Blue Nevus


Article Author:
Steve Austad


Article Editor:
Leela Athalye


Editors In Chief:
David Wood
Andrew Wilt
Hajira Basit


Managing Editors:
Avais Raja
Orawan Chaigasame
Khalid Alsayouri
Kyle Blair
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Abbey Smiley
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beenish Sohail
Hajira Basit
Phillip Hynes
Sandeep Sekhon


Updated:
11/5/2019 6:52:55 PM

Introduction

The term "blue nevus" is used to describe a group of skin lesions characterized by dermal proliferation of melanocytes presenting as blue to black nodules on the head, extremities, or buttocks. In most cases, they are acquired and present as a solitary lesion but may also be congenital and appear at multiple sites. In addition to multiple less-known variants, there are two widely known histological subtypes: common blue nevus (dendritic blue nevus or Jadassohn-Tieche type) and cellular blue nevus.[1] Additionally, there are several variants of common nevi, including epithelioid, sclerosing, amelanocytic, and combined.[2]

Etiology

Blue nevi are most commonly acquired, but in rare cases, they can be congenital and associated with familial or other syndromes, such as LAMB (lentigines, atrial myxomas, and blue nevi) and NAME (nevi, atrial myxoma, myxoid neurofibromas, and ephelides). One variant, the epithelioid type, is a common manifestation in the Carney complex,[1] a form of multiple endocrine neoplasia distinguished by pigmented skin and mucosal lesions and cardiac myxomas.[3]

Epidemiology

Epidemiology differs amongst the two common subtypes. Common blue nevus typically presents in young adults, while cellular blue nevus is commonly diagnosed in middle-aged individuals and shows a greater than 2 to 1 predilection for women to men. Additionally, cellular blue nevi may measure up to several centimeters as opposed to common blue nevi, which usually measure no more than 1 cm.[1]

Pathophysiology

The exact etiology of blue nevus is unclear. Some postulate that components of blue nevus are remnants of migrating neural crest melanocytes during development. Others theorize that they arise from specific stem cells within the dermis.[2] The proliferation of melanocytes in the dermis and surrounding melanophages containing abundant melanin pigment create a distinctive blue hue. The characteristic blue color is a result of reflection, rather than absorption, of shorter wavelengths of light corresponding to the color blue by dermal melanin. This phenomenon is known as the Tyndall effect.[1][2]

Histopathology

Histopathology of blue nevi varies by subtype, but general characteristics include a vertical wedge or bulbous shaped proliferation of spindle cells, dendritic melanocytes, and melanophages into a sclerotic dermis or subcutis. Histologic components of various nevi types, including blue nevus, may occur together and classify as a combined blue nevus. Additional features such as atypia increased mitotic rate, and cell overcrowding, vascular invasion, and necrosis are suggestive of malignancy and more characteristic of blue nevus-like melanoma (BNLM).[1] Another hybrid variant, atypical cellular nevus, has histologic features of a cellular nevus with some atypia but without the overt malignant characteristics seen in BNLM.[1] HMB-45, S-100, and MART-1 stains are usually positive[2], and CD68, Melan-A, and MiTF may also be positive in the epithelioid subtype.[1]

History and Physical

Blue nevi may present as a solitary, well-demarcated, blue to black nodule or confluence of nodules at a single site or maybe diffusely distributed in the case of familial syndromes such as NAME and LAMB. Common blue nevi tend to present on the face and extremities, while cellular blue nevi occur more commonly on the buttock and sacrococcygeal region.[1][2] Blue nevi have also presented less commonly at extracutaneous sites, including conjunctivae,[4] oral mucosa,[5] gastrointestinal tract,[6] genitourinary tract,[7] and subungual.[8]

Evaluation

The diagnosis of blue nevus is generally clinical, made grossly, or with the use of a dermatoscope, though biopsy and pathologic evaluation is the gold standard for definitive diagnosis.[9] There are no other standard laboratory, radiographic, or other tests commonly used to establish the diagnosis.

Because melanoma can present clinically over a broad spectrum of morphologies, it is crucial to make the distinction with blue nevus as the former may also commonly present as a nodule with a blue to black hue.[10] One standard methodology is screening for ABCDE’s (Asymmetry, irregular Borders, Color variation, Diameter greater than 6 mm, Evolving). Another more modern clinical tool is the “Ugly Duckling” sign based on the premise that concerning lesions typically don’t mirror surrounding ones. More recently, there have been suggestions that the two be used in conjunction with one another to improve sensitivity.[11]

When high suspicion for melanoma exists, an incisional biopsy is not a recommendation. An excisional biopsy, as opposed to punch or shave, should be performed, with only a few exceptions to include larger lesions and cosmetically sensitive areas. An excisional biopsy allows more accurate and timely tumor staging and prompt referral for appropriate management in the case of malignant lesions.[12]

Treatment / Management

Given both the potential for misdiagnosis and association with blue nevus-like melanoma, blue nevi require monitoring, and a biopsy performed in cases of rapid change in morphology or size. This latter point is especially true in the case of cellular blue nevi, from which malignant blue nevus most commonly arise.[1][2][13][14] The definitive treatment of blue nevus is excision, though it is appropriate to monitor stable lesions clinically. In rare cases, blue nevus may recur at sites of prior excision. Though excision is considered curative, the appearance of recurrent blue nevus at a prior site should warrant biopsy and/or re-excision as it could represent emerging malignant blue nevus or other melanoma.[1]

Differential Diagnosis

Blue nevi have a distinct appearance but are often misdiagnosed. One less common variant, amelanocytic blue nevus, may be mimicked by dermatofibroma or scar due to lack of melanin pigment and the histologic presence of spindle cells, collagen, and/or sclerotic stroma. It also may be confused with amelanocytic melanoma. Another variant, desmoplastic blue nevus, histologically shows exaggerated dermal fibrosis and may be confused with desmoplastic melanoma.[1] Additionally, blue nevus-like melanoma must carefully be distinguished from blue nevi, especially the cellular subtype, to avoid delayed diagnosis and treatment, as the two frequently get mistaken for one another.[1][2]

Prognosis

The prognosis of blue nevus is good, as the lesion in its pure form is benign.[1] However, though blue nevus-like melanoma arising from blue nevus is rare, most known cases have behaved aggressively and resulted in metastasis and death.[1] A retrospective analysis showed that BNLM carries a risk of metastasis and prognosis similar to conventional melanoma when comparing lesions of equivalent depth and staging.[2][15]

Complications

There are no common significant complications associated with benign blue nevi. Malignant transformation or de novo melanoma involving cellular blue nevi carries the risk of metastasis but is rare.[1][2]

Deterrence and Patient Education

Due to their benign nature, blue nevi that remain clinically stable do not require biopsy.[1] Lesions that are new and/or changing should have a biopsy to rule out blue nevus-like or other melanoma.[1][2][13][14]

Enhancing Healthcare Team Outcomes

Considerable controversy exists with regards to the classification and identification of blue nevi, especially as it pertains to blue nevus-like melanoma. A more traditional term, malignant blue nevus, has been used to describe melanoma arising at the site of the blue nevus. The term is somewhat antiquated, as many have pointed out that the term implies that all cases involve a malignant transformation of an existing blue nevus, which is inaccurate. Melanoma may arise de novo with features of blue nevus, at the site of a previous blue nevus excision, or within a preexisting blue nevus.[1] The term blue nevus-like melanoma has been adopted by others, though some argue the term is also limiting, as it implies all melanomas appearing in blue nevi have histologic and epidemiological characteristics of the latter, which is not necessarily the case.[2]

It is essential that healthcare providers, particularly dermatologists and pathologists, understand the distinction and communicate appropriately to minimize morbidity and mortality and maximize patient outcomes.

Additionally, because blue nevi often get treated as melanomas, and clinicians may mistake the latter for benign lesions, primary care providers, including nurse practitioners, should be familiar with how blue nevi present clinically and recognize red flag signs that warrant biopsy and/or dermatology referral. Dermatologists should be comfortable and familiar enough with the presentation of blue nevi to avoid unnecessary procedures while maintaining a healthy respect for their malignant potential and appropriate clinical acumen to biopsy them when necessary. Dermatology specialized nursing staff can be valuable in the assessment and treatment of these lesions, especially during excision and subsequent followup and patient counsel. All these clinicians, specialists, and nursing staff need to collaborate as an interprofessional team to guide these cases to optimal outcomes. [Level V]


  • Image 11677 Not availableImage 11677 Not available
    Image courtesy S Bhimji MD
Attributed To: Image courtesy S Bhimji MD

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Blue Nevus - Questions

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A 16-year-old Asian boy presents with a three-year history of a 1.5 cm blue nodule on the scalp. A biopsy report classifies the lesion as a cellular blue nevus. What should the physician tell this patient?



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A 3-year-old child is brought to the clinic by her mother for a dark-colored bump on her right cheek. Examination reveals a 2 mm blue-colored papule, and a biopsy is subsequently performed. Pathology reveals dendritic melanocytes and macrophages, forming a wedge-shape protrusion into the dermis. Which of the following is the most likely diagnosis?



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A 42-year-old woman presents to the clinic with a blueish black spot on the buttocks. Pathology reveals bulbous extension of oval spindle cells, dendritic melanocytic cells and melanophages into the dermis, atypia and high mitotic rate, and areas of necrosis. Which of the following subtypes is the most common precursor of this lesion?



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A 15-year-old boy with a history of Carney complex presents with a 5 mm deep blue nodule on the distal arm. Which of the following immunohistochemical stains would best distinguish this lesion from other blue nevi?



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A patient presents to the clinic with a dark-colored nodule on the frontal scalp, and biopsy shows a bulb-shaped dermal proliferation of spindle-shaped cells, dendritic melanocytes, and melanophages. What phenomenon is most likely responsible for its distinguishable color?



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A 62-year-old woman presents to the clinic after noticing black, irregular skin discoloration at the site of a previously excised blue nevus. A biopsy is performed, and histopathology reveals blue nevus-like histology with extensive necrosis. Which of the following suggests the highest risk of malignant potential?



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Blue Nevus - References

References

Murali R,McCarthy SW,Scolyer RA, Blue nevi and related lesions: a review highlighting atypical and newly described variants, distinguishing features and diagnostic pitfalls. Advances in anatomic pathology. 2009 Nov;     [PubMed]
Zembowicz A,Phadke PA, Blue nevi and variants: an update. Archives of pathology     [PubMed]
Sayed-Ahmed I,Murillo JC,Monsalve P,Ulloa JP,Fernandez MP,Wong J,Elgart G,Galor A,Dubovy SR,Karp CL, Blue Nevi of the Ocular Surface: Clinical Characteristics, Pathologic Features, and Clinical Course. Ophthalmology. 2018 Aug;     [PubMed]
Kauzman A,Rei N,Avon SL, The blue nevus: a rare lesion of the oral cavity. General dentistry. 2014 Sep-Oct;     [PubMed]
Lam KY,Law S,Chan GS, Esophageal blue nevus: an isolated endoscopic finding. Head     [PubMed]
Fitzhugh VA,Houck K,Heller DS, Vaginal blue nevus: report of a case and review of the literature. Journal of lower genital tract disease. 2011 Oct;     [PubMed]
Kim HS,Kim YJ,Kim JW,Yu DS, Subungal blue nevus. Journal of the European Academy of Dermatology and Venereology : JEADV. 2007 Feb;     [PubMed]
Granter SR,McKee PH,Calonje E,Mihm MC Jr,Busam K, Melanoma associated with blue nevus and melanoma mimicking cellular blue nevus: a clinicopathologic study of 10 cases on the spectrum of so-called 'malignant blue nevus'. The American journal of surgical pathology. 2001 Mar;     [PubMed]
Aloi F,Pich A,Pippione M, Malignant cellular blue nevus: a clinicopathological study of 6 cases. Dermatology (Basel, Switzerland). 1996;     [PubMed]
Ferrara G,Soyer HP,Malvehy J,Piccolo D,Puig S,Sopena J,Zalaudek I,Argenziano G, The many faces of blue nevus: a clinicopathologic study. Journal of cutaneous pathology. 2007 Jul;     [PubMed]
Martin RC,Murali R,Scolyer RA,Fitzgerald P,Colman MH,Thompson JF, So-called     [PubMed]
Correa R,Salpea P,Stratakis CA, Carney complex: an update. European journal of endocrinology. 2015 Oct     [PubMed]
Rastrelli M,Tropea S,Rossi CR,Alaibac M, Melanoma: epidemiology, risk factors, pathogenesis, diagnosis and classification. In vivo (Athens, Greece). 2014 Nov-Dec     [PubMed]
Daniel Jensen J,Elewski BE, The ABCDEF Rule: Combining the "ABCDE Rule" and the "Ugly Duckling Sign" in an Effort to Improve Patient Self-Screening Examinations. The Journal of clinical and aesthetic dermatology. 2015 Feb     [PubMed]
Tadiparthi S,Panchani S,Iqbal A, Biopsy for malignant melanoma--are we following the guidelines? Annals of the Royal College of Surgeons of England. 2008 May     [PubMed]

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