ALK阳性大B细胞淋巴瘤4例临床及病理特征分析

Clinicopathologic characteristics of ALK positive large B cell lymphoma:an analysis of four cases

目的探讨ALK阳性大B细胞淋巴瘤的临床特点、组织病理学特征、诊断和鉴别诊断要点以及生物学行为。方法收集4例ALK阳性大B细胞淋巴瘤,观察其临床特点、组织形态学和免疫表型以及预后,并结合相关国内外文献进行总结和复习。结果 4例中男性3例,女性1例,发病年龄22~50岁。活检部位2例为淋巴结(右侧锁骨上窝淋巴结、左侧颈部淋巴结),1例为颌下腺,1例为乙状结肠和颈部淋巴结。临床分期中2例为Ⅱ期,2例为Ⅳ期。4例中3例为穿刺标本,1例为根治切除标本(乙状结肠)。组织学上肿瘤细胞弥漫生长,3例肿瘤细胞呈典型的免疫母细胞样、浆母细胞样,细胞体积大,细胞核圆而淡染,核膜厚、清晰,具有大的中位核仁;1例肿瘤细胞不典型,细胞体积大,部分胞质淡染,核不规则,似肾形核,有的呈双核,部分胞质嗜酸,核深染、固缩,不规则状。免疫组化显示常用的B细胞标记物CD20、CD79a、PAX5(-),以及常用的T细胞标记物CD3、CD2为(-);终末分化B细胞/浆细胞的标记物CD38、CD138(+),B细胞特异性转录因子BOB-1、OCT-2均(+);T细胞标记物CD4常异常表达(2/4);EMA(+)(4/4);1例CD30局灶弥漫(+);ALK蛋白强(+)(4/4),4例均为胞质颗粒状着色;EBER均(-)。4例均获得随访资料,随访6~17个月,1例于治疗后10个月死亡,3例存活(淋巴结仍有肿大)。结论 ALK阳性大B细胞淋巴瘤是弥漫大B细胞淋巴瘤的一种罕见亚型,具有高度侵袭性,预后不良,确诊主要依靠其特征性的组织形态学及免疫表型,诊断时需要与ALK阳性的间变性大细胞淋巴瘤、低分化癌、恶性黑色素瘤以及具有浆母细胞/免疫母细胞形态的一系列B细胞淋巴瘤相鉴别,尤其是CD30局灶阳性表达时易误诊为间变性大细胞淋巴瘤。

Objective To investigate the clinical and histopathological characteristics,diagnosis and differential diagnosis and biological behavior of ALK-positive large B-cell lymphoma.Methods Four cases of ALK-positive large B-cell lymphoma were collected and their clinical features,histomorphology,immunophenotype and prognosis were observed.The relevant literature was summarized and reviewed.Results Among the 4 tumors,3 were male and 1 was female,with age ranging from 22 to 50 years;Biopsy site included lymph nodes(right supraclavicular fossae lymph nodes,left cervical lymph nodes)in 2 patients,submandibular gland in 1 patient,sigmoid colon and cervical lymph nodes in 1 patient.2 of the 4 cases were clinically stage II and 2 cases in stageⅣ.Of the 4 cases,3 were puncture specimens and 1 was radical resection specimens(sigmoid colon).Histologically,tumor cells were diffusely grown.The tumor cells in 3 cases showed typical immunoblastic and plasmablastic appearance,with large cell size,round and pale nuclei,thick and clear nuclear membranes,and large median nucleoli.In one case,the tumor cells were atypical,with large size,light staining of some cytoplasm,irregular nuclei,kidney-like nucleation,some of which were binuclear or eosinophilic,with hyperchromatic,pyknotic and irregular nuclei.Immunohistochemistry showed that the commonly used B cell markers CD20,CD79 a and PAX5 tumor cells were negative,and the commonly used T cell markers CD3 and CD2 were negative.Tumor cells expressed markers of terminal differentiation of B cells/plasma cells,including CD38,CD138 and MUM1,and B cell specific transcription factors BOB-1 and OCT-2.T cell marker CD4 was often abnormally expressed(2/4)and EMA was positive(4/4);1 case was focally diffuse positive for CD30.ALK protein was strongly positive(4/4),4 cases were cytoplasmic granular staining,and EBER was negative(0/4).All 4 patients were followed up for 6-17 months:1 died 10 months after treatment,and 3 survived(lymph node enlargement).Conclusion ALK-positive large B-cell lymphoma is a rare aggressive subtype of diffuse large B-cell lymphoma.It is highly aggressive and has a poor prognosis.The diagnosis of ALK-positive large B-cell lymphoma depends mainly on its characteristic histomorphology and immunophenotype.At the same time,the diagnosis should be differentiated from ALK-positive anaplastic large cell lymphoma,poorly differentiated cancer,malignant melanoma and a series of B-cell lymphomas with plasma/immunoblastic morphology,especially when CD30 is focally positive;it is easy to be misdiagnosed as anaplastic large cell lymphoma.