1st Department of Pathology and Experimental Cancer Research, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
Histopathology. 2012 May;60(6B):E66-75. doi: 10.1111/j.1365-2559.2012.04187.x. Epub 2012 Mar 6.
Follicular lymphoma (FL) is associated with bone marrow (BM) involvement in approximately 40-70% of cases. Previous studies have suggested that the immune-microenvironment of FL plays an important role in the clinical behaviour of the disease. To investigate the role of the microenvironment in BM involvement of FL, we performed immunophenotypical analysis of the reactive cell populations in lymph nodes (LN) and corresponding BM of 35 patients with FL. Microenvironment patterns of BM infiltrates were compared to the corresponding features of the LN in cases with BM manifestation, and the LN microenvironment was compared in FL cases with and without BM involvement.
Automated image-segmentation-based quantitation was performed in whole digital slides of tissue microarrays of formalin-fixed paraffin-embedded tissue biopsies. We found significantly more CD8(+) T lymphocytes, forkhead box protein 3 (FoxP3)(+) T lymphocytes and CD68(+) macrophages and fewer PD1(+) T lymphocytes in the BM than in the matching LN samples. Furthermore, we observed significantly fewer CD8(+) T cells and CD68(+) macrophages in cases involving the BM compared to those localized only to the LNs.
Our study showed that different tumour cell growth in the LN and BM may generate different microenvironments, and suggested that the reduced number of cytotoxic T lymphocytes and macrophages in LNs favours BM infiltration of neoplastic cells in FL.
滤泡性淋巴瘤（FL）约有 40-70%的病例伴有骨髓（BM）受累。先前的研究表明，FL 的免疫微环境在疾病的临床行为中起着重要作用。为了研究微环境在 FL 骨髓受累中的作用，我们对 35 例 FL 患者的淋巴结（LN）和相应 BM 的反应细胞群进行了免疫表型分析。将 BM 浸润的微环境模式与有 BM 表现的病例的 LN 相应特征进行比较，并比较了有和无 BM 受累的 FL 病例的 LN 微环境。
对福尔马林固定石蜡包埋组织活检的组织微阵列的全数字切片进行了基于自动化图像分割的定量分析。我们发现 BM 中的 CD8(+) T 淋巴细胞、叉头框蛋白 3（FoxP3)(+) T 淋巴细胞和 CD68(+) 巨噬细胞明显多于匹配的 LN 样本，而 PD1(+) T 淋巴细胞则明显减少。此外，我们观察到 BM 受累的病例中 CD8(+) T 细胞和 CD68(+) 巨噬细胞明显少于仅局限于 LN 的病例。
我们的研究表明，LN 和 BM 中不同的肿瘤细胞生长可能产生不同的微环境，并表明 LN 中细胞毒性 T 淋巴细胞和巨噬细胞数量减少有利于 FL 中肿瘤细胞向 BM 的浸润。
