Benign Melanocytic Neoplasms Flashcards
What is the difference between ephelides and lentigo?
Ephelides can come and go with sun exposure
Pathogenesis of ephelides?
Increased melanogenesis and melanin transfer to keratinocytes
Histology of ephilids
Increased basilar keratinocyte pigmentation and enlarged melanocytes w/o increased density
Multiple cafe au lait macucles (CALMs) is a/w what conditions?
Russell-Silver, Bloom syndrome, Neurofibromatosis type 1>type 2, tuberous sclerosis, ataxia telangietasias, noonan sydrome, fanconi syndrome, mccune-albright syndrome; MEN-1
What are the CALMS like in Mccune Albright syndrome?
Fewer CALMs, larger, midline demarcation, segmental distribution, patter, broad bands along Blaschko lines
What are the CALMS like in NF type 1?
Can have superimposed lentigines
Which melanocytic lesion increases hair and can have acneiform lesions?
becker’s nevus
What is becker’s nevus a/w?
Hypoplasia of ipsilateral breast, areola, nipple and arm, ipsilateral arm shortening, lumar spina bifida, thoracic scoliosis, pectus carnatum, enlargement of the ipsilateral foot.
Do solar lentigines fade over time?
No
Histology of solar lentigines?
Dirty socks (hyperpigmentation of the bottom of the rete pegs), epidermal hypoplasia, and sun damage
What lentigos are in younger people?
Lentigo simplex and mucosal melanotic lesions
The most common location for lentigines or melanosis of the female genital area?
Labia minor most common
What can lentigo simplex and mucosal melanotic lesions be a/w?
Cronkhite-Canada, Carney complex (LAMB/NAME), LEOPARD (aka Noonan w/ multiple lentigines), Laugier-Hunziker, Bannayan-Riley-Ruvalcaba (penile), Peutz-Jeghers (especially oral/perioral), xeroderma pigmetosum, Cowden syndrome
Why are dermal melanocytosis grey-blue appearing
Tyndall effect
Extensive dermal melanocytosis could be related to which genetic disorders?
Phakomatosis cesioflammea (type II phakomatosis pigmentosvascularis (PPV)), phakomatosis cesiomarmorata (type V PPV)
Epidemiology of the nevus of Ota?
First year of life or puberty, increased in Asians and Blacks
Most common location of nevus of Ota?
Coalescing gray/blue mauces in V1/V2 distribution. frequent scleral involvment (60%); unilateral (90%)>bilateral
What is the mutation in nevus of Ota that degenerates to uveal melanoma?
GNAQ
What can nevus of Ota turn in to?
Uveal melanoma
What is nevus of Ito?
Located on shoulder, suprclavicular, scalpular regions; essentially no risk of progression to melanotic
What is a Hori’s nevus?
Acquired nevus of Ota-like macules bilateral zygomatic regions; Most common in East Asian females
What is a Sun’s nevus?
Acquired, unilateral (Only one sun) nevus. This is different because nevus of Ota/Ito are usually present at birth
Histology differences between nevus of Ota and dermal melanocytosis?
Elongated dendritic melanocytes are more numerous in nevus of Ota and involve levels of the dermis to varying degrees (superficial dominant, deep dominant, etc)
Epidemiology of blue nevi?
Onset is usually in childhood or adolescence 25% are cellular blue nevi
Most common sites of blue nevus?
Scalp, sacral area, distal extensor extremities
Where do the melanocytes that make up blue nevi come from?
They are retained melanocytes in the dermis that persist during embryogenesis rather than populating epidermis
What mutations can you see in blue nevi?
GNAQ and GNA11
What are the different variants of blue nevus?
Common blue nevi (<1cm), hands, feet, face scalp cellular (larger 1-3cm, favors buttocks or scalp) epithelioid blue nevus (a/w carney complex, trunk, and extremities) Malignant blue nevus (melanoma, GNAQ/GNA11, and BAP-1 mutations)
How to distinguish blue nevus from nevus of Ota or dermal melanocytosis?
Sclerotic collagen in the dermis which is seen in blue nevus and not in nevus of Ota or dermal melanocytosis
What blue nevus type does malignant blue nevus arise from?
Cellular blue nevus
What location is most common with malignant blue nevus?
Scalp
What two diseases can you see with eruptive acquired nevi?
Epidermolysis bullosa and LS+A
What is the abtopfung hypothesis
Nevus cells start as juncitonal proliferation–>subsequently migrate into dermis (compound) –> later become entirely intradermal –> may involute
What mutations are in nevi?
BRAF mutation in up to 80% more so than NRAS
So what is a key between malignant vs benign pigment on the acral surface on dermoscopy?
Should affect the furrows not the ridges
Epidemiology of spitz nevi?
Most common on the head and neck,
On children, acquired during first two decades
What mutations commonly occur in spitz nevi?
HRAS/11p gains NO BRAF
What stains are + in spitz nevi?
S100A6+, S100+, melan A +, p16 + (if negative more scary)
What stain is important for atypical spitz or spitzoid melanoma?
Loss of P16 is often lost or diminished
What is the epidemiology of pigmented spindle cell nevus of reed?
Most common in F>M
Most commonly located on the thigh
What are the key components on the histology of pigmented spindle cell nevus of Reed?
Pigmented parakeratosis, spindle cell melanocytes
What disease can be associated with multple dyplastic nevi?
Familial atypical multiple mole melanoma syndrome (FAMMM)
What mutations is FAMMM associated with?
CDKN2A which encodes p16 and p14 ARF
What is the heritibility of FAMMM
AD
Description of FAMMM
AD; multip melanocytic nevi (50+), family hx of melanoma, mutation in CDKN2A
Treatment of dysplastic nevi?
severly atypical are excised
What are the components of a dysplastic nevus?
Asymmetry
- Lack of circumscription, junctional shoulder extends >3 rete ridges beyond dermal component, irregular size, and placement of junctional nests with bridging or lentiginous pattern (single-cell junctional growth)
- Papillary dermal concentric and or lamellar fibrosis
- Cytologica atypia: nuclei enlarged (can have prominent nucleoli), “dirty” gray cytoplasm
What mutations are associated w/ congenital melanocytic nevus?
NRAS mutations > BRAF mutations
What are the divisions of congenital melanocytic nevus?
Small (<1.5cm), medium (1.5-19.9cm), large (>20cm)
What congenital melanocytic nevi are associated with problems?
Large (>20cm)
note that this is projected size it is not current size)
What is the risk associated with large congenital melanocytic nevus?
Increased melanoma risk (2-3%) majority develop melanoma in the first decade
What is the tx of a congenital melaocytic nevus?
if larger posterior axial congenital nevi or multiple satellite lesions –> MRI screening for neurocutaneous melanosis
For large ones surgical resection in stages after 6 months of age
What is the difference between deep penetrating nevus and blue nevus?
Lack of GNAQ/GNA11 mutations, wedge-shaped, dark melanocytes
What is the clinical presentation of nevus spilus?
Presents within the first year of life
- Most commonly located on the trunk and extremities
- Presents as a tan patch w/ pigmented macules and papules
What disorders can nevus spilus be associated with?
Phakomatosis pigmentovascularis and phakomatosis pigmentokeratotica
What is the risk of melanom in nevus spilus?
Very low
What is the clinical presentation of a halo nevus?
Most commonly occurs in the second decade, and most commonly occurs on the back
Presents as a pigmented nevus with surrounding hypopigmented zone
What medications are associated with halo nevi?
infliximab
What is the difference in histology between a halo nevus and a regressing melanoma?
bland nevus w/ lymphocytes intertwined with melanocytes. it is throughout rather than around it like you might see w/ melanoma
What are the 3 key features of recurrent melanocytic nevus (vs melanoma)?
- Dermal scar which the nevus is confined within
- Atypical junctional melanocytic proliferation which resembles MIS but is confined to the area above the dermal scar
- Bland dermal nevus remnants below or adjacent to scar.
What is the histology of a solar lentigo?
Elongated bulbous rete ridges with hyperpigmentation (“Dirty socks”)
+/- mild increase in melanocyte density
Solar elastosis in the dermis
What is Cronkite Canada syndrome?
Happens in 50-60 y/o, extremely rare.
They get GI polyps, alopecia, lentigo simplex/mucosal melanocytic lesions, and basically FAP that is acquired. Happens in 50-60 y/o, extremely rare. They get GI polyps, alopecia, lentigo simplex/mucosal melanocytic lesions, and onychodystrophy.
What is the difference between Hori’s nevus and Sun’s nevus?
Hori’s: acquired macules b/l zygomatic region; east Asian women
Sun’s Nevus: acquired, a unilateral variant of Hori’s nevus
What is the difference between nevus of Ota and dermal melanocytosis on path?
Melanocytes are more numerous and more superficial in nevus of Ota.
3 components of recurrent melanocytic nevus?
Dermal scar, atypical junctional melanocytic proliferation confined to the area above the dermal scar, and dermal nevus remnants below/adjacent to scar.
What eye findings can occur in Nevus of Ota?
Glaucoma can develop in 10%
What is the significance of concomitant BAP-1 loss in uveal melanoma?
Leads to increased risk of metastasis and death
What is the presentation and histology of a common blue nevus?
- Blue/gray macule or papule < 1cm
- Elongated, dendritic melanocytes containing melanin pigment in the upper 2/3 of derms associated w/ sclerotic collagen *no junctional component*
What is the clinical and histology of the cellular blue nevus?
- Blue/gray/black plaques or nodules, larger often (1-3cm), favors buttocks or scalp
- Dense proliferation of plump/fusiform pale gray melanocytes w/ little pigment + admixed dendritic melanocytes
- Bulges into the subcutis (dumbell configuration)
Which type of blue nevus is associated with epithelioid blue nevus?
Carney complex
What type of blue nevus does malignant blue nevus/melanoma arise from?
Often arises within cellular blue nevi (Scalp #1)
What is the histology of a balloon cell nevus?
Histology: >50% dermal melanocytes are “balloon cells” (large, pale, and polygonal melanocytes with foamy/vacuolated cytoplasm and variable pigmentation)
-This is a result of melanosome degeneration
Conventional nevus is always
What is the most common location for Spitz nevus?
Most common on the lower extremities overall, in children can also be common on the head and neck
Can Spitz nevi be diagnosed later in life?
They can occur, but if they are older than 30’s use caution, this has a higher likelihood of being a melanoma
What is the clinical presentation of a Spitz nevus?
Rapidly growing pink-red papulonodule (usually <1cm)
What is the histology of the Spitz nevus?
Symmetric and circumscribed, epidermal hyperplasia is present, large junctional nests w/ clefting around the whole nest (not the individual cells like discohesion in melanoma), Kamino bodies: pink clumps of BMZ material (collagen IV) within the epiderms
What would suggest that a spitz nevus is actually a melanoma?
Mitoses in the deeper parts of the lesion, lack of cells “maturing” with depth, and loss of p16
FISH w/ homozygous loss of 9p11 –> corresponds to p16/CDKN2a –> increased risk of metastasis and death
What is the histology of pigmented spindle cell nevus of Reed?
Similar to a Spitz (related) but much heavier melanosome component and also the melanocytes are more superficial/kept to the junction
Clinical presentation of deep penetrating nevus?
Well-circumscribed blue to black papule <1cm in size
Face, upper trunk and extremities; usually second and third decades
What is the histology of the deep penetrating nevus?
Compound melanocytic proliferation with the minimal junctional component, superficial dermal nests resembling ordinary nevus nests
- Prominent wedge-shaped dermal component that extends deep into the dermis or subcutis, tracks along with adnexal structures or neurovascular bundles
- Has epithelioid pigmented melanocytes in loose nests with lots of melanophages
What is neurocutaneous melanosis/melanocytosis and what is its relation to congenital melanocytic nevus?
Occurs w/ large congenital nevi posterior axial or multiple satellitis it is a melanocytic proliferation within the leptomeninges and brain parenchyma can have a high mortality in symptomatic patients
What is the histology of congenital melanocytic nevi?
Compound or intradermal melanocytic proliferation. The dermal component extends deeper and can surround infiltrates vessels, adnexal structures, muscle, and nerve (not concerning)
What should be done if a pt has a congenital nevus that is posterior axial or has multiple satellites?
Recommend MRI screening for neurocutaneous melanosis
What is the recommended excision margins for dysplastic nevi (if they need to be removed)?
2-3mm
What is the histology of a Becker’s nevus?
Increased basal melanocytes, epidermal thickening (perhaps androgen-mediated), elongation of rete ridges, and dermal smooth muscle hamartoma-like changes
Clinical presentation of Becker’s nevus?
Hyperpigmented plaque w/ thickening, irregularity, and/or hypertrichosis on upper torso most commonly
Can see ipsilateral breast hypoplasia in some patients and even skeletal defects or limb asymmetry rarely
