Cutaneous melanoma: In transit metastases
- Kenneth K Tanabe, MD
Kenneth K Tanabe, MD
- Section Editor — Gastrointestinal Malignancies
- Professor of Surgery
- Harvard Medical School
- Douglas Tyler, MD
Douglas Tyler, MD
- Department of Surgery
- University of Texas Medical Branch at Galveston
- Section Editors
- Michael B Atkins, MD
Michael B Atkins, MD
- Section Editor — Malignant Melanoma and Other Cutaneous Neoplasms; Cancer of the Kidney
- Deputy Director
- Georgetown Lombardi Comprehensive Cancer Center
- Russell S Berman, MD
Russell S Berman, MD
- Section Editor — Skin and Soft Tissue Surgery
- Chief of Surgical Oncology
- New York University Langone Medical Center
For patients with primary cutaneous melanoma, the term "locoregional metastases" includes local recurrences, in transit and satellite metastases, and regional lymph node metastases.
The clinical presentation, evaluation, and management of patients with in transit metastases will be reviewed here. Local recurrences and nodal metastases are discussed separately. (See "Cutaneous melanoma: Management of local recurrence" and "Evaluation and treatment of regional lymph nodes in melanoma".)
In transit metastases are located within regional dermal and subdermal lymphatics prior to reaching the regional lymph nodes. The American Joint Committee on Cancer (AJCC) defines in transit metastases as any skin or subcutaneous metastases that are more than 2 cm from the primary lesion but are not beyond the regional nodal basin . Lesions occurring within 2 cm of the primary tumor are classified as satellite metastases. The 2010 tumor, node, metastasis (TNM) staging system (table 1A-B) considers in transit and satellite metastases to be a component of nodal (N) staging, assigning a separate N2c designation when they arise in the absence of nodal metastases. In the eighth (2017) AJCC TNM staging system, non-nodal regional disease is stratified by category according to the number of tumor-involved lymph nodes (table 2A and table 2B). (See "Tumor node metastasis (TNM) staging system and other prognostic factors in cutaneous melanoma".)
In transit metastases are differentiated from satellite lesions, which are skin or subcutaneous lesions within 2 cm of the primary tumor that are considered intralymphatic extensions of the primary mass. Despite this distinction, the tumor biology associated with satellite and in transit metastases is similar, and they are not considered as distinct entities for treatment or prognosis [2,3].
Melanoma in transit metastases typically appear as erythematous nodules ranging in size from 0.2 to 2 cm that may or may not be pigmented. Occasionally, the lesions are flat rather than nodular.To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Melanoma of the Skin. In: American Joint Committee on Cancer Staging Manual, 7th, Edge SB, Byrd DR, Compton CC, et al (Eds), Springer, New York 2010. p.325.
- Balch CM, Buzaid AC, Soong SJ, et al. Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol 2001; 19:3635.
- Balch CM, Soong SJ, Gershenwald JE, et al. Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol 2001; 19:3622.
- Read RL, Haydu L, Saw RP, et al. In-transit melanoma metastases: incidence, prognosis, and the role of lymphadenectomy. Ann Surg Oncol 2015; 22:475.
- Pawlik TM, Ross MI, Johnson MM, et al. Predictors and natural history of in-transit melanoma after sentinel lymphadenectomy. Ann Surg Oncol 2005; 12:587.
- Kretschmer L, Beckmann I, Thoms KM, et al. Factors predicting the risk of in-transit recurrence after sentinel lymphonodectomy in patients with cutaneous malignant melanoma. Ann Surg Oncol 2006; 13:1105.
- Kang JC, Wanek LA, Essner R, et al. Sentinel lymphadenectomy does not increase the incidence of in-transit metastases in primary melanoma. J Clin Oncol 2005; 23:4764.
- Morton DL, Thompson JF, Cochran AJ, et al. Final trial report of sentinel-node biopsy versus nodal observation in melanoma. N Engl J Med 2014; 370:599.
- Thomas JM, Clark MA. Selective lymphadenectomy in sentinel node-positive patients may increase the risk of local/in-transit recurrence in malignant melanoma. Eur J Surg Oncol 2004; 30:686.
- Estourgie SH, Nieweg OE, Kroon BB. High incidence of in-transit metastases after sentinel node biopsy in patients with melanoma. Br J Surg 2004; 91:1370.
- Beasley GM, Speicher P, Sharma K, et al. Efficacy of repeat sentinel lymph node biopsy in patients who develop recurrent melanoma. J Am Coll Surg 2014; 218:686.
- Dong XD, Tyler D, Johnson JL, et al. Analysis of prognosis and disease progression after local recurrence of melanoma. Cancer 2000; 88:1063.
- Vrouenraets BC, in't Veld GJ, Nieweg OE, et al. Long-term functional morbidity after mild hyperthermic isolated limb perfusion with melphalan. Eur J Surg Oncol 1999; 25:503.
- Calvo DB 3rd, Patt YZ, Wallace S, et al. Phase I-II trial of percutaneous intra-arterial cis-diamminedichloro platinum (II) for regionally confined malignancy. Cancer 1980; 45:1278.
- Calabro A, Singletary SE, Carrasco CH, Legha SS. Intraarterial infusion chemotherapy in regionally advanced malignant melanoma. J Surg Oncol 1990; 43:239.
- Eton O, East M, Legha SS, et al. Pilot study of intra-arterial cisplatin and intravenous vinblastine and dacarbazine in patients with melanoma in-transit metastases. Melanoma Res 1999; 9:483.
- Roberts MS, Wu ZY, Siebert GA, et al. Pharmacokinetics and pharmacodynamics of melphalan in isolated limb infusion for recurrent localized limb malignancy. Melanoma Res 2001; 11:423.
- Lindnér P, Thompson JF, De Wilt JH, et al. Double isolated limb infusion with cytotoxic agents for recurrent and metastatic limb melanoma. Eur J Surg Oncol 2004; 30:433.
- Minor DR, Allen RE, Alberts D, et al. A clinical and pharmacokinetic study of isolated limb perfusion with heat and melphalan for melanoma. Cancer 1985; 55:2638.
- Klaase JM, Kroon BB, van Geel BN, et al. Patient- and treatment-related factors associated with acute regional toxicity after isolated perfusion for melanoma of the extremities. Am J Surg 1994; 167:618.
- Cheng TY, Grubbs E, Abdul-Wahab O, et al. Marked variability of melphalan plasma drug levels during regional hyperthermic isolated limb perfusion. Am J Surg 2003; 186:460.
- Kroon HM, Moncrieff M, Kam PC, Thompson JF. Outcomes following isolated limb infusion for melanoma. A 14-year experience. Ann Surg Oncol 2008; 15:3003.
- Brady MS, Brown K, Patel A, et al. A phase II trial of isolated limb infusion with melphalan and dactinomycin for regional melanoma and soft tissue sarcoma of the extremity. Ann Surg Oncol 2006; 13:1123.
- Beasley GM, Petersen RP, Yoo J, et al. Isolated limb infusion for in-transit malignant melanoma of the extremity: a well-tolerated but less effective alternative to hyperthermic isolated limb perfusion. Ann Surg Oncol 2008; 15:2195.
- Cornett WR, McCall LM, Petersen RP, et al. Randomized multicenter trial of hyperthermic isolated limb perfusion with melphalan alone compared with melphalan plus tumor necrosis factor: American College of Surgeons Oncology Group Trial Z0020. J Clin Oncol 2006; 24:4196.
- Kroon HM, Coventry BJ, Giles MH, et al. Australian Multicenter Study of Isolated Limb Infusion for Melanoma. Ann Surg Oncol 2016; 23:1096.
- Beasley GM, Caudle A, Petersen RP, et al. A multi-institutional experience of isolated limb infusion: defining response and toxicity in the US. J Am Coll Surg 2009; 208:706.
- Dossett LA, Ben-Shabat I, Olofsson Bagge R, Zager JS. Clinical Response and Regional Toxicity Following Isolated Limb Infusion Compared with Isolated Limb Perfusion for In-Transit Melanoma. Ann Surg Oncol 2016; 23:2330.
- Jiang BS, Beasley GM, Speicher PJ, et al. Immunotherapy following regional chemotherapy treatment of advanced extremity melanoma. Ann Surg Oncol 2014; 21:2525.
- Hafström L, Rudenstam CM, Blomquist E, et al. Regional hyperthermic perfusion with melphalan after surgery for recurrent malignant melanoma of the extremities. Swedish Melanoma Study Group. J Clin Oncol 1991; 9:2091.
- CLINICAL PRESENTATION
- INCIDENCE AND INFLUENCE OF NODE DISSECTION
- General approach
- - Positive resection margins
- Regional chemotherapy
- - Isolated limb perfusion
- - Isolated limb infusion
- - Outcomes
- ILI or ILP after resection of in transit recurrence
- High-risk primary melanoma
- - Progression after regional chemotherapy treatment
- Radiation therapy
- Intralesional therapy
- Adjuvant systemic therapy
- Systemic therapy
- SUMMARY AND RECOMMENDATIONS