Department of Pathology, Hematopathology Section and Lymph Node Registry, Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
Haematologica. 2013 Jan;98(1):50-6. doi: 10.3324/haematol.2012.065664. Epub 2012 Jul 6.
Anaplastic large cell lymphomas are peripheral T-cell lymphomas that are characterized by a proliferation of large anaplastic blasts expressing CD30. In children, systemic anaplastic large cell lymphomas often present at advanced clinical stage and harbor translocations involving the anaplastic lymphoma kinase (ALK) gene leading to the expression of chimeric anaplastic lymphoma kinase (ALK)-fusion proteins. Primary cutaneous anaplastic large cell lymphoma is regarded as an ALK-negative variant confined to the skin and is part of the spectrum of primary cutaneous CD30-positive T-cell lymphoproliferative disorders. Thirty-three of 487 pediatric patients registered within the Anaplastic Large Cell Lymphoma-99 trial (1999 to 2006) presented with a skin limited CD30-positive lympho-proliferative disorder. In 23 of the 33 patients, material for international histopathological review was available, and the cases were studied for histopathological, immunophenotypical and clinical features as well as for breaks within the ALK gene. Five of 23 cases and one additional case (identified after closure of the trial) expressed ALK-protein. Complete staging excluded any other organ involvement in all children. Expression of ALK proteins was demonstrated by immunohistochemistry in all cases and the presence of breaks of the ALK gene was genetically confirmed in 5 evaluable cases. The histopathological and clinical picture of these skin-restricted ALK-positive lymphomas was indistinguishable from that of cutaneous anaplastic large cell lymphoma. Five children presented with a single skin lesion that was completely resected in 4 and incompletely resected in one. Three of these patients received no further therapy, 2 additional local radiotherapy, and one chemotherapy. All children remain in complete remission with a median follow up of seven years (range 1-8 years). We present 6 pediatric cases of ALK-positive primary cutaneous anaplastic large cell lymphomas. After thorough exclusion of systemic involvement, therapy confined to local measures seems to be sufficient to induce cure.
间变大细胞淋巴瘤是外周 T 细胞淋巴瘤的一种，其特征为大量表达 CD30 的间变大细胞增生。在儿童中，系统性间变大细胞淋巴瘤常表现为晚期临床阶段，且存在涉及间变性淋巴瘤激酶（ALK）基因的易位，导致嵌合性间变性淋巴瘤激酶（ALK）-融合蛋白的表达。原发性皮肤间变大细胞淋巴瘤被认为是一种局限于皮肤的 ALK 阴性变体，属于原发性皮肤 CD30 阳性 T 细胞淋巴增生性疾病谱的一部分。在 Anaplastic Large Cell Lymphoma-99 试验（1999 年至 2006 年）中登记的 487 例儿科患者中，有 33 例出现皮肤局限性 CD30 阳性淋巴增生性疾病。在这 33 例患者中，有 23 例的国际组织病理学复查材料可用，对这些病例进行了组织病理学、免疫表型和临床特征研究，以及 ALK 基因内的断裂研究。在 23 例病例中，有 5 例和另外 1 例（在试验结束后发现）表达 ALK 蛋白。所有儿童的完整分期均排除其他器官受累。所有病例均通过免疫组化证实表达 ALK 蛋白，5 例可评估病例的 ALK 基因均存在断裂。这些皮肤局限的 ALK 阳性淋巴瘤的组织病理学和临床表现与皮肤间变大细胞淋巴瘤无法区分。5 例患儿仅出现单个皮肤病变，其中 4 例完全切除，1 例不完全切除。这 3 例患儿未接受进一步治疗，2 例接受局部放疗，1 例接受化疗。所有患儿均在完全缓解中，中位随访 7 年（1-8 年）。我们报告了 6 例儿童 ALK 阳性原发性皮肤间变大细胞淋巴瘤病例。在彻底排除系统性受累后，仅局限于局部措施的治疗似乎足以诱导治愈。
