Wobser Marion, Schummer Patrick, Appenzeller Silke, Kneitz Hermann, Roth Sabine, Goebeler Matthias, Geissinger Eva, Rosenwald Andreas, Maurus Katja
Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, 97080 Würzburg, Germany.
Comprehensive Cancer Center Mainfranken, University Hospital Würzburg, 97080 Würzburg, Germany.
Cancers (Basel). 2022 Oct 27;14(21):5274. doi: 10.3390/cancers14215274.
Primary cutaneous follicular B-cell lymphoma (PCFBCL) represents an indolent subtype of Non-Hodgkin's lymphomas, being clinically characterized by slowly growing tumors of the skin and common cutaneous relapses, while only exhibiting a low propensity for systemic dissemination or fatal outcome. Up to now, only few studies have investigated underlying molecular alterations of PCFBCL with respect to somatic mutations.
Our aim was to gain deeper insight into the pathogenesis of PCFBCL and to delineate discriminatory molecular features of this lymphoma subtype.
We performed hybridization-based panel sequencing of 40 lymphoma-associated genes of 10 cases of well-characterized PCFBCL. In addition, we included two further ambiguous cases of atypical B-cell-rich lymphoid infiltrate/B-cell lymphoma of the skin for which definite subtype attribution had not been possible by routine investigations.
In 10 out of 12 analyzed cases, we identified genetic alterations within 15 of the selected 40 target genes. The most frequently detected alterations in PCFBCL affected the , , and genes. Our analysis unrevealed novel mutations of the gene in PCFBCL. All patients exhibited an indolent clinical course. Both the included arbitrary cases of atypical B-cell-rich cutaneous infiltrates showed somatic mutations within the gene. As these mutations have previously been designated as subtype-specific recurrent alterations in primary cutaneous marginal zone lymphoma (PCMZL), we finally favored the diagnosis of PCMZL in these two cases based on these molecular findings.
To conclude, our molecular data support that PCFBCL shows distinct somatic mutations which may aid to differentiate PCFBCL from pseudo-lymphoma as well as from other indolent and aggressive cutaneous B-cell lymphomas. While the detected genetic alterations of PCFBCL did not turn out to harbor any prognostic value in our cohort, our molecular data may add adjunctive discriminatory features for diagnostic purposes on a molecular level.
原发性皮肤滤泡性B细胞淋巴瘤（PCFBCL）是非霍奇金淋巴瘤的一种惰性亚型，临床特征为皮肤肿瘤生长缓慢且常见皮肤复发，而全身播散或致命结局的倾向较低。到目前为止，仅有少数研究调查了PCFBCL在体细胞突变方面的潜在分子改变。
我们的目的是更深入地了解PCFBCL的发病机制，并描绘该淋巴瘤亚型的鉴别性分子特征。
我们对10例特征明确的PCFBCL进行了40个淋巴瘤相关基因的基于杂交的panel测序。此外，我们还纳入了另外2例皮肤非典型富含B细胞的淋巴浸润/ B细胞淋巴瘤的疑难病例，常规检查无法明确其亚型归属。
在12例分析病例中的10例中，我们在选定的40个靶基因中的15个基因中发现了基因改变。PCFBCL中最常检测到的改变影响了 、 、 和 基因。我们的分析未发现PCFBCL中 基因的新突变。所有患者均表现为惰性临床病程。纳入的2例非典型富含B细胞的皮肤浸润病例均在 基因中出现体细胞突变。由于这些突变先前已被指定为原发性皮肤边缘区淋巴瘤（PCMZL）的亚型特异性复发改变，基于这些分子发现，我们最终在这2例病例中倾向于诊断为PCMZL。
总之，我们的分子数据支持PCFBCL显示出独特的体细胞突变，这可能有助于将PCFBCL与假性淋巴瘤以及其他惰性和侵袭性皮肤B细胞淋巴瘤区分开来。虽然在我们的队列中检测到的PCFBCL基因改变没有显示出任何预后价值，但我们的分子数据可能在分子水平上为诊断目的增加辅助鉴别特征。
