Diagnoses of Cases 1. Lentigo, other melanosis and the acquired nevus 2. Variations on the acquired nevus 3. Dermal melanocytosis

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1 Diagnoses of Cases 1. Lentigo, other melanosis and the acquired nevus 1 1A. Lentigo simplex 4 1B. Psoralens and ultraviolet A (PUVA) lentigo 6 1C. Solar lentigo 8 1D. Café au lait macule 10 1E. Ink-spot lentigo 12 1F. Lower labial macule/mucosal melanotic macule 14 1G. Vulvar melanosis 16 1H. Nevus spilus/speckled lentiginous nevus 18 1I. Junctional nevus 20 1J. Compound nevus 22 1K. Dermal nevus Variations on the acquired nevus 29 2A. Combined compound congenital and inverted type-a nevus 30 2B. Combined compound congenital and inverted type-a variant of deep penetrating nevus 33 2C. Desmoplastic type-c nevus 36 2D. Balloon cell nevus 39 2E. Halo lentiginous compound nevus 42 2F. Dermal nevus with neurotization 44 2G. Dermal nevus with fatty infiltration 47 2H. Nevus with ossification (nevus of Nanta) 49 2I. Meyerson s (inflamed) nevus 51 2J. Recurrent nevus 53 2K. Nevus with trichostasis spinulosa 56 2L. Nevus with pseudovascular lacunae 58 2M. Nevus with basal cell carcinoma 60 2N. Traumatized dermal nevus 62 2O. Compound nevus with focal myxoid change 64 2P. Deep penetrating nevus, clonal lesion Dermal melanocytosis 71 3A. Mongolian spot 72 3B. Nevus of Ota 74 Blue nevus and variants 3C. Common blue nevus 76 3D. Plaque-like blue nevus 79 3E. Sclerosing blue nevus 82 3F. Epithelioid blue nevus 85 3G. Cellular blue nevus 87 M.P. Hoang, M.C. Mihm Jr. (eds.), Melanocytic Lesions, DOI / , Springer Science+Business Media New York

2 474 Diagnoses of Cases 3H. Cellular blue nevus with cystic change 92 3I. Atypical cellular blue nevus 96 3J. Predominantly amelanotic cellular blue nevus 100 3K. Neurocristic hamartoma (dermal melanocyte hamartoma) Congenital nevus and variants 111 4A. Congenital dermal nevus 114 4B. Congenital combined nevus with Type A/penetrating features with atypia 117 4C. Lentiginous junctional dysplastic nevus arising in association with a congenital nevus 120 4D. Congenital nevus with benign proliferative nodule 123 4E. Congenital nevus with atypical proliferative nodule 128 4F. Congenital nevus with severely atypical proliferative nodule 131 4G. Congenital nevus with atypical proliferative nodule and myxoid change 134 4H. Congenital nevus with severely atypical epithelioid cell tumor Spindle and epithelioid cell (Spitz) nevus and variants 143 5A. Spindle and epithelioid cell (Spitz) nevus, compound type 144 5B. Sclerosing (desmoplastic) Spitz nevus 147 5C. Compound dysplastic nevus with Spitzoid features 150 5D. Combined compound dysplastic nevus and desmoplastic Spitz nevus 152 5E. Pigmented spindle cell nevus of Reed, compound type 155 5F. Pigmented spindle cell nevus of Reed with moderate cytologic atypia 158 5G. Atypical Spitz nevus 161 5H. Polypoid and atypical Spitz nevus 164 5I. Atypical Spitz tumor 168 5J. Atypical Spitz tumor with borderline features Vulvar nevus and malignant melanoma 179 6A. Lentiginous compound nevus of special site (vulva) with moderate cytologic atypia 182 6B. Lentiginous compound nevus of special site (vulva) with moderate to focally severe cytologic atypia 185 6C. Lentiginous compound nevus of special site (vulva) with severe cytologic atypia 188 6D. Lentiginous compound nevus of special sites (vulva) with severe atypia of the intraepidermal and 191 superficial dermal components 6E. Malignant melanoma in situ, mucosal lentiginous and nested pattern 193 6F. Malignant melanoma, superficial spreading type 197 6G. Malignant melanoma arising in association with lichen sclerosus Dysplastic nevus 205 7A. Lentiginous compound dysplastic nevus with mild to moderate cytologic atypia of the intraepidermal 208 component 7B. Lentiginous compound dysplastic nevus with moderate cytologic atypia of the intraepidermal 211 component 7C. Lentiginous compound dysplastic nevus with focally severe cytologic atypia of the intraepidermal 214 component 7D. Lentiginous compound dysplastic nevus with severe cytologic atypia of intraepidermal and dermal 216 components 8. Problems in various subtypes of malignant melanoma 223 8A. Nevoid malignant melanoma 224 8B. Nevoid malignant melanoma 228 8C. Nevoid malignant melanoma 233 8D. Verrucous malignant melanoma 236 8E. Plexiform and inverted type-a, borderline melanocytic lesion 239 8F. Desmoplastic and neurotropic malignant melanoma 242 8G. Lentigo maligna melanoma with myxoid features 247 8H. Amelanotic melanoma 252

3 Diagnoses of Cases 475 8I. Amelanotic melanoma 256 8J. Malignant melanoma with Spitzoid features 259 8K. Malignant blue nevus 261 8L. Borderline melanocytic lesion arising in a neurocristic hamartoma 265 8M. Malignant melanoma arising in a neurocristic hamartoma 269 8N. Acral lentiginous melanoma 273 8O. Malignant melanoma arising in association with dysplastic nevus Primary versus metastatic malignant melanoma 283 9A. Blue nevus-like metastasis 284 9B. Epidermotropic metastasis 287 9C. Sarcomatoid or pleomorphic metastasis 289 9D. In-transit metastasis 292 9E. Metastatic melanoma with balloon cell features 295 9F. Tumoral melanosis Conjunctival melanocytic lesions A. Lentiginous compound conjunctival nevus with prominent hyperpigmentation of the submucosal 306 component 10B. Combined compound and blue conjunctival nevus C. Hypermelanosis with focal junctional melanocytic hyperplasia D. Primary acquired melanosis with focal severe cytologic atypia E. Primary acquired melanosis with foci of melanoma in situ F. Malignant melanoma, lentiginous mucosal site, arising in association with a compound nevus with 323 marked cytologic atypia 11. Special variants of malignant melanoma A. Myxoid melanoma B. Small cell melanoma C. Rhabdoid melanoma D. Rhabdoid melanoma E. Clear cell sarcoma F. Pigment synthesizing melanoma G. Malignant melanoma with osteoclast- like giant cells H. Balloon cell melanoma I. Signet-ring cell melanoma Approach to microstaging of primary melanoma and evaluation of prognostic variables 359 Growth phases 360 Levels of invasion 360 Breslow thickness 361 Ulceration 362 Mitotic index 362 Microscopic satellites 362 Host response 363 Regression 363 Vascular invasion A. Malignant melanoma with regression B. Malignant melanoma with brisk host response C. Acral lentiginous melanoma with extensive eccrine gland involvement D. Malignant melanoma with microsatellite metastases Ancillary techniques in diagnosing melanocytic lesions 379 Immunohistochemistry 379 Special stains 383

4 476 Diagnoses of Cases Electron microscopy A. Solar lentigo versus lentigo maligna B. Melanocytic nevus versus nevoid melanoma C. Severely atypical compound dysplastic nevus versus invasive melanoma D. Benign versus atypical proliferative nodule E. Dermal scar versus desmoplastic melanoma F. Cellular blue nevus versus spindle cell/desmoplastic melanoma G. Atypical Spitz tumor versus Spitzoid melanoma H. Nodal/capsular nevus versus metastatic melanoma I. Metastatic malignant melanoma J. Clear cell sarcoma versus malignant melanoma K. Spindle cell melanoma versus sarcomatoid carcinoma versus atypical fibroxanthoma L. Primary versus secondary extramammary Paget disease versus squamous cell carcinoma in situ 419 versus melanoma in situ 13M. Merkel cell carcinoma versus malignant melanoma N. High grade lymphoma versus malignant melanoma Molecular ancillary techniques 437 Molecular tests Comparative genomic hybridization 437 Fluorescence in situ hybridization 438 Mutation analysis A. Combined nevus (inverted type-a and compound) B. Atypical Spitz tumor, borderline C. Atypical Spitz tumor D. Atypical Spitz tumor with lymph node metastasis E. Spitzoid malignant melanoma F. Metastatic melanoma Melanoma: molecular classification and therapy 461 Histologic subtypes of malignant melanoma 462 Superficial spreading malignant melanoma (SSM) 462 Lentigo maligna melanoma (LMM) 462 Nodular malignant melanoma (NMM) 462 Acral lentiginous malignant melanoma (ALM) and mucosal lentiginous malignant melanoma 462 Other types of malignant melanoma 463 Molecular classification of melanoma 463 BRAF positive melanoma 463 BRAF therapy, BRAF inhibitors and MEK inhibitors Adverse effects Resistance and combination therapy NRAS positive melanoma 465 KIT positive melanoma 466 GNAQ or GNA11 positive melanoma 467 Immunotherapy 467

5 Index A Acral lentiginous malignant melanoma (ALM), AFX. See Atypical fibroxanthoma (AFX) AJCC. See American Joint Committee on Cancer (AJCC) ALM. See Acral lentiginous malignant melanoma (ALM) Amelanotic melanoma, 252, 256 American Joint Committee on Cancer (AJCC), 359, 361, 362 Atypical fibroxanthoma (AFX) diagnosis, 415 immunohistochemistry, 415 osteoclast giant cells, 348 Atypical genital nevus moderate atypia, 163, 182, 183 severe atypia, 185, 188, 191 Atypical Spitz nevus diagnosis, 161 Atypical Spitz tumor CGH, 442 diagnosis, 173 FISH, 446, 449 sentinel lymph nodes, 449 treatment, 173 Atypical Spitz tumor with borderline features, 173 B Balloon cell melanoma diagnosis, 352 metastatic, microscopic description, 352 primary, 352 Balloon cell nevus diagnosis, 39 microscopic description, 39 ultrastructural study, 39 Basal cell carcinoma and nevus, Blue nevus amelanotic diagnosis, 100 microscopic description, 100 atypical cellular blue, 96 cellular diagnosis, 87, 96 histologic criteria, 87 liquefactive degeneration, 87 microscopic description, 87, 96 cellular with cystic change diagnosis, 92 microscopic description, 92 necrosis, 92, 95 perineural invasion, 92, 94 common blue, 76 epithelioid blue, plaque-like diagnosis, 79 linear distribution, melanocytes, 79, 80 microscopic description, 79 sclerosing blue, 82 Blue-nevus like metastasis, 284 Borderline melanocytic lesion arising in a neurocristic hamartoma, 265 plexiform and inverted type-a, 239 severely atypical proliferative nodule, 137 BRAF positive melanoma adverse effects, 464 characterization, 463 dabrafenib, 464 kinase genes, cancer cell, 463 MEK inhibitor, 464 mutational analysis, 456 resistance and combination therapy, SSM, vemurafenib, 464 Breslow thickness in primary melanoma, C Café au lait macule clinical appearance, 10 diagnosis, 10 giant melanosome, 10, 11 microscopic description, 10 CDK4 inhibitor, CGH. See Comparative genomic hybridization (CGH) Chronic sun damage (CSD), 466 M.P. Hoang, M.C. Mihm Jr. (eds.), Melanocytic Lesions, DOI / , Springer Science+Business Media New York

6 478 Clear cell sarcoma description, 410 diagnosis, 342, 410 immunohistochemistry, 410, 412 microscopic description, 342 molecular analyses, 342 multinucleated tumor, 342, 344 ultrastructural study, Combined nevus compound and blue conjunctival nevus, 309 compound and inverted type-a, 439 congenital and deep penetrating, 33 congenital and inverted type-a, 30, 33 dysplastic and desmoplastic Spitz, 152 Comparative genomic hybridization (CGH), 437 Compound dysplastic nevus and Spitzoid features, 150 Compound nevus diagnosis, 22 microscopic description, 22 Congenital melanocytic nevus (CMN) BRAF, 112 classification, 111 diagnosis, 112 dysplastic features, 120 giant/garment, 111 immunohistochemistry, 396, 398 leptomeningeal melanocytosis, 112 malignant melanoma, 111 myxoid features, 134 neural crest migrate, 112 neurocristopathy, 112, 113 neurocutaneous melanosis, 112 nevus tardive, 111 proliferative nodules, proliferative nodules vs. malignant melanoma, 112, 113 vascular involvement, 114, 116 Congenital nevus. See Congenital melanocytic nevus Conjunctival melanoma, 319, 323 Conjunctival nevus combined, 309 glandular cyst formation, 309, 310 grading of cytologic atypia, 306 hypermelanosis, 312 primary acquired melanosis, 312 prominent pigmentation, 306 CSD. See Chronic sun damage (CSD) D Deep penetrating nevus clonal lesion, 66 inverted type-a nevus/variant, 30, 33 Dermal melanocytosis blue nevus (see Blue nevus) clinical appearance, 71 Mongolian spot (see Mongolian spot) neurocristic hamartoma ( see Neurocristic hamartoma) nevus of Ota ( see Nevus of Ota) Tindal effect, 71 Dermal nevus clinical appearance, 24 microscopic description, 24 Dermal nevus, fatty infiltration, 47 Dermal nevus, neurotized, 44 Desmoplastic and neurotrophic melanoma, 242 mucin deposition, Desmoplastic nevus, 36 Desmoplastic Spitz nevus, 147 diagnosis, 147 Dysplastic nevus architectural disorder and cytologic atypia, 205, 206 association with melanoma, 278 criteria for diagnosis, 207 familial atypical multiple moles and melanoma syndrome, 205 genetic mutation, 205 grading of atypia, 207 mild atypia, 208 moderate atypia, 211 severe atypia, 214, 216 treatment, 207 E Electron microscopy in melanocytic lesions, atypical/aberrant melanosomes, 384, 386 clear cell sarcoma, malignant melanoma, 384, 386 premelanosome, 384, 385 rhabdoid melanoma, 339 EMPD. See Extramammary Paget s disease (EMPD) Epidermotropic metastatic malignant melanoma, 287 Extramammary Paget s disease (EMPD), 419 diagnosis, 419 immunohistochemistry, 419, 421 special stain, 419, 420 tumor cells, 419, 422 F FISH. See Fluorescence in situ hybridization (FISH) Fluorescence in situ hybridization (FISH), 438 G Genital nevus, 179, 180 GNAQ/GNA11 positive melanoma, 467 Growth phase of primary melanoma, 360 H Halo nevus diagnosis, 42 lymphocyte-mediated regression, 42 lymphocyte satellitosis, 42, 43 microscopic description, 42 HMB-45 invasive melanoma, 395 nevoid melanoma, 392 nodal nevus, 407 Index

7 Index I Immunohistochemistry in melanocytic lesions D2-40, HMB-45, 380 KBA.62 monoclonal antibody, 381 Mart1/Ki67, 382 Melan-A and MART-1, 380 melanoma cells, 383 Mel-CAM, 381 MiTF, MPM-2, 383 MUM1, 381 NGFR, 382 NKI/C3, PHH3, 382 S100, 379 S100 and D2-40, 383 Sox10, 381 tyrosinase, 381 Ink-spot lentigo diagnosis, 12 microscopic description, 12 reticulated melanotic macule, 12 striking density, 12 In-transit metastases distant, 292 locoregional, 292 Inverted type-a nevus, 117, 439 J Junctional nevus diagnosis, 20 microscopic description, 20 K Ki-67 proliferation index, 333, 336 KIT positive melanoma, L Lentigo maligna melanoma (LMM) myxoid type, 247 Lentigo simplex clinical appearance, 4 diagnosis, 4 hyperpigmentation, 4, 5 ink-spot, 1 microscopic description, 4 Leptomeningeal melanocytosis, 112 Level of invasion of primary melanoma, Lichen sclerosus and malignant melanoma, Locoregional metastases, 292 Lower labial macule/mucosal melanotic macule clinical appearance, 13 dendrites, 13, 14 diagnosis, 13 microscopic description, 13 M Malignant blue nevus, 261 Malignant melanoma clinical and morphological parameters, 461 diagnosis, 405 familial atypical multiple moles and melanoma syndrome, 205 histologic subtypes, 462 ALM, 462 LMM, 462 NMM, 462 SSM, 462 immunohistochemistry, 393, 408 immunotherapy, molecular classification BRAF-positive melanoma, description, 463 GNAQ-/GNA11-positive melanoma, 467 KIT positive melanoma, NRAS-positive melanoma (see NRAS positive melanoma) primary vs. metastatic (See Primary melanoma) prognostic parameters, 463 Malignant melanoma variants acral lentiginous, 273 amelanotic, 252, 256 association with dysplastic nevus, 278 balloon cell, 252 clear cell sarcoma, desmoplastic, 242 malignant neurocristic hamartoma, 269 myxoid, 247, neurotropic, 242 nevoid, 224, 228, 233 osteoclast-like giant cells, 348, 350 pigmented epithelioid melanocytoma, 345, 346 pigment synthesizing, 345 rhabdoid melanoma, 337, 340 signet-ring cell melanoma, 355 small cell, Spitzoid, 259, 453 verrucous, 236 Malignant neurocristic hamartoma, 269 MART-1. See Melanoma antigen recognized by T cells (MART-1) Melan A HMB-45, 399 and MART-1, 22, 380 and MiTF, 380 and S100, 298 Melanocytic nevus. See Nevus Melanocytic proliferations and molecular ancillary techniques, 438 Melanoma and dysplastic nevi, 205, 206 Melanoma and evaluation of prognostic variables. See Primary melanoma Melanoma antigen recognized by T cells (MART-1) Ki-67 double stain, 382 and Melan-A, 380 and tyrosinase,

8 480 Melanoma cell adhesion molecule (Mel-CAM), 381 Melanosis conjunctival (see Conjunctival melanoma) lower labial macule/mucosal ( see Lower labial macule/mucosal melanotic macule) Mel-CAM. See Melanoma cell adhesion molecule (Mel-CAM) Merkel cell carcinoma, 423 immunohistochemistry, 423, 426 Metastatic melanoma balloon cell, 295 blue nevus-like, 284 epidermotropic, 284 immunohistochemistry, 408 mutational analyses, 456 pleomorphic, 289 sarcomatoid, 289 tumoral melanosis, 298 Meyerson s nevus, 51 Microphthalmia transcription factor (MiTF) nuclear positivity, 380 and Sox10, 387 Microscopic satellite of primary melanoma, 362 MiTF. See Microphthalmia transcription factor (MiTF) Mitotic protein monoclonal-2 (MPM-2), 383 Mitotic rate, 362 Molecular ancillary techniques CGH, 437 FISH, 438 mutational analysis, 438 Mongolian spot characteristic features, 72 diagnosis, 72 microscopic description, 72 MPM-2. See Mitotic protein monoclonal-2 (MPM-2) Mucosal lentiginous malignant melanoma and ALM, 462 diagnosis, 193 Multiple myeloma oncogene 1 (MUM1), 381 MUM1. See Multiple myeloma oncogene 1 (MUM1) Myxoid melanoma, 330, 331 N Nanta nevus, 49 Neonatal skin lesions, 111 Nerve growth factor receptor (NGFR), 382 Neurocristic hamartoma borderline, 265 dermal melanocyte hamartoma, 104 diagnosis, 104 hamartomatous process, 104, 107 malignant neurocristic hamartoma, 269 microscopic description, 104 perineural invasion, 104, 107 Neurocutaneous melanosis, 112 Nevoid melanoma, 224, 228, 233 immunohistochemistry, 392 Nevus combined conventional and dysplastic nevus, 30 combined nevus, 30 halo, inverted type-a nevus, 66 lentiginous compound, 306 neurotization, 29 Nevus, myxoid change, 64 Nevus of Nanta, 49 Nevus of Ota acquired dermal melanocytosis, 74 clinical appearance, 74 diagnosis, 74 microscopic description, 74 Nevus spilus clinical appearance, 18 diagnosis, 18 microscopic description, 18 speckled lentiginous nevus, 18 Nevus, traumatized, 62 Nevus with basal cell carcinoma, 60, 61 Nevus with mature adipocytes, 49, 50 Nevus with pseudovascular lacunae, 58 Nevus with trichostasis spinulosa, 56 NGFR. See Nerve growth factor receptor (NGFR) NMM. See Nodular malignant melanoma (NMM) Nodal nevus, 406 Nodular malignant melanoma (NMM), 224, 462 NRAS positive melanoma, Index P PAM. See Primary acquired melanosis (PAM) PHH3. See Phosphohistone H3 (PHH3) Phosphohistone H3 (PHH3), 382 Pigmented spindle cell nevus of Reed cytologic atypia, 158 diagnosis, 155 Plexiform and inverted type-a melanocytic lesion, PNs. See Proliferative nodule (PNs) Polypoid Spitz nevus, 164, 166 Primary acquired melanosis (PAM) malignant transformation, 304 microscopic description, 315 Primary melanoma adnexal extension, 371 AJCC, 359 Breslow thickness, growth phases, 360 histologic subtypes, host response, 363 immunohistochemistry, 395 level of invasion, melanoma staging system, microscopic satellites, 362 mitotic index, 362 molecular classification, 463 regression, 363 ulceration, 362 vascular invasion, 363 Prognostic variables of primary melanoma. See Primary melanoma

9 Index Proliferative nodule (PNs) atypical, 128, 131, 134, 396 benign, 123 immunohistochemistry, 396, 398 myxoid change, 125, 134 Psoralen and ultraviolet A (PUVA) lentigo clinical appearance, 6 microscopic description, 6 PUVA lentigo. See Psoralen and ultraviolet A (PUVA) lentigo R Recurrent nevus diagnosis, 53 pseudomelanoma, 53 Rhabdoid melanoma cytoplasmic eosinophilic globules, 340, 341 diagnosis, 340 ultrastructural study, 337, 339 S S100, 379 Signet-ring cell melanoma diagnosis, 355 large cytoplasmic vacuole, 355, 356 microscopic description, 355 Small cell melanoma association with congenital nevus, 333, 336 diagnosis, 333 immunohistochemistry, 333, 336 microscopic description, 333 nevoid melanoma, 333 verrucous proliferation, 333, 334 Solar lentigo, 8, 9 Sox10 metastatic melanomas, 381 and MiTF, 387 and tyrosinase, Special stain azure B, 383, 384 reticulin, 383, 384 Speckled and lentiginous nevus. See Nevus Spilus Spindle and epithelioid cell nevus. See Spitz nevus Spindle cell lesion atypical fibroxanthoma, diagnosis, 415 immunohistochemistry, 415, 418 squamous cell carcinoma, 415 Spitz nevus atypical, 161 atypical and polypoid, 164 dysplastic and desmoplastic Spitz, 152 dysplastic nevus with Spitzoid features, 150 sclerosing or desmoplastic, 147 Spitzoid melanoma, 259 FISH, 453 SSM. See Superficial spreading malignant melanoma (SSM) Superficial spreading malignant melanoma (SSM), T Telomerase reverse transcriptase gene (TERT), 305 TERT. See Telomerase reverse transcriptase gene (TERT) Tindal effect, 71 Tumoral melanosis, 298 U Ulceration, 362 V Verrucous melanoma, 236 VGP, 330 Vulvar melanoma association with lichen sclerosus, 200 melanoma in situ, 193 superficial spreading, 197 Vulvar melanosis clinical appearance, 16 diagnosis, 16 genital lentigines, 16 microscopic description, 16 Vulvar nevus moderate atypia, 182, 185, 186 severe atypia, 185, 188, 191