Annals of Surgical Oncology

, Volume 21, Issue 9, pp 3108–3116

Melanoma Patients with an Unknown Primary Tumor Site Have a Better Outcome than Those with a Known Primary Following Therapeutic Lymph Node Dissection for Macroscopic (Clinically Palpable) Nodal Disease

  • Augustinus P. T. van der Ploeg
  • Lauren E. Haydu
  • Andrew J. Spillane
  • Richard A. Scolyer
  • Michael J. Quinn
  • Robyn P. M. Saw
  • Kerwin F. Shannon
  • Jonathan R. Stretch
  • John F. Thompson
Melanomas

Abstract

Background

Several reports in the literature suggest a difference in outcome between melanoma patients with macroscopic (clinically palpable) nodal disease from an unknown primary (MUP) and a known primary (MKP). The purpose of this study was to compare the outcomes for MUP and MKP patients after therapeutic lymph node dissection (TLND) for macroscopic nodal disease.

Methods

From a large, prospective, single-institution database, the details of melanoma patients who first presented with macroscopic nodal disease and underwent TLND between 1971 and 2010 were extracted and analyzed.

Results

There were 287 MUP patients and 264 MKP patients who fulfilled the study selection criteria. MUP patients had better disease-free, distant metastasis-free, and melanoma-specific survival after their TLND than MKP patients (all p < 0.001). Extranodal melanoma extension, >3 positive lymph nodes, and administration of adjuvant radiotherapy were all independent predictors of reduced disease-free and melanoma-specific survival (all p < 0.05). MUP patients also had a better prognosis than MKP patients whose primary melanoma had regression (p = 0.001).

Conclusions

The occurrence and improved outcome of MUP patients may be due to immune-induced total regression of the primary tumor and better immunologic prevention or control of distant metastatic disease. Alternatively, in some MUP patients, melanoma may not be metastatic but may originate de novo from nevus cells in lymph nodes, with the more favorable prognosis attributable to their primary nodal origin and complete surgical resection.

Supplementary material

10434_2014_3679_MOESM1_ESM.tif (960 kb)
Supplementary Fig. 1 Disease-free survival (TIFF 959 kb)
10434_2014_3679_MOESM2_ESM.tif (960 kb)
Supplementary Fig. 2 Disease metastasis–free survival (TIFF 959 kb)
10434_2014_3679_MOESM3_ESM.tif (960 kb)
Supplementary Fig. 3 Melanoma-specific survival for unknown primary versus known primary with regression versus known primary without regression (TIFF 959 kb)

References

  1. 1.
    Chang AE, Karnell LH, Menck HR. The National Cancer Data Base report on cutaneous and noncutaneous melanoma: a summary of 84,836 cases from the past decade. The American College of Surgeons Commission on Cancer and the American Cancer Society. Cancer. 1998;83:1664–78.PubMedCrossRefGoogle Scholar
  2. 2.
    Anbari KK, Schuchter LM, Bucky LP, et al. Melanoma of unknown primary site: presentation, treatment, and prognosis—a single institution study. University of Pennsylvania Pigmented Lesion Study Group. Cancer. 1997;79:1816–21.PubMedCrossRefGoogle Scholar
  3. 3.
    Baab GH, McBride CM. Malignant melanoma: the patient with an unknown site of primary origin. Arch Surg. 1975;110:896–900.PubMedCrossRefGoogle Scholar
  4. 4.
    Chang P, Knapper WH. Metastatic melanoma of unknown primary. Cancer. 1982;49:1106–11.PubMedCrossRefGoogle Scholar
  5. 5.
    Dasgupta T, Bowden L, Berg JW. Malignant melanoma of unknown primary origin. Surg Gynecol Obstet. 1963;117:341–5.PubMedGoogle Scholar
  6. 6.
    Katz KA, Jonasch E, Hodi FS, et al. Melanoma of unknown primary: experience at Massachusetts General Hospital and Dana-Farber Cancer Institute. Melanoma Res. 2005;15:77–82.PubMedCrossRefGoogle Scholar
  7. 7.
    Schlagenhauff B, Stroebel W, Ellwanger U, et al. Metastatic melanoma of unknown primary origin shows prognostic similarities to regional metastatic melanoma: recommendations for initial staging examinations. Cancer. 1997;80:60–5.PubMedCrossRefGoogle Scholar
  8. 8.
    Wong JH, Cagle LA, Morton DL. Surgical treatment of lymph nodes with metastatic melanoma from unknown primary site. Arch Surg. 1987;122:1380–3.PubMedCrossRefGoogle Scholar
  9. 9.
    Kamposioras K, Pentheroudakis G, Pectasides D, et al. Malignant melanoma of unknown primary site. To make the long story short. A systematic review of the literature. Crit Rev Oncol Hematol. 2010;78:112–26.PubMedCrossRefGoogle Scholar
  10. 10.
    McCarthy WH, Shaw HM, Milton GW. Spontaneous regression of metastatic malignant melanoma. Clin Oncol. 1978;4:203–7.PubMedGoogle Scholar
  11. 11.
    Shaw HM, McCarthy SW, McCarthy WH, et al. Thin regressing malignant melanoma: significance of concurrent regional lymph node metastases. Histopathology. 1989;15:257–65.PubMedCrossRefGoogle Scholar
  12. 12.
    Reintgen DS, McCarty KS, Woodard B, et al. Metastatic malignant melanoma with an unknown primary. Surg Gynecol Obstet. 1983;156:335–40.PubMedGoogle Scholar
  13. 13.
    Morton DL, Thompson JF, Cochran AJ, et al. Sentinel-node biopsy or nodal observation in melanoma. N Engl J Med. 2006;355:1307–17.PubMedCrossRefGoogle Scholar
  14. 14.
    Cormier JN, Xing Y, Feng L, et al. Metastatic melanoma to lymph nodes in patients with unknown primary sites. Cancer. 2006;106:2012–20.PubMedCrossRefGoogle Scholar
  15. 15.
    Lee CC, Faries MB, Wanek LA, et al. Improved survival after lymphadenectomy for nodal metastasis from an unknown primary melanoma. J Clin Oncol. 2008;26:535–41.PubMedCrossRefGoogle Scholar
  16. 16.
    Prens SP, van der Ploeg AP, van Akkooi AC, et al. Outcome after therapeutic lymph node dissection in patients with unknown primary melanoma site. Ann Surg Oncol. 2011;18:3586–92.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Rutkowski P, Nowecki ZI, Dziewirski W, et al. Melanoma without a detectable primary site with metastases to lymph nodes. Dermatol Surg. 2010;36:868–76.PubMedCrossRefGoogle Scholar
  18. 18.
    Norman J, Cruse CW, Wells KE, et al. Metastatic melanoma with an unknown primary. Ann Plast Surg. 1992;28:81–4.PubMedCrossRefGoogle Scholar
  19. 19.
    Vijuk G, Coates AS. Survival of patients with visceral metastatic melanoma from an occult primary lesion: a retrospective matched cohort study. Ann Oncol. 1998;9:419–22.PubMedCrossRefGoogle Scholar
  20. 20.
    de Wilt JH, Farmer SE, Scolyer RA, et al. Isolated melanoma in the lung where there is no known primary site: metastatic disease or primary lung tumour? Melanoma Res. 2005;15:531–7.PubMedCrossRefGoogle Scholar
  21. 21.
    Murali R, Doubrovsky A, Watson GF, et al. Diagnosis of metastatic melanoma by fine-needle biopsy: analysis of 2,204 cases. Am J Clin Pathol. 2007;127:385–97.PubMedCrossRefGoogle Scholar
  22. 22.
    Doubrovsky A, Scolyer RA, Murali R, et al. Diagnostic accuracy of fine needle biopsy for metastatic melanoma and its implications for patient management. Ann Surg Oncol. 2008;15:323–32.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Spillane AJ, Cheung BL, Stretch JR, et al. Proposed quality standards for regional lymph node dissections in patients with melanoma. Ann Surg. 2009;249:473–80.PubMedCrossRefGoogle Scholar
  24. 24.
    Spillane AJ, Cheung BL, Winstanley J, et al. Lymph node ratio provides prognostic information in addition to AJCC N stage in patients with melanoma, even if quality of surgery is standardized. Ann Surg. 2011;253:109–15.PubMedCrossRefGoogle Scholar
  25. 25.
    Xing Y, Badgwell BD, Ross MI, et al. Lymph node ratio predicts disease-specific survival in melanoma patients. Cancer. 2009;115:2505–13.PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Shenoy BV, Fort L III, Benjamin SP. Malignant melanoma primary in lymph node. The case of the missing link. Am J Surg Pathol. 1987;11:140–6.PubMedCrossRefGoogle Scholar
  27. 27.
    Smith JL Jr, Stehlin JS Jr. Spontaneous regression of primary malignant melanomas with regional metastases. Cancer. 1965;18:1399–415.PubMedCrossRefGoogle Scholar
  28. 28.
    Koomen ER, de Vries E, van Kempen LC, et al. Epidemiology of extracutaneous melanoma in the Netherlands. Cancer Epidemiol Biomarkers Prev. 2010;19:1453–9.PubMedCrossRefGoogle Scholar
  29. 29.
    Tos T, Klyver H, Drzewiecki KT. Extensive screening for primary tumor is redundant in melanoma of unknown primary. J Surg Oncol. 2011;104:724–7.PubMedCrossRefGoogle Scholar
  30. 30.
    Giuliano AE, Cochran AJ, Morton DL. Melanoma from unknown primary site and amelanotic melanoma. Semin Oncol. 1982;9:442–7.PubMedGoogle Scholar
  31. 31.
    Everson TC. Spontaneous regression of cancer. Ann N Y Acad Sci. 1964;114:721–35.CrossRefGoogle Scholar
  32. 32.
    Kalialis LV, Drzewiecki KT, Klyver H. Spontaneous regression of metastases from melanoma: review of the literature. Melanoma Res. 2009;19:275–82.PubMedCrossRefGoogle Scholar
  33. 33.
    Emanuel PO, Mannion M, Phelps RG. Complete regression of primary malignant melanoma. Am J Dermatopathol. 2008;30:178–81.PubMedCrossRefGoogle Scholar
  34. 34.
    Hsueh EC, Gupta RK, Yee R, et al. Does endogenous immune response determine the outcome of surgical therapy for metastatic melanoma? Ann Surg Oncol. 2000;7:232–8.PubMedCrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2014

Authors and Affiliations

  • Augustinus P. T. van der Ploeg
    • 1
  • Lauren E. Haydu
    • 1
    • 2
  • Andrew J. Spillane
    • 1
    • 2
  • Richard A. Scolyer
    • 1
    • 2
  • Michael J. Quinn
    • 1
    • 2
  • Robyn P. M. Saw
    • 1
    • 2
  • Kerwin F. Shannon
    • 1
    • 2
  • Jonathan R. Stretch
    • 1
    • 2
  • John F. Thompson
    • 1
    • 2
  1. 1.Melanoma Institute AustraliaSydneyAustralia
  2. 2.Sydney Medical SchoolThe University of SydneySydneyAustralia

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