A desmoplastic-neurotropic of malignant metastases, and Abtropfung hypo thesis melanoma, 290 prognosis, 386 of melanocyte histogenesis, 7 of halo nevi, 90 of the primary melanoma, and of the origin of melanocytic nevi, 51 of melanocytic nevi, 55 prognosis, 380 Acanthoma, large-cell, transition of solar of melanoma, 136-144 of Spitz nevi, 149 to, 41 of small cell , 314-315 as a factor in differentiating Acquired dermal melanocytosis, of the face of solar lentigines, 40 melanoma from, 170 and extremities, 201 of solar melanoma, 248, 267-275 Ancient melanocytic nevi, 65-66 Acquired melanocytic nevi, common, of subungual melanoma, 284 Ancillary studies, for evaluation 55- 64 of vulvar melanoma, 98 of melanocytic lesions, 13-16 Acral melanomas, 280-284 and prognosis, in malignant melanoma, of reeurrent Spitz nevi, 193-194 defined, 241 380 Aneuploidy, and prognosis, 381 distribution of, by skin color, and recurrence of Spitz nevi, 188-190 Angiogenesis 248-249 Agminate Spitz nevi, 150-151 and pro gnosis in cutaneous malignant Acral , melanocytic, 89-90 AgNORs (silver-staining nueleolar melanoma, 379 Activating transcription factor 1 (STF-l) organizer region) in zones of regression of melanomas, gene, on chromosome 12, counts of, as a prognostic factor, 382 339 translocation of, in elear-cell of Spitz nevi, 171 Angiomatoid , variant of sarcoma, 327 Albright syndrome, melanotic macules desmoplastic Spitz nevi, 175 Adipocytes, accumulation of, in some nevi, associa ted with, 40 Angiotropic tumor aggregates, as 66 Alternative reading frame (ARF) tumor microscopic satellites, 261 Adnexal involvement, of Spitz nevi, 160 suppressor gene of CDKN2A Angiotropism Age identification of, 23 of and at diagnosis of melanoma associated penetrant melanoma locus, 21 desmoplastic-neurotropie with congenital melanocytic nevi, Amelanotic , 204-206 melanoma, 293 113 , 249, 330 of melanomas, 301-302 as a factor in differential diagnosis of Ameriean Joint Committee on Cancer of Spitz nevi, 160 Spitz nevus, 170 (AJCC) Angio-tumoral complex, 302 and melanoma arising from small classification of satellite and in-transit Animal-type melanoma, 331-333 congenital melanocytic nevi, 131 metastases of malignant me!anoma, Architecture and occurrence 357- 358 of atypieal nevi, 75-76, 124-125 of acral melanoma, 280 stage III disease, 383-385 of cellular blue nevi, 210 of ancient , 65 stage IV disease, 358 general, of melanocytic nevi, 64 of balloon cell melanoma, 90 staging oflocalized disease, 373 of pigmented spindle cell nevi, of Becker's melanosis, 44-45 Anatomie level of tumor invasion in the 180-185 of elonal nevi, 98 dermis and sub cutis, 375-376 Atypical intraepidermal melanoeytie of congenital nevi in the first year of Anatomic site proliferation, with indeterminate life, 115 importance of, in classifying melanomas, biologie potential, 345-346 of desmoplastic melanoma and 242-243 Atypical melanocytic nevi (AMN), 263-265

395 396 Index

Atypical nevi (dysplastic nevi), 66-89 plaque-type, 217-219 loss of heterozygosity in Spitz nevi, arehitecture of, 124-125 sderosing, differentiating from 175 cellular blue, 215-216 desmoplastic melanoma and mapping of the p16 gene to, 20-22 differentiating from atypical melanocytic neurotropic melanoma, 300 9p21, inaetivation in the germ eellline eells in a fibrotic matrix, 346 See also Malignant blue nevus and melanoma development, 73-74 melanocytic, Pagetoid spread in, 263-265 Body skin, fetal, pigment synthesis in, 8-9 11 p, study of alterations in Spitz nevi, p16 pro tein levels in, 25 Borderline lesions, suggesting melanoma, 174-175, 193-194 relationship with the number of nevi in diagnosis and management of, 12q13, mutational hot spot in the CDK4 ehildren, 140 343-346 loeus of, 27 significance of, 69-75 Bowen's disease, differentiating junctional multiple gains and losses consistent with Spitz tumors, 160-171 Spitz nevus from, 164 melanoma, 194 numerieal aberrations of, in atypical B C melanocytic proliferation, 132-133 Balloon cell melanoma, 330 Cafe-au-Iait macule (CALM)' t(I1;22) translocation in clear-eell age at occurrence of, 90 distinguishing from Beeker's nevus, 46 sareoma, 362, 368 Balloon eell nevus, 90 distinguishing from freckles, 37, 39-40 t(12;22) transloeation in melanoma of Balloon eells CAM 5.2 antibody, specifieity of, for soft parts, 17, 327 changes within nevi, 65 mammary Paget's disease, 265 Cireulating melanoma cells, 382-383 morphology of, in metastatie melanoma, Caspase-3,8,9 caseade, apoptosis via, 31 Classifieation 362 CDKN2A (pI6) of melanoeytic lesions with phenotypie Basilar epidermis association with melanoma, 73-74 hererogeneity, 225 density of melanocytes along, in lentigo identifieation of, 22 of melanocytic nevi, 52-53 simplex, 54 loeus and homologs of, 21-26 of melanoma, eriteria for, 239-244 proliferation of pigmented dendritie meehanism of action of, 20, 25-26 of metastatie disease in malignant melanoeytes, 209 target for germline mutation in familial melanoma, 358 Basilar melanocytes melanoma, 32 Clear-eell melanoma, 333-334 cireumscribed pigmented lesions upregulation of, by ultraviolet radiation, Clear-eell sareoma, 327-328 composed of, 37-50 28 differentiating from eellular blue nevi, correlation of the number of and sun CDKN2A-Leiden mutation, melanoma risk 216 exposure, 278 assoeiated with, 29 differentiating from a nodule derived in solar melanoma, 277- 278 CDKN2B (pI5) melanoma eellline, 22 from cutaneous melanoma, 362 Bathing trunk nevus, 114 aberrations of, in melanoma, 24 Clinical atypia versus histologie atypia, for Bax, promotion of apoptosis by, 31 regulation of eell-eyde progression assessing risk of melanoma, 71-72 Bd-2 involving the CDKN2A/RB Clinical faetors affeeting prognosis in as an antiapoptotic faetor, 31 pathway, 25-26 malignant melanoma, 380-381 expression of, in Spitz nevus compared eDNA microarrays, for identifying control Clinical features with melanoma, 172 elements in evolution of metastatic of acral melanoma, 280-282 Becker's melanosis (BM), 44-46 melanoma, 30 of acral nevi, 89 differentiating from cafe-au-Iait macules, Cell-division eyde, 25-26 of angiotropic melanoma, 302 40 melanoma genes aeting within, 32 of atypical nevi, 74-75 Benign juvenile melanoma. See Spitz nevi S phase, mutant eells expressing 14pARF of balloon celllesions, 90 Benign nevus, residual, in a regressed protein followed by p53 aetivation, ofballoon cell melanoma, 330 melanoma, 343 26 ofblue nevi Bilirubin, distinguishing from melanin, 2 Cellular blue nevus (CBN), 209-216, 223 common, 202-203 Biologie course ofSpitz nevi, 149-150 nodal,217 compound, 209 Biopsies, types of, 11-12 Cellular density, of eonventional eellular, 209 Biphasie pattern of cellular blue nevi, melanomas, 251 malignant, 324 214-215 Cellular type, classification of melanoeytic plaque-type, 217 Bleaehing to remove melanin, in evaluation nevi by, 53- 54 target, 220 studies, 13 C-erb protein, reaetion with 21N antibody of cafe-au-Iait maeules, 39 Bloom syndrome, assoeiation of cafe-au• of adenoeareinomas, 265 of clear-cell sarcoma, 328 lait macules with, 40 Childhood melanoma, 136-144 of clonal nevi, 98 Blue nevi, 199-222 Children's Hospital, Boston, eongenital of congenital melanocytie nevi, 114 criteria for designation as, 223 melanocytie nevi study at, 115 of conventional melanomas, 244-249 differentiating from desmoplastie Spitz Chromosomes invasive, with linie adjaeent nevi, 178 9p intraepidermal component, 266 HMB-45 marker for, 14-15 deletions from, and adverse outeome of deep penetrating nevi, 233 melanomas arising in, 322-327 in malignant melanoma, 383 of dermal melanocytie tumor, 333 INDEX 397

of desmoplastic melanoma and Congenital anoma!ies, association of, with Cyclins desmoplastic-neurotropic neuroid congenital melanocytic A, protein levels of, and stage or melanoma, 290-291 nevi, 123 melanoma, 383 of desmoplastic Spitz nevi, 175 Congenitallesions D 1, expression of, in Spitz nevi, 172 of ephelides, 37 charaeteristie attributes of, 65 D-type, as rate-limiting growth sensors, of halo nevi, 92 melanomas, 134-136 26 of lentigo simplex, 54 Congenital melanocytic nevi (CMN), Cysteinyldopas, pheomelanin formed of melanocytic nevi, 56-57 111-134 from, 1 of the genital skin, 98 with atypical features, 124-125 Cytogenetics, of human melanoeytic reeurrent, 96 differentiating from Beeker's melanosis, tumors, 17 with phenotypie heterogeneity, 226 46 Cytologie atypia of melanoma assoeiated with dermal giant, small eell type melanomas arising of basilar melanocytes, in solar lentigo, nevi, 319-320 from, 129, 140 41 of mucocutaneous melanotic maeules smalI, melanomas arising from, 140 of congenital melanocytie nevi, 115, and lentigines, 47-48 Congenital nevi 124-125 of neurotropic melanoma, 295 blue nevi, 323 of melanocytes, in nevoid melanoma, of nevoid melanoma, 303-304 comparison with malignant blue nevi, 310 of , 94 327 Cytology of recurrent Spitz nevi, 188-190 in the first year of life, 115 of atypical nevi, 83-85 of small cell melanoma, 313 loeation of, in the skin, 53 of nevoid melanomas, 307-310 of solar intraepidermal melanocytic punch biopsies of, 11 of nevus cells, 61-64 proliferations, 44 Spitz nevi, 149 of solar lentigo, 41 See also Congenital melanocytic nevi D of solar melanoma, 268-271 Congenital nevi tardive, 111 Danish Birth Registry, melanoma risk of spindle cell nevus Connecticut Tumor Registry, data on from, association with congenital pigmented, 180 desmoplastie melanomas, 290 melanocytic nevi, 113 plexiform, 235 Continent melanocytes, defined, 2 Deep-penetrating nevus, 233 of Spitz nevi, 149-160 Contours of growth, irregular, at deep morphological similarity to melanocytic of Spitzoid melanomas, 317-319 margins in Spitz nevi, 159 nevi with phenotypic heterogeneity, of subungual melanoma, 284-286 Conventional melanoma, 244-256 226-227 of verrucous melanoma, 311 defined, 241 Demarcation, sharp lateral, of Spitz nevi, Clon al nevus, 98-100 invasive, 260-266 158 Cohesion, loss of, in Spitz nevi, 160 with !ittle adjaeent intraepidermal Dermal cohesive eellular nodules, 346 Combined nevus, 98-100 eomponent, 266-269 Dermal component, of Spitz nevus, atypical published aecounts of, summary, 225 mieroinvasive, 256-260 features of, 164-165 Combined Spitz nevus, 178 Criteria for diagnosis. See Diagnosis Dermal epithelioid eell, melanocytic nevus Common acquired nevi, differenees from Cross-genomie hybridization (CGH), for with components of, 226 congenital melanoeytie nevi, 111, studying reeurrent Spitz nevi, Dermal fibroplasia, in atypical nevi, 85-86 123-124 193-194 Dermal melanoeyte hamartoma, 202 Common blue nevus, 202-204 Cross-seetional profile, of tumors, and Dermal melanocytie tumor, atypieal, 331-333 Common nevus, combination with blue prognosis, 379 Dermal melanoeytoses, 199-222 nevus, in melanoeytie nevi with Cultured eelliines, genetic alterations in, Dermal nevi, melanoma associated with, phenotypic heterogeneity, 226 reflecting adaptive change to in 319-322 Comparative genomie hybridization vitro conditions, 24 Dermal nodular pro!iferations, 125-127 (CGH), Spitz nevus studies using, Curettage biopsy, 12 Dermal nodules, 230-233 174 Cutaneous melanoma Dermallsubeutaneous tumoral pattern, in Competitive inhibition, of CDKN2A with age at diagnosis of, 238-239 reeurrent Spitz nevi, 191-193 eyclin Dl for CDK4 binding sites, stratification of risk factors for, 69 Dermal variations, of melanoeytie nevi, 26 Cutaneous nevus versus cutaneous 65-66 Complexity of conventional melanomas, metastasis, 366 Dermoepidermal junction 251 Cyclin-dependent kinases appearanee of spindie cells of Spitz nevi Composition of eellular blue nevi, 210-214 CDK4 at, 153 Compound nevus penetrant melanoma loeus, 20-21 giant nevus cells at, in Spitz nevi, 159 blue, 209 role of, in cell division, 22 Desmoplasia histopathologie features of, 61 role of, in familial melanoma, 27 in nevi, defined, 65 Concentric fibroplasia interaction with retinoblastoma gene and prognosis, 379 in atypical nevi, 85-86 product and D-type eyclins in early Desmoplastic melanomas (DM), 289-293 in tissue affeeted by lentiginous nevi, 57 GI> 26 defined, 290 398 Index

Desmoplastic-neurotropic melanoma of Mongolian spots, 200 in Spitz nevi, 160 (DNM), 290-293 of mucocutaneous melanotic macules in melanocytic nevi, 64-65 Desmoplastic Spitz nevus, 171, 175-178 and lentigines, 49 Epidermal growth factor (EGF) receptor, distinguishing from desmoplastic of myxoid melanoma, 331 73-74 melanoma, 300 of nevoid melanoma, 309-311 Epidermal melanin unit, dcfincd, 1 similarity with recurrent Spitz nevus, 190 of nevus spilus, 94-96 Epidermal nevus, differentiating from Developmental abnormalities ofrecurrent Spitz nevi, 195-196 Becker' s melanosis, 46 association with Becker's melanosis, 44 of regressed melanoma, 341 Epithelioid cell association with congenital melanocytic hypopigmented,341 atypical nevus, 86 nevi, 114 with residual benign nevus, 343 histiocytoma, differentiating from Spitz Diagnosis of regression in melanoma, 342-343 nevus, 171 of atypical nevi, 75-86 of small cell melanoma, 313 morphology of, 359-364 of melanoma, criteria for, 239-244 of small congenital melanocytic nevi, 131 variant, ofblue nevi, 206 conventional microinvasive, 257-260 of solar intraepidermal melanocytic Epithelioid-cell type melanomas in intraepidermal, 287 proliferations, 44 childhood, 141-142 malignant,358-370 of solar lentigo, 41-42 Epithelioid melanocytes (type A cells) of solar intraepithelial melanocytic of solar melanocytic hyperplasia, 279 appearance of, 7 proliferation, 278-279 of spindIe cell nevi of Spitz nevi, 153-157 of Spitz nevus, 161-162 pigmented, 185 zonation of, 158-159 special techniques for, 171-175 plexiform, 236-237 Epithelioid melanoma cells, 260-261 Differential diagnosis of Spitz nevi, 150-151 in desmoplastic melanoma and of acral melanoma, 287 with halo reaction, 180 desmoplastic-neurotropic of acral nevi, 89-90 of Spitzoid melanoma, 319 melanoma,291 of amelanotic blue nevi, 205-206 of verrucous melanoma, 312 and Pagetoid scatter, 254 of atypical nevi, 86-88 5,6-Dihydroxyindole units, in Epithelioid melanomas, diagnosis with of balloon celliesions, 90 eumelanins, 1 melanocyte differentiation of balloon cell melanoma, 331 DNA, abnormal content of markers, 14 of Becker's melanosis, 46 in congenital melanocytic nevi, Etiology ofblue nevi 133-134 ofballoon cell melanoma, 330-331 atypical cellular, 216 in Spitz nevus, 173 of childhood melanoma, 140-141 common,204 DNA mismatch repair genes, expression in of depigmentation in halo nevi, compound, 209 atypical , 74 92-94 epithelioid, 209 DNA-ploidy, as a prognostic factor in Eumelanin, 1 malignant, 327 malignant melanoma, 381 production of, binding of -melanocytic• sclerosing, 204 DNA repair, defective, in solar melanomas, stimulating hormone in, 28-29 target, 220 267 Eumelanosomes, stages of formation of, of cafe-au-Iait macules, 40 3-4 of dear-cell sarcoma, 328 E Evaluation, of melanoma, ancillary of donal nevi, 100-103 Ectasia, in zones of regression of techniques for, 13-16 of conventional melanomas with melanomas, 339 Ewing sarcoma oncogene, translocation in intraepithelial components, 261 Edema, in Spitz nevi, 160 clear-cell sarcoma, 327 of dermal melanocytic tumor, 333 Electron microscopy EWS-ATFI fusion gene, in melanoma of of desmoplastic melanoma and of melanocytes soft parts, 368 neurotropic melanoma, 300-301 for differential diagnosis, 16-17 Excisional biopsies, 11 of desmoplastic Spitz nevi, 175-178 for observing morphology, 3-4 Extravascular migratory metastasis, 302 of freckles, 37 for observing the morphology of Eyelid, congenital divided nevus of, of halo nevi, 92-94 desmoplastic melanoma, 299 113-114 of intraepidermal Spitz nevi, 163-171 Embryology, of melanocytes, 8-9 of , 274-275 Enzyme histochemistry, for evaluating F of lentigo simplex, 54-55 melanocytic lesions, 13-14 Familial aggregation, of congenital of melanocytic nevi Epidemiology melanocytic nevi, 114 of the genital skin, 98 descriptive, of malignant melanoma, Familial melanoma susceptibility loci, with phenotypic heterogeneity, 238-239 20-29 232-233 of Spitz nevi, 149 major melanoma genes of, 32 recurrent, 96 Epidermal changes Fas (CD95), role in cellular homeostasis, of melanoma associated with dermal atrophy in solar melanomas, 251 utilizing apoptosis, 30-31 nevi, 322 in congenital melanocytic nevi, 123-124 FasL, upregulation of the soluble form, of melanoma with little adjacent hyperplasia interaction with membrane intraepidermal component, 267 in melanomas from acral skin, 251 FasL,31 INDEX 399

Feedback loops, integration of the of atypical nevi, 88-89 Histologie variations p 16/retinoblastoma and alternate See also Classification within atypical nevi, 86 reading frame/p53 path, 27 Grenz zone, separation of epidermis from within common acquired melanocytic Fibrotic papillary dermis, of atypical dermal infiltration of nevus eells, nevi,64-66 melanocytic nevi, entrapment of 120 Histomorphologic eriteria, defining atypical nevus cells in, 264 Guidelines, for grading atypical nevi, 88-89 eonventional invasive melanomas, Fibrous histiocytoma, malignant, 260-266 distinguishing from desmoplastic H Histopathologie criteria melanoma, 301 Hair for eonventional invasive melanomas Fibroxanthoma, atypical, distinguishing human, melanins of, 1 with little intraepidermal from desmoplastic melanoma, 301 transfer of melanin from the hair matrix component, 266 Field effect, from melanoma" 279 cells to the follicles, 1 for diagnosis of melanoma, 240-241 Fixation, of skin excisions, 11 , 90-94 for identifying acral melanoma, 282-284, evaluation of, 13 atypical, differentiating from nevoid 287-288 Fluorescenee in situ hybridization (FISH) melanoma, 310 for identifying angiotropic melanoma, 302 for identification differentiating from Pagetoid melanoma, for identifying balloon eell melanoma, of clear-eell-sarcoma, 328 264 330 of HRAS gene mutation in Spitz nevi, differentiation from hypopigmented for identifying blue nevus 175 regressed melanomas, 341 amelanotic, 205 for study variant of, 86 cellular, 209-216 of acral melanomas, 279-280 Halo reaction in a Spitz nevus variant, 180 common, 203-204 of recurrent Spitz nevi, 193-194 Hamartoma compound, 209 Fontana-Masson stain, 13 dermal melanoeyte, 202 epithelioid, 206-208 Freekles (ephelides), 37-38 epidermal nevus as, 46 malignant, 324-326 carriers of variant alleles of melanocortin melanocytie nevus as, 51 target, 220 1 receptor genes, 29 neurocristie, 219-220 for identifying clear-cell sarcoma, 328 Frozen sections, for assessment of margins, Hamartoma, Beeker's pigmentary. See for identifying congenital melanocytic 12-13 Beeker's melanosis nevi, 115-124 HDM2 marker, prognostic significance of, fur identifying conventional melanomas, G 16 249-256 Gender, and prognosis in melanomas, 380 Hemosiderin, distinguishing fra m for identifying dermal melanoeytie Genes melanin, 2 tumor, 333 alterations at the CDKN2A locus, 23-24 Histochemical evaluation of Pagetoid fur identifying dermal melanocytoses, 202 cancer, types of, 20 involvement of the epidermis, 265 for identifying desmoplastic melanoma melanoma, major, 21 Histogenesis and desmoplastic-neurotropic N -ras, association with congenital of congenital melanoeytic nevi, melanoma, 291-293 melanoeytie nevi and melanoma, 113-114 for identifying desmoplastic Spitz nevi, 133-134 of dermal melanoeytoses and blue nevi, 175 See also Chromosomes; Inheritanee 199-200 for identifying melanoma associated with Genetic basis, for growth and development of desmoplastic melanoma, 297-299 dermal nevi, 320-321 of nevi, 51-52 of melanocytes, 4-7 for identifying Mongolian spots, 200 Genetic control of melanocytie nevi, 51-52 for identifying neurotropic melanoma, of development of nevi, 55-56 of nevus eells, 7-8 295 of the risk for melanoma, 69 Histogenetie type, and prognosis in for identifying nevoid melanoma, 304-309 of the type of melanin pigmentation, 1 malignant melanoma, 378-379 fur identifying pigmented spindIe cell Genetic pathology of melanoma, 20-36 Histologie eriteria, for melanocytie lesions, nevi, 180-185 Genital skin, melanocytic nevi of, 96-100 53-54 for identifying pilar neurocristic Genomic structure of CDKN2A/ ARF, 23 Histologie features hamartoma, 220 Giant nevus cells of acral nevi, 89 fur identifying plaque-type blue nevi, 218 intradermal, 61 of balloon celllesions, 90 for identifying sderosing blue nevi, 204 in Spitz nevi, 159 of blue nevi and variant blue nevi, for identifying small ccll mclanoma, 313 gpl00 223-225 for identifying solar melanoma, 271-274 antibody to, for recognizing metastatic of clonal ncvi, 98-100 for identifying Spitz nevi, 151-158 tumor deposits in scntinellymph of halo nevi, 92 versus melanomas, 190-193 nodes, 358 of melanocytic nevi for identifying Spitzoid melanomas, 319 premelanosomal glycoprotein, 14-15 of the genital skin, 98 for identifying verrucous melanoma, Grading reeurrent, 96 311-312 of arehitectural disorder in atypical nevi, of metastatie melanoma, 358 of solar intraepidermal melanocytie 86 of nevus spilus, 94 proliferations, 44 400 Index

Histopathologie features Immunohistochemistry Intraepidermal pigmented spin dIe cell, of atypical nevi, 75 for evaluating desmoplastic melanoma, differentiating from intraepidermal of Becker's melanosis, 46 299 melanoma, 263 of cafe-au-Iait macules, 39-40 for evaluating desmoplastic-neurotropic Intraepithelial melanoma, histopathologic of deep penetrating nevi, 233 melanoma, 295-296 features of, 249 of ephelides, 37 for evaluating melanocytic lesions, 14-16 In-transit metastases, defined, 357-358 of lentigo simplex, 54 of Kamino bodies in Spitz nevi, 159 of melanocytic nevi, 57-61 of metastatic melanoma with phenotypic heterogeneity, distinguishing from nodal nevi, 368 Junctional cleavage, in Spitz nevi, 160 226-228 with epithelioid or spindIe cell Junctional nests of melanomas in childhood, 141-144 morphology, 362 of the basal epidermal zone, 57 of mucocutaneous melanotic macules of sentinellymph nodes, 358 of Spitz nevi, 155-157 and lentigines, 48-49 of Spitz nevi, 171-172 Junctional nevus of plexiform spindIe cell nevi, 235-236 Immunolabeling, of metastatic tumors, defined, 57-61 of solar lentigo, 41 PECAM-l and VEGF, 386 lentiginous, defined, 55 Histopathologic reporting Immunophenotype analysis, of infiltrating lransiLion of melanoeytes to, 52 of atypical nevi, 88-89 cells of halo nevi, 92 of melanoma, 346 Immunostaining K Historical perspeetives, on classification of for melanocyte differentiation antigens, Kamino bodies melanoma, 242-244 199-200 in pigmented spindIe cell nevi, 183 HMB-45 tumor marker unusual results associated with in Spitz nevi, 159 for distinguishing desmoplastic melanomas, 16 Keratinocytes, transfer of melanin pigment melanoma from other lesions, 300 Incidence particles to, 1 for melanocytes, 14-15 of congenital melanocytic nevi, 111 Keratoses negative, in neurotropic melanoma, of Spitz nevi, 149 lichenoid, 341 295-296 lnflammatory infiltrate, perivascular, in transition of solar lentigo to, 41 Hochsteigerung hypothesis, of melanocyte Spitz nevi, 160 melanomas resembling, 249 histogenesis, 7 Inflammatory patterns, of congenital nevi, reticulated seborrheic, transition of solar Homogentisic acid pigment, 2 121-123 lentigo to, 41 Hormones Inflammatory response, participation of Ki-67 nuclear antigen association of androgen with Becker's melanocytes in, 1 assessing melanocytic lesions using, 16 melanosis, 44 lnheritance immunolabeling of, to assess association of estrogen with papillomatous autosomal dominant proliferation rate, 382 changes in nevi, 64-65 of freckling, 37-38 levels of, and stage of melanoma, 383 Host response of neurofibromatosis, 40 Knockout models, CDKN2A deficient in atypical nevi, 85 See also Genes; Genetic entries mice, 25 in invasive melanoma, 261 INK4 gene family, 23 in malignant melanoma, effect on Ink-spot solar lentigo, clinical features of, L pro gnosis, 378 41. See also Solar lentigo Lactate dehydrogenase (LDH) levels and HRAS gene mutation, fluorescence in si tu Institutional review board (IRB), consent prognosis in metastatic malignant hybridization (FISH) for of, to obtain tissue for research, 13 melanoma, 358 identifying, 175 Interobserver concordance Lamellar fibroplasia Hutchinson melanotic freckle, melanoma in judging clinical atypia of nevi, 70-71 in atypical nevi, 86 associated with, 267-275 study of Spitz nevus criteria, 166-168 in melanocytic nevi of the genital skin, 98 Hydroxyl radicals from irradiation of in judging histologic diagnosis of atypia Leiomyosarcoma, cutaneous, distinguishing pheomelanin, 1 of nevi, 75 from desmoplastic melanomas, 301 Hyperkeratosis in conventional Intraepidermal component Lentigines, mucocutaneous, 46-49 melanomas, 251 missing, in malignant blue nevus, 323 Lentiginous compound nevi, atypical, Hyperpigmentation of the basilar of Spitz nevi, atypical features of, 163 differentiating from small cell epidermis, in lentigo simplex, 54 Intraepidermal epithelioid eells, melanocytie melanoma,313 Hypopigmentation of completely regressed proliferations of, 262-263 Lentiginous melanocytic hyperplasia, melanoma,341 Intraepidermal melanocytic proliferation defined, 3 atypical, 343-346 Lentiginous melanocytic nevi, 275-280 I disordered, in atypical nevi, 78-82 Lentiginous melanocytic proliferation Idl repressor, of the CDKN2A gene, 24 with intermediate biologie potential, (LMP),345 Immune systems 345-346 falling short of melanoma in situ, association of responses with halo nevi, 92 Intraepidermal Pagetoid spread, of 271-274 genes functioning to evade, 30-31 melanocytes, 125 of the sun-damaged skin, 254 INDEX 401

Lentiginous melanomas involvement of, by blue nevi, 216-217 melanocyte differentiation, for evaluating association with desmoplastic melanoma metastasis to, and prognosis in sentincllymph nodes, 357 and desmoplastic-neurotropic malignant melanoma, 383-385 NKI/C3, for identifying melanocytic melanoma, 291 See also Metastasis lesions, 15-16 overlap with Pagetoid melanomas, 265 Lymphocytes p75 neurotrophin receptor, 15, 291 Lentiginous nevi resemblance of type B melanocytes to, 7 T311 antibody to tyrosinase, for differentiating from atypical nevi, 86-88 response to microinvasive melanomas, melanocytes, 15 differentiating from solar lentigo, 41 260 tyrosinase-related protein I, for histopathologie features of, 57 Lymphocytoid ceIls (type B nevus), 61 melanocyte differentiation, 15 Lentiginous pattern See also HMB45; S-100 protein in conventional melanomas, 254 M Mart-l differentiating variants of, 265 M2-7ClO antibody, to the Mart-l as a marker for Spitz nevus, 171 , 141-142,254, melanoma celiline, 15 for recognizing metastatic tumor deposits 267-275 Macroglobules, melanin, in cate-au-Iait in sentinellymph nodes, 358 definition of, 42-44 macules, 39-40 Masson-Fontana stain, 13 differentiating from atypical nevi, 87 Macromelanosomes, association with Maturation punch biopsies of, 11 melanocytic lesions, 2 of melanocytes, defined, 158 similarities with pigmented spindIe ceH Macular phase, of acral melanoma in melanomas, 345-346 nevus, 185 development, 280-282 of nevoid melanocytes, 61 See also Solar melanoma Major histocompatibility complex (MHC), of pigmented spindie ceIl nevi, 181 Lentigo malin des vieillards of Dubreuilh, role in apoptosis of melanoma cells, in Spitz nevi, 158-159 267-275 31 Mean nuclear volume, of Spitz nevi, 172 Lentigo senilis. See Solar lentigo Malignant blue nevus (MBN), 128, MeI-5 antibody, 15 Lentigo simplex, 40-44, 54-55 322-327 Melan A differentiating from Becker's melanosis, 46 differentiating from ceIlular blue nevus, for identifying melanocytes, 15 Leptomeningeal melanoma, 130 216 prediction of outcome from levels of, Leukoderma acquisitum centrifugum. See Malignant degeneration of congenital 383 Halo nevus melanocytic nevi, 114 for recognizing metastatic tumor Lichen sclerosus, melanoma associated Malignant epithelioid schwannoma, deposits in sentinellymph nodes, with, 140-141 associated with congenital 358 Lichenoid keratosis, 341 melanocytic nevi, 128 Melanin pigment, 1-2 transition of solar lentigo to, 41 Malignant fibrous histiocytoma, Melanin stains, 13 Lichenoid pattern, in regressed melanomas, distinguishing from desmoplastic Melanin-stimulating hormone (MSH), 1 341-342 melanoma, 301 Melanocortin I receptor (MCIR), 28-29 Light microscopy, to observe the Malignant melanoma, 238-356 association with freckles, 37 morphology of melanocytes, 2-3 differentiating halo nevus from, 94 mediation of the response to ultraviolet Lipofuscin (wear-and-tear pigment), 2 Malignant melanoma of soft parts, 327-328 light by, 21 Liverspot. See Solar lentigo Malignant neuroectodermal tumor, role in pheomelanin synthesis, versus Location, of melanocytes in the skin, 289-301 eumelanin synthesis, 32 defining melanocytic nevi in terms Malignant Spitz nevus, defined, 162 Melanocytes, 1-10 ot: 53 Management of cohesive cellular nodules, in ephelides, size and appearance of, 37 Locoregional metastases, 357-358 346 large epithelioid, in Spitz nevus, 151-158 Longitudinal melanonychia, 287-288 Mapping of melanoma genes, 21-26 spindle-shaped, in Spitz nevi, 151-158 Loss of function, of CDKN2A and ARF Markers Melanocytic nevi loci, 25 A-I03, for identifying human melanoma acquired, 7-8, 51-110 Loss of heterozygosity ceIls, 15 comparison with nevoid melanoma, 310 bracketing the CDKN2A locus on HDM2, prognostic significance of, 16 congenital. See Congenital melanocytic chromosome 9p in atypical nevi, 25 Mart-l nevi on chromosome 9p, in Spitz nevi, 175 for recognizing metastatic tumor conventional melanomas associated with, of the neurofibromatosis 1 gene, in deposits in sentinellymph nodes, 358 261 neurotropic melanoma, 299 for Spitz nevus, 171 differentiating from lentigo simplex, 55 Lupus erythematosus, cutaneous, Melan A with focal dermal epithelioid cell distinguishing from regression of for identifying melanocytes, 15 components (MNFDECC), 230-233 melanomas, 341 prediction of outcome from levels of, of the genital skin, 96-100 Lymphatic invasion by Spitz nevi, 160 383 with phenotypic heterogeneity, 223-237 Lymph no des for recognizing metastatic tumor defined,225-226 benign meta stasis to, in congenital blue deposits in sentinellymph nodes, recurrent, diagnosing, 345 nevus, 324 358 status of CDKN2A in, 25 402 Index

Melanocytie nuclear volume, and distally acting melanoma loci involved Morphologie features, of cellular blue nevi, prognosis, 381 in, 29-30 214-215 Melanocytic proliferation, benign, pattern of malignant melanoma, 357-371 Morphology of,3 ofmelanoma of melanocytes, 2-4 Melanoma in dermis, distinction from distinguishing from nevoid of metastatic melanoma, 359 dermal nevus ceHs, 345-346 melanoma,310-311 Mortality from cutaneous melanoma, Melanoma in situ to a fetus, 134 among white populations, 238-239. criteria for defining, 271-274 with unknown primary site, 368-369 See also Survival rate criteria for differentiating from solar of radial and vertical growth phases, Mucin, interstitial accumulation of, in nevi, intraepidermal melanocytic 242-243 66 proliferations, 44 of Spitz tumors, 171 Mucosal blue nevi, 220 histopathologie data for diagnosing, 249 visceral, sites in malignant melanoma, , 335-336 threshold for diagnosing, 254-256 358 Mulberry-type giant cells, 61 Melanoma of soft parts (MMSP), t(12,22) See also Lymph no des Multiple lentigines, syndromes associated chromosome translocation in, 17, 327 Metastatie malignant melanoma, 357-371 with,54 Melanoma of the nail apparatus, 284-289 MIB-l labeling index, for distinguishing Multiple melanomas Melanomas melanomas and Spitz nevi, 16 CDKN2A mutations in, 24 association with nevi, 66-89 Microinvasive melanoma primary, incidence of, 368 association with involving conventional, 256-260 Multiple Spitz nevi, 150-151 the eye, 201 regression in, 336-337 Multiple tumor suppressor 1 (MTSl), childhood, and giant congenital nevi, Micrometastatic disease, as a prognostic identification with p 16, 22 140-141 factor, 375 Mutagenic agents, expression of 14pARF criteria for differentiating from atypical Microphthalmia transcription factor protein by, 26 nevi,87 (MITF) Mutation analysis, of CDKN2A/ARF, development of, in congenital nevi, expression of, and pro gnosis in 23-25 126-134 malignant melanoma, 383 Myxoid melanoma, 331 primary cutaneous, versus melanoma as a marker for melanocytes, 15 Myxoid stromal reaction, in metastatic metastatic to the skin, 364 Microsatellite instability near the CDKN2A malignant melanoma, 362-363 primary mucosal, versus melanoma locus,74 Myxomas, distinguishing from metastatic to the skin, 364-366 Microscopic metastases, survival rate, 380 desmoplastic melanomas, 301 Melanoma with nodular component, 249 Microscopic satellites Melanonychia striata, 57, 287-289 of invasive melanomas, 261 N Melanosis, in metastatic melanoma, prognosis predicted from, 377-378 National Institutes of Health (NIH), 369-370 Minimal deviation melanoma (MDM), definition of nevus with Melanosomes, enzymes of, 3-4 302-303, 379 architectural disorder and cytologic Melanotic macules Minor susceptibility melanoma loci, 32 atypia,68 of Albright, differentiating from freckles, Mitosis Natural history of desmoplastic melanoma 37 dermal, in nevoid melanoma, 309 and desmoplastic-neurotropic mucocutaneous, 46-49 rate of, and prognosis in cutaneous melanoma, 299-300 Melasma malignant melanoma, 375-376 Neoplasms, melanocytic nevi as, 51 clinical appearance of, 40 in Spitz nevi, 159 Nerve growth factor (NGF) receptor, differentiating from freckles, 37 Models association with melanoma, 73-74 Melastatin of histogenesis of melanocytic nevi, 51-52 Nerve sheath tumors, distinguishing control of metastasis by, 30 prognostie, in malignant melanoma, desmoplastic-neurotropic inactivation of, and neoplastie 386-388 melanoma from, 301 progression, 21 Mohs micrographie surgery, for basal ceH Nested intraepidermal melanocytic Memorial Sloan-Kettering Cancer Center, and squamous cell carcinoma proliferation, in conventional data on satellite metastases, 357 treatment, 12 melanomas, 256, 345 Meningeal melanorna, neurocutaneous Molecular pathology of melanoma, 20-36 NestsInested pattern melanosis as aprecursor to, 114-115 Molecular pathways, and the development distribution of, in atypical nevi, 82-83 Merkel ceH carcinoma, smaH cell ofmelanoma, 31-32 junctional melanoma mimicking, 312-314 Moles. See Common acquired nevi of the basal epidermal zone, 57 Mesenchymal tumors, arising from giant Mongolian spot, 200 of Spitz nevi, 155-157 congenital melanocytic nevi, 131 Monoclonal antibodies in melanoma, distinguishing from Metastasis A-I03, for identifying human melanoma melanocytic nevi, 265-266 of desmoplastic melanoma and cells, 15 of nevocellular nevi, 7 desmoplastic-neurotropic for identifying human melanoma cells, 16 Neural nevus, 94 melanoma, 300 See also Markers Neurocristic hamartoma, 219-220 INDEX 403

Neurocutaneous melanosis (NCM), 111, N omenclature defined, 53 126 of borderline lesions, 343-346 in melanoeytic nevi, recurrent, 96 association with congenital melanocytic of p16, 22 Pagetoid Spitz nevus, 163 nevi, 114-115 terminology for describing the Spitz Pagetoid spread Neuroectodermal tumors, 289-290 nevus, 148-149 association with melanomas of sun• N eurofibromatosis (von Recklinghausen' s Nonmelanoeytie tumor, differentiating exposed skin, 251 disease), density of melanocytes in from metastatie melanoma, in eonventional melanomas, 251-254 cafe-au-lait maeules and normal 359-364 intraepidermal, of melanoeytes, 125, skin, 39-40 N -ras gene, assoeiation with congenital 343-345 Neurofibromatosis 1 gene, loss of melanocytie nevi and melanoma, in pigmented spindIe cell nevi, 185 heterozygosity of, in neurotropic 133-134 in Spitz nevi, 157 melanoma, 299 Nudear atypia intraepidermal, 163 Neuroid eongenital melanoeytie nevi, and arehiteetural disorder, 75 of melanoeytes, 159-160 differentiation in, resembling continuum of, 83-85 Papillary dermis, invasion of, by in situ neurofibroma histology, 123 Nudei, of melanocytes, eleetron melanomas, 256 Neuromelanin, accumulation of, in mieroseopie appearanee of, 3 Parakeratosis, in eonventionalmelanomas, catcholaminergic neurons during Nucleolar organizer regions (NORs) 251 aging,2 and prognosis, 382 Patehlike blue nevus, 217 Neurothekeoma of Spitz nevi, 171 Pathologie faetors, and prognosis, in eellular, differentiating from Spitz nevi, See also AgNORs malignant melanoma, 374-380 171 Nudeus of melanoeytes, appearance under Penetrance distinguishing from desmoplastie light microseopy, 3 of familialmelanoma loci, 20 melanoma,300-301 of germline mutations in CDKN2A, Neurotized nevus o 24-25 differentiating from a neurofibroma, Oneogenes minor, of familialmelanoma genes, 94 CDK4,21 27-29 melanocytic, 66 metastasis promoted by, 29-30 Perinevoid leukoderma. See Halo nevus Neurotropie melanoma (NM), 290, Outeomes, in reeurrent Spitz nevus, 196 Perinevoid vitiligo, See Halo nevus 293-301 Peutz-Jeghers syndrome, lentigines of the Neurotropic tumor aggregates, as P oralmucosa and vermillion border microseopie satellites, 261 p14ARF, gene product ofthe alternate in, 47 N eurotropism reading frame ARF, 23 Phaeomelanosomes, development of, stages defined, 295 p16 (CDKN2A). See CDKN2A (pI6) in, 4 and prognosis, 379 p53, activation of, by expression of p 14ARF Phase, of tumor progression, and of Spitz nevi, 160 in the S phase of cell division, 27 prognosis, 376 Nevocellular nevi, nests of, 7. See also p75 neurotrophin receptor (p75NR) Phenotypes, histomorphologic, of Common aequired nevi marker far desmoplastic melanoma and neuroectodermal tumors, 290 Nevoid melanoma, 303-311 desmoplastie-neurotropie Phenotypic heterogeneity, and Nevoid melanosis. See Becker's melanosis melanoma, 291 nomenclature, 223-225 Nevus cells, morphology of, 7 marker for spindIe cell melanomas, 15 Pheomelanin, 1 as the site for melanoma development, Paget' s disease, differentiating junctional produetion of, in response to low• 239 Spitz nevus from, 164 affinity binding of melanocortin Nevus fuscocaeruleus acromiodeltoideus, Pagetoid melanocytosis ligands, 28-29 201-202 in eonventional melanomas, 253-254 synthesis ot~ promotion by melanoeortin Nevus fuscocaeruleus ophthalmomaxillaris, defined, 53 1 receptor polymorphisms, 32 200-201 Pagetoid melanoma Photoehemotherapy (PUVA), lentigo Nevus fuscoeaeruleus zygomatieus, 201 anatomie sites of, 247-248 indueed by, 41 Nevus ofIto, 201-202 eharaeteristics of, compared with Photoprotection, by eumelanin, 28 Nevus of Ota, 200-201 pigmented spindie cell nevus, 189 Pigmentation, of Spitz nevi, 160 Nevus spilus (Speekled lentiginous nevus), Pagetoid pattern Pigmented aetinic keratosis, differentiating 94-96 and diagnosis of conventional from solar lentigo, 41-42 NKI/C3 monodonal antibody, for melanomas, 251-254 Pigmented hairy epidermal nevus. See identifying melanoeytic lesions, and diagnosis of melanomas with Beeker' s melanosis 15-16 intraepidermal components, Pigmented spindIe cell nevus (PSCN), Nodal nevus versus metastasis, 366-368 261-265 180-185 , 243 Pagetoid proliferation, defined, 3 with atypieal features, 183-185 acral melanoma as, 282 Pagetoid seatter intraepidermal, differentiating from defined, 266 in aeral nevi of the palms and soles, 89 intraepidermalmelanoma, 263 404 Index

Pigmented spindie cell variant, of solar Proliferation index Rhabdomyosarcoma, alveolar, by melanoma,271-274 of nevi and melanomas, 74 metastatie melanoma, 362 Pigment incontinence, in desmoplastic prognostic value of, 382 RhoC gene melanoma,291 Proliferation rate of Spitz nevi, compared overexpression of, and metastatic Pilar neurocristic hamartoma, elinical with melanomas, 171-172 propensity of melanomas, 30 features of, 219-220 Proto-oncogenes, 20 promotion of neoplastie progression by, 21 Plaque-type blue nevus, 217-219 Pseudomelanosis coli, pigment of, 2 Risk factars, for melanoma Pleomarphism, of nevus cells, 61 Punch biopsies of cutaneous pigmented associated with red hair and inability to Plexiform spindie cell nevus, 233-237 lesions, 11 tan, 29 pigmented, marphological similarity atypical nevi as markers for, 69-72 with melanocytie nevi with R in childhood, 140-141 phenotypic heterogeneity, 227-228 Radial growth phase (RGP) of melanoma, in congenital melanocytic nevi, 111-112, Plexiform Spitz nevus, 178-179 242-243 131-132 Pmel 17 gene family, role in Ras protein, upregulation of, 31 correlation of histologie melanocytic melanogenesis, 1 Recurrence atypia with, 74 Point mutations, in CDKN2A inactivation of elear-cell sarcoma, 328 malignant, 238-239 in familial melanoma, 23 of desmoplastic melanoma, 300 melanocytic nevi, 51-52 Polypoid configuration of melanoma, 329 local, and prognosis, 381 stratification of, 69 Postinflammatory hyperpigmentation, of malignant melanoma, 357 distinguishing from cafe-au-Iait of melanotic nevi, 88, 96 S macules,40 of Spitz nevi, 185-196 S-100 protein Postzygotie inactivation, of the CDKN2A Red hair and freckle gene, and the risk of as a marker locus, cancers associated with, 24 melanoma, 27-29 for desmoplastic melanoma and Postzygotic mutations, at genomic loci, in Regressing nevoid nail melanosis, 284-285 desmoplastic-neurotropic melanomas, 20 Regression melanoma, 291 Precursors, to melanoma, atypical nevi as, effects of, on prognosis in melanoma, far epithelioid melanomas, 14 72-74 376-377 far Spitz nevus, 171 Pregnancy status, and survival from of halo nevi, 92 serum levels of, and survival rates, melanoma, 380-381 of melanomas, 336-343 382-383 Presentation, of Spitz nevi, 149 invasive, 261 Satellite metastases, 357-358 Primary melanoma, complete regression of, leading to metastatic melanoma with Satellites, of congenital melanocytic nevi, 341 unknown primary site, 368 114, 139 Primary melanoma of soft parts versus microinvasive, 260 Satellitosis, of lymphocytes, in invasive metastatic melanoma to soft tissue, Pagetoid, 248 melanomas,261 368 Regulation, of melanogenesis, 1 Schmor! stain, 13 Prognosis Relative risk of melanoma Schwann cell, differentiating from a blue of balloon cell melanoma, 330 association with polymorphisms of the nevus, 199-200 of melanomas in children, 141 melanocartin 1 receptor, 29 Schwannomas, distinguishing from in metastatic melanoma, correlation with relationship with the numbers of nevi, 71 melanoma, 16 increased soluble FasL levels, 31 Research, tissue for, 13 Selerosing blue nevus, 204 of mucosal melanomas, 336 Restriction points, in the cell-division cyele, differentiating from desmoplastic of subungual melanoma, 284 result of lass of control at, 25-26 melanoma and neurotropic Prognostic factars Rete ridges, epidermal melanoma, 300 in cutaneous malignant melanoma, in lentigo simplex, 54 Seborrheic keratosis, reticulated, transition 372-394 in solar lentigo, 41 of solar lentigo to, 41 in stage land II malignant melanoma, Reticular dermis, invasion of, by Secretory melanocytes, defined, 1 373-383 melanomas, 261 Sentinellymph node (SLN) biopsy table, 384 Reticulohistioeytoma, differentiating from to assess atypical Spitz-like tumors, 163 in stage III malignant melanoma, table, Spitz nevus, 171 in conjunction with excisional biopsy, 11 385 Retinablastoma (RB) gene product, as a prognosis indicated by the results of, 385 in stage IV malignant melanoma, 385-386 gatekeeper of the G1/S cell-division far staging risk far regional melanoma Prognostie indieatar, melastatin levels in eyele, 25-26 metastases, 357-358 metastatic melanomas, 30 Reverse transcriptase-polymerase chain status from, and prognosis, 375 Prognostic models, in malignant reaetion (RT -PCR) Shave biopsy, 11-12 melanoma, 386-388 for identifying elear-cell sarcoma, 328 Shoulder phenomenon, in atypical nevus Proliferating cell nuelear antigen (PCNA), for identifying melanoma markers, 385 architecture, 75-76 labeling far, in assessing outcome, for identifying tyrosinase mRNA Signaling pathway, far the melanocortinl 382 expression, 358, 382-383 receptor, 28 INDEX 405

Signet-ring cell melanoma, 334 characteristics of, compared with distinguishing from desmoplastic Signet-ring cell morphology, in metastatic pigmented spin die cell nevus, 189 melanomas, 301 malignant melanoma, 362 defined, 241 Squamous epithelium, organization Silver-Russell syndrome, association with differentiating from Pagetoid melanoma, patterns within, in conventional cafe-au-lait macules, 40 265 melanomas, 251 Silver-staining nucleolar organizer region lentiginous pattern in, 254 Stage III melanoma, prognostic factors for, (AgNORs). See AgNORs similarities with pigmented spindie ceH 383-385 Simple lentigines, differentiating from nevus, 185, 263 Staghorn-like vascular pattern, in freckles, 37-38 See also Lentigo maligna melanoma metastatic melanomas, 363 Size Solar melanoma in situ, differentiating Staging system, for melanoma, 373. See also of conventional melanomas, 249-251 from solar lentigo, 41 American Joint Committee on and histopathology Spin die cell melanocytes of Spitz nevi, Cancer of giant congenital melanocytic nevi, 153-158 Standardized morbidity ratio (SMR), of 123 Spindie cell melanomas patients with giant congenital of larger congenital melanocytic nevi, desmoplastic, S-1 00 protein as a marker melanocytic nevi, 113 119-123 for, 14 Starb urst ceHs, in solar melanomas, of small congenital melanocytie nevi, speeifieity of monoclonal p75 271-274 115-119 neurotrophin receptor antibody for, Stroma, 53-54 Skin and Cancer Foundation, Sydney, 15 Stromal fibrotic reaction, in vulvar nevi, 98 Australia, 313 Spindie cell morphology, of metastatie Subcutaneous fat, extension of nevus eells Skin color melanomas, 362 into, 120 and incidenee of acral melanoma, 280 Spindie ceH nevi, pigmented, 180-185 in congenital nevi, 118 and incidenee of subungual melanoma, differentiating from atypical nevi, 88 Subungual melanoma (SUM), 249, 284 differentiating from Spitz nevi, 171 284-287 and number of nevi in individuals, 55 See also Spitz nevi Sunlight, exposure to and prevalence of longitudinal Spindie cells intermittent, and conventional melanonychia, 289 proliferation of, in desmoplastic melanomas, 244-248 Skin exeisions, routine handling of, 12 melanoma and desmoplastic• protection against the effects of, by SmaH ceH melanomas, 312-316 neurotropic melanoma, 291 melanin, 1 in ehildhood, histopathologie features of, in solar melanoma, differentiating from as a risk factor for malignant melanoma, 142-143 PSCNs, 276-277 239 Solar intraepidermal melanocytie neoplasia, Spindie eell squamous carcinoma, as a risk factor for sm all cellmelanoma, differentiating from solar distinguishing from desmoplastic 313 melanocytic hyperplasia, 278 melanomas, 301 Superficial spreading melanoma, 243 Solar intraepidermal melanocytic Spitz nevi, 148- 198 Surgical margins, interpretation of, 279 proliferations (SIMPs) eombined,98-100 Survival rate with atypia, differentiating from solar eontinuum of histologie features with in clear-cell sarcoma, 327-328 lentigo, 42-44 pigmented spindie cell nevus, 181 in desmoplastic melanoma, 300 differentiating from solar lentigo, 41 differentiating from atypical nevi, 88 in locally recurrent melanoma, 381 progression to invasive melanoma, hyalinizing, 178 in metastatic malignant melanoma, 357 267-268 melanomas simulating, in children, Sutton's nevus. See Halo nevus sampling or removing lesions with 144 Symmetry, of Spitz nevi, 157-158 features of, 256 Pagetoid variant, differentiating from Solar lentigines conventional melanomas, 263 T association with melanoeortin 1 relationship with ordinary nevi in T311 antibody to tyrosinase, as a marker receptor,37 melanoeytie nevi with phenotypie for melanocytes, 15 differentiating from freckles, 37-38 heterogeneity, 227-228 Target blue nevus, 220 Solar lentiginous melanocytic nevi, 275-276 Spitzoid melanoma, 313-319 T -cells, mediation of antitumor immunity Solar lentiginous melanomas (LMM), Spitz tumors by,31 desmoplastic melanoma and atypical, 160- 171 Telangiectasia, in Spitz nevi, 160 desmoplastic-neurotropie defined, 148- 149 Territorial behavior, of melanoeytes of the melanoma assoeiated with, 290 differentiating from desmoplastic human epidermis, 2-3 Solar lentigo, 40, 275-280 melanoma and neurotropie Theque. See Junctional nest Solar melanocytic hyperplasia (SMH), melanoma, 300 Thickness of a primary tumor, and 278- 280 differentiating from nodular melanomas, prognosis, 373-375 defined, 278 267 Tisch nodules (pigmented hamartomas of Solar melanoma, 267-275 Sporadic melanoma, gene changes in, 21 the iris), diagnostie of age at development of, 248 Squamous carcinoma, spin die cell, neurofibromatosis, 40 406 Index

Tissue processing, for biopsies of See also Epithelioid melanocytes V melanocytic lesions, 12-13 Type B nevus cells, 61 Variants Tissue regeneration, proliferation of Type C nevus cells, 61 cytologic, of melanocytes in nevi, 7, epidermal melanocytes in response in the dermal component, 66 89-102 to,3 Tyrosinase of melanomas, 241-242 Tuberous sclerosis (epiloa), association activity of, demonstration with the and histomorphologic alterations, with cafe-au-Iait macules, 40 DOPA oxidase technique, 13-14 328-336 Tubular Spitz nevus, 180 blood levels of, measuring to predict morphological and cytological, 289-328 Tumoral melanosis, regression in, 342-343 clinical relapse, 382-383 morphologic, of nevoid melanoma, Tumor cells for recognizing metastatic tumor 304--305 dissociation of, in metastatic melanoma deposits in sentinellymph nodes, ofSpitz nevus, 171, 178-180 mimicking other neoplasms, 362 358 Pagetoid, 263 type of, and prognosis in malignant role of, in melanogenesis, 1 Vascular invasion, and prognosis in melanoma,379 nIl antibody to, as a marker for malignant melanoma, 377 Tumor-infiltrating Iymphocytes (TILs), 261 melanocytes, 15 Verrucous melanoma, 311-312 presence of, and prognosis in malignant Tyrosinase-related protein 1 (TRP-I; Vcrtical growth phase (VGP), of melanoma,378 gp75), as a melanocyte melanoma, 242-243 Tumor invasion, depth of, and pro gnosis, differentiation marker, 15 Vimentin, of melanocytes, electron 374-375 L-Tyrosine, substrate for the melanin micrographs of, 3 Tumor necrosis factor (TNF) pathway,1 Visceral blue nevi, 220 transmembrane family, role in Vulvar lentigo, 48 apoptosis in melanoma cells, 30-31 U Tumor-suppressor genes Ulceration of the primary tumor W CDKN2A and ARF, 21 and pro gnosis, 375-376 Warthin-Starry stain, 13 control of metastasis by, 30 in stage III disease, 385 Watson syndrome, association with cafe• loss-of-function mutation of, in Ultraviolet light (UV light) au-Iait macules, 40 melanomas, 20 effect of, on development of nevi, 52 Westerhof syndrome, association of cafe• pI4ARF, structure and function of, 26 response to au-Iait macules with, 40 Tumor vascularity, and prognosis, in mediation by the melanocortin 1 malignant melanoma, 379 receptor,21 X Tumor volume, and prognosis, 379 proliferation of epidermal Xanthogranuloma, differentiating from 21N antibody, specificity of, for mammary melanocytes, 3 Spitz nevus, 171 Paget' s disease, 265 upregulation of melanocortins in the Xeroderma pigmentosum (XP) Twin data skin, 28 lentiginous lesions associated with, 267 concordance of nevus phenotype See also Sunlight, exposure to melanomas diagnosed in patients with, between identical twins, 56 Ultraviolet radiation (UV radiation), 141-142 indicating genetic control of growth of signature mutations of, involving C solar lentigines in, 41 nevi,52 to T transitions, 24 Type A nevus ceoosk 61 Uniformity, of cells and nuclei of Spitz Z inverted, 98-100, 228-230 nevi,154--157 Zonation, in Spitz nevi, 158-159