ALK-positive histiocytosis is a rare subtype of histiocytic neoplasm first described in 2008 in three infants with multisystemic disease involving the liver and hematopoietic system. This entity has subsequently been documented in case reports and series to occupy a wider clinicopathologic spectrum with recurrent KIF5B-ALK fusions. The full clinicopathologic and molecular spectra of ALK-positive histiocytosis remain, however, poorly characterized. Here, we describe the largest study of ALK-positive histiocytosis to date, with detailed clinicopathologic data of 39 cases, including 37 cases with confirmed ALK rearrangements. The clinical spectrum comprised distinct clinical phenotypic groups: infants with multisystemic disease with liver and hematopoietic involvement, as originally described (Group 1A: 6/39), other patients with multisystemic disease (Group 1B: 10/39), and patients with single-system disease (Group 2: 23/39). Nineteen patients of the entire cohort (49%) had neurologic involvement (seven and twelve from Groups 1B and 2, respectively). Histology included classic xanthogranuloma features in almost one third of cases, whereas the majority displayed a more densely cellular, monomorphic appearance without lipidized histiocytes but sometimes more spindled or epithelioid morphology. Neoplastic histiocytes were positive for macrophage markers and often conferred strong expression of phosphorylated-ERK, confirming MAPK pathway activation. KIF5B-ALK fusions were detected in 27 patients, while CLTC-ALK, TPM3-ALK, TFG-ALK, EML4-ALK and DCTN1-ALK fusions were identified in single cases. Robust and durable responses were observed in 11/11 patients treated with ALK inhibition, ten with neurologic involvement. This study presents the existing clinicopathologic and molecular landscape of ALK-positive histiocytosis, and provides guidance for the clinical management of this emerging histiocytic entity.

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Background: Sickle cell disease (SCD) is a lifelong disease characterized by both acute and chronic morbid conditions that often result in acute care utilization. There is limited data on SCD patients in medically underserved areas of the United States. Methods: We conducted a retrospective analysis of SCD patients in a mixed rural/nonrural partially medically underserved area in southwest Virginia without access to an adult comprehensive sickle cell center to describe patterns of disease-related morbidities and acute care utilization, as well as the effects of other comorbid diseases. Results: Of the 71 patients who met inclusion criteria, the majority (59.1%) were insured by Medicaid, 15.5% were insured by Medicare, 14.1% through a commercial insurer, and 11.3% were self-pay. Medicare- and Medicaid-insured patients utilized acute care services more often than those insured by other means. Medicare patients had 124% more acute pain crises than patients insured by other means. Obesity was a risk factor for direct admission to the hospital. Additionally, admissions from the ED were 18.3% lower in females than males, despite the average age of the female cohort being approximately 8 years older than males. Conclusion: For this patient cohort without access to an adult comprehensive sickle cell center, public insurance status through Medicare or Medicaid was associated with more acute care utilization. Obesity and male sex were identified as risk factors for hospitalization. Further study of and targeted interventions for SCD patients in rural and medically underserved communities is warranted.