Mazabraud 綜合征一例

陸國(guó)強(qiáng) 李自強(qiáng)

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Mazabraud 綜合征一例

陸國(guó)強(qiáng) 李自強(qiáng)

作者單位：200438 上海市楊浦區(qū)市東醫(yī)院骨科

【關(guān)鍵詞】黏液瘤；腫瘤，肌組織；腫瘤；Mazabraud 綜合征；骨纖維結(jié)構(gòu)不良

Mazabraud 綜合征是一種非常罕見(jiàn)的散發(fā)性疾病。臨床上以骨纖維結(jié)構(gòu)不良 ( fibrous dysplasia，F(xiàn)D ) 和肌肉黏液瘤 ( intramuscular myxoma，IM ) 見(jiàn)于同一患者時(shí)被稱為Mazabraud 綜合征。1926 年，Henschen 對(duì)此病首次進(jìn)行了描述，1957 年 Mazabraud 進(jìn)一步描述二者相關(guān)性，并被命名為 Mazabraud 綜合征[1]。目前為止報(bào)道不滿 80 例[2]。2014 年 9 月我院經(jīng)治 1 例，現(xiàn)報(bào)告如下。

臨床資料

患者，男，70 歲。因“發(fā)現(xiàn)左臀部腫塊半月余”于2014 年 9 月 18 日入院。入院檢查：左臀部外上方可捫及 4 cm×4 cm×3 cm 大小包塊，表面光滑，邊界清楚，活動(dòng)度差，質(zhì)韌，無(wú)明顯壓痛。左下肢肢體較右下肢短縮 2 cm。雙下肢感覺(jué)、運(yùn)動(dòng)正常。雙下肢末梢血運(yùn)正常。既往史除有高血壓外均無(wú)異常。否認(rèn)外傷手術(shù)史。入院檢查：血常規(guī)，肝腎功能，電解質(zhì)，血糖，血脂，免疫相關(guān)檢查，腫瘤標(biāo)志物篩選均未見(jiàn)異常，血沉，C-反應(yīng)蛋白均正常。骨代謝檢查：骨鈣素 N 端中分子片段：153.80 ng / ml ( 正常 14～46 ng / ml )，總 1I 型膠原羧基端前肽：1141. ng / ml ( 正常 16.27～73.87 ng / ml )，25 羥維生素 D 測(cè)定：15.52 ng / ml ( 正常＞20 ng / ml )，β-膠原降解產(chǎn)物：1.09 ng / ml ( 正常 0.1～1 ng / ml )，甲狀旁腺素：46.98 pg / ml ( 正常 15～65 pg / ml )，堿性磷酸酶 289 U / L ( 正常 35～123 U / L )。影像學(xué)檢查：( 1 ) X 線：骨盆攝片：所見(jiàn)髖部諸骨皂泡樣病變，考慮骨纖維結(jié)構(gòu)不良；左右股骨上段攝片：左右股骨上段及右髖諸骨皂泡樣病變，考慮骨纖維結(jié)構(gòu)不良，伴右髖退行性變。( 2 ) CT：盆腔平掃：骨盆畸形狀，雙側(cè)髂骨、股骨及部分骶骨、髖臼、恥骨、坐骨膨脹伴多發(fā)皂泡樣變，部分病灶內(nèi)見(jiàn)增密影，以左側(cè)為甚。左臀部肌肉區(qū)見(jiàn)一直徑約 3 cm 囊性灶，CT 值約 2～7 Hu，邊緣光滑。前列腺內(nèi)鈣化灶。結(jié)論：骨纖維結(jié)構(gòu)不良可能。左臀部肌肉區(qū)囊性灶。經(jīng)適當(dāng)術(shù)前準(zhǔn)備，于 9 月 22 日在全麻下行左臀部肌肉腫塊切除，左股骨大轉(zhuǎn)子活檢術(shù)。手術(shù)完整切除左臀部肌肉內(nèi)腫塊，并取左股骨大轉(zhuǎn)子病灶處穿刺活檢并送病理檢查。病理檢查：大體標(biāo)本：( 1 ) 左臀部外側(cè)肌肉腫塊呈橢圓形，直徑為 5 cm，表面光滑，有滑囊及滑液包繞，血供較豐富。剖面呈半透明、魚(yú)肉樣。( 2 ) 左股骨大轉(zhuǎn)子穿刺活檢，長(zhǎng)約 1.2 cm 直徑 0.3 cm 條索狀組織，灰白色，質(zhì)較硬。病理診斷：左臀大?。杭∪怵ひ毫觥Ｗ蠊晒谴筠D(zhuǎn)子：纖維結(jié)構(gòu)不良。結(jié)合臨床，Mazabraud 綜合征。( 本病例經(jīng)上海市臨床病理讀片會(huì)討論確定 )。術(shù)后隨訪 7 個(gè)月，一般情況良好，能正常行走。

圖 1　Mazabraud 綜合征 X 線片：骨盆、雙髖關(guān)節(jié)、雙股骨上段均見(jiàn)皂泡樣病變，考慮骨纖維結(jié)構(gòu)不良Fig.1 Mazabraud syndrome. X-rays of the pelvis, bilateral hip joints and bilateral femurs show soap bubble-like appearance, which are typical fi ndings of osteo fi brous dysplasia

圖 2　Mazabraud 綜合征 CT 全盆腔平掃：骨盆畸形狀，雙側(cè)髂骨、股骨及部分骶骨、髖臼、恥骨、坐骨膨脹伴多發(fā)皂泡樣變，部分病灶內(nèi)見(jiàn)增密影，以左側(cè)為甚。左臀部肌肉區(qū)見(jiàn)一直徑約 3 cm 囊性灶，CT 值約 2～7 Hu，邊緣光滑。結(jié)論：骨纖維結(jié)構(gòu)不良可能。左臀部肌肉區(qū)囊性灶Fig.2 CT scan of whole pelvic shows soap-bubble-like appearance of bilateral ilium, patial sacrum, acetabulum, pubis and ischium. Thereis a 3 cm-diameter cystic mass in left gluteus max imus muscle, of which CT value was 2 - 7 Hu

圖 3　左股骨大轉(zhuǎn)子骨纖維結(jié)構(gòu)不良顯微鏡示排列疏松的梭形纖維組織及不成熟編織骨，骨小梁纖細(xì)，排列不規(guī)則，呈英文字母形，周圍有少量扁平的骨母細(xì)胞圍繞 ( HE × 40 )Fig.3 Under microscope, loose arrangement of fusiform fi brous tissue and immature fi brous bone, as well as irregular arrangement, Englishlettershaped tenuity bone trabeculacanbe seen, which is surrounded by a few fl at osteoblasts ( HE × 40 )

圖 4　左臀大肌內(nèi)粘液瘤顯微鏡示腫瘤邊界清楚但無(wú)包膜，腫瘤組織富含大量黏液樣物質(zhì)少細(xì)胞性，細(xì)胞小，呈星狀突起，無(wú)異型性( HE × 40 )Fig.4 Under microscope, the tumor shows clear boundary without capsule. There were much mucus-like substance and few cells. Cells are small, star-shaped andhad no speci fi city ( HE × 40 )

討 論

Mazabraud 綜合征好發(fā)于女性。男性少見(jiàn)。Zoccali 等[3]報(bào)道超過(guò) 2 / 3 的病例為女性。發(fā)病年齡骨纖維結(jié)構(gòu)不良中位年齡 34 歲，而肌肉黏液瘤發(fā)病中位年齡 43 歲。

Mazabraud 綜合征的骨纖維結(jié)構(gòu)不良是一種原因不明，進(jìn)展緩慢的良性纖維性骨病。大部分患者病變?yōu)槎喙切該p傷，也可為單骨性損傷。常見(jiàn)于股骨，其次為盆骨，也可見(jiàn)于肋骨。一般無(wú)癥狀，后期可出現(xiàn)病理性骨折或肢體彎曲畸形。肌內(nèi)黏液瘤是一種生長(zhǎng)緩慢的良性間葉組織來(lái)源腫瘤。發(fā)病較晚，同樣肌內(nèi)黏液瘤也可單發(fā)或多發(fā)，以多發(fā)為主，常見(jiàn)于大腿。腫瘤一般不大，有文獻(xiàn)報(bào)道直徑最大 20 cm，平均 5～10 cm[4]。本例為 70 歲男性，以發(fā)現(xiàn)左臀部腫塊而就醫(yī)，以前無(wú)任何骨骼 X 線片檢查，與描述相符。Mazabraud 綜合征中骨纖維結(jié)構(gòu)不良的 X 線表現(xiàn)為在長(zhǎng)骨骨干之界限清楚的囊狀透亮區(qū)，呈現(xiàn)模糊不清的磨砂玻璃狀。骨皮質(zhì)膨脹，一般無(wú)骨膜反應(yīng)[5]。CT 和 MRI 能更好地反應(yīng)病變特征和范圍。Mazabraud 綜合征病因不明，近年來(lái)，現(xiàn)代分子遺傳學(xué)研究提示骨纖維結(jié)構(gòu)不良和肌內(nèi)黏液瘤都與 Gsa 基因突變有關(guān)。2002 年版WHO“骨與軟組織腫瘤”明確骨纖維結(jié)構(gòu)不良是由于位于 20 號(hào)染色體長(zhǎng)臂 1 區(qū) 3 帶 GNAS1 基因變異，導(dǎo)致 Gsa活性異常，環(huán)腺苷酸 ( cAMP ) 活性增加，使骨母細(xì)胞分化異常而產(chǎn)生異常的不成熟骨小梁。肌內(nèi)黏液瘤也有染色體20q13.2-20q13.3 的 GNAS1 基因變異，使編碼 Gsa 蛋白突變。Ohamoto 推測(cè)肌內(nèi)黏液瘤的基因突變發(fā)生時(shí)間比骨纖維結(jié)構(gòu)不良遲，因此解釋骨纖維結(jié)構(gòu)不良發(fā)病比肌內(nèi)黏液瘤早[6]。

Mazabraud 綜合征的治療，對(duì)于肌內(nèi)黏液瘤可手術(shù)完整切除，一般很少惡變，但可復(fù)發(fā)[7]。骨纖維結(jié)構(gòu)不良必須密切隨訪，有文獻(xiàn)報(bào)道可偶發(fā)生骨肉瘤變[7]。但也有報(bào)道認(rèn)為其惡變率較高[8]。另外，由于臨床上對(duì)于骨纖維結(jié)構(gòu)不良患者很少關(guān)注肌肉癥狀和相關(guān)檢查，多數(shù)患者被漏診。為獲得早期診斷，建議對(duì)所有骨纖維結(jié)構(gòu)不良患者進(jìn)行常規(guī)肌肉體格檢查，必要時(shí)輔以 MRI 檢查，注意有無(wú)合并肌內(nèi)黏液瘤存在。同樣對(duì)肌內(nèi)黏液瘤的患者，也須注意有無(wú)骨纖維結(jié)構(gòu)不良存在，必要時(shí)可進(jìn)行全身骨掃描。一旦二者同時(shí)存在即可診斷為 Mazabraud 綜合征。

參 考 文 獻(xiàn)

[1] Mazabraud A, GirardI J. A peculiar case of fibrous dysplasia with osseous and tendinous localizations. Rev Rhum Mal Osteoartic, 1957, 24(9-10):652-659.

[2] 趙葉紅, 張惠箴, 蔣智銘, 等. Mazabraud綜合征臨床病理特征. 臨床與實(shí)驗(yàn)病理學(xué)雜志, 2008, 24(1):47-49.

[3] Zoccali C, Teori G, Prencipe U, et al. Mazabraud’s syndrome: a new case and review of the literature. Int Orthop, 2009, 33(3):605-610.

[4] Hashimoto H, Tsuneyoshi M, Daimaru Y, et al. Intramuscular myxoma. A clinicopathologic, immunohistochemical, and electron microscopic study. Ancer, 1986, 58(3):740-747.

[5] 李景學(xué), 孫鼎元. 骨關(guān)節(jié)X線診斷學(xué). 北京: 人民衛(wèi)生出版社. 1996: 347.

[6] Okamoto S, Hisaoka M, Ushijima M, et al. Activating Gs (alpha) mutation in intramuscular myxomas with and without fi brous dysplasia of bone. Virchows Arch, 2000, 437(2):133-137.

[7] Szendrói M, Rahóty P, Antal I, et al. Fibrous dysplasia associated with intramuscular myxoma (Mazabraud’s syndrome): a long-term follow-up of three cases. J Cancer Res Clin Oncol, 1998, 124(7):401-406.

[8] Sanctis L, Delmastro L, Russo MC, et al. Genetics of Mc Cune-Albright syndrome. J Pediaer Endocrinol Metub, 2006, 19(Suppl 2):577-582.

( 本文編輯：李貴存 )

Mazabraud syndrome: 1 case report

LU Guo-qiang, LI Zi-qiang. Department of Orthopedics, Shanghai Yongpu District Shidong Hospital, Shanghai, 200438, PRC

【Abstract】Objective To investigate clinicopathological characteristics of Mazabraud syndrome by reviewing the data of the fi rst case of the Mazabraud syndrome in China with literature review. Methods We have analyzed the clinical data of a case of hospitalized Mazabraud syndrome patient to clearly diagnose with pathological examination. Result The patient was a 70-year-old male hospitalized for a lump in the left hip for more than half a month. The X-ray fi lms of the pelvis, bilateral hip joints and bilateral upper femurs showed soap bubble-like appearance, which are typical fi ndings of osteo fi brous dysplasia. The CT scan of whole pelvis showed soap-bubble-like appearance of bilateral ilium, patial sacrum, acetabulum, pubis and ischium. There was a 3-cm-diameter cystic mass in left gluteus max imus muscle, of which CT value was 2 - 7 Hu. Postoperative histopathological examination showed loose arrangement of fusiform fi brous tissue and immature fi brous bone, as well as irregular arrangement, English alphabet-shaped tenuity bone trabecula, which was surrounded by a few fl at osteoblasts. This was amyxoma in the left gluteus max imus. Under microscope, the tumor showed clear boundary without capsule. There were much mucus-like substance and few cells. Cells were small, star-shaped and had no speci fi city. Conclusions Mazabraud syndrome is a rare disease, which is de fi ned as fi brous dysplasia associated wish intramuscular myxoma. Development of Mazabraud syndrome may be related to the Gsa gene mutation. Pathology plays an important role in diagnosis of Mazabraud syndrome.

【Key words】Myxoma; Neoplasms, muscle tissue, Neoplasms; Mazabraud syndrome; Fibrous dysplasia

( 收稿日期：2015-07-07 )

DOI:10.3969/j.issn.2095-252X.2016.03.018

中圖分類號(hào)：R738.6