Blue Nevi 

Updated: Sep 18, 2020
Author: Rudolf R Roth, MD; Chief Editor: William D James, MD 

Overview

Background

Two clinically recognized variants of blue nevus exist: the common blue nevus and the cellular blue nevus.

Tièche, a student of Jadassohn, first described the common blue nevus in 1906. Earlier authors described similar lesions as chromatophoroma and melanofibroma. The common blue nevus is a flat to slightly elevated, smooth surfaced macule, papule, or plaque that is gray-blue to bluish black in color. Lesions are usually solitary and found on the head and the neck, the sacral region, and the dorsal aspects of the hands and feet.

The cellular blue nevus was first described as a variant of melanoma. Later, it was classified as a variant of blue nevus. Controversy still arises over the precise distinction of atypical cellular blue nevus from melanoma.[1] The cellular blue nevus is a less common lesion but often clinically similar to the common blue nevus. These lesions tend to be large, usually measuring 1-3 cm in diameter. Lesions are elevated, smooth-surfaced papules or plaques that are gray-blue to bluish black in color. Lesions are usually solitary and found on the buttocks, the sacral region, and occasionally on the dorsal aspects of the hands and the feet.

In addition to the common blue nevus and the cellular blue nevus, there are variants similar to typical nevi, such as the combined blue nevus, the sclerosing (desmoplastic) blue nevus, the amelanotic blue nevus, and the epitheliod blue nevus.[2]

Pathophysiology

Although definitive experimental evidence is lacking, blue nevi are believed to represent dermal arrest in embryonal migration of neural crest melanocytes that fail to reach the epidermis. Collections of melanocytes can be found in fetal dermis, but they involute during later gestation.

Because of the variation of blue nevi in different populations, a genetic predisposition has been suggested. However, familial cases of blue nevi are exceedingly rare.

The clinically noted blue color is due to the depth of melanin in the epidermis and the Tyndall effect. The Tyndall effect is the preferential absorption of long wavelengths of light by melanin and the scattering of shorter wavelengths, representing the blue end of the spectrum, by collagen bundles.

Common blue nevi show fewer BRAF mutations compared with congenital and acquired nevi,[3] but they show somatic mutations in the heterotrimeric G protein α-subunit, GNAQ, in up to 83% of cases.[4, 5]

Etiology

See Pathophysiology. Although blue nevi are most frequently seen on the skin, they have also been reported in the oral cavity, subungually,[6] in lymph nodes, and in organs such as the brain, pulmonary tract, and prostate.

Epidemiology

Frequency

The international incidence of blue nevi varies with the population examined.

Sex

Blue nevi are more common in women than in men, with a 3:2 reported predominance.[7]

Age

Blue nevi may develop at any age but are usually noticed in the second decade of life or later.

Prognosis

The prognosis of blue nevi is excellent. Most cases remain entirely benign. Blue nevi usually persist unchanged throughout life and are asymptomatic. Rare cases of malignant melanoma have been reported arising in association with cellular blue nevi.[8]

 

Presentation

History

Once a blue nevus appears, it tends to remain unchanged throughout life. Occasionally, common blue nevi flatten and fade in color. These changes are evenly distributed throughout the lesion.

Malignant change in cellular blue nevi may be heralded by a sudden increase in size and occasionally ulceration.

Cases of eruptive blue nevi have been reported, some following skin trauma, such as sunburn.

Physical Examination

Blue nevi are usually smooth-surfaced, dome-shaped papules that slowly develop from a macule to a papule.[9]

Common blue nevi tend to be smaller than 1 cm, and cellular blue nevi tend to be larger than 1 cm.

Blue nevi are most commonly found on the skin. Rare cases of common blue nevi have been reported in the vagina, the spermatic cord, the uterine cervix, the lymph node, the prostate, the oral mucosa, and the bronchus.[10]

See the images below.

Common blue nevus on the scalp. Common blue nevus on the scalp.
Common blue nevus on the hand. Common blue nevus on the hand.

Complications

Common blue nevi are clinically benign. Lesions tend to persist unchanged throughout life.

Cellular blue nevi are usually clinically benign. Because of their large size, biopsy and excision tend to be performed more often on cellular blue nevi than on common blue nevi.

Rare cases of malignant melanoma have been reported to arise in cellular blue nevi. Any change in these lesions is an indication for biopsy or excision.

 

DDx

Diagnostic Considerations

Also consider the following:

  • Combined nevus (a nevus that contains 2 or more separate types of nevi, such as a blue nevus in combination with a compound nevus or a spindle cell nevus) [11]
  • Congenital nevus
  • Foreign body
  • Deep penetrating nevus
  • Desmoplastic melanoma [12]
  • Carney syndrome (complex) [13, 14, 15, 16] : Carney syndrome (complex) is the rare association of blue nevi with other cutaneous and systemic findings. This condition is thought to arise in an autosomal dominant fashion. Synonyms include lentigines, atrial myxomas, mucocutaneous myxomas, and blue nevi (LAMB) and nevi, atrial myxomas, myxoid tumors (neurofibromas), and ephelides (NAME). Few-to-many blue nevi, ephelides, and mucocutaneous lentigines are found in approximately half the patients. Most often, they are noted on the head and the neck. Lesions may also be noted on the extremities and the genitalia. Lesions arise after birth and develop throughout life. Skin lesions usually precede the detection of cardiac myxomas. Patients with 2 or more clinical findings should undergo a complete evaluation for other associated findings. First-degree relatives of these patients should also undergo an evaluation. Additional associations reported with Carney syndrome (complex) include myxoid fibroadenoma of the breast, growth hormone producing pituitary adenoma causing acromegaly, pheochromocytoma, Sertoli cell tumor of the testes, myxoid uterine leiomyomas, acoustic neuroma, blue nevi, and psammomatous melanotic schwannoma. Mutations in the PRKAR1A gene (a tumor suppressor gene that encodes protein kinase A ) cause most cases of Carney complex. [17]
  • Familial multiple blue nevi [18] : From birth, multiple lesions are present on the head and the neck, the trunk, the extremities, and the sclera. This condition is not associated with other cutaneous or systemic findings. This condition is thought to arise in an autosomal dominant fashion.

Differential Diagnoses

 

Workup

Laboratory Studies

Laboratory studies are not necessary.

Imaging Studies

Imaging studies generally are not necessary; however, dermoscopy is a useful method for separating common blue nevi from a melanoma. The classic dermatoscopic features include a homogeneous steel-blue color with no pigment network, no aggregated globules, and no branched streaks,[19, 20, 21] although variations, including blue globules and dots and pigmented networks, have been reported.[22]

Histologic Findings

A histologic continuum exists from common blue nevi to cellular blue nevi.

In common blue nevus, a vaguely nodular collection of poorly melanized spindled melanocytes and deeply pigmented dendritic melanocytes within thickened collagen bundles is seen. Scattered melanophages are usually noted. No mitoses are present.

Common blue nevus. Numerous elongated dendritic me Common blue nevus. Numerous elongated dendritic melanocytes with a subepidermal grenz zone. Courtesy of Rose Elenitsas, MD.

In cellular blue nevus, a well-demarcated nodule formed by fascicles and nests of tightly packed, moderately sized, spindled to oval melanocytes with scattered melanophages is seen. The lesion is centered in the reticular dermis; blunt-ended, bulbus extensions that extend into the subcutaneous fat may be noted. Occasional mitoses may be present, but significant cytologic atypia and areas of necrosis are absent. Often, a component of common blue nevus is seen within these lesions.

Cellular blue nevus. Deep proliferation of dendrit Cellular blue nevus. Deep proliferation of dendritic melanocytes, broader at the surface than the base, with islands of paler cells with larger nuclei. Courtesy of Rose Elenitsas, MD.

A number of variants of blue nevi with corresponding histologic changes have been described, including epithelioid blue nevus (classic description is with the Carney complex, but also is seen without this condition), atypical blue nevus, deep penetrating blue nevus, sclerosing blue nevus, and amelanotic blue nevus.[23, 24]

The term malignant blue nevus is synonymous with malignant melanoma arising in association with a cellular blue nevus or growing in a histologic pattern similar to that of a cellular blue nevus. These lesions typically have a pronounced cytologic atypia, hyperchromasia, necrosis, an increased mitotic rate, and an infiltrative growth pattern.[25] Complete excision with a margin of healthy skin according to National Comprehensive Cancer Network (NCCN) guidelines should be performed.

 

Treatment

Medical Care

No medical therapy is available.

Surgical Care

A biopsy should be performed on any changing pigmented lesion. For a solitary lesion, simple excision is usually curative. Rare cases of persistent blue nevi, manifesting as satellite lesions around the original excision site, have been reported. These must be distinguished from malignant blue nevus, and reexcision is recommended.

Consultations

Clinical experience with pigmented lesions is necessary to determine the proper diagnosis. Persons with unusual or many lesions may benefit from consultation with a dermatologist.

 

Questions & Answers