Well-Differentiated Liposarcoma of the Hypopharynx Exhibiting Myxoid Liposarcoma-like Morphology with MDM2 and DDIT3 Co-Amplification

Abstract

Well-differentiated liposarcoma (WDL) is one of the most common soft tissue sarcomas in adults. It has a predilection for middle-aged males and arises in deep-seated locations such as retroperitoneum, mediastinum, and spermatic cord. Its occurrence in young individuals at the hypopharyngeal region is an exceedingly rare event. Myxoid liposarcoma (ML)-like changes can seldom occur in some cases of WDL, which makes the diagnosis of WDL more challenging. Amplification of DDIT3 gene in a subset of cases of WDL has shown to be associated with such unique morphology. Herein, we present a case of a 36-year-old gentleman who presented with difficulty in breathing and swallowing for 3 months duration. CT scan of the neck revealed a lesion along the posterior wall of the hypopharynx measuring 3.5 cm. Histopathologic examination revealed a tumor composed of lobules of oval to spindle cells in a prominent myxoid stroma with delicate chicken-wire vasculature. In the vicinity, there were lobules composed of variably sized adipocytes separated by thick fibrous septa that contains atypical hyperchromatic spindle cells. By immunohistochemistry, the tumor cells in both components were immunoreactive for CDK4, but negative for MDM2. Fluorescence in-situ hybridization (FISH) confirmed the presence of MDM2 gene amplification. There was no evidence of FUS-DDIT3 gene rearrangement, however, DDIT3 gene was also amplified. The diagnosis of well-differentiated liposarcoma with prominent myxoid stroma was rendered. This is the first documentation of WDL with ML-like morphology harboring co-amplification of MDM2 and DDIT3 in the hypopharynx.

Primary Sarcomas of the Larynx: A Case Series of Four Different Histopathologic Types

“…In such cases, the use of MDM2 and CDK4 by immunohistochemistry and/or FISH is helpful to establish the diagnosis. 13,14 Positive staining for MDM2 and/or CDK4 or the detection of their amplified genes by FISH confirms the diagnosis of WDL. 13,14 It is also essential to extensively sample the tumor to rule out the possibility of dedifferentiated liposarcoma, which is characterized by the presence of highgrade spindle cell sarcoma adjacent to the well-differentiated component.…”

“…13,14 Positive staining for MDM2 and/or CDK4 or the detection of their amplified genes by FISH confirms the diagnosis of WDL. 13,14 It is also essential to extensively sample the tumor to rule out the possibility of dedifferentiated liposarcoma, which is characterized by the presence of highgrade spindle cell sarcoma adjacent to the well-differentiated component. 12 It has been found that up to 50% of laryngeal liposarcomas recur; therefore, the current recommendation is to perform wide surgical excision with negative margins.…”

Dedifferentiated Liposarcoma with Heterologous and Homologous Elements-A Report of Three Cases

“…Well-differentiated and dedifferentiated liposarcomas can contain prominent myxoid stroma, which can present as a diagnostic challenge when confronted with a small biopsy sample. Such tumors have been shown to contain coamplifications of MDM2 and DDIT3 [22][23][24][25], further adding to a potential diagnostic dilemma. Helpful morphologic clues to exclude the presence of a ML would be absence of the characteristic uniform histomorphology with presence of pleomorphic cells/lipoblasts in the tumor.…”

“…The answer was only possible through FISH testing for MDM2 and DDIT3 amplification. DDIT3 amplification appears not to affect the prognosis, including recurrence free survival or disease specific survival, nor the rate of distant metastasis [22][23][24][25]. The role of DDIT3 in the pathogenesis of DDL as a possible driver/non-driver mutation or regulating adipocytic differentiation requires larger studies to further characterize.…”