背景:间变性淋巴瘤激酶(ALK)阳性组织细胞增生症,一种新的罕见组织细胞增殖,首次描述于2008年;它发生在婴儿早期,肝脏和造血受累。随后扩大了范围,包括年龄较大的儿童和年轻人的局部疾病。然而,其完整的临床病理特征和分子谱系尚未完全阐明。
结果:这里,我们报告了4例多系统ALK阳性组织细胞增生症,但没有造血受累。临床上,3例患者为32~51岁的成年人.两个病人,主要表现为颅内肿块、胸腹腔器官微结节和皮肤丘疹,手术后对ALK抑制剂有部分反应。一名患者出现纵隔肿瘤,未经手术治疗,和进行性疾病发生后两年的ALK抑制剂治疗。第四例患者是一名17个月大的男性,颅内肿块大,对ALK抑制剂和放化疗的反应较差;他在手术后八个月死亡。病理上,组织细胞很大,有丰富的嗜酸性细胞浆,并混合了不同数量的泡沫细胞和Touton巨细胞。还观察到间质纤维化。组织细胞对巨噬细胞标志物(CD68和CD163)和ALK呈阳性。2例检测到KIF5B-ALK融合,EML4-ALK合二为一,1例同时检测到DCTN1-ALK和VRK2-ALK融合。
结论:我们观察到ALK抑制剂在成年患者中表现出稳健和持久的反应,但在中枢神经系统受累的幼儿中反应较差。关于最佳治疗方案尚无共识,长期预后需要进一步观察。此外,每个不寻常的组织细胞增生性病变,尤其是不可切除和多系统参与,应进行常规ALK免疫组织化学染色检测以鉴定这种罕见疾病。
Anaplastic lymphoma kinase (ALK)-positive histiocytosis, a novel rare histiocytic proliferation, was first described in 2008; it occurs in early infancy with liver and hematopoietic involvement. The spectrum was subsequently broadened to include localized diseases in older children and young adults. However, its full clinicopathological features and molecular lineage have not been fully elucidated.
Here, we report four cases of multisystem ALK-positive histiocytosis without hematopoietic involvement. Clinically, three patients were adults aged between 32 and 51 years. Two patients\', whose main manifestations were intracranial mass and numerous micronodules in the thoracoabdominal cavity organs and skin papules respectively, had a partial response to ALK inhibitors after surgery. One patient presented with mediastinal neoplasm without surgical treatment, and progressive disease occurred after two years of ALK inhibitor therapy. The fourth patient was a 17-month-old male with a large intracranial mass and presented with a poor response to ALK inhibitor and chemoradiotherapy; he died eight months after surgery. Pathologically, the
histiocytes were large, with abundant eosinophilic cytoplasm, and mixed with variable numbers of foamy cells and Touton giant cells. Interstitial fibrosis was also observed.
Histiocytes were positive for macrophage markers (CD68 and CD163) and ALK. KIF5B-ALK fusions were detected in two cases, EML4-ALK in one, and both DCTN1-ALK and VRK2-ALK fusions were detected in one case.
We observed that ALK inhibitors present robust and durable responses in adult patients but a poor response in young children with central nervous system involvement. There is no consensus on the optimal treatment regimen and long-term prognosis requires further observation. Moreover, every unusual histiocytic proliferative lesion, especially unresectable and multisystem involvement, should be routinely tested for ALK immunohistochemical staining to identify this rare disease.