Pathology Department, University Hospital of Bordeaux, Hôpital Haut-Lévêque, Bordeaux, France.
INSERM U1053, Team 3 Oncogenesis of Cutaneous Lymphomas, University of Bordeaux, Bordeaux, France.
Histopathology. 2019 Jun;74(7):1067-1080. doi: 10.1111/his.13832. Epub 2019 Apr 25.
We applied the 2017 World Health Organization (WHO) classification criteria to categorise a series of 64 primary cutaneous large B-cell lymphomas (PCLBCLs), containing a majority (≥80%) of large cells and a proliferative rate of ≥40%, raising the problem of the differential diagnosis between PCLBCL, leg type (PCLBCL-LT) and primary cutaneous follicle centre lymphoma, large cell (PCFCL-LC). The aims were to determine the reproducibility and prognostic relevance of the 2017 WHO criteria.
Morphology and phenotype identified 32 PCLBCLs-LT and 25 PCFCLs-LC; seven cases (11%) remained unclassified. Morphology was less reproducible than immunophenotype. Pertinent markers for the differential diagnosis were MUM1, FOXP1, CD10, and IgM. bcl-2 and bcl-6 were expressed by both PCFCLs-LC and PCLBCLs-LT at substantial levels. Neither Ki67 expression nor p63 expression was of diagnostic value. MYD88 was found to be mutated only in PCLBCLs-LT (n = 22, 69%). According to Hans/Hans modified algorithms, 23 of 25 PCFCLs-LC had germinal centre (GC) status, and the 32 PCLBCLs-LT had non-GC status. Overall survival was poorer for PCLBCLs-LT than PCFCLs-LC (P = 0.0002). Non-GC cases had poorer overall survival than GC cases (P = 0.0007). In PCLBCLs-LT, MYC expression was associated with cutaneous relapses (P = 0.014). When GC/non-GC status was applied to unclassified cases, only a single case remained discordant.
Our results support the 2017 WHO classification criteria for PCLBCL diagnosis. The Hans modified algorithm using CD10 and MUM1 distinguished PCFCLs-LC from PCLBCLs-LT with optimal diagnostic value without requiring bcl-6 immunolabelling (poorly reproducible). Rare unclassified cases may constitute a provisionally heterogeneous subgroup for which GC/non-GC status (relevant for prognosis) may guide therapeutic decisions.
我们应用 2017 年世界卫生组织（WHO）分类标准对一系列 64 例原发性皮肤大 B 细胞淋巴瘤（PCLBCL）进行分类，这些病例中大多数（≥80%）为大细胞，增殖率≥40%，这就提出了 PCBCL-LT 与原发性皮肤滤泡中心淋巴瘤、大细胞型（PCFCL-LC）之间的鉴别诊断问题。本研究旨在确定 2017 年 WHO 标准的可重复性和预后相关性。
形态学和表型鉴定出 32 例 PCLBCL-LT 和 25 例 PCFCL-LC；7 例（11%）病例未分类。形态学的可重复性不如免疫表型。鉴别诊断的相关标志物为 MUM1、FOXP1、CD10 和 IgM。bcl-2 和 bcl-6 在 PCFCL-LC 和 PCLBCL-LT 中均有大量表达。Ki67 表达和 p63 表达均无诊断价值。仅在 PCLBCL-LT（n=22，69%）中发现 MYD88 突变。根据 Hans/Hans 改良算法，25 例 PCFCL-LC 中有 23 例具有生发中心（GC）状态，32 例 PCLBCL-LT 无 GC 状态。PCLBCL-LT 的总体生存率低于 PCFCL-LC（P=0.0002）。非 GC 病例的总体生存率低于 GC 病例（P=0.0007）。在 PCLBCL-LT 中，MYC 表达与皮肤复发相关（P=0.014）。当应用 GC/非 GC 状态于未分类病例时，仅有 1 例结果不一致。
我们的研究结果支持 2017 年 WHO 对 PCLBCL 诊断的分类标准。使用 CD10 和 MUM1 的 Hans 改良算法可以最佳地鉴别 PCFCL-LC 和 PCLBCL-LT，具有最佳的诊断价值，而无需进行 bcl-6 免疫标记（可重复性差）。少数罕见的未分类病例可能构成一个暂时异质性亚组，GC/非 GC 状态（与预后相关）可能指导治疗决策。
