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
Melanocytic nevi on acral skin 2
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, 2003 3
Nevi on special sites Acral-volar Nail matrix/bed Genitalia Scalp (children) Back (two patterns) Flexural Ear Conjunctiva Spitz acral Spitz ear 4
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Melanocytic Acral Nevus with Intraepidermal Ascent of Cells 7
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The American Journal of Surgical Pathology 27(3): 411-412; Mar 2003 9
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Inflamed melanocytic nevi 12
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
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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
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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
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What s ailing this nevus? 20
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Dysplastic nevi 22
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Superficial Spitz nevus 26
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Inflamed or traumatized junctional Reed nevus 28
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Persistent/recurrent nevi 32
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Genital nevi 34
Masson, 1981 35
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Pagetoid scatter in congenital nevi in neonates 37
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Large single melanocytes overlying intradermal nevi 39
Large single melanocytes in sun damaged skin: Actinic melanocytosis Actinic melanocytosis Gilchrest et al. 1979 J.Invest.Dermatol. Paired biopsies, exposed and non-exposed skin, adjacent sites donors aged 28-80 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
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. 1996 Dec;18(6):560-6. 41
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. 2006 Jul;142(7):871-6. Hendi, A. et al. Arch Dermatol 2006;142:871-876. Copyright restrictions may apply. 42
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;142:871-876. Copyright restrictions may apply. Non-melanocytic simulators of melanoma in situ 43
Angiofibromas with prominent junctional melanocytes 44
Pagetoid Bowen s disease 45
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Pagetoid reticulosis 47
Pageoid spread in Merkel cell carcinoma 48
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Pagetoid dyskeratosis 51
Paget s disease And extramammary Paget s disease 52
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Spitz nevus 54
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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
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Deep penetrating nevus 62
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Combined nevi Combined nevi Small round and blue Small round and Spitz Spitz and blue Deep penetrating and small round 64
5/28/2011 65
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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):127-130, April 2011. DOI: 10.1097/IAE.0b013e31817f7b58 FIGURE 2. Ancient melanocytic nevus. Dome-shaped asymmetric brownish tumor with a bluish cast. 2011 Lippincott Williams & Wilkins, Inc. Published by Lippincott Williams & Wilkins, Inc. 2 67
Halo nevus 68
Proliferative nodules in congential nevi 69
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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
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
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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
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