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Abstract：
BACKGROUND: Primary breast lymphoma (PBL) is rare, and most cases occur in female patients, with few reported cases in male patients. The clinical presentation is similar to that of breast cancer, but the condition needs to be well understood, as treatment options and clinical course vary. Hence, we provide a relatively rare case of primary breast diffuse large B cell lymphoma (PB-DLBCL) in a male, including its complete clinicopathological features, radiological findings, genomic mutational profiles, and clinical course.
METHODS: A 45-year-old male presented with a lump in his right breast for 1 week and was pathologically diagnosed with breast malignancy after a breast puncture biopsy at the local hospital. He came to our hospital for further treatment and underwent breast ultrasound and systemic positron emission tomography/computed tomography (PET/CT) imaging, followed by right mastectomy and sentinel lymph node biopsy. Histomorphology showed diffuse hyperplasia of tumor cells with clear boundaries and surrounding normal breast ducts. The adhesion of tumor cells was poor with obvious atypia. Immunohistochemical results showed that the tumor cells were positive for CD20, Bcl6, and MUM-1 but negative for CK (AE1/AE3), ER, PR, CD3, and CD10. Forty percent of the tumor cells were positive for c-Myc, and 80% of tumor cells were positive for Bcl2. The Ki-67 proliferation index was up to 80%. The tumor cells were negative for MYC and BCL2 rearrangements but positive for BCL6 rearrangement by fluorescent in situ hybridization. No abnormality was found in the pathological examination of bone marrow aspiration. Therefore, the male was diagnosed with PB-DLBCL, nongerminal center (non-GCB) phenotype, dual-expression type. The sample were sequenced by a target panel of 121 genes related to lymphoma. Next-generation sequencing revealed six tumor-specific mutated genes (IGH/BCL6, TNFAIP3, PRDM1, CREBBP, DTX1, and FOXO1). The patient was given six cycles of orelabrutinib plus R-CHOP chemotherapy and two cycles of intrathecal injection of cytarabine. The last follow-up was on April 13, 2023 (17 months). No recurrence or metastasis was found in laboratory and imaging examinations.
CONCLUSIONS: We reported a relatively rare PB-DLBCL in a male, non-GBC phenotype, dual-expression type. It is worth mentioning that this case had IgH/BCL6 fusion, nonsense mutations in TNFAIP3, frameshift mutations in PRDM1, and missense mutations in CREBBP, DTX1, and FOXO1. To the best of our knowledge, this case is the first report of genomic mutational profiles of PB-DLBCL in males.
METHODS: A 45-year-old male presented with a lump in his right breast for 1 week and was pathologically diagnosed with breast malignancy after a breast puncture biopsy at the local hospital. He came to our hospital for further treatment and underwent breast ultrasound and systemic positron emission tomography/computed tomography (PET/CT) imaging, followed by right mastectomy and sentinel lymph node biopsy. Histomorphology showed diffuse hyperplasia of tumor cells with clear boundaries and surrounding normal breast ducts. The adhesion of tumor cells was poor with obvious atypia. Immunohistochemical results showed that the tumor cells were positive for CD20, Bcl6, and MUM-1 but negative for CK (AE1/AE3), ER, PR, CD3, and CD10. Forty percent of the tumor cells were positive for c-Myc, and 80% of tumor cells were positive for Bcl2. The Ki-67 proliferation index was up to 80%. The tumor cells were negative for MYC and BCL2 rearrangements but positive for BCL6 rearrangement by fluorescent in situ hybridization. No abnormality was found in the pathological examination of bone marrow aspiration. Therefore, the male was diagnosed with PB-DLBCL, nongerminal center (non-GCB) phenotype, dual-expression type. The sample were sequenced by a target panel of 121 genes related to lymphoma. Next-generation sequencing revealed six tumor-specific mutated genes (IGH/BCL6, TNFAIP3, PRDM1, CREBBP, DTX1, and FOXO1). The patient was given six cycles of orelabrutinib plus R-CHOP chemotherapy and two cycles of intrathecal injection of cytarabine. The last follow-up was on April 13, 2023 (17 months). No recurrence or metastasis was found in laboratory and imaging examinations.
CONCLUSIONS: We reported a relatively rare PB-DLBCL in a male, non-GBC phenotype, dual-expression type. It is worth mentioning that this case had IgH/BCL6 fusion, nonsense mutations in TNFAIP3, frameshift mutations in PRDM1, and missense mutations in CREBBP, DTX1, and FOXO1. To the best of our knowledge, this case is the first report of genomic mutational profiles of PB-DLBCL in males.
摘要：
背景：原发性乳腺淋巴瘤（PBL）很少见，大多数病例发生在女性患者身上，在男性患者中报道的病例很少。临床表现与乳腺癌相似，但是需要很好地理解这种情况，随着治疗方案和临床疗程的变化。因此，我们提供了一个相对罕见的男性原发性乳腺弥漫性大B细胞淋巴瘤（PB-DLBCL），包括其完整的临床病理特征，放射学发现，基因组突变谱，和临床课程。
方法：一名45岁男性患者，在当地医院行乳腺穿刺活检后右乳腺肿块1周，病理诊断为乳腺恶性肿瘤。他来到我们医院接受进一步治疗，并接受了乳腺超声和全身正电子发射断层扫描/计算机断层扫描（PET/CT）成像，然后是右乳房切除术和前哨淋巴结活检。组织形态学显示肿瘤细胞弥漫性增生，边界清晰，周围正常乳腺导管。肿瘤细胞粘附性差，异型明显。免疫组化结果显示肿瘤细胞CD20、Bcl6、MUM-1阳性,CK(AE1/AE3)阴性,ER,PR,CD3和CD10。40%的肿瘤细胞c-Myc阳性,80%的肿瘤细胞Bcl2阳性。Ki-67增殖指数高达80%。通过荧光原位杂交，肿瘤细胞对MYC和BCL2重排呈阴性，但对BCL6重排呈阳性。骨髓穿刺病理检查未见异常。因此,男性被诊断为PB-DLBCL,非发中心（非GCB）表型，双表达式类型。通过与淋巴瘤相关的121个基因的靶组对样品进行测序。下一代测序揭示了六个肿瘤特异性突变基因（IGH/BCL6，TNFAIP3，PRDM1，CREBBP，DTX1和FOXO1)。患者给予6个周期奥雷拉布替尼加R-CHOP化疗和2个周期鞘内注射阿糖胞苷。最后一次随访是在2023年4月13日（17个月）。实验室和影像学检查均未发现复发或转移。
结论：我们报道了男性中相对罕见的PB-DLBCL，非GBC表型，双表达式类型。值得一提的是，该病例有IgH/BCL6融合，TNFAIP3中的无义突变，PRDM1中的移码突变和CREBBP中的错义突变，DTX1和FOXO1。据我们所知,该病例是男性PB-DLBCL基因组突变谱的首例报道.
方法：一名45岁男性患者，在当地医院行乳腺穿刺活检后右乳腺肿块1周，病理诊断为乳腺恶性肿瘤。他来到我们医院接受进一步治疗，并接受了乳腺超声和全身正电子发射断层扫描/计算机断层扫描（PET/CT）成像，然后是右乳房切除术和前哨淋巴结活检。组织形态学显示肿瘤细胞弥漫性增生，边界清晰，周围正常乳腺导管。肿瘤细胞粘附性差，异型明显。免疫组化结果显示肿瘤细胞CD20、Bcl6、MUM-1阳性,CK(AE1/AE3)阴性,ER,PR,CD3和CD10。40%的肿瘤细胞c-Myc阳性,80%的肿瘤细胞Bcl2阳性。Ki-67增殖指数高达80%。通过荧光原位杂交，肿瘤细胞对MYC和BCL2重排呈阴性，但对BCL6重排呈阳性。骨髓穿刺病理检查未见异常。因此,男性被诊断为PB-DLBCL,非发中心（非GCB）表型，双表达式类型。通过与淋巴瘤相关的121个基因的靶组对样品进行测序。下一代测序揭示了六个肿瘤特异性突变基因（IGH/BCL6，TNFAIP3，PRDM1，CREBBP，DTX1和FOXO1)。患者给予6个周期奥雷拉布替尼加R-CHOP化疗和2个周期鞘内注射阿糖胞苷。最后一次随访是在2023年4月13日（17个月）。实验室和影像学检查均未发现复发或转移。
结论：我们报道了男性中相对罕见的PB-DLBCL，非GBC表型，双表达式类型。值得一提的是，该病例有IgH/BCL6融合，TNFAIP3中的无义突变，PRDM1中的移码突变和CREBBP中的错义突变，DTX1和FOXO1。据我们所知,该病例是男性PB-DLBCL基因组突变谱的首例报道.
