Clay Michael R, Martinez Anthony P, Weiss Sharon W, Edgar Mark A
Department of Pathology, Emory University Hospital, Atlanta, GA.
Am J Surg Pathol. 2016 Dec;40(12):1647-1652. doi: 10.1097/PAS.0000000000000713.
Although most cases of atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) can be diagnosed solely on the basis of histologic features, those lacking diagnostic histologic features require ancillary studies for accurate classification. Fluorescent in situ hybridization (FISH) for amplification of MDM2 has been considered the gold standard for diagnosis in these situations. Immunostaining for MDM2 and/or CDK4 has been adopted as a surrogate method because of its high concordance rate with FISH and lower cost. However, studies examining the concordance of the 2 methods have been based preferentially on cases in which the diagnosis could be established histologically. No study has explored the concordance between the 2 methods in histologically ambiguous cases or in cases in which the diagnosis of ALT/WDL is not apparent after a review of all slides. To address this, we performed immunostaining for MDM2 and CDK4 on 183 well-differentiated lipomatous tumors that could not be diagnosed on purely histologic grounds and that were, therefore, subjected to FISH analysis. These included ALT/WDLs (n=56), lipomas (n=96), and lipoma variants (n=31). Staining for MDM2 and CDK4 was noted in 25/56 and 23/56 ALT/WDL, respectively, giving a sensitivity of 45% and 41% and a specificity of 98% and 92%. Staining was noted exclusively in the nuclei of atypical cells and not in the nuclei of adipocytes. Staining for MDM2 and CDK4 occurred in 2/125 and 10/117 benign lipomatous lesions, respectively. False-positive staining was equivalent in intensity to ALT/WDL. We conclude that MDM2 and CDK4 staining is a relatively insensitive method for diagnosing ALT/WDL in cases that are histologically ambiguous, as staining is restricted to neoplastic cells with atypia that are underrepresented in these cases. Therefore, in cases like ours that closely simulate clinical practice, FISH is the more reliable and cost-effective option.
虽然大多数非典型脂肪瘤性肿瘤/高分化脂肪肉瘤（ALT/WDL）病例仅根据组织学特征即可诊断，但那些缺乏诊断性组织学特征的病例需要辅助检查以进行准确分类。MDM2基因扩增的荧光原位杂交（FISH）被认为是这些情况下诊断的金标准。由于MDM2和/或CDK4免疫染色与FISH的一致性高且成本较低，已被用作替代方法。然而，研究这两种方法一致性的研究主要基于组织学上可确诊的病例。尚无研究探讨这两种方法在组织学不明确的病例中或在复查所有切片后ALT/WDL诊断不明确的病例中的一致性。为解决这一问题，我们对183例不能单纯根据组织学诊断的高分化脂肪瘤性肿瘤进行了MDM2和CDK4免疫染色，因此这些病例均进行了FISH分析。其中包括ALT/WDL（n = 56）、脂肪瘤（n = 96）和脂肪瘤变异型（n = 31）。MDM2和CDK4染色在56例ALT/WDL中分别为25例和23例，敏感性分别为45%和41%，特异性分别为98%和92%。染色仅见于非典型细胞的细胞核，而不见于脂肪细胞的细胞核。MDM2和CDK4染色分别出现在125例良性脂肪瘤性病变中的2例和117例中的10例。假阳性染色强度与ALT/WDL相当。我们得出结论，在组织学不明确的病例中，MDM2和CDK4染色诊断ALT/WDL是一种相对不敏感的方法，因为染色仅限于这些病例中代表性不足的具有异型性的肿瘤细胞。因此，在像我们这样接近临床实际的病例中，FISH是更可靠且性价比更高的选择。
