Melanoma metastasis

Melanoma metastasis refers to the spread of melanoma, a type of skin cancer that originates from melanocytes, to other parts of the body.

 

Cause and Etiology

Genetic Factors: Mutations in genes such as BRAF, NRAS, and KIT are commonly associated with melanoma. These mutations can lead to uncontrolled cell growth.

Environmental Factors: Ultraviolet (UV) radiation from sun exposure is a significant risk factor. Tanning beds also contribute to increased risk.

Family History: A family history of melanoma or other skin cancers can increase an individual's risk.

Skin Type: Individuals with fair skin, light hair, and light eyes are at higher risk due to lower melanin levels.

Pathophysiology

Melanoma begins in the melanocytes and can invade surrounding tissues.

It can metastasize through lymphatic and hematogenous routes.

The metastatic process involves several steps: local invasion, intravasation into blood or lymphatic vessels, survival in circulation, extravasation into distant tissues, and colonization.

Epidemiology

Melanoma is one of the most common cancers in young adults, particularly in those aged 15-29.

The incidence has been rising, particularly in fair-skinned populations.

Geographic variations exist, with higher rates in regions with intense UV exposure (e.g., Australia, New Zealand).

Clinical Presentation

Primary Melanoma: Often presents as a new or changing mole, characterized by asymmetry, irregular borders, multiple colors, and a diameter greater than 6 mm (ABCDE criteria).

Metastatic Melanoma: Symptoms depend on the site of metastasis:

Lymph Nodes: Swelling or lumps in the lymph nodes.

Skin: New lesions or changes in existing moles.

Lungs: Cough, chest pain, or difficulty breathing.

Liver: Abdominal pain, jaundice, or weight loss.

Brain: Headaches, seizures, or neurological deficits.

Imaging Features

CT Scans: Useful for assessing lymph node involvement and distant metastases.

MRI: Particularly useful for brain metastases.

Large cerebral haematoma with a fluid-fluid level. There is a smaller low signal area anteriorly, which corresponds to the known metastasis. This smaller area was enhanced after gadolinium, as was the overlying dura.

 This patient has a known cerebral melanoma metastasis in the left frontal lobe.

Melanoma metastases may be hyperintense on T1W images and demonstrate signal loss on T2 or T2* sequences. This is due to the presence of both melanin and blood products. Melanoma metastases are 5x more likely to show signal loss on T2* images than lung metastases, and 4.5 times more likely to be T1 hyperintense. T1 hyperintensity correlates with melanin content better than does T2* signal loss. T2* imaging (or susceptibility-weighted imaging) may be useful in screening for melanoma metastases as lesions are more conspicuous.

 PET Scans: Can help identify metabolically active metastatic lesions.

FDG-PET scan images of a patient with metastatic melanoma before (A) and after (B) treatment with a BRAF inhibitor. Therapy consisted of 15 days of treatment with 960mg of the BRAFV600E inhibitor, PLX4032, given orally twice daily as a single agent. (with permission from the Molecular Imaging Department of the Peter MacCallum Cancer Centre, Melbourne).

 Ultrasound: Often used for evaluating lymph nodes.

Treatment

Surgical Resection: The primary treatment for localized melanoma. Metastatic lesions may also be surgically removed if feasible.

Immunotherapy: Agents like checkpoint inhibitors (e.g., pembrolizumab, nivolumab) have revolutionized treatment for advanced melanoma.

Targeted Therapy: For patients with specific mutations (e.g., BRAF inhibitors like vemurafenib).

Chemotherapy: Less commonly used but may be considered in certain cases.

Radiation Therapy: Can be used for palliation or in specific cases of brain metastases.

Prognosis

The prognosis for melanoma metastasis varies widely based on several factors:

Stage at Diagnosis: Early-stage melanoma has a better prognosis than advanced-stage.

Location of Metastasis: Metastases to the brain or liver generally have a poorer prognosis.

Response to Treatment: Patients who respond well to immunotherapy or targeted therapy may have improved outcomes.

The 5-year survival rate for metastatic melanoma has improved with new therapies but remains lower than for localized disease.

Melanoma metastasis is a complex process influenced by genetic, environmental, and biological factors. Early detection and advances in treatment have significantly improved outcomes for many patients.

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Melanoma Metastasis of an Upper Arm Tumor in an 83-Year-Old Woman with a History of Breast Cancer and Melanoma
History and Imaging Findings

1. An 83-year-old woman was referred by her general practitioner to the breast clinic for evaluation of a right upper arm mass.

2. Her medical history was notable for right-sided breast cancer and melanoma.

3. She had been diagnosed with breast cancer in 2013 and subsequently underwent a right mastectomy. She had been maintained on tamoxifen as adjuvant therapy.

4. In 2015, she was first diagnosed with melanoma after presenting with an enlarging cutaneous lesion on her right forearm.

5. Biopsy revealed a superficial spreading malignant melanoma with a Breslow thickness of 4.4 mm and associated ulceration.

6. She underwent a wide local excision of the scar on her right forearm.

7. At that time, staging CT scans of the head, chest, abdomen, and pelvis showed no evidence of metastatic disease.

8. Sentinel lymph node biopsy was recommended and discussed, but the patient declined the procedure.

9. In 2016, she was diagnosed with a right axillary mass, and a biopsy confirmed metastatic melanoma.

10. She subsequently underwent a right axillary lymph node dissection, which revealed melanoma involvement in 3 out of 12 lymph nodes, without evidence of extracapsular extension.

11. The multidisciplinary melanoma team (MDT) recommended adjuvant radiotherapy.

12. However, after discussing the potential risks and benefits, the patient chose not to proceed with radiation treatment.

13. She now reports a 2–3 month history of swelling in the right upper arm, along with pain in the right arm and shoulder.

14. She also reports an unintentional weight loss of 19 kg over the past 12 months.

15. Clinical examination revealed a large palpable mass in the right upper arm associated with the biceps muscle.

16. Mammography of the left breast was unremarkable.

17. Ultrasound of the right axilla and right upper arm revealed no abnormal axillary lymph nodes, but identified an intramuscular soft tissue mass involving the right biceps muscle.

18. An ultrasound image of the left axilla is presented.

Quiz 1

1. When this lesion is detected in a breast clinic, performing a fine needle aspiration biopsy would be appropriate.
   (1) True
   (2) False
   Explanation: Current guidelines recommend that a suspected soft tissue sarcoma be evaluated with a core needle biopsy rather than fine needle aspiration. The biopsy approach should be planned carefully to allow for complete excision of the biopsy tract during definitive surgery, minimizing the risk of tumor seeding.

2. Which imaging modality is most appropriate for further evaluation of this lesion?
   (1) CT
   (2) PET
   (3) MRI

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Additional Imaging (MRI)

Quiz 2

1. Which MDT (Multidisciplinary Team) should initially manage this patient?
   (1) Melanoma MDT
   (2) Sarcoma MDT
   (3) Breast Cancer MDT
   (4) Unknown Primary MDT

2. A diagnosis can be made based on imaging alone, and therefore, biopsy is not necessary.
   (1) True
   (2) False
   Explanation: Radiologic appearances of sarcoma and metastatic melanoma are highly variable. Histopathological examination is required for a definitive diagnosis.

3. High signal intensity on T1-weighted imaging is a diagnostic feature of melanoma metastases.
   (1) True
   (2) False
   Explanation: Melanoma and melanoma metastases often appear hyperintense on T1-weighted MRI; however, this is a nonspecific feature, and definitive diagnosis requires histological confirmation.

4. FDG PET/CT can help detect additional distant metastases.
   (1) True
   (2) False
   Explanation: According to a meta-analysis of the literature, PET/CT is superior to CT, PET alone, or ultrasound for detecting distant metastases in patients with melanoma, both for initial staging and follow-up. However, current NICE guidelines do not recommend PET/CT for evaluating suspected metastatic melanoma. Instead, they recommend CT staging for patients suspected of having Stage III or IV melanoma.

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Findings and Diagnosis

Finding:

Ultrasound of the right axilla and upper arm demonstrated an intramuscular soft tissue mass within the right biceps muscle, measuring 42 × 37 × 70 mm. The mass appeared relatively well-circumscribed, with markedly heterogeneous internal echotexture and internal vascularity.

MRI of the right upper arm lesion
Axial and coronal T1-weighted images demonstrate areas of high signal intensity centrally within the lesion, suggestive of intralesional hemorrhage. T2 fat-saturated images show surrounding edema without evidence of periosteal reaction or underlying bony involvement.

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Differential Diagnosis

• Sarcoma

• Melanoma metastasis

• Breast cancer metastasis

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Diagnosis
Melanoma metastasis

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Treatment
This case was discussed at a melanoma specialist multidisciplinary team (MDT) meeting. Surgical resection combined with adjuvant therapy, including immunotherapy or radiotherapy, was recommended.

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Discussion

Melanoma Metastasis
Melanoma is the fifth most common cancer in the United Kingdom, with approximately 16,200 new cases diagnosed annually, and its incidence has been rising over recent decades. However, skeletal muscle metastases from melanoma, particularly to the upper limb, are extremely rare, with only a few cases reported in the literature. Melanoma typically metastasizes to the skin, subcutaneous tissue, and distant lymph nodes, followed by the brain, liver, and bone.

Skeletal muscle metastasis is generally rare across all solid tumors, with the most frequently involved muscles including the thigh, extraocular muscles, gluteal muscles, and paraspinal muscles.

The underlying mechanisms for the rarity of muscle metastases remain unclear. Studies suggest the incidence of skeletal muscle metastasis from various malignancies ranges between 0.8% and 16%. Factors such as variable blood flow and high lactic acid concentrations in muscle tissue are proposed to limit metastatic growth.

Moreover, autopsy studies indicate that skeletal muscle metastases often occur late in the course of malignancy when multiple metastases are already present, which may contribute to underreporting, especially in palliative patients who may not undergo further imaging. Furthermore, many patients do not survive long enough for muscle metastases to develop.

In addition to being rare, muscle metastases exhibit highly variable radiological features, complicating diagnosis.

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MRI Findings of Melanoma Metastasis

While definitive diagnosis of metastatic melanoma requires biopsy and histopathological confirmation, literature describes certain imaging features, particularly on MRI, that may suggest the diagnosis. However, evidence is limited due to the rarity of such metastases.

Melanoma and its metastases frequently demonstrate high signal intensity on T1-weighted MRI sequences. This appearance is attributed to two main factors: (1) the paramagnetic effects of stable free radicals within melanin, and (2) the presence of methemoglobin from subacute hemorrhage.

Several case reports support this finding. Yoshioka et al. reported a case of lower limb intramuscular melanoma metastasis with intermediate-to-high signal on T1-weighted and mixed signal intensities on T2-weighted MRI. Viswanathan et al. described a necrotic muscle metastasis with heterogeneous T1 enhancement and high T2 signal. Dalle Carbonare et al. presented a case of metastatic melanoma to the temporalis muscle, appearing as a lobulated T1 hyperintense mass without internal fat, and diffusely hypointense on T2-weighted imaging. Pirlamarla et al. reported a case of recurrent vulvar melanoma metastasizing to the extraocular muscles, showing heterogeneous high T1 and high T2 signal intensity on orbital MRI.

Nevertheless, T1 hyperintensity is not universally present. Other case reports describe variable appearances. For example, Kuo-Feng Hsu et al. reported a scalp melanoma metastasizing to the rectus abdominis muscle, with T1 hypointensity and T2 hyperintensity, along with enhancement and diffusion restriction. This patient underwent surgery but succumbed to widespread metastatic disease within six months.

Some metastases, such as those reported by Shih et al., may even appear cystic with fluid levels on MRI, further highlighting the diagnostic variability of melanoma muscle metastases.

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CT Findings of Melanoma Metastasis

Compared to MRI, much less data exist regarding CT appearances of muscle metastases. Retrospective cohort studies suggest that primary muscle metastases often appear as intramuscular masses with peripheral contrast enhancement and central low attenuation; however, melanoma was not among the primary tumors evaluated in these studies.

In the few case reports describing CT features of melanoma muscle metastases, findings include spindle-shaped orbital muscle swelling (Weiss et al.), peripheral enhancement with central low attenuation in the quadriceps (Viswanathan et al.), and a well-defined enhancing soft tissue mass in the subcutaneous tissue of the temporal region (Dalle Carbonare et al.).

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Differentiation Between Muscle Metastasis and Sarcoma

The variability in radiologic features between muscle metastases and primary soft tissue sarcomas poses significant diagnostic challenges. No imaging feature reliably distinguishes between them. This distinction is critical because biopsy approaches differ: guidelines recommend core needle biopsy rather than fine-needle aspiration for suspected soft tissue sarcomas, with biopsy tract planning to allow complete surgical excision and minimize seeding risk.

The diagnostic difficulty is compounded by the fact that well-differentiated liposarcomas can also appear hyperintense on T1-weighted MRI, similar to melanoma metastases. However, liposarcoma typically shows signal suppression on fat-saturated sequences, whereas melanin-induced T1 hyperintensity does not.

Melanoma metastases may also demonstrate dedifferentiation with loss of melanocytic markers, altering their radiologic appearance. Furthermore, the coexistence of separate malignancies, such as sarcoma and melanoma, cannot be excluded based solely on patient history.

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Role of PET/CT in Metastatic Melanoma

Gómez-León et al. reported increased FDG uptake in a skeletal muscle metastasis detected by FDG PET/CT, although such findings were rare. PET/CT is increasingly utilized for staging and restaging in metastatic melanoma and can help identify other metastases or alternative biopsy sites.

Meta-analyses suggest that PET/CT is superior to CT, PET alone, and ultrasound for detecting distant metastases in melanoma patients. According to guidelines from the Royal College of Radiologists, staging with PET/CT is evidence-based for assessing disease extent before treatment in disseminated melanoma.

However, current NICE guidelines do not recommend PET/CT as the preferred modality for investigating suspected metastatic melanoma. The reported sensitivity and specificity (90.6% and 77.2%, respectively) are based on limited evidence, and instead, CT staging is recommended for patients with suspected stage III or IV melanoma.

Conculusion

• Breast clinics provide highly accessible services and play a critical role in the evaluation of extra-breast lesions, including axillary and upper arm tumors.

• Collaboration across multiple specialties—particularly the input of radiologists during MDT (multidisciplinary team) meetings—is crucial for planning the investigation of intramuscular lesions (e.g., selecting the appropriate biopsy method) and for achieving an accurate diagnosis.

• Muscle metastases demonstrate a wide range of imaging appearances, including on MRI, which can complicate diagnosis.

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