Resident Program - Case of the Month

August 2022 – Presented by Dr. Jacob Donnelly (Mentored by Dr. Meighan Tomic)

Discussion

The most common malignant mesenchymal neoplasms are liposarcomas comprising around 20% of all sarcomas⁽³⁾. The WHO classification of soft tissue and bone tumors recognize five major subtypes of liposarcomas⁽¹⁾:

1. ALT/WDLPS
2. Dedifferentiated Liposarcoma
3. Myxoid Liposarcoma
4. Pleomorphic Liposarcoma
5. Mixed Type Liposarcoma

The subtypes of these tumors have distinct morphological and genetic features⁽³⁾:

1. ALT/WDLPS and dedifferentiated liposarcoma have amplification of the 12q13-15 region
2. Myxoid liposarcoma have rearrangement of the DDIT3 gene
3. Pleomorphic liposarcoma have complex karyotypic alterations (NF1 mutations)

Dedifferentiated liposarcomas make up around 10% of all liposarcomas⁽²⁾. This subtype of liposarcomas usually occurs in the following locations⁽⁴⁾:

1. Retroperitoneum
2. Deep soft tissue of the:
   1. Limbs
   2. Trunk
   3. Mediastinum
   4. Head and neck
   5. Spermatic cord

Dedifferentiated liposarcoma most commonly occurs in men that are in their 60s-70s⁽²⁾. Histologically you will see an abrupt or gradual transition from a ALT/WDLPS to a non-lipogenic cellular sarcoma. The non-lipogenic component often demonstrates high grade features with >5 mitotic figures per 10 HPF⁽⁴⁾. Overexpression in the lipogenic and non-lipogenic components of dedifferentiated liposarcoma of MDM2 and CDK4 is present on immunohistochemistry⁽⁴⁾. Pleomorphic leiomyosarcoma must be ruled out to make the diagnosis of dedifferentiated liposarcoma. Leiomyosarcoma will rarely demonstrate positivity for MDM2 and CDK4, and will usually be positive for smooth muscle actin, desmin, and h-caldesmon⁽³⁾. Despite having a high-grade histologic appearance, dedifferentiated liposarcomas are less aggressive than other sarcomas with a metastatic rate of around 20%⁽¹⁾. Mortality is most commonly due to local recurrences with an overall 5-year mortality of ~25%⁽⁴⁾.

Works Cited

1. Antonescu, Christina R. “Chapter 1.” Soft Tissue and Bone Tumours, 5th ed., vol. 3, International Agency for Research on Cancer, Lyon, 2020, pp. 34–47.
2. Clay, Michael R. “Dedifferentiated Liposarcoma.” Pathology Outlines - Dedifferentiated Liposarcoma, 12 Nov. 2021.
3. Hornick, Jason L. Practical Soft Tissue Pathology: A Diagnostic Approach. Elsevier, 2019.
4. Lindberg, Matthew R. “Dedifferentiated Liposarcoma.” ExpertPath, 18 Mar. 2020.
5. Schaberg, Kurt. “Soft Tissue Tumors - UC Davis.” Soft Tissue Tumors, 3 Apr. 2020.