J Cutan Pathol 2007: 34: 543–551 Copyright # Blackwell Munksgaard 2006 doi: 10.1111/j.1600-0560.2006.00650.x Blackwell Munksgaard. Printed in Singapore Journal of Cutaneous Pathology The many faces of blue nevus: A clinicopathologic study Background: In recent years, several histopathologic variants of Gerardo Ferrara1, H. Peter blue nevus have been identified, whose clinical and dermoscopic Soyer2, Josep Malvehy3, correlates need further clarification. Domenico Piccolo4, Susana Methods: A comparative evaluation of histopathologic and Puig3, Juan Sopena5, Iris dermoscopic features was carried out on 52 melanocytic proliferations Zalaudek6 and Giuseppe belonging to the morphologic spectrum of blue nevus. Argenziano7 Results: On dermoscopy, all lesions showed a homogeneous, 1Pathologic Anatomy Service, Gaetano structureless pigment pattern, with a curious variety of colors (blue, Rummo General Hospital, Benevento, Italy, white–blue, black, brown, and polychromatic). Histopathologically, the 2Department of Dermatology, Medical University of Graz, Graz, Austria, majority of blue lesions were common blue nevi (11/19); the majority 3 Ô Department of Dermatology, Melanoma Unit, of white–blue lesions were hypochromic’ (sclerotic, hypomelanotic, Hospital Clı´nic, IDIBAPS, University of and amelanotic) blue nevi (17/22); all the black lesions were Barcelona, Barcelona, Spain, Ôcompound’ blue nevi (2/2); the majority of brown lesions were 4Department of Dermatology, University of L’Aquila, L’Aquila, Italy, combined blue nevi (3/4); the unusual polychromatic dermoscopic 5 appearance was often associated with a histopathologic diagnosis of Fundacio´n Hospital Alcorco´n, Madrid, Spain, 6Department of Dermatology, Medical deep penetrating nevus (2/5). University of Graz, Graz, Austria, and Conclusion: A dermoscopic–pathologic approach now allows us to 7Department of Dermatology, Second identify Ôblue’ (common) blue nevi, Ôwhite’ (hypochromic) blue nevi, University of Naples, Naples, Italy Ôblack’ (compound) blue nevi, Ôbrown’ (combined) blue nevi, and Ôpolychromatic’ (deep penetrating) blue nevi. A better recognition of Gerardo Ferrara, MD, Pathologic Anatomy Service, the many dermoscopic faces of blue nevi is expected to give Gaetano Rummo General Hospital, Via dell’Angelo 1, a morphologic guideline for the clinical management of these lesions. I-82100 Benevento, Italy Tel: 139 082457315 Ferrara G, Soyer HP,Malvehy J, Piccolo D, Puig S, Sopena J, Zalaudek I, Fax: 139 082457332 e-mail: [email protected] Argenziano G. The many faces of blue nevus: A clinicopathologic study. J Cutan Pathol 2007; 34: 543–551. # Blackwell Munksgaard 2006. Accepted for publication July 19, 2006 Dermal dendritic melanocytic proliferations Table 1 shows a comprehensive histopathologic (DDMP) can be defined as a spectrum of congenital classification of these entities, many of which are and/or acquired melanocytic lesions whose histo- still poorly defined from a clinical and dermoscopic pathologic hallmark is the presence of variable point of view. proportions of oval/spindle and bipolar dendritic In the present study, we evaluate the clinical and cells, the latter being usually heavily pigmented.1 dermoscopic correlates in a series of melanocytic Three categories of DDMP were identified in the lesions belonging to the histopathologic spectrum of classical dermatopathology literature: hamartoma- blue nevus. tous dermal melanocytoses (Mongolian spot, nevi of Ota and Ito), classic and cellular blue nevi, and melanoma arising in blue nevus.1 In addition Materials and methods Ôcombined’ lesions made up of DDMP admixed Lesions were collected from the pathology files of with any other benign melanocytic proliferation the University Dermatology Departments in Graz, (congenital non-blue, common acquired, dysplastic/ Austria, L’Aquila and Naples, Italy, and Barcelona Clark, and Spitz nevi) were considered as well.2–4 and Madrid, Spain. They had been consecutively In recent years, a number of additional histopath- excised with a clinical and dermoscopic diagnosis of ologic variants of DDMP have been described.1–22 Ôblue nevus with atypical features’, namely a lesion 543 Ferrara et al. Table 1. A classification of dermal dendritic melanocytic proliferations Molemax system, Derma Medical Systems, Vienna, Benign Austria). Since blue nevi are dermoscopically Hamartomatous characterized by a diffuse, structureless pigmenta- Mongolian spot 23–26 Nevus of Ota tion, attention was mainly given to the different Nevus of Ito colors that typify the pigmentation seen by dermo- Non-hamartomatous scopy. Each lesion was thus recorded as blue, white– Common blue nevus Cellular blue nevus blue, black, brown, or polychromatic. Lesions were classical evaluated as white–blue in the presence of white angiomatoid areas clearly discernible from areas of blue color. In with schwannian differentiation (Masson neuronevus) ÔHypochromic’ blue nevus/cellular blue nevus these lesions, the percentage of white areas was myxoid (cystic) recorded as well. Polychromatic lesions were defined desmoplastic/sclerotic hypomelanotic as having at least three easily discernible colors. amelanotic In each case, the detailed histopathologic catego- Deep penetrating nevus rization was made by one of us (G. F.) on a single Compound blue (Kamino) nevus Combined blue nevus hematoxylin–eosin-stained specimen, which had Atypical blue nevusà been considered as representative of the lesion by Borderline the referring histopathologists. Paraffin blocks were Large infiltrative cellular blue nevus of the scalp not available for further studies. The histopathologic of other sites evaluation was made based on the classification Cellular blue nevus with prominent vascular network (paraganglioma-like dermal melanocytic tumor) given in Table 1. Each entity was defined according Cutaneous neurocristic hamartoma/ malignant neurocristic tumor to the criteria listed in Table 2. These criteria were Pigmented epithelioid melanocytomaÃà Malignant Melanoma arising in blue nevus Blue nevus-like (dendritic cell) primary melanoma Table 2. Histopathologic features of benign, non-hamartomatous dermal Blue nevus-like metastatic melanoma dendritic melanocytic proliferations ÃIf strict morphologic criteria are used, atypical blue nevus has a Dendritic cell proliferation Hallmark features completely favorable clinical outcome.1,5 ÃÃCases of epithelioid blue nevus in Carney complex did not metastasize Common blue nevus A heavily and uniformly pigmented to date. However, they cannot be morphologically distinguished from proliferation of dendritic melanocytes cases of metastasizing epithelioid blue nevus and from animal-type with a subepidermal grenz zone melanoma, thereby justifying their inclusion into a unique category Cellular blue nevus, A proliferation of heavily pigmented designated Ôpigmented epithelioid melanocytoma’.1 classical dendritic melanocytes with island of pale and plump cells Cellular blue nevus, A cellular blue nevus with wide angiomatoid congested vascular spaces with overall clinical and dermoscopic features of Cellular blue nevus, with A cellular blue nevus with Ôneuroid’ blue nevus but with some atypical findings. Atypical schwannian differentiation fascicles of spindle cells with a findings included large size, history of recent growth (Masson neuronevus) wavy silhouette ÔHypochromic’ blue nevus, A common/cellular blue nevus with or change, inflammatory perilesional halo or dermo- myxoid (cystic) either intercellular mucin deposition scopic features deviating from the stereotypical steel or a central empty mucinous-like blue pigmentation.23–26 The previously reported or myxohyaline core 16 ÔHypochromic’ blue nevus, A common/cellular blue nevus with a cases of Ôcompound’ blue nevus were also included desmoplastic/sclerotic central area of dense sclerosis in the study. Cases with incomplete clinical data harboring only a few interspersed pigmented cells and/or no preoperative dermoscopic documenta- ÔHypochromic’ blue nevus, A common blue nevus with loss of tion were excluded. The study was conceived as hypomelanotic melanin within the 10–95% of the a comparative evaluation of specific histopathologic area of the lesion ÔHypochromic’ blue nevus, A common/cellular blue nevus with loss diagnoses and dermoscopic features. Therefore, amelanotic of melanin in more than 95% of the both histopathologic specimens and dermoscopic area of the lesion Deep penetrating nevus A wedge-shaped lesion composed by images needed to be first reviewed blindly by the fascicles of spindle cells and dendritic respective experts and then re-evaluated in order to cells with some interspersed produce a combined set of dermoscopic and Ôsebocyte-like’ epithelioid cells Compound blue (Kamino) A blue nevus with no appreciable histopathologic data. nevus subepidermal grenz zone and Dermoscopic evaluation, performed by one of us prominent intraepidermal dendritic (G. A.), was based on JPEG files either obtained melanocytes arranged in single units Combined blue nevus A common/cellular blue nevus mixed from 35-mm color slides (acquired by Dermaphot and regularly merged with a nevus lens, Heine Optotechnik, Herrsching, Germany, of different kind Atypical blue nevus A common/cellular blue nevus with mounted on a standard reflex camera) or by using one or several atypical features a digital imaging dermoscopy system (Dermlite Foto, (typical mitoses up to 3–4/mm2, 3-Gen llc, Salvador Bay, Dana Point, CA, USA; ulceration, size .50 mm, deep Videocap system, DS