title: Thoracic epithelioid malignant vascular tumors: a clinicopathologic study of 52 cases with emphasis on pathologic grading and molecular studies of WWTR1-CAMTA1 fusions.
abstract: Malignant thoracic epithelioid vascular tumors are an uncommon and heterogenous group of tumors that include low-grade to intermediate-grade epithelioid hemangioendothelioma (EHE) and high-grade epithelioid angiosarcoma (EAS). We examine the morphologic and immunohistochemical features of 52 malignant epithelioid vascular tumors (10 low-grade EHE, 29 intermediate-grade EHE, and 13 EAS) involving the thorax (lung, pleura, mediastinum, heart, great vessels) including cases with exclusively thoracic disease (35) and with multiorgan disease including the thorax (17). Intermediate-grade EHE differs from low-grade EHE by the presence of necrosis, increased mitotic activity, and increased atypia. Morphologic features such as intranuclear inclusions, intracytoplasmic vacuoles, and stromal changes (chondroid, myxoid, or hyalinized stroma) are seen more frequently in EHE, whereas blood lakes, proliferation of slit-like vessels, and prominent nucleoli favor EAS. Fluorescence in situ hybridization analysis showed CAMTA1-WWTR1 fusions in 4/7 low-grade and 23/23 intermediate-grade EHE (P<0.001). In EAS, CAMTA1 rearrangement was negative in all cases, whereas a WWTR1 complex abnormality was found in 1/5 cases (P<0.001). This offers an objective means of differentiating intermediate-grade EHE from EAS, especially on limited biopsies. All cases show expression of at least 1 vascular marker, which allows differentiation from primary thoracic epithelial malignancies, although keratin expression is a potential pitfall with 29% of EHE and 25% of EAS showing keratin expression. Survival analysis shows that higher tumor grade for all tumors (P=0.026) as well as lung and pleural tumors only (P=0.010) and the presence of pleural involvement in lung and/or pleural tumors (P=0.042) correlate with poor prognosis.
authors.affiliation: *Department of Pathology †Department of Surgery, Thoracic Service, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Todd
authors.initials: T
authors.lastname: Anderson
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Meera
authors.initials: M
authors.lastname: Hameed
authors.forename: Valerie
authors.initials: V
authors.lastname: Rusch
authors.forename: William D
authors.initials: WD
authors.lastname: Travis
authors.forename: Cristina R
authors.initials: CR
authors.lastname: Antonescu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D001706:Biopsy; D002135:Calcium-Binding Proteins / Q000235:genetics*; D049109:Cell Proliferation; D005260:Female; D050939:Gene Fusion; D018323:Hemangioendothelioma, Epithelioid / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D006394:Hemangiosarcoma / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D008940:Mitotic Index; D009336:Necrosis; D060787:Neoplasm Grading; D011237:Predictive Value of Tests; D013899:Thoracic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C487554:CAMTA1 protein, human; D002135:Calcium-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; C551991:WWTR1 protein, human