以自发性脾脏破裂为首发症状的B细胞前淋巴细胞性白血病1例临床病理观察

目的探讨1例以自发性脾破裂的B细胞前淋巴细胞性白血病(B-PLL)的临床病理特征,进行鉴别诊断、治疗和预后评估。方法回顾性分析1例上海市第一人民医院宝山分院以自发性脾脏破裂的B-PLL大体形态和镜下特点、免疫表型、细胞遗传学及分子生物学特征,与外周血涂片、骨髓涂片和骨髓活检结果相互印证,并复习相关文献。结果患者男性,57岁,因发热、怕冷、乏力6天就诊,一般检查:白细胞18.8×10^9/L,血小板为25×10^9/L,血红蛋白96 g/L,C-反应蛋白200 mg/L,乳酸脱氢酶:3 867μ/L。影像学表现:上腹部CT平扫示脾脏肿大伴斑片状高低密度影,腹腔积液;下腹部CT平扫示盆腔大量血性积液,诊断脾脏自发性破裂出血。大体检查:①脾脏重1 225 g,大小22 cm×15 cm×8 cm,表面不规则破裂长约5 cm,切面暗红色,未见肿块。②副脾重15 g,大小2.7 cm×2.5 cm×1.3 cm,切面暗红色未见肿块。显微镜观察:低倍镜下脾脏红髓和白髓的正常结构破坏;高倍镜下见大量中等大小圆形肿瘤细胞,少量嗜碱性胞质,核染色质浓染,嗜酸性核仁中央突出,弥漫浸润于脾脏。免疫组化显示肿瘤细胞CD20、CD79a、MUM-1、Pax-5均(+),Ki-67平均增殖指数80%,bcl2、bcl6、C-myc灶(+),MPO、CD23、CD43、Td T、CD3、CD4、CD8、CD56、CD99、CD10、CD34、CD21、CD68、Cyclin D1、CD5、S-100、EBV、Lysozyme均(-)。病理诊断:(脾脏) B-PLL,累及副脾。外周血涂片、骨髓涂片、骨髓活检和流式学分析证实B幼淋巴细胞占71%,粒、红、巨三系增生减低。分子生物学特征:IGHV基因重排检测到单克隆重排,IGH单克隆V区测序检测到IGH单克隆V区超突变,用Sanger测序检测到MYD88基因L265P突变,未检测到p53基因突变。细胞遗传学染色体核型分析:核型46,XY。术后随访36个月,患者在上海市交通大学医学院附属第九人民医院行R-EPOCH化疗后,病情完全缓解未进展。结论 B-PLL好发于老年男性,侵袭性临床过程,以自发性脾脏破裂为首发症状的B-PLL罕见,而R-EPOCH方案化疗为B-PLL治疗带来希望。

B-cell prolymphocytic leukemia with spontaneous splenic rupture as the first symptom: a clinicopathologic analysis of one case

Objective To investigate the clinicopathological characteristics and differential diagnosis of B-cell prolymphocytic leukemia(B-PLL)with spontaneous splenic rupture,and to analyze the treatment and prognosis.Methods Retrospective analysis of 1 case of B-PLL admitted to hospital with spontaneous splenic rupture was carried out on general morphology,microscopic characteristics,immunophenotype,cytogenetic and molecular biological characteristics.The diagnosis was confirmed with the results of peripheral blood smear,bone marrow smear and bone marrow biopsy,and review of relevant literature.Results A 57-year-old male patient presented fever,aversion to cold and fatigue for 6 days.The general examination showed white blood cells were 18.8×10^9/L,platelet 25×10^9/L,hemoglobin 96 g/L,c-reactive protein 200 mg/L,and lactate dehydrogenase 3867μ/L.The plain CT images of the entire abdomen showed splenomegaly with patchy high and low density shadows,and a large amount of bloody fluid in the abdominal and pelvic cavity,which was diagnosed as spontaneous splenic rupture and bleeding.Macroscopically,the spleen weighed 1225 g,the size was 22×15×8 cm,the surface was irregularly ruptured and the length was about 5 cm;the cut surface was dark red,and there were no masses.The accessory spleen weighed 15 g,with size of 2.7×2.5×1.3 cm,and the cut surface was dark red with no lumps.Microscopically,in low power field the normal structure of the red and white pulp of the spleen was destroyed;in high power field a large number of medium-sized round tumor cells diffusely infiltrated the spleen,which had basophilic cytoplasm,nuclear chromatin condensation,and prominent eosinophilic nucleoli.Immunohistochemistry of the pathological section of this patient showed that the tumor cells were positive for CD20,CD79 a,MUM-1 and Pax-5,confirming that the tumor was derived from B cells.Average proliferation index of Ki-67 was 80%.The expression of bcl2,bcl6 and C-myc was focally positive,The expression of MPO,CD23,CD43,Td T,CD3,CD4,CD8,CD56,CD99,CD10,CD34,CD21,CD68,cyclin D1,CD5,S-100,EBV and lysozyme was all negative.Pathological diagnosis was B-PLL of the spleen with involvement of accessory spleen.Peripheral blood smear,bone marrow smear,bone marrow biopsy and flow cytometry analysis confirmed that B prolymphocytes accounted for 71%.The proliferation of granulocyte,erythrocyte and megakaryocyte series were all reduced.Molecular biological features were that IGHV gene rearrangement detection showed monoclonal amplification,DNA sequencing showed that IGH gene V region hypermutation,Sanger sequencing showed that the MYD88 gene L265 P mutation,and no P53 gene mutation was detected.Cytogenetic karyotype analysis showed karyotype 46,XY.The patient was followed up for 36 months after surgery.After undergoing chemotherapy with the REPOCH the patients showed no progress in complete remission.Conclusion B-PLL occurs in older men,with aggressive clinical course.B-PLL with spontaneous splenic rupture as the first symptom is rare,and R-EPOCH chemotherapy brings hope to B-PLL patients.