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Liposarcoma masquerading as an inflammatory pseudotumor: a case report
© Reagh et al. 2016
Received: 22 July 2015
Accepted: 2 March 2016
Published: 18 March 2016
Distinguishing an atypical lipomatous tumor/well-differentiated liposarcoma from a benign lipomatous tumor on morphology alone can be difficult and there is an established role for MDM2 fluorescent in situ hybridization studies in making this differential diagnosis. There is no literature on the role for MDM2 fluorescent in situ hybridization studies in distinguishing between a well-differentiated liposarcoma with extreme fibrosis and a fibrosing inflammatory pseudotumor.
We report the case of a 76-year-old Australian woman initially diagnosed by an excision biopsy with a retroperitoneal fibrosing inflammatory pseudotumor. She was then diagnosed 5 years later with a pleomorphic undifferentiated sarcoma. Upon review of the original resection specimen, we were able to show that the tumor demonstrated MDM2 amplification. MDM2 amplification was also present in some adjacent bland adipose tissue, and also in the tumor recurrence as a pleomorphic undifferentiated sarcoma.
Taken together, our findings provide strong evidence that the original tumor was a misdiagnosed well-differentiated liposarcoma with extreme fibrosis, and the pleomorphic undifferentiated sarcoma represented a recurrence of the same tumor with dedifferentiation.
The distinction between atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDLPS) and benign lipomatous tumors can be difficult, and fluorescent in situ hybridization (FISH) studies for MDM2 amplification have an established role in the pathological differential diagnosis [1–8]. Distinguishing between WDLPS with extreme sclerosis and fibrosing inflammatory pseudotumor can be equally problematic, but FISH studies for MDM2 are infrequently used in this setting. We present a case of low grade liposarcoma initially misdiagnosed as a fibrosing retroperitoneal pseudotumor and discuss the utility of MDM2 FISH in establishing a definitive tissue diagnosis.
Immunohistochemistry again demonstrated that the neoplastic cells were negative for S100, CD34, cKit, desmin, and ALK. Given the identical location and presence of a rim of inflammatory cells it was clear that the recurrence represented dedifferentiation of the primary tumor. Upon review of both cases, the possibility of dedifferentiated liposarcoma was considered. The primary tumor, the bland adipose tissue resected from the inguinal canal at the time of surgery, and the recurrent tumor all underwent FISH testing, which demonstrated MDM2 amplification in all three specimens (Figs 1d and 2d). Therefore a final diagnosis of ALT/WDLPS with subsequent dedifferentiation and recurrence as a dedifferentiated liposarcoma was made.
The demonstration of amplification of MDM2 with FISH has proven to be a robust and reliable method of differentiating ALT/WDLPS from benign lipomatous tumors [1–8]. For example, Kimura et al. found MDM2 amplification in 98 % (48 of 49) of ALT/WDLPS but in no benign adipose tumors . Similarly Weaver et al. demonstrated MDM2 amplification in 100 % of ALT/WDLPS (13 out of 13) and dedifferentiated liposarcomas (14 out of 14) . Of note MDM2 amplification has been consistently demonstrated in areas of WDLPS with minimal cellular atypia, indicating that the presence of MDM2 amplification even in cytologically bland adipose tissue can be considered prima facie evidence of ALT/WDLPS . That is, if MDM2 FISH studies had been available and were performed prospectively in our case at first presentation in 2010, a diagnosis of ALT/WDLPS could have been justified despite the bland cytology.
There is also emerging evidence that the presence of MDM2 amplification in an otherwise undifferentiated sarcoma is strong evidence that the tumor has arisen from dedifferentiation of a liposarcoma. For example, in Le Guellec et al.  reported that tumors that would otherwise be classified as pleomorphic undifferentiated sarcoma, but that demonstrated MDM2 amplification, had similar clinical characteristics, morphology, genomic profile, and outcome to conventional dedifferentiated liposarcoma and were significantly less aggressive than pleomorphic undifferentiated sarcomas without MDM2 amplification. Our case, which provides clear evidence of a pleomorphic undifferentiated sarcoma arising from a lower grade tumor with MDM2 amplification, further supports this finding.
To exclude ALT/WDLPS, it has been recommended that MDM2 FISH studies be performed in any atypical adipose tumors, including any adipose tumor with equivocal cytological atypia or cytologically bland tumors with recurrence, large size, deep location, and/or retroperitoneal location . This case demonstrates that there may also be a role for MDM2 studies to exclude a diagnosis of WDLPS with extreme sclerosis in patients apparently presenting with a retroperitoneal inflammatory pseudotumor.
Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
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