Derm Dx: Bluish papules on the scalp

This is an example of in-transit and satellite metastases of malignant melanoma. Metastasis of a primary cutaneous melanoma can be divided into local recurrences, in-transit and satellite metastasis, regional lymph node metastases, and distant metastases.An in-transit melanoma metastasis is a...

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This is an example of in-transit and satellite metastases of malignant melanoma.

Metastasis of a primary cutaneous melanoma can be divided into local recurrences, in-transit and satellite metastasis, regional lymph node metastases, and distant metastases.

An in-transit melanoma metastasis is a melanoma that is in the process of metastasizing to the regional lymph nodes. The American Joint Committee on Cancer (AJCC) defines in-transit metastases as any skin or subcutaneous metastasis that is more than 2 cm from the primary lesion but not beyond the regional nodal basin.

In-transit metastases present as pigmented or non-pigmented erythematous nodules that range in diameter from 0.2cm to 2 cm. In rare cases, the lesions are flat rather than nodular. They are classically located between the primary site of the original primary cutaneous melanoma and the regional lymph nodes.

However, in patients with extensive melanoma metastasis, in-transit lesions may be found in the direction opposite to the closest regional nodal basin due to theoretical tumor blockage of lymphatic channels from extensive metastases.

If uncontrolled tumor growth continues, the lesions of metastasis may coalesce or form ulcerations.

Both in-transit and satellite metastases are located within regional dermal and subdermal lymphatics and proximal to the primary melanoma towards the regional lymph nodes.

In-transit metastases are differentiated from satellite lesions in two ways:

1. In-transit metastases are 2 cm from the primary lesion, while satellite lesions are within 2 cm from the primary tumor.
2. Satellite lesions are considered intralymphatic extensions of the primary mass while in-transit metastasis are considered metastasis.

The tumor biology of satellite and in-transit metastasis are similar and the distinction between the two does not affect treatment or prognosis of the metastasis, as both indicate a poorer prognosis with frequent development of distant metastasis.

The 2010 TMN staging system considers both in-transit and satellite lesions a component of nodal (N) staging, with a separate N2c designation arising in the absence of nodal metastases.  More advanced stages of the primary tumor and location of the tumor increase the risk of in-transit metastasis. In-transit metastases are especially common in melanomas that present in lower extremity lesions.

Distinction between a local recurrence and in-transit metastases is difficult. A local recurrence is defined as recurrence within 2 cm of the surgical scar following definitive excision of a primary melanoma with appropriate surgical margins.

Recurrence results from extension of the primary tumor or intralymphatic spread. Nodules growing more than 2 cm from the excision scar are termed in-transit metastases. These definitions have minimal effect on the next best step in condition management.

For a patient who presents with in-transit metastases, a detailed history and physical and imaging assessment is necessary to determine whether disseminated disease is present and to look for distant metastases. Sentinel lymph node biopsy may be useful in determining the extent of surgery necessary. 

In-transit metastases in the absence of extensive metastases are best treated with surgical resection. When surgical resection is not feasible, isolated limb perfusion or limb infusion with melphalan may be indicated if the tumor is located on an extremity.

When all three are not feasible, radiation therapy may provide palliative benefit.

Choice treatment of single or multiple in-transit metastases is resection in patients without distant metastases. If the sentinel lymph node biopsy is positive, a lymph node dissection may be included during resection.

Unfortunately, the majority of patients will develop disseminated disease, though a small proportion will enjoy long-term, relapse-free survival.

Isolated limb perfusion (ILP) and isolated limb infusion (ILI) with mephalan are alternative therapies for in-transit metastasis, and are used to treat unresectable in-transit metastases confined to an extremity. The benefits of ILP and ILI are high concentrations of cytotoxic agents to the involved extremity, although ILI is slightly more effective than ILP and less toxic.

In some cases, radiation therapy may provide palliative benefits and prolonged regional control. In patients with positive regional lymph nodes, adjuvant high-dose interferon alpha (IFNa) is often recommended following surgical resection of the regional lymph node.

Christopher Chu is a medical student at Baylor College of Medicine.

Adam Rees, MD,is a graduate of the University of California Los Angeles School of Medicine and a resident in the Department of Dermatology at Baylor College of Medicine in Houston.