Department of Pathology, Institut Gustave Roussy, Villejuif, France.
Department of Otolaryngology - Head and Neck Surgery, Assistance Publique-Hopitaux de Paris, Lariboisière Hospital, Paris, France.
Histopathology. 2019 Dec;75(6):853-864. doi: 10.1111/his.13954. Epub 2019 Oct 6.
Olfactory neuroblastomas (ONBs) are rare malignant tumours that arise in the nasal vault. To date, the Hyams grade remains the only widely used histological grading system. However, it is based only on morphological criteria, and has not been updated since 1988. The objective of this study was to explore the prognostic potential of the Ki67 proliferation index (PI) and tumour-infiltrating lymphocytes (TILs) in ONB.
A retrospective study was conducted on a bicentric series of 45 cases. The Ki67 PI was determined by counting at least 1000 nuclei on whole slides. TILs were evaluated with CD20, CD4 and CD8 immunohistochemical markers on whole slides. In this series, Hyams grades I, II, III and IV accounted for 13.4%, 44.4%, 20% and 22.2% of all cases, respectively. The Ki67 PI ranged from 1 to 93; the Ki67 PI was significantly higher in Hyams grade III-IV ONBs than in Hyams grade I-II ONBs (P < 0.0001). A Ki67 PI of ≥25 was associated with poorer survival (P = 0.02). TILs were present in both stromal and intratumoral compartments, but were located predominantly in the stromal component of the tumour. The numbers of intratumoral CD8+ cells/mm and CD4+ cells/mm were greater in high-grade ONBs than in low-grade ONBs (P = 0.0015 and P = 0.043, respectively). The numbers of T cells/mm and B cells/mm were not associated with survival, but a CD4/CD8 ratio of >2 was significantly associated with shorter survival (P = 0.04).
Our findings suggest that the Ki67 PI and TILs could be used as prognostic markers, as a potential alternative to the Hyams grade.
嗅神经母细胞瘤（ONB）是一种罕见的恶性肿瘤，起源于鼻腔穹窿。迄今为止，Hyams 分级仍然是唯一广泛使用的组织学分级系统。然而，它仅基于形态学标准，自 1988 年以来并未更新。本研究的目的是探讨 Ki67 增殖指数（PI）和肿瘤浸润淋巴细胞（TILs）在 ONB 中的预后潜力。
对两个中心的 45 例病例进行了回顾性研究。通过在整个幻灯片上计数至少 1000 个细胞核来确定 Ki67 PI。TILs 用 CD20、CD4 和 CD8 免疫组化标志物在整个幻灯片上进行评估。在本系列中，Hyams 分级 I、II、III 和 IV 分别占所有病例的 13.4%、44.4%、20%和 22.2%。Ki67 PI 范围为 1 至 93；Hyams 分级 III-IV ONB 的 Ki67 PI 明显高于 Hyams 分级 I-II ONB（P<0.0001）。Ki67 PI≥25 与生存率较差相关（P=0.02）。TILs 存在于基质和肿瘤内部位，但主要位于肿瘤的基质成分中。高分级 ONB 的肿瘤内 CD8+细胞/mm 和 CD4+细胞/mm 数量高于低分级 ONB（P=0.0015 和 P=0.043）。T 细胞/mm 和 B 细胞/mm 的数量与生存率无关，但 CD4/CD8 比值>2 与生存率较短显著相关（P=0.04）。
我们的研究结果表明，Ki67 PI 和 TILs 可用作预后标志物，作为替代 Hyams 分级的潜在方法。
