US, CT and MRI play a pivotal role in the evaluation of primary tumor, assessment of metastatic disease and local recurrence.

CM

On sonography, CM appears as a hypoechoic fusiform thickening of the skin, commonly infiltrating the dermis, bordered by an echoic epidermal surface. Thickness should be always measured at the deepest point, usually well defined.

CM usually shows increased blood flow: flow signals are found at Color-Doppler in lesions thicker than 2 mm, particularly at their basis.

OM

OM is diagnosticated at fundoscopic examination; ocular ultrasound shows a biconvex echogenic mass and is useful for detecting scleral invasion and trans-scleral extension.

On CT, uveal melanoma appears as a hyperdense lenticular or mushroom-shaped lesion with post-contrast enhancement.

The MRI appearance depends on the histological features of the lesion (melanotic vs amelanotic) and presence of haemorrhage within the lesion. Melanotic melanomas typically exhibit T1 hyperintensity and intermediate hypointensity on T2-weighted MRI, due to paramagnetic effects of melanin, which causes T1 and T2 shortening. Amelanotic melanomas are generally hypointense on T1- and hyperintense on T2-WI. OM shows restricted diffusion and demonstrate mild to moderate enhancement at contrast-enhanced T1-WI with significant enhancement during the early phase, due to the hypervascular nature of these tumors. MRI is useful for evaluation of optic nerve and retrobulbar soft tissue (Fig.1).

LM

LM may present with either localized intra-/extraaxial mass lesions or diffuse meningeal melanomatosis. The mass can be extraaxial, intracerebral, intraventricular or intramedullary in locations.

On imaging, LM is indistinguishable from metastatic melanoma. The lesions are generally hyperdense on CT and show variable appearance on MRI, as described for OM. Diffuse meningeal melanomatosis shows diffuse dural leptomeningeal thickening and enhancement on CT/MRI (Fig.2).

MM

-Head and neck MM

Most frequent sites are nasal cavity (nasal septum, lateral nasal wall, inferior and middle turbinates) and oral cavity (upper alveolus and hard palate).

The CT appearance is nonspecific and consists of enhancing mass lesion with adjacent osseous destruction. Lymph node metastases (25% of patients), mostly involve the submandibular and upper jugular groups. MM commonly metastasizes to the liver.

-Vulvovaginal melanoma

CT findings are nonspecific and consist of infiltrating and enhancing mass lesion. It has a predilection for early peritoneal tumor spread, due to the close anatomic relationship.

-Anorectal Melanoma

It is usually seen as an intraluminal polypoid or fungating mass in the distal rectum or anal canal.

Perirectal infiltration is common in the pelvic side wall and the pre-sacral space. MRI is particularly useful for preoperative staging to assess bowel wall invasion.

Lymph node spread occurs in the perirectal, internal iliac, obturator and inguinal groups.

On MRI, all MM shows same signal intensity and post-gadolinium characteristics of OM.

METASTATIC DISEASE

Ultrasound is mainly used in detecting local recurrence and metastasis, in the surveillance of nodes during follow-up and to guide fine-needle aspiration for histopathological confirmation.

CT is the preferred technique for the evaluation of distant metastasis.

MRI is used as a problem-solving technique to characterize questionable lesions, and in patients suspected for liver and brain metastasis. Whole-body (WB) MRI is a promising new technique, superior to PET-TC in detecting liver, bone, and brain metastasEs.

Multifocal organ involvement is quite common in both CM and EM and virtually any organ can be affected.

Secondary lesions show specific imaging features in localization, lesions heterogeneity, contrast enhancement and signal intensity:

Skin, subcutaneous tissue and regional lymph nodes

These sites are the most common ones for recurrent disease.

Melanoma metastases are classified as satellite metastases, when located within 2 cm of the primary tumor (or its scar) and as in-transit metastases, if the lesion is located at a greater distance, along the lymphatic pathway toward the draining lymph node.

Satellite metastases appear as subcutaneous, hypoechoic nodules, with irregular margin, often with very low-level internal echoes, owing to the poor beam reflection of the melanin, and posterior enhancement. Larger lesions may show anechoic necrotic areas internally.

In-transit metastasis can be single or multiple. Sometimes thin, hypoechoic bands are recognizable at one or both nodule poles, indicating dilated lymphatic ducts filled with tumor cells. They present variable degrees of vascularity: flow signals are especially encountered in larger lesions (Fig.3).

Metastatic lymph nodes show a round or broad oval shape, with lobulated borders and loss of the internal echoic hilum, which may be complete (diffuse node hypoechogenicity) or partial (diffuse and asymmetric cortical thickening). Color Doppler imaging demonstrates loss of normal hilar vascularization with capsular vessels penetrating the nodal cortex and chaotically spreading toward the inner portions of the lymph node (Fig.4).

Chest

The lung is the most affected organ in metastatic melanoma, both in the lung parenchyma or the pleura. Pulmonary nodules can be variable in size, mostly 1-2 cm, and appear as well circumscribed, rounded lesions, with soft tissue attenuation, mostly located in the periphery of the lung. A prominent vessel is often seen, due to hematogenous spread (feeding vessel sign).

Both miliary pattern (innumerable disseminate small metastases) and single pulmonary metastasis are commonly described in melanoma. Mediastinal or hilar lymph node enlargement are commonly associated.

Brain and Spine

The brain is the second most common site of organ involvement. Lesions may be located either intra-axially or within the leptomeninges. The majority of the lesions measure 1-4 cm and are surrounded by abundant perilesional edema. Intratumoral hemorrhage is a prominent feature (Fig.5).

Both unenhanced and CECT are mandatory to correctly detect and characterize intralesional hemorrhage; MRI shows higher sensitivity and specificity due to the peculiar signal behavior of melanin. Only 10% of metastases are amelanotic with nonspecific MRI appearances.

70% of metastases located in the central nervous system are spinal lesions. Based on the location, they are classified as osseous, intramedullary (rare), extramedullary intradural (leptomeningeal, the most common ones), and extradural (epidural metastases, extremely rare) lesions.

Liver and biliary system

The liver is the third most affected organ in metastatic melanoma (20% of cases). Liver metastasis can be solitary or multiple and may vary in size ranging from very small to large lesions. Intralesional hemorrhage (appearing as fluid-fluid level within the lesion), calcifications, and severe necrosis are common in larger lesions.

Administration of intravenous contrast and multiphasic scan are mandatory for both CT and MRI. Metastatic melanomas are hypervascular and appear hyperdense on arterial hepatic CECT phase, becoming hypoattenuating to background liver parenchyma in the portal venous phase (Fig.6 and 7).

Metastasis from uveal melanoma often show a miliary pattern with diffuse small nodules in the liver parenchyma.

Rarely, melanoma can infiltrate and spread along the hepatic sinusoids, causing intraluminal metastases often radiologically occult: CT and MRI depict hepatomegaly only.

Bone

The bone is the fourth most frequent site of metastases (15% of patients). Common locations are the axial skeleton and ribs, but virtually any bone can be affected. The majority of the lesions are osteolytic and slightly expansile.

Muscle

Muscle metastasis only appears in advanced disease, rarely isolated. The most common sites are muscles of lower extremities, trunk, and upper extremities.

On CT, lesions are isodense to muscle, often embedded in hypodense subcutaneous fat, and show contrast enhancement. MRI is the gold standard for the evaluation of muscle disease.

Others

Spleen, gallbladder, adrenals are less commonly involved in metastatic pathways (Fig.8).

Malignant melanoma is the third most common tumor to metastasize to the breast, more often in the upper outer quadrant (Fig.9).

Cardiac metastases are rare, even if the prevalence of metastasis involving the heart is higher in melanoma compared with other tumors.