Melanoma

Todd M. Blodgett, MD

Alex Ryan, MD

Omar Almusa, MD

Key Facts

Terminology

Malignant melanoma (MM)

Imaging Findings

CT
- CECT is better than FDG PET for detection of small pulmonary metastases
- Less sensitive than FDG PET for bone, skin, lymph node, abdominal metastases
- Combination of FDG PET and conventional imaging (CT/MR) more accurate than either one alone
- CT generally performed for staging and restaging purposes
PET/CT
- Detects more lesions than CT, particularly intramuscular and other unsuspected metastases
- More exact method of determining FDG uptake in a mass
- Staging: Sensitivity 83%, specificity 91%
- Restaging: 74% sensitivity 74%, specificity 86% for recurrence
In one study, 16% of patients underwent further imaging &/or biopsies that ultimately had no effect on patient care

Top Differential Diagnoses

Other Neoplasms
Inflammation/Infection
Brown Fat

Clinical Issues

Tumor thickness = most important histologic prognostic indicator

Coronal PET (A), axial CT (B) and fused PET/CT (C) show foci of increased FDG activity within the bowel

, corresponding to melanoma metastases.

Gross pathology shows the partially hemorrhagic intraluminal bowel metastasis

from the same patient as the previous image.

TERMINOLOGY

Abbreviations and Synonyms

Malignant melanoma (MM)
Skin cancer

Definitions

Melanoma: Neoplasm of melanin-producing cells

IMAGING FINDINGS

General Features

Best diagnostic clue: FDG-avid focal uptake on PET seen in primary, satellite lesions, lymph nodes (LN), visceral organs, and bone
Location
- Primary melanoma
  - Men: Torso most common
  - Women: Upper extremities most common
  - 4-5% of primary melanoma may arise in extracutaneous location
  - Locations include eye, meninges, mucous membranes of digestive, genitourinary, respiratory tracts
  - Multiple primaries occur in ˜ 5% of patients
- Local spread
  - At or near previous excision site
  - Recent biopsy or other inflammation may produce false positive on FDG PET
  - Sentinal node tumor may alter stage
- Metastatic disease
  - In-transit nodal metastases: Between primary and regional lymph nodes
  - Regional lymph nodes
  - Common sites: Spine, brain, lung, liver, spleen, bowel
  - Clinically apparent brain metastases found in 18-46% of patients with stage IV disease
  - Conjunctival melanoma may present with systemic metastases in 26% of cases without regional lymph node involvement
Size
- Size considerations usually relative to depth of lesion
- Stage is dependent on depth

Morphology: Malignant lymph nodes are typically round with absence of fatty hilum

Imaging Recommendations

Best imaging tool
- FDG PET
  - May reveal focal increased uptake in lymph node bed, soft tissue, and organs
  - More sensitive than CT for skin, LN, bone, and abdominal metastases
- CECT
  - Exclusion of benign structures with FDG uptake
  - Accurate delineation of primary and metastatic tumor in lymph node bed, soft tissue, and organs
  - Superior detection of small pulmonary metastases
  - Inclusion of lymph nodes by size or morphology (round without fatty hilum)
- MR
  - For definition of brain metastases
Protocol advice
- FDG PET
  - Evaluate skin for lesions with non-attenuation corrected PET images
  - Attenuation correction can smooth data, obscuring lesions
  - PET scan often extended to true whole-body coverage due to metastatic behavior of melanoma
  - Clinical history crucial: False positives with recent surgery, biopsy, inflammation
- Total lesion glycolysis (TLG) approach
  - More exact method of determining FDG uptake in a mass
  - Has failed to show superiority over simpler SUV measurement
- Longer FDG uptake times may correlate to better overall sensitivity/specificity
  - In general, more uptake in malignant lesions and less uptake in benign lesions is seen at 2 or 3 hour time point

CT Findings

CT generally performed for staging and restaging purposes
- Not used to evaluate primary lesions
NECT: Less sensitive for detecting metastatic lesions than CECT
CECT: More sensitive for evaluation of organs and non-nodal soft tissue such as muscle
- General
  - After typical search pattern, look again at muscle, gallbladder, and other subcutaneous soft tissues
- Brain
  - Imaging performed for patients with known metastatic disease
  - Also performed for patients with neurological symptoms in the absence of known metastases
  - MR with contrast much more sensitive for detecting small brain metastases
- Chest
  - May detect asymptomatic lesions
  - NECT and CECT approximately equal for detecting small pulmonary metastases
  - FDG PET less sensitive in general for detecting lung metastases ≤ 6 mm
- Abdomen
  - Organ metastases may show hyperenhancement
  - Intramuscular metastases will generally show some abnormal enhancement, but may be otherwise undetectable
- Pelvis
  - More likely positive in patients with primary disease below waist
- Bone
  - Some may demonstrate enhancement, making them more conspicuous
  - Extensive bone metastasis may be missed altogether

Nuclear Medicine Findings

General
- Melanoma is almost always FDG avid
- True positives have significantly higher SUV than false positives in lesions > 1 cm on PET/CT
- PET/CT has considerable but non-significant advantage over PET in characterization of lesions
  - Possibly due to high avidity of melanoma metastases
  - Certainty of lesion localization significantly improved with combined modality
  - Especially in detection of visceral metastases
- Accuracy of PET/CT higher when equivocal lesions are considered negative
- PET/CT recommended for stage III/IV patients
- Thorough physical exam and US of draining nodes for lower stage patients
- PET/CT may detect unheralded occult primary malignancy in patients with primary melanoma
- Choroidal melanoma reported to have low FDG uptake
  - Correlated strongly to lesion size
- Intra-operative FDG PET/CT
  - Handheld gamma probe used to find lesions during surgery
  - Used to verify intra-operative US findings
  - Used to verify excised tissue as being the FDG-avid lesion
  - Can evaluate residual sites of hypermetabolic activity immediately post-operatively
Staging
- PET established as useful modality for staging and restaging of cutaneous melanoma and for evaluating distant metastases
  - Large meta-analysis: Sensitivity 83% and specificity 91% for staging
  - Changes management in 26-50% of patients
  - In one study, 16% of patients underwent further imaging &/or biopsies that ultimately had no effect on patient care
- Local or early disease
  - PET/CT found to have high accuracy for evaluation of regional metastases
  - Sensitivity 23% if metastases ≤ 5 mm (e.g., small lung nodules)
  - One study concluded that PET reliably detects lymph node tumor deposits > 80 mm³
  - Loses sensitivity rapidly below that volume
  - Not reimbursable by Medicare for evaluation of regional lymph nodes in stage I/II disease
  - More sensitive in setting of clinical or radiographic evidence of disease
- Distant disease
  - Sensitivity ≥ 90% for lesions > 1 cm
  - Reimbursable by Medicare for evaluation of extranodal metastases during initial staging
  - Sensitivity of 60% with FDG PET for brain metastases due to high physiologic uptake in the brain
  - Organ-based accuracy in liver, lung, and brain variable
  - Accuracy of PET/CT for M-staging higher than that of PET or CT alone (98%, 93%, 84%, respectively)
  - Superior sensitivity for lung metastases compared to MR
- PET/CT of node positive melanoma at time of sentinal lymphadenectomy had management change in 31% of one patient cohort
  - CT/MR in this circumstance shown to yield less than 1%; not clinically indicated
  - Level of uptake in lymph node metastases correlates with recurrence risk
Restaging
- FDG PET detects recurrent disease with sensitivity/specificity 74%/86%
- Elevated laboratory markers or clinical evidence of recurrence should prompt re-imaging
- Pre-surgical evaluation may detect more extensive disease and alter surgical planning
- FDG PET reimbursed by Medicare for pre-surgical evaluation of recurrence
Response to therapy
- PET/CT not routinely performed
  - Likely will play a more significant role in evaluating patients after various immunomodulating therapies
- One study showed complete agreement differentiating chemo-responders and nonresponders between CT and PET/CT
  - Baseline FDG PET very helpful for evaluating response to therapy
  - Melanoma differs from malignancies such as lymphoma, in which metabolic changes precede morphologic changes
  - PET/CT has benefit of relative ease of interpretation, but some controversy exists as to cost/benefit ratio
  - FDG PET pitfall: Cytokine therapy results in diffuse hypermetabolism in normal lymph nodes for months

MR Findings

More accurate in detection of mets to liver and bone
- Hepatic metastases ≤ 1 cm and containing melanin have bright signal on T1 weighted MR

DIFFERENTIAL DIAGNOSIS

Other Neoplasms

May appear similar to melanoma in FDG avidity
If suspicion of melanoma recurrence is low, consider
- Primary or metastatic disease from second primary
  - Unheralded second primary malignancies detected in 1.2% of patients (lung most common)
- Squamous or basal cell carcinoma
- Lymphoma in the presence of lymphadenopathy