Extranodal marginal zone lymphomas (eMZL) can occur in any organ and site of the body. Recent research has shown that they differ from organ to organ in terms of their mutational profile. In this study, we investigated a cohort of primary breast marginal zone lymphomas (PBMZL) to get a better insight into their morphologic and molecular profile. A cohort of 15 cases (14 female and 1 male) was characterized by immunohistochemistry (IHC) for 19 markers, fluorescence in situ hybridization (FISH), and high throughput sequencing (HTS) using a lymphoma panel comprising 172 genes. In addition, PCR for the specific detection of Borrelia spp. and metagenomics whole genome sequencing were performed for infectious agent profiling. Follicular colonization was observed in most cases, while lymphoepithelial lesions, though seen in many cases, were not striking. All 15 cases were negative for CD5, CD11c, and CD21 and positive for BCL2 and pan B-cell markers. There were no cases with BCL2, BCL10, IRF4, MALT1, or MYC translocation; only 1 had a BCL6 rearrangement. HTS highlighted TNFAIP3 (n=4), KMT2D (n=2), and SPEN (n=2) as the most frequently mutated genes. There were no Borrelia spp., and no other pathogens detected in our cohort. One patient had a clinical history of erythema chronicum migrans affecting the same breast. PBMZL is a mutation-driven disease rather than fusion-driven. It exhibits mutations in genes encoding components affecting the NF-κB pathway, chromatin modifier-encoding genes, and NOTCH pathway-related genes. Its mutational profile shares similarities with ocular adnexal and nodal MZL.

中文翻译：

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原发性乳房边缘区淋巴瘤的遗传景观确定了一种与眼附件淋巴瘤相似的突变驱动疾病。


结外边缘区淋巴瘤 (eMZL) 可发生在身体的任何器官和部位。最近的研究表明，不同器官的突变特征不同。在这项研究中，我们研究了一组原发性乳腺边缘区淋巴瘤 (PBMZL)，以更好地了解其形态和分子特征。使用包含 172 个基因的淋巴瘤组，通过 19 种标记物的免疫组织化学 (IHC)、荧光原位杂交 (FISH) 和高通量测序 (HTS) 对 15 例病例（14 名女性和 1 名男性）组成的队列进行表征。此外，还可以使用 PCR 来特异性检测疏螺旋体属 (Borrelia spp)。并进行了宏基因组全基因组测序以进行感染因子分析。在大多数病例中观察到滤泡定植，而淋巴上皮病变虽然在许多病例中可见，但并不引人注目。所有 15 例 CD5、CD11c 和 CD21 均为阴性，BCL2 和泛 B 细胞标记物呈阳性。无BCL2、BCL10、IRF4、MALT1或MYC易位病例；只有 1 个发生 BCL6 重排。 HTS 强调 TNFAIP3 (n=4)、KMT2D (n=2) 和 SPEN (n=2) 是最常见的突变基因。我们的队列中没有检测到疏螺旋体属，也没有检测到其他病原体。一名患者有影响同一乳房的慢性游走性红斑的临床病史。 PBMZL 是一种突变驱动的疾病，而不是融合驱动的疾病。它表现出编码影响 NF-κB 通路的成分的基因、染色质修饰物编码基因和 NOTCH 通路相关基因的突变。其突变谱与眼附属器和结节 MZL 具有相似之处。