Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel.
Institute of Pathology, Cantonal Hospital Baselland, Liestal, Switzerland.
Am J Surg Pathol. 2024 Oct 1;48(10):1259-1269. doi: 10.1097/PAS.0000000000002257. Epub 2024 Jun 12.
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.
结外黏膜边缘区淋巴瘤（eMZL）可发生于身体任何器官和部位。最近的研究表明，它们在突变谱方面存在器官间的差异。在本研究中，我们研究了一组原发性乳腺黏膜边缘区淋巴瘤（PBMZL），以更好地了解其形态学和分子特征。我们对 15 例病例（14 例女性和 1 例男性）进行了免疫组织化学（IHC）检测 19 种标志物、荧光原位杂交（FISH）和使用包含 172 个基因的淋巴瘤面板进行高通量测序（HTS）。此外，还进行了针对特定病原体的聚合酶链反应（PCR）检测和宏基因组全基因组测序。大多数病例观察到滤泡浸润，而虽然许多病例存在淋巴上皮病变，但并不显著。所有 15 例病例均为 CD5、CD11c 和 CD21 阴性，BCL2 和泛 B 细胞标志物阳性。没有病例存在 BCL2、BCL10、IRF4、MALT1 或 MYC 易位；仅有 1 例存在 BCL6 重排。HTS 突出了 TNFAIP3（n=4）、KMT2D（n=2）和 SPEN（n=2）为最常突变的基因。我们的队列中没有检测到 Borrelia spp.，也没有其他病原体。1 例患者有相同乳腺影响的慢性游走性红斑病史。PBMZL 是一种驱动突变的疾病，而非融合驱动。它表现为编码影响 NF-κB 途径、染色质修饰基因和 NOTCH 途径相关基因的基因的突变。其突变谱与眼部附属器和结外 MZL 具有相似性。
