20 - 115: MELANOCYTIC NEVI Flashcards
Pigmented lesions attaining a diameter of ____ cm or more are likely to be CMN, dysplastic nevi, or melanoma
1.5
Which of the following statements is INCORRECT?
a. The risk of melanoma appears to be proportionate to the number of melanocytes that comprise the nevus.
b. The most important complication of congenital nevi is that they can give rise to melanoma.
c. Symptomatic NCM presents with failure to thrive in the first few years of life
d. Most CMNs present as flat brown patches or plaques with smooth or slightly uneven borders
c. Symptomatic NCM presents with failure to thrive in the first few years of life
Which of the following statements is INCORRECT?
a. CMNs generally expand in direct proportion to growth of a given anatomic region
b. CMNs may also develop a halo of depigmentation, potentially heralding spontaneous regression
c. Asians are more predisposed to melanoma developing from CMN in contrast to Caucasians.
d. Symptomatic NCM carries a poor prognosis, even in the absence of malignant degeneration
c. Asians are more predisposed to melanoma developing from
CMN in contrast to Caucasians.
Lesion presents with two components: a light brown patch (café-au-lait) containing speckled dark macules or papules.
nevus spilus
Dermoscopy reveals dark speckled foci with a reticuloglobular pattern in a background light brown and reticular pattern.
nevus spilus
Related lesions include nevus of Ota/Ito, Mongolian spot, dermal dendritic hamartoma. Initiating mutations in GNAQ or GNA11 are present in most cases
blue nevus
Flat or raised with smooth or “pebbly” surface, irregular shape, indistinct borders, variable pigmentation, and measure at least 5 mm in diameter.
dysplastic melanocytic nevus
Clinically, lesions are hyperpigmented macules, occurring alone, in focal clusters, or have a generalized distribution. They occur on the skin, conjunctivae and mucous membranes.
lentigo simplex
Children with xeroderma pigmentosum develop _______ during the first year of life.
solar lentigo
Acquired, benign melanocytic tumor composed of heavily pigmented characteristically-shaped melanocytes in nests confined primarily to the epidermis. Lesions are jet black often with “starburst” appearance on dermoscopy.
reed nevus
Melanocytic nest is defined as having at least how many melanocytes?
3 or more melanocytes in direct dontact
melanocytic cells forming nevi are referred to as
Nevomelanocytes
descriptive term used to indicate increased melanocytes confined to the basal layer of the epidermis in the absence of nest formation
melanocytic hyperplasia
Cranial or midline congenital melanocytic nevi and those with satellite lesions have an increased risk of?
leptomeningeal involvement
Most common location of congenital melanocytic nevus
Trunk and extremities
What is the size of small congenital melanocytic nevus
Less than 1.5 cm
Size of M1 CMN
1.5 to 10 cm
Size of M2 CMN
More than 10 to 20 cm
Size of L1 CMN
More than 20 to 30 cm
Size of L2 CMN
More than 30 to 40 cm
Size of G1 CMN
More than 40 to 60 cm
Size of G2 CMN
More than 60 cm
How many satellite nevi are present in S1?
Less than 20
How many satellite Nevi are present in S2
More than 20 to 50
How many satellite are present in S3?
More than 50
These mutations are most prevalent in large- and giant-sized congenital melanocytic nevus
NRAS
One of the most important related physical conditions in patients with CMNs on the head neck or posterior midline
Neurocutaneous melanosis (NCM)
- In this condition, the cells of the congenital nevus involve the meninges or even the parenchymal cells of the brain.
- Most patients with NCM have many cutaneous congenital nevi, either in the form of a giant nevus with many satellites or in the form of many medium-sized lesions.
- Symptomatic NCM presents with seizures and hydrocephalus in the first few years of life when melanocytes are diffusely distributed along the meninges.
- There may be neurologic deficits and vomiting from increased intracranial pressure
The most important complication of congenital nevi is that they can give rise to what malignacy?
melanoma
In CMNs, it is probably prudent to delay treatment until after the first ___ months of life to reduce surgical and anesthetic risks.
6 months
Histology shows localized collections of nevus elements forming in the background of mild melanocytic hyperplasia
NEVUS SPILUS
Lesion presents with two components, a light brown patch (café-au-lait) containing speckled dark macules or papules.
NEVUS SPILUS
Macular variety of nevus spilus is associate with what disease?
phakomatosis spilorosea
constitutes presentation of both nevus flammeus and nevus spilus with or without nevus anemicus.
Papular variant of nevus spilus is typically seen in what condition
phakomatosis pigmentokeratotica
includes nevus spilus plus organoid nevus with or without systemic symptoms, which include neurologic deficits and skeletal abnormalities.
Phakomatosis spilorosea constitutes presentation of what type of nevus
both nevus flammeus and nevus spilus with or without nevus anemicus
It is likely the risk of melanoma increases to some degree with the size of the nevus spilus, particularly with larger segmental lesions greater than
40 cm
Differentiate intradermal and junctional nevus based on size and color
Intradermal
- papillomatous/dome-shaped
- lighter in color
Junctional
- flatter
- more pigmentation
Lesions that are papillomatous or dome shaped tend to be lighter in color and display a more dominant intradermal component, but flat lesions tend to show more pigmentation and a more robust junctional component.
presents as an asymptomatic or slightly pruritic, red, and slightly scaly eczematous halo around a central nevus.
Meyerson’s nevus
- Lesions occur most often on the trunk and proximal extremities and may be multiple.
- Unlike halo nevi, the skin does not depigment, and regression of the nevus does not occur.
- Eczematous changes often self-resolve over the course of months.
spontaneous and concurrent development of multiple nevi, often similar in appearance
Eruptive nevi
- This phenomenon has been described in the context of blistering diseases of the skin (immunobullous as well as erythema multiforme–Stevens-Johnson syndrome–toxic epidermal necrolysis spectrum), immunosuppression, neoplasia, and drugs (particularly chemotherapeutic and immune-modulating agents).
- Eruptive nevi may be of the common acquired type, Spitz, or blue nevus varieties.
Halo nevus may be associated with what conditions?
Vitiligo
Turner syndrome
Halo nevi, particularly when multiple, may be associated with concurrent or subsequent development of vitiligo or other autoimmune disease. 37 Halo nevi are also more frequent in patients with Turner syndrome.
In one study of melanomas, the presence of this history predicted the greatest risk for nevus-associated melanoma.
history of frequent sunburns
the most critical risk factor for the development of acquired nevi
Environmental exposure to UV radiation
Intermittent intense sun exposure appears to impose greatest risk for nevus development
In patients with Turner syndrome, there was a significantly higher association of ________in those who developed halo nevi, suggesting a genetic predisposition.
HLA-CW6
refers to the intermingling of two different nevus types in one lesion
combined nevus
Most such lesions are composed of either an acquired or congenital nevus and blue nevus.
Worrisome features for possible melanoma on hostopath
- pagetoid upward migration of cells in the epidermis,
- cytologic atypia of melanocytes (including irregularity of size and shape of cells and nuclear hyperchromasia),
- failure of the cells to “mature” in the deeper dermis,
- persistence of pigment production in the deep dermis,
- lack of symmetry,
- increased or deep dermal mitotic figures,
- focal areas of necrosis, and
- desmoplasia or fibroplasia.
What type of blue nevi may have an elevated risk for development of melanoma?
Cellular blue nevi
What mutations are present in most blue nevi?
GNAQ or GNA11
most frequent sites for blue nevi
dorsal hands and feet, scalp, and buttocks or sacral skin
The blue hue seen in many blue nevi comes from the _______, the result of the refraction of light reflected from the nevus by the overlying dermis.
Tyndall effect
Histopath findings of blue nevus
All types of blue nevus have components that include some of the following:
- deeply pigmented dendritic melanocytes,
- spindled and less pigmented melanocytes,
- oval melanocytes,
- melanophages, and
- fibrotic stroma
Almost all blue nevi lack a junctional component.
The stereotypic common blue nevus is an inverted dermal wedge-shaped mass in which pigmented dendritic melanocytes are admixed with melanophages within a fibrotic stroma.
Syndromes or diseases associated with blue nevus
Carney complex/LAMB syndrome and phakomatosis pigmentovascularis
Acquired, benign melanocytic tumor composed of heavily pigmented spindle-shaped melanocytes in nests confined primarily to the epidermis
pigmented spindle cell nevus (PSCN)/ reed nevus
Lesions are jet black often with “starburst” appearance on dermoscopy.
pigmented spindle cell nevus (PSCN)/ reed nevus
Histopathologic features of pigmented spindle cell nevus
The PSCN is a sharply circumscribed lesion composed of fascicles of uniform pigment-synthesizing melanocytes with spindled appearance along the junction and to a lesser extent the superficial dermis (Fig. 115-13). Melanocytes have uniform nuclei and small nucleoli. Occasionally, there is an admixture of epithelioid appearing cells. Pagetoid cells may be seen but are usually limited to the central portion of the nevus. Extension of the spindle cells along skin adnexal structures is relatively common. There are invariably pigment-laden macrophages in the papillary dermis with a mild perivascular infiltrate of lymphocytes.
Spitz nevus often harbor what mutations?
HRAS mutations
Spitz tumors often either harbor HRAS mutations or demonstrate genomic rearrangements involving kinase genes (ALK, ROS1, NTRK1, BRAF, RET, MET).
Histopathologic features of Spitz tumor
Spitz nevi are characterized by melanocytic cells with large epithelioid nuclei, often with prominent nucleoli and surrounded by a rim of eosinophilic cytoplasm with “ground-glass” appearance
These lesions are well-circumscribed and symmetric from side to side and from top to bottom. In contrast to melanoma, the melanocytic cells in Spitz nevi show progressive maturation with increasing depth, becoming smaller with the overall distribution of cells in the dermis being wedge shaped, with narrowing of the wedge toward the subcutaneous fat.
In spitz nevus, Small intraepidermal eosinophilic globules, which are positive for periodic acid–Schiff and diastase resistant (resembling colloid bodies), may be seen. What do you call these globules?
Kamino bodies
Lentigo simplex may be associated with what disorders?
- LEOPARD (lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonary valve stenosis, abnormalities of genitalia, growth retardation, and sensorineural deafness) syndrome,
- Carney syndrome,
- Peutz-Jeghers syndrome,
- LaugierHunziker syndrome (idiopathic lenticular mucocutaneous pigmentation), and
- centrofacial lentiginosis.
True or false. Avoidance of sun exposure and UVR does not reduce the risk of development of lentigo simplex.
True
Avoidance of UVR exposure may decrease the risk of developing additional solar lentigines.
Clinically, dysplastic nevi often measure at least how many millimeters in diameter
5 mm
dysplastic nevi frequently have a flat macular component, which corresponds to what finding histopathologically?
‘shoulder’ or junctional component of a compound lesion
most significant clinical features that had the highest correlation to histologically proven dysplastic nevi
nevus size and irregular borders
Criteria for atypical nevi
Atypical nevi typically have a diameter (diameter in one dimension at least 5 mm and a prominent flat component) and two of three other features (irregular asymmetric outline, indistinct borders, and variable pigmentation).
most common site of malignant transformation in dysplastic nevus syndrome
Trunk
most clinically concerning complication, associated with dysplastic nevi.
Melanoma
factors associated with congential melanocytic nevi with higher risk for development of melanoma
- large- and giant-sized lesions have greater risk
- presence of satellite nevi
- Other clinical features that should raise concern for melanoma include very dark pigmentation, ulceration, bleeding, or onset of other sensory symptoms.
features of CMN associated with risk of leptomeningeal involvement (NCM)
cranial, midline, or CMN with multiple satellite lesions
small- and medium-sized CMN lesions have been reported to have what mutations?
either NRAS mutations or in a small number of cases, activating mutations in BRAF
two distinct forms of nevus spilus
- macular variant - more commonly associated with phakomatosis spilorosea
- papular - typically seen in phakomatosis pigmentokeratotica
- constitutes presentation of both nevus flammeus and nevus spilus with or without nevus anemicus
- Systemic disease may or may not be present, which include vascular anomalies, ocular abnormalities, limb hemihypertrophy, or development of multiple granular cell tumors
Phakomatosis spilorosea
- includes nevus spilus plus organoid nevus with or without systemic symptoms, which include neurologic deficits and skeletal abnormalities
Phakomatosis pigmentokeratotica
It is likely the risk of melanoma increases to some degree with the size of the nevus spilus, particularly with larger segmental lesions greater than how many cm?
40 cm
associated mutation in nevus spilus
HRAS
The majority of common acquired nevi are less than how many mm in diameter?
6 mm
commonly seen dermoscopic pattern in acquired nevi
reticular or globular pattern
nevi on the palms and soles can show what pattern in dermoscopy?
parallel-furrow pattern, lattice-like, or fibrillar pattern.
eruptive nevi is associated with what conditions?
bullous disease or immunosuppression
his phenomenon has been described in the context of blistering diseases of the skin (immunobullous as well as erythema multiforme–Stevens-Johnson syndrome–toxic epidermal necrolysis spectrum), immunosuppression, neoplasia, and drugs (particularly chemotherapeutic and immune-modulating agents).
Halo nevi, particularly when multiple, may be associated with concurrent or subsequent development of what condition?
They are are also more frequent in patients with what syndrome?
vitiligo or other autoimmune disease
Turner Syndrome
risk factors significantly associated with increased number of nevi
- spending 5 to 6 hours per week outside between 10 AM and 4 PM,
- painful sunburn(s),
- decreased UV barrier protection,
- male gender
These mutations are present in most blue nevi.
GCAQ or GNA11
Multiple blue nevi and epithelioid blue nevi may be associated with what conditions?
lentigines, cardiac myxoma, and mucocutaneous myxomas (Carney complex/LAMB syndrome [lentigines, atrial myxomas, mucocutaneous myxomas, and blue nevi])
- solitary, asymptomatic, pink or red, hairless, firm, and dome shaped papule in pediatric population
Spitz nevus
how can you differentiate spitz nevi and spizoid melanoma based on staining?
- In most Spitz nevi, there is full or partial retention of p16 staining, but Spitzoid melanomas tend to lose p16 expression.
- Ki-67 proliferation marker is low in nevi but elevated in melanoma.
- Benign melanocytic neoplasia present in a lymph node.
- Nevomelanocytes are characteristically located in the capsule.
- They are generally asymptomatic and found incidentally as a result of lymph node removal
Nodal Nevi
lentigo simplex can occur in what syndromes?
- LEOPARD (lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonary valve stenosis, abnormalities of genitalia, growth retardation, and sensorineural deafness) syndrome,
- Carney syndrome,
- Peutz-Jeghers syndrome,
- Laugier-Hunziker syndrome (idiopathic lenticular mucocutaneous pigmentation),
- centrofacial lentiginosis
histopathologic findings of lentigo simplex
What id the difference of solar lentigo?
- Histologic sections of lentigo simplex show slight to moderate elongation of rete ridges, basilar melanocytic hyperplasia, and **increased pigmentation **within the epidermis and melanophages in the papillary dermis. Melanocytes lack atypia
- Solar lentigo characteristically shows** greater elongation of rete ridges **and prominent solar elastosis with the papillary dermis.
criteria for dysplastic nevus
diameter in one dimension at least 5 mm + prominent flat component + two of three other features:
1. irregular asymmetric outline
2. indistinct borders,
3. variable pigmentation
