title: A subset of fat-predominant angiomyolipomas label for MDM2: a potential diagnostic pitfall.
abstract: Angiomyolipomas (AMLs) are typically benign mesenchymal tumors with variable histologic composition. Fat-predominant AMLs can mimic well-differentiated liposarcomas (WDLSs) both radiographically and histologically because of the abundance of fat with admixed atypical cells resembling lipoblasts. However, the treatment and prognosis of AMLs and WDLSs are vastly different. Immunohistochemistry for murine double minute 2 (MDM2) has been used to support a diagnosis of WDLS; however, MDM2 labeling has not been specifically evaluated in fat-predominant AMLs. Here, we evaluated MDM2 immunohistochemistry in 36 AMLs (including 14 conventional AMLs, 13 fat-predominant AMLs, 6 fat-rich AMLs, 3 epithelioid AMLs) and 10 WDLSs. In addition, we labeled cases for HMB45, calponin, or actin, which are immunostains traditionally used to label AML. We performed fluorescence in situ hybridization (FISH) for MDM2 amplification on selected cases. By immunohistochemistry, 14% (5/36) of AMLs were MDM2+, including 23% (3/13) of fat-predominant AMLs. All MDM2+ AMLs evaluated by FISH (n=4) were negative for MDM2 amplification. By immunohistochemistry, 90% of WDLSs were MDM2+, and both MDM2+ WDLSs evaluated by FISH (n=2) were MDM2 amplified. All 36 AMLs labeled with HMB45 and calponin or actin. No WDLS labeled with HMB45; however, 80% of WDLSs labeled with calponin or actin. Although uncommon, MDM2 labeling is seen in a subset of fat-predominant AMLs and is a potential diagnostic pitfall in the evaluation of fatty tumors of the retroperitoneum. HMB45 is more sensitive and specific for AML than calponin or actin, and an immunopanel containing both HMB45 and MDM2 may be warranted to distinguish between fat-predominant AML and WDLS in histologically ambiguous cases.
authors.affiliation: Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD, 21287, United States.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Asch-Kendrick
authors.affiliation: Department of Pathology, Cleveland Clinic, Cleveland, OH, 44195, United States.
authors.forename: Shashi
authors.initials: S
authors.lastname: Shetty
authors.affiliation: Department of Pathology, Cleveland Clinic, Cleveland, OH, 44195, United States.
authors.forename: John R
authors.initials: JR
authors.lastname: Goldblum
authors.affiliation: Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD, 21287, United States.
authors.forename: Rajni
authors.initials: R
authors.lastname: Sharma
authors.affiliation: Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD, 21287, United States.
authors.forename: Jonathan I
authors.initials: JI
authors.lastname: Epstein
authors.affiliation: Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD, 21287, United States.
authors.forename: Pedram
authors.initials: P
authors.lastname: Argani
authors.affiliation: Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD, 21287, United States. Electronic address: acimino1@jhmi.edu.
authors.forename: Ashley
authors.initials: A
authors.lastname: Cimino-Mathews
mesh_terms: D000199:Actins / Q000032:analysis; D000273:Adipose Tissue / Q000737:chemistry* / Q000473:pathology; D000328:Adult; D000368:Aged; D018207:Angiomyolipoma / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000032:analysis; D003937:Diagnosis, Differential; D003951:Diagnostic Errors; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008080:Liposarcoma / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D008297:Male; D058950:Melanoma-Specific Antigens / Q000032:analysis; D008840:Microfilament Proteins / Q000032:analysis; D008875:Middle Aged; D011237:Predictive Value of Tests; D051736:Proto-Oncogene Proteins c-mdm2 / Q000032:analysis* / Q000235:genetics; D015203:Reproducibility of Results; D012186:Retroperitoneal Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D012189:Retrospective Studies; D058951:gp100 Melanoma Antigen; D000096985:Calponins
chemical_list: D000199:Actins; D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D058950:Melanoma-Specific Antigens; D008840:Microfilament Proteins; D051736:Proto-Oncogene Proteins c-mdm2; D058951:gp100 Melanoma Antigen; D000096985:Calponins; C548637:PMEL protein, human; C497206:MDM2 protein, human
keywords: Angiomyolipoma; Fat-predominant angiomyolipoma; Immunohistochemical pitfalls; MDM2; Retroperitoneal tumors; Well-differentiated liposarcoma