Department of Pathology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
Department of Oral and Maxillofacial Surgery / Head and Neck Surgery, Amsterdam University Medical Center/Antoni Van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
Virchows Arch. 2022 Oct;481(4):671-675. doi: 10.1007/s00428-022-03341-4. Epub 2022 May 25.
Non-ossifying fibroma (NOF) and central giant cell granuloma (CGCG) are both benign tumours of bone with overlapping morphology and similar mutations in the RAS/MAPK pathway. However, NOF is located in the long bones with regression after puberty in contrast to CGCG which is located in the jaw bones and does not regress spontaneously. We hypothesised that endocrine regulation by oestrogen plays a role in the spontaneous regression in NOF. Therefore, we examined the expression of ERα in a series of NOF and CGCG. ERα expression (EP1) was determined using immunohistochemistry on 16 NOFs (whole slides), and 47 CGCGs (tissue microarrays (TMA's n = 41 and whole slide n = 6)). As comparison, we included TMAs of other giant cell containing bone lesions: giant cell tumour of bone (n = 75), chondroblastoma (n = 12), chondromyxoid fibroma (n = 12), aneurysmal bone cyst (n = 6) and telangiectatic osteosarcoma (n = 6). All 16 NOF samples demonstrated ERα protein expression, while all 47 CGCG and all other giant cell containing bone tumours were negative. Most NOF samples had moderate staining intensity and between 24 and 49% of the spindle cells were ERα-positive. Our findings further support the role of endocrine regulation via oestrogen in the spontaneous regression in NOF. Whether oestrogen signalling at puberty is involved in the induction of senescence in the neoplastic cells of NOF harbouring RAS/MAPK pathway mutations needs further research. Since ERα expression was not observed in other giant cell containing bone lesions with overlapping morphological features, positive ERα expression may favour the diagnosis of NOF in challenging diagnostic cases.
非骨化性纤维瘤 (NOF) 和中央性 giant cell 肉芽肿 (CGCG) 都是具有重叠形态学特征和相似 RAS/MAPK 通路突变的良性骨肿瘤。然而，NOF 位于长骨中，青春期后会自行消退，而 CGCG 则位于颌骨中，不会自行消退。我们假设雌激素的内分泌调节在 NOF 的自发消退中发挥作用。因此，我们检查了一系列 NOF 和 CGCG 中 ERα 的表达。使用免疫组织化学方法在 16 个 NOF（全切片）和 47 个 CGCG（组织微阵列 (TMA)n=41 和全切片 n=6）上测定 ERα 表达 (EP1)。作为比较，我们还包括了其他含有 giant cell 的骨病变的 TMA：骨巨细胞瘤 (n=75)、软骨母细胞瘤 (n=12)、软骨黏液样纤维瘤 (n=12)、动脉瘤样骨囊肿 (n=6) 和毛细血管扩张性骨肉瘤 (n=6)。所有 16 个 NOF 样本均显示 ERα 蛋白表达，而所有 47 个 CGCG 和所有其他含有 giant cell 的骨肿瘤均为阴性。大多数 NOF 样本染色强度中等，24%至 49%的梭形细胞为 ERα 阳性。我们的发现进一步支持了雌激素通过内分泌调节在 NOF 自发消退中的作用。青春期雌激素信号是否参与携带 RAS/MAPK 通路突变的 NOF 肿瘤细胞的衰老诱导，需要进一步研究。由于在具有重叠形态学特征的其他含有 giant cell 的骨病变中未观察到 ERα 表达，因此阳性 ERα 表达可能有利于在具有挑战性的诊断病例中诊断 NOF。
