Appendix. Table 1 MPATH-Dx Histology Reporting Form

Transcription

1 Appendix Table 1 MPATH-Dx Histology Reporting Form R.L. Barnhill et al. (eds.), Pathology of Melanocytic Nevi and Melanoma, DOI / , Springer-Verlag Berlin Heidelberg

2 628 Appendix Table 1 (continued)

3 Appendix 629 Source: Piepkorn MW, Barnhill RL, Elder DE, Knezevich SR, Carney PA, Reisch LM, Elmore JG (2014) The MPATH-Dx reporting schema for melanocytic proliferations and melanoma. J Am Acad Dermatol 70(1): Table 2 MPATH-Dx Diagnostic-Treatment Mapping Tool assume the margins are positive Class Clinical outcome Terms on histology form 0 Repeat testing or Incomplete study due to sampling and/or technical limitations short term follow up Significant pathology not necessarily ruled out by this examination 1 No further treatment Nevus and related- Common nevus junctional, compound, intradermal, No apparent risk required combined, congenital pattern for continued Nevus and related- Lentiginous nevus, junctional or compound local Nevus and related- Blue nevus and related lesions: common proliferation Lentigo related- Ephelis and adverse outcome Atypia- Dysplastic nevus (nevus with architectural disorder and cytological atypia; Clark s nevus, junctional or compound), mild Nevus and related- Congenital melanocytic nevus: junctional, compound, or intradermal Lentigo related- Solar lentigo Lentigo related- Lentigo simplex Nevus and related- Blue nevus and related lesions: Ito/Ota/Mongolian spot Nevus and related- Halo nevus Atypia- Persistent (recurrent) nevus Atypia- Lentiginous melanocytic proliferation (of sun-damaged OR non-sun-damaged skin) with atypia: mild Nevus and related- Nevus of special anatomic site: acral, genital, flexural, milkline and breast, scalp Atypia- Atypical nevus NOS including atypical nevus of special anatomic site (acral, genital, flexural, milkline/breast, etc.), mild

4 630 Appendix Table 2 (continued) Class Clinical outcome Terms on histology form 2 Low level risk for local proliferation of remaining cells; probability of progressive disease unlikely; potentially adverse outcome in some cases 3 Higher likelihood of local tumor progression and greater need for intervention; No reliable data for actual risk 4 Substantial risk for locoregional progression Narrow but complete re-excision (<5 mm) Repeat excision with at least 5 mm (but <1 cm) margins Wide excision ( 1 cm) T1a Atypia- Dysplastic nevus (nevus with architectural disorder and cytological atypia; Clark s nevus, junctional or compound), moderate Atypia- Atypical nevus NOS, including atypical nevus of special anatomic site: acral, genital, flexural, milkline and breast, scalp moderate Nevus and related-pigmented spindle cell nevus: junctional or compound Nevus and related-spitz nevus conventional: junctional, compound, or intradermal Atypia-Lentiginous melanocytic proliferation with moderate atypia (of sun-damaged OR non-sun-damaged skin) Nevus and related- Blue nevus: cellular or epithelioid Nevus and related- Deep penetrating nevus/dermal plexiform spindle cell nevus Atypia- Proliferative nodules in congenital melanocytic nevi (moderate or no atypia or no mitotic activity) Atypia- Dysplastic nevus (nevus with architectural disorder and cytological atypia; Clark s nevus, junctional or compound), severe Melanoma, in situ (common/pagetoid/superficial spreading melanoma) Melanoma, in situ, lentiginous, sun-damaged skin (lentigo maligna) Melanoma, in situ, lentiginous non-solar (i.e., acral or other) Melanoma, in situ, not otherwise specified (NOS) Atypia- Lentiginous melanocytic proliferation with severe atypia (of sun-damaged OR non-sun-damaged skin) Atypical spitzoid lesion-atypical/dysplastic/spitz tumor (junctional, compound, or dermal) Atypical spitzoid lesion-atypical pigmented spindle cell tumor, (junctional or compound) Atypia- Atypical nevus NOS including atypical nevus of special anatomic site (acral, genital, flexural, milkline/breast, scalp, etc.), severe Atypia- Proliferative nodules in congenital melanocytic nevi (moderate/ severe atypia and/or mitotic activity) Melanocytic lesion of uncertain malignant potential- Pagetoid intraepidermal melanocytic proliferation (PIMP) Invasive melanoma-acral-lentiginous melanoma Invasive melanoma-blue nevus-like, a melanoma resembling or originating from a blue nevus Invasive melanoma-desmoplastic melanoma Invasive melanoma- Heavily pigmented melanoma, a melanoma resembling epithelioid blue nevi or melanomas developing in animals Invasive melanoma- Invasive melanoma, unclassifiable Invasive melanoma- Lentigo maligna melanoma Invasive melanoma- Melanoma arising in a congenital nevus Invasive melanoma- Metastatic melanoma Invasive melanoma- Neurotropic melanoma Invasive melanoma- Nevoid melanoma (a melanoma resembling a common nevus) Invasive melanoma- Nodular melanoma Invasive melanoma- Persistent melanoma (if invasive melanoma T1a) Invasive melanoma- Pigmented spindle cell-like, a melanoma resembling pigmented spindle cell nevus or plexiform spindle cell nevus Invasive melanoma- Spitz-like, a melanoma that resembles a Spitz nevus/ tumor Invasive melanoma- Superficial spreading melanoma

5 Appendix 631 Class Clinical outcome Terms on histology form 5 Greater risk for regional and/or distant metastasis Variable classification (Classes 2 4) Wide excision ( 1 cm) T1b or more Melanocytic lesions of uncertain malignant potential Invasive melanoma- Acral-lentiginous melanoma Invasive melanoma- Blue nevus-like, a melanoma resembling or originating from a blue nevus Invasive melanoma- Desmoplastic melanoma Invasive melanoma- Heavily pigmented melanoma, a melanoma resembling epithelioid blue nevi or melanomas developing in animals Invasive melanoma- Invasive melanoma, unclassifiable Invasive melanoma- Lentigo maligna melanoma Invasive melanoma- Melanoma arising in a giant congenital nevus Invasive melanoma- Metastatic melanoma Invasive melanoma- Nevoid (a melanoma resembling a common nevus) melanoma Invasive melanoma- Neurotropic melanoma Invasive melanoma- Nodular melanoma Invasive melanoma- Persistent melanoma (if invasive melanoma T1b) Invasive melanoma- Pigmented spindle cell-like, a melanoma resembling pigmented spindle cell nevus or plexiform spindle cell nevus Invasive melanoma- Spitz-like, a melanoma that resembles a Spitz nevus/ tumor Invasive melanoma- Superficial spreading melanoma Melanocytic lesion of uncertain malignant potential- Atypical melanocytic neoplasm, junctional Class 2 or 3 Melanocytic lesion of uncertain malignant potential- Atypical intraepithelial melanocytic proliferation (AIMP) Class 2 or 3 Melanocytic lesion of uncertain malignant potential- Pagetoid intraepidermal melanocytic proliferation (PIMP) Class 2 or 3 Melanocytic lesion of uncertain malignant potential- Superficial atypical melanocytic proliferation of uncertain significance (SAMPUS) Class 3 or 4 Melanocytic lesion of uncertain malignant potential- Melanocytic tumor of uncertain malignant potential (MELTUMP) Class 3, 4, or 5 Melanocytic lesion of uncertain malignant potential- Atypical melanocytic neoplasm, compound Class 3, 4, or 5 Source: Piepkorn MW, Barnhill RL, Elder DE, Knezevich SR, Carney PA, Reisch LM, Elmore JG (2014) The MPATH-Dx reporting schema for melanocytic proliferations and melanoma. J Am Acad Dermatol 70(1): Classification of 4 vs. 5 is defined as follows: T1a (class 4): Breslow thickness of 1.00 mm, no ulceration and no mitotic rate or mitotic rate <1 mm 2 T1b (class 5): Breslow thickness of 1.01 mm or more or Breslow thickness of 1.00 mm, with yes ulceration and/or mitotic rate 1 mm 2

6 632 Table 3 Synoptic report for primary cutaneous melanoma Pathological feature Feature recorded Location Left back Diagnosis Melanoma Histological subtype Lentigo maligna Breslow thickness (mm) 1.55 Mitotic rate (per mm 2 ) 6 Ulceration Absent Clark level IV Vascular or lymphatic invasion Absent Neurotropism Absent Desmoplasia Absent Microscopic satellites Absent Regression Absent Tumor-infiltrating lymphocytes Present, brisk Associated nevus Dermal nevus Margin positive No Nearest peripheral margin to in 5 situ or invasive component (mm) Distance from tumor to deep 5 margin (mm) Appendix Table 4 American Joint Commission on Cancer Staging System for Melanoma, 7th Version (2010) Stage Criteria 0 Melanoma in situ IA Tumor thickness 1.0 mm without ulceration and mitosis 0/mm 2 IB Tumor thickness 1.0 mm with ulceration or mitosis 1/mm 2 or tumor thickness mm without ulceration IIA Tumor thickness mm with ulceration or tumor thickness mm without ulceration IIB Tumor thickness mm with ulceration or tumor thickness >4 mm without ulceration IIC Tumor thickness >4 mm with ulceration IIIA Any tumor thickness with no ulceration and 1 3 microscopic nodes IIIB Any tumor thickness with ulceration and 1 3 microscopic node(s) or any tumor thickness without ulceration and 1 3 microscopic nodes or any tumor thickness without ulceration and 1 3 clinically detectable nodes or nodal metastasis exhibiting extracapsular extension or satellite(s)/in transit metastases without metastatic nodes IIIC Any tumor thickness with ulceration and either 1 3 macroscopic node(s) or satellite(s)/in transit metastases without metastatic node or any tumor thickness with 4 or more metastatic nodes or matted nodes or satellite(s)/in transit metastasize(s) with metastatic node(s) IV Any tumor thickness, any number of nodes, and any distant skin, subcutaneous or nodal or visceral metastases

7 Index A Acquired melanocytic nevi clinical features, cross-sectional silhouette correlates, 100 cytological features dermal nevus, lymphocytoid cells, 97, 99 mitoses, 98 nevus giant cells, 98 Schwannian cells, 97 dermal variations, description, 93 epidermal changes, 100 compound nevus, 96, 97 dermal nevus, 97, 98 junctional nevus, 95 lentiginous nevus, 95, 96 papillomatous dermal nevus, 97, 99 Acquired melanosis. See Primary acquired melanosis (PAM) Acral melanoma (AM) atypical melanosis, 377 Caucasian populations, 376 clinical features, 378 definition, 376, 377 dorsal skin, 376 foot, heels, metatarsal areas and toes, 378 attributes, glabrous skin, 378 dermal component, 379, intraepidermal melanocytes, 347, 379, 380 recognition, 379 SUM, 379, 383 lentiginous macular lesions, molecular genetics, 378 nail apparatus, 376 subtypes, viruses and chemical carcinogens, 378 Acral melanosis. See Volar melanotic macules (VMM) Acral nevus clinical features, description, 139 diagnosis, 140 histological features, 140 Adnexotropism, 222 AJCC. See American Joint Committee on Cancer (AJCC) Alternative reading frame (ARF) genomic structure, 38, 39 mutation/deletion analysis epigenetic mechanisms, 40 melanocytic tumors, 41 penetrance, CDKN2A mutations, 41 promoter sequence variation, 40 sporadic cancers, 39 AM. See Acral melanoma (AM) α-melanocytic stimulating hormone (α-msh) autocrine and paracrine expression, 46 eumelanin and pheomelanin, 47 high and lower affinity binding, 46 peptides, 46 Amelanotic blue nevus, Amelanotic melanoma, American Joint Commission on Cancer Staging System, 632 American Joint Committee on Cancer (AJCC), 570, 571, 574, 575, 588 Angiotropic melanoma extravascular migratory metastasis (EVMM), 408 immunohistochemistry, 409 nerves and skin appendages, 408 pericytic markers, 409 pericytic mimicry, 408 Animal-type melanoma (ATM) clinical features, differential diagnosis atypical and malignant variants, 447, 449 epithelioid blue nevi, 447 tumoral melanosis, 445, 447 epithelioid blue nevus, 446, 447, 448 regional lymph node involvement, Anorectal melanoma description, 498 differential diagnosis, 498, 500 histopathology, Anorectal region anorectal melanoma, mucosal melanomas, 497, 498 R.L. Barnhill et al. (eds.), Pathology of Melanocytic Nevi and Melanoma, DOI / , Springer-Verlag Berlin Heidelberg

8 634 ATM. See Animal-type melanoma (ATM) Atypical/dysplastic nevi architecture grading, 122 intraepidermal nesting, melanocytes, 122 lentiginous proliferation, 121 papillary dermis, 118, 121 single-cell melanocytic arrays, 121 chronology, descriptions, 104 clinical features, clinical phenotypes, 103, 104 clinicopathologic continuum, 105 cytological features basilar melanocytes, nuclear atypia, 123 diagnosis de novo intraepidermal epithelioid melanocytic dysplasia (DNIEMD), 126 epidermal hyperplasia and stromal reaction, 127 epithelioid cytomorphology, lentigo maligna, 125 in situ/microinvasive melanoma., 124 epithelioid cell dysplastic nevus, grading and histopathological reporting, halo nevus variant, 124 architectural and cytological features, 113, 121 dense lymphocytic infiltrate fills, 113, diagnosis, 118 epithelioid cell variant, 113, high-grade cytological atypia, 113, intraepidermal component, 113, 115 lentiginous melanocytic proliferation and variation, 117 lentiginous pattern, junction, 113, 115 nesting and nuclear characteristics, 113, nuclear atypia, 115 population-based study, 114 host response dermal fibroplasia, 123 lymphocytic infiltrates, 123 papillary dermis, 123 markers CKN2A mutations, 107 clinically atypical nevi, 107, 108, 110 epidemiological studies, 109 follow-up, patients, 107 nevus phenotypes, 107, 110 risk, melanoma, 107, 109 melanoma CDKN2A, 111, 112 genetic alterations, 111 nevus remnants, tumor-related antigens, 111 prevalence, melanoma risk and genetics, 104 syndrome, 106 Atypical/dysplastic nevi (AN), Atypical plexiform spindle cell melanocytic tumor clinical and, 321 Atypical Spitz tumor assessment, 226 atypical features, 225 cellular fascicles of spindle cells, 224 in children and adolescents, concept, 223 de novo epithelioid cell dysplasia, 227 dermal component, differential diagnosis, dysplastic Spitz tumor, 226 features, 224 intraepidermal component, 226 mitoses and focal necrosis, 224 pagetoid Spitz tumor, 226 regional lymph node spread, Index B Balloon cell melanoma (BCM) clinical features, 443 differential diagnosis, 442, 444 pagetoid spread, epidermis, 443 pathogenesis, recognition, 442 Balloon cell morphology, 543 Balloon cell nevus clinical features, 128 description, 128 diagnosis, 128, 128, 129 BCM. See Balloon cell melanoma (BCM) Becker nevus (BN) characteristics, 76 clinical features, 76 description, 75 diagnosis, epidermal nevus/lentigo simplex, 77 smooth muscle, 77 syndrome, 76 Biopsies curettage, 14 excisional, 13, 14 fixation, 15 Mohs micrographic surgery, punch, research, tissue, 15 shave, 14 tissue processing, 15 Biopsy techniques and tissue submission en bloc longitudinal excision, 615 hard keratin, 616 microscopic interpretation, proximal nail fold and plate, 615 softening agents, 616 Blue nevus amelanotic, 281 CBN, (see also Cellular blue nevus (CBN)) compound, dendritic-fibrotic type,

9 Index epithelioid cell variant, 281 lymph node involvement, patch-like, 294 plaque-type, sclerosing, 278, spindle cell component, 276 target, Blue nevus-like melanoma (BNLM) advanced stage, 433 atypical epithelioid cells, CBN, 290 characteristics, 430 clinical features, 433, 435 diagnosis, 430 differential diagnosis, , 435 lymph nodes, 430 MBN, 430 (see also Malignant blue nevus (MBN)) molecular genetics, 435 spindled and epithelioid melanoma cells, 429, 433 BN. See Becker nevus (BN) BNLM. See Blue nevus-like melanoma (BNLM) BRACA-associated protein 1 (BAP1), 21 BRAF locus MAPK, 35, 36 oncogene-induced senescence, 35 serine-threonine kinase, 35 BRAFV600E, 21, 22 C Café-au-lait Macule (CALM) clinical features, 61, 62 description, 61 diagnosis, 64 diseases and syndromes, electron microscopy, 62 epidermis and basal layer hyperpigmentation, 61, 62 melanocytic density, 62 CALM. See Café-au-lait Macule (CALM) CBN. See Cellular blue nevus (CBN) CCS. See Clear cell sarcoma (CCS) CDK4. See Cyclin-dependent kinase 4 (CDK4) CDKN2A. See Cyclin-dependent kinase inhibitor 2A (CDKN2A) Cellular blue nevus (CBN) architecture, 284 atypical aggregates, tumor cells, 290, 291 BNLM, 290, 292 clear cell sarcoma, 292 dermatofibrosarcoma protuberans, 293 metastases, 292 composition alveolar, 284 fascicles, spindle cells, multinucleate giant cells, 290 description, morphologic features, natural history, 284 CGH. See Comparative genomic hybridization (CGH) Clear cell melanoma, 449 Clear cell sarcoma (CCS) characteristic reciprocal translocation, clinical features, 437 cutaneous, , 439 description, 26 differential diagnosis, Ewing s sarcoma oncogene (EWS), 436 gastrointestinal tract, 436, 438 fascicles, spindle cells, 439, 440 nuclear size and shape, 440 oval/fusiform cells, 437 markers, 436 vs. metastatic melanoma, q12 (EWS) and 12q13 (ATF1), 27 survival rates, 436 CLND. See Completion lymph node dissection (CLND) C-MIN. See Conjunctival melanocytic intraepithelial neoplasia (C-MIN) CMN. See Congenital melanocytic nevi (CMN) Combined common and blue nevus junctional, compound, intradermal, 306 melanophages, 314 plexiform arrangements, Combined melanocytic nevi amelanotic spitzoid epithelioid and spindle cells, 316 cellular blue, 316 chromosomal aberrations, 305 clonal nevus, 305 comparison, combined nevus and melanoma, 316, 317 cytological atypia, 317 GNAQ and GNA11 mutations, 316 atypical, 314 cell types, 314 common and blue nevus, nomenclature, 305 Spitz, 314, 315 inverted type A, 303, 308, 309 MNFDECC, oral mucosa and conjunctiva, 304 Combined Spitz nevus, 244 Comparative genomic hybridization (CGH) array, chromosomal aberrations, 22 copy number, cytogenetic abnormalities, 24 description, 21 negative melanomas, 24 nevi and melanoma differ cytogenetically, 22 spitzoid lesions, 23 tumor cell heterogeneity,

10 636 Completion lymph node dissection (CLND), 530, 533 Composite melanocytic neoplasms Breslow thickness, 451 classification, clinical and, description, 450 desmoplastic trichoepithelioma, 452 differential diagnosis, 452, 456 prevalence, 451 squamous cell carcinomas, 451 Compound blue nevus, Compound dysplastic Spitz tumor, Congenital melanocytic nevi (CMN) anatomic structures, 156 associations, 160 clinical features melanocytic proliferation/melanoma, 160, 161 NCM, size and age, 160 definition, 155 diagnosis, 181, 183, 185 familial aggregation, 160 histological characteristics architectural disorder/cytological atypia, 173 cytological atypia, 162 dermal involvement, 162 dermal nodular proliferations (see Dermal nodular proliferations, CMN) epidermal changes, 170 frequency distribution, nevus depth vs. size, 162 immature disordered patterns, 162 large congenital nevus (see Large/giant CMN (LGCMN)) neurocutaneous melanosis, 174 pagetoid melanocytosis, 173, 174 periadnexal/perivascular pattern, 162 small congenital nevus (see Small CMN) incidence and melanoma risk, NCM, 158 NRAS and BRAF mutations, 159 and pediatric melanoma, small, medium and large sized, 156, 157 stem cells/pluripotential cells, 159 Congenital melanosis characterization, 509 oculodermal melanocytosis, 509 postinflammatory hyperpigmentation/medicationrelated phenomenon, 509 Congenital/neonatal melanoma array CGH, 197 classification, 188, 189 de novo, 197, 198 DNA ploidy, 196 proliferative nodules development, 196 Conjunctiva congenital melanosis, 509 description, 509 melanocytic nevi, melanoma, PAM (see Primary acquired melanosis (PAM)) Conjunctival melanocytic intraepithelial neoplasia (C-MIN) conjunctival melanoma in situ, 514, 515 PAM with atypia, 514, 515 Conjunctival melanocytic nevi clinical features, 512 bulbar conjunctiva, 510, 511 differential diagnosis, genetics, 511, treatment, 513 Conjunctival melanoma clinical features Caucasians ranges, DNA repair deficiency, 515 ill-defined borders and irregular color/shape, 515 precursor lesion, 515, 516 squamous cell carcinoma, 514 differential diagnosis, 516 genetics, 516, management, prognosis AJCC classification, 518, 519 lymphatic channels, 517 staging system, variables, 517 Curettage biopsy, 14 Cutaneous melanoma amelanotic melanoma, angiotropic melanoma, ATM (see Animal-type melanoma (ATM)) BCM, BNLM (see Blue nevus-like melanoma (BNLM)) CCS, classification morphological, cytological and molecular variants, 337 progressive proliferation, melanocytes, 333, 334 RGP (see Radial growth phase (RGP)) VGP (see Vertical growth phase (VGP)) WHO classification, clear cell melanoma, 449 common acquired nevus, dermal component cellular density, melanocytes, 425, clinical features, 425, 427 differential diagnosis427, 430 inflammatory cell, 426 composite melanocytic neoplasms, cytological characteristics, 346 description, 331 DM (see Desmoplastic melanoma (DM)) epidemiology data and facts, 331, 332 diagnostic drift, 333 incidence and mortality, 332 men and women, sex ratio, 333 risk factors, Index

11 Index histopathological criteria dermal component, epidermal component, (see also Epidermis) reporting, 472, 474, 629 melanocytic matricoma, myxoid melanoma, nevoid melanoma, NTM, (see also Neurotropic melanoma (NTM)) polypoid configuration, 441 risk factors, 333 SDM, signet-ring cell melanoma, spitzoid melanoma, SSM (see Superficial spreading melanomas (SSM)) sun-damaged skin, small cell nevoid melanomas (see Small cell melanoma) unusual/rare variations, 441 Cutaneous nevus vs. metastatic, Cyclin-dependent kinase 4 (CDK4), Cyclin-dependent kinase inhibitor 2A (CDKN2A) ARF (see Alternative reading frame (ARF)) chromosomal arm, 37 genetic linkage analysis, 37 homologues, 38 INK4 family, 38, 39 melanocytic nevi, murine knockout models, nomenclature, p16, 38 RB pathway, 44 restriction points, 43 retinoblastoma gene, 43 Cytogenetic studies CGH (see Comparative genomic hybridization (CGH)) FISH analysis (see Fluorescence in situ hybridization (FISH)) D Deep penetrating nevus, description, 326 non-plexiform pigmented spindle and epithelioid nevus, 327 Dendritic-fibrotic type. See also Blue nevus fibrotic nodule, 277, 278 fluorescence in situ hybridization, 277 De novo intraepidermal epithelioid melanocytic dysplasia (DNIEMD), 126 Dermal melanocytoses blue nevus (see Blue nevus) differential features, 272, 273 face and extremities, hamartoma, 275 histogenesis, Mongolian spot, 272 neurocristic hamartoma, 296 nevus fusco-caeruleus 637 acromiodeltoideus, 275 ophthalmomaxillaris, zygomaticus, 274 reticular dermis, 271 Dermal nodular proliferations (proliferative nodules, in), CMN angiotropism, 173, large/giant, 173, medium-size, 173, Dermoepidermal junction, 216 Desmoplastic melanoma (DM) antecedent lesion, 390 benign fibroblasts, 390 characteristics, clinical and, 390 composite phenotypes, electron microscopy, spindle cells, immunohistochemistry, 390, 391 molecular genetics, 392 neural differentiation, 388 Desmoplastic-neurotropic melanoma (DMN) clinical features, 392 de novo, 393 fascicles, spindle cells, intraepidermal component, 393 myxoid alteration, 398 neurofibroma and DMN, 398 paucicellular dermal spindle cell proliferation, prominent perineurial and endoneurial infiltration, Desmoplastic Spitz nevus angiomatoid Spitz nevus, 241 clinical features, 240 differential diagnosis, melanoma and, 244 Differential diagnosis desmoplastic nevus, 409 desmoplastic Spitz tumor, 409 fibroxanthoma and pleomorphic sarcoma, myxomas, 410 neurothekeoma, scarring and fibrous, 408 Schwannian differentiation, 409 squamous cell carcinoma, 410 SSM nested pattern, 361 pagetoid pattern, sun-damaged skin, 408 Distant metastases BRAF, 535 description, 535 ipilimumab and PD-1 inhibitors, 535 lungs, 535 systemic therapies, 535 TNM staging system, 535 DM. See Desmoplastic melanoma (DM) DMN. See Desmoplastic-neurotropic melanoma (DMN) DNIEMD. See De novo intraepidermal epithelioid melanocytic dysplasia (DNIEMD)

12 638 Dopa oxidase technique, 16 Dysplastic Spitz tumor, 226 Dysplastic nevi, pagetoid melanocytosis atypical nevus cells, discrimination, 359 halo nevi, 360 lymphoid cells, 360 Paget disease (PD), E Electron microscopy melanosome, 4 phaeomelanosomes, 4 skin pigmentation, 5 stages, eumelanosome formation, 4, 5 Ephelis. See Freckle Epidermis, in melanoma cellular density, 341 circumscription, 341 configuration, lesional diameter, 339 melanocytosis lentiginous pattern, 344, 345, 347 nested pattern, 344, 348, 349 pagetoid pattern, symmetry, Epithelioid, blue nevus Carney s complex, 281 melanophages and fibrosis, 281 pigmented melanocytoma, 282 Epithelioid cell morphology, in melanoma metastases in brain, 540, 543 description, 540 in liver, 540, 543 SLNs, , 540 small intestine, 540, Epithelioid melanocytes, Esophageal melanoma clinical features, 500 description, 500 differential diagnosis, , 500, 501 EVMM. See Extravascular migratory metastasis (EVMM) Excisional biopsies description, 13 sentinel lymph node (SLN) biopsy, 13 skin excisions, pigmented lesions, 13, 14 ulceration, 13, 14 Extravascular migratory metastasis (EVMM), 408 Eye. See Melanocytic proliferations F Fas (CD95) apoptotic pathway, 52 IGF-1, 51 master transcriptional regulator, 51 MHC, 50, 51 TNF, 50 FISH. See Fluorescence in situ hybridization (FISH) Fluorescence in situ hybridization (FISH), 24 26, 583 advantages, 24 and CCS, disadvantages, 24 histopathologically ambiguous melanocytic tumors, 26 melanoma FISH test, negative melanomas, 27 nevus distinction adjunct test, 25 blue nevus, 26 conjunctival nevus, 26 microstaging primary melanoma, 26 Spitz nevi, 26 positive melanocytic nevi, 27 and UM, 26 Freckle clinical features, 59 description, 59 diagnosis, 61 basal layer hyperpigmentation, 59, 61 dopa-stained sections, 60 lentigo simplex, 59, 60 solar lentigo, 59, 60 G Gastrointestinal tract and anorectal region (see Anorectal region) description, 497 primary melanoma, 499 Genitourinary tract description, primary melanoma, 501 urinary tract, 503 vulvar and vaginal melanomas, Giant nevus cells, GNAQ/GNA11, Gp100 (HMB-45), 17 H Halo nevus clinical features, 130 description, diagnosis, 133 etiology, , Halo Spitz tumor BAP1 mutations, 246 biphasic and asymmetrical lesions, 246 dermal melanocytes, 246 occurrence, 246 Hamartoma, dermal melanocyte developmental abnormalities, 275 HMB-45, 17. See also Gp100 Hyalinizing Spitz nevus, 244 Hypermelanosis basilar epithelial cells, 513 intramucosal melanocytes, 514 Index

13 Index I IDCs. See Interdigitating dendritic cells (IDCs) IGF-1. See Insulin-like growth factor-1 (IGF-1) IHC. See Immunohistochemistry (IHC) Immune system, Immunohistochemistry (IHC), 16, 539 Insulin-like growth factor-1 (IGF-1), 51 Interdigitating dendritic cells (IDCs), Invasive melanoma anatomic levels, 354 granular eosinophilic cytoplasm in melanoma cells, 354, 355 microscopic satellites, 356, 357 regression, 355, 357 tropisms, 354 tumor thickness, 355 ulceration, epidermis, 354, 355 J Junctional cleavage in Spitz nevi, 221 Juvenile melanoma, 205 K Kamino bodies, 221 KBA62, 19 Ki-67, 20 Ki-67/MIB-1 index, 20, 531 KIT (c-kit, CD117), 29 L Large/giant CMN (LGCMN) atypical nodular melanocytic proliferation (proliferative nodule), 183 clinical and, 183, 185 dermal component, distinctive features, 169 intraepidermal and dermal proliferations development, 180 leptomeningeal melanoma, 183 lesions simulating melanoma, 169, neurotization, nevus cells, 169, 170 nodular proliferations development, predominant dermal pattern, Lentigo maligna melanoma (LMM) atypical lentiginous melanocytic proliferations, 367 clinical features, definition, 364 description, 362 head and neck, predilection, 364 melanocytic dysplasia, 364 melanoma in situ epidermal rete ridges, 370 nesting, melanocytes, pleomorphic and hyperchromatic nuclei, 345, 371 retraction, cytoplasm, 370 starburst cells, 370 molecular genetics, pigmented spindle cell variant dermal-epidermal junction, 371, 372 epithelioid and small nevus-like cells, 371, 373 stroma and mesenchymal cells, 371 premelanoma in situ, 367 PSCT, PUVA therapy and xeroderma pigmentosum, 365 solar lentigo and lentiginous melanocytic nevi adnexal structures, heterogeneity, 372 junctional nests, 373 melanin pigmentation, epidermis, 371 spectrum, lesions, 351, 364 tumor progression, 360 Lentigo simplex clinical features, 92 description, diagnosis, 93, 60, melanocytes, 65 LGCMN. See Large/giant CMN (LGCMN) Lichen sclerosus, 188 Li-Fraumeni syndrome, 33 Light (conventional) microscopy epidermal melanocytes, 3 histochemical stains, 3 4 Locoregional metastases prognosis, 534 satellites and in-transit metastases, SLN (see Sentinel lymph nodes (SLN)) SLNB, 530 Lymph node involvement, blue nevus, M Major histocompatibility complex (MHC), 50, 51 MAPK. See Mitogen-activated protein kinase (MAPK) McCune-Albright syndrome, 63, 64 MC1R. See Melanocortin 1 receptor (MC1R) MDM. See Minimal deviation melanoma (MDM) Melan-A/Mart-1, Melanin pigment description, 5 Epidermal Melanocyte Unit, 6 hemosiderin and lipofuscin, 7 MC1R, 6 neuromelanin, 7 pheomelanin, 6 Melanocortin 1 receptor (MC1R), 6 camp, 46, 47 α-msh, 46 proopiomelanocortin, 46 ultraviolet radiation, 47 wild-type and variant, 46, 48 Melanocytes anatomic distribution, 2 3 atypical SIMP (see Solar intraepidermal melanocytic proliferations (SIMP)) Becker nevus (BN), CALM, embryology and histogenesis

14 640 Melanocytes (cont.) cell type-specific markers, 1 MITF, 1 proliferation and migration, 2 specification, 2 stem cells, 1 freckle, lentigo simplex, 65 melanin pigment, 5 7 melanotic macules and lentigines, morphology electron microscopy, 4 5 light microscopy, 3 4 nevus cells, 7 9 SL (see Solar lentigo (SL)) VMM, (see also Volar melanotic macules (VMM)) Melanocyte stem cell (melsc), 1 Melanocytic lesions antigens Gp100 (HMB-45), 17 KBA62, 19 Melan-A/Mart-1, MITF, 18 NKI/C3, PNL2, 19 p75nr, 18 Sox 10, 19 S-100 protein, TRP-1, 18 tyrosinase, 18 biomarkers BAP1, 21 BRAFV600E, 21, 22 electron microscopy, 21 Ki-67, 20 p16, 21 phh3, 20 R21, enzyme histochemistry, 16 immunohistochemistry, 16 melanin stains, nonmelanocytic markers, Melanocytic matricoma clinical features, 456 differential diagnosis, , melanocytic and epithelial differentiation, 455 pilomatricomas, 456 pilomatrix carcinoma, 456 stem cell reservoir, 456 Melanocytic neoplasms with indeterminate biological potential classification, 471 diagnostic evaluation, malignant behavior, 471 management, 472, 473 nomenclature, 472 Melanocytic nevi Abtropfung hypothesis derives, acquired melanocytic nevi (see Acquired melanocytic nevi) Index acral nevus, atypical/dysplastic nevi (see Atypical/dysplastic nevi) balloon cell nevus, 128 cell type, 91 classification, 90 clinical features, 92 dermal nevi, 90 description, 87 diagnosis, 93 environmental factors, focal epithelioid cell component, 145 genetic and environmental factors, 88 halo nevus, , junctional nevus, 89 and lentigines, 89 lentigo simplex, neural nevus, 133 nevus spilus (see Speckled lentiginous nevus) recurrent melanocytic nevus (see Recurrent melanocytic nevus) site-specific nevus atypical genital nevus, 137 clinical features, description, 137 diagnosis, , 138, 139 special-site scalp nevus (scalp nevus with site-specific features) clinical features, 141 description, 141 diagnosis, , stages, 88 stroma, 91 tissue elements, 88 Melanocytic nevus with focal atypical dermal epithelioid cell component (MNFDECC), Melanocytic nevus with phenotypic heterogeneity (MNPH) combined nevus, 301, 303 atypical plexiform spindle cell melanocytic tumor, biphasic melanocytic lesions, 301 combined melanocytic nevi (see Combined melanocytic nevi) comparison, histological features, 301, 302 deep penetrating nevus, definition, 301 plexiform spindle cell melanoma, plexiform spindle cell nevus, potential developmental explanations, 303 Melanocytic proliferations conjunctiva (see Conjunctiva) orbital cavity, 526 uveal tract (see Uveal tract) Melanoma activation, BRAF locus, American Joint Commission on Cancer Staging System, 632 congenital nevi

15 Index development, 181 hamartomatous mesenchymal tumors, 183 intraepidermal and dermal proliferations, 180, 183 LGCMN, lymph nodes, 183, 186 skin, placenta and lymph nodes, 183, 186 small and medium CMN, familial susceptibility loci CDK4, CDKN2A and homologues, minor penetrant, tumor suppressor, genetic elements, 52 immune system, Li-Fraumeni syndrome, 33 metastasis, 49 MPATH-Dx diagnostic-treatment mapping tool, MPATH-Dx histology reporting form, mutational target, 34 neoplastic pathway, 34 pediatric melanoma (see Pediatric melanoma) primary cutaneous, 632 proto-oncogenes, 33 Melanosis epidermis, 560 skin/internal organs, 560 slate blue-gray/ brown discoloration, tumor-derived pigment, Melanotic macules and lentigines clinical features, 80 diagnosis, 80 81, 80 mucocutaneous sites, 78 syndromes, 79 Melanotic schwannomas, 541, 547 Melastatin, 50 MelSC. See Melanocyte stem cell (melsc) Metastasis oncogenes, 49 tumor suppressor genes, Metastatic melanoma blue nevus-like melanoma, 539 vs. CCS, vs. cutaneous nevus, cytologic diagnosis, description, 529 distant, 535 histopathologic guidelines, 558 IHC, 539 locoregional (see Locoregional metastases) lymph nodes, 539 molecular pathology mutation testing (see Molecular pathology mutation testing) morphology architectural and cytologic variants, in brain, 540, 543 histochemical stains, 540, 540 in liver, 540, 544 in lung, melanin pigment, 540 small intestine, 540, vs. nodal nevus, vs. non-melanocytic tumor (see Non-melanocytic tumor vs. metastatic melanoma) pathologic diagnosis, 539 vs. primary cutaneous melanoma, primary dermal melanoma, 539 (see also Solitary dermal melanoma (SDM)) vs. primary mucosal melanoma, primary tumor, 539 with unknown primary site adrenal gland, cutaneous primary sites, 559 intranodal nevus cells, 558 ophthalmoscopic and radiographic studies, 559 in women, 558 MHC. See Major histocompatibility complex (MHC) Microinvasive melanoma level II invasion, 352 papillary dermis, 352 regression, 353, 354 skin appendages, 352 Microphthalmia transcription factor (MITF), 1, 2, 6, 18, 586 Minimal deviation melanoma (MDM) cellular phenotypes, 410 nodular proliferation, 410 verrucous melanoma, Minor penetrant definition, 46 MC1R, red hair, freckle and risk, MITF. See Microphthalmia transcription factor (MITF) Mitogen-activated protein kinase (MAPK), 35, 36 MMs. See Mucosal melanomas (MMs) MNFDECC. See Melanocytic nevus with focal atypical dermal epithelioid cell component (MNFDECC) MNPH. See Melanocytic nevus with phenotypic heterogeneity (MNPH) Mohs micrographic surgery basal cell and squamous cell carcinomas, 14 debulking, 15 description, 14 melanocytic lesions, Molecular pathology mutation testing advantages and disadvantages, 536 BRAF and NRAS, 536 cell blocks, 536 description, formalin-fixed and paraffin embedded tissue, 536 IHC, 539 lymph node, BRAF VE1 antibody, 538, 539 pyrosequencing and mass spectroscopy assays, Roche cobas test, 538 Sanger sequencing, Mongolian spot, dermal melanocytosis dermis, 272 melanophages/fibrosis, 272 skin texture, 272

16 642 MPATH-Dx diagnostic-treatment mapping tool, MPATH-Dx histology reporting form, α-msh. See α-melanocytic stimulating hormone (α-msh) Mucosal melanomas (MMs) BRAF and KIT(c-Kit) inhibitors, 490 characteristics, 490 clinical trials, 490 description, 489 gastrointestinal tract and anorectal region, genetic tests, 490 genitourinary tract, head and neck region description, oral cavity, pharynx and larynx, prognosis, 491 sinonasal melanoma, lymph nodes, melanocytic markers, 490 multicentricity and angioinvasion, 490 prognostic implications and management approach, 490 Mutation analysis clinical utility, 29 melanoma BRAF, 28 GNAQ/GNA11, KIT, 29 melanocytic nevi, 29 NRAS, 28 testing, genetic changes, Myxoid melanoma, N Nail apparatus anatomy and histology bed, 604, 606 description, immunohistochemistry, 607 immunoperoxidase stains, 607 keratinization, 604 mamelons, 604 melanocytes, 604, 607 plate, 604 proximal matrix, 604 red chromogen/giemsa, 607 biopsy, 603 clinical features amelanotic melanoma, 615 demographic data, 608 dermatoscopy, desmoplastic melanoma, 615 Hutchinson s sign, 609 lentigo, 609, longitudinal pigmented bands, melanocytic activation, NAM, 609 nevus, 609, description, 603 Index lentigo (melanocytic hyperplasia), melanocytic activation (hypermelanosis), 616 melanocytic nevi, 617 melanonychia, 616 non-melanocytic causes, subungual/ungual melanoma, non-melanocytic conditions, 603 specimen type, 603 suboptimal specimens, 603 tissue submission and biopsy techniques, NCM. See Neurocutaneous melanosis (NCM) Neural nevus, 133 Neurocristic hamartoma, 296 Neurocutaneous melanosis (NCM), 158, , 174 Neurotropic melanoma (NTM) clinical presentation, 402 dermal component, desmoplastic, 389, 401 differential diagnosis (see also desmoplasticneurotropic melanoma) desmoplastic nevus, 407 desmoplastic Spitz tumor, 407 fibroxanthoma and pleomorphic sarcoma, myxomas, 408 neurothekeoma, scarring and fibrous, 406 Schwannian differentiation, 407 squamous cell carcinoma, 408 sun-damaged skin, 406 DM/DMN, epidermis, skin appendages and mucosa, nerve-centered variant, 400, 404 pagetoid involvement, 403 perineurium and endoneurium, Schwannian differentiation, 404 spindle cells, 401, 404 immunohistochemistry, neural transforming, 401, 402 Nevoid melanoma ancillary techniques, 417, 419 clinical features, 410, 411 differential diagnosis atypical halo/halo-like nevi, effacement and thinning, 419 metastatic melanoma, 420 nonmelanocytic tumors, 419 sheetlike arrangements, nevus cells, 419 heterogeneity, cell type, maturation and melanocytes, mitoses, 417 morphological variants, 417 verrucous variants, 417, 418 MDM, vs. melanocytic nevus, 409, 410 verrucous and pseudonevoid melanomas, 409 Nevus cells dropping off (Abtropfung), 9 epithelioid, lymphoid and Schwannian, 8 nevocytes and nevoblasts, 8 9 OIS, 9

17 Index Nevus fusco-caeruleus acromiodeltoideus, 275 Nevus fusco-caeruleus ophthalmomaxillaris macule, 272 melanoma, in, 273 slender pigmented fusiform and dendritic melanocytes, Nevus fusco-caeruleus zygomaticus, 274 NKI/C3, NM. See Nodular melanoma (NM) Nodal nevus vs. metastasis capsular lymphatic spaces, 553 cellular variants, 552, description, 552 lymphatic spread, 555 in lymph nodes, MIB-1, morphology, 552, 556 nodal melanocytic lesions, Nodular melanoma clinical features, 362 differential diagnosis, 362, 365 epithelioid cells, 362 expansile pattern, growth, 362, 363 Non-melanocytic causes, nail pigmentation benzidine stain, 622 fontana stain, 622 iron stains, 622 microorganisms stain, 622 mimickers, 622, 623 nail dyspigmentation, 622 pigmented onychomycosis, 622 squamous cell carcinoma, 622 subungual hemorrhage, 622 Nonmelanocytic markers, Non-melanocytic tumor vs. metastatic melanoma balloon cell morphology, 543 epithelioid cell morphology, 540, lymphoma, carcinoma and sarcoma, 540 malignant fibrous histiocytoma, 545 myxoid stromal reaction, 544 other neoplasms, 540, 548 signet ring cell morphology, spindle cell morphology, staghorn-like vascular pattern, NORs. See Nucleolar organizer regions (NORs) NTM. See Neurotropic melanoma (NTM) Nucleolar organizer regions (NORs), 584 O OIS. See Oncogene-induced senescence (OIS) Oncogene-induced senescence (OIS), 9 Oral cavity, pharynx and larynx clinical features hard palate and upper alveolus, laryngeal melanomas, 496 prognosis, description, 494 differential diagnosis, 497 histopathologcial features confluent proliferation, atypical melanocytes, 495, 496 in situ component, 496 invasive oral mucosal melanoma, polygonal melanoma cells, 495, 496 spindle shaped melanocytes, 497 Orbital cavity, 526 P P16, 21 Pagetoid melanocytosis cytological atypia, 342, 343 epithelioid melanoma cells, 344, 348 free-floating, 342, 343 Paget disease, breast, 342 Pagetoid Spitz tumor, 226 PAM. See Primary acquired melanosis (PAM) Patch-like blue nevus, 294 Pediatric melanoma childhood and adolescent, 187, 189 classification, 187, 188 congenital/neonatal melanoma, diagnosis, 198 epidemiology childhood and adolescence, 185 SEER database, 185 simulants, children, 190 congenital/neonatal melanoma, epithelioid cell type, small round cell malignancies, 190 Spitz tumor, 190, 194 phenotypic characteristics, 188 preexisting lesions dysplastic nevi and atypical nevus phenotype, lichen sclerosus, 188 prognosis, PEM. See Pigmented epithelioid melanocytoma (PEM) PHH3. See Phospho-histone H3 (phh3) Phospho-histone H3 (phh3), 20 Pigmented epithelioid melanocytoma (PEM), Pigmented spindle cell nevus (PSCN) and atypical variants, 255 in children, 247 clinical features, 247 differential diagnosis, 252 epithelioid cells, 248 fascicles, 247 granular melanin, 248 pigmented epithelioid cell nevus, 251 Spitz nevus and, 251 Pigmented spindle cell tumor (PSCT). See also Pigmented spindle cell nevus (PSCN) description, epidermal hyperplasia, 374 pagetoid melanocytosis and intraepidermal nesting, single-cell proliferation,

18 644 Pigmented spindle nevus. See Pigmented spindle cell nevus (PSCN) Plaque-type blue nevus clinical and, 294 cytogenetic analysis, 295 hypercellular nodules, 294 Plexiform spindle cell melanoma clinical and, 325 HMB-45, 326 primary and metastatic, 323 sentinel lymph node, 323, 325 Spitz tumors, 326 Plexiform spindle cell nevus (PSCN) clinical features, 319 deep penetrating nevus, 317, molecular characterization, 317, 318 Plexiform Spitz nevus, P75 neurotrophin receptor (p75nr), 18 PNL2, 19 Prepubertal melanoma, 205 Primary acquired melanosis (PAM) clinical features, 513 and C-MIN, 514, 515 description, 513 hypermelanosis, prognosis, 514 treatment, 514 Primary cutaneous melanoma synoptic report, 632 vs. metastatic melanoma collarette, 548 dermal, description, , 549 epidermotropism, , 550 location and architecture, lesion, 548 noninvasive precursor lesion, 546 primary dermal melanomas, in situ component, 546 Primary mucosal melanoma vs. metastatic melanoma, Prognostic factors 5-and 10-year survival rates, 591, 592 clinical prognostications, 569 four-variable model, 592 microinvasive melanomas, 569 stage III melanoma, 586, stage I-II melanoma (see Stage I-II melanoma) stage IV melanoma, staging system, melanoma, 571, 572 PSCN. See Pigmented spindle cell nevus (PSCN); Plexiform spindle cell nevus (PSCN) PSCT. See Pigmented spindle cell tumor (PSCT) Pseudogranulomatous Spitz nevus, Punch biopsies bisection, 14 cutaneous pigmented lesions, macroscopic description, 14 R R21, Radial growth phase (RGP) epidermis, 334, 335 nodular melanoma, 339 pagetoid melanocytosis and papillary dermis, 334, 336 Recurrent melanocytic nevus clinical features, 135 description, 135 diagnosis, 137, Recurrent/persistent Spitz nevus clinical course, 262, 265 clinical features, 256 comparative genomic hybridization (CGH), 262 dermal/subcutaneous tumoral pattern, differential diagnosis, 262 fluorescence in situ hybridization (FISH), 262 original Spitz nevus pattern, recurrence, 252 Spitz-like melanoma, Spitz melanocytes, 256 Red hair and freckle gene allelic variations, 47 Arg84Glu variant, 48 germline mutations, 48 pheomelanin production, 49 Regression, melanoma definition, 462 differential diagnosis, early, 462, 463 hypopigmented/vitiligo-like lesion, 463, 465 intermediate, 462, 464 intraepidermal component, 463 late-stage, lichenoid pattern, 466 prevalence, 462 primary melanoma, 463 residual benign nevus remnant, tumoral melanosis (nodular melanosis) characterization, , 471 differential diagnosis, Reverse transcriptase-polymerase chain reaction (RT-PCR), 534, 536, 542, 557, 584, 585, 590 RGP. See Radial growth phase (RGP) RT-PCR. See Reverse transcriptase-polymerase chain reaction (RT-PCR) S SAC. See Soluble adenylyl cyclase (sac) Satellites and in-transit metastases definition, 534 Melanoma Institute Australia study, 535 primary tumor site and regional lymph nodes, 534 synchronous nodal, Index

19 Index SCCs. See Squamous cell carcinomas (SCCs) Sclerosing blue nevus clinical and, 278 dermatofibromas, 280 desmoplastic-neurotropic melanoma, fibrous component, GNA11/GNAQ mutations, 281 SDM. See Solitary dermal melanoma (SDM) Second messenger adenosine monophosphate (camp), 46, 47 Sentinel lymph node biopsy (SLNB) and CLND, 530 description, 530 and MSLT-I, 530 MSLT-II and MINITUB clinical trials, 530 tumor-harboring status, 530 Sentinel lymph nodes (SLN) and CLND, 533 definition, 531 H&E and with immunochemistry, 530 and IDC, immunohistochemical stains, 531 Ki-67/MIB-1 index, 531 Melan-A/MART-1, 530, 533 metastatic melanoma, preoperative lymphoscintigraphy, 530 prognostic factor, 530 and RT-PCR, 534 scoring system, 533 Sharp lateral demarcation of melanocytic lestion, 219 Shave biopsy, 14 Signet-ring cell melanoma, Signet ring cell morphology, SIMP. See Solar intraepidermal melanocytic proliferations (SIMP) Sinonasal melanoma clinical features nasal cavity and paranasal sinuses, 492 ulcerated, bulky, exophytic and polypoid tumor, description, differential diagnosis, 494, 494 SL. See Solar lentigo (SL) SLN. See Sentinel lymph nodes (SLN) SLNB. See Sentinel lymph node biopsy (SLNB) Small cell melanoma children, 190 clinical features, 190, 420, 422 confluent nests, 420, 424 dermal nests, 421 description, 420, 422 differential diagnosis, 421, 423 dysplastic nevus, 420, 421, intraepidermal proliferation, 420, large congenital nevus, , 190 pediatric melanoma, Small CMN vs. acquired nevi, 170 distribution, nevus cells, 162, 169 melanoma arising in, nevus cells, 168 patchy periadnexal/perivascular pattern, 162, prominent junctional component, 168 SMH. See Solar melanocytic hyperplasia (SMH) Solar intraepidermal melanocytic proliferations (SIMP) categories, lesions, 70 clinical features, 70 description, diagnosis, epidermal configuration, 71 melanocytic nuclear characteristics, 71 lentigo maligna, 70 pigmented lesions suggesting actinic keratosis/lichenoid inflammatory reaction, 72 immunohistochemistry (IHC), 72 lichenoid inflammation and sun-damaged skin, 72, 74 melan-a/mart-1, 72, 75 pseudomelanocytic nests, 72, 74, 75 solar melanocytic hyperplasia, 72, 74 and solar lentigo, Solar lentigo (SL) clinical features, 65 description, 65 diagnosis, club-shaped epidermal rete, 65, 66 epidermal rete ridges, 65, 67 photochemotherapy (PUVA) lentigo, 68 reticulated seborrheic keratosis, 65 Solar melanocytic hyperplasia (SMH) criteria, definition, 374 distinction, LM and LMM, 374 field effect, 375 intraepidermal nesting, melanocytes, 375 melanocytic nevi, fibrous papules and other neoplasms, surgical procedure, 375 Solitary dermal melanoma (SDM) biological behavior, 459 clinical features, 461 definition, 459 description, differential diagnosis, 462, paraganglioma-like dermal melanocytic tumor, primary melanoma, 458

20 646 Index Soluble adenylyl cyclase (sac), Sox 10, 19 Speckled lentiginous nevus clinical features, 133 description, 133 diagnosis, , 134 Spindle and epithelioid cell nevus, 206 Spindle cell melanocytes, Spindle cell morphology, metastatic melanoma vs. melanotic schmannoma Carney complex, 541 cytogenetics, 542 description, immunohistochemical studies, 542 Spitz nevus adnexal involvement, 222 in adults, anatomic sites, 207 appearance and presentation, 207 biological course, clinical differential diagnosis, 208 combined, 244 compound, compound dysplastic Spitz tumor, dermoepidermal junction, 216 desmoplastic (see Desmoplastic Spitz nevus) ancillary diagnostic techniques analysis of mutations, 239 comparative genomic hybridization and fluorescence in situ hybridization, DNA ploidy, 237 immunohistochemistry, 237 loss of heterozygosity, 239 sentinel lymph node biopsy, diffuse inflammatory infiltrate, 222 epidemiology adult patients, overrepresentation, age and sex distribution, 207 Caucasians, 207 sexual predilection, 207 epidermal hyperplasia, 223 epithelioid melanocytes, giant nevus cells, ground-glass cytoplasms, growth, at deep margin, 220 halo Spitz tumor (see Halo Spitz tumor) hyalinizing, 244 intraepidermal and dermal component immunohistochemistry, 235 interpretation, 235 reticulohistiocytoma, 236 junctional cleavage, , 221 juvenile melanoma, 205 Kamino bodies, 221 loss of cohesion, lymphatic spaces, 223 maturation, 217, 220 meaningful artifact, 221 mitoses, in deep part, 220 multiple Spitz nevi, 208 pagetoid melanocytosis, 221 pigmentation, 223 plexiform, prepubertal melanoma, 205 pseudogranulomatous, sharp lateral demarcation, 219 spindle and epithelioid cell nevus, 206 spindle cell melanocytes, Spitzoid features, 206 symmetry, telangiectasia and edema, 223 tubular, variants, 206 zonation, 220 Spitzoid melanocytic neoplasms, 223 Spitzoid melanoma characterization, 424 chromosomal aberrations, 425 clinical features, 424 cytological features, 425 differential diagnosis, 425 scanning magnification, Spitz tumors atypical spitzoid melanocytic neoplasms, 194 and conventional melanomas, 194 clinical and, 190 S-100 protein acidic calcium-binding protein family, 17 nonmelanocytic tumors, 17 nuclear and cytoplasmic staining, 16 rabbit polyclonal antibody against, 17 Squamous cell carcinomas (SCCs), 535 Stage III melanoma AJCC dataset, 588 lymph node ratio (LNR), 589 macrometastatic nodal relapse, 588 multivariate logistic regression, 588 mutations, NRAS and BRAF genes, 590 regional lymph node involvement, 588, 589 RT-PCR, 590 sentinel lymphatic mapping, 586 survival rate, 589 Stage I-II melanoma AJCC dataset, anatomic level, angiotropism, circulating melanoma cells, clinical factors age, anatomic site, 581 development, local recurrence, gender, 581 pregnancy status, cross-sectional profile, 580 DNA ploidy, FISH, 583 histogenetic type, 579 histopathologic and clinical prognostic factors, 586, 587