0
May 14, 1997, Vol 277, No. 18 >
ARTICLE | May 14, 1997

Clinically Recognized Dysplastic Nevi: Title and subTitle BreakA Central Risk Factor for Cutaneous Melanoma FREE

Margaret A. Tucker, MD; Allan Halpern, MD; Elizabeth A. Holly, PhD; Patricia Hartge, ScD; David E. Elder, MD; Richard W. Sagebiel, MD; DuPont Guerry, IV, MD; Wallace H. Clark, Jr, MD
[+] Author Affiliations

Reprints: Margaret A. Tucker, MD, Genetic Epidemiology Branch, Executive Plaza North, Suite 439, 6130 Executive Blvd, MSC 7372, Bethesda, MD20892-7372 (e-mail: tuckerp@epndce.nci.nih.gov).


JAMA. 1997;277(18):1439-1444. doi:10.1001/jama.1997.03540420035026
Text Size: A A A
Published online
Article
References

Objective.  —To investigate the relationship of number and type of nevi to the development of melanoma.

Design.  —Case-control study.

Setting.  —Outpatient clinics in referral hospitals.

Patients.  —Cases were 716 consecutive patients with newly diagnosed melanoma identified at 2 melanoma centers between January 1,1991, and December 31, 1992. Stratified random sampling of patients from outpatient clinics was used to identify 1014 participating controls of the same age, sex, race, and geographic distribution as the melanoma cases. All study subjects underwent an interview, a complete skin examination, photography of the most atypical nevi, and, if the patient was willing, a biopsy of the most atypical nevus.

Main Outcome Measures.  —Number and type of nevi on the entire body were systematically reported. All diagnoses of clinically dysplastic nevi were confirmed by expert examiners.

Results.  —Risk for melanoma was strongly related to number of small nevi, large nondysplastic nevi, and clinically dysplastic nevi. In the absence of dysplastic nevi, increased numbers of small nevi were associated with an approximately 2-fold risk, and increased numbers of both small and large nondysplastic nevi were associated with a 4-fold risk. One clinically dysplastic nevus was associated with a 2-fold risk (95% confidence interval, 1.4-3.6), while 10 or more conferred a 12-fold increased risk (95% confidence interval, 4.4-31). Congenital nevi were not associated with increased risk of melanoma.

Conclusions.  —Although nondysplastic nevi confer a small risk, clinically dysplastic nevi confer substantial risk for melanoma. On the basis of nevus number and type, clinicians can identify a population at high risk of this epidemic cancer for screening and intervention.

REFERENCES

1 +
Clark WH Jr, Reimer RR, Greene MH, Ainsworth AM, Mastrangelo MJ.  Origin of familial malignant melanomas from heritable melanocytic lesions: the B-K mole syndrome . Arch Dermatol . 1978;; 114:732-738.
2 +
Frichot BC III, Lynch HT, Guirgis HA, Harris RE, Lynch JF.  New cutaneous phenotype in familial malignant melanoma . Lancet . 1977;;1:864-865.
3 +
Lynch HT, Frichot BC III, Lynch JF.  Familial atypical multiple mole-melanoma syndrome . J Med Genet . 1978;;15:352-356.
4 +
Tucker MA, Fraser MC, Goldstein AM, Elder DE, Guerry D IV, Organic SM.  The risk of melanoma and other cancers in melanoma-prone families . J Invest Dermatol . 1993;;100:350S-355S.
5 +
Elder DE, Goldman LI, Goldman SC, Greene MH, Clark WH Jr.  Dysplastic nevus syndrome: a phenotypic association of sporadic melanoma . Cancer . 1980;;46:1787-1794.
6 +
Nordlund JJ, Kirkwood J, Forget BM, et al.  Demographic study of clinically atypical (dysplastic) nevi in patients with melanoma and comparison subjects . Cancer Res . 1986;;46:1005-1009.
7 +
Swerdlow AJ, English J, MacKie RM, et al.  Benign melanocytic naevi as a risk factor for malignant melanoma . BMJ . 1986;;292:1555-1559.
8 +
Cristofolini M, Franceschi S, Tasin L, et al.  Risk factors for cutaneous malignant melanoma in a northern Italian population . Int J Cancer . 1987;;39:150-154.
9 +
Holly EA, Kelly JW, Shpall SN, Chiu S-H.  Number of melanocytic nevi as a major risk factor for malignant melanoma . J Am Acad Dermatol . 1987;; 17:459-468.
10 +
Roush GC, Nordlund JJ, Forget B, Gruber SB, Kirkwood JM.  Independence of dysplastic nevi from total nevi in determining risk for nonfamilial melanoma . Prev Med . 1988;;17:273-279.
11 +
Halpern AC, Guerry D IV, Elder DE, et al.  Dysplastic nevi as risk markers of sporadic (nonfamilial) melanoma: a case-control study . Arch Dermatol . 1991;;127:995-999.
12 +
Newton JA, Bataille V, Griffiths K, et al.  How common is the atypical mole syndrome phenotype in apparently sporadic melanoma? J Am Acad Dermatol . 1993;;29:989-996.
13 +
Kang S, Barnhill RL, Mihm MC Jr, Fitzpatrick TB, Sober AJ.  Melanoma risk in individuals with clinically atypical nevi . Arch Dermatol . 1994;;130: 999-1001.
14 +
Marghoob AA, Kopf AW, Rigel DS, et al.  Risk of cutaneous malignant melanoma in patients with 'classic' atypical-mole syndrome: a case-control study . Arch Dermatol . 1994;;130:993-998.
15 +
Schneider JS, Moore DH II, Sagebiel RW.  Risk factors for melanoma incidence in prospective followup: the importance of atypical (dysplastic) nevi . Arch Dermatol . 1994;;130:1002-1007.
16 +
Garbe C, Buttner P, Weiss J, et al.  Risk factors for developing cutaneous melanoma and criteria for identifying persons at risk: multicenter case-control study of the Central Malignant Melanoma Registry of the German Dermatological Society . J Invest Dermatol . 1994;;102:695-699.
17 +
Augustsson A, Stierner U, Rosdahl I, Suurkula M.  Common and dysplastic naevi as risk factors for cutaneous malignant melanoma in a Swedish population . Acta Derm Venereol . 1990;;71:518-524.
18 +
 NIH Consensus Development Panel on Early Melanoma. Diagnosis and treatment of early melanoma . JAMA . 1992;;268:1314-1319.
19 +
Weinstock MA.  Dysplastic nevi revisited . J Am Acad Dermatol . 1994;;30:807-810.
20 +
Hartge P, Holly EA, Halpern A, et al.  Recognition and classification of clinically dysplastic nevi from photographs: a study of interobserver variation . Cancer Epidemiol Biomarkers Prev . 1995;;4: 37-40.
21 +
Elder DE, Clark WH Jr, Elenitsas R, Guerry D IV, Halpern AC.  The early and intermediate precursor lesions of tumor progression in the melanocytic system: common acquired nevi and atypical (dysplastic) nevi . Semin Diagn Pathol . 1993;;10: 18-35.
22 +
Boice JD Jr, Lubin JH, Preston DL. EPITOME: Epidemiologic Analysis With a Personal Computer . Bethesda, Md: National Institutes of Health; 1996;. NIH publication 96-3180.
23 +
BMDP Statistical Software. Los Angeles: University of California Press; 1992.
24 +
Foulds L. Neoplastic Development . New York, NY: Academic Press; 1969;:41-96.
25 +
Clark WH Jr.  The role of tumor progression in prevention of cancer and reduction of cancer mortality . In: Greenwald P, Kramer BS, Weed DL, eds. Cancer Prevention and Control . New York, NY: Marcel Dekker Inc; 1995;:135-160.
26 +
Kinzler KW, Nilbert MC, Su LK, et al.  Identification of FAP locus genes from chromosome 5q21 . Science . 1991;;253:661-665.
27 +
Kinzler KW, Vogelstein B.  Lessons from hereditary colorectal cancer . Cell . 1996;;87:159-170.
28 +
Kurman RJ, Henson DE, Herbst AL, Noller KL, Schiffman MH.  Interim guidelines for management of abnormal cervical cytology . JAMA . 1994;; 271:1866-1869.
29 +
Schiffman MH, Brinton LA.  The epidemiology of cervical carcinogenesis . Cancer . 1995;;76:1888-1901.
30 +
Clark WH Jr, Elder DE, Guerry D, Epstein MH, Greene MH, Van Horn M.  A study of tumor progression: the precursor lesions of superficial spreading and nodular melanoma . Hum Pathol . 1984;; 15:1147-1165.
31 +
Clark WH.  Tumor progression and the nature of cancer . Br J Cancer . 1991;;64:631-644.
32 +
Elder DE, Herlyn M.  Antigens associated with tumor progression in melanocytic neoplasia . Pigment Cell Res . 1992;;82:136-143.
33 +
Albelda SM, Mette SA, Elder DE, et al.  Integrin distribution in malignant melanoma: association of the β3 subunit with tumor progression . Cancer Res . 1990;;50:6757-6764.
34 +
Taylor MR, Guerry DIV, Bondi EE, et al.  Lack of association between intraocular melanoma and cutaneous dysplastic nevi . Am J Ophthalmol . 1984;; 98:478-482.
35 +
Roush GC, Barnhill RL, Ernstoff MS, Kirkwood JM.  Inter-clinician agreement on the recognition of patients with cutaneous malignant melanoma: studies of melanocytic nevi, VI . Br J Cancer . 1991;;64:373-376.
36 +
Piepkorn MW, Barnhill RL, Cannon-Albright LA, et al.  A multiobserver, population-based analysis of histologic dysplasia in melanocytic nevi . J Am Acad Dermatol . 1994;;30:707-714.
37 +
Goldstein AM, Dracopoli NC, Ho EC, et al.  Further evidence for a locus for cutaneous malignant melanoma—dysplastic nevi (CMM/DN) on chromosome lp and evidence for genetic heterogeneity . Am J Hum Genet . 1993;;52:537-550.
38 +
Goldstein AM, Dracopoli NC, Engelstein M, Fraser MC, Clark WH Jr, Tucker MA.  Linkage of cutaneous malignant melanoma/dysplastic nevi (CMM/DN) to chromosome 9p and evidence for genetic heterogeneity . Am J Hum Genet . 1994;;54: 489-496.
39 +
MacGeoch C, Newton Bishop J, Bataille V, et al.  Genetic heterogeneity in familial malignant melanoma . Hum Mol Genet . 1994;;3:2195-2200.
40 +
Nicholls EM.  Development and elimination of pigmented moles, and the anatomical distribution of primary malignant melanoma . Cancer . 1973;;32: 191-195.
41 +
Stegmaier OC.  Natural regression of the melanocytic nevus . J Invest Dermatol . 1959;;32:413-421.
42 +
Cooke KR, Spears GFS, Skegg DCG.  Frequency of moles in a defined population . J Epidemiol Commun Health . 1985;;39:48-52.
43 +
Halpern AC, Guerry D IV, Elder DE, Trock B, Synnestvedt M, Humphreys T.  Natural history of dysplastic nevi . J Am Acad Dermatol . 1993;;29:51-57.
44 +
Cooke KR, Speare GFS, Elder DE, Greene MH.  Dysplastic nevi in a population-based survey . Cancer . 1989;;63:1240-1244.

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Clark WH Jr, Reimer RR, Greene MH, Ainsworth AM, Mastrangelo MJ.  Origin of familial malignant melanomas from heritable melanocytic lesions: the B-K mole syndrome . Arch Dermatol . 1978;; 114:732-738.
2 +
Frichot BC III, Lynch HT, Guirgis HA, Harris RE, Lynch JF.  New cutaneous phenotype in familial malignant melanoma . Lancet . 1977;;1:864-865.
3 +
Lynch HT, Frichot BC III, Lynch JF.  Familial atypical multiple mole-melanoma syndrome . J Med Genet . 1978;;15:352-356.
4 +
Tucker MA, Fraser MC, Goldstein AM, Elder DE, Guerry D IV, Organic SM.  The risk of melanoma and other cancers in melanoma-prone families . J Invest Dermatol . 1993;;100:350S-355S.
5 +
Elder DE, Goldman LI, Goldman SC, Greene MH, Clark WH Jr.  Dysplastic nevus syndrome: a phenotypic association of sporadic melanoma . Cancer . 1980;;46:1787-1794.
6 +
Nordlund JJ, Kirkwood J, Forget BM, et al.  Demographic study of clinically atypical (dysplastic) nevi in patients with melanoma and comparison subjects . Cancer Res . 1986;;46:1005-1009.
7 +
Swerdlow AJ, English J, MacKie RM, et al.  Benign melanocytic naevi as a risk factor for malignant melanoma . BMJ . 1986;;292:1555-1559.
8 +
Cristofolini M, Franceschi S, Tasin L, et al.  Risk factors for cutaneous malignant melanoma in a northern Italian population . Int J Cancer . 1987;;39:150-154.
9 +
Holly EA, Kelly JW, Shpall SN, Chiu S-H.  Number of melanocytic nevi as a major risk factor for malignant melanoma . J Am Acad Dermatol . 1987;; 17:459-468.
10 +
Roush GC, Nordlund JJ, Forget B, Gruber SB, Kirkwood JM.  Independence of dysplastic nevi from total nevi in determining risk for nonfamilial melanoma . Prev Med . 1988;;17:273-279.
11 +
Halpern AC, Guerry D IV, Elder DE, et al.  Dysplastic nevi as risk markers of sporadic (nonfamilial) melanoma: a case-control study . Arch Dermatol . 1991;;127:995-999.
12 +
Newton JA, Bataille V, Griffiths K, et al.  How common is the atypical mole syndrome phenotype in apparently sporadic melanoma? J Am Acad Dermatol . 1993;;29:989-996.
13 +
Kang S, Barnhill RL, Mihm MC Jr, Fitzpatrick TB, Sober AJ.  Melanoma risk in individuals with clinically atypical nevi . Arch Dermatol . 1994;;130: 999-1001.
14 +
Marghoob AA, Kopf AW, Rigel DS, et al.  Risk of cutaneous malignant melanoma in patients with 'classic' atypical-mole syndrome: a case-control study . Arch Dermatol . 1994;;130:993-998.
15 +
Schneider JS, Moore DH II, Sagebiel RW.  Risk factors for melanoma incidence in prospective followup: the importance of atypical (dysplastic) nevi . Arch Dermatol . 1994;;130:1002-1007.
16 +
Garbe C, Buttner P, Weiss J, et al.  Risk factors for developing cutaneous melanoma and criteria for identifying persons at risk: multicenter case-control study of the Central Malignant Melanoma Registry of the German Dermatological Society . J Invest Dermatol . 1994;;102:695-699.
17 +
Augustsson A, Stierner U, Rosdahl I, Suurkula M.  Common and dysplastic naevi as risk factors for cutaneous malignant melanoma in a Swedish population . Acta Derm Venereol . 1990;;71:518-524.
18 +
 NIH Consensus Development Panel on Early Melanoma. Diagnosis and treatment of early melanoma . JAMA . 1992;;268:1314-1319.
19 +
Weinstock MA.  Dysplastic nevi revisited . J Am Acad Dermatol . 1994;;30:807-810.
20 +
Hartge P, Holly EA, Halpern A, et al.  Recognition and classification of clinically dysplastic nevi from photographs: a study of interobserver variation . Cancer Epidemiol Biomarkers Prev . 1995;;4: 37-40.
21 +
Elder DE, Clark WH Jr, Elenitsas R, Guerry D IV, Halpern AC.  The early and intermediate precursor lesions of tumor progression in the melanocytic system: common acquired nevi and atypical (dysplastic) nevi . Semin Diagn Pathol . 1993;;10: 18-35.
22 +
Boice JD Jr, Lubin JH, Preston DL. EPITOME: Epidemiologic Analysis With a Personal Computer . Bethesda, Md: National Institutes of Health; 1996;. NIH publication 96-3180.
23 +
BMDP Statistical Software. Los Angeles: University of California Press; 1992.
24 +
Foulds L. Neoplastic Development . New York, NY: Academic Press; 1969;:41-96.
25 +
Clark WH Jr.  The role of tumor progression in prevention of cancer and reduction of cancer mortality . In: Greenwald P, Kramer BS, Weed DL, eds. Cancer Prevention and Control . New York, NY: Marcel Dekker Inc; 1995;:135-160.
26 +
Kinzler KW, Nilbert MC, Su LK, et al.  Identification of FAP locus genes from chromosome 5q21 . Science . 1991;;253:661-665.
27 +
Kinzler KW, Vogelstein B.  Lessons from hereditary colorectal cancer . Cell . 1996;;87:159-170.
28 +
Kurman RJ, Henson DE, Herbst AL, Noller KL, Schiffman MH.  Interim guidelines for management of abnormal cervical cytology . JAMA . 1994;; 271:1866-1869.
29 +
Schiffman MH, Brinton LA.  The epidemiology of cervical carcinogenesis . Cancer . 1995;;76:1888-1901.
30 +
Clark WH Jr, Elder DE, Guerry D, Epstein MH, Greene MH, Van Horn M.  A study of tumor progression: the precursor lesions of superficial spreading and nodular melanoma . Hum Pathol . 1984;; 15:1147-1165.
31 +
Clark WH.  Tumor progression and the nature of cancer . Br J Cancer . 1991;;64:631-644.
32 +
Elder DE, Herlyn M.  Antigens associated with tumor progression in melanocytic neoplasia . Pigment Cell Res . 1992;;82:136-143.
33 +
Albelda SM, Mette SA, Elder DE, et al.  Integrin distribution in malignant melanoma: association of the β3 subunit with tumor progression . Cancer Res . 1990;;50:6757-6764.
34 +
Taylor MR, Guerry DIV, Bondi EE, et al.  Lack of association between intraocular melanoma and cutaneous dysplastic nevi . Am J Ophthalmol . 1984;; 98:478-482.
35 +
Roush GC, Barnhill RL, Ernstoff MS, Kirkwood JM.  Inter-clinician agreement on the recognition of patients with cutaneous malignant melanoma: studies of melanocytic nevi, VI . Br J Cancer . 1991;;64:373-376.
36 +
Piepkorn MW, Barnhill RL, Cannon-Albright LA, et al.  A multiobserver, population-based analysis of histologic dysplasia in melanocytic nevi . J Am Acad Dermatol . 1994;;30:707-714.
37 +
Goldstein AM, Dracopoli NC, Ho EC, et al.  Further evidence for a locus for cutaneous malignant melanoma—dysplastic nevi (CMM/DN) on chromosome lp and evidence for genetic heterogeneity . Am J Hum Genet . 1993;;52:537-550.
38 +
Goldstein AM, Dracopoli NC, Engelstein M, Fraser MC, Clark WH Jr, Tucker MA.  Linkage of cutaneous malignant melanoma/dysplastic nevi (CMM/DN) to chromosome 9p and evidence for genetic heterogeneity . Am J Hum Genet . 1994;;54: 489-496.
39 +
MacGeoch C, Newton Bishop J, Bataille V, et al.  Genetic heterogeneity in familial malignant melanoma . Hum Mol Genet . 1994;;3:2195-2200.
40 +
Nicholls EM.  Development and elimination of pigmented moles, and the anatomical distribution of primary malignant melanoma . Cancer . 1973;;32: 191-195.
41 +
Stegmaier OC.  Natural regression of the melanocytic nevus . J Invest Dermatol . 1959;;32:413-421.
42 +
Cooke KR, Spears GFS, Skegg DCG.  Frequency of moles in a defined population . J Epidemiol Commun Health . 1985;;39:48-52.
43 +
Halpern AC, Guerry D IV, Elder DE, Trock B, Synnestvedt M, Humphreys T.  Natural history of dysplastic nevi . J Am Acad Dermatol . 1993;;29:51-57.
44 +
Cooke KR, Speare GFS, Elder DE, Greene MH.  Dysplastic nevi in a population-based survey . Cancer . 1989;;63:1240-1244.

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