Marilyn Bui, MD, PhD, Talks About TGCT and Diagnosis of the Disease

In an interview with Oncology Learning Network, Marilyn M. Bui, MD, PhD, Senior Member, Departments of Anatomic Pathology & Sarcoma, Moffitt Cancer Center, Tampa, Florida, provided some insight on tenosynovial giant cell tumor (TGCT) and how diagnosis of the disease has evolved thus far.

What is TGCT and how is the disease diagnosed?

TGCT is a tumor of synovium of joints, bursae, and tendon sheaths caused by the gene translocation of CSF1 and COL6A3. The tumor cells produce a high level of colony-stimulating factor 1 that attracts inflammatory cells, some of which are multi-nucleated giant cells.

When pathologists explore the histology of the tumor, the giant cells are numerous and striking, thus the name of the tumor reflects this observation. TGCT tumors are designated as localized or diffuse type.

The localized type is benign, capable of local recurrence, but typically non-destructive and curative by surgery.

The diffuse type (pigmented villonodular tenosynovitis) is usually not metastatic, but is locally aggressive, and frequently recur after surgical resection. Malignant transformation of pigmented villonodular tenosynovitis is exceptionally rare but can occur.

TGCT is diagnosed through consideration of the following factors:

• clinical presentation (ie, patients aged 30-50 years old; women to men ratio, 2:1; involving hands, feet, or knees; starts with joint swelling, pain, decreased range of motion, eventually debilitating),
• radiology (peri-articular or intra-articular mass; the diffuse-type shows collagen deposition, subchondral bone erosion or cystic change, and hemosiderin deposition),
• pathology (gross and histological examination of the tissue is the key to diagnosis; the sample from the diffuse type is hemorrhagic, multinodular, and with villous projections, and histology shows neoplastic mononuclear cells, numerous associated giant cells, hemosiderin laden histiocytic cells, and collagen deposition), and
• molecular testing (experienced or expert pathologists are capable of diagnosing this tumor without cytogenetic study or molecular study, such as CSF1-COL6A3 translocation, when the clinical, radiology, and pathology fit well for TGCT; however, molecular testing is useful to confirm cases with unusual presentations. It is interesting to point out that only the mononuclear cells are tumor cells that are positive by molecular testing—the giant cells are not the culprits).

Because TGCT shares a clinical and radiologic histology with certain other joint diseases and a lack of standardization for management exists, many patients do not receive an accurate and definitive diagnosis of TGCT at the early stage of the disease.

In recent years, with the availability of effective novel therapy, precise diagnosis of TGCT as early as possible becomes very important.

Can TGCT grow in more than one joint at a time? How does the disease affect a patient’s quality of life?

Yes. The diffuse-type disease can severely impair and disable patients. It could also present as a reason for narcotic use and addiction.   

In your opinion, what is the future outlook of detection of this disease?

Educate clinicians to recognize this disease at an early stage, especially training pathologists, who should be able to diagnose this entity when the first patient sample arrives.

An artificial intelligence application (eg, a working algorithm that will “prompt” the clinician to consider this entity when a “joint disease patient” exhibits the features we discussed above) may be helpful for sniffing out TCGT so that the patient can be biopsied for the pathologist to make the final diagnosis.