Report of Two Cases of ALK-Positive Histiocytosis in Young Children with Localized Lesions

Abstract

Abstract Introduction/Objective ALK-positive histiocytosis is a recently described entity which occurs in both children and adults and can present with localized or disseminated disease. Limited case reports and series describe histiocytic infiltrates with irregular morphologic features and typical immunoreactivity for CD68, CD163, lysozyme, S100(variable), CD4, and cytoplasmic ALK. ALK rearrangements are often confirmed by FISH or molecular sequencing. The presence of such rearrangements may make ALK inhibitor therapy possible, although further investigation is necessary. We report two cases of ALK-positive histiocytosis diagnosed at our institution. Methods/Case Report Patient 1 is a 4-year-old girl with a prior history of high-risk neuroblastoma status-post resection, bone marrow transplant, radiation, and chemotherapy. An MRI performed due to neurologic symptoms revealed a left frontal-enhancing mass. With concern for metastatic neuroblastoma, a biopsy was performed, which showed brain parenchyma infiltrated by large atypical histiocytes with moderate eosinophilic cytoplasm and irregular folded nuclei. The histiocytes stained positive for CD68, lysozyme, Factor XIIIa, CD163, CD4, S100(variable), and cytoplasmic ALK. An ALK rearrangement was confirmed by FISH studies. The patient is reportedly doing well on therapy. Patient 2 is a previously healthy 2-year-old boy with a midline palate lesion. An incisional biopsy revealed a submucosal infiltrate of small lymphocytes and enlarged atypical histiocytes with abundant eosinophilic cytoplasm and vesicular folded nuclei. Histiocytes stained positive for CD68, CD163, Factor XIIIa, lysozyme, S100(variable), CD4, and cytoplasmic ALK. Given presence of an ALK rearrangement detected by FISH, the patient was started on single agent crizotinib therapy and has responded with near complete resolution. Results (if a Case Study enter NA) NA Conclusion ALK-positive histiocytosis is a clinicopathologically distinct entity with predilection for young children and presence of ALK rearrangements which may be amenable to ALK inhibitors, such as crizonitib. We report two additional cases to contribute to the expanding spectrum of this rare and relatively new entity.