Chondromyxoid fibroma (CMF) is a rare benign bone neoplasm that manifests histologically as a lobular proliferation of stellate to spindle-shaped cells in a myxoid background, exhibiting morphologic overlap with other cartilaginous and myxoid tumors of bone. CMF is characterized by recurrent genetic rearrangements that place the glutamate receptor gene GRM1 under the regulatory control of a constitutively active promoter, leading to increased gene expression. Here, we explore the diagnostic utility of GRM1 immunohistochemistry as a surrogate marker for GRM1 rearrangement using a commercially available monoclonal antibody in a study of 230 tumors, including 30 CMF cases represented by 35 specimens. GRM1 was positive by immunohistochemistry in 97% of CMF specimens (34/35), exhibiting moderate to strong staining in more than 50% of neoplastic cells; staining was diffuse (>95% of cells) in 25 specimens (71%). Among the 9 CMF specimens with documented exposure to acid decalcification, 4 (44%) exhibited diffuse immunoreactivity (>95%) for GRM1, whereas all 15 CMF specimens (100%) with lack of exposure to decalcification reagents were diffusely immunoreactive (P=0.003). High GRM1 expression at the RNA level was previously observed by quantitative reverse transcription polymerase chain reaction in 9 CMF cases that were also positive by immunohistochemistry; low GRM1 expression was observed by quantitative reverse transcription polymerase chain reaction in the single case of CMF that was negative by immunohistochemistry. GRM1 immunohistochemistry was negative (<5%) in histologic mimics of CMF, including conventional chondrosarcoma, enchondroma, chondroblastoma, clear cell chondrosarcoma, giant cell tumor of the bone, fibrous dysplasia, chondroblastic osteosarcoma, myoepithelial tumor, primary aneurysmal bone cyst, brown tumor, phosphaturic mesenchymal tumor, CMF-like osteosarcoma, and extraskeletal myxoid chondrosarcoma. These results indicate that GRM1 immunohistochemistry may have utility in distinguishing CMF from its histologic mimics.

软骨粘液样纤维瘤（CMF）是一种罕见的良性骨肿瘤，组织学上表现为粘液样背景中星状细胞到梭形细胞的小叶增殖，与其他软骨和粘液样骨肿瘤表现出形态重叠。CMF 的特点是反复发生基因重排，将谷氨酸受体基因GRM1置于组成型活性启动子的调控之下，从而导致基因表达增加。在这里，我们使用市售单克隆抗体在 230 个肿瘤的研究中探索GRM1 免疫组织化学作为GRM1重排替代标记的诊断效用，其中包括 35 个标本代表的 30 个 CMF 病例。免疫组织化学显示，97% 的 CMF 标本 (34/35) 呈 GRM1 阳性，在超过 50% 的肿瘤细胞中呈现中度至强染色；25 个样本 (71%) 的染色呈弥漫性（>95% 的细胞）。在记录暴露于酸脱钙的 9 份 CMF 标本中，4 份 (44%) 对 GRM1 表现出弥漫性免疫反应性 (>95%)，而所有 15 份未接触脱钙剂的 CMF 标本 (100%) 均表现出弥漫性免疫反应性 ( P = 0.003）。先前通过定量逆转录聚合酶链反应在 9 例 CMF 病例中观察到了 RNA 水平的高GRM1表达，免疫组化也呈阳性；在免疫组化阴性的 CMF 病例中，通过定量逆转录聚合酶链反应观察到GRM1低表达。CMF 组织学模拟中 GRM1 免疫组织化学呈阴性（<5%），包括传统软骨肉瘤、内生软骨瘤、软骨母细胞瘤、透明细胞软骨肉瘤、骨巨细胞瘤、纤维异常增生、软骨母细胞性骨肉瘤、肌上皮肿瘤、原发性动脉瘤性骨囊肿、棕色肿瘤、磷酸尿性间质肿瘤、CMF 样骨肉瘤和骨外粘液样软骨肉瘤。这些结果表明 GRM1 免疫组织化学可能有助于区分 CMF 与其组织学模拟物。