Anatomical Pathology, Douglass Hanly Moir Pathology, Macquarie Park, NSW, Australia.
Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, NSW, Australia.
Histopathology. 2021 Jul;79(1):106-116. doi: 10.1111/his.14339. Epub 2021 Apr 14.
Myxoid liposarcoma (MLPS) is characterised by DNA damage-inducible transcript 3 (DDIT3) gene rearrangements, confirmation of which is commonly used diagnostically. Recently, DDIT3 immunohistochemistry (IHC) has been reported to be highly sensitive and, when strict criteria are employed, specific for the diagnosis of MLPS. The aim of this study was to independently investigate DDIT3 IHC as a diagnostic marker for MLPS.
DDIT3 IHC was performed on 52 MLPS and on 152 mimics on whole sections, and on 515 non-MLPS sarcomas in tissue microarray format. Only one MLPS (which had undergone acid-based decalcification) was completely negative. With inclusion of this case if any nuclear expression is considered to indicate positivity, the overall sensitivity of DDIT3 is 98% (51 of 52 cases) and the specificity is 94% (633 of 667 non-MLPS cases are negative). If a cut-off of >10% of neoplastic cells is required for positivity, then the sensitivity remains 98% (51/52) and the specificity is 98.5% (657 of 667 non-MLPS cases are negative). If a cut-off of >50% of cells is required for positivity, then the sensitivity is 96% (50 of 52 cases) but the specificity improves to 100%.
Diffuse nuclear DDIT3 expression occurs in the overwhelming majority of MLPSs, and can be used to confirm the diagnosis in most cases without the need for molecular testing. A complete absence of expression argues strongly against MLPS, and almost completely excludes this diagnosis, particularly if there is consideration of technical factors such as decalcification. The significance of focal DDIT3 expression should be interpreted in the morphological and clinical context, although most tumours showing only focal expression are not MLPS.
黏液样脂肪肉瘤（MLPS）的特征在于 DNA 损伤诱导转录 3（DDIT3）基因重排，通常将其确认为诊断标准。最近，有报道称 DDIT3 免疫组化（IHC）具有高度敏感性，并且当采用严格标准时，对 MLPS 的诊断具有特异性。本研究的目的是独立研究 DDIT3 IHC 作为 MLPS 的诊断标志物。
在全切片上对 52 例 MLPS 和 152 例模拟物进行了 DDIT3 IHC，在组织微阵列格式上对 515 例非 MLPS 肉瘤进行了检测。只有一例 MLPS（经过基于酸的脱钙处理）完全呈阴性。如果将任何核表达视为阳性，则包括该病例在内，DDIT3 的总体敏感性为 98%（52 例中的 51 例），特异性为 94%（667 例非 MLPS 病例中 633 例为阴性）。如果要求阳性需要>10%的肿瘤细胞，则敏感性仍为 98%（51/52），特异性为 98.5%（667 例非 MLPS 病例中 657 例为阴性）。如果要求阳性需要>50%的细胞，则敏感性为 96%（52 例中的 50 例），但特异性提高至 100%。
绝大多数 MLPS 中均出现弥漫性核 DDIT3 表达，并且在大多数情况下无需进行分子检测即可使用该表达来确认诊断。完全缺乏表达强烈反对 MLPS，几乎完全排除了该诊断，尤其是在考虑脱钙等技术因素时。只有局灶性 DDIT3 表达的意义应在形态学和临床背景下进行解释，尽管大多数仅表现为局灶性表达的肿瘤不是 MLPS。
