Pleuropulmonary Blastoma and Diagnostic Pitfalls: A Report from the International Pleuropulmonary Blastoma/DICER1 Registry.

Context.—: Pleuropulmonary blastoma (PPB) is a rare primary lung neoplasm predominantly occurring in infancy and early childhood, which, because of rarity and/or confusion with congenital cystic lung lesions and its variable architectural and morphologic features, can be a diagnostic challenge. Objective.—: To characterize the diagnostic challenges in cases submitted to the International PPB/DICER1 [dicer 1, ribonuclease III] Registry (Registry) with a possible PPB diagnosis. Design.—: This study reviews lesions submitted to the Registry during a 35-year period. Pathologic diagnoses, ancillary studies, and genetic information were reviewed. Results.—: Of the 868 thoracic tumors submitted to the Registry from 1987 to 2022, 79% (685 of 868) were confirmed as PPB by central review. In the remaining 21% (183 of 868) of cases, PPB was either excluded or could not be confirmed with available material. Most of these cases (64%; 117 of 183) were malignant; 31% (56 of 183) were benign, and 5% (10 of 183) were of uncertain malignant potential. The most common benign discrepant diagnosis was congenital pulmonary airway malformation (n = 19), and the most common malignant discrepant or indeterminate diagnosis was rhabdomyosarcoma, including sarcoma with rhabdomyoblastic differentiation (n = 24). DICER1 RNase IIIb hotspot variants were detected by tumor testing in 4 cases with histology discrepant from or inconclusive for classical PPB. Additionally, 4 patients with non-PPB histology were found to have a germline DICER1 pathogenic or likely pathogenic variant without available tumor testing. Conclusions.—: The histomorphologic heterogeneity of PPB resulted in a variety of non-PPB diagnoses among cases not initially classified as PPB. Molecular testing may clarify the diagnosis and provide prognostic and therapeutic insights.