F-18 Fluoro-2-Deoxyglucose Positron Emission Tomography (PET)/Computed Tomography (CT) Imaging in Melanoma: Normal Variants, Pitfalls, and Artifacts

Abstract

Multimodality imaging has revolutionized diagnostic imaging for several oncologic pathologies including melanoma. Although F-18 fluoro-2-deoxyglucose positron emission tomography/ computed tomography [18F]FDG PET/CT has a high sensitivity in stage III and IV melanoma, several normal variants, and imaging pitfalls may result in falsely increased or reduced tracer uptake that may negatively impact diagnostic accuracy. In addition to normal physiologic tracer uptake, differences in the biological and molecular characteristics of different types of melanoma are also responsible for pitfalls. For instance, [18F]FDG PET/CT has a low sensitivity for detecting brain metastases due to normal physiologic [18F]FDG uptake in brain tissue while hepatic metastases from cutaneous melanoma are more [18F]FDG-avid than hepatic metastases from uveal melanoma. With the introduction of immunotherapies for melanoma, treatment response assessment using [18F]FDG PET/CT has a reduced specificity. This is due to hypermetabolic immune-related adverse effects such as hepatitis, dermatitis, and colitis resulting in false-positive uptake. In addition, immune therapy-induced initial increase in tumor uptake followed by disease response (pseudo-progression) is a cause of false-positive scan interpretation. Specific technical artifacts impact disease detection in [18F]FDG PET/CT melanoma imaging. The identification of small metastatic lymph nodes and lung nodules may be limited by the resolution of the PET/CT camera (partial volume effect). Computed tomography (CT) attenuation correction results in less apparent skin and subcutaneous lesions. Pictorial illustrations will be central to this paper for the description of these normal variants, imaging artifacts, and pitfalls. It is critical for the imaging specialist to have a clear understanding of these potential limitations of 18F-FDG PET/CT imaging in individuals who are referred with melanoma.

Skin Cancer Pathobiology at a Glance: A Focus on Imaging Techniques and Their Potential for Improved Diagnosis and Surveillance in Clinical Cohorts

“…18 F-FDG is the only PET radioactive tracer that received FDA approval in the 1990s and subsequent reimbursement by the Centers for Medicare and Medicaid Services (CMS); since then, its use for imaging applications in oncology has grown steadily [ 364 ]. 18 F-FDG PET/CT plays a limited role in staging early melanoma (AJCC stages I and II); however, it is more useful in the initial staging of advanced cutaneous melanoma (AJCC stages III and IV) and the assessment of disease recurrence, demonstrating a high accuracy in the detection of lymph node, soft tissue, and visceral metastases [ 241 ]. However, increasing evidence suggests that PET/CT may not be sensitive enough in assessing melanoma brain metastases, which are one of the most life-threatening complications of the disease.…”

“…Imaging pitfalls are considerably affected by several factors, including patient preparation and lesion characteristics as well as the preferential bio-distribution of 18 F-FDG in certain tissues or organs. Pitfalls dramatically impact scan sensitivity and specificity, as they may result in false positives or negatives [ 241 ]. False-positive findings may result in unnecessary and invasive procedures; yet, false-negative scans may be associated with delayed diagnosis and treatment, thereby dramatically affecting the patient and clinician [ 242 ].…”

“…Almost all the described optical methods have limitations, such as high cost, the need for specialized medical personnel, low specificity, and reduced efficiency when employed singularly in the clinical setting [ 365 , 366 ]. Another issue to consider is that most are not readily applicable to lesions with hyperkeratosis and inflammation or lesions located in unconventional anatomic sites [ 241 , 242 ]. One possibility that has been suggested to overcome the limited sensitivity and specificity values is the combined use of optical modalities, which may result in performances larger than those achieved by the sole use of one of the technologies.…”

“…Given that the glucose metabolism is manifold increased in malignant cells than in normal tissues, 18 F-FDG PET is the preferred technique for cancer imaging in oncology [ 244 ]. Nonetheless, 18 F-FDG PET/CT plays a limited role in staging early melanoma (AJCC stages I and II); still, it proved more useful in the initial staging of advanced cutaneous melanoma (AJCC stages III and IV) and assessment of disease recurrence, demonstrating a high accuracy in the detection of lymph node, soft tissue, and visceral metastases [ 241 ]. It was found that among sonography, CT, PET, and PET/CT, US is the most efficient for node staging, whereas PET/CT is more appropriate for the detection of distant metastases (80% sensitivity and 87% specificity) [ 245 ].…”

“…Post-inflammatory changes around the site of a surgical resection, benign conditions, bone fractures and degenerative bone disorders, thyroiditis, esophagitis, and pancreatitis display increased 18 F-FDG uptake and can be easily confounded with metastases [ 242 ]. Moreover, FDG PET seems inappropriate for assessing brain melanoma metastases due to high physiologic 18 F-FDG metabolism in those tissues [ 241 ]; yet, 18 F-FDG PET/CT displays a reduced sensitivity for detecting small metastatic lung lesions due to partial volume effect, leading to underestimation of the tracer uptake [ 264 ]. Given these limitations, brain MRI and lung CT imaging should remain the primary detection methods for melanomas spreading to those secondary sites.…”