KJ Busam, M.D. Paris, 2017 Blue Nevi and Melanomas Natural Blue BLUE NEVUS Blue Nevus (BN)
• Spectrum of blue nevi – Common, Sclerosing, Epithelioid, Cellular, Plaque type blue nevi
• Differential diagnosis – Melanoma ex BN or simulating BN – BN vs other tumors – Biphenotypic/collision lesions Common Blue Nevus
Clinical: - Circumscribed small bluish macule/papule - Preferred sites: Scalp, wrist, foot
Pathology: - Predominantly reticular dermal lesion - Pigmented fusiform and dendritic cells - Admixed melanophages - Bland cytology Common Blue Nevus Blue Nevus Sclerosing Blue Nevus
Pigm BN Cellular Blue Nevus - 49 yo woman - Buttock nodule CBN Cellular Blue Nevus
Thrombi and stromal edema Multinucleated giant melanocytes Cellular Blue Nevus
Hemorrhagic cystic (“aneurysmal”) change Amelanotic Cellular Blue Nevus
19 yo man with buttock lesion Atypical CBN Plaque-Type Blue Nevus Plaque-type Blue Nevus Plaque Type Blue Nevus Mucosal Blue Nevus
Conjunctival Blue Nevus Nodal Blue Nevus Combined epithelioid BN Blue Nevus
• M Tieche 1906; Virchow Arch Pathol Anat “Blaue Naevus”
• B Upshaw 1947; Surgery “Extensive Blue Nevus” (plaque-type BN)
• A Allen 1949; Cancer “ Cellular Blue Nevus”
Blue Nevus – Mutation Analysis
Type of Lesion GNAQ GNA11 Number Common BN 6.7% 65% 60 Cellular BN 8.3% 72.2% 36 Amelanotic BN 0% 70% 10 Nevus of Ota 5% 10% 20 Nevus of Ito 16.7% 0% 7 TOTAL 6.5% 55% 139
Van Raamsdonk et al NEJM 2010; 2191-9 Blue Nevus – Mutation Analysis
Type of Blue Nevus GNAQ Number Common Blue Nevus 40% 4/10 Cellular Blue Nevus 44% 4/9 Hypomelanotic BN 12.5% 1/8
Emley et al Hum Pathol 2011; 42:136-40
Chromosomal aberrations are frequent in malignant blue tumors BAP1 loss is common in malignant blue tumors
Diagnostic Problems
• BN vs Other Benign Lesions – Pigmented NF, DF, scar, PEM • BN vs Primary Malignant Tumor – Pigmented melanoma – Malignant blue tumor – Sarcoma (DFSP, clear cell sarcoma, Melanotic Schwannian Tumor) – Melanoma-associated melanosis • BN vs Metastatic Melanoma – Cutaneous BN vs metastatic melanoma – Nodal BN vs metastatic melanoma Melanoma ex or simulating BN (“Malignant Blue Nevus” or Malignant Blue Tumor)
• Fisher ER. Arch Dermatol 1956; 71:227 - 31
• Connelly and Smith. Cancer 1991; 67:2653-7
• Granter et al Am J Surg Pathol 2991; 25:316-23
• Loghavi et al Mod Pathol 2014;27:1468-78. Malignant Blue Melanocytic Tumors
• Heterogeneous group of melanomas
• Range of clinical behavior: many tumors are highly aggressive; a few have a protracted course
• Predilection for: head and neck, trunk, buttock
• Controversy regarding diagnostic and prognostic features Melanoma ex CBN
Loghavi et al Mod Pathol 2014 Melanoma ex CBN Diff Dx: Cellular Lesions CBN or Melanoma?
Cellular Blue Nevus Melanoma ex CBN
• Stable lesion • Changing lesion • Bi-phasic pattern • Tumor overgrowing stroma
• Cytology • Cytology – Spindle cells – Epithelioid cells – Bland nuclei – Nuclear atypia – No or rare mitoses – Mitoses – Necrosis – usually absent – Necrosis – often present
Melanoma ex CBN: Necrosis
Melanoma ex CBN Melanoma ex Plaque BN Cellular Blue Nevus vs Melanoma
How many mitoses are acceptable for a CBN?
Mitosis FISH/CGH for the distinction of CBN from Melanoma
• Gammon B et al J Cutan Pathol 2011; 38:335-41
• Yeh I et al Am J Surg Pathol 2012;36:1258-63
• North JP et al J Cutan Pathol 2012; 39:1094-9 CGH – Findings
Yeh et al Am J Surg Pathol 2012;36:1258-63
Diagnostic Problems
• Malignant Blue Tumor vs Other Melanoma – Pigmented nodular melanoma – Pigment-synthesizing melanoma
• Tumoral Melanosis
• BN vs metastatic melanoma Tumoral Melanosis 53 yo man, lesion on back; r/o MM Nodular melanoma with tumoral melanosis Summary
• Spectrum of features of blue nevi
• Melanoma associated with a blue nevus
• Differential diagnosis
• Value of ancillary studies
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