Melanoma Arising in Association With Blue Nevus

A Clinical and Pathologic Study of 24 Cases and Comprehensive Review of the Literature

Sanam Loghavi; Jonathan L Curry; Carlos A Torres-Cabala; Doina Ivan; Keyur P Patel; Meenakshi Mehrotra; Roland Bassett; Victor G Prieto; Michael T Tetzlaff

Disclosures

Mod Pathol. 2014;27(11):1468-1478. 

In This Article

Abstract and Introduction

Abstract

Melanomas arising in association with blue nevi or mimicking cellular blue nevi comprise a relatively rare and heterogeneous group of melanomas. It remains controversial which prognostic indicators predictive of outcome in conventional cutaneous melanomas are applicable to this type of melanoma. Here, we describe the clinical and histopathologic features of 24 melanomas arising in association with blue nevi and correlate these with clinical outcome. The mean patient age was 49 years (range: 23–85) with a slight female predominance (15 females:9 males). The most common anatomic locations included the head and neck region (50%), the trunk (21%), and the buttock/sacrococcygeum (17%). Histologically, the tumors were typically situated in the mid to deep dermis with variable involvement of the subcutis, but uniformly lacked a prominent intraepithelial component. The mean tumor thickness (defined as either the standard Breslow thickness or, if not available due to the lack of orientation or lack of epidermis, the largest tumor dimension) was 20.9 mm (range: 0.6–130 mm). The mean mitotic figure count was 6.5/mm2 (range: 1–30/mm2). Perineural invasion was common (38%). Follow-up was available for 21 cases (median 2.1 years). The median overall survival, recurrence-free survival, time to local recurrence, and time to distant recurrence were 5.2, 0.7, 2.6, and 1.6 years, respectively. Logistic regression analyses demonstrated a significant association between tumor thickness and recurrence-free survival (hazard ratio=1.02 per mm; P=0.04) and reduced time to distant metastasis (hazard ratio=1.03 per mm; P=0.02) with a similar trend toward reduced time to local recurrence (hazard ratio=1.02 per mm; P=0.07). No other parameters (age, anatomic location, mitotic figures, lymphovascular or perineural invasion, or type of associated blue nevus) emerged as significant. In addition, we provide a comprehensive review of 109 cases of melanoma blue nevus type described in the English literature and summarize our findings in this context.

Introduction

Blue nevi represent a broad spectrum of melanocytic proliferations with distinctive clinical and histopathologic features. Common blue nevi were first described by Jadassohn-Tieche.[1] These nevi typically develop congenitally or de novo on the extremities, scalp, and buttocks and exhibit a characteristic blue–black-grey–black clinical discoloration of variable sizes.[2,3] Histopathologically, common blue nevi are characterized by a wedge-shaped, variably cellular dermal proliferation of distinctive spindled, dendritic melanocytes with elongated, hyperchromatic nuclei and variable amounts of coarse intracytoplasmic pigment. An associated desmoplastic stromal reaction and melanophages are typical.[2,3] Cellular blue nevi most commonly arise on the buttock/sacrococcygeal area and less commonly, the scalp and extremities. They typically grow as larger, multilobulated masses (often with a characteristic 'dumbbell shape') and consist of a biphenotypic proliferation of dendritic melanocytes reminiscent of classic blue nevus admixed with cellular nodules of spindled oval-shaped melanocytes with a variable admixture of pigmented macrophages.[2–4] The term melanoma blue nevus type designates a heterogeneous group of malignant melanocytic proliferations (melanomas) that either (A) arise in association with common or cellular blue nevi or (B) develop de novo but architecturally or cytologically mimic cellular blue nevus.[3–5] Diagnostic histopathologic features include a proliferation of melanocytes with malignant cytology (nuclear pleomorphism, coarse chromatin, prominent nucleoli), increased and/or atypical mitotic figures, tumor necrosis, and invasive and/or destructive pattern of growth and occasionally, an adjacent/associated proliferation of distinctly benign blue nevus dendritic melanocytes.[6]

Although melanoma blue nevus type have been shown to exhibit outcomes similar to conventional melanoma when matched for Breslow thickness, age, Clark level, and ulceration,[7] it remains controversial which—if any—of the discrete clinical and pathologic indicators (like age, gender, Breslow thickness, mitotic figures, and ulceration) predictive of clinical outcome in conventional cutaneous melanomas might apply to this group of melanomas. This is especially contentious considering the typical restriction of melanoma blue nevus type to the dermis and/or subcutaneous tissue without an associated intraepidermal component, which has been suggested to undermine the biological relevance of Breslow thickness and tumor ulceration as predictors of outcome.[5] Further complicating this issue, the constellation of distinctive diagnostic features described above is not apparent in every case; thus, the unequivocal distinction of melanoma (arising with or resembling blue nevus) from benign cellular blue nevus or atypical cellular blue nevus[8,9] also remains controversial—even among experienced dermatopathologists.[10] It is therefore not surprising that there are only ~100 cases described in the literature to date[4,5,7,11–54] and the majority of these are individual case reports or small case series—too few to achieve statistical significance in correlating histopathologic features with clinical behavior.

Here, we describe the clinical and histopathologic features of 24 melanomas arising in association with common or cellular blue nevi. We further correlate the clinical and histopathologic features of these lesions with annotated clinical follow-up information. We demonstrate a statistically significant association between tumor thickness (defined as either the standard Breslow thickness or, if not available due to lack of orientation or lack of epidermis, the largest tumor dimension) and both recurrence-free survival and reduced time to distant metastasis. In addition, we provide a comprehensive review of the 109 cases of melanoma blue nevus type described in the English literature and summarize our findings in the context of the clinical and pathologic features of these lesions.

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