This video presents a detailed pathology case study of a deep intramuscular thigh mass in a 60-year-old woman, focusing on the diagnostic challenges posed by high-grade pleomorphic spindle cell sarcomas. The initial core needle biopsy revealed an aggressive cellular neoplasm showing marked atypia and mitotic figures, but yielded a non-specific immunohistochemical profile (patchy Actin, negative for S100, Keratin, and Desmin). The initial diagnosis was High Grade Pleomorphic Sarcoma. The subsequent resection specimen confirmed the diagnosis as Undifferentiated Pleomorphic Sarcoma (UPS), the modern term for what was previously called Malignant Fibrous Histiocytoma (MFH). The presentation extensively discusses the rationale behind the initial high-grade diagnosis, the importance of excluding specific sarcoma subtypes and mimics (like melanoma or carcinoma), and the role—or lack thereof—of markers like Vimentin and MDM2 FISH in the workup of these difficult, undifferentiated tumors.
Pathology Case Study: Undifferentiated Pleomorphic Sarcoma (UPS)
0:10 Patient and Specimen: Case involves a 60-year-old woman with a deep intramuscular thigh mass. Samples include a core needle biopsy and sections from a wide local excision.
0:59 Biopsy Morphology: The needle biopsy showed a cellular neoplasm consisting of sheets of hyperchromatic, pleomorphic spindle cells with clear mitotic activity.
2:07 Immunostains: Initial stains were non-specific: weak/patchy Actin (non-specific, possibly myofibroblastic differentiation) and negative results for S100, Keratin, and Desmin.
3:29 Diagnosis on Biopsy: The recommended diagnosis for an atypical, high-grade, spindle cell neoplasm with a non-specific IHC profile on a needle biopsy is High Grade Pleomorphic Sarcoma.
3:34 Terminology: This high-grade, undifferentiated diagnosis is now known as Undifferentiated Pleomorphic Sarcoma (UPS), which replaces the outdated term Malignant Fibrous Histiocytoma (MFH).
3:56 Biopsy Limitation: A core biopsy is insufficient to definitively rule out specific high-grade sarcomas (like Pleomorphic Liposarcoma or Dedifferentiated Liposarcoma) because the diagnostic components (e.g., lipoblasts, well-differentiated fat) may be present in other areas of the tumor.
4:40 Management Consistency: The clinical management (wide local excision, usually with radiation) is similar for most adult high-grade pleomorphic sarcomas, regardless of the subtle subtype differences.
5:34 Resection Features: The subsequent resection specimen confirmed high-grade features, including necrosis, hemorrhage, and marked atypia, solidifying the Grade III designation.
6:42 Final Diagnosis: The tumor was confirmed as Undifferentiated Pleomorphic Sarcoma, possibly a giant cell rich variant.
8:07 Standard Workup: The presenter’s standard initial IHC panel for high-grade spindle cell tumors includes Actin, Desmin, Keratin, and S100 (or SOX10). Actin is considered the least helpful.
11:39 Vimentin: The presenter strongly advocates against using Vimentin in soft tissue pathology, as it is non-specific and adds no meaningful diagnostic information.
13:41 MDM2 FISH in Extremity: Testing for MDM2 amplification (associated with liposarcoma) is appropriate but not routinely performed by the presenter on UPS in the extremities, though some experts do recommend it to rule out occult Dedifferentiated Liposarcoma (which has a slightly better prognosis).
15:25 MDM2 FISH in Retroperitoneum: MDM2 testing is considered mandatory for high-grade pleomorphic sarcomas in the retroperitoneum, where the differential diagnosis is heavily weighted toward Dedifferentiated Liposarcoma.
16:28 Cell of Origin: UPS is fundamentally a diagnosis of exclusion. It is hypothesized to arise from a primitive mesenchymal precursor/stem cell that fails to undergo any specific line of differentiation.