Loss of Retinoblastoma Protein Expression in Spindle Cell/Pleomorphic Lipomas and Cytogenetically Related Tumors: An Immunohistochemical Study with Diagnostic Implications
Benjamin J Chen, Leona A Doyle, Christopher DM Fletcher, Jason L Hornick. Brigham and Women's Hospital & Harvard Medical School, Boston, MA
Background: Spindle cell lipoma is a circumscribed subcutaneous tumor that typically arises on the upper back or neck of older male patients. Spindle cell lipoma is composed of an admixture of adipocytes, short spindle cells, and ropey collagen bundles in variable proportions, sometimes with a myxoid stroma; pleomorphic lipoma is a variant containing floret-like giant cells. Consistent rearrangements of chromosomes 13q and 16q have been identified by cytogenetics. Mammary-type myofibroblastoma and cellular angiofibroma show overlapping histologic features and similar chromosomal losses, suggesting a possible relationship among these tumor types. The tumor suppressor gene RB1, encoding the retinoblastoma (Rb) protein, is located at 13q14, within a minimally deleted region in spindle cell lipoma. The purpose of this study was to examine expression of Rb by immunohistochemistry (IHC) in spindle cell lipoma, pleomorphic lipoma, mammary-type myofibroblastoma, and cellular angiofibroma, as well as histologic mimics, to determine its potential diagnostic utility.
Design: Whole tissue sections of 194 tumors were evaluated: 18 spindle cell lipomas, 20 pleomorphic lipomas, 19 mammary-type myofibroblastomas, 16 cellular angiofibromas, 22 conventional lipomas (8 intramuscular), 18 atypical lipomatous tumors (all positive for MDM2 and CDK4), 19 solitary fibrous tumors, 19 myxoid liposarcomas, 14 hibernomas, 11 deep (aggressive) angiomyxomas, 9 angiomyofibroblastomas, and 9 vulval fibroepithelial stromal polyps. IHC was performed following pressure cooker antigen retrieval using a mouse anti-Rb monoclonal antibody (1:100; G3-245; BD Biosciences). Nuclear staining for Rb was scored as "intact" or "deficient".
Results: Rb expression was deficient in all spindle cell lipomas, pleomorphic lipomas, and cellular angiofibromas and in 17 (89%) mammary-type myofibroblastomas. Rb staining was sometimes difficult to interpret in cellular angiofibromas with reactive stromal changes. Rb was also deficient in 2 (9%) conventional lipomas. Rb expression was intact in all other tumor types evaluated.
Conclusions: Of the soft tissue tumors associated with 13q deletions, all spindle cell lipomas, pleomorphic lipomas, and cellular angiofibromas and most mammary-type myofibroblastomas show loss of Rb expression. Rb expression is intact in histologic mimics. These findings reinforce the pathogenetic relationship among this group of tumors and demonstrate the potential diagnostic utility of IHC for Rb.
Category: Bone & Soft Tissue
Tuesday, March 20, 2012 11:00 AM
Platform Session: Section G, Tuesday Morning