You are on page 1of 8

Large Congenital Melanocytic Nevi and the Risk for Development of Malignant Melanoma and Neurocutaneous Melanocytosis Flavia

V. Bittencourt, Ashfaq A. Marghoob, Alfred W. Kopf, Karen L. Koenig and Robert S. Bart Pediatrics 2000;106;736

The online version of this article, along with updated information and services, is located on the World Wide Web at:
http://pediatrics.aappublications.org/content/106/4/736.full.html

PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. PEDIATRICS is owned, published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007. Copyright 2000 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

Downloaded from pediatrics.aappublications.org at Indonesia:AAP Sponsored on August 4, 2013

Large Congenital Melanocytic Nevi and the Risk for Development of Malignant Melanoma and Neurocutaneous Melanocytosis
Flavia V. Bittencourt, MD*; Ashfaq A. Marghoob, MD; Alfred W. Kopf, MD*; Karen L. Koenig, PhD; and Robert S. Bart, MD*
ABSTRACT. Objective. To determine the risk for developing malignant melanoma and neurocutaneous melanocytosis (NCM) in patients with large congenital melanocytic nevi. Design. Follow-up data suitable for calculations were available on 160 patients in the New York University Registry of Large Congenital Melanocytic Nevi who had been free of known melanomas or NCM when entered into the Registry. The cumulative 5-year life-table risks for developing melanoma and NCM were calculated. The relative risk for developing melanoma, using a control general population reference group, was determined. Results. The 160 patients (median age at entry: 14 months) were followed prospectively for an average of 5.5 years. Three extracutaneous melanomas developed: 2 were in the central nervous system (CNS) and 1 was retroperitoneal. The 5-year cumulative life-table risk for developing melanoma was 2.3% (95% confidence interval [CI]: .8 6.6) and the relative risk was 101 (95% CI: 21 296). No melanoma occurred within a large congenital melanocytic nevus. Four patients developed manifest NCM, 2 with CNS melanomas. The 5-year cumulative life-table risk for developing NCM was 2.5% (95% CI: .8 7.2). Ten patients were excluded from the calculations because of preexisting disease on entry into the Registry: 5 with manifest NCM and 5 with melanomas (3 in large congenital melanocytic nevi, 1 in nonnevus skin, and 1 unknown primary). Conclusions. Patients with large congenital melanocytic nevi are at increased risk for developing melanomas. There is also a significant increased risk for developing NCM. The high incidence of CNS involvement may influence decisions concerning treatment of the large congenital melanocytic nevi. Pediatrics 2000;106: 736 741; large congenital melanocytic nevus, neurocutaneous melanocytosis, malignant melanoma.
ABBREVIATIONS. NYU-LCMN Registry, Registry of Large Congenital Melanocytic Nevi of the New York University School of Medicine; LCMN, large congenital melanocytic nevus/nevi; CNS, central nervous system; MRI, magnetic resonance imaging; NCM, neurocutaneous melanocytosis; SMR, standardized morbidity ratio; RR, relative risk; CI, confidence interval.

his report concerns the follow-up of patients who are in the Registry of Large Congenital Melanocytic Nevi of the New York University School of Medicine (NYU-LCMN Registry). The Registry was created in 19791 with the purpose of determining the risk of melanoma in patients who have large congenital melanocytic nevi (LCMN). At that time, physicians worldwide were invited to participate in the Registry by submitting patients in the database. Results from this Registry were first published in 19882 at which time data on 47 patients were suitable for analysis. The mean follow-up time of those patients was 4.4 years. One patient had developed a primary central nervous system (CNS) melanoma during follow-up. In 1996, Marghoob et al3 published an update of the NYU-LCMN Registry, at which time there were 92 patients, with an average follow-up of 5.4 years. Two more melanomas had developed for a total of 3: 2 in the CNS and 1 in the retroperitoneum. No melanomas had developed within the LCMN themselves. Currently, data on 194 patients with LCMN have been entered into the NYU-LCMN Registry, which accrued 3 additional years and 102 additional patients since the last report in 1996.3
METHODS
Data on 194 patients with LCMN were entered into the NYULCMN Registry from March 1979 to January 1999. A LCMN was defined as a congenital melanocytic nevus that has, or is predicted to attain in adulthood, a largest diameter of at least 20 cm.1,4 After entry into the Registry, attempts were made to follow the status of each patient. Information concerning most patients was obtained from the physicians who initially provided the data for entering their patients into the Registry. Most follow-up information was obtained by mail, telephone, and/or e-mail from physicians or the patients themselves. Some of the 194 patients were examined and followed at New York University Medical Center and in the private practice of one of the authors (A.W.K.). The information recorded for each patient included: age at time of entry into the Registry; sex; location of the LCMN; number of melanocytic nevus satellites; any treatment of the LCMN; presence of cutaneous or noncutaneous melanoma; and family history of melanoma. Since 1996, follow-up inquiries included questions specifically concerning CNS symptoms and/or signs and the results of magnetic resonance imaging (MRI) scans. Photographs of the LCMN were available in most patient records. Of the 194 patients who were entered into the NYU-LCMN Registry, 34 were excluded from the prospective analysis and calculations of risk for developing melanoma or neurocutaneous melanocytosis (NCM): 24 patients with 1 month of follow-up time, 5 patients who had developed melanomas before entry into the Registry, and 5 patients who had developed NCM before entry into the Registry.

From the *Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York; Department of Dermatology, State University of New York at Stony Brook Health Sciences Center, Stony Brook, New York; and Department of Environmental Medicine, New York University School of Medicine, New York, New York. Received for publication Jan 29, 1999; accepted Feb 7, 2000. Reprint requests to (A.W.K.) Ronald O. Perelman Department of Dermatology, New York University School of Medicine, 550 First Ave, New York, NY 10016. E-mail:akopf@compuserve.com PEDIATRICS (ISSN 0031 4005). Copyright 2000 by the American Academy of Pediatrics.

736

PEDIATRICS Vol. 106 No. 4 October 2000 Downloaded from pediatrics.aappublications.org at Indonesia:AAP Sponsored on August 4, 2013

The cumulative 5-year risk of developing melanoma was calculated, based on 160 patients, using the method of Kaplan and Meier,5 and the exact binomial confidence limits were computed.6 Rates of melanoma from the white population of the Surveillance, Epidemiology, and End Results7 database were applied to the age/sex and length of follow-up distribution of our 160 patients to determine the number of melanomas that would have been expected to occur in our patients had they experienced the same melanoma rates as the general population. The standardized morbidity ratio (SMR), which is the ratio of the observed to the expected number of melanomas and an estimation of the relative risk (RR), was calculated along with exact confidence limits.8 The statistical significance of the SMR was determined by treating the observed number of melanomas as a Poisson variable.8 The cumulative 5-year risk of developing NCM and the exact binomial confidence limits were also calculated.

RESULTS

The median age of the 160 prospectively followed patients with LCMN on entry into the study was 14 months (Table 1). Seventy-seven patients (48%) were entered into the Registry within the first year of life, and 120 (75%) within the first 5 years of life. There were 71 males and 89 females. One patient was black and all others were white. The average length of follow-up was 66.2 months (5.5 years). One hundred thirty-two of the 160 patients (82%) had their LCMN in an axial distribution (trunk, head, and/or neck). Of these, 22 (14%) were located on the head/neck. The LCMN were limited to the extremities in 28 patients (17%). Satellite nevi were present in 145 of the 160 patients (91%). The treatments for the LCMN were complete excision in 20 patients (12%) and partial removals in 73 patients (46%). Observation only was the approach in 66 (41%) and for 1 patient it was not known whether treatment had been undertaken. Of the 93 patients (58%) who had their LCMN treated, excision with direct closure was performed in 19 patients (20%), excision with graft in 20 (21%), tissue expanders followed by excision in 22 (24%), dermabrasion in 1, and 1 of the above types of surgical procedures in 16 (17%). Three patients had other types of surgical procedures, such as cryotherapy. In 12 patients (13%) the precise type of treatment rendered was not known. Since the last follow-up (1996) of the patients in the NYU-LCMN Registry, which reported that 3 patients developed melanoma, no additional patients have
TABLE 1. Study Population Statistics Age in Months: Mean SD at Entry in Study (Range; Median) 76.6 141.6 (1756; 14) 3.6 2.0 (26; 3) 3.0 2.6 (112; 2) Sex, No. (%)

developed melanomas within their LCMN or elsewhere. Thus, of the 160 prospectively followed patients, 3 patients have developed melanomas on follow-up (2%): 2 melanomas in the CNS and 1 in the retroperitoneum (Tables 1 and 2). Note that the 2 patients (case 2 and 3) with CNS melanomas (Table 2) are also included as patients with NCM (Table 3). In addition, of the 34 patients excluded from the prospective data analysis, 5 had melanoma (Table 2). Of these 5 retrospectively diagnosed melanoma cases, 3 patients had developed melanomas within their LCMN (at 36 years, 52 years, and 1 month of age, respectively), 1 patient had melanoma with an unknown primary site (diagnosed at 3 years of age) and 1 had a melanoma arising in normal skin (at 57 years of age). These 5 patients with melanomas were not included in the calculations of risk, because their melanomas were diagnosed before entry into the Registry (Table 2). In summary, 8 patients (4.1%) of the 194 in the NYU-LCMN Registry developed melanoma, of which 3 were diagnosed during prospective follow-up (Table 2). All 6 patients with the diagnosis of melanoma arising in noncutaneous sites or within the LCMN had their LCMN located on the back (posterior axis or paravetebral). The seventh melanoma patient (case 7) had developed melanoma in normal skin (nonnevus-associated skin) and his LCMN was located on an extremity. For the eighth patient, the primary site was unknown. Each of the 8 patients with melanoma had 20 satellite nevi. MRI scans were performed in 30 of the 160 prospectively followed patients (19%) in this analysis. The MRI was considered positive for NCM in 5 of these 30 patients (17%). Of these 5, 3 developed manifest NCM, ie, exhibited symptoms and/or signs of CNS involvement (Table 3; cases 2, 9, and 10). The 2 patients with MRI findings reported to be suggestive of NCM, but not exhibiting any clinical manifestations, have had follow-ups of 16 and 23 months, respectively (Table 4; cases 16 and 17). Because the results of MRI scans were not available for all patients, it is not known what proportion of patients without manifestations of NCM might have positive MRI scans. Three patients with MRI findings suggestive of NCM but with no neurological signs and/or

No. of Patients

Follow-Up in Months: Mean SD (Range; Median) 66.2 64.1 (1238; 42) 12.0 6.5 (518; 13) 33.3 38.4 (577; 18)

Age in Months at Diagnosis of Melanoma or NCM: Mean SD (Range; Median) NA 15.7 4.5 (1120; 16) 36.3 29.7 (1178; 25)

Age in Months at Time of Death From Melanoma or NCM: Mean SD (Range; Median) NA 19.3 5.7 (1324; 21) 42.0 33.3 (1387; 30)

All (n 160) Patients with melanoma (n 3)* Patients with NCM (n 4)*

M: 71 (44%) F: 89 (56%) M: 1 (33.3%) F: 2 (66.6%) M: 2 (50%) F: 2 (50%)

NA indicates not applicable; SD, standard deviation. * Two patients with CNS melanomas are included in both groups. Months of follow-up to the diagnosis of melanoma. Months of follow-up to the diagnosis of NCM.

Downloaded from pediatrics.aappublications.org at Indonesia:AAP Sponsored on August 4, 2013

ARTICLES

737

TABLE 2. Patient Case #

Melanomas in NYU-LCMN Registry Age at Entry Into the Study and (Sex) Age at Diagnosis of Melanoma Predominant Location of the Nevus Back Back Lumbosacral Back Lumbosacral Back Right leg Back Location of the Melanoma Status

Melanomas diagnosed during follow-up 1 3 mo (F) 16 mo 2 3 6 mo (M) 2 mo (F) 11 mo 20 mo

Retroperitoneum CNS CNS Back (within the nevus) (minimal deviation MM)42 Groin (within the nevus) Back (within the nevus minimal deviation MM)42 Left leg (in normal skin) Primary Unknown

Dead of noncutaneous MM at age 24 mo Dead of NCM and MM mets at age 13 mo Dead of NCM and MM mets at age 21 mo Alive at age 40 y Dead of MM after 7 mo follow-up Alive at age 69 mo Alive at age 63 y Dead of metastatic MM after 3 mo follow-up

Melanomas diagnosed before entry into registry* 4 36 y (F) 36 y 5 6 7 8 52 y (M) 12 mo (M) 57 y (M) 36 mo (F) 52 y 1 mo 57 y 36 mo

MM, indicates malignant melanoma; mets, metastasis. * Excluded from the life-table calculations. TABLE 3. Patient Case # Manifest NCM in NYU-LCMN Registry Age at Entry Into the Study and (Sex) Age at Diagnosis of NCM Predominant Location of the Nevus Lumbosacral Trunk Lumbosacral CNS Symptoms MRI Status

Manifest NCM diagnosed during follow-up 9 1 mo (M) 78 mo 2* 6 mo (M) 11 mo 3* 2 mo (F) 20 mo

10 12 mo (F) 36 mo Trunk Manifest NCM diagnosed before entry into registry 11 1 mo (M) 1 mo Trunk 12 5 mo (M) 1 mo Lower back 13 11 mo (F) 10 mo Bathing trunk 14 13 mo (M) 3 mo Bathing trunk 15 22 mo (M) 1 mo Bathing trunk

Dandy-Walker syndrome Hydrocephalus paraparesias Decreased function of the right arm Seizures, hydrocephalus Seizures, hydrocephalus Seizures Seizures Seizures Hydrocephalus

Positive Positive None Positive Positive Positive Positive Positive Postive

Died of NCM at 87 mo Died of CNS MM at 13 mo Died of CNS MM and mets at 21 mo Died of NCM at 47 mo Alive Alive Alive Alive Alive at at at at at 8y 13 mo 26 mo 20 mo 6y

MM indicates malignant melanoma. * Patients 2 and 3 same as patients in Table 2 (melanomas diagnosed during follow-up). A myelogram was performed (positive for tumor on spinal cord). Cases excluded from calculations.

symptoms were excluded from the 160 used for calculations: 2 because there was no follow-up (Table 4; cases 18 and 19) and 1 because the patient had a melanoma before being entered into the Registry database (Tables 2 and 4; case 6). In total, 38 patients (30 patients as stated above, 3 patients on Table 4 who were excluded, and 5 patients on Table 3 with NCM diagnosed retrospectively) of 194 had an MRI scan performed. In 13 of the 38 patients (34%), the MRI scan was suggestive of NCM. Eight of the 13 patients with positive MRI scans developed manifest NCM, and 3 of these 8 symptomatic patients have died of NCM. Another patient also developed manifest NCM (Table 3; case 3) but had not had an MRI performed, only a myelogram that showed tumors along the spinal cord.2 Thus, of the 160 prospectively followed patients in the NYU-LCMN Registry, 4 have developed NCM on follow-up (Table 3). All 4 patients with manifest NCM died: 2 from neurological com738

plications of NCM and 2 from melanomas in the CNS. The mean age of the 4 patients at the time of the diagnosis of NCM was 36 months, and the mean age at death was 42 months (Table 1). One of the 4 patients had Dandy-Walker syndrome. The association of NCM and Dandy-Walker syndrome is rare, with only 6 cases having been reported.9 11 The syndrome represents an uncommon developmental anomaly characterized by aplasia or hypoplasia of the cerebellar vermis, with cystic dilatation of the fourth ventricle and enlargement of the posterior fossa.9 In addition, of the 34 patients excluded from the prospective analysis, 5 patients had manifest NCM before they were entered into the NYU-LCMN Registry and were not included in the calculations of risk. Thus, 9 of the 194 patients (4.6%) of the NYULCMN Registry developed manifest NCM (Table 3). The LCMN were in posterior axial location in all 9 patients with manifest NCM (Table 3), and in the 5 patients with suggestive MRI findings of NCM but

LARGE CONGENITAL MELANOCYTIC NEVI: RISK FOR MELANOMA AND CNS MELANOSIS Downloaded from pediatrics.aappublications.org at Indonesia:AAP Sponsored on August 4, 2013

TABLE 4. Symptoms* Patient Case #

Patients in the NYU-LCMN Registry With MRI Findings Suggestive of NCM But Without Neurologic Signs and/or Age at Entry into the Study and (Sex) 1 mo (M) 3 mo (M) 12 mo (M) 1 mo (F) 26 mo (M) Predominant Location of the Nevus Upper back Upper back Back Back Lumbosacral Age When the MRI was Performed 1 mo 1 mo 7 mo 1 mo Unknown MRI Clinical Status

16 17 6 18 19

Multiple foci of increased T1 signal High signal on T1 imaging in the uncus of the right temporal lobe Suggestive Multiple foci of increased T1 signal Diffuse T1 shortening

No neurological signs and/ or symptoms at 24 mo of follow-up No neurological signs and/ or symptoms at 19 mo of follow-up No neurological signs and/ or symptoms at 69 mo of follow-up No follow-up No follow-up

* All the cases had the MRI performed before entry into the Registry. Case excluded from all calculations because had a melanoma before entry into the Registry. Cases excluded from all calculations because lack of follow-up.

without neurological manifestations (Table 4). Satellites were present in all these 14 patients. The 5-year cumulative risk of developing melanoma (Fig 1) for the 160 prospectively followed patients was 2.3% (95% confidence interval [CI]: .8 6.6). The expected number of melanomas in our study group based on the Surveillance, Epidemiology, and End Results program rates was .029, and the SMR (RR) was calculated to be 101 (95% CI: 21296; P .0001). The 5-year cumulative risk of developing NCM (Fig 1) for the 160 followed patients was 2.5% (95% CI: 0.8 7.2). The risk of developing melanoma and/or NCM (Fig 1) was 3.3% (95% CI: 1.3 8.2). The number who developed melanoma and/or NCM of all 194 patients, including those who had melanomas and/or NCM before entry into the Registry, in various categories of largest diameter of the LCMN is shown in Fig 2. Of the 15 patients who

developed melanomas and/or NCM (6, melanomas only; 7, NCM only; and 2, both melanoma and NCM), 14 had LCMN 50 cm or larger in diameter.
DISCUSSION

Fig 1. Cumulative 5-year life-table risk for developing melanoma or NCM. The cumulative 5-year life-table risks for developing melanoma (MM), or NCM, or melanoma and/or NCM are plotted. The calculations are based on 160 patients with LCMN who were followed prospectively. Note that the 2 CNS melanomas were counted twice in calculating the risk for MM and again for calculating the risk for NCM.

The increased risk for developing melanomas in patients with LCMN is well-established.1 4,1222 The reported lifetime risk ranges from 4.5% to 8.5% in various studies.1216 No additional melanomas have developed in patients in the NYU-LCMN Registry since the last report3 in 1996; thus, melanomas occurred in 3 of the 160 prospectively followed patients: 2 in the CNS and 1 in the retroperitoneum. So far no melanomas developed within the LCMN in our prospective follow-up. The life-table analysis yielded a cumulative 5-year risk for development of melanoma of 2.3% (95% CI: .8 6.6). It is possible that the surgical treatments of the LCMN in 93 of our 160 patients (58%) were in part responsible for the relatively low occurrence of melanomas within the nevi in our series. The median age of the 160 patients at entry into our study was 14 months, and the average follow-up time was 5.5 years. Because 70% of the melanomas reported in patients with LCMN are diagnosed before puberty,3 many of our patients were followed during those years of life in which such patients are at greatest risk for developing melanomas. The average follow-up (5.5 years) was 1 month longer than that in the last report,3 although the Registry has accrued 3 additional years of new cases to a total of 883 patient-years of follow-up. The reason for the small increase in average follow-up is that the large number of patients68 entered into the Registry in the last 3 years have had short follow-ups, thus reducing the average. In addition to the risk of developing melanoma, attention has recently focused on the development of NCM in patients with LCMN.2229 NCM is rare, with 100 cases reported in the world literature.30 NCM is characterized by the presence of benign and/or malignant melanocytic proliferations in the CNS in association with a LCMN or 3 or more smaller congenital melanocytic nevi.28 The majority of cases of
ARTICLES 739

Downloaded from pediatrics.aappublications.org at Indonesia:AAP Sponsored on August 4, 2013

Fig 2. Occurrence of melanoma and/or NCM by diameter of the LCMN. Occurrence of melanoma and/or NCM by largest diameter of the 194 LCMN in the NYU-LCMN Registry. There were a total of 15 patients with melanoma and/or NCM. Fourteen of these 15 patients had a LCMN 50 cm. These 14 patients with melanoma and/or NCM were distributed as follows: 5 patients with melanomas only, 7 with NCM only, and 2 with both melanoma and NCM. One of the 15 patients who had a melanoma had a LCMN 30 cm. He was a 57-year-old man with a LCMN on the right leg and the melanoma in uninvolved skin of the left leg.

manifest NCM occur early in life, usually before the age of 3 years, although there are several reports of manifest NCM starting in adulthood.27,3134 The clinical findings are mostly attributable to increased cerebrospinal fluid pressure and hydrocephalus as a result of blockage of the cisternal pathways and obliteration of arachnoid villi by the proliferating melanocytes.28,35 The prognosis of manifest NCM is poor, with 90% dying secondary to benign and/or malignant CNS melanocytosis.28 The majority of the patients die within 3 years of their initial neurological symptoms,28 70% dying before the age of 10 years.28 Approximately 40% to 50% of the patients with manifest NCM develop primary CNS melanomas.36 The risk for patients with LCMN of developing manifest NCM is not known but patients with such nevi located on the head, posterior neck, and/or paravertebral area seem to have the highest risk.24,26,28 DeDavid et al24 reviewed 289 cases of LCMN and found that 33 (12%) had developed manifest NCM. CNS melanomas occurred in 21 of the 33 patients (64%) with manifest NCM. Furthermore, all 33 patients with NCM had their large nevi in axial locations (cephalic, posterior cervical, and paravertebral), and of the 31 patients for whom the presence or absence of satellites was known, all had satellite nevi. An additional risk factor may be the diameter of the LCMN. As shown in Fig 2, 118 LCMN of the 194 (61%) had diameters of 50 cm or greater. Strikingly, 14 of the 15 patients (93%) who developed melanoma and/or NCM fell in this category. All 14 of these patients had LCMN in posterior axial locations (paravetebral) and had multiple satellite nevi. Only 1 melanoma occurred in the remaining 76 of 194 patients (39%) who had LCMN 50 cm in diameter. This 1 patient differed from the other 14 in that his melanoma developed on normal skin as opposed to within the LCMN or extracutaneous sites. In our series of 160 patients, 4 developed manifest NCM. The life-table analysis yielded a cumulative 5-year risk for NCM of 2.5% (95% CI: .8 7.2). All 4 patients with manifest NCM died: 2 of CNS melanomas and 2 of benign neural melanocytosis. It seems that, in our series, the risk for develop740

ment of fatal NCM (with or without CNS melanoma) is higher than for development of fatal non-CNS melanoma (Tables 2 and 3). In our Registry, the LCMN were at least in part in paravertebral location in all 9 patients with manifest NCM and in the 5 with nonmanifest NCM (Tables 3 and 4). Satellites were present in all 14 patients. The presence of manifest NCM is extremely important in the management of a patient with a LCMN because of its generally poor prognosis. The goal of removing all the melanocytic tissue with extensive surgical procedures would be unachievable when the melanocytic proliferation also involves the CNS. In addition, it has been suggested that in patients with manifest NCM the risk of developing melanoma is higher in the CNS than in the skin.11,28 MRI with contrast is the best diagnostic imaging modality for diagnosing NCM.37,38 T1-weighted shortening in an MRI scan suggests the presence of melanin in the CNS.37,38 However, other substances in the CNS are also known to cause T1-weighted shortening, including fat and subacute hemorrhage.30 With the advent of MRI scans, it has been possible to identify more patients who have nonmanifest NCM.25 That such patients exist was previously suggested by the incidental finding of NCM in autopsies of asymptomatic patients with LCMN who died of unrelated causes.39,40 We now recommend MRI scans for all patients with LCMN, especially those judged to be at greatest risk for the development of NCM (ie, with paravertebral, posterior cervical and/or cephalic involvement). Because of the more frequent use of MRI scans, more patients with putative nonmanifest NCM are being identified. Two patients in our prospective series of 160 (5 patients in our entire series of 194; Table 4) who had MRI scans performed had MRI findings suggestive of NCM but without any neurologic manifestations. The prevalence of nonmanifest NCM in persons with LCMN is not known.25 Frieden et al25 found brain abnormalities on MRI scans of the cerebrum in 45% of the asymptomatic patients with LCMN. Although it is not known what percentage of asymptomatic patients with MRI findings suggestive of NCM will develop manifest neurological disease, these authors

LARGE CONGENITAL MELANOCYTIC NEVI: RISK FOR MELANOMA AND CNS MELANOSIS Downloaded from pediatrics.aappublications.org at Indonesia:AAP Sponsored on August 4, 2013

believe that is unlikely that all infants with suggestive evidence of melanocytosis on MRI scans will develop symptomatic neurologic disease. It is important to clarify this issue to help determine which patients would benefit most from the surgical removal of their LCMN. Because most of the patients with manifest NCM have had neurological symptoms or signs within the first 3 years of life,28 perhaps surgical intervention for LCMN should be postponed until age 3 years for asymptomatic patients with MRI findings suggestive of NCM.24 The decision to postpone surgery is made very difficult by the fact that many of the cutaneous melanomas reported to have arisen in association with LCMN also occurred by 3 years of age.24
CONCLUSION

16.

17. 18. 19. 20.

21.

22.

Patients with LCMN are at increased risk for developing cutaneous melanoma, extracutaneous melanoma, and NCM. It seems that individuals at greatest risk are those with very large LCMN (50 cm), LCMN in axial locations, and those with multiple satellite nevi.
ACKNOWLEDGMENTS
This work was supported by the Ronald O. Perelman Department of Dermatology, NYU School of Medicine; the Joseph H. Hazen Foundation; the Niarchos Fund of the Skin Cancer Foundation; the Mary and Emanuel Rosenfeld Foundation; and the Kaplan Comprehensive Cancer Center (Cancer Center Support Core Grant 5P30-16087-18).

23. 24.

25.

26. 27. 28. 29. 30.

REFERENCES
1. Kopf AW, Bart RS, Hennessey P. Congenital nevocytic nevi and malignant melanomas. J Am Acad Dermatol. 1979;1:123130 2. Gari LM, Rivers JK, Kopf AW. Melanomas arising in large congenital nevocytic nevi: a prospective study. Pediatr Dermatol. 1988;5:151158 3. Marghoob AA, Schoenbach SP, Kopf AW, Orlow SJ, Nossa R, Bart RS. Large congenital melanocytic nevi and the risk for the development of malignant melanoma. Arch Dermatol. 1996;132:170 175 4. DeDavid M, Orlow SJ, Provost N, et al. A study of large congenital melanocytic nevi and associated malignant melanomas: review of cases in the New York University Registry and the world literature. J Am Acad Dermatol. 1997;36:409 416 5. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457 464 6. Rothman JK. Estimation of confidence limits for the cumulative probability of survival in life table analysis. J Chron Dis. 1978;31:557560 7. Ries LAG, Kosary CL, Hankey BF, Miller BA, Edwards BK, eds. SEER Cancer Statistics Review, 19731995. Bethesda, MD: National Cancer Institute; 1998 8. Sahai M, Khurshid A. Statistics in Epidemiology. Boca Raton, FL: CRC Press; 1996:197198 9. Kadonaga JN, Barkovich AJ, Edwards MSB, Frieden IJ. Neurocutaneous melanosis in association with Dandy-Walker complex. Pediatr Dermatol. 1992;9:37 43 10. Chaloupka JC, Wolf RJ, Varma PK. Neurocutaneous melanosis with the Dandy-Walker malformation: a possible rare pathoetiologic association. Neuroradiology. 1996;38:486 489 11. Green LJ, Nanda VS, Roth GM, Barr RJ. Neurocutaneous melanosis and Dandy-Walker syndrome in an infant. Int J Dermatol. 1997;36:356 359 12. Egan CL, Oliveira SA, Elenitsas R, Hanson J, Halpern AC. Cutaneous melanoma risk and phenotypic changes in large congenital nevi: a follow-up study of 46 patients. J Am Acad Dermatol. 1998;39:923932 13. Swerdlow AJ, English JSC, Qiao Z. The risk of melanoma in patients with congenital nevi: a cohort study. J Am Acad Dermatol. 1995;32: 595599 14. Ruiz-Maldonado R, Tamayo L, Laterza AM, Duran C. Giant pigmented nevi: clinical, histopathologic, and therapeutic considerations. J Pediatr. 1992;120:906 911 15. Quaba AA, Wallace AF. The incidence of malignant melanoma (0 to 15

31.

32.

33.

34.

35.

36.

37. 38.

39.

40. 41.

42.

years of age) arising in large congenital nevocellular nevi. Plast Reconstr Surg. 1986;78:174 179 Lorentzen M, Pers M, Bretteville-Jensen G. The incidence of malignant transformation in giant pigmented nevi. Scand J Plast Reconstr Surg. 1977;11:163167 Lanier VC, Pickrell KL, Georgiade NG. Congenital giant nevi: clinical and pathological considerations. Plast Reconstr Surg. 1976;58:48 54 Management of congenital nevocytic nevi. Pediatr Dermatol 1984;2: 14356 Management of congenital melanocytic nevi: a decade later. Pediatr Dermatol. 1996;13:321340 Rigel DS, Friedman RJ, Kopf AW, Rogers GS, Heilman ER. Precursors of malignant melanoma: problems in computing the risk of malignant melanoma arising in dysplastic and congenital nevocytic nevi. Dermatol Clin. 1985;3:361365 Rhodes AR, Wood WC, Sober AJ, Mihm MC. Nonepidermal origin of malignant melanoma associated with giant congenital nevocellular nevus. Plast Reconstr Surg. 1981;67:782790 Ruiz-Maldonado R, Barona-Mazuera M, Hidalgo-Galvan LR, et al. Giant congenital melanocytic nevi, neurocutaneous melanosis and neurological alterations. Dermatology. 1997;195:125128 Cruz MA, Cho ES, Schwartz RA, Janniger CK. Congenital neurocutaneous melanosis. Cutis. 1997;60:178 181 DeDavid M, Orlow SJ, Provost N, et al. Neurocutaneous melanosis: clinical features of large congenital melanocytic nevi in patients with manifest central nervous system melanosis. J Am Acad Dermatol. 1996; 35:529 538 Frieden IJ, Williams ML, Barkovich AJ. Giant congenital melanocytic nevi: brain magnetic resonance findings in neurologically asymptomatic children. J Am Acad Dermatol. 1994;31:423 429 Sandsmark M, Eskelan G, Skullerud K, Abyholm F. Neurocutaneous melanosis. Scand J Plast Reconstr Hand Surg. 1994;28:151154 Vadoud-Seyedi R, Heenen M. Neurocutaneous melanosis. Dermatology. 1994;188:62 65 Kadonaga JN, Frieden IJ. Neurocutaneous melanosis: definition and review of the literature. J Am Acad Dermatol. 1991;24:747755 Reyes-Mugica M, Chou P, Byrd S, et al. Nevomelanocytic proliferations in the central nervous system of children. Cancer. 1993;72:22772285 Poe LB, Roitberg D, Galyon DD. Neurocutaneous melanosis presenting as an intradural mass of the cervical canal: magnetic resonance features and the presence of melanin as a clue to diagnosis: case report. Neurosurgery. 1994;35:741743 Juang JM, Silva AC, Pires MC, Valente NY, Sittart JA. Neurocutaneous melanosis: case report of a malignant melanoma of the central nervous system. Rev Assoc Med Bras. 1998;44:50 52 Frisoni GB, Gasparotti R, Di Monda V. Giant congenital nevus and chronic progressive ascending hemiparesis (Mills syndrome): report of a case. Ital J Neurol Sci. 1992;13:259 263 Barbieri F, Santangelo R, Indaco A, De Furio M, Buscaino GA. Neurocutaneous melanosis, neurofibromatosis and spinal meningioma: an unusual association. Acta Neurol (Napoli). 1990;12:115121 Kasantikul V, Shuangtshoti S, Pattanaruenglai A, Kaoroptham S. Intraspinal melanotic arachnoid cyst and lipoma in neurocutaneous melanosis. Surg Neurol. 1989;31:138 141 Reed WB, Becker SW, Becker SW Jr, Nickel WR. Clinical studies: giant pigmented nevi, melanoma, and leptomeningeal melanocytosis: a clinical and histopathological study. Arch Dermatol. 1965;91:100 119 Rhodes RE, Friedman HS, Hatten HP, Hockenberger B, Oakes WJ, Tomita T. Contrast-enhanced MR imaging of neurocutaneous melanosis. AJNR Am J Neuroradiol. 1991;12:380 382 Barkovich AJ, Frieden IJ, Williams ML. MR of neurocutaneous melanosis. AJNR Am J Neuroradiol. 1994;15:859 867 Byrd SE, Darling CF, Tomita T, Chou P, Leon GA, Radkowski MA. MR imaging of symptomatic neurocutaneous melanosis in children. Pediatr Radiol. 1997;27:39 44 Slaughter JC, Hardman JM, Kempe LG, Earle KM. Neurocutaneous melanosis and leptomeningeal melanosis in children. Arch Pathol. 1969; 88:298 304 Pascual-Castroviejo I. Neurocutaneous melanosis. In: Gomez M, ed. Neurocutaneous Diseases. Boston, MA: Butterworth; 1987:329 334 Barnhill RL, Mihm MC. Histopathology of malignant melanoma and its precursor lesions. In: Balch CM, Houghton AN, Milton GW, Sober AJ, Soong S, eds. Cutaneous Melanoma. 2nd ed. Philadelphia, PA: JB Lippincott Company; 1992:249 250 Balch CM, Houghton AN, Milton GW, Sober AJ, Soong S-J, eds. Cutaneous Melanoma. Philadelphia, PA: JP Lippincott Company; 1992: 249 250

Downloaded from pediatrics.aappublications.org at Indonesia:AAP Sponsored on August 4, 2013

ARTICLES

741

Large Congenital Melanocytic Nevi and the Risk for Development of Malignant Melanoma and Neurocutaneous Melanocytosis Flavia V. Bittencourt, Ashfaq A. Marghoob, Alfred W. Kopf, Karen L. Koenig and Robert S. Bart Pediatrics 2000;106;736
Updated Information & Services References including high resolution figures, can be found at: http://pediatrics.aappublications.org/content/106/4/736.full.ht ml This article cites 35 articles, 1 of which can be accessed free at: http://pediatrics.aappublications.org/content/106/4/736.full.ht ml#ref-list-1 This article has been cited by 4 HighWire-hosted articles: http://pediatrics.aappublications.org/content/106/4/736.full.ht ml#related-urls This article, along with others on similar topics, appears in the following collection(s): Dermatology http://pediatrics.aappublications.org/cgi/collection/dermatolog y_sub Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://pediatrics.aappublications.org/site/misc/Permissions.xht ml Information about ordering reprints can be found online: http://pediatrics.aappublications.org/site/misc/reprints.xhtml

Citations

Subspecialty Collections

Permissions & Licensing

Reprints

PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. PEDIATRICS is owned, published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007. Copyright 2000 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

Downloaded from pediatrics.aappublications.org at Indonesia:AAP Sponsored on August 4, 2013