Melanocytic Nevi

Melanocytic (or Melanotic) Nevi 

Represent benign proliferations of a type of melanocyte known as a "nevus cell" that clusters as nests within the lower epidermis and/or dermis.  Melanocytic nevi can be congenital or acquired. 

Congenital Melanocytic Nevi (CMN)

• Defined as melanocytic nevi present at birth or within the first few months of life
•  Speckled lentiginous nevi are a subtype of CMN

5-day-old girl (head to right) with giant congenital melanocytic nevus over back, neck, buttocks and left thigh. Histopathological findings showed nevomelanocytes throughout the thickness of the dermis and extending into the subcutaneous tissue. No other complications were reported. S. Sharma , N.L. Sharma, V. Sharma - Giant Bathing Trunk Naevus with Multiple Congenital Melanocytic Naevi. The Internet Journal of Pediatrics and Neonatology. 2012 Volume 14 Number 1. DOI: 10.5580/2aa3 
https://en.wikipedia.org/wiki/Congenital_melanocytic_nevus

When the histologic features of CMN are compared with those of acquired melanocytic nevi, the nevomelanocytes in CMN tend to extend deeper into the dermis and subcutaneous tissues, to be arranged single file between collagen bundles, and to track along skin appendages and neurovascular structures

Epidemiology

• Approximately 1 to 3 percent of neonates have pigmented lesions that are clinically compatible with a diagnosis of congenital melanocytic nevi 
• Large or giant CMN occur in approximately 1 of 20,000 births
• Acquired melanocytic nevi are virtually ubiquitous
  • ​At 14 years of age, median counts increased to 96 for girls and 120 for boys
  • Mean number of nevi are higher in white adolescents, and lower in adolescents of African, Asian, or Native American heritage 

Pathogenesis

• Clonal proliferations of benign melanocytes that arise during embryogenesis 
• Somatic mutations of BRAF at V600 in small CMN, as well as in acquired melanocytic nevi and cutaneous melanomas 
• 70 to 95 percent of large and giant CMN harbor somatic gain-of-function mutations in NRAS
• In contrast to acquired melanocytic nevi, CMN tend to extend deeper into the dermis and subcutaneous tissues

Categorization

1. Small- < 1.5cm - tan to brown irregular shaped macules. Darken at puberty and may become elevated and develop hair
2. Medium 1.5- 20 cm.- tan to brown macules. Darken with puberty and may become elevated and develop hair 
3. Giant > 20 cm. - incidence of 1/20000 with irregular margin and may have verrucous texture. They are usually dark and covered with dark hair. Satellite lesions may be present. Because of their large size, often referred to as "bathing suit nevi". Also may have extension into the leptomeninges and have associated neurological manifestations that include seizures and neurological focal deficits.

Appearance

• Usually small or medium-sized, solitary and may occur in any cutaneous location
• Color ranges from tan to black, the borders are often geographic and irregular
•  Many, but not all, have an increased density of dark, coarse (terminal) hairs

In addition to their predictable size increase in proportion to the child's growth, CMN commonly undergo morphologic changes over time.

1. They may begin as flat, evenly pigmented patches or thin plaques and later become more elevated with lighter, darker, or mottled (due to focal lightening or darkening) pigmentation and a mammillated, pebbly, verrucous, or even cerebriform surface.
2. CMN can develop superimposed papules and nodules, and those with concerning clinical characteristics, such as rapid growth, ulceration, or black or red color, require histologic evaluation to exclude the possibility of melanoma. 

Risk of Malignant transformation- A controversial area with many varied opinions

1. is a 2.5-4.6% chance of malignant transformation. The risk is greater for giant nevi and usually will occur prior to puberty. 
2. Small and medium sized nevi will rarely change prior to puberty although estimates are that 15% of melanomas originate in small congenital nevi. 
3. 5-10% of giant nevi will result in melanomas and 50% will arise prior to the age of 5.

Management

1. Management remains controversial and based on risk of malignant transformation, cosmetic appearance, risk of scarring, and psychological issues.
2. Giant nevi are often removed because of the increased incidence of malignant transformation and cosmetic disfigurement. Also, because of their irregular features, it may be difficult to recognize significant changes. All patients should have imaging studies to rule out involvement of the central nervous system. Surgical procedures are difficult and may be associated with great disfigurement.
3. All non- giant nevi should be observed yearly for changes that may be indicative of malignant transformation. Specimens that change should be biopsied. Also, location of the nevus and ability to observe for changes is important in decision to remove.

Acquired Pigmented Nevi

1. are benign accumulation of melanocytes that increase during childhood and peak during 30-40s. The greater the number of nevi, the greater the risk of melanoma. Increased numbers are associated with sun exposure, especially in fair skinned individuals.
2. With maturation, they may become raised, dome shaped, and pedunculated. Eventually, they disappear with aging.
3. Rarely undergo malignant transformation. Increased risk factors for melanoma include fair skin, increased sun exposure, positive family history, increased number of nevi, presence of giant nevus, some familial syndromes, and immunosuppression. Should observe for
   
   1. rapid increase in size
   2. irregularity of the border
   3. development of asymmetry
   4. variation of color within nevus
   5. development of satellite lesions
   6. changes in texture.
4. Most observed changes are due to irritation or natural maturation of the nevus.
5. If there is concern about changes or parental anxiety, nevus should be removed

Resources:

For Practioners:  The Society for Pediatric Dermatology

For Families: Frequently asked questions regarding congenital melanocytic nevi

Reference

1. From, L. Congenital Nevi: Let's Be Practical. Pediatric Dermatology. 1992 Vol 9 No. 4 345-46.
2. Kincannon J and Boutzale C. The Physiology of Pigmented Nevi. Pediatrics. 1999; 104(4 Suppl.):1042-1045.
3. Nelson's Textbook of Pediatrics. 15th Edition.
4. Morelli and Weston Sun,Moles, and Melanoma. Contemporary Pediatrics June 1999
5. Chamlin Sarah.Shedding light on moles, melanoma, and the sun.  Contemporary Pediatrics June 2002
6. Naeyaert JM, Brochez L. Clinical Practice. Dysplastic Nevi. N Engl J Med. 2003 Dec 4;349(23): 2233-40. Review
7. Ferrari A. et al. Does Melanoma Behave Differently in Younger Children than Adults?  A Retrospective Study of 33 Cases of Childhood Melanoma From a Single Institution. Pediatrics March 2005
8. Lange JR and Balch CM. Melanoma in Children.  Pediatrics March 2005
9. Price HN, Schaffer JV. Congenital melanocytic nevi-when to worry and how to treat: Facts and controversies. Clin Dermatol 2010; 28:293.