Final Diagnosis -- Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins

FINAL DIAGNOSIS

Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins

DISCUSSION

The differential diagnosis of a newborn with severe pulmonary hypertension and hypoxemia includes persistent pulmonary hypertension of the new born, pulmonary hypoplasia, surfactant protein-B deficiency, and Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins (ACD-MPV). ACD-MPV is a rare, fatal developmental lung disorder of neonates and infants. The clinical scenario presented in this case is typical for ACD-MPV, mainly intractable, sudden and rapidly progressing respiratory failure, respiratory acidosis and cyanosis within 24h of extrauterine life, with uneventful pregnancy and delivery with normal APGAR scores at birth. The diagnosis of ACD-MPV requires a high level of suspicion and is made through lung biopsy or necropsy. Microscopically, ACDMPV, as observed in this case, shows reduced number of capillaries, which are located far away from the alveolar surface, impairing the alveolar-capillary gas exchange. In addition, there is arrested or immature lung development, thickening of pulmonary arterioles and malposition of veins, which run adjacent to pulmonary arteries and airways. All these features were observed in this case. This patient presented with spontaneous pneumothorax, and although uncommon, there is at least one case report on record with this particular presentation (1). The pathogenesis of this disease remains to be fully elucidated, but at least one gene has been implicated: the FOX gene cluster, and mutations of FOXF1 at 16q24.1 have been described in patients with ACD-MPV(2). Approximately 10 % of ACD-MPV cases occur with a familial pattern suggestive of an autosomal recessive inheritance. This entity is sometimes associated with other malformations, including gastrointestinal atresias, hydronephrosis and hypoplastic left heart, with the gastrointestinal anomalies being the most frequently associated. ACD-MPV can be differentiated from other causes of pulmonary hypertension by it lacks of response to vasodilator and other clinical interventions, which in fact is a diagnostic clue. Unfortunately, ACD-MPV is a lethal disease; therapies like extra-corporeal membrane oxygenation will only briefly prolong survival. Because none of the supportive therapies has changed the expected mortality due to ACD-MPV, lung transplantation is currently the only option that might prolong survival for these patients.

REFERENCES

1. Castilla-Fernandez Y, Copons-Fernández C, Jordan-Lucas R, Linde-Sillo A, Valenzuela-Palafoll I, Piñas JC, Moreno-Galdó A, Castillo-Salinas F. Alveolar capillary dysplasia with misalignment of pulmonary veins: concordance between pathological and molecular diagnosis. J Perinatol. 2013 May;33(5):401-3
2. Rabah R, Poulik JM. Congenital alveolar capillary dysplasia with misalignment of pulmonary veins associated with hypoplastic left heart syndrome. Pediatr Dev Pathol. 2001 Mar-Apr;4(2):167-74.
3. Gutierrez C, Rodriguez A, Palenzuela S, Forteza C, Rossello JL. Congenital misalignment of pulmonary veins with alveolar capillary dysplasia causing persistent neonatal pulmonary hypertension: report of two affected siblings. Pediatr Dev Pathol. 2000 May-Jun;3(3):271-6.
4. Hung SP, Huang SH, Wu CH, Chen WC, Kou KE, Wang NK, Lin LH. Misalignment of lung vessels and alveolar capillary dysplasia: a case report with autopsy. Pediatr Neonatol. 2011 Aug;52(4):232-6
5. Husain, Aliya. Thoracic Pathology. 1st Edition. Elsevier Editors, 2012.
6. Corrin, Bryan and Nicholson, Andrew. Pathology of the Lungs. 3rd Edition. Churchil Livingstone Elsevier, 2012

Contributed by Humberto Trejo Bittar, MD and Miguel Reyes-Mugica, MD