Immunohistochemistry (IHC) for c-Myc in the Differential Diagnosis of Vascular Tumors of the Liver
Jared M Orrock, Tsung-Teh Wu, Andrew L Folpe, Sukov R William. Mayo Clinic, Rochester, MN
Background: Angiosarcoma (AS) is a rare, aggressive malignancy that may involve the liver, either primarily or as a metastasis. The distinction of hepatic AS from potential morphological mimics, including low-grade malignant vascular tumors such as epithelioid hemangioendothelioma (EHE) and benign lesions including hemangioma (HEM) and peliosis hepatis (PH), is clinically significant and may be difficult in some cases. For this reason there has been continued interest in the development of ancillary markers that may assist in the differential diagnosis of vascular tumors. Recently, up-regulation of c-Myc has been reported to be a common event in AS, and IHC for c-Myc has been shown to be helpful in evaluating post-radiation vascular lesions of the breast. We evaluated c-Myc IHC in a series of well-characterized hepatic vascular tumors.
Design: Formalin-fixed, paraffin-embedded blocks from 13 AS, 8 EHE (including 3 with high-grade cytology), 14 HEM and 2 PH were immunostained for c-Myc using a commercially available antibody and the Dako Envision detection system. Cases were scored as “positive” and “negative” based on the presence of at least focal nuclear immunoreactivity for c-Myc in endothelial cells.
Results: Nuclear c-Myc expression was seen in 10/13 (77%) AS, significantly higher than in EHE 0/8 (0%) (p=0.001) and HEM, 2/14 (14%) (p=0.002). The two HEM positive cases were both cavernous type. 2 cases of PH were also negative. The sensitivity and specificity of c-Myc expression for the diagnosis of AS were 77% and 95%, respectively. c-Myc expression was also occasionally noted in hepatocytes, a potential pitfall.
Conclusions: IHC for c-Myc shows high sensitivity and specificity in the differential diagnosis of AS involving the liver from potential mimics, both malignant and benign. Absent c-Myc expression in EHE, including cases showing high-grade cytology, is diagnostically useful and suggests that the molecular pathogenesis of EHE differs from that of conventional AS. On-going FISH studies for c-Myc amplification should help to clarify the significance of limited c-Myc expression in cavernous HEM, a lesion which is unlikely to be mistaken for AS in most instances.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 259, Monday Morning