malignant melanoma in a black child: predisposing precursors and

Malignant Melanoma in a Black Child:Predisposing Precursors and ManagementOlanrewaju T. Adedoyin, MB, BS, FWACP (Paed.); Abdul-Wahab B.R. Johnson, MB,BS, FWACP(Paed.); Ayodele 1. Ojuawo, MB, BS, FMCPaed.; Enoch A.O. Afolayan, MB, BS, FMCPath; andKayode A. Adeniji, MB, ChB, FMCPathllorin, Nigeria

Malignant melanoma (MM) remains a pediatric rarity world-wide, but perhaps more so in black Africans. To the best ofour knowledge, the current report of MM in a two-and-a-half-year-old Nigerian who had a pre-existing congenitalgiant hairy nevus is probably the first (in an accessible litera-ture) in a black African child. Primary neoplastic transforma-tion and metastatic spread were suggested by the appear-ance of multiple swellings over the "garment' precursornevus at the posterior trunk, multiple ipsilateral axillary nodalenlargement, and fresh occipital swellings postadmission.Smaller-sized hyperpigmented lesions with irregular, nonlob-ulated, and frequently hairy surfaces were also discernibleover the upper and lower extremities, but the face, anteriortrunk, and mucosal surfaces were relatively spared. A diag-nosis of MM was confirmed by the subsequent histopatho-logic findings from the fine-needle aspirate and biopsyspecimens. Chemotherapy was initiated but was truncatedshortly after by parent-pressured discharge.

Despite the rarity of MM in a tropical African setting wheremanagement options are few, the current case under-scores the need for a high clinical index of diagnostic suspi-cion, an eardy pursuit of investigative confirmotion, and pro-phylactic excision in children with the predisposing skinlesions, like congenital giant hairy nevus. An expounded dis-course of the possible precursors and management optionsof MM is provided. We emphasize the need for institutionalcost subsidy for anticancer care in tropical children.

Key words: pnrmary malignant melanoma * risk factors agiant hairy nevus

© 2004. From Department of Pediatrcs and Child Health (Adedoyin, John-son, Ojuawo) and Department of Pathology (Afolayan, Adeniji), University ofllorin Teaching Hospital, llorin, Nigeria. Send correspondence and reprintrequests for J NatI Med Assoc. 2004;96:1368-1373 to: Abdul-Wahab B.R.Johnson, Professor of Pediatrcs, Department of Pediatrcs & Child Health,University of llorn, PMB 1515, llorin, Kwara State, Nigera; fax: +234 31 220020;e-mail: [email protected]

INTRODUCTIONWhereas the overall incidence of malignant

melanoma (MM) has surged by 150% in the last 30years,' the pediatric morbidity burden remains lowwith 4.2 cases per million in persons younger than 20years. Most cases occur in whites, and only 0.30.5%of cases are diagnosed before the age of 13 years.",3Indeed, MM accounts for only 1-3% of all pediatricmalignancies.' Whereas a recognizable congenitalnevocellular nevus (NCN) constitutes an importantpredisposing lesion for malignant transformation ininfancy and early childhood, a potential precursor ofMM in adolescents is the BK mole syndrome, or dys-plastic melanocytic nevus (DMN).145 The averagenumber ofacquired pigmented nevi, or moles per per-son, is comparatively fewer in black Africans com-pared with that of whites,6-8 and this may partlyexplain the correspondingly rarer incidence of pri-mary MM in black Afiicans. Against the backgroundof the scorching tropical sunshine of sub-SaharanAfrica, the local rarity ofMM and other cutaneousmalignancies may well be due to a relative immunityofthe pigmented skin ofblack Africans to the noxiouseffects of solar "inducers" of malignant transforma-tion. Because of their distinct rarity, a low index ofclinical suspicion, as well as the paucity of investiga-tive tools, previous reports on MMs in the Africanchild hardly existed in accessible literature. Besides arecent report of three Nigerian siblings in whomMMunderstandably coexisted with a pre-existing xeroder-ma pigmentosum,9 the present report to the best ofourknowledge, is probably the first of a primary MM inan indigenous black African child. The authors' intentis to use this report to sensitize clinicians on the diag-nostic reality ofMM in the black African child, pro-vide an overview of the current concepts on the high-risk lesions/clinical scenarios, as well as the possiblemanagement options.

CASE REPORTA.O., a female Nigerian of black racial parentage

was two-and-a-half years old at presentation. Follow-

1368 JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION VOL. 96, NO. 10, OCTOBER 2004

MALIGNANT MELANOMA IN A CHILD & LITERATURE REVIEW

ing an earlier referral from a private health institution,consultation was sought at the Emergency PediatricUnit of the University of Ilorin Teaching Hospital,Ilorin (UITH), a tertiary care facility located in northcentral Nigeria. The presenting features included theappearance of multiple swellings at the upper backand the left axilla in the preceding five months. Pre-ceding the (sudden) appearance of these swellingswere several black/hyperpigmented areas on the trunkand extremities, including the palms and soles. Someof these hyperpigmented lesions had been presentsince birth, with a few of these developing noticeablehair growth as early as when the child was about 12months. Significant events and "therapeutic" inter-ventions in the two months preceding her presentationat UITH included a fairly rapid increase in the sizesand number of the aforementioned swellings, thelocal application of topical home remedies (includingshea butter and palm oil), an earlier misdiagnosis ofthe axillary swelling as a "giant boil" (finruncle), andconsequently an incision followed by antimicrobialtherapy. Subsequently, there was purulent dischargefrom the same lesion, as well as noticeable sponta-neous ulceration and bleeding in some of the othermasses. Systemic symptoms at the time of referralincluded some weight loss and a progressive loss ofappetite. The possibility of a superficial lymphadeni-tis of tuberculous etiology was considered remote,especially on account of a satisfactory immunizationrecord (BCG inclusive), the significant absence ofpreceding respiratory symptoms, and indeed, theemphatic denial of a positive history of contact. Also,neither the only eight-year-old sibling nor the parentshad similar skin lesions.

The relevant physical findings at presentationincluded an extensive hyperpigmented skin area

Figure 1. Photographs of the two-and-a-halfyear old child showing the anatomic locationsand sizes of the hairy nevi and the overlyingtumor masses. Note the "garment" size of theprecursor hairy nevus over the posterior trunkand the associated hyperkeratosis (rightpicture). The huge ulcerative mass at the leftaxilla is more clearly shown in the close-uppicture on the left.

A B

over the posterior trunk, extending inferiorly as faras the posterior superior iliac spine, anteriorly to theanterior axillary line on the right, and the mid-axil-lary line on the left (Figure 1 A and B ). Elsewhere,the anterior trunk, the face, as well as the mucosalsurfaces of the mouth and nostrils, were relativelyfree of the lesions. Varying sizes of other hyperpig-mented nevi were also apparent on the upperextremities, anterolateral aspects of the thighs, aswell as the dorsal surfaces of the legs and feet (Fig-ure 2). Some of the lesions, especially the garmentnevus at the back and the largest lesion over theanterior left thigh, were visibly hairy, with areas ofhyperkeratosis. Particularly striking were four mass-es, ranging in sizes from -3 to 10 cm, situated overthe giant nevus at the back (Figure 1B), and a largeleft axillary swelling (presumably lymph node sec-ondaries) measuring 10 cm in its longest diameter.Whereas the axillary mass was fairly firmly attachedto the deeper tissues/structures, those at the backwere devoid of a similar characteristic. Areas of skindiscoloration and prominent superficial vessels werealso discernible over the larger masses at the backand left axilla. Over the four-week duration ofadmission, these lesions (some of which bled spon-taneously), had grown significantly bigger, with newones becoming apparent over the posterior trunk andthe occipital scalp. Postadmission, serial weightrecording suggested progressive wasting, and lowermotor neuron facial (seventh) nerve palsy was sub-sequently demonstrable (Figure 3).

Pathologic FindingsA fine-needle aspirate of the axillary mass was

done. This was reportedly consistent with a malig-nant lymph node infiltration showing "very cellular"smears with large pleomorphic cells and hyperchro-matic nuclei. A pathologic diagnosis of axillarylymph node metastasis was made, with a strong sug-gestion of a subsequent biopsy of the adjoining skinlesion for further diagnostic clarification and identi-fication of the tissue of origin. An excision (skin)biopsy of the adjoining lesion over the garment

Figure 2. A close-upphotograph of anotherfgiant hairy nevus situatedin the low-risk location ofthe thigh (left side) andseveral other small neviover both lowerextremities; none of thenevi had palpable tumormasses or significantlyenlarged regional lymphnodes.

JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION VOL. 96, NO. 10, OCTOBER 2004 1369


nevus was eventually carried out after someinevitable delay, processed, examined, and reportedseparately by two consultant histopathologists(EAOA and KAA). Their individual findings weresubsequently reconciled at a joint clinicopathologi-cal review. As shown in Figure 4, findings includedmelanin pigments in the superficial dermis, alongwith nests and alveolar patterns of proliferatingmelanocytes arranged around blood vessels in retic-ular dermis. The morphology of the melanocyteswas reported as "biphasic." While some of the cellswere polygonal or epithelioid with prominent nucle-oli, others were spindle-shaped with ovoid nuclei.These findings and those from an earlier fine-needleaspirate ofthe axillary mass were considered consis-tent with a diagnosis of MM with axillary nodalmetastasis.

In the absence of facilities for exploring "hi-tech,"but otherwise potentially more informative imagingmodalities, like lymphoscintigraphy, magnetic reso-nance imaging (MRI), or computerized tomography(CT) scan of the brain, only a plain skull radiographcould be done. Predictably, this proved unrevealingexcept for a small occipital soft tissue mass. Addition-ally, the peripheral blood film showed a total whitecell count (6.8 x 109/L), mild/moderate anemia(packed cell volume of 27%), and thrombocytopenia(platelet count of3 1.0 X 109/L).

Treatment and OutcomeFollowing the diagnosis, chemotherapy was initi-

ated with two subsequent intravenous doses of vin-cristine and cyclophosphamide. Unfortunately, theparents subsequently cited the prohibitive costs ofthe chemotherapeutic agents as the major reason fortheir preference for discharge against medicaladvice, so that they could pursue traditional/nativetreatment. Despite assuring them of our willingness

to take the child back shouldthey reconsider their deci-sion, they did not show up in

Figure 3. Close-up photographof the face,showing featuresof a facial(seventh cranial)nerve palsy

S~~~~~~~~~~~~~~~~~~~r~~~~~~~~~~~~~~~~~~~

Figure 4. Photomicrograph of the skin biopsyspecimen taken from the axilla and from whicha diagnosis of malignant melanoma was made.Although some details were lost tophotographicpreparation, a"biphasic" pattern ofthe malignant cells isshown; some of the F_cells are epithelioidwith round to oval ,nuclei (right side offield), while some others have spindle-shapednuclei (hematoxylin and eosin X 512).

the subsequent nine months, and it is our presump-tion that the child has long succumbed to the disease.

DISCUSSION ANDLITERATURE REVIEW

Whereas the frequently benign juvenile melanomais not an unusual lesion in children,4'5 MM hasremained a rare affliction of infants and young chil-dren of all races.24"0 In indigenous black African chil-dren, MM is probably even rarer still. The 22 cases(all Caucasians), reported by Scalzo et al." over a 33-year period in a temperate setting were aged mostly12-15 years, while a female gender skewing wasidentified in an earlier Australian series.'2 The currentcase of MM in an indigenous Nigerian African isremarkable not only for the unusual age oftwo-and-a-half years but also for the black racial background.Indeed, we are not aware of an earlier case ofprimaryMM in our tertiary health facility (since inceptionsome 22 years ago), or one emanating from an indige-nous African child of the Negro stock. AlthoughChamlin and Williams'3 had earlier linked the occur-rence ofmelanoma to sun sensitivity, the abundanceof solar rays in the tropical setting would make therarity of primary MM (and indeed, other skin malig-nancies), a counterintuitive reality. It is our view thatthe abundance ofmelanin pigment in the heavily pig-mented skin of most black Africans may indeed beprotective against solar radiation-induced skin dam-age. That the latter is a common antecedent event inthe evolution ofMM is well recognized.4An early surgical excision of cutaneous precursor

lesions remains a valid management strategy ofMM. Hence, a discourse ofMM and managementwould be incomplete without an overview of suchprecursors. A pigmented precursor lesion is usuallyfound in 15-85% of pediatric MM.14"5'14 CongenitalNCN, the precursor lesion in our patient, is amelanocyte-derived hamartoma, appearing betweenthe 10th week and sixth month ofprenatal life.4 Witha freauencv of one in every 20.000 newborns.",'5

giant congenital NCN (videinfra) remains a rarity, butits lifetime risk of malignantdegeneration has been esti-mated to be approximately5-10%.1,16 Indeed, up to 33%or more of prepubertal MMwould have a pre-existinggiant congenital NCN.4''17The sizes of congenitalNCN vary widely. A nevusof <3-4 cm in diameter isregarded as small." 4"15Lesions between 3 cm and10 cm are regarded as inter-



mediate, while the terms "giant" or "garment"lesions are reserved for larger lesions, especiallythose with a diameter above 20 cm and covering amajor anatomic area of the body (most commonlythe posterior trunk)."' 6'18"19 In the current case, theprecursor lesion (which covered an extensive area ofthe back and had visible hair growth) was clearlyabove 10 cm in diameter. Hence, the descriptiveterm of a "garment" hairy nevus was consideredmost appropriate. Despite the therapeutic value ofearly detection of a malignant degeneration in suchlesions, such a diagnosis is rarely possible in chil-dren below three years.4 This is partly attributable tothe tendency of such lesions to arise from deeperlocations in the reticular dermis, subcutaneous fat,or even a nonepidermal origin.'6" 9 Even in superfi-cial lesions with secondaries in the nodal basins, orthe leptomeninges, the diagnosis may still be missedbecause of the frequent absence of gross morpho-logical changes like (surface) lobulation, ulceration,or deeper pigmentation.'6"'9'20 Indeed, it is our viewthat the complicating facial nerve palsy in the pres-ent case could be attributed to an undiagnosed lep-tomeningeal, or brain parenchymal seedlings withnevus cells, which may sometimes result in raisedintracranial pressure, seizures, and motor deficits.'However, the local absence of appropriate investiga-tive tools like MRI for detecting such lep-tomeningeal melanosis' constituted a formidablediagnostic limitation in our setting. Furthermore, thereferral misdiagnosis of the axillary metastasis asfurunculosis in the current child would have beenaverted if there were local facilities for other rele-vant "smart" imaging modalities like lymphoscintig-raphy/lymph node mapping and CT scan. In view ofthese diagnostic limitations, preventive excision ofhigh-risk premalignant lesions is conceivably a moreattractive management option in resource-poorcountries. Although opinions differ regarding thepotential for malignant transformation in small con-genital NCN (<3 cm in diameter, or one that can beexcised without needing a skin flap or graft to closethe defect),4 and the normal acquiredNCN (specklesof tiny tan/medium brown papules, which distort theskin surface slightly and are not apparent at birth),4prophylactic excision is hardly necessary becauseassociated prepubertal MM is rare."4 Hence, unlessthere are gross morphological changes (like surfacelobulation, irregular, or very dark pigmentation, andulceration/bleeding), small congenital NCN arepreferably monitored closely until the 10th birthday,when preventive excision may be carried out.4Although the trigger agent of neoplastic transforma-tion in a precursor lesion may not be apparent,2'antecedent solar or hormonal exposure,22'23 or rarelya coexisting blistering disease have been reported.24

Given the investigative/management inadequacies inthe current case, and the prevailing higher risk ofsolar radiation exposure in sub-Saharan Africa(where year-round sunshine subsists), a policy ofearly prophylactic excision of high-risk precursorlesions remains an attractive strategy for decreasingMM morbidity and mortality in tropical Africa.

Another recognizable lesion with a distinctpropensity for contiguous transformation to MM inthe older child is the DMN, BK mole, or familialmole-melanoma syndrome."4'5'25-27DMN is rarer thancongenital NCN, and despite a dominant pattern ofinheritance, the phenotype rarely manifests beforepuberty.4'5'25'26 The characteristically larger lesions ofDMN (5-10 cm in diameter) are haphazardly coloredmacules and papules with irregular or ill-definededges.5 Unlike the present case with a "garment"nevus over the posterior trunk, DMN lesions are typi-cally located over the scalp, the "horse collar" areas ofthe torso, and the buttocks.45 Although, MM-pronekindreds with DMN are particularly sensitive to thenoxious effects of (solar) ultraviolet radiation,' thepubertal expression of this inherited lesion has alsobeen ascribed to the effects of hormonal inducers andaltered host immunity.4'5 Against the background ofabundant opportunities for solar exposure, the rarityof DMN, even amongst adult Nigerians (personalcommunication, Dr. A.O. George, consultant derma-tologist, University College Hospital, Ibadan, Nige-ria), is rather counterintuitive and may also be con-ceivably attributed to a possible protective effect ofthe abundant melanin pigment in the African Negro.Sunscreen, protective clothing, avoidance of intensesolar exposure, and indeed, regular dermatologicalevaluation (for early detection of MM) had earlierbeen suggested as preventive measures in MM-proneDMN kindreds.4527 The local relevance of these meas-ures in the low-risk tropical African child with anequally important need for solar generation of vita-min-D precursors remains to be seen.

Other pigmented nevi in children and adolescentswhich can be confused with high-risk precursorlesions ofMM include the NCN, dermal melanosis(nevi of Ota and Ito), epithelial and Becker nevi. "4Becker nevus (otherwise known as Becker melanosisor pigmented hairy epidermal nevus) is a benignlesion with no risk of malignant transformation.Lesions evolve into irregular hyperpigmented plaquesover the upper arm and torso. On account ofthe asso-ciated local hypertrichosis,4 this lesion can be con-fused with congenital hairy NCN, which precededprimary MM in our patient. Similarly, despite itsbenign nature, the deceptively malignant histologicalcharacteristics of Spitz nevus (spindle and epithelioidcell nevus, or juveline melanoma)5 would make it asource of misdiagnosis. These pink, firm, smooth-



surfaced, dome-shaped hairless papules are seen asgrouped lesions (usually <3 cm in size) mostly on theface, shoulder, and upper limb.' Xeroderma pigmen-tosum (XP) is another rare disorder with a distinctpropensity for malignant transformation to MM,basal, or squamous-cell carcinoma.459 This autosomalrecessive disorder is characterized by a defectivemechanism for the cellular repair of DNA damagefollowing solar exposure and, hence, the associatedphotosensitivity. For children with such a high-risklesion in a tropical setting, the need for regular evalu-ation and solar-protective clothing is self-evident.

An ideal strategy for managing metastatic MM isyet to evolve, but significant progress has beenrecorded in the last few years in early detection andtreatment ofprimary cases.4'5 However, when there isa high index of clinical suspicion in resource-poortropical countries, early diagnosis in those with theprecursor lesions, and prophylactic surgical excisionremain the sensible preemptive management strate-gies. Early dermabrasion had been suggested in chil-dren with giant congenital NCN,28 but MM may stillarise from a deeper dermal location.4 Also, modemapplications of molecular biology, like reverse tran-scriptase-polymerase chain reaction (RT-PCR)assays and double-round PCR, have recently proveduseful in detecting the melanocyte-specific tyrosi-nase in messenger RNA of sentinel nodemicrometastasis.29 The result is a more accurate pre-diction of lymph node status (the single most impor-tant determinant ofrecurrence and/or survival29) and,hence, disease staging, prognosis, and therapeuticresponse prediction.30 Preoperative lymphoscintigra-phy has also proved an accurate imaging modalityfor defining cutaneous lymph flow, and identifyingnodal basin(s) at the highest risk of metastaticspread.29'3' Exploring this investigation was clearlyprecluded in our patient despite the high-riskanatomic location of the primary lesion over theposterior trunk. The latter location constitutes one ofthe so-called "TANS regions" (i.e. Thorax, upperArms, Neck, and Scalp), reportedly associated witha higher propensity for early fatality.3' For primaryMM with low-risk features (of early death) liketumor thickness of 1 mm or less, and a location atthe lower extremities, hands, and face,4 32 the recom-mendation is surgical excision with a margin of <1mm.33 A wide margin excision of 1-3 cm (dependingon tumor depth and location) possibly followed byskin grafting is recommended forMM with interme-diate thickness of 1.1-2 mm.14 Lymphoscintigraphy,elective lymph node dissection (ELND), and micro-scopic confirmation are also indicated in such cases(stages I and JJ).3s On the other hand, and except foryoung infants, the treatment regimens for childrenwith advanced metastatic disease (stages III and IV),

high-risk anatomic location(s), and ulcerativelesions are based on adult models.5

Chemotherapeutic regimens in MM with a highrisk of early death include regional limb perfusionwith melphalan; for children <12 years, this regimenhas been associated with a 93% five-year survivalrate.36 Dacarbazine as a single, systemically admin-istered agent has been shown to produce a responserate of approximately 10-20%.37 38 Such responsesare usually not durable.38 The combination of dacar-bazine with cisplatin, carmustine, and tamoxifen(Darmouth regimen) may induce a slightly bettertumor response in stage-IV disease, but the toxicitycosts would make it an unattractive option to dacar-bazine alone.38'39 On the other hand, combinationtherapy with interferon-alpha-2b (intron-A) andinterleukin-2 (IL-2) has also proved useful inadvanced MM with a response rate of 50-60% andcomplete responses in 20% of patients.38'39'40 Up to50% of the latter would have a durable response.38However, unlike the expectation in high-risk MM inadults, the traditional triple-drug combination ofcyclophosphamide, vincristine, and dactinomycin, isalso associated with good response and survival sta-tistics in children.41 For our patient, only cyclophos-phamide and vincristine were available. Even then,the prohibitive cost, and perhaps a parental percep-tion of hopelessness led to their opting for dischargeagainst medical advice. Finally, in addition to inter-feron-alpha, other immunotherapeutic tools (likevaccines and monoclonal antibodies) have proveduseful as adjuvant therapy in high-risk patients38'42'43but have little effect in advanced disease.37 However,the combination of interleukin-2, with or withouttumor-infiltrating lymphocytes (reputed for recog-nizing specific tumor antigens)44'45 and indeed,genetic modification ofthese cells (using retrovirus-mediated gene transduction for example),5 constitutepromising tools in advanced disease. Unfortunately,for the foreseeable future, these newer therapeuticfrontiers will remain unexplored in resource-poortropical countries. Nevertheless, early identificationand prophylactic removal of high-risk precursors ofMM, and the provision of institutional subsidy foranticancer management presently constitute thepractical strategies for achieving better disease out-comes in tropical Africa.

ACKNOWLEDGEMENTSWe acknowledge the contributions of the pedi-

atric surgical team in helping to obtain the requiredbiopsy specimen. To the entire nursing and pediatricmedical team of Ward Three (Pediatric MedicalWard), we thank you all for your compassion anddedication (despite the inevitable limitations) in thecourse of managing this child. Finally, the corre-



sponding author is indebted to our consultant plasticsurgeon, Dr. Ismail Adigun, FWACS, for his assis-tance in the course of the literature review and forperusing the revised manuscript with suggestions.

REFERENCES1. Damstadt GL, Sidsbury R. Cutaneous Nevi. In: Behrman RE, Kliegman RM,Jenson HB, eds. Nelson Textbook of Pediatrics (17th ed). Philadelphia:Saunders Co., 2004:2172-2176.2. Herzog CE. Rare tumors. In: Behrman RE, Kliegman RM, Jenson HB, eds.Nelson Textbook of Pediatrcs (17th ed). Philadelphia: Saunders Co., 2004:1726-1727.3. Boddie Jr AW, Smith JL, McBride CM. Malignant melanomas in childrenand young adults: effect of diagnostic crtera on staging and end results.South Med J. 1 978;71 :1074-1078.4. Rhodes AR. Pigmented birthmarks and precursor melanocytic lesions ofcutaneous melanoma identifiable in childhood. Ped Clin N Am. 1983;3:435-463.5. Ceballos PI, Ruiz-Maldonado R, Mihm Jr MC. Melanoma in children. NEng J Med. 1995;332:656-662.6. Pack GT, Lenson N, Gerber DM. Regional distribution of moles. Arch Surg.1 952;65: 862-870.7. Pack GT, Davis J. The relation of race and complexion to the incidenceof moles and melanomas. Ann N YAcad Sci. 1963;100:719-742.8. Lewis MG, Johnson K. The incidence and distrbution of pigmented neviin Ugandan Afrcans. BrJ Dermatol. 1968;80:362-366.9. Ahmed H, Hassan RY, Pindiga HU. Xeroderma pigmentosum in three con-secutive Nigerian siblings: observations on oculo-cutaneous manifesta-tions. BrJ Opthalmol. 2001;85:1 10-1 1 1.10. Barnhill RL, Flottwe TJ, Fleishli M, et al. Cutaneous melanoma and atypi-cal Spitz tumors in childhood. Cancer. 1995;76:1833-1845.11. Scalzo DA, Hida CA, Toth G, et al. Childhood melanoma: a clinico-pathological study of 22 cases. Melanoma Res. 1997; 7:63-68.12. McWhirter WR, Dobson C. Childhood melanoma in Australia. World JSurg. 1995;1 9:334-336.13. Chamlin SL, Williams ML. Moles and melanoma. Curr Opin Pediatr. 1998;10:399-404.14. Elder DE, Greene MH, Bondi EE, et al. Acquired melanocytic nevi andmelanoma. The dysplastic nevus syndrome. In: Ackerman AB, ed. Patholo-gy of malignant melanoma. New York: Mason Publishing USA, Inc.1981:185-215.15. Castilla EE, DaGraca Dutra M, Oroli-Parreiras IM. Epidemiology of con-genital pigmented nevi; incidence rates and relative frequencies. Br J Der-matol. 1981;104:307-315.16. Rhodes AR, Wood WC, Sober AJ, et al. Nonepidermal origin of malig-nant melanoma associated with giant congenital nevocellular nevus. PlastReconstrSurg. 1981;67:782-790.17. Trozak DJ, Rowland WD, Hu F. Metastatic malignant melanoma in pre-pubertal children. Pediatrics. 1975;55:191-204.18. Kopf AW, Bart RS, Hennessey P. Congenital nevocytic nevi and malig-nant melanoma. J Am Acad Dermatol. 1979;1 :123-130.19. Reed WB, Becker Sr SW, Becker Jr SW, et al. Giant pigmented nevi,melanoma and leptomeningeal melanocytosis. Arch Dermatol. 1965;91:100-119.20. Sober AJ, Fitzpatrick TB, Mihm MC, et al. Eady recognition of cutaneousmelanoma JAMA. 1979; 242:2795- 2799.21. Coskey RJ. Eruptive nevi. Arch Dermatol. 1975;1 1 1:1658.22. Goldman L, Richfield DF. Effect of corticotropin and cortisone on thedevelopment and progress of pigmented nevi. JAMA. 1951;1 147:941-943.23. Kopf AW, Lazar M, Bart RS, et al. Prevalence of nevocytic nevi on lateraland medial aspects of arms. J Dermatol Surg Oncol. 1978;4:153-158.24. Soltani K, Bernstein JE, Lorinez AL. Eruptive nevocytic nevi following ery-thema multiforme. J Am Acad Dermatol. 1979;1:503-505.

25. Clark WH, Reimer RR, Greene M, et al. Origin of familial malignantmelanomas from heritable melanocytic lesions: the BK mole syndrome."Arch Dermatol. 1978;1 14:732-738.26. Reimer RR, Clark WH, Greene MH, et al. Precursor lesions in familialmelanoma: a new genetic preneoplastic syndrome. JAMA. 1978;239:744-746.27. Rhodes AR, Sober AJ, Melski JW, et al. Possible risk factors for primarycutaneous malignant melanoma. Clin Res. 1 980;28:252A (Abtr.).28. Johnson HA. Permanent removal of pigmentation from giant hairy nae-vi by dermabrasion in eady life. BrJ Plast Surg. 1977;30:321-323.29. Reintgen D, Balch CM, Kirkwood J, et al. Recent advances in the careof the patient with malignant melanoma. Ann Surg. 1997;225:1-14.30. Reintgen DS, Albertini J, Berman C, et al. Accurate nodal staging ofmalignant melanoma: cancer control. J Moffitt Cancer Center. 1995;2:405-414.31. McCarthy WH, Uren RF, Thompson J. How lymphangiography aidsmelanoma treatment. Skin Cancer Found J. 1996;14:32-35.32. Garbe C, Buttner P, Bertz J, et al. Pnmary cutaneous melanoma: prog-nostic classification of anatomic location. Cancer. 1995;75:43-49.33. Veronesi U, Cascinelli N. Narrow excision (1-cm margin): a safe proce-dure for thin cutaneous melanoma. Arch Surg. 1991;126:438-441.34. Ho VC, Sober AJ. Therapy for cutaneous melanoma: an update. J AmAcad Dermatol. 1990;22:159-176.35. Balch CM, Soong S-J, Bartollucci A, et al. Efficacy of an elective region-al lymph node dissection of 1-4 mm thick melanomas for patients 60 yearsof age or younger. Ann Surg. 1996;224:255-266.36. Baas PC, Hoekstra HJ, Schraffordt Koops H, et al. Hyperthermic isolatedregional perfusion in the treatment of extremity melanoma in children andadolescents. Cancer. 1989;63:199-203.37. Boddie Jr AW, Cangir A. Adjuvant and neoadjuvant chemotherapywith dacarbazine in high-nsk childhood melanoma. Cancer. 1987;60:1720-1723.38. Anderson CM, Buzaid AC, Legha SS. Systemic treatments for advancedcutaneous melanoma. Oncology (Hurtingt.). 1995;9:1149-1158.39. Chapman PB, Einhorn LH, Meyers ML, et al. Phase-lIl multicenter ran-domized tnal of the Darmouth regimen versus darcarbazin in patients withmetastatic melanoma. J Clin Oncol. 1999;17:2745-2751.40. Falkson Cl, Falkson G, Falkson HC. Improved results with the addition ofinterferon alpha-2b to dacarbazine in the treatment of patients withmetastatic malignant melanoma. J Clin Oncol. 1991;9:1403-1408.41. Hayes FA, Green AA. Malignant melanoma in childhood: clinicalcourse and response to chemotherapy. J Clin Oncol. 1984;2:1229-1234.42. Mays SR, Nelson BR. Current therapy of cutaneous melanoma. Cutis.1999;63: 293-298.43. Rosenberg SA. Immunotherapy of patients with advanced cancerusing intedeukin-2 alone or in combination with lymphokine activated killercells. In: DeVita Jr VT, Hellman, Rosenberg SA, eds. Important advances inoncology. Vol. 4. Philadelphia: JB Lippincott. 1988:217-257.44. Rosenberg SA. Immunotherapy and gene therapy of cancer. CancerRes. 1991; 51 (Suppl.):5074s-5079s. U

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