Nuclear expression of MDM2 in hibernoma: a potential diagnostic pitfall
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ORIGINAL ARTICLE
Nuclear expression of MDM2 in hibernoma: a potential diagnostic pitfall Yojiro Tsuda 1 & Atsuji Matsuyama 1 & Kosuke Makihara 2 & Koichi Higaki 3 & Toru Motoi 4 & Tomotake Okuma 5 & Masanori Hisaoka 1 Received: 29 May 2020 / Revised: 31 July 2020 / Accepted: 14 August 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Hibernoma is a rare benign adipocytic tumor composed of a proliferation of brown and white fat cells varying in their proportions. The tumor may also contain fat cells resembling lipoblasts, which makes it difficult to distinguish it from atypical lipomatous tumor/well differentiated liposarcoma (ALT/WDLS). Although nuclear expressions of murine double minute 2 (MDM2) and cyclin-dependent kinase 4 (CDK4) are widely used as immunohistochemical surrogate markers for ALT/ WDLS, the utility of these proteins in distinguishing between hibernoma and ALT/WDLS still remains to be elucidated. We evaluated immunohistochemical expressions of MDM2 and CDK4 in 10 hibernomas expressing uncoupling protein-1 (UCP-1), a mitochondrial protein transporter consistently expressed in brown fat cells, and lacking MDM2 gene amplification, which was analyzed by fluorescence in situ hybridization (FISH). In contrast to the data previously obtained, nuclear expression of MDM2 was observed in 100% (10/10 cases) of the hibernomas irrespective of the proportion of brown fat cells, whereas no cases were positive for CDK4. The tumors also showed almost concurrent expression of p53 (in 9/10 cases) and ubiquitin-specificprocessing protease 7 (USP7) (in 10/10 cases), which deubiquitinates and stabilizes MDM2, potentially resulting in its nuclear expression without MDM2 gene amplification. MDM2 expression may thus be a diagnostic pitfall for hibernoma particularly in differentiating it from ALT/WDLS. Keywords Hibernoma . MDM2 . Atypical lipomatous tumor/well differentiated liposarcoma . Immunohistochemical pitfalls . FISH
Introduction This article is part of the Topical Collection on Quality in Pathology * Yojiro Tsuda [email protected] 1
Department of Pathology and Oncology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-Ku, Kitakyushu 807-8555, Japan
2
Department of Surgical Pathology, Kyushu Rosai Hospital, Kitakyushu 800-0296, Japan
3
Division of Pathology, St Mary Hospital, Kurume 830-8543, Japan
4
Department of Pathology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo 113-8677, Japan
5
Department of Orthopedic Surgery and Musculoskeletal Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo 113-8677, Japan
Hibernoma is a rare, benign adipocytic tumor displaying brown fat differentiation. It commonly arises in young or middle-aged adults as a slowly growing, small subcutaneous mass located mainly in the thigh, trunk, chest wall, upper extremity, or head and neck [1]. Some hibernomas show a large tumor size of more than 10 cm and are deeply seated
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