Multisystem ALK-positive histiocytosis: a multi-case study and literature review

Abstract

Background 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. Results 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. Conclusions 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.

Anaplastic lymphoma kinase‐positive histiocytosis with multisystem involvement: A case report

“…3,4 Furthermore, favorable outcomes of ALK inhibitors on ALK-positive histiocytosis have been observed. 1,3,5 Our case demonstrates the possibility of spontaneous resolution of skin lesions in children with multisystem involvement, indicating that conservative treatment is an option when ALK inhibitors are unavailable or undesired. However, the persistent abnormal gait in this child indicates that early treatment during critical periods of bone and brain development may have had a beneficial impact in maintaining the child's quality of life.…”

Case report: Systemic presentation of ALK-positive Histiocytosis

“…Prognosis is generally better for multiple lesions, while systemic presentations vary depending on the affected sites. Reviewing literature cases with follow-ups ranging from 2 to 14 years, one case resulted in death, one survived the disease, and the rest showed no abnormalities or disease recurrence (2,3,(5)(6)(7). Recently, some scholars have successively reported isolated cases, raising whether they are related to systemic ALK-HSs, which requires further investigation (10).…”

“…The prognosis for this condition is primarily favorable, but in a few cases, it can be poor. Searching in the international medical literature, fewer than 50 cases have been reported to date, making systemic ALK-HSs extremely rare (2,3). This article presents one case of systemic ALK-HSs, detailing the patient's treatment, follow-up, and prognosis.…”

Imaging features of ALK-positive histiocytosis with neurological involvement: a case report and literature review

“…To date, less than 100 cases of APH have been reported. Previous relevant literature primarily focused on genetic characteristics, histopathology, treatment, and prognosis (2)(3)(4)(5)(6), with limited descriptions regarding imaging manifestations of this disease (7).…”