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Diagnosis and Discussion: Case 1143

Final Diagnosis

The histopathologic, immunohistochemical, and molecular studies support a diagnosis of dedifferentiated liposarcoma with a French Federation of Cancer Centers Sarcoma Group (FNCLCC) grade 2 of 3.  The FNCLCC grade results from scoring tumor differentiation (score 3 of 3), mitosis count (score 1 of 3), and tumor necrosis (score 0 of 2) to arrive at a total score of 4 of 8 [1].

Histopathologic analysis of the patient’s previous biopsy showed a spindle cell lesion consistent with a dedifferentiated liposarcoma.  FISH studies for MDM2 amplification were also positive.  Taken together, these findings are concordant with the diagnosis rendered on the resection specimen.

Discussion

Soft tissue sarcomas are a group of relatively rare neoplastic entities that account for approximately 0.7% of cancers [2].  Liposarcomas encompass around 20% of soft tissue sarcomas and include the entities of atypical lipomatous tumor / well-differentiated liposarcoma (ALT / WDLPS), myxoid liposarcoma, pleomorphic liposarcoma, and dedifferentiated liposarcoma (DDLPS) [2, 3].  DDLPS is a neoplasm that arises either de novo or in the setting of progression of an ALT / WDLPS to a non-lipogenic sarcoma [2].  Estimates show that the risk of dedifferentiation of an ALT / WDLPS is about 10% and is dependent upon the anatomic location with retroperitoneal tumors having a higher risk of dedifferentiation [4].  Epidemiologically, the incidence of DDLPS in the United States is less than 2,500 cases per year with approximately 90% of cases arising de novo and the remainder accounting for recurrent tumors [4, 5].

Clinically, while DDLPS can affect any site within the body, the predominant anatomic locations include the extremities, trunk, and the retroperitoneum.  DDLPS that arises in the extremities can present as a palpable mass, whereas DDLPS that originates within the retroperitoneum can grow to a large size before causing symptoms, particularly gastrointestinal symptoms secondary to local mass effect [5].  Retroperitoneal DDLPS may even be identified incidentally.  Radiologic imaging studies may demonstrate heterogeneity which corresponds to the lipomatous and non-lipomatous components of the tumor [4].  Prognostic data indicate that anatomic location is the most important factor in determining clinical outcome with retroperitoneal disease portending a worse prognosis.  Local recurrence is estimated to occur in approximately 40% of cases with near universal recurrence for patients with retroperitoneal DDLPS when observed for a period of 10-20 years [4].  Unfortunately, metastatic disease occurs in about 15-20% of cases with about a 30% rate of mortality when observed over a period of 5 years [4].

Grossly, DDLPS can appear as a nodular mass with varying color ranging from yellow to tan-gray areas, the latter of which corresponds to the dedifferentiated areas of the tumor.  Histologically, the cellular features of DDLPS can present as spindle cells with mild cellular atypia to a higher-grade appearance with pleomorphic spindle and undifferentiated cells arranged in varying architectural patterns.  It is important to note that the dedifferentiated component is non-lipogenic, and the lipogenic component, which can be subtle, is comprised of well-differentiated cells that are morphologically similar to mature adipocytes [3, 4].  A phenomenon known as heterologous differentiation can be present in around 10% of cases of DDLPS in which osteosarcomatous, chondrosarcomatous, angiosarcomatous, or myogenic differentiation can occur; the latter leads to a more aggressive course of disease [4, 5].  The characteristic molecular findings in DDLPS include amplification of MDM2 and CDK4 which occurs as a result of amplification of the 12q13-15 chromosomal region [2, 3, 5].  This chromosomal region amplification serves as the key oncogenic driver with the subsequently increased expression of MDM2 serving to inhibit p53 transactivation which subsequently promotes tumorigenesis [3].

In conclusion, we present a case of DDLPS arising de novo in the pelvis of an adult patient.  Evaluation of the morphologic features in conjunction with the immunohistochemical and molecular studies demonstrates characteristic findings which support the diagnosis of DDLPS.

Works Cited

  1. Protocol for the Examination of Resection Specimens From Patients With Soft Tissue Tumors. 2020  [cited 2025 January 11]; Available from: https://documents.cap.org/protocols/cp-other-softtissue-resection-20-4020.pdf.
  2. Kyriazoglou, A., et al., Well-differentiated liposarcomas and dedifferentiated liposarcomas: Systemic treatment options for two sibling neoplasms. Cancer Treat Rev, 2024. 125: p. 102716.
  3. Gruel, N., et al., Cellular origin and clonal evolution of human dedifferentiated liposarcoma. Nat Commun, 2024. 15(1): p. 7941.
  4. Pedeutour, F. and A. Marino-Enriquez, Dedifferentiated Liposarcoma. 2025, WHO Classification of Tumors (5th Edition).
  5. Haddox, C.L., et al., Diagnosis and management of dedifferentiated liposarcoma: A multidisciplinary position statement. Cancer Treat Rev, 2024. 131: p. 102846.