Simulators of melanoma
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1 Simulators of melanoma Philip E. LeBoit, M.D. Depts. of Pathology and Dermatology University of California, San Francisco Simulators of melanoma Simulators of melanoma in situ Melanocytic Non-melanocytic Simulators of invasive melanoma Melanocytic Non-melanocytic Simple lentigo with suprabasilar scatter 1
2 Melanocytic nevi on acral skin 2
3 What makes a site special? Nevi on the scalp of children Everone is special -Barney Everyone is different. Few people are special. - Jonah M. Peterschild,
4 Nevi on special sites Acral-volar Nail matrix/bed Genitalia Scalp (children) Back (two patterns) Flexural Ear Conjunctiva Spitz acral Spitz ear 4
5 5
6 6
7 Melanocytic Acral Nevus with Intraepidermal Ascent of Cells 7
8 8
9 The American Journal of Surgical Pathology 27(3): ; Mar
10 10
11 11
12 Inflamed melanocytic nevi 12
13 Inflamed melanocytic nevi Rapid epidermopoiesis can lead to upward scatter of single melanocytes Inflammation can result in increased pigment synthesis (increased pigmentation, more cytoplasm) No proof that inflammation can cause nuclear atypia, mitotic activity 13
14 14
15 A peculiar papulosquamous eruption involving pigmented nevi LB Meyerson, Arch Dermatol 1971, 103:510-2 Two patients with multiple pruritic papulosquamous lesions Scaly and red aspects resolved with topical steroid treatment Pigmented nevi persisted Speculated about koebnerization of pityriaisis rosea as cause 15
16 16
17 Meyerson s nevus Subsequent contributions Co-existence of Meyerson s and Sutton s nevus after sunburn (Dermatol. 1994;189:269-70) Halo eczema- resolution after excision of central lesion alone (Clin Exp Dermatol 1991; 16:66-7) Halo eczema surrounding seborrheic keratoses (Australas. J Dermatol. 1990; 30: 73-6 Nevus with lichen sclerosus 17
18 18
19 19
20 What s ailing this nevus? 20
21 21
22 Dysplastic nevi 22
23 23
24 24
25 25
26 Superficial Spitz nevus 26
27 27
28 Inflamed or traumatized junctional Reed nevus 28
29 29
30 30
31 31
32 Persistent/recurrent nevi 32
33 33
34 Genital nevi 34
35 Masson,
36 36
37 Pagetoid scatter in congenital nevi in neonates 37
38 38
39 Large single melanocytes overlying intradermal nevi 39
40 Large single melanocytes in sun damaged skin: Actinic melanocytosis Actinic melanocytosis Gilchrest et al J.Invest.Dermatol. Paired biopsies, exposed and non-exposed skin, adjacent sites donors aged yr Density of DOPA+ melanocytes ~2x in exposed > nonexposed skin at all ages, suggesting an irreversible effect of sun exposure Melanocyte density declined ~ 6 to 8% /decade in both sites Dopa-positivity of individual melanocytes was consistently greater in chronically exposed skin > nonexposed skin of same subject and did not vary with age 40
41 Features that point to melanoma in situ over actinic melanocytosis : Irregular intervals between melanocytes Nests may be present (but sometimes levels needed to show them) Pagetoid spread may be present (but sometimes levels needed to show it) Prominent dendrites in melanoma in situ, sometimes More irregular pigmentation Adnexal involvement more marked and more deep in melanoma in situ (there may be increased melanocytes in follicular infundibula and acrosyringia in actinic melanocytosis) Immunostains do not help distinguish MIS from actinic melanocytosis (HMB45, Ki-67) Weyers W, Bonczkowitz M, Weyers I, Bittinger A, Schill WB. Melanoma in situ versus melanocytic hyperplasia in sun-damaged skin. Assessment of the significance of histopathologic criteria for differential diagnosis.am J Dermatopathol Dec;18(6):
42 Typical melanoma antigen recognized by T cells 1-staining normal sun-exposed skin with a focal area of increased melanocyte density (arrows) (original magnification x200) Arch Dermatol Jul;142(7): Hendi, A. et al. Arch Dermatol 2006;142: Copyright restrictions may apply. 42
43 Melanoma antigen recognized by T cells 1-staining normal sun-exposed skin shows extension of melanocytes along the follicle (original magnification x200) Biopsy of the contralateral side? Hendi, A. et al. Arch Dermatol 2006;142: Copyright restrictions may apply. Non-melanocytic simulators of melanoma in situ 43
44 Angiofibromas with prominent junctional melanocytes 44
45 Pagetoid Bowen s disease 45
46 46
47 Pagetoid reticulosis 47
48 Pageoid spread in Merkel cell carcinoma 48
49 49
50 50
51 Pagetoid dyskeratosis 51
52 Paget s disease And extramammary Paget s disease 52
53 53
54 Spitz nevus 54
55 55
56 56
57 57
58 Spitz nevus- genomics Usually b-raf wild type H-ras mutated in a minority Most have normal CGH profile 20% with 11p gain Blue nevus, esp. cellular 58
59 59
60 60
61 61
62 Deep penetrating nevus 62
63 63
64 Combined nevi Combined nevi Small round and blue Small round and Spitz Spitz and blue Deep penetrating and small round 64
65 5/28/
66 66
67 Ancient nevus FIGURE 2 Ancient Melanocytic Nevus: A Simulator of Malignant Melanoma. Kerl, Helmut; Wolf, Ingrid; Kerl, Katrin; Cerroni, Lorenzo; Kutzner, Heinz; Argenyi, Zsolt American Journal of Dermatopathology. 33(2): , April DOI: /IAE.0b013e31817f7b58 FIGURE 2. Ancient melanocytic nevus. Dome-shaped asymmetric brownish tumor with a bluish cast Lippincott Williams & Wilkins, Inc. Published by Lippincott Williams & Wilkins, Inc. 2 67
68 Halo nevus 68
69 Proliferative nodules in congential nevi 69
70 70
71 71
72 72
73 73
74 Cytogenetic changes in proliferative nodules Papules have no cytogenetic abnormalities Nodular proliferations usually normal, or with losses or gains of whole chromosomes Focused losses and gains (typical of melanoma) not seen in proliferative nodules Prognostic values of CGH not yet 74
75 Non-melanocytic simulators of melanoma in the dermis Cellular and epithelioid schwannoma Cellular neurothekeoma Atypical fibroxanthoma Desmoplastic leiomyosarcoma and squamous cell carcinoma Pigmented dermatofibrosarcoma protuberans Pigmented basal and sqaumous cell carcinoma Pigmented matricoma Rosai-Dorfman disease Monsel s granuloma Carcinoma metastastic to nevus Pigmented metastatic carcinoma Cellular neurothekeoma 75
76 76
77 77
78 Rosai-Dorfman Disease Cutaneous Rosai-Dorfman Disease Rare: about 60 cases Papules, plaques, nodules, many sites Rare presentations: acneiform, vasculitic, panniculitic, pigmented macules, in zoster scars, bilateral cauliflower ear deformities Affects older patients, different epidemiology Often no significant symptoms, rare laboratory anomalies* Spontaneous remissions, and/or recurrence 78
79 79
80 80
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