Misalignment of Lung Vessels and Alveolar Capillary Dysplasia: A Case Report With Autopsy

Abstract

Misalignment of lung vessels (MLV) with or without alveolar capillary dysplasia (ACD) is a rare cause of idiopathic persistent pulmonary hypertension of the neonate. This report describes a full-term infant with severe and intractable pulmonary hypertension. The patient's condition progressively deteriorated despite high-frequency oscillatory ventilation, infusion of magnesium sulfate, dopamine, and dobutamine to control blood pressure, and nitric oxide inhalation therapy. The infant died at 5 days of age. The diagnosis of MLV with ACD was established by autopsy. Histopathologic analysis revealed a failure of formation and an ingrowth of alveolar capillaries, thickening of the alveolar walls, poor contact of capillaries with alveolar epithelium, small intra-acinar muscularized arterioles, and anomalous pulmonary veins within bronchovascular bundles. The low rate of diagnosis of MLV with or without ACD may be because of the early high mortality rate or patchy involvement in some cases. Increasing awareness of this clinical entity may prevent the use of costly, invasive, and probably ineffective procedures. Short-term improvement after inhalation of nitric oxide does not lead to long-term survival but merely provides time for potential lung transplantation.

Alveolar capillary dysplasia with misalignment of pulmonaryz veins: concordance between pathological and molecular diagnosis

“…9 Half the patients have associated gastrointestinal (40%), genitourinary (32%) or cardiovascular anomalies (16%). 1 Cardiac malformations, esophageal and anal atresia, renal and vertebral/axial malformations, and single umbilical artery appear to be common to both the VACTERL association and 16q24.1 microdeletion. However, although lung malformations have been reported occasionally in cases of VACTERL association, ACD/MPV has not been described in this context.…”

“…Some researchers believe that although ACD probably reflects a vasculogenesis imbalance, MPV suggests an imbalance of angiogenesis. 1,2 Most cases are sporadic, although familial cases also occur (10%), suggesting an autosomal recessive inheritance. The disorder is associated with persistent pulmonary hypertension of the neonate and shows varying degrees of lability and severity.…”

“…Mutations (deletions or point mutations) of this gene have been identified in patients with ACD/MPV. 1,6 FOXF1 belongs to the forkhead family of transcription factors and contributes to regulation of pulmonary genes and embryonic development. In a group of patients with ACD/MPV, Sen et al 6 identified six overlapping microdeletions encompassing the FOX transcription factor gene cluster on chromosome 16q24.1-24.2, all but one of which included the FOXF1 gene.…”

“…11 The definite diagnosis is based on lung biopsy examination or autopsy by a pediatric pathologist with prior experience in the diagnosis of ACD/MPV. 1,7 Overall, 90% of cases are diagnosed at autopsy, and 10% by premortem lung samples. It is important to point out that our patient was diagnosed while alive, and that biopsy was performed because pathologic study provides valuable prognostic information.…”

“…Currently, no specific treatment is available for ACD/MPV, and despite the various strategies used for the management of pulmonary hypertension, the mortality rate is nearly 100%. 1 Treatment with NO and ECMO provide time for a potential lung transplantation; hence, even with the current mortality rate, it is important to diagnose this condition at an early stage to avoid costly procedures. In our case, we considered the possibility of including the child on the waiting list for lung transplant, but because of her poor clinical status and the expectation of a long wait, the family decided against it after considering the risks and benefits.…”