Mazabraud 综合征一例

陆国强 李自强



Mazabraud 综合征一例

陆国强 李自强

作者单位：200438 上海市杨浦区市东医院骨科

【关键词】黏液瘤；肿瘤，肌组织；肿瘤；Mazabraud 综合征；骨纤维结构不良

Mazabraud 综合征是一种非常罕见的散发性疾病。临床上以骨纤维结构不良 ( fibrous dysplasia，FD ) 和肌肉黏液瘤 ( intramuscular myxoma，IM ) 见于同一患者时被称为Mazabraud 综合征。1926 年，Henschen 对此病首次进行了描述，1957 年 Mazabraud 进一步描述二者相关性，并被命名为 Mazabraud 综合征[1]。目前为止报道不满 80 例[2]。2014 年 9 月我院经治 1 例，现报告如下。

临床资料

患者，男，70 岁。因“发现左臀部肿块半月余”于2014 年 9 月 18 日入院。入院检查：左臀部外上方可扪及 4 cm×4 cm×3 cm 大小包块，表面光滑，边界清楚，活动度差，质韧，无明显压痛。左下肢肢体较右下肢短缩 2 cm。双下肢感觉、运动正常。双下肢末梢血运正常。既往史除有高血压外均无异常。否认外伤手术史。入院检查：血常规，肝肾功能，电解质，血糖，血脂，免疫相关检查，肿瘤标志物筛选均未见异常，血沉，C-反应蛋白均正常。骨代谢检查：骨钙素 N 端中分子片段：153.80 ng / ml ( 正常 14～46 ng / ml )，总 1I 型胶原羧基端前肽：1141. ng / ml ( 正常 16.27～73.87 ng / ml )，25 羟维生素 D 测定：15.52 ng / ml ( 正常＞20 ng / ml )，β-胶原降解产物：1.09 ng / ml ( 正常 0.1～1 ng / ml )，甲状旁腺素：46.98 pg / ml ( 正常 15～65 pg / ml )，碱性磷酸酶 289 U / L ( 正常 35～123 U / L )。影像学检查：( 1 ) X 线：骨盆摄片：所见髋部诸骨皂泡样病变，考虑骨纤维结构不良；左右股骨上段摄片：左右股骨上段及右髋诸骨皂泡样病变，考虑骨纤维结构不良，伴右髋退行性变。( 2 ) CT：盆腔平扫：骨盆畸形状，双侧髂骨、股骨及部分骶骨、髋臼、耻骨、坐骨膨胀伴多发皂泡样变，部分病灶内见增密影，以左侧为甚。左臀部肌肉区见一直径约 3 cm 囊性灶，CT 值约 2～7 Hu，边缘光滑。前列腺内钙化灶。结论：骨纤维结构不良可能。左臀部肌肉区囊性灶。经适当术前准备，于 9 月 22 日在全麻下行左臀部肌肉肿块切除，左股骨大转子活检术。手术完整切除左臀部肌肉内肿块，并取左股骨大转子病灶处穿刺活检并送病理检查。病理检查：大体标本：( 1 ) 左臀部外侧肌肉肿块呈椭圆形，直径为 5 cm，表面光滑，有滑囊及滑液包绕，血供较丰富。剖面呈半透明、鱼肉样。( 2 ) 左股骨大转子穿刺活检，长约 1.2 cm 直径 0.3 cm 条索状组织，灰白色，质较硬。病理诊断：左臀大肌：肌肉黏液瘤。左股骨大转子：纤维结构不良。结合临床，Mazabraud 综合征。( 本病例经上海市临床病理读片会讨论确定 )。术后随访 7 个月，一般情况良好，能正常行走。

图 1　Mazabraud 综合征 X 线片：骨盆、双髋关节、双股骨上段均见皂泡样病变，考虑骨纤维结构不良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

图 2　Mazabraud 综合征 CT 全盆腔平扫：骨盆畸形状，双侧髂骨、股骨及部分骶骨、髋臼、耻骨、坐骨膨胀伴多发皂泡样变，部分病灶内见增密影，以左侧为甚。左臀部肌肉区见一直径约 3 cm 囊性灶，CT 值约 2～7 Hu，边缘光滑。结论：骨纤维结构不良可能。左臀部肌肉区囊性灶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

图 3　左股骨大转子骨纤维结构不良显微镜示排列疏松的梭形纤维组织及不成熟编织骨，骨小梁纤细，排列不规则，呈英文字母形，周围有少量扁平的骨母细胞围绕 ( 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 )

图 4　左臀大肌内粘液瘤显微镜示肿瘤边界清楚但无包膜，肿瘤组织富含大量黏液样物质少细胞性，细胞小，呈星状突起，无异型性( 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 )

讨 论

Mazabraud 综合征好发于女性。男性少见。Zoccali 等[3]报道超过 2 / 3 的病例为女性。发病年龄骨纤维结构不良中位年龄 34 岁，而肌肉黏液瘤发病中位年龄 43 岁。

Mazabraud 综合征的骨纤维结构不良是一种原因不明，进展缓慢的良性纤维性骨病。大部分患者病变为多骨性损伤，也可为单骨性损伤。常见于股骨，其次为盆骨，也可见于肋骨。一般无症状，后期可出现病理性骨折或肢体弯曲畸形。肌内黏液瘤是一种生长缓慢的良性间叶组织来源肿瘤。发病较晚，同样肌内黏液瘤也可单发或多发，以多发为主，常见于大腿。肿瘤一般不大，有文献报道直径最大 20 cm，平均 5～10 cm[4]。本例为 70 岁男性，以发现左臀部肿块而就医，以前无任何骨骼 X 线片检查，与描述相符。Mazabraud 综合征中骨纤维结构不良的 X 线表现为在长骨骨干之界限清楚的囊状透亮区，呈现模糊不清的磨砂玻璃状。骨皮质膨胀，一般无骨膜反应[5]。CT 和 MRI 能更好地反应病变特征和范围。Mazabraud 综合征病因不明，近年来，现代分子遗传学研究提示骨纤维结构不良和肌内黏液瘤都与 Gsa 基因突变有关。2002 年版WHO“骨与软组织肿瘤”明确骨纤维结构不良是由于位于 20 号染色体长臂 1 区 3 带 GNAS1 基因变异，导致 Gsa活性异常，环腺苷酸 ( cAMP ) 活性增加，使骨母细胞分化异常而产生异常的不成熟骨小梁。肌内黏液瘤也有染色体20q13.2-20q13.3 的 GNAS1 基因变异，使编码 Gsa 蛋白突变。Ohamoto 推测肌内黏液瘤的基因突变发生时间比骨纤维结构不良迟，因此解释骨纤维结构不良发病比肌内黏液瘤早[6]。

Mazabraud 综合征的治疗，对于肌内黏液瘤可手术完整切除，一般很少恶变，但可复发[7]。骨纤维结构不良必须密切随访，有文献报道可偶发生骨肉瘤变[7]。但也有报道认为其恶变率较高[8]。另外，由于临床上对于骨纤维结构不良患者很少关注肌肉症状和相关检查，多数患者被漏诊。为获得早期诊断，建议对所有骨纤维结构不良患者进行常规肌肉体格检查，必要时辅以 MRI 检查，注意有无合并肌内黏液瘤存在。同样对肌内黏液瘤的患者，也须注意有无骨纤维结构不良存在，必要时可进行全身骨扫描。一旦二者同时存在即可诊断为 Mazabraud 综合征。

参 考 文 献

[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] 赵叶红, 张惠箴, 蒋智铭, 等. Mazabraud综合征临床病理特征. 临床与实验病理学杂志, 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] 李景学, 孙鼎元. 骨关节X线诊断学. 北京: 人民卫生出版社. 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.

( 本文编辑：李贵存 )

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

中图分类号：R738.6