Pulmonary artery intimal sarcoma – A primeval or rediscovered tumor? A report of 14 new cases with literature review

Pulmonary artery sarcomas (PAS) are rare with many being undifferentiated pleomorphic or spindle cell (UPSC) sarcomas with variable atypia. The term pulmonary artery intimal sarcoma (PAIS) was rarely coined in the early literature and sometimes used for luminal sarcomas. With the advent of immunohistochemistry and molecular genetics, many of these UPSC sarcomas were found to frequently overpress MDM2 and/or CDK4 and PDGFRA with genetic alterations in 12q12-15 and 4q12, where the MDM2, CDK4 and PDGFRA genes are located. These recent developments enabled refinement in diagnosis of PAIS. We diagnosed 14 cases of PAIS (6 males and 8 females, mean age 44 years) in 2015 - 2020 in our institution. Six were initially misdiagnosed as thromboembolism and the remaining pulmonary artery tumors. The tumors were pulmonary artery intraluminal polypoid masses with histology of spindle cell sarcomas exhibiting immunohistochemical positivity for MDM2 (100%) and CDK4 (79%) with MDM2 gene amplification (100%). Ten surgically treated patients fared better than four other biopsy only and not surgically treated patients, who died of disease within 5-11 months. PAIS needs to be differentiated from other spindle cell tumors and those exhibiting MDM2 gene amplification, especially dedifferentiated liposarcoma. The use of biopsy to provide diagnostic material poses a sampling error problem and correlation with clinical, radiologic, histologic, immunophenotypic and genotypic features are essential for accurate diagnosis and early surgical intervention of PAIS.