Myxofibrosarcoma, formerly known as myxoid malignant fibrous histiocytoma, stands as a unique entity among soft tissue sarcomas. With a predilection for the limbs of elderly patients, myxofibrosarcoma presents a spectrum of histopathological features that correlate with its clinical behavior. This blog post delves into the histopathological and immunohistochemical hallmarks of myxofibrosarcoma and discusses its differential diagnosis.

Histopathological Features

Myxofibrosarcoma is known for its heterogeneous appearance, making it a challenging diagnosis. It typically exhibits a myxoid stroma, characterized by abundant extracellular mucoid material. Within this myxoid matrix, there is a proliferation of spindle-shaped cells and pleomorphic, curvilinear capillary blood vessels.

The degree of cellularity can vary greatly, with more aggressive tumors showing higher cellularity and pleomorphism.

The tumor often demonstrates an infiltrative growth pattern, with cells extending into the adjacent fat and muscle, which contributes to a high local recurrence rate. These cells can range from relatively uniform spindle cells to markedly atypical, pleomorphic cells. The presence of multinucleated giant cells and a variable amount of collagenous stroma can also be seen.

Immunohistochemistry

Immunohistochemical staining is pivotal in confirming the diagnosis of myxofibrosarcoma. Typically, the tumor cells express vimentin, a marker of mesenchymal origin. Expression of CD34 is variable and can help in differentiating myxofibrosarcoma from other myxoid tumors. In contrast, cytokeratin and S100 protein are usually negative, helping to rule out epithelial and neural tumors, respectively.

The immunohistochemical profile may also include:

• SMA (smooth muscle actin) – variably positive
• Desmin – usually negative, which helps to exclude myogenic sarcomas
• MDM2 and CDK4 – amplification may be seen in higher-grade myxofibrosarcomas

Differential Diagnosis

The differential diagnosis for myxofibrosarcoma is broad due to its varied morphology. It includes:

• Myxoid liposarcoma: Characterized by a t(12;16) translocation, which is not present in myxofibrosarcoma. It also has a more uniform myxoid appearance and the presence of lipoblasts.
• Low-grade fibromyxoid sarcoma: Typically exhibits a whorled growth pattern and lacks the pleomorphism seen in myxofibrosarcoma.
• Neurofibroma: S100 positive, which can be used to differentiate it from myxofibrosarcoma.
• Nodular fasciitis: A benign myxoid lesion that grows rapidly and is composed of plump spindle cells with a tissue culture-like growth pattern.

Conclusion

Myxofibrosarcoma represents a complex and challenging diagnosis that requires a careful integration of histopathologic and immunohistochemical findings. Its variable presentation underscores the importance of considering a broad differential diagnosis. The pathologist’s expertise in recognizing the subtleties of myxofibrosarcoma can significantly impact the management and prognosis of patients. With continued research and the development of molecular diagnostic tools, we hope to refine our understanding of myxofibrosarcoma and improve the outcomes for those affected by this enigmatic tumor.