PLAG1 Immunohistochemical Staining Is a Surrogate Marker for Fusions in Lipoblastomas

Authors

Mikako Warren, Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles, California.
Nishant Tiwari, Department of Pathology and Laboratory Medicine, Phoenix Children's Hospital, Phoenix, Arizona.Follow
Sabrina Sy, Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles, California.
Gordana Raca, Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles, California.
Ryan J. Schmidt, Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles, California.
Bruce Pawel, Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles, California.

Document Type

Article

Abstract

BACKGROUND: The hallmark of lipoblastoma is a PLAG1 fusion. PLAG1 protein overexpression has been reported in sporadic PLAG1-rearranged lipoblastomas. METHODS: We evaluated the utility of PLAG1 immunohistochemical staining (IHC) in 34 pediatric lipomatous tumors, correlating the results with histology and conventional cytogenetics, FISH and/or next generation sequencing (NGS) results. RESULTS: The study included 24 lipoblastomas, divided into 2 groups designated as "Lipoblastoma 1" with both lipoblastoma histology and PLAG1 rearrangement (n = 16) and "Lipoblastoma 2" with lipoblastoma histology but without PLAG1 cytogenetic rearrangement (n = 8), and 10 lipomas with neither lipoblastoma histology nor a PLAG1 rearrangement. Using the presence of a fusion as the "gold standard" for diagnosing lipoblastoma (Lipoblastoma 1), the sensitivity of PLAG1 IHC was 94%. Using histologic features alone (Lipoblastoma 1 + 2), the sensitivity was 96%. Specificity, as defined by the ability to distinguish lipoma from lipoblastoma, was 100%, as there were no false positives in the lipoma group. CONCLUSIONS: Cytogenetics/molecular testing is expensive and may not be ideal for detecting PLAG1 fusions because PLAG1 fusions are often cytogenetically cryptic and NGS panels may not include all partner genes. PLAG1 IHC is an inexpensive surrogate marker of PLAG1 fusions and may be useful in distinguishing lipoblastomas from lipomas.

Medical Subject Headings

Biomarkers; Child; DNA-Binding Proteins (genetics); Gene Fusion; Humans; In Situ Hybridization, Fluorescence; Lipoblastoma (diagnosis, genetics); Transcription Factors (genetics)

Publication Date

1-1-2022

Publication Title

Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society

E-ISSN

1615-5742

Volume

25

Issue

2

First Page

134

Last Page

140

PubMed ID

34601996

Digital Object Identifier (DOI)

10.1177/10935266211043366

Recommended Citation

Warren, Mikako; Tiwari, Nishant; Sy, Sabrina; Raca, Gordana; Schmidt, Ryan J.; and Pawel, Bruce, "PLAG1 Immunohistochemical Staining Is a Surrogate Marker for Fusions in Lipoblastomas" (2022). Neuropathology. 12.
https://scholar.barrowneuro.org/neuropathology/12