儿童ALK阳性的淋巴组织细胞型间变性大细胞淋巴瘤临床病理分析

Anaplastic large cell lymphoma,lymphohistiocytic variant:report of 2 ALK^+ children and review of literatures

目的探讨儿童淋巴组织细胞型间变性大细胞淋巴瘤(ALCL-LH)的临床病理特征、诊断及预后。方法通过光镜、免疫组化对2例ALCL-LH进行临床病理观察及原位杂交检测EB病毒,并结合文献加以分析。结果2例ALCL-LH儿童患者临床主要表现为高热、淋巴结肿大伴肝脾肿大。形态学示淋巴结结构大部分破坏,背景中组织细胞、淋巴细胞和小血管增生较多,肿瘤细胞较少,细胞中等偏大,但比普通型小,核型不规则,可见围绕血管周围生长。免疫组化示2例大部分瘤细胞CD30、ALK-1、EMA和GranzymeB阳性表达,例1CD43、例2CD7阳性表达,2例CD45、CD2、CD3、CD4、CD5、CD8、CD45RO、CD56、CD20、CD79a、CD15、MPO、CK、TdT、LMP1阴性,原位杂交EBER1/2阴性。随访2例均死亡,分别存活10d及3个月。结论ALCL-LH是恶性淋巴瘤的极少见类型,好发于儿童,形态学特征为反应性组织细胞和淋巴细胞数量超过并掩盖肿瘤细胞。免疫组化染色CD30、ALK、EMA和细胞毒性颗粒相关蛋白(如GranzymeB等)阳性表达对诊断和鉴别诊断有重要作用。

Objective To study the clinicopathological characteristics, diagnosis and prognosis ot anaplastic large cell lymphoma, lymphohistiocytic variant （ALCL-LH）. Methods Two cases of ALCL-LH ,sere diagnosed according to the WHO standard of lymphoma classification. Their clinical manifestations were analyzed. Lymphoma sample sections were prepared for pathological features and immunohistochemical assays, and examined by in situ hybridization for Epstein-Barr virus （EBV） DNA. Concerning literatures were reviewed. Results Both 2 cases occurred in children. The clinical manifestations presented with fever and enlarged lymph nodes as well as hepatomegaly and splenomegaly. Microscopically, the neoplastic cells, with irregular nuclei, were more often medium to large in size but smaller than those in the common type, and sparsely intermixed with a large number of histiocytes and lymphocytes that exceeded and masked the tumor cell population. The tumor cells clustered around blood vessels. Case 1 showed evidence of erythrophagocytosis. Immunohistoehemical stainings showed that tumor ceils of 2 cases were positive to CD30, anaplastic lymphoma kinase （ALK）, EMA, and Granzyme B, as well as case 1 to CD43, and case 2 to CD7. But both cases were negative to CD45, CD2, CD3, CD4, CD5, CD8, CD45RO, CD56, CD20, CD79a, CD15, MPO, CK, TdT, and LMP1. In addition, the EBV DNA was not detected in the lymphoma. Case 1 and case 2 died 10 d and 3 months after pathological diagnosis respectively. Conclusion ALCL-LH variant is rare subtype, and often occurs in pediatric patients. Morphologically, ALCL-LH is characterized by a few medium to large size cells admixed with a large number of histiocytes and lymphocytes that exceed and mask the tumor cell population. The expressions of CD30, ALK, EMA and eytotoxic granule associated proteins contribute to diagnosis and differential diagnosis.