Cutaneous Melanoma Clinical Presentation

  • Author: Susan M Swetter, MD; Chief Editor: Dirk M Elston, MD   more...
 
Updated: Feb 23, 2012
 

History

A new or changing mole or blemish is the most common warning sign for melanoma. Variation in color and/or an increase in diameter, height, or asymmetry of borders of a pigmented lesion are noted by the majority of patients with melanoma at the time of diagnosis. Symptoms such as bleeding, itching, ulceration, and pain in a pigmented lesion are less common but warrant an evaluation. Again, because the majority of cutaneous melanoma arises de novo (ie, on normal appearing skin and not in association with a precursor nevus), the wholesale removal of melanocytic nevi is not warranted for melanoma prevention. However, individuals with numerous moles (common or dysplastic) or a family history of melanoma should be educated regarding the importance of skin self-examination for early detection of skin cancer.

A total-body skin examination is critical when evaluating a patient at risk for melanoma, particularly those with increased mole count, presence of clinical atypical nevi, prior nonmelanoma skin cancer, and/or strong family history of melanoma. Multiple studies have demonstrated that thinner melanomas are associated with physician detection during routine skin or physical examinations, compared with patient detection of melanoma when a lesion changes or becomes symptomatic.[16]

Clinician and patient education regarding the warning signs of early melanoma (particularly the superficial spreading subtype) has been achieved successfully through the use of the ABCDE criteria for a changing mole,[17, 18] which are as follows:

  • Asymmetry: Half the lesion does not match the other half.
  • Border irregularity: The edges are ragged, notched, or blurred.
  • Color variegation: Pigmentation is not uniform and may display shades of tan, brown, or black; white, reddish, or blue discoloration is of particular concern.
  • Diameter: A diameter greater than 6 mm is characteristic, although some melanomas may be smaller in size; any growth in a nevus warrants an evaluation.
  • Evolving: Changes in the lesion over time are characteristic; this factor is critical for nodular or amelanotic (nonpigmented) melanoma, which may not exhibit the ABCD criteria above.

The ABCDEs have the greatest diagnostic accuracy when used in combination. Lesions exhibiting these features should be considered potential melanoma, although severely atypical/dysplastic nevi may be difficult to distinguish clinically. More recent use of the "ugly duckling" warning sign, in which skin examination is focused on recognition of a pigmented or clinically amelanotic lesion that simply looks different from the rest, may assist with detection of lesions that lack the classic ABCDE criteria (eg, nodular, amelanotic, or desmoplastic melanomas).[19, 20]

Next

Physical

Melanoma occurs most commonly on the trunk in white males and the lower legs and back in white females. In African American, Hispanic, and Asian persons, the most common site is the plantar foot, followed by subungual, palmar, and mucosal sites. Melanoma can occur on any skin or mucosal surface, although a history of cutaneous melanoma does not appear to increase the risk of developing primary intraocular, oral, or other mucosal melanoma.

Four major clinicopathologic (or histogenetic) subtypes of primary cutaneous melanoma have been identified. These include superficial spreading melanoma, nodular melanoma, lentigo maligna melanoma, and acral lentiginous melanoma. Distinction among the subtypes is based on histologic growth pattern (predominantly junctional in lentiginous types vs buckshot scatter in superficial spreading and nodular), anatomic site, and degree of sun damage. The pattern of sun exposure varies between the types (chronic in lentigo maligna vs intermittent in superficial spreading and nodular subtypes vs noncontributory in acral lentiginous and mucosal subtypes). Whether the melanoma subtype affects the overall prognosis remains controversial. However, molecular analysis has demonstrated different patterns of cell death, oncogene expression, gene amplification, and BRAF and KIT mutation frequency among the 4 main histogenetic types.[21, 22, 23]

A pooled analysis of more than 30 studies from 1989-2010 concludes that the incidence of BRAF and NRAS mutations differ based on histologic subtype and anatomic site.[4] BRAF mutations are more commonly detected in superficial spreading melanomas and melanomas that arise on nonchronically sun-damaged skin. NRAS mutations are more common in patients with nodular melanomas and melanomas arising on chronically sun-damaged skin.

With the exception of nodular melanoma, the growth patterns of the other subtypes are characterized by a preceding in situ (radial growth) phase that lacks the biologic potential to metastasize and may last from months to years before dermal invasion occurs. While all in situ melanoma may not necessarily progress to invasive melanoma, complete excision is recommended to prevent invasion and result in cure.

Superficial spreading melanoma characteristics are as follows:

  • It accounts for nearly 70% of cutaneous melanoma and is the most common subtype in individuals aged 30-50 years, as well as those with clinical atypical/dysplastic nevi.
  • It is most common on the trunk in men and women and on the legs in women. See the image below.Superficial spreading melanoma, left breast, 1.3-mSuperficial spreading melanoma, left breast, 1.3-mm Breslow depth.
  • Superficial spreading melanoma commonly displays the ABCD warning signs. It manifests as a flat or slightly elevated brown lesion with variegate pigmentation (ie, black, blue, pink, or white discoloration).
  • It is generally greater than 6 mm in diameter.
  • Irregular asymmetric borders are characteristic.
  • Histologically, it is characterized by buckshot (pagetoid) scatter of atypical melanocytes within the epidermis.

Nodular melanoma characteristics are as follows:

  • This subtype occurs in 15-30% of patients.
  • It is seen most commonly on the legs and trunk in men and women.
  • Rapid growth occurs over weeks to months; this subtype is responsible for most thick melanomas.[24, 25]
  • It may be clinically amelanotic (ie, not pigmented); thus, any rapidly growing flesh-colored lesion that persists after 1 month or ulcerates or bleeds should prompt medical evaluation.
  • It manifests as a dark brown-to-black papule or dome-shaped nodule, which may ulcerate and bleed with minor trauma; it may be clinically amelanotic (ie, not pigmented).
  • It tends to lack the typical ABCDE melanoma warning signs and, thus, may elude early detection. More commonly, it exhibits elevation, ulceration with bleeding, or both at presentation.
  • Histologically, it is believed to lack a preceding radial or in situ growth phase.

Lentigo maligna melanoma characteristics are as follows:

  • The incidence of lentigo maligna subtypes (in situ and invasive) appears to be rising in the United States.[26]
  • It is typically located on the head, neck, and arms (chronically sun-damaged skin) of fair-skinned older individuals (average age 65 y). See the image below. Lentigo maligna melanoma, right lower cheek. CentrLentigo maligna melanoma, right lower cheek. Centrally located erythematous papule represents invasive melanoma with surrounding macular lentigo maligna (melanoma in situ).
  • It grows slowly over 5-20 years.
  • The in situ precursor lesion (termed lentigo maligna) is usually large (>1-3 cm in diameter), present for a minimum of 10-15 years, and demonstrates macular (flat) pigmentation ranging from dark brown to black, although hypopigmented (white) areas are common within lentigo maligna.
  • Dermal invasion (progression to lentigo maligna melanoma) is characterized by the development of raised blue-black nodules within the in situ lesion.
  • Histologically, it is characterized by a predominantly junctional confluent proliferation of melanocytes and extension along adnexal structures, although dysplastic nevuslike features are not uncommon.[27] Solar elastosis is typically prominent.

Acral lentiginous melanoma characteristics are as follows:

  • This is the least common subtype of melanoma in white persons (2-8% of melanoma cases).
  • It is the most common subtype of melanoma in dark-skinned individuals (ie, African American, Asian, and Hispanic persons), representing 29-72% of melanoma cases and, because of delays in diagnosis, may be associated with a worse prognosis.[28, 29]
  • Acral lentiginous melanoma occurs on the palms, on the soles, or beneath the nail plate (subungual variant). See the image below. Acral lentiginous melanoma (1-mm Breslow depth), lAcral lentiginous melanoma (1-mm Breslow depth), left sole. Diagnostic punch biopsy site is located superiorly.
  • Subungual melanoma may manifest as diffuse nail discoloration or a longitudinal pigmented band (melanonychia striata) within the nail plate.
  • It must be differentiated from a benign junctional melanocytic nevus of the nail bed, which has a similar appearance.
  • Pigment spread to the proximal or lateral nail folds is termed the Hutchinson sign, which is a hallmark for subungual melanoma.
  • Subungual melanoma may be mistaken for a subungual hematoma, which is usually due to trauma and resolves with time.
  • Fungal infection of the nail (onychomycosis) can also be confused with subungual melanoma, particularly in the setting of nail dystrophy without suspicious pigmentation. Nonresponsiveness to antifungal agents should prompt more thorough evaluation, including potential biopsy.

Rare melanoma variants (< 5% of melanomas) include (1) desmoplastic/neurotropic melanoma, (2) mucosal (lentiginous) melanoma,[30] (3) malignant blue nevus, (4) melanoma arising in a giant/large congenital nevus, and (5) melanoma of soft parts (clear cell sarcoma).

Desmoplastic melanoma is a less common but important melanoma subtype, given its predilection for older-age individuals, clinical features similar to nonmelanoma (keratinocytic) skin cancer, and potential indication for adjuvant radiation therapy following wide excision.

Desmoplastic melanoma characteristics are as follows:

  • It may occur in association with macular, lentigo maligna-type pigmentation, or it may present de novo as a firm, amelanotic nodule orscar.
  • It occurs most often on sun-exposed areas of the head and neck, with a mean age of 60-65years.[31]
  • Lack of pigmentation and clinical features more suggestive of keratinocytic skin cancer may result in delay in detection and thicker tumors at diagnosis.
  • Desmoplastic melanoma frequently exhibits perineural extension and has a predilection for local recurrence. Wide excisional margins (≥2 cm) and adjuvant radiation therapy are frequently recommended for improved local control of this uncommon melanoma subtype.

Amelanotic melanoma (< 5% of melanomas) can occur with any subtype and its characteristics are as follows:

  • This type is nonpigmented and, clinically, appears pink or flesh-colored, often mimicking basal cell or squamous cell carcinoma, dermatofibroma, or a ruptured hair follicle.
  • It occurs most commonly in the setting of the nodular or desmoplastic melanoma subtype or melanoma metastasis to the skin, presumably because of the inability of these poorly differentiated cancer cells to synthesize melanin pigment.
Previous
Next

Causes

Melanoma shows an increased worldwide incidence in fair-complexioned individuals living in sunny climates and nearer the equator, suggesting a causative role for ultraviolet radiation. Most data support the hypothesis that melanoma development is related to intermittent, intense sun exposure, particularly in childhood or adolescence.[32, 33] In contrast, chronic sun exposure does not appear to confer increased risk, except for the more UV-related melanoma subtypes (lentigo maligna and lentigo maligna melanoma). The use of tanning beds has also increased the risk of melanoma in young patients.[34]

  • Primary risk factors and clinical warning signs for melanoma include the following:
  • Changing mole (most important clinical warning sign)
  • Presence of xeroderma pigmentosum or familial atypical mole melanoma syndrome: These genodermatoses confer a 500- to 1000-fold greater relative risk of developing melanoma.
  • Clinical atypical/dysplastic nevi in familial melanoma
  • Sporadic (nonfamilial) clinical atypical/dysplastic nevi (particularly >5-10)
  • Melanoma in first-degree relative(s) (especially multiple)
  • Large numbers of common nevi (>100)
  • Previous melanoma
  • Male sex
  • Age older than 50 years
  • Sun sensitivity/history of excessive sun exposure or sunburns
  • Large (giant) congenital nevi (>20 cm diameter in an adult)
  • Prior nonmelanoma skin cancer (basal cell and squamous cell carcinoma)[34]
  • Immunosuppression

A fair-skin phenotype (blue/green eyes, blond or red hair, light complexion, sun sensitivity) and the occurrence of blistering sunburn(s) in childhood and adolescence are universal risk factors for melanoma. Individuals with these traits have been the focus of preventive efforts worldwide.

Pregnancy or hormonal therapy with oral contraceptives or hormone replacement does not appear to be a risk factor for melanoma development.[35, 36, 37, 38, 39]

Previous
Proceed to Differential Diagnoses
 
 
Contributor Information and Disclosures
Author

Susan M Swetter, MD  Director, Pigmented Lesion and Melanoma Program, Professor, Department of Dermatology, Stanford University Medical Center and Cancer Institute, Veterans Affairs Palo Alto Health Care System

Susan M Swetter, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, American Society of Clinical Oncology, Eastern Cooperative Oncology Group, Pacific Dermatologic Association, Society for Investigative Dermatology, Society for Melanoma Research, and Women's Dermatologic Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Günter Burg, MD  Professor and Chairman Emeritus, Department of Dermatology, University of Zürich School of Medicine; Delegate of The Foundation for Modern Teaching and Learning in Medicine Faculty of Medicine, University of Zürich, Switzerland

Günter Burg, MD is a member of the following medical societies: American Academy of Dermatology, American Dermatological Association, International Society for Dermatologic Surgery, North American Clinical Dermatologic Society, and Pacific Dermatologic Association

Disclosure: Nothing to disclose.

Michael J Wells, MD  Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine

Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association

Disclosure: Nothing to disclose.

John G Albertini, MD  Consulting Staff, Dermatologic Surgery, The Skin Surgery Center; Program Director, ACGME Accredited Fellowship in Procedural Dermatology

John G Albertini, MD is a member of the following medical societies: American Academy of Dermatology and American College of Mohs Micrographic Surgery and Cutaneous Oncology

Disclosure: Nothing to disclose.

Catherine M Quirk, MD  Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania

Catherine M Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD  Director, Ackerman Academy of Dermatopathology, New York

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

References

  1. Demierre MF, Nathanson L. Chemoprevention of melanoma: an unexplored strategy. J Clin Oncol. Jan 1 2003;21(1):158-65. [Medline].

  2. Whiteman DC, Watt P, Purdie DM, Hughes MC, Hayward NK, Green AC. Melanocytic nevi, solar keratoses, and divergent pathways to cutaneous melanoma. J Natl Cancer Inst. Jun 4 2003;95(11):806-12. [Medline].

  3. Maldonado JL, Fridlyand J, Patel H, et al. Determinants of BRAF mutations in primary melanomas. J Natl Cancer Inst. Dec 17 2003;95(24):1878-90. [Medline].

  4. Lee JH, Choi JW, Kim YS. Frequencies of BRAF and NRAS mutations are different in histologic types and sites of origin of cutaneous melanoma: a meta-analysis. Br J Dermatol. Dec 16 2010;[Medline].

  5. Sober AJ, Fitzpatrick TB, Mihm MC, et al. Early recognition of cutaneous melanoma. JAMA. Dec 21 1979;242(25):2795-9. [Medline].

  6. Rhodes AR, Weinstock MA, Fitzpatrick TB, Mihm MC Jr, Sober AJ. Risk factors for cutaneous melanoma. A practical method of recognizing predisposed individuals. JAMA. Dec 4 1987;258(21):3146-54. [Medline].

  7. Williams ML, Sagebiel RW. Melanoma risk factors and atypical moles. West J Med. Apr 1994;160(4):343-50. [Medline].

  8. ACS. 2011 Cancer Facts and Figures. Cancer.org. Available at http://89. http://www.cancer.org/Research/CancerFactsFigures/CancerFactsFigures/cancer-facts-figures-2011. Accessed September 2, 2011.

  9. Cockburn M, Swetter SM, Peng D, Keegan TH, Deapen D, Clarke CA. Melanoma underreporting: why does it happen, how big is the problem, and how do we fix it?. J Am Acad Dermatol. Dec 2008;59(6):1081-5. [Medline].

  10. Purdue MP, Freeman LE, Anderson WF, Tucker MA. Recent trends in incidence of cutaneous melanoma among US Caucasian young adults. J Invest Dermatol. Dec 2008;128(12):2905-8. [Medline]. [Full Text].

  11. Hausauer AK, Swetter SM, Cockburn MG, Clarke CA. Increases in melanoma among adolescent girls and young women in California: trends by socioeconomic status and UV radiation exposure. Arch Dermatol. Jul 2011;147(7):783-9. [Medline].

  12. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. Mar-Apr 2005;55(2):74-108. [Medline].

  13. Geller AC, Miller DR, Annas GD, Demierre MF, Gilchrest BA, Koh HK. Melanoma incidence and mortality among US whites, 1969-1999. JAMA. Oct 9 2002;288(14):1719-20. [Medline].

  14. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. Jul-Aug 2009;59(4):225-49. [Medline].

  15. Swetter SM, Geller AC, Kirkwood JM. Melanoma in the older person. Oncology (Williston Park). Aug 2004;18(9):1187-96; discussion 1196-7. [Medline].

  16. Terushkin V, Halpern AC. Melanoma early detection. Hematol Oncol Clin North Am. Jun 2009;23(3):481-500, viii. [Medline].

  17. Friedman RJ, Rigel DS, Kopf AW. Early detection of malignant melanoma: the role of physician examination and self-examination of the skin. CA Cancer J Clin. May-Jun 1985;35(3):130-51. [Medline].

  18. Abbasi NR, Shaw HM, Rigel DS, et al. Early diagnosis of cutaneous melanoma: revisiting the ABCD criteria. JAMA. Dec 8 2004;292(22):2771-6. [Medline].

  19. Grob JJ, Bonerandi JJ. The 'ugly duckling' sign: identification of the common characteristics of nevi in an individual as a basis for melanoma screening. Arch Dermatol. Jan 1998;134(1):103-4. [Medline].

  20. Gachon J, Beaulieu P, Sei JF, et al. First prospective study of the recognition process of melanoma in dermatological practice. Arch Dermatol. Apr 2005;141(4):434-8. [Medline].

  21. Miracco C, Santopietro R, Biagioli M, et al. Different patterns of cell proliferation and death and oncogene expression in cutaneous malignant melanoma. J Cutan Pathol. May 1998;25(5):244-51. [Medline].

  22. Bastian BC, Kashani-Sabet M, Hamm H, et al. Gene amplifications characterize acral melanoma and permit the detection of occult tumor cells in the surrounding skin. Cancer Res. Apr 1 2000;60(7):1968-73. [Medline].

  23. Sasaki Y, Niu C, Makino R, et al. BRAF point mutations in primary melanoma show different prevalences by subtype. J Invest Dermatol. Jul 2004;123(1):177-83. [Medline].

  24. Richard MA, Grob JJ, Avril MF, et al. Melanoma and tumor thickness: challenges of early diagnosis. Arch Dermatol. Mar 1999;135(3):269-74. [Medline].

  25. Demierre MF, Chung C, Miller DR, Geller AC. Early detection of thick melanomas in the United States: beware of the nodular subtype. Arch Dermatol. Jun 2005;141(6):745-50. [Medline].

  26. Swetter SM, Boldrick JC, Jung SY, Egbert BM, Harvell JD. Increasing incidence of lentigo maligna melanoma subtypes: northern California and national trends 1990-2000. J Invest Dermatol. Oct 2005;125(4):685-91. [Medline].

  27. Farrahi F, Egbert BM, Swetter SM. Histologic similarities between lentigo maligna and dysplastic nevus: importance of clinicopathologic distinction. J Cutan Pathol. Jul 2005;32(6):405-12. [Medline].

  28. Cress RD, Holly EA. Incidence of cutaneous melanoma among non-Hispanic whites, Hispanics, Asians, and blacks: an analysis of california cancer registry data, 1988-93. Cancer Causes Control. Mar 1997;8(2):246-52. [Medline].

  29. Byrd KM, Wilson DC, Hoyler SS, Peck GL. Advanced presentation of melanoma in African Americans. J Am Acad Dermatol. Jan 2004;50(1):21-4; discussion 142-3. [Medline].

  30. Rogers RS 3rd, Gibson LE. Mucosal, genital, and unusual clinical variants of melanoma. Mayo Clin Proc. Apr 1997;72(4):362-6. [Medline].

  31. Jain S, Allen PW. Desmoplastic malignant melanoma and its variants. A study of 45 cases. Am J Surg Pathol. May 1989;13(5):358-73. [Medline].

  32. Elwood JM, Jopson J. Melanoma and sun exposure: an overview of published studies. Int J Cancer. Oct 9 1997;73(2):198-203. [Medline].

  33. Gilchrest BA, Eller MS, Geller AC, Yaar M. The pathogenesis of melanoma induced by ultraviolet radiation. N Engl J Med. Apr 29 1999;340(17):1341-8. [Medline].

  34. Cust AE, Armstrong BK, Goumas C, et al. Sunbed use during adolescence and early adulthood is associated with increased risk of early-onset melanoma. Int J Cancer. May 1 2011;128(10):2425-35. [Medline]. [Full Text].

  35. Lederman JS, Lew RA, Koh HK, Sober AJ. Influence of estrogen administration on tumor characteristics and survival in women with cutaneous melanoma. J Natl Cancer Inst. May 1985;74(5):981-5. [Medline].

  36. Hannaford PC, Villard-Mackintosh L, Vessey MP, Kay CR. Oral contraceptives and malignant melanoma. Br J Cancer. Mar 1991;63(3):430-3. [Medline].

  37. Driscoll MS, Grin-Jorgensen CM, Grant-Kels JM. Does pregnancy influence the prognosis of malignant melanoma?. J Am Acad Dermatol. Oct 1993;29(4):619-30. [Medline].

  38. Smith MA, Fine JA, Barnhill RL, Berwick M. Hormonal and reproductive influences and risk of melanoma in women. Int J Epidemiol. Oct 1998;27(5):751-7. [Medline].

  39. Schwartz JL, Mozurkewich EL, Johnson TM. Current management of patients with melanoma who are pregnant, want to get pregnant, or do not want to get pregnant. Cancer. May 1 2003;97(9):2130-3. [Medline].

  40. Weiss M, Loprinzi CL, Creagan ET, Dalton RJ, Novotny P, O'Fallon JR. Utility of follow-up tests for detecting recurrent disease in patients with malignant melanomas. JAMA. Dec 6 1995;274(21):1703-5. [Medline].

  41. Johnson TM, Bradford CR, Gruber SB, Sondak VK, Schwartz JL. Staging workup, sentinel node biopsy, and follow-up tests for melanoma: update of current concepts. Arch Dermatol. Jan 2004;140(1):107-13. [Medline].

  42. Wang TS, Johnson TM, Cascade PN, Redman BG, Sondak VK, Schwartz JL. Evaluation of staging chest radiographs and serum lactate dehydrogenase for localized melanoma. J Am Acad Dermatol. Sep 2004;51(3):399-405. [Medline].

  43. Hafner J, Schmid MH, Kempf W, et al. Baseline staging in cutaneous malignant melanoma. Br J Dermatol. Apr 2004;150(4):677-86. [Medline].

  44. Miranda EP, Gertner M, Wall J, Grace E, Kashani-Sabet M, Allen R. Routine imaging of asymptomatic melanoma patients with metastasis to sentinel lymph nodes rarely identifies systemic disease. Arch Surg. Aug 2004;139(8):831-6; discussion 836-7. [Medline].

  45. Bichakjian CK, Halpern AC, Johnson TM, et al. Guidelines of Care for the Management of Primary Cutaneous Melanoma. American Academy of Dermatology. Available at http://www.aad.org/education-and-quality-care/clinical-guidelines/current-and-upcoming-guidelines. Accessed June 9, 2011.

  46. National Comprehensive Cancer Care Network. Clinical Practice Guidelines in Oncology - v.1.2011: Melanoma. Accessed January 4, 2011. Available at http://www.nccn.org/professionals/physician_gls/PDF/melanoma.pdf.

  47. Kaskel P, Berking C, Sander S, Volkenandt M, Peter RU, Krahn G. S-100 protein in peripheral blood: a marker for melanoma metastases: a prospective 2-center study of 570 patients with melanoma. J Am Acad Dermatol. Dec 1999;41(6):962-9. [Medline].

  48. Morris KT, Busam KJ, Bero S, Patel A, Brady MS. Primary cutaneous melanoma with regression does not require a lower threshold for sentinel lymph node biopsy. Ann Surg Oncol. Jan 2008;15(1):316-22. [Medline].

  49. Elder DE, Guerry D 4th, Epstein MN, et al. Invasive malignant melanomas lacking competence for metastasis. Am J Dermatopathol. 1984;6 Suppl:55-61. [Medline].

  50. Guerry D 4th, Synnestvedt M, Elder DE, Schultz D. Lessons from tumor progression: the invasive radial growth phase of melanoma is common, incapable of metastasis, and indolent. J Invest Dermatol. Mar 1993;100(3):342S-345S. [Medline].

  51. Clark WH Jr, Elder DE, Guerry D 4th, et al. Model predicting survival in stage I melanoma based on tumor progression. J Natl Cancer Inst. Dec 20 1989;81(24):1893-904. [Medline].

  52. Balch CM. Cutaneous melanoma: prognosis and treatment results worldwide. Semin Surg Oncol. Nov-Dec 1992;8(6):400-14. [Medline].

  53. Buzaid AC, Ross MI, Balch CM, et al. Critical analysis of the current American Joint Committee on Cancer staging system for cutaneous melanoma and proposal of a new staging system. J Clin Oncol. Mar 1997;15(3):1039-51. [Medline].

  54. Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A, et al. Melanoma of the Skin. In: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer; 2009:325-40.

  55. Balch CM, Buzaid AC, Atkins MB, et al. A new American Joint Committee on Cancer staging system for cutaneous melanoma. Cancer. Mar 15 2000;88(6):1484-91. [Medline].

  56. 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. Aug 15 2001;19(16):3635-48. [Medline].

  57. Balch CM, Soong SJ, Atkins MB, et al. An evidence-based staging system for cutaneous melanoma. CA Cancer J Clin. May-Jun 2004;54(3):131-49; quiz 182-4. [Medline].

  58. Agarwala SS, Glaspy J, O'Day SJ, et al. Results from a randomized phase III study comparing combined treatment with histamine dihydrochloride plus interleukin-2 versus interleukin-2 alone in patients with metastatic melanoma. J Clin Oncol. Jan 1 2002;20(1):125-33. [Medline].

  59. Veronesi U, Adamus J, Aubert C, et al. A randomized trial of adjuvant chemotherapy and immunotherapy in cutaneous melanoma. N Engl J Med. Oct 7 1982;307(15):913-6. [Medline].

  60. Kirkwood JM, Strawderman MH, Ernstoff MS, Smith TJ, Borden EC, Blum RH. Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial EST 1684. J Clin Oncol. Jan 1996;14(1):7-17. [Medline].

  61. Kirkwood JM, Ibrahim JG, Sondak VK, et al. High- and low-dose interferon alfa-2b in high-risk melanoma: first analysis of intergroup trial E1690/S9111/C9190. J Clin Oncol. Jun 2000;18(12):2444-58. [Medline].

  62. Kirkwood JM, Ibrahim JG, Sosman JA, et al. High-dose interferon alfa-2b significantly prolongs relapse-free and overall survival compared with the GM2-KLH/QS-21 vaccine in patients with resected stage IIB-III melanoma: results of intergroup trial E1694/S9512/C509801. J Clin Oncol. May 1 2001;19(9):2370-80. [Medline].

  63. Kirkwood JM, Manola J, Ibrahim J, et al. A pooled analysis of eastern cooperative oncology group and intergroup trials of adjuvant high-dose interferon for melanoma. Clin Cancer Res. Mar 1 2004;10(5):1670-7. [Medline].

  64. Eggermont AM, Suciu S, Santinami M, et al. Adjuvant therapy with pegylated interferon alfa-2b versus observation alone in resected stage III melanoma: final results of EORTC 18991, a randomised phase III trial. Lancet. Jul 12 2008;372(9633):117-26. [Medline].

  65. Gogas H, Ioannovich J, Dafni U, et al. Prognostic significance of autoimmunity during treatment of melanoma with interferon. N Engl J Med. Feb 16 2006;354(7):709-18. [Medline].

  66. Demierre MF, Swetter SM, Sondak VK. Vaccine therapy of melanoma: an update. Curr Canc Ther Rev. 2005;1:115-25.

  67. Schwartzentruber DJ, Lawson D, Richards J, et al. A phase III multi-institutional randomized study of immunization with the gp100:209-217(210M) peptide followed by high-dose IL-2 compared with high-dose IL-2 alone in patients with metastatic melanoma. J Clin Oncol. 2009;27:18 s (suppl; abstr CRA9011).

  68. Schwartzentruber DJ, Lawson DH, Richards JM, et al. gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma. N Engl J Med. Jun 2 2011;364(22):2119-27. [Medline].

  69. Long GV, Menzies AM, Nagrial AM, et al. Prognostic and Clinicopathologic Associations of Oncogenic BRAF in Metastatic Melanoma. J Clin Oncol. Apr 1 2011;29(10):1239-46. [Medline].

  70. Chapman PB, Hauschild A, Robert C, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. Jun 30 2011;364(26):2507-16. [Medline].

  71. National Institutes of Health. NIH Consensus conference. Diagnosis and treatment of early melanoma. JAMA. Sep 9 1992;268(10):1314-9. [Medline].

  72. Kunishige JH, Brodland DG, Zitelli JA. Surgical margins for melanoma in situ. J Am Acad Dermatol. Mar 2012;66(3):438-44. [Medline].

  73. Balch CM, Urist MM, Karakousis CP, et al. Efficacy of 2-cm surgical margins for intermediate-thickness melanomas (1 to 4 mm). Results of a multi-institutional randomized surgical trial. Ann Surg. Sep 1993;218(3):262-7; discussion 267-9. [Medline].

  74. Veronesi U, Cascinelli N, Adamus J, et al. Thin stage I primary cutaneous malignant melanoma. Comparison of excision with margins of 1 or 3 cm. N Engl J Med. May 5 1988;318(18):1159-62. [Medline].

  75. Thomas JM, Newton-Bishop J, A'Hern R, et al. Excision margins in high-risk malignant melanoma. N Engl J Med. Feb 19 2004;350(8):757-66. [Medline].

  76. Heaton KM, Sussman JJ, Gershenwald JE, et al. Surgical margins and prognostic factors in patients with thick (>4mm) primary melanoma. Ann Surg Oncol. Jun 1998;5(4):322-8. [Medline].

  77. Gillgren P, Drzewiecki KT, Niin M, et al. 2-cm versus 4-cm surgical excision margins for primary cutaneous melanoma thicker than 2 mm: a randomised, multicentre trial. Lancet. Nov 5 2011;378(9803):1635-42. [Medline].

  78. Zitelli JA, Brown C, Hanusa BH. Mohs micrographic surgery for the treatment of primary cutaneous melanoma. J Am Acad Dermatol. Aug 1997;37(2 Pt 1):236-45. [Medline].

  79. Balch CM. Randomized surgical trials involving elective node dissection for melanoma. Adv Surg. 1999;32:255-70. [Medline].

  80. Balch CM, Soong SJ, Bartolucci AA, et al. Efficacy of an elective regional lymph node dissection of 1 to 4 mm thick melanomas for patients 60 years of age and younger. Ann Surg. Sep 1996;224(3):255-63; discussion 263-6. [Medline].

  81. Cascinelli N, Morabito A, Santinami M, MacKie RM, Belli F. Immediate or delayed dissection of regional nodes in patients with melanoma of the trunk: a randomised trial. WHO Melanoma Programme. Lancet. Mar 14 1998;351(9105):793-6. [Medline].

  82. Morton DL, Thompson JF, Essner R, et al. Validation of the accuracy of intraoperative lymphatic mapping and sentinel lymphadenectomy for early-stage melanoma: a multicenter trial. Multicenter Selective Lymphadenectomy Trial Group. Ann Surg. Oct 1999;230(4):453-63; discussion 463-5. [Medline].

  83. Gershenwald JE, Thompson W, Mansfield PF, et al. Multi-institutional melanoma lymphatic mapping experience: the prognostic value of sentinel lymph node status in 612 stage I or II melanoma patients. J Clin Oncol. Mar 1999;17(3):976-83. [Medline].

  84. McMasters KM, Reintgen DS, Ross MI, et al. Sentinel lymph node biopsy for melanoma: controversy despite widespread agreement. J Clin Oncol. Jun 1 2001;19(11):2851-5. [Medline].

  85. [Best Evidence] Morton DL, Thompson JF, Cochran AJ, et al. Sentinel-node biopsy or nodal observation in melanoma. N Engl J Med. Sep 28 2006;355(13):1307-17. [Medline].

  86. Hancock BW, Wheatley K, Harris S, et al. Adjuvant interferon in high-risk melanoma: the AIM HIGH Study--United Kingdom Coordinating Committee on Cancer Research randomized study of adjuvant low-dose extended-duration interferon Alfa-2a in high-risk resected malignant melanoma. J Clin Oncol. Jan 1 2004;22(1):53-61. [Medline].

  87. Hodi FS, O'Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. Aug 19 2010;363(8):711-23. [Medline].

  88. Robert C, Thomas L, Bondarenko I, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. Jun 30 2011;364(26):2517-26. [Medline].

  89. Levi F, Randimbison L, Te VC, La Vecchia C. High constant incidence rates of second cutaneous melanomas. Int J Cancer. Jun 14 2005;[Medline].

  90. Francis DM, Busmanis I, Becker G. Peritoneal calcification in a peritoneal dialysis patient: a case report. Perit Dial Int. 1990;10(3):237-40. [Medline].

  91. Atkins MB, Hsu J, Lee S, et al. Phase III trial comparing concurrent biochemotherapy with cisplatin, vinblastine, dacarbazine, interleukin-2, and interferon alfa-2b with cisplatin, vinblastine, and dacarbazine alone in patients with metastatic malignant melanoma (E3695): a trial coordinated by the Eastern Cooperative Oncology Group. J Clin Oncol. Dec 10 2008;26(35):5748-54. [Medline]. [Full Text].

  92. Leachman SA, Carucci J, Kohlmann W, et al. Selection criteria for genetic assessment of patients with familial melanoma. J Am Acad Dermatol. Oct 2009;61(4):677.e1-14. [Medline].

  93. American Joint Committee on Cancer. Manual for Staging of Cancer. 6th ed. Philadelphia, Pa: Lippincott; 2002:209-20.

 
Previous
Next
 
Superficial spreading melanoma, left breast, 1.3-mm Breslow depth.
Lentigo maligna melanoma, right lower cheek. Centrally located erythematous papule represents invasive melanoma with surrounding macular lentigo maligna (melanoma in situ).
Acral lentiginous melanoma (1-mm Breslow depth), left sole. Diagnostic punch biopsy site is located superiorly.
Malignant melanoma. Courtesy of Hon Pak, MD.
Cutaneous melanoma with characteristic asymmetry, irregular borders, and color variation. Courtesy of Wendy Brick, MD.
Table. AJCC 2002 Revised Melanoma Staging
StageTNM ClassificationHistologic/Clinical Features5-Year Survival Rate, %
0Tis N0 M0Intraepithelial/in situ melanoma100
IAT1a N0 M0≤1 mm without ulceration and mitotic rate < 1/mm297
IBT1b N0 M0



T2a N0 M0



≤1 mm with ulceration or mitotic rate ≥1/mm2



1.01-2 mm without ulceration



91-94
IIAT2b N0 M0



T3a N0 M0



1.01-2 mm with ulceration



2.01-4 mm without ulceration



79-82
IIBT3b N0 M0



T4a N0 M0



2.01-4 mm with ulceration



4 mm without ulceration



68-71
IICT4b N0 M0>4 mm with ulceration53
IIIAT1-4a N1a M0



T1-4a N2a M0



Single regional nodal micrometastasis, nonulcerated primary



2-3 microscopic positive regional nodes, nonulcerated primary



78
IIIBT1-4b N1a M0



T1-4b N2a M0



T1-4a N1b M0



T1-4a N2b M0



T1-4a/b N2c M0



Single regional nodal micrometastasis, ulcerated primary



2-3 microscopic regional nodes, nonulcerated primary



Single regional nodal macrometastasis, nonulcerated primary



2-3 macroscopic regional nodes, no ulceration of primary



In-transit met(s)* and/or satellite lesion(s) without metastatic lymph nodes



54-59
IIICT1-4b N2a M0



T1-4b N2b M0



Any T N3 M0



Single macroscopic regional node, ulcerated primary



2-3 macroscopic metastatic regional nodes, ulcerated primary



4 or more metastatic nodes, matted nodes/gross extracapsular extension, or in-transit met(s)/satellite lesion(s) and metastatic nodes



40
IVAny T any N M1a



Any T any N M1b



Any T any N M1c



Distant skin, subcutaneous, or nodal mets with normal LDH levels



Lung mets with normal LDH



All other visceral mets with normal LDH or any distant mets with elevated LDH



< 20
*Met is metastasis.
Previous
Next
 
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.