# FDG PET/CT in Melanoma and Sarcoma

## Melanoma

### Indications for PET/CT

FDG PET/CT is indicated for initial staging and restaging of stage III and IV melanoma. It is not routinely indicated for stages I and II, where the yield for distant metastases is low and the false-positive rate is high. Other indications include evaluation of suspected recurrence or rising tumor markers (LDH and S-100B levels) and assessment of treatment response to immunotherapy (checkpoint inhibitors) or targeted therapy (BRAF/MEK inhibitors).

### Staging and Detection

PET/CT achieves a sensitivity of approximately 85 to 95% for distant metastases and is excellent for detecting soft tissue, lymph node, visceral, and skeletal involvement. It is superior to conventional imaging with CT alone for identifying unsuspected distant disease and can detect in-transit metastases, which are dermal or subcutaneous deposits located between the primary site and the regional nodal basin. PET/CT changes management in 15 to 30% of stage III and IV patients by upstaging or downstaging.

### Limitations

PET/CT has limited sensitivity for pulmonary metastases smaller than 1 cm, making thin-section chest CT the superior modality for detecting small lung lesions. Brain metastases are poorly detected because of high physiologic cortical FDG uptake, and gadolinium-enhanced MRI is the standard for brain staging. Micrometastases below PET resolution in sentinel lymph nodes and small skin or subcutaneous lesions below 5 mm may also be missed.

<image>FDG PET/CT maximum intensity projection (MIP) in a patient with metastatic melanoma showing widespread nodal, hepatic, and skeletal metastases</image>

### Immunotherapy Response Assessment

Pseudoprogression, seen in 5 to 10% of patients on checkpoint inhibitors, involves an initial apparent increase in tumor burden or metabolic activity followed by subsequent response. Hyperprogression represents rapid true disease progression on immunotherapy. The iRECIST and iPERCIST criteria account for pseudoprogression by requiring confirmatory imaging at 4 to 8 weeks before declaring true progression. New lesions on the initial post-treatment scan should be confirmed on follow-up imaging. Sarcoid-like granulomatous reactions can cause diffuse nodal FDG uptake that mimics metastatic disease.

### Uveal Melanoma

Uveal melanoma has distinct biology from cutaneous melanoma and metastasizes preferentially to the liver. PET/CT has limited sensitivity for small hepatic metastases below 1 cm, and liver MRI is preferred for hepatic surveillance. PET/CT remains useful for detecting extrahepatic metastatic disease.

<image>PET/CT showing in-transit melanoma metastases as multiple small FDG-avid subcutaneous deposits along the extremity between the primary site and inguinal nodal basin</image>

## Sarcoma

### Soft Tissue Sarcoma

FDG avidity in soft tissue sarcoma correlates with tumor grade. High-grade sarcomas are intensely FDG-avid, while low-grade lesions may show minimal uptake. An SUVmax above 6 to 8 suggests high-grade sarcoma and is useful for guiding biopsy toward the most aggressive component of a heterogeneous tumor. PET/CT aids in initial staging by detecting pulmonary and distant metastases. For monitoring neoadjuvant chemotherapy response, a decrease in SUVmax of more than 35 to 40% suggests a favorable response. PET also guides biopsy to the most metabolically active portion of heterogeneous tumors, which is important because sampling the wrong area may lead to undergrading.

| Sarcoma Subtype | FDG Avidity | Key PET/CT Role |
|---|---|---|
| GIST | Variable; responds rapidly to imatinib | Early response assessment (1–2 weeks) |
| Ewing sarcoma | Intensely avid | Superior to bone scan for skeletal staging |
| Osteosarcoma | Avid | Staging and chemotherapy response |
| Dedifferentiated liposarcoma | Avid (dedifferentiated component) | Guides biopsy to aggressive component |
| Well-differentiated liposarcoma | Low/absent | May be FDG-negative |
| Myxoid sarcoma | Low/absent | False-negative risk despite malignancy |
| Undifferentiated pleomorphic sarcoma | Intensely avid | Staging and response monitoring |

### Specific Sarcoma Subtypes

Gastrointestinal stromal tumors (GIST) are a particularly notable application. FDG PET/CT shows rapid metabolic response to imatinib, often within 1 to 2 weeks, preceding anatomic changes on CT by months. This early response assessment can confirm drug sensitivity. Ewing sarcoma is typically intensely FDG-avid, and PET/CT is superior to bone scan for skeletal staging. Osteosarcoma is FDG-avid and PET is useful for initial staging and assessment of chemotherapy response. Liposarcoma shows variable avidity: well-differentiated subtypes may be FDG-negative, while dedifferentiated components are FDG-avid, producing a heterogeneous uptake pattern. Myxoid sarcomas may have low or absent FDG uptake despite being malignant, which is an important cause of false-negative results.

### Bone Sarcoma

FDG PET/CT complements MRI for local staging of bone sarcomas and detects skip lesions and distant metastases. Post-chemotherapy reduction in SUVmax correlates with the percentage of histologic necrosis, and greater than 90% histologic necrosis is a favorable prognostic factor. PET can estimate this non-invasively.

<image>FDG PET/CT of a high-grade undifferentiated pleomorphic sarcoma of the thigh showing heterogeneous intense uptake with a central photopenic area representing necrosis</image>

## Technical Pearls for Melanoma and Sarcoma PET/CT

Whole-body imaging from vertex to toes is preferred for melanoma because lower extremity primary sites are common. For sarcoma, imaging should include the primary site and lungs at minimum. Contrast-enhanced PET/CT improves anatomic delineation in sarcoma, especially for surgical planning. Dual time-point imaging may help distinguish malignant from inflammatory uptake in equivocal cases.

<image>Pre- and post-neoadjuvant chemotherapy PET/CT comparison in Ewing sarcoma showing marked reduction in FDG uptake indicating favorable treatment response</image>

## Clinical Pearls

In melanoma, PET/CT should not replace sentinel lymph node biopsy for nodal staging in clinically node-negative patients. PET lacks the sensitivity to detect micrometastatic disease in sentinel nodes.

Brain MRI should always accompany PET/CT in advanced melanoma because PET has poor sensitivity for brain metastases due to high background cortical uptake.

In GIST, FDG response precedes CT size change. An early PET scan 1 to 4 weeks after starting imatinib can confirm drug sensitivity.

Low-grade sarcomas may be PET-negative. A non-avid mass does not exclude malignancy.

Always correlate PET findings with histologic grade, as management differs markedly between low- and high-grade sarcomas.

Granulomatous reactions from checkpoint inhibitor therapy can mimic widespread metastatic disease on PET/CT and should be considered in the differential when diffuse nodal uptake appears on post-treatment imaging.

## References

- NCCN Guidelines: Melanoma and Soft Tissue Sarcoma -- Imaging Recommendations.
- Bastiaannet, E., et al. "FDG PET/CT for Melanoma Staging." *Annals of Surgery*, 2012.
- Choi, H., et al. "CT and PET Response Criteria in GIST." *Journal of Clinical Oncology*, 2007.
- Quartuccio, N., et al. "PET/CT in Soft Tissue Sarcomas." *European Journal of Nuclear Medicine*, 2019.