: 10.1038/sj.ki.5001853. Epub 2006 Sep 27.
Abstract/Text Tuberous sclerosis complex is a genetic disorder characterized by hamartomatous lesions in multiple organs, frequently involving the kidney. We conducted a retrospective review of the clinical and radiographic records of 167 patients with tuberous sclerosis to determine the frequency of renal disease, the likelihood of significant renal morbidity, and the effects of genotype (TSC1 vs TSC2) and gender on renal phenotype. Renal lesions were seen in 57.5% of patients. Of these, angiomyolipoma (AML) occurred in 85.4%, cysts in 44.8%, and renal cell carcinoma in 4.2%. Both AML and cysts were significantly more common and more numerous in TSC2 than in TSC1. AML was significantly more common in female than in male patients, but cysts showed no correlation with gender. Eleven patients developed renal abnormalities during their care in this practice at an average age of onset of 11.3 years (range 3.8-23 years). The frequency and number of renal lesions were positively correlated with age. Interventions, including arterial embolization and nephrectomy, were performed in 11 (6.6%) patients. Among female patients with lymphangioleiomyomatosis, renal AML was universally present. Our findings confirm a high rate of renal involvement; a low rate of serious complications; significant associations between renal involvement, genotype, and gender; and a significant association between renal and pulmonary involvement in female patients.

PMID 17003820  Kidney Int. 2006 Nov;70(10):1777-82. doi: 10.1038/sj.ki・・・
著者: Yoshiko Tokuyama, Tetsuo Fujita, Takahiro Hirayama, Masahiro Shirai, Akio Kazama, Masatsugu Iwamura, Shiro Baba
雑誌名: Hinyokika Kiyo. 2010 Feb;56(2):103-6.
Abstract/Text A 50-year-old male was referred to our hospital for a left renal mass which was incidentally found during a medical check-up. Abdominal ultrasonography, computed tomography, and magnetic resonance imaging showed a weak enhancement tumor devoid of fat densities at the lower pole of the left kidney. Under the diagnosis of renal cell carcinoma, radical nephrectomy was performed. Histopathological examination revealed large epithelioid cells, and immunohistochemical staining showed strongly positive for HMB-45. The patient was diagnosed with epithelioid angiomyolipoma of the kidney. Epithelioid angiomyolipoma is a rare variant of angiomyolipoma, which is sometimes occurred aggressive clinical behavior. However, our case remains without evidence of recurrence or metastasis after radical nephrectomy, and showed relatively better prognosis than in previous reports.

PMID 20185996  Hinyokika Kiyo. 2010 Feb;56(2):103-6.
著者: Hakan Aydin, Cristina Magi-Galluzzi, Brian R Lane, Linda Sercia, Jose I Lopez, Brian I Rini, Ming Zhou
雑誌名: Am J Surg Pathol. 2009 Feb;33(2):289-97. doi: 10.1097/PAS.0b013e31817ed7a6.
Abstract/Text The majority of renal angiomyolipoma (AML) is sporadic and occasionally it occurs as part of tuberous sclerosis complex (TSC). Epithelioid AML (EAML), an uncommon variant, is considered potentially malignant based on anecdotal case reports. The prognostic significance of epithelioid component in an otherwise typical AML is uncertain. We studied 194 AMLs for the clinicopathologic features of epithelioid and TSC-associated AMLs. Epithelioid component was present in 15 cases (7.7%) with an average amount of 51% (range: 10% to 100%). Histologically, the epithelioid tumor cells were categorized into small, intermediate, and large cell type based on the cell size. Worrisome histologic features were seen in many EAMLs, including coagulative tumor necrosis in 27% (4/15), nuclear atypia in 93% (14/15), mitosis in 47% (7/15), and atypical mitosis in 1 case. All 15 EAML patients had a mean follow-up time of 5.1 years and none had local recurrence or distant metastasis. Sixteen (8.2%) AMLs occurred in patients with definitive TSC. Three histologic features, namely microscopic AML foci, epithelioid component, and epithelial cysts, were present in 10 (62.5%), 4 (25%), and 44% (7/16), respectively, of TSC-associated AMLs, compared with 11 (6.2%), 11 (6.2%), and 6 (3.4%), respectively, in non-TSC-associated AMLs (P value all <0.01). In summary, all 15 cases of EAMLs in our study had benign clinical outcomes despite adverse pathologic features. Epithelioid component, epithelial cysts, and microscopic AML foci are strongly associated with TSC and the presence of all 3 features should raise strong suspicion for TSC.

PMID 18852677  Am J Surg Pathol. 2009 Feb;33(2):289-97. doi: 10.1097/P・・・
著者: Mitsuru Komeya, Tatsuya Matsumoto, Kiyoshi Fujinami, Yutaka Senga, Tomoyuki Asakura, Akihiko Goto
雑誌名: Hinyokika Kiyo. 2010 May;56(5):261-4.
Abstract/Text A 39-year-old woman, who was followed because of a 4 cm asymptomatic angiomyolipoma (AML) in the left kidney, presented with an acute onset of lower left back pain in the 38th week of her first pregnancy. An ultrasound revealed an 8 cm mass suggestive of AML rupture and retroperitoneal hemorrhage. An emergency caesarean delivery was performed. A post-delivery computed tomographic scan confirmed the AML rupture and selective embolization was performed. This was a case in which the AML grew rapidly during the pregnancy ; therefore, we discuss the relationship between AML and pregnancy.

PMID 20519923  Hinyokika Kiyo. 2010 May;56(5):261-4.

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