Defining the spatial landscape of KRAS mutated congenital pulmonary airway malformations: a distinct entity with a spectrum of histopathologic features

Nelson, Nya D.; Xu, Feng; Chandrasekaran, Prashant; Litzky, Leslie A.; Peranteau, William H.; Frank, David B.; Li, Marilyn; Pogoriler, Jennifer

doi:10.1038/s41379-022-01129-0

Cited by 8 publications

(24 citation statements)

References 63 publications

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“…We hypothesized that type 2 CPAMs, ILS, ELS, and BC are pathogenetically distinct from KRAS -mutated type 1 and 3 CPAMs and would have a wild-type KRAS sequence. We sought to sequence lesions that clinically and morphologically most closely approximated previously sequenced type 1 and 3 CPAMs,15 and hence selected type 2 CPAMs, ILS, and ELS with prominent cystic changes that were resected from young infants (Figs. 1A–H).…”

Section: Resultsmentioning

confidence: 99%

“…With institutional review board approval (eIRB 20-017451), congenital cystic lung lesions were identified via a database search of surgical pathology reports issued by the Children's Hospital of Philadelphia. Cases of type 1 and 3 CPAMs were previously identified based on subjectively similar histology, 15 while for this study new cases were identified for type 2 CPAMs, intrapulmonary BCs, ILS, and ELS. Cases were identified over a 20-year period, from January 2000 to March 2020.…”

Section: Case Identification and Retrospective Chart Reviewmentioning

confidence: 86%

“…We have previously demonstrated that the KRAS -mutated CPAMs in our series had features of type 1 or 3 CPAMs or had intermediate features and that histologic features strongly correlated with specific amino acid substitutions. The few cases that were negative for mutations had predominantly type 3 histology that was indistinguishable from other type 3 cases with the exception of an absence of mucinous cells 15. These cases were initially selected based on our subjective impression that they did not fit with typical type 2 CPAM morphology.…”

Section: Discussionmentioning

confidence: 99%

“…Congenital cystic lung lesions with prominent cystic change that were resected early in infancy were selected for KRAS exon 2 sequencing. As previously described, 15 dissection of lesional tissue focused on areas that were predominantly lined by columnar epithelium. For each formalin-fixed paraffin-embedded tissue block with tissue of interest, multiple 20 µm unstained sections were cut and cystic areas were macrodissected using a fresh scalpel blade to prevent cross contamination.…”

Section: Macrodissection and Kras Sequencingmentioning

confidence: 99%

“…The features were compared with previously described type 1 and 3 CPAMs. 15 In contrast to type 1 and 3 CPAMs, type 2 CPAMs and sequestrations rarely required surgery in the immediate perinatal period (Table 2).…”

Section: Histologic Evaluation Of Congenital Cystic Lung Lesionsmentioning

confidence: 99%

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Morphologic Features in Congenital Pulmonary Airway Malformations and Pulmonary Sequestrations Correlate With Mutation Status

Nelson

Xu²,

Peranteau

et al. 2023

American Journal of Surgical Pathology

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Case Identification and Retrospective Chart Reviewmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Section: Macrodissection and Kras Sequencingmentioning

confidence: 99%

Section: Histologic Evaluation Of Congenital Cystic Lung Lesionsmentioning

confidence: 99%

See 3 more Smart Citations

Morphologic Features in Congenital Pulmonary Airway Malformations and Pulmonary Sequestrations Correlate With Mutation Status

Nelson

Xu²,

Peranteau

et al. 2023

American Journal of Surgical Pathology

Self Cite

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Congenital lung malformations

Pederiva,

Rothenberg,

Hall

et al. 2023

Nat Rev Dis Primers

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Neonatal and Infant Lung Disorders

Yoon,

Concepcion,

DiPrete

et al. 2023

Journal of Thoracic Imaging

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A multitude of lung disorders ranging from congenital and genetic anomalies to iatrogenic complications can affect the neonate or the infant within the first year of life. Neonatal and infant chest imaging, predominantly by plain radiography and computed tomography, is frequently employed to aid in diagnosis and management; however, these disorders can be challenging to differentiate due to their broad-ranging, and frequently overlapping radiographic features. A systematic and practical approach to imaging interpretation which includes recognition of radiologic patterns, utilization of commonly accepted nomenclature and classification, as well as interpretation of imaging findings in conjunction with clinical history can not only assist radiologists to suggest the diagnosis, but also aid clinicians in management planning. The contents of this article were endorsed by the leadership of both the World Federation of Pediatric Imaging (WFPI), and the International Society of Pediatric Thoracic Imaging (ISPTI).

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Defining the spatial landscape of KRAS mutated congenital pulmonary airway malformations: a distinct entity with a spectrum of histopathologic features

Cited by 8 publications

References 63 publications

Morphologic Features in Congenital Pulmonary Airway Malformations and Pulmonary Sequestrations Correlate With Mutation Status

Morphologic Features in Congenital Pulmonary Airway Malformations and Pulmonary Sequestrations Correlate With Mutation Status

Congenital lung malformations

Neonatal and Infant Lung Disorders

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