Pathology Unit, Department of Laboratories, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Neuropathology Unit, Pathology Division, Fondazione Policlinico Universitario A.Gemelli IRCCS, Università Cattolica S.Cuore, Rome, Italy.
Neuropathol Appl Neurobiol. 2021 Oct;47(6):878-881. doi: 10.1111/nan.12739. Epub 2021 Jun 18.
Histiocytoses are a heterogeneous group of localized or disseminated diseases. Clinical presentation and patients' outcome vary greatly, ranging from mild to life-threatening disorders. Rare cases of systemic or localized histiocytosis harboring ALK rearrangement have been reported.
Two cases of CNS histiocytosis were thoroughly investigated by implementing multiple molecular tests, i.e. FISH, RT-qPCR, NGS analysis.
In a 10-month old girl (patient #1), MRI showed two left hemispheric lesions and a right fronto-mesial lesion histologically consisting of a moderately cellular infiltrative proliferation, composed by CD68(PGM1)+/CD163+ spindle cells. ALK 5'/3'-imbalance and a KIF5B(exon 24)-ALK(exon 20) fusion were documented by RT-qPCR and NGS analysis, respectively. A subsequent CT scan showed multiple hepatic and pulmonary lesions. The patient was started on chemotherapy (vinblastine) associated to an ALK-inhibitor (Alectinib) with remarkable response. In a 11-year-old girl (patient #2), MRI showed a right frontal 1.5 cm lesion. Neuropathological examination revealed a histiocytic proliferation composed by medium sized CD68(PGM1)+/HLA-DR+ cells, showing moderate ALK1 positivity. ALK rearrangement and a KIF5B(exon 24)-ALK(exon 20) fusion were demonstrated also in this case. Subsequent CT, 18F-FDG-PET and MRI scans showed the presence of a single right femoral lesion, proved to be a fibrous cortical defect.
In ALK-histiocytoses, CNS involvement may occur as part of a systemic disease or, rarely, as its only primary disease localization, which could remain otherwise asymptomatic. The diagnosis often relies on neuropathological examination of brain biopsy, which may pose a diagnostic challenge due to the variable histopathological features. An integrated histological and molecular approach in such cases is recommended.
组织细胞增多症是一组异质性的局限性或播散性疾病。临床表现和患者的预后差异很大，从轻症到危及生命的疾病都有。已经报道了少数伴有 ALK 重排的系统性或局限性组织细胞增多症的罕见病例。
对 2 例中枢神经系统组织细胞增多症患者进行了彻底研究，实施了多种分子检测，即 FISH、RT-qPCR、NGS 分析。
在一名 10 个月大的女孩（患者 #1）中，MRI 显示两个左侧半球病变和右侧额内侧病变，组织学上由中等细胞浸润性增生组成，由 CD68(PGM1)+/CD163+梭形细胞组成。通过 RT-qPCR 和 NGS 分析分别记录了 ALK 5'/3'-失衡和 KIF5B(exon 24)-ALK(exon 20)融合。随后的 CT 扫描显示多个肝和肺病变。患者开始接受化疗（长春碱）联合 ALK 抑制剂（阿来替尼）治疗，效果显著。在一名 11 岁女孩（患者 #2）中，MRI 显示右侧额部有 1.5 厘米病变。神经病理学检查显示中等大小的 CD68(PGM1)+/HLA-DR+细胞组成的组织细胞增生，显示中度 ALK1 阳性。在这个病例中也证实了 ALK 重排和 KIF5B(exon 24)-ALK(exon 20)融合。随后的 CT、18F-FDG-PET 和 MRI 扫描显示右侧股骨单发病变，证实为纤维皮质缺损。
在 ALK 组织细胞增多症中，中枢神经系统受累可能是系统性疾病的一部分，也可能很少见，作为其唯一的原发性疾病定位，且可能保持无症状。诊断通常依赖于脑活检的神经病理学检查，由于组织病理学特征的变化，这可能构成诊断挑战。在这种情况下，建议采用综合的组织学和分子方法。
