van Roggen J F Graadt, van Unnik J A M, Briaire-de Bruijn I H, Hogendoorn P C W
Department of Pathology, Leiden University Medical Centre, Building I, L1-Q, P.O. Box 9600, 2300RC, Leiden, The Netherlands.
Virchows Arch. 2005 Feb;446(2):157-63. doi: 10.1007/s00428-004-1135-9. Epub 2004 Nov 3.
To report the clinicopathological and immunohistochemical features and longer term biological behaviour of aggressive angiomyxoma, an uncommon mesenchymal neoplasm occurring predominantly in the pelvi-perineal region of adults. Using immunohistochemistry, possible overexpression of CDK4 and MDM2 was analysed, which might point to (cyto)genetic alteration(s) in chromosome region 12q13-15, an area reported to be altered in this tumour entity.
Cases (n=11) of aggressive angiomyxoma were retrieved from the consultation files of the Comprehensive Cancer Centre of the Middle Netherlands (IKMN) panel for soft tissue tumours. Clinical and follow-up information were obtained, and immunohistochemical analysis was performed using antibodies directed against vimentin, cytokeratin AE1/AE3, desmin, alpha-smooth-muscle actin, CD34, S-100 protein, oestrogen receptors, CDK4 and MDM2. Five patients were female (age range 24-47 years; median 39 years), and six patients were male (age range 36-69 years; median 44.5 years). Of 11 cases, 10 arose in the pelvi-perineal area and 1 arose in the abdominal cavity in close relation to the bladder. Morphology was consistent with previous reports of this entity. Immunohistochemically, 8 of 11 cases were desmin positive (5 of 5 positive in females; 3 of 6 positive in males), 6 of 11 cases were positive for alpha-smooth-muscle actin, 5 of 11 cases were CD34 positive, 11 of 11 cases, irrespective of gender, were positive for oestrogen receptors and 3 of 11 cases were positive for cytokeratin AE1/AE3. Strong, diffuse nuclear positivity for CDK4 expression was present in all 6 cases tested, while only 1 of 11 cases tested for MDM2 showed weak focal positivity. Clinical follow-up in all cases (range 1-216 months; median 72 months) showed one local recurrence (9%) after 36 months. No metastases or tumour-related deaths were noted.
The sex distribution of cases reported in this study was roughly equal, in contrast to previous reports emphasising the predominance of this tumour in females. Our study confirms the local aggressive nature of aggressive angiomyxoma, although our local recurrence rate is lower than previous reports (9% versus 36-72%); no metastases and/or disease-related patient deaths were documented. All cases arising in females were positive for desmin, while three of the six cases arising in males were negative for desmin, supporting previous findings and indicating that the lesion may be somewhat different in males. The strong diffuse positivity for CDK4 in all six cases tested goes some way in implicating CDK4, either directly or indirectly, in tumourigenesis. The negative immunostaining for MDM2 would argue against functional amplification of this gene.
报告侵袭性血管黏液瘤的临床病理、免疫组化特征及长期生物学行为。侵袭性血管黏液瘤是一种罕见的间叶性肿瘤，主要发生于成年患者的盆腔 - 会阴区。通过免疫组化分析CDK4和MDM2是否可能过度表达，这可能提示12q13 - 15染色体区域的（细胞）遗传学改变，该区域据报道在这一肿瘤实体中发生改变。
从荷兰中部综合癌症中心（IKMN）软组织肿瘤会诊档案中检索出11例侵袭性血管黏液瘤病例。获取临床及随访信息，并使用针对波形蛋白、细胞角蛋白AE1/AE3、结蛋白、α - 平滑肌肌动蛋白、CD34、S - 100蛋白、雌激素受体、CDK4和MDM2的抗体进行免疫组化分析。5例为女性（年龄范围24 - 47岁；中位年龄39岁），6例为男性（年龄范围36 - 69岁；中位年龄44.5岁）。11例病例中，10例发生于盆腔 - 会阴区，1例发生于腹腔，与膀胱关系密切。形态学与该实体先前报道一致。免疫组化结果显示，11例中有8例结蛋白阳性（女性5例均阳性；男性6例中有3例阳性），11例中有6例α - 平滑肌肌动蛋白阳性，11例中有5例CD34阳性，11例无论性别均雌激素受体阳性，11例中有3例细胞角蛋白AE1/AE3阳性。所有6例检测的病例中CDK4表达均呈强弥漫性核阳性，而11例检测MDM2的病例中仅1例呈弱局灶性阳性。所有病例的临床随访（范围1 - 216个月；中位72个月）显示36个月后有1例局部复发（9%）。未发现转移或肿瘤相关死亡。
本研究报道病例的性别分布大致相等，与先前强调该肿瘤女性占优势的报道相反。我们的研究证实了侵袭性血管黏液瘤的局部侵袭性，尽管我们的局部复发率低于先前报道（9% 对36 - 72%）；未记录到转移和/或疾病相关的患者死亡。所有女性病例结蛋白均阳性，而男性6例中有3例结蛋白阴性，支持先前研究结果，提示该病变在男性中可能有所不同。所有6例检测病例中CDK4的强弥漫性阳性在一定程度上直接或间接表明CDK4参与肿瘤发生。MDM2免疫染色阴性表明该基因无功能扩增。
