Section of Histopathology, Department of Pathology and Laboratory Medicine, Aga Khan University Hospital, Karachi, Pakistan.
Department of Orthopaedic Surgery, Aga Khan University Hospital, Karachi, Pakistan.
Ann Diagn Pathol. 2020 Apr;45:151479. doi: 10.1016/j.anndiagpath.2020.151479. Epub 2020 Feb 14.
Denosumab is Receptor Activator of Nuclear factor Kappa-B Ligand (RANKL) inhibitor which is being used in the treatment of locally advanced, recurrent and metastatic Giant Cell Tumor of Bone (GCTB). It causes reduction in monocyte recruitment and Osteoclast-Like Giant Cell (OLGC) formation which limits bone destruction. After Denosumab treatment, GCTB exhibit diverse morphological features which can pose diagnostic challenge. Our aim was to study the spectrum of histologic features seen in Denosumab treated GCTB which could be helpful in establishing correct diagnosis.
We retrieved and reviewed H&E stained microscopic glass slides of 38 GCTB cases who received Denosumab as neoadjuvant treatment. These cases were treated at different institutes and diagnosed at our institute between January 2017 and October 2019. Morphologic features such as presence of residual OLGC, appearances of mononuclear stromal and bony components were assessed along with other non-specific features.
Patients' median age was 29 years. Male to female ratio was 1.53:1. Femur was the most commonly involved bone. Microscopically, peripheral shell of reactive bone was observed in all cases. In 20 (52.6%) cases, there was complete elimination of OLGC. Mononuclear stromal cells were predominantly bland spindle shaped and arranged in fascicular and storiform patterns. Focal atypia was noted in 3 cases. Bony component manifested as trabeculae of woven bone with osteoblastic rimming and immature trabeculae of unmineralized osteoid with haphazardly present osteoblasts. Spectrum of stromal changes included cystic spaces, foamy macrophages, inflammatory infiltrate, hemangiopericytoma-like (HPC-like) vessels, hyalinization, edematous areas and hemosiderin pigment. The tumors showed areas which resembled other bony and soft tissue lesions such non-ossifying fibroma, fibrous dysplasia, osteoblastoma, sclerosing epithelioid fibrosarcoma and osteosarcoma.
Denosumab treatment induces a variety of changes in GCTB. Clinical history and knowledge of these features are necessary for excluding differential diagnoses and avoiding misdiagnosis.
地舒单抗是核因子κB 受体激活配体（RANKL）抑制剂，用于治疗局部晚期、复发性和转移性骨巨细胞瘤（GCTB）。它可减少单核细胞募集和破骨细胞样巨细胞（OLGC）的形成，从而限制骨破坏。地舒单抗治疗后，GCTB 表现出多种形态特征，这可能会对诊断造成挑战。我们的目的是研究地舒单抗治疗的 GCTB 中观察到的组织学特征谱，这有助于建立正确的诊断。
我们检索并复习了 38 例接受地舒单抗新辅助治疗的 GCTB 患者的 H&E 染色显微镜玻片。这些病例分别在不同的机构治疗，并在 2017 年 1 月至 2019 年 10 月在我们的机构诊断。评估了残留 OLGC 的存在、单核间质和骨成分的外观等形态特征以及其他非特异性特征。
患者的中位年龄为 29 岁，男女比例为 1.53:1，最常受累的骨骼是股骨。所有病例均观察到反应性骨的外周壳。20 例（52.6%）中，OLGC 完全消除。单核间质细胞主要为温和的梭形，呈束状和板层状排列。3 例有局灶性异型性。骨成分表现为编织骨小梁，伴有成骨细胞包绕和未矿化的类骨质小梁，随机存在成骨细胞。基质变化的范围包括囊性空间、泡沫状巨噬细胞、炎症浸润、血管外皮细胞瘤样（HPC 样）血管、玻璃样变、水肿区和含铁血黄素色素。肿瘤表现出与其他骨和软组织病变相似的区域，如非骨化性纤维瘤、纤维结构不良、骨母细胞瘤、硬化性上皮样纤维肉瘤和骨肉瘤。
地舒单抗治疗可引起 GCTB 发生多种变化。了解这些特征的临床病史和知识对于排除鉴别诊断和避免误诊是必要的。
