1] EA2406 Histology and Molecular Pathology of Tumors, University of Bordeaux, Bordeaux, France [2] Dermatology Department, CHU Bordeaux, Bordeaux, France.
EA2406 Histology and Molecular Pathology of Tumors, University of Bordeaux, Bordeaux, France.
Mod Pathol. 2014 Mar;27(3):402-11. doi: 10.1038/modpathol.2013.156. Epub 2013 Sep 13.
Primary cutaneous large B-cell lymphoma, leg type has been individualized from nodal diffuse large B-cell lymphoma. The objective of this study was to screen primary cutaneous large B-cell lymphoma, leg type for genetic alterations recently described in nodal diffuse large B-cell lymphoma. Skin biopsies from 23 patients were analyzed for IRF4, BCL2, BCL6, and MYC expression. FISH testing was performed for BCL2, BCL6, MYC with separation probes and for CDKN2A and PRDM1/BLIMP1 deletion. Multiple sequential FISH analyses with up to six probes were performed to define samples with multiple cytogenetic alterations. MYD88 mutations were studied by Sanger sequencing. All cases but one displayed at least one genetic alteration (96%). Nine patients exhibited a single genetic mutation and 12 combined several alterations (52%). We observed a split for BCL2, BCL6, or MYC in 1/23, 6/23, and 3/23 of cases, respectively. No double-hit lymphoma was observed. CDKN2A deletion was detected by FISH in only 5/23 cases. BLIMP1 and/or 6q deletion was observed at a higher rate in 10/20 of cases. No correlation between rearrangement and immunohistochemical expression was found for BCL2 or MYC. FISH tracking of sequential hybridizations showed that several alterations were carried by the same nuclei. The p.L265P MYD88 mutation was found in 11/18 (61%) of cases. Contrary to most cutaneous lymphomas that rarely harbor primary genetic alteration of their nodal histological equivalent, primary cutaneous large B-cell lymphoma, leg type seems to be a 'cutaneous counterpart' of activated B-cell-like diffuse large B-cell lymphoma with a similar cytogenetic profile and a high rate of MYD88 oncogenic L265P mutation. This also suggests a common lymphomagenesis with NF-κB activation, strong IRF4 expression and terminal B-cell differentiation blockage. Our data support the use of therapies targeting NF-κB, as most patients displayed disease progression and resistance to conventional therapies.
原发性皮肤大 B 细胞淋巴瘤，腿型已从结内弥漫性大 B 细胞淋巴瘤中分离出来。本研究的目的是筛选最近在结内弥漫性大 B 细胞淋巴瘤中描述的原发性皮肤大 B 细胞淋巴瘤，腿型的遗传改变。对 23 例患者的皮肤活检进行了 IRF4、BCL2、BCL6 和 MYC 表达的分析。使用分离探针进行了 BCL2、BCL6、MYC 的 FISH 检测，以及 CDKN2A 和 PRDM1/BLIMP1 缺失的检测。进行了多达 6 个探针的多次连续 FISH 分析，以确定具有多种细胞遗传学改变的样本。通过 Sanger 测序研究了 MYD88 突变。除 1 例外，所有病例均显示至少一种遗传改变（96%）。9 例患者表现出单一基因突变，12 例患者联合多种改变（52%）。我们观察到在 23 例病例中的 1/23、6/23 和 3/23 分别出现了 BCL2、BCL6 或 MYC 的分裂。未观察到双打击淋巴瘤。FISH 在仅 5/23 例中检测到 CDKN2A 缺失。在 10/20 的病例中观察到 BLIMP1 和/或 6q 缺失的发生率更高。在 BCL2 或 MYC 中，未发现重排与免疫组化表达之间的相关性。对连续杂交的 FISH 跟踪显示，几个改变由相同的核携带。在 18 例中的 11 例（61%）发现了 p.L265P MYD88 突变。与很少携带与其结内组织学等效物的原发性遗传改变的大多数皮肤淋巴瘤相反，原发性皮肤大 B 细胞淋巴瘤，腿型似乎是激活 B 细胞样弥漫性大 B 细胞淋巴瘤的“皮肤对应物”，具有相似的细胞遗传学特征和高 MYD88 致癌 L265P 突变率。这也表明共同的淋巴瘤发生与 NF-κB 激活、强烈的 IRF4 表达和末端 B 细胞分化阻断有关。我们的数据支持使用针对 NF-κB 的治疗方法，因为大多数患者表现出疾病进展和对常规治疗的耐药性。
