Undifferentiated Pleomorphic Sarcoma (UPS) : A High-Grade Oral and Maxillofacial Soft Tissue Malignancy




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Undifferentiated pleomorphic sarcoma (UPS) is a rare but highly aggressive malignant tumor of mesenchymal origin. Formerly termed malignant fibrous histiocytoma, UPS is now recognized as a diagnosis of exclusion, applied only when no specific line of differentiation can be identified despite thorough histopathologic and immunohistochemical evaluation. Although uncommon in the oral and maxillofacial region, its rapid growth and destructive potential make early recognition critical for dental professionals.


Definition and Biological Behavior

UPS is a high-grade sarcoma composed of pleomorphic spindle and polygonal cells without identifiable epithelial, muscular, neural, or vascular differentiation. The tumor is characterized by:

- Marked cellular pleomorphism
- High mitotic activity
- Aggressive local invasion
- Early recurrence and potential for distant metastasis


Epidemiology and Etiology

- Rare in the oral cavity and jaws
- Predominantly affects middle-aged and older adults
- Slight male predilection
- Known associations include:
   = Previous radiation therapy
   = Chronic inflammation or scar tissue
   = Genetic instability of mesenchymal cells

Radiation-associated UPS tends to be particularly aggressive.


Common Oral and Maxillofacial Sites

- Mandible and maxilla
- Gingiva and alveolar mucosa
- Buccal mucosa
- Tongue
- Paranasal sinuses
- Deep facial soft tissues

Both soft tissue and intraosseous presentations have been documented.


Clinical Presentation

UPS typically presents as:

- A rapidly enlarging mass
- Firm, poorly defined swelling
- Pain or tenderness in advanced cases
- Ulceration of overlying mucosa
- Tooth displacement or loosening (jaw involvement)
- Facial asymmetry or paresthesia

Early lesions may mimic benign fibrous or reactive oral lesions, leading to delayed diagnosis.


Pathology

Gross Features

- Poorly circumscribed tumor
- Infiltrative margins
- Gray-white, fleshy cut surface
- Areas of hemorrhage and necrosis

Histopathological Features

Microscopic examination reveals:

- Highly pleomorphic spindle and polygonal cells
- Storiform (cartwheel) growth pattern
- Hyperchromatic nuclei
- Numerous atypical mitotic figures
- Multinucleated tumor giant cells
- Areas of necrosis and hemorrhage
- Infiltrative growth into adjacent tissues

No specific differentiation is identifiable.

Immunohistochemistry

Immunohistochemical staining is essential to exclude other malignancies:

- Vimentin: positive
- Cytokeratins: negative
- Desmin and SMA: negative
- S100: negative
- CD31/CD34: negative
- High Ki-67 proliferation index

Differential Diagnosis

- Fibrosarcoma
- Leiomyosarcoma
- Rhabdomyosarcoma
- Spindle cell carcinoma
- Angiosarcoma
- Malignant peripheral nerve sheath tumor

UPS is diagnosed only after these entities are excluded.


Imaging Characteristics

Radiographic Features

- Ill-defined radiolucency in jaw lesions
- Cortical bone destruction
- Possible tooth root resorption

CT and MRI

- Poorly defined soft tissue mass
- Heterogeneous enhancement
- MRI best demonstrates soft tissue invasion

Imaging helps assess tumor extent but is not diagnostic.


Management and Treatment

- UPS requires aggressive multidisciplinary management:

- Wide surgical excision with clear margins (primary treatment)


- Adjuvant radiotherapy for:

    = High-grade tumors

    = Close or positive margins

    = Inoperable lesions
- Chemotherapy in selected advanced or metastatic cases

- Complete excision is often difficult in the head and neck region.


Prognosis

UPS has an overall poor prognosis:

- High local recurrence rate
- Hematogenous metastasis, commonly to the lungs
- Five-year survival approximately 30–60%

Prognosis worsens with:

  = Large tumor size
  = Deep tissue invasion
  = Positive surgical margins
  = Radiation-induced origin

Early diagnosis improves outcomes.


Importance for Dental Professionals

Dental practitioners are often the first clinicians to encounter these lesions. Key responsibilities include:

- Recognizing rapidly enlarging or atypical oral masses
- Avoiding assumptions of benignity
- Prompt biopsy and referral
- Long-term follow-up and oral rehabilitation after treatment


Conclusion

Undifferentiated pleomorphic sarcoma is a rare but highly aggressive malignancy of the oral and maxillofacial region. Its nonspecific clinical appearance and complex histopathology demand a high index of suspicion from dental professionals. Early detection, accurate diagnosis, and prompt multidisciplinary treatment are essential to improve patient survival and quality of life.


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