Melanoma and Melanocytic Tumors of Uncertain Malignant Potential in Children, Adolescents and Young Adults—The Stanford Experience 1995–2008
David R. Berk M.D.
Departments of Dermatology, Pigmented Lesion and Melanoma Program
Current author affiliation: Department of Internal Medicine, Division of Dermatology, Washington University School of Medicine, St. Louis, Missouri.
Search for more papers by this authorElizabeth LaBuz M.D.
Departments of Dermatology, Pigmented Lesion and Melanoma Program
Search for more papers by this authorSoheil S. Dadras M.D., Ph.D.
Pathology
Current author affiliation: Departments of Dermatology and Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, Connecticut.
Search for more papers by this authorDenise L. Johnson M.D.
Surgery, Stanford University Medical Center, Stanford, California
Search for more papers by this authorSusan M. Swetter M.D.
Departments of Dermatology, Pigmented Lesion and Melanoma Program
Veterans Affairs Palo Alto Health Care System, Palo Alto, California
Search for more papers by this authorDavid R. Berk M.D.
Departments of Dermatology, Pigmented Lesion and Melanoma Program
Current author affiliation: Department of Internal Medicine, Division of Dermatology, Washington University School of Medicine, St. Louis, Missouri.
Search for more papers by this authorElizabeth LaBuz M.D.
Departments of Dermatology, Pigmented Lesion and Melanoma Program
Search for more papers by this authorSoheil S. Dadras M.D., Ph.D.
Pathology
Current author affiliation: Departments of Dermatology and Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, Connecticut.
Search for more papers by this authorDenise L. Johnson M.D.
Surgery, Stanford University Medical Center, Stanford, California
Search for more papers by this authorSusan M. Swetter M.D.
Departments of Dermatology, Pigmented Lesion and Melanoma Program
Veterans Affairs Palo Alto Health Care System, Palo Alto, California
Search for more papers by this authorAbstract
Abstract: Pediatric melanoma is difficult to study because of its rarity, possible biological differences in preadolescents compared with adolescents, and challenges of differentiating true melanoma from atypical spitzoid neoplasms. Indeterminant lesions are sometimes designated as melanocytic tumors of uncertain malignant potential (MelTUMPs). We performed a retrospective, single-institution review of melanomas, MelTUMPs and Spitz nevi with atypical features (SNAFs) in patients at 21 years of age and younger from 1995 to 2008. We identified 13 patients with melanoma, seven with MelTUMPs, and five with SNAFs. The median age for melanoma patients was 17 years, 10 for MelTUMPs, and six for SNAFs. Of the 13 melanoma patients, only four were younger than 15 years, while six were adolescents, and three were young adults. Nine melanoma patients (69%) were female. The most common histologic subtype was superficial spreading. The median depth for melanomas was 1.2 mm, and 3.4 mm for MelTUMPs. Microscopic regional nodal involvement detected on elective or sentinel lymph node (SLN) dissection was present in 2/10 (20%) of primary melanomas and 2/6 (33%) of Mel-TUMPs. Complete lymphadenectomy was performed on four melanoma patients, with three positive cases. Patient outcome through March 31, 2009 revealed no in-transit or visceral metastasis in patients with MelTUMPs or SNAFs. One SLN-positive patient (8%) with melanoma developed recurrent lymph node and liver metastasis and died 15 months after primary diagnosis. Our data highlight the rarity, female predominance, and significant rate of SLN positivity of pediatric melanoma. The high rate of MelTUMPs with regional nodal disease reinforces the need for close follow-up.
References
- 1 Strouse JJ, Fears TR, Tucker MA et al. Pediatric melanoma: risk factor and survival analysis of the surveillance, epidemiology and end results database. J Clin Oncol 2005; 23: 4735–4741.
- 2 Lange JR, Palis BE, Chang DC et al. Melanoma in children and teenagers: an analysis of patients from the National Cancer Data Base. J Clin Oncol 2007; 25: 1363–1368.
- 3 Li J, Thompson TD, Miller JW et al. Cancer incidence among children and adolescents in the United States, 2001–2003. Pediatrics 2008; 121: e1470–1477.
- 4 U.S. Cancer Statistics Working Group. United States Cancer Statistics: 1999–2005 incidence and mortality web-based report. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute. Available at: http://www.cdc.gov/uscs. Accessed on July 12, 2009.
- 5 Pappo AS. Melanoma in children and adolescents. Eur J Cancer 2003; 39: 2651–2661.
- 6 Conti EM, Cercato MC, Gatta G et al. Childhood melanoma in Europe since 1978: a population-based survival study. Eur J Cancer 2001; 37: 780–784.
- 7 Lewis KG. Trends in pediatric melanoma mortality in the United States, 1968 through 2004. Dermatol Surg 2008; 34: 152–159.
- 8 Karlsson P, Boeryd B, Sander B et al. Increasing incidence of cutaneous malignant melanoma in children and adolescents 12–19 years of age in Sweden 1973–92. Acta Derm Venereol 1998; 78: 289–292.
- 9 De Vries E, Steliarova-Foucher E, Spatz A et al. Skin cancer incidence and survival in European children and adolescents (1978–1997). Report from the Automated Childhood Cancer Information System project. Eur J Cancer 2006; 42: 2170–2182.
- 10 Vinceti M, Bergomi M, Borciani N et al. Rising melanoma incidence in an Italian community from 1986 to 1997. Melanoma Res 1999; 9: 97–103.
- 11 Ferrari A, Bono A, Baldi M et al. Does melanoma behave differently in younger children than in adults? A retrospective study of 33 cases of childhood melanoma from a single institution Pediatrics 2005; 115: 649–654.
- 12
Saenz NC,
Saenz-Badillos J,
Busam K
et al.
Childhood melanoma survival.
Cancer
1999; 85: 750–754.
10.1002/(SICI)1097-0142(19990201)85:3<750::AID-CNCR26>3.0.CO;2-5 CAS PubMed Web of Science® Google Scholar
- 13 Melnik MK, Urdaneta LF, Al-Jurf AS et al. Malignant melanoma in childhood and adolescence. Am Surg 1986; 52: 142–147.
- 14 Livestro DP, Kaine EM, Michaelson JS et al. Melanoma in the young: differences and similarities with adult melanoma: a case-matched controlled analysis. Cancer 2007; 110: 614–624.
- 15 Elder DE, Xu X. The approach to the patient with a difficult melanocytic lesion. Pathology 2004; 36: 428–434.
- 16 Strungs I. Common and uncommon variants of melanocytic naevi. Pathology 2004; 36: 396–403.
- 17 Averbook BJ, Jukic D, Rao J et al. First analysis of an international pediatric melanoma and atypical melanocytic neoplasm database. J Clin Oncol 2009; 27; (15s, Suppl.) Abstract:9013.
- 18 Zembowicz A, Carney JA, Mihm MC. Pigmented epithelioid melanocytoma: a low-grade melanocytic tumor with metastatic potential indistinguishable from animal-type melanoma and epithelioid blue nevus. Am J Surg Pathol 2004; 28: 31–40.
- 19 Spatz A, Calonje E, Handfield-Jones S et al. Spitz tumors in children: a grading system for risk stratification. Arch Dermatol 1999; 135: 282–285.
- 20 Barnhill RL. The Spitzoid lesion: rethinking Spitz tumors, atypical variants, ‘Spitzoid melanoma’ and risk assessment. Mod Pathol 2006; 19(Suppl. 2): S21–33.
- 21 Sulit DJ, Guardiano RA, Krivda S. Classic and atypical Spitz nevi: review of the literature. Cutis 2007; 79: 141–146.
- 22 Dahlstrom JE, Scolyer RA, Thompson JF et al. Spitz naevus: diagnostic problems and their management implications. Pathology 2004; 36: 452–457.
- 23 Quatresooz P, Pierard-Franchimont C, Pierard GE. Highlighting the immunohistochemical profile of melanocytomas: review. Oncol Rep 2008; 19: 1367–1372.
- 24
Yu LL,
Flotte TJ,
Tanabe KK
et al.
Detection of microscopic melanoma metastases in sentinel lymph nodes.
Cancer
1999; 86: 617–627.
10.1002/(SICI)1097-0142(19990815)86:4<617::AID-CNCR10>3.0.CO;2-S CAS PubMed Web of Science® Google Scholar
- 25 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: 3635–3648.
- 26 Schmid-Wendtner MH, Berking C, Baumert J et al. Cutaneous melanoma in childhood and adolescence: an analysis of 36 patients. J Am Acad Dermatol 2002; 46: 874–879.
- 27 De Sa BC, Rezze GG, Scramim AP et al. Cutaneous melanoma in childhood and adolescence: retrospective study of 32 patients. Melanoma Res 2004; 14: 487–492.
- 28 Kelley SW, Cockerell CJ. Sentinel lymph node biopsy as an adjunct to management of histologically difficult to diagnose melanocytic lesions: a proposal. J Am Acad Dermatol 2000; 42: 527–530.
- 29 Lohmann CM, Coit DG, Brady MS et al. Sentinel lymph node biopsy in patients with diagnostically controversial spitzoid melanocytic tumors. Am J Surg Pathol 2002; 26: 47–55.
- 30 Su LD, Fullen DR, Sondak VK et al. Sentinel lymph node biopsy for patients with problematic spitzoid melanocytic lesions: a report on 18 patients. Cancer 2003; 97: 499–507.
- 31 Urso C, Borgognoni L, Saieva C et al. Sentinel lymph node biopsy in patients with “atypical Spitz tumors.” A report on 12 cases. Hum Pathol 2006; 37: 816–823.
- 32 Gamblin TC, Edington H, Kirkwood JM et al. Sentinel lymph node biopsy for atypical melanocytic lesions with spitzoid features. Ann Surg Oncol 2006; 13: 1664–1670.
- 33 Murali R, Sharma RN, Thompson JF et al. Sentinel lymph node biopsy in histologically ambiguous melanocytic tumors with spitzoid features (so-called atypical spitzoid tumors). Ann Surg Oncol 2008; 15: 302–309.
- 34 Kwon EJ, Winfield HL, Rosenberg AS. The controversy and dilemma of using sentinel lymph node biopsy for diagnostically difficult melanocytic proliferations. J Cutan Pathol 2008; 35: 1075–1077.
- 35 Roaten JB, Partrick DA, Pearlman N et al. Sentinel lymph node biopsy for melanoma and other melanocytic tumors in adolescents. J Pediatr Surg 2005; 40: 232–235.
- 36 McArthur GJ, Banwell ME, Cook MG et al. The role of sentinel node biopsy in the management of melanocytic lesions of uncertain malignant potential (MUMP). J Plast Reconstr Aesthet Surg 2007; 60: 952–954.
- 37 Kayton ML, La Quaglia MP. Sentinel node biopsy for melanocytic tumors in children. Semin Diagn Pathol 2008; 25: 95–99.
- 38 Busam KJ, Pulitzer M. Sentinel lymph node biopsy for patients with diagnostically controversial Spitzoid melanocytic tumors? Adv Anat Pathol 2008; 15: 253–262.
- 39 Ludgate MW, Fullen DR, Lee J et al. The atypical Spitz tumor of uncertain biologic potential: a series of 67 patients from a single institution. Cancer 2009; 115: 631–641.
- 40 Cerroni L, Kerl H. Tutorial on melanocytic lesions. Am J Dermatopathol 2001; 23: 237–241.
- 41 Barnhill RL, Argenyi ZB, From L et al. Atypical Spitz nevi/tumors: lack of consensus for diagnosis, discrimination from melanoma, and prediction of outcome. Hum Pathol 1999; 30: 513–520.
- 42 Mones JM, Ackerman AB. “Atypical” Spitz’s nevus, “malignant” Spitz’s nevus, and “metastasizing” Spitz’s nevus: a critique in historical perspective of three concepts flawed fatally. Am J Dermatopathol 2004; 26: 310–333.
- 43 Steiner A, Pehamberger H, Binder M et al. Pigmented Spitz nevi: improvement of the diagnostic accuracy by epiluminescence microscopy. J Am Acad Dermatol 1992; 27: 697–701.
- 44 Psaty EL, Halpern AC. Current and emerging technologies in melanoma diagnosis: the state of the art. Clin Dermatol 2009; 27: 35–45.
- 45 Becker B, Roesch A, Hafner C et al. Discrimination of melanocytic tumors by cDNA array hybridization of tissues prepared by laser pressure catapulting. J Invest Dermatol 2004; 122: 361–368.
- 46 Takata M, Lin J, Takayanagi S et al. Genetic and epigenetic alterations in the differential diagnosis of malignant melanoma and spitzoid lesion. Br J Dermatol 2007; 156: 1287–1294.
- 47 Da Forno PD, Fletcher A, Pringle JH et al. Understanding spitzoid tumours: new insights from molecular pathology. Br J Dermatol 2008; 158: 4–14.
- 48 Carlson JA, Ross JS, Slominski A et al. Molecular diagnostics in melanoma. J Am Acad Dermatol 2005; 52: 743–775; Quiz 775–748.
- 49 Dadras SS. Molecular diagnostics in melanoma: current status and perspectives. Arch Pathol 2009 (in press).
- 50 Kashani-Sabet M, Rangel J, Torabian S et al. A multi-marker assay to distinguish malignant melanomas from benign nevi. Proc Natl Acad Sci USA 2009; 106: 6268–6272.
- 51 Curtin JA, Fridlyand J, Kageshita T et al. Distinct sets of genetic alterations in melanoma. N Engl J Med 2005; 353: 2135–2147.
- 52 Braun-Falco M, Schempp W, Weyers W. Molecular diagnosis in dermatopathology: what makes sense, and what doesn’t. Exp Dermatol 2009; 18: 12–23.
- 53 Bastian BC, Wesselmann U, Pinkel D et al. Molecular cytogenetic analysis of Spitz nevi shows clear differences to melanoma. J Invest Dermatol 1999; 113: 1065–1069.
- 54 Mandal RV, Murali R, Lundquist KF et al. Pigmented epithelioid melanocytoma: favorable outcome after 5-year follow-up. Am J Surg Pathol 2009; 33: 1778–1782.
- 55 Van Dijk MC, Bernsen MR, Ruiter DJ. Analysis of mutations in B-RAF, N-RAS, and H-RAS genes in the differential diagnosis of Spitz nevus and spitzoid melanoma. Am J Surg Pathol 2005; 29: 1145–1151.
- 56 Daniotti M, Ferrari A, Frigerio S et al. Cutaneous melanoma in childhood and adolescence shows frequent loss of INK4A and gain of kit. J Invest Dermatol 2009; 129: 1759–1768.
Citing Literature
