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Home , Amelanotic melanoma, Balloon cell nevus, Blue nevus, Desmoplastic melanoma, Dysplastic nevus, Lentigo maligna melanoma

Diagnoses of Cases

1. , other melanosis and the acquired 1 1A. 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. /speckled lentiginous nevus 18 1I. Junctional nevus 20 1J. Compound nevus 22 1K. Dermal nevus 24 2. 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. 39 2E. Halo lentiginous compound nevus 42 2F. Dermal nevus with neurotization 44 2G. Dermal nevus with fatty infi ltration 47 2H. Nevus with ossifi cation (nevus of Nanta) 49 2I. Meyerson’s (infl amed) 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 66 3. Dermal melanocytosis 71 3A. 72 3B. 74 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, 473 DOI 10.1007/978-1-4939-0891-2, © Springer Science+Business Media New York 2014 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 hamartoma) 104 4. 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 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 137 5. Spindle and epithelioid cell (Spitz) nevus and variants 143 5A. Spindle and epithelioid cell (Spitz) nevus, compound type 144 5B. Sclerosing (desmoplastic) 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 173 6. Vulvar nevus and malignant 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 superfi cial dermal components 6E. Malignant melanoma in situ, mucosal lentiginous and nested pattern 193 6F. Malignant melanoma, superfi cial spreading type 197 6G. Malignant melanoma arising in association with lichen sclerosus 200 7. 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. melanoma with myxoid features 247 8H. 252 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 278 9. 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 298 10. Conjunctival melanocytic lesions 303 10A. Lentiginous compound conjunctival nevus with prominent of the submucosal 306 component 10B. Combined compound and blue conjunctival nevus 309 10C. Hypermelanosis with focal junctional melanocytic hyperplasia 312 10D. Primary acquired melanosis with focal severe cytologic atypia 315 10E. Primary acquired melanosis with foci of melanoma in situ 319 10F. Malignant melanoma, lentiginous mucosal site, arising in association with a compound nevus with 323 marked cytologic atypia 11. Special variants of malignant melanoma 329 11A. Myxoid melanoma 330 11B. Small cell melanoma 333 11C. Rhabdoid melanoma 337 11D. Rhabdoid melanoma 340 11E. Clear cell sarcoma 342 11F. Pigment synthesizing melanoma 345 11G. Malignant melanoma with osteoclast- like giant cells 348 11H. Balloon cell melanoma 352 11I. Signet-ring cell melanoma 355 12. 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 363 12A. Malignant melanoma with regression 364 12B. Malignant melanoma with brisk host response 367 12C. Acral lentiginous melanoma with extensive eccrine gland involvement 371 12D. Malignant melanoma with microsatellite metastases 374 13. Ancillary techniques in diagnosing melanocytic lesions 379 Immunohistochemistry 379 Special stains 383 476 Diagnoses of Cases

Electron microscopy 383 13A. Solar lentigo versus lentigo maligna 387 13B. versus 390 13C. Severely atypical compound dysplastic nevus versus invasive melanoma 393 13D. Benign versus atypical proliferative nodule 396 13E. Dermal scar versus 399 13F. Cellular blue nevus versus spindle cell/desmoplastic melanoma 402 13G. Atypical Spitz tumor versus Spitzoid melanoma 405 13H. Nodal/capsular nevus versus metastatic melanoma 406 13I. Metastatic malignant melanoma 408 13J. Clear cell sarcoma versus malignant melanoma 410 13K. Spindle cell melanoma versus sarcomatoid carcinoma versus atypical fi broxanthoma 415 13L. Primary versus secondary extramammary Paget disease versus squamous cell carcinoma in situ 419 versus melanoma in situ 13M. Merkel cell carcinoma versus malignant melanoma 423 13N. High grade lymphoma versus malignant melanoma 427 14. Molecular ancillary techniques 437 Molecular tests Comparative genomic hybridization 437 Fluorescence in situ hybridization 438 Mutation analysis 438 14A. Combined nevus (inverted type-A and compound) 439 14B. Atypical Spitz tumor, borderline 442 14C. Atypical Spitz tumor 446 14D. Atypical Spitz tumor with lymph node metastasis 449 14E. Spitzoid malignant melanoma 453 14F. Metastatic melanoma 456 15. Melanoma: molecular classifi cation and therapy 461 Histologic subtypes of malignant melanoma 462 Superfi cial spreading malignant melanoma (SSM) 462 (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 classifi cation 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

Index

A cellular Acral lentiginous malignant melanoma (ALM) , 273–277 diagnosis , 87, 96 AFX. See Atypical fi broxanthoma (AFX) histologic criteria , 87 AJCC. See American Joint Committee on Cancer liquefactive degeneration , 87 (AJCC) microscopic description , 87, 96 ALM. See Acral lentiginous malignant cellular with cystic change melanoma (ALM) diagnosis , 92 Amelanotic melanoma , 252, 256 microscopic description , 92 American Joint Committee on Cancer (AJCC) , 359, 361, necrosis , 92, 95 362 perineural invasion , 92, 94 Atypical fi broxanthoma (AFX) common blue , 76 diagnosis , 415 epithelioid blue , 85–86 immunohistochemistry , 415 plaque-like osteoclast giant cells , 348 diagnosis , 79 Atypical genital nevus linear distribution, , 79, 80 moderate atypia , 163, 182, 183 microscopic description , 79 severe atypia , 185, 188, 191 sclerosing blue , 82 Atypical Spitz nevus Blue-nevus like metastasis , 284 diagnosis , 161 Borderline melanocytic lesion Atypical Spitz tumor arising in a neurocristic hamartoma , 265 CGH , 442 plexiform and inverted type-A , 239 diagnosis , 173 severely atypical proliferative nodule , 137 FISH , 446, 449 BRAF positive melanoma sentinel lymph nodes , 449 adverse effects , 464 treatment , 173 characterization , 463 Atypical Spitz tumor with borderline features , 173 dabrafenib , 464 kinase genes, cancer cell , 463 MEK inhibitor , 464 B mutational analysis , 456 Balloon cell melanoma resistance and combination therapy , 464–465 diagnosis , 352 SSM , 463–464 metastatic , 295–297 vemurafenib , 464 microscopic description , 352 Breslow thickness in primary melanoma , 361–362 primary , 352 Balloon cell nevus diagnosis , 39 C microscopic description , 39 Café au lait macule ultrastructural study , 39 clinical appearance , 10 Basal cell carcinoma and nevus , 367–368 diagnosis , 10 Blue nevus giant melanosome , 10, 11 amelanotic microscopic description , 10 diagnosis , 100 CDK4 inhibitor , 298–300 microscopic description , 100 CGH. See Comparative genomic hybridization (CGH) atypical cellular blue , 96 Chronic sun damage (CSD) , 466

M.P. Hoang, M.C. Mihm Jr. (eds.), Melanocytic Lesions, 477 DOI 10.1007/978-1-4939-0891-2, © Springer Science+Business Media New York 2014 478 Index

Clear cell sarcoma clinical appearance , 24 description , 410 microscopic description , 24 diagnosis , 342, 410 Dermal nevus, fatty infi ltration , 47 immunohistochemistry , 410, 412 Dermal nevus, neurotized , 44 microscopic description , 342 Desmoplastic and neurotrophic melanoma , 242 molecular analyses , 342 mucin deposition , 242–243 multinucleated tumor , 342, 344 Desmoplastic nevus , 36 ultrastructural study , 413–414 Desmoplastic Spitz nevus , 147 Combined nevus diagnosis , 147 compound and blue conjunctival nevus , 309 Dysplastic nevus compound and inverted type-A , 439 architectural disorder and cytologic atypia , 205, 206 congenital and deep penetrating , 33 association with melanoma , 278 congenital and inverted type-A , 30, 33 criteria for diagnosis , 207 dysplastic and desmoplastic Spitz , 152 “familial atypical multiple moles and melanoma Comparative genomic hybridization (CGH) , 437 syndrome” , 205 Compound dysplastic nevus and Spitzoid features , 150 genetic mutation , 205 Compound nevus grading of atypia , 207 diagnosis , 22 mild atypia , 208 microscopic description , 22 moderate atypia , 211 Congenital melanocytic nevus (CMN) severe atypia , 214, 216 BRAF , 112 treatment , 207 classifi cation , 111 diagnosis , 112 dysplastic features , 120 E giant/garment , 111 Electron microscopy in melanocytic lesions , 383–386 immunohistochemistry , 396, 398 atypical/aberrant melanosomes , 384, 386 leptomeningeal melanocytosis , 112 clear cell sarcoma , 413–414 malignant melanoma , 111 malignant melanoma , 384, 386 myxoid features , 134 premelanosome , 384, 385 neural crest migrate , 112 rhabdoid melanoma , 339 neurocristopathy , 112, 113 EMPD. See Extramammary Paget’s disease (EMPD) neurocutaneous melanosis , 112 Epidermotropic metastatic malignant melanoma , 287 “nevus tardive” , 111 Extramammary Paget’s disease (EMPD) , 419 proliferative nodules , 123–134 diagnosis , 419 proliferative nodules vs. malignant melanoma, 112, 113 immunohistochemistry , 419, 421 vascular involvement , 114, 116 special stain , 419, 420 Congenital nevus. See Congenital melanocytic nevus tumor cells , 419, 422 Conjunctival melanoma , 319, 323 Conjunctival nevus combined , 309 F glandular cyst formation , 309, 310 FISH. See Fluorescence in situ hybridization (FISH) grading of cytologic atypia , 306 Fluorescence in situ hybridization (FISH) , 438 hypermelanosis , 312 primary acquired melanosis , 312 prominent pigmentation , 306 G CSD. See Chronic sun damage (CSD) Genital nevus , 179, 180 GNAQ/GNA11 positive melanoma , 467 Growth phase of primary melanoma , 360 D Deep penetrating nevus clonal lesion , 66 H inverted type-A nevus/variant , 30, 33 Dermal melanocytosis diagnosis , 42 blue nevus (see Blue nevus) lymphocyte-mediated regression , 42 clinical appearance , 71 lymphocyte satellitosis , 42, 43 Mongolian spot (see Mongolian spot) microscopic description , 42 neurocristic hamartoma ( see Neurocristic hamartoma) HMB-45 nevus of Ota (see Nevus of Ota) invasive melanoma , 395 “Tindal” effect , 71 nevoid melanoma , 392 Dermal nevus nodal nevus , 407 Index 479

I M Immunohistochemistry in melanocytic lesions Malignant blue nevus , 261 D2-40 , 382–383 Malignant melanoma HMB-45 , 380 clinical and morphological parameters , 461 KBA.62 monoclonal antibody , 381 diagnosis , 405 Mart1/Ki67 , 382 “familial atypical multiple moles and melanoma Melan-A and MART-1 , 380 syndrome” , 205 melanoma cells , 383 histologic subtypes , 462 Mel-CAM , 381 ALM , 462 MiTF , 379–380 LMM , 462 MPM-2 , 383 NMM , 462 MUM1 , 381 SSM , 462 NGFR , 382 immunohistochemistry , 393, 408 NKI/C3 , 381–382 immunotherapy , 467–468 PHH3 , 382 molecular classifi cation S100 , 379 BRAF-positive melanoma , 463–465 S100 and D2-40 , 383 description , 463 Sox10 , 381 GNAQ-/GNA11-positive melanoma , 467 tyrosinase , 381 KIT positive melanoma , 466–467 Ink-spot lentigo NRAS-positive melanoma (see NRAS positive diagnosis , 12 melanoma) microscopic description , 12 primary vs. metastatic (See Primary melanoma) reticulated melanotic macule , 12 prognostic parameters , 463 striking density , 12 Malignant melanoma variants In-transit metastases acral lentiginous , 273 distant , 292 amelanotic , 252, 256 locoregional , 292 association with dysplastic nevus , 278 Inverted type-A nevus , 117, 439 balloon cell , 252 clear cell sarcoma , 410–414 desmoplastic , 242 J malignant neurocristic hamartoma , 269 Junctional nevus myxoid , 247, 330–332 diagnosis , 20 neurotropic , 242 microscopic description , 20 nevoid , 224, 228, 233 osteoclast-like giant cells , 348, 350 pigmented epithelioid melanocytoma , 345, 346 K pigment synthesizing , 345 Ki-67 proliferation index , 333, 336 rhabdoid melanoma , 337, 340 KIT positive melanoma , 466–467 signet-ring cell melanoma , 355 small cell , 333–336 Spitzoid , 259, 453 L verrucous , 236 Lentigo maligna melanoma (LMM) Malignant neurocristic hamartoma , 269 myxoid type , 247 MART-1. See Melanoma antigen recognized by T cells Lentigo simplex (MART-1) clinical appearance , 4 Melan A diagnosis , 4 HMB-45 , 399 hyperpigmentation , 4, 5 and MART-1 , 22, 380 ink-spot , 1 and MiTF , 380 microscopic description , 4 and S100 , 298 Leptomeningeal melanocytosis , 112 Melanocytic nevus. See Nevus Level of invasion of primary melanoma , 360–361 Melanocytic proliferations and molecular ancillary Lichen sclerosus and malignant melanoma , techniques, 438 200–202 Melanoma and dysplastic nevi , 205, 206 Locoregional metastases , 292 Melanoma and evaluation of prognostic variables. See Lower labial macule/mucosal melanotic macule Primary melanoma clinical appearance , 13 Melanoma antigen recognized by T cells (MART-1) dendrites , 13, 14 Ki-67 double stain , 382 diagnosis , 13 and Melan-A , 380 microscopic description , 13 and tyrosinase , 382 480 Index

Melanoma cell adhesion molecule (Mel-CAM) , 381 “combined nevus” , 30 Melanosis halo , 42–43 conjunctival ( see Conjunctival melanoma) inverted type-A nevus , 66 lower labial macule/mucosal (see Lower labial lentiginous compound , 306 macule/mucosal melanotic macule) neurotization , 29 Mel-CAM. See Melanoma cell adhesion molecule Nevus, myxoid change , 64 (Mel-CAM) Nevus of Nanta , 49 Merkel cell carcinoma, 423 Nevus of Ota immunohistochemistry , 423, 426 acquired dermal melanocytosis , 74 Metastatic melanoma clinical appearance , 74 balloon cell , 295 diagnosis , 74 blue nevus-like , 284 microscopic description , 74 epidermotropic , 284 Nevus spilus immunohistochemistry , 408 clinical appearance , 18 mutational analyses , 456 diagnosis , 18 pleomorphic , 289 microscopic description , 18 sarcomatoid , 289 speckled lentiginous nevus , 18 tumoral melanosis , 298 Nevus, traumatized , 62 Meyerson’s nevus , 51 Nevus with basal cell carcinoma , 60, 61 Microphthalmia transcription factor (MiTF) Nevus with mature adipocytes , 49, 50 nuclear positivity , 380 Nevus with pseudovascular lacunae , 58 and Sox10 , 387 Nevus with trichostasis spinulosa , 56 Microscopic satellite of primary melanoma , 362 NGFR. See Nerve growth factor receptor (NGFR) MiTF. See Microphthalmia transcription factor (MiTF) NMM. See Nodular malignant melanoma (NMM) Mitotic protein monoclonal-2 (MPM-2) , 383 Nodal nevus , 406 Mitotic rate , 362 Nodular malignant melanoma (NMM) , 224, 462 Molecular ancillary techniques NRAS positive melanoma , 465–466 CGH , 437 FISH , 438 mutational analysis , 438 P Mongolian spot PAM. See Primary acquired melanosis (PAM) characteristic features , 72 PHH3. See Phosphohistone H3 (PHH3) diagnosis , 72 Phosphohistone H3 (PHH3) , 382 microscopic description , 72 Pigmented spindle cell nevus of Reed MPM-2. See Mitotic protein monoclonal-2 (MPM-2) cytologic atypia , 158 Mucosal lentiginous malignant melanoma diagnosis , 155 and ALM , 462 Plexiform and inverted type-A melanocytic lesion, 239–241 diagnosis , 193 PNs. See Proliferative nodule (PNs) Multiple myeloma oncogene 1 (MUM1) , 381 Polypoid Spitz nevus , 164, 166 MUM1. See Multiple myeloma oncogene 1 (MUM1) Primary acquired melanosis (PAM) Myxoid melanoma , 330, 331 malignant transformation , 304 microscopic description , 315 Primary melanoma N adnexal extension , 371 Nanta nevus , 49 AJCC , 359 Neonatal skin lesions , 111 Breslow thickness , 361–362 Nerve growth factor receptor (NGFR) , 382 growth phases , 360 Neurocristic hamartoma histologic subtypes , 462–463 borderline , 265 host response , 363 dermal melanocyte hamartoma , 104 immunohistochemistry , 395 diagnosis , 104 level of invasion , 360–361 hamartomatous process , 104, 107 melanoma staging system , 359–360 malignant neurocristic hamartoma , 269 microscopic satellites , 362 microscopic description , 104 mitotic index , 362 perineural invasion , 104, 107 molecular classifi cation , 463 Neurocutaneous melanosis , 112 regression , 363 Nevoid melanoma , 224, 228, 233 ulceration , 362 immunohistochemistry , 392 vascular invasion , 363 Nevus Prognostic variables of primary melanoma. See Primary combined conventional and dysplastic nevus , 30 melanoma Index 481

Proliferative nodule (PNs) Spindle cell lesion atypical , 128, 131, 134, 396 atypical fi broxanthoma , 415–416 benign , 123 diagnosis , 415 immunohistochemistry , 396, 398 immunohistochemistry , 415, 418 myxoid change , 125, 134 squamous cell carcinoma , 415 Psoralen and ultraviolet A (PUVA) lentigo Spitz nevus clinical appearance , 6 atypical , 161 microscopic description , 6 atypical and polypoid , 164 PUVA lentigo. See Psoralen and ultraviolet A (PUVA) dysplastic and desmoplastic Spitz , 152 lentigo dysplastic nevus with Spitzoid features , 150 sclerosing or desmoplastic , 147 Spitzoid melanoma , 259 R FISH , 453 Recurrent nevus SSM. See Superfi cial spreading malignant melanoma diagnosis , 53 (SSM) , 53 Superfi cial spreading malignant melanoma (SSM) , 462 Rhabdoid melanoma cytoplasmic eosinophilic globules , 340, 341 diagnosis , 340 T ultrastructural study , 337, 339 Telomerase reverse transcriptase gene (TERT) , 305 T E R T . See Telomerase reverse transcriptase gene (TERT) “Tindal” effect , 71 S Tumoral melanosis , 298 S100 , 379 Signet-ring cell melanoma diagnosis , 355 U large cytoplasmic vacuole , 355, 356 Ulceration , 362 microscopic description , 355 Small cell melanoma association with congenital nevus , 333, 336 V diagnosis , 333 Verrucous melanoma , 236 immunohistochemistry , 333, 336 VGP , 330 microscopic description , 333 Vulvar melanoma nevoid melanoma , 333 association with lichen sclerosus , 200 verrucous proliferation , 333, 334 melanoma in situ , 193 Solar lentigo , 8, 9 superfi cial spreading , 197 Sox10 Vulvar melanosis metastatic , 381 clinical appearance , 16 and MiTF , 387 diagnosis , 16 and tyrosinase , 379–380 genital lentigines , 16 Special stain microscopic description , 16 azure B , 383, 384 Vulvar nevus reticulin , 383, 384 moderate atypia , 182, 185, 186 Speckled and lentiginous nevus. See Nevus Spilus severe atypia , 185, 188, 191 Spindle and epithelioid cell nevus. See Spitz nevus