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Congenital pulmonary airway malformations (CPAMs) have a range of morphologies with varying cyst sizes and histologic features (types 1 to 3). Evidence suggested they arise secondary to bronchial atresia, however, we recently showed that cases with type 1 and 3 morphology are driven by mosaic KRAS mutations. We hypothesized that 2 distinct mechanisms account for most CPAMs: one subset is secondary to KRAS mosaicism and another is due to bronchial atresia. Cases with type 2 histology, similar to sequestrations, would be related to obstruction and therefore negative for KRAS mutations regardless of cyst size. We sequenced KRAS exon 2 in type 2 CPAMs, cystic intralobar and extralobar sequestrations, and intrapulmonary bronchogenic cysts. All were negative. Most sequestrations had a large airway in the subpleural parenchyma adjacent to the systemic vessel, anatomically confirming bronchial obstruction. We compared morphology to type 1 and 3 CPAMs. On average, type 1 CPAMs had significantly larger cysts, but there remained substantial size overlap between KRAS mutant and wild-type lesions. Features of mucostasis were frequent in sequestrations and type 2 CPAMs, while their cysts were generally simple and round with flat epithelium. Features of cyst architectural and epithelial complexity were more common in type 1 and 3 CPAMs, which rarely showed mucostasis. Similarity in histologic features among cases that are negative for KRAS mutation support the hypothesis that, like sequestrations, the malformation of type 2 CPAMs is related to obstruction during development. A mechanistic approach to classification may improve existing subjective morphologic methods., Competing Interests: Conflicts of Interest and Source of Funding: Supported by the Society for Pediatric Pathology Young Investigator Grant (J.P.). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Congenital malformations of the bronchopulmonary airway and related arterial blood supply are a complex group of lesions in which abnormalities of venous drainage and lung parenchyma may coexist. Twenty five cases have been analysed, by a method whereby each anatomical component is separately considered. All 25 patients had abnormalities of the tracheobronchial tree, with no connection to the abnormal segment in nine cases. The aberrant arterial blood supply was single in 16 cases and multiple in nine cases, one patient from the latter group having a mixed pulmonary and systemic arterial supply to a part of the abnormal segment. Seventeen patients had anomalous venous drainage. In nine of these the vein or veins (they were multiple in four cases) drained the major part or the whole of the lung, whereas the aberrant arterial supply was limited to the right lower zone--that is, mismatched anomalous venous drainage. Abnormalities of lung parenchyma included changes within the lesion (for example, cysts, foregut inclusions) and associated abnormalities of surrounding lung (for example, hypoplasia, abnormal lobation). This information, together with the clinical features and haemodynamic data, was found to be essential for decisions on appropriate management. Patients presenting in infancy with haemodynamic disturbance continue to present major management problems (50% mortality), particularly if there are associated congenital heart defects. The role of aberrant systemic artery occlusion or ligation as a first stage procedure is well established in patients with haemodynamic abnormalities. There may be a place for this procedure in selected patients who have no haemodynamic disturbance at presentation.

The pulmonary sequestration spectrum and related congenital lung anomalies present an extremely complex and varied group of bronchopulmonary-vascular malformations. Previous attempts at nomenclature and classification have proved inadequate. In this article we present a classification of the newly named pulmonary malinosculation spectrum, which includes all congenital lung anomalies where there is abnormal connection (that is, malinosculation) of one or more of the four major components of lung tissue--namely, tracheobronchial airway, lung parenchyma, arterial supply, and venous drainage, which in various combinations make up these lesions. We feel that this simple descriptive approach will improve our understanding and management of these complicated lesions and this is supported by the clinical experience we report in the next article.