Morphometric study of pulmonary arterial changes in pulmonary langerhans cell histiocytosis

Context.—Pulmonary hypertension (PHT) is a complication of pulmonary Langerhans cell histiocytosis (PLCH); however, the pathogenesis remains largely unknown. Few studies have evaluated histopathologic changes in pulmonary arteries (PAs) of patients with PLCH; systematic quantification of arterial remodeling has yet to be undertaken. Objective.—To quantify the extent of arterial remodeling among patients with PLCH through morphometry and to correlate these results with pertinent clinical parameters. Design.—Patients with PLCH were identified from institutional files (1995–2015) along with age-, sex-, and smoking status–matched controls. Morphometric analysis of intimal and medial thickness of small to medium PAs was performed in patients with PLCH (within PLCH lesions [lesional] and away from PLCH lesions [nonlesional]) and controls. Paired measures were compared with Wilcoxon signed rank tests. Results.—Twenty-five patients with PLCH (14 men: median age, 46 years; interquartile range, 37–55 years) and 25 controls were included. The lesional arteries of patients with PLCH demonstrated thicker PA intima and media than controls (P, .001 and P, .001, respectively), as did PLCH nonlesional arteries compared to controls (P, .001 and P, .001, respectively). The PA intima and media were thicker within the PLCH lesions than nonlesional arteries (P ¼ .02 and P ¼ .002, respectively). Patients with PLCH-related PHT had a worse prognosis than those without PHT (P ¼ .04; hazard ratio, 4.5 [1.1, 22.2]). Echocardiography parameters including right atrial size (P ¼ .007), estimated right atrial pressure (P ¼ .01), and right ventricular systolic pressure (P ¼ .01) were inversely associated with survival. Conclusions.—Our findings suggest that factors other than direct vascular obstruction or inflammatory cell infiltration contribute, at least in part, to the vascular remodeling in PLCH.