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Melanocytic Nevi and Neoplasms Andrews chapter 30 Michael Hohnadel, D.O.


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Title: Melanocytic Nevi and Neoplasms Andrews chapter 30 Michael Hohnadel, D.O.

Melanocytic Nevi and NeoplasmsAndrews chapter
30Michael Hohnadel, D.O.
  • 4/20/04

Nevus Spilus
  • Pigmented, light brown or tan macule, varied
    diameter, speckled with smaller, darker-colored
    macules or papules.
  • Lower extremity trunk frequently.
  • When these nevi follow a dermatomal distribution
    they may be referred to as a zosteriform, or
    sometimes a speckled lentiginous nevus. Usually
    do not cross the midline.

Nevus Spilus
  • Syndromes
  • Phakomatosis pigmentovascularis - nevus spilus is
    present with a nevus flammeus.
  • Phakomatosis pigmentokeratotica- Organoid nevus
    with sebaceous differentiation, hemiatrophy with
    muscular weakness other neurologic findings
    speckled lentiginous nevus.
  • The darker speckles usually contain nevus cells.
    Melanoma might arise with greater frequency than
    in normal skin.
  • TX Removal is not necessary. Q-switched ruby
    laser has been reported effective.

Lentigo Simplex
  • Sharply defined, rounded, brown or black macules
    found anywhere on body or mucosa. No predilection
    for sun exposed regions.
  • Usually arise in childhood but can arise anytime.
  • Histologically Elongation of rete ridges,
    increase in number of melanocytes in basal layer,
    increase of melanin in both melanocytes, and
    basal keratinocytes, and melanophages in the
    upper dermis.
  • No therapy is needed/ there is no predisposition
    to neoplastic change.

Solar Lentigines
  • Discrete hyperpigmented macules in areas of sun
  • May evolve into sks or lichenoid keratoses.
    Possibility of lentigo maligna or lentigo
    maligna melanoma.
  • Tx liquid nitrogen, laser. Peels. Hydroquinones
  • Photochemotherapy or frequent tanning salons may
    develop lentigines on non-sun-exposed areas and
    these may show cellular atypia

Solar Lentigines
Hyperpigmented elongated rete ridges with diffuse
increase in non-nested melanocytes, and solar
Penile and Vulvar Melanosis
  • Localized pigmentary alterations
  • Most often show basilar hyperpigmentation
  • May appear in large patches or in smaller,
    well-demarcated lesions
  • Present on the penis or in women on the labia

Bannayan-Riley-Ruvalcaba Syndrome
  • Rare, AD disorder that manifests in childhood.
    80 of the pts are male
  • Characterized by genital lentiginosis,
    macrocephaly, motor and speech delay, mental
    retardation, lipomas, hemangiomas, verruca
    vulgaris, and many types of facial papules.

Multiple Lentigines Syndrome
  • Multiple lentigines which are dark brown macules,
    1-5 mm. in diameter.
  • Preponderance on the trunk
  • Multiple generalized lentigines may occur with a
    number of associated signs as an dominantly
    inherited syndrome.
  • l

Multiple Lentigines Syndrome
  • LEOPARD Syndrome
  • lentigines
  • electrocardio abnorm.
  • ocular hypertelorism
  • pulmonary stenosis
  • abnormalities of genitalia
  • retardation of growth
  • deafness

  • Moynahan Syndrome
  • Multiple lentigines, Congenital mitral stenosis,
    Dwarfism, Genital hypoplasia and Mental
  • Centrofacial Lentiginosis
  • Characterized by lentigines on the nose, and
    adjacent cheeks
  • Sometimes associated with status dysraphicus,
    multiple skeletal anomalies, and CNS disorders
  • Spares the mucous membranes
  • Onset is first years of life

Inherited Patterned Lentiginosis in Blacks
  • A.D. syndrome. Ten, light-complexioned black
    patients who developed numerous lentigines in
    infancy or early childhood
  • Distribution is central face, lips, with variable
    involvement of dorsal hands and feet, elbows, and
  • Sparing of mucous membranes and no internal

Carneys Syndrome
  • AKA NAME syndrome or LAMB syndrome
  • Carney syndrome (2 of following)
  • Cardiac Atrial Myxoma (79) Can be life
  • Cutaneous myxomas (45) papules which develop by the age of 18 and occur
    on ears, eyelids and nipples.
  • Mammary myxoid fibromas (30)
  • Spotty mucocutaneous pigmentation (blue nevi)
    (65) or lentigines
  • Prim. Pig. Nodular adrenocortical disease. (45)
  • Testicular tumors (56)
  • Pituitary G.H. secreting tumors. (10)

Peutz-Jeghers Syndrome
  • A.D.
  • Pigmented macules on the lips, oral mucosa,
    perioral acral areas
  • Associated with gastrointestinal polyps,
    especially prominent in the jejunum.

  • Uncommon, benign epidermal melanocytic neoplasm,
    occurring on the head
  • Resembles a pigmented sk or a pigmented BCC.
  • Predominantly seen in white men 60 yrs

Cellular Nevi
  • Appear in first yrs of life, increases in number
    over the next 2-3 decades, after which there is a
    steady decline. FM
  • Less common in sun-protected areas
  • Maximum number is at age 20- 25 yrs, the average
    number is 40
  • Sun exposure increases the number of nevi in the
    exposed skin.
  • Eruptive nevi are rare, but may occur after
    severe bullous disease such as TEN, EM, or severe
    sunburn, Addisons disease or immunosuppresion

Junctional Nevi
  • A smooth, hairless, light to dark brown macule,
    varying in size from 1 6 mm. Occurs on any
    site, especially on palms, soles, scrotum.
  • It is characterized by single melanocytes, or
    nest of melanocytes, in the lower epidermis.
  • During adolescence some will become compound or

Compound Nevus
  • The compound nevus is one that is still
    manifesting so-called junctional activity
    (accumulation of melanocytes in the epidermis)
    but has formed structure of a cellular nevus in
    the dermis as well

Compound Nevus
  • Nests of nevus cells in the epidermis overlying a
    dermal component of orderly nevus cells

Intradermal Nevus
  • A compound nevus in which junctional activity
    has ceased, and all the nevus cells are in the

Intradermal Nevus
  • At the base of this dermal nevus the melanocytic
    cells resemble neural structures -neurotization
  • Nevus cells that are recognized at this power by
    tendency to be arranged in nests

Treatment of Nevi
  • Signs of malignant degeneration
  • ABCDE changes. Thickening, ulceration, pain, ugly
    duckling sign. Dot extensions. New lesion in
    patient over 35 years.
  • Changes may occur during pregnancy or with oral
  • Biopsy if you think melanoma.
  • Treatment Andrews recommends biopsy and removal
    of scalp nevi if atypical due to difficulty in
    following. Single oral or vaginal lesions

Balloon Cell Nevus
  • A pigmented nevus, varying in size from 1 5 mm,
    usually occurring on the head, neck, and trunk.
  • Clinically indistinguishable from ordinary
    pigmented or nonpigmented nevus
  • Histologically Composed of peculiar vesicular
    cells that appear to be foamy and form large pale
    polyhedral balloon cells that may be
    multinucleated giant cells in addition to nevus
  • Not considered potentially malignant, and
    treatment is same as other nevi

Halo Nevus
  • AKA Suttons nevus, perinevoid vitilgo,
    leukoderma acquisitum centrifugum
  • Pigmented nevus with surrounding depigmented
  • Immune response to melanin.
  • No tx indicated - central nevus disappears with
    time, leukodermic area will usually repigment
    with time
  • A search for melanoma should be done.

Halo Nevus
  • The nevus architecture is obscured by a dense
    lymphocytic infiltrate
  • Lymphocytes infiltrate among the dermal nevus
    cells, which eventually degenerate and disappear

Giant Pigmented Nevus
  • Presentation
  • Characterized by a large, darkly pigmented hairy
    patch in which smaller, darker patches are
    interspersed or present as small satellite
    lesions. Skin may be thickened or verrucous
  • By definition 20cm.
  • Has a tendency to follow a dermatome distribution
  • Trunk favored site.

Giant Hairy Nevi
  • Present at birth and grow proportionally to the
    site of the body where they are located.
  • When a large congenital nevus involves the axial
    skin, there may be an associated neurocutaneous
  • Hydrocephalus, leptomingeal melanoma
  • Incidence of melanoma
  • Overall risk is 3 to 7. (40 of melanoma in
  • Risk is greatest in axial lesions. Seldom in
  • Only 1/3 of melanoma arise from epidermal sites
    (makes) for more difficult surveillance.

Giant Hairy Nevi
  • Treatment
  • Most recommend total surgical excision and
    resurfacing autografts.
  • Alternative treatments dermabrasion, curettage,
    and laser ablation. These eliminate some of the
    nevus cells, with theoretic lowering of the
    risk of melanoma
  • Monitoring. Serial MRIs for neurocutaneous

Small and Medium-sized Congenital Nevocytic Nevus
  • Small -
  • Medium- 1.5 cm but
  • Found in 1 of newborns.
  • Half eventually become hairy.
  • Data indicates that those which do progress to
    melanoma occur in Pts older than 18 yrs and in
    the epidermis (Hence monitoring is effective)
  • Treatment Excision is recommended for lesions of
    the hairy scalp, or those of great cosmetic
    concern or nevi with unusual clinical features.
    Otherwise, observation.

Epitheliod and Spindle-Cell Nevus(Benign
Juvenile Melanoma, Spitz Nevus)
  • Firm, 310 mm diameter, rosy papule on the
    face, especially on the cheek. Lesion has
    distinctive pink, brownish red, or purplish red
  • Female predominance. 2/3 in first two decades of
  • Should be completely excised and examined
    histologically. Full excision recommended to
    prevent confusion with melanoma at future date.

Spitz Nevus
  • A variant of the compound nevus
  • Epidermal irregular acanthosis,
    pseudoepitheliomatous hyperplasia, and thinning
    of the epidermis
  • Nevus cells are pleomorphic, but mostly
    spindle-shaped (fusiform), or polygonal
    (epithelioid) cells

Spitz Nevus
  • Immunohistochemical staining for MIB-1 and bcl-2
    will distinguish most Spitz nevi from melanoma
  • Melanomas are immunoreactive
  • Spitz nevi not reactive.are not
  • Differential diagnosis Pyogenic granuloma,
    mastocytoma, juvenile xanthogranuloma, or

Dysplastic Nevus
  • Variegated tan, brown, pink coloration with pink
    hues seen in macular portion. Macular portion
    always present, frequently surrounds a papular
  • Generally larger than are common nevi, usually
    512mm, with irregular borders.
  • Develop new lesions over a lifetime. Sun
    protected areas.

Dysplastic Nevus
  • Occurrence 5 -20 of pts have at least one
    clinically dysplastic nevus.
  • Importance
  • Careful history and evaluation of family members.
  • DNs provide another risk factor for melanoma
    predisposition. 3 lesions increases the risk of
    melanoma from 3 to 43 times.
  • Increased risk of melanoma in the DN AND in the
    rest of epidermis

Dysplastic Nevus
  • Histologic features as per an NIH consensus
  • Basilar melanocytic hyperplasia with elongation
    of rete ridges.
  • Spindle-shaped or occasionally, epithelioid
    melanocytes arranged horizontally and aggregating
    in nests that fuse with adjacent rete ridges.
  • Lamellar and concentric superficial dermal
  • Cytologic atypia, usually present but not
    essential for diagnosis.

Dysplastic Nevus
  • Elongated rete ridges, bridging between rete
    ridges, fibroplasia, and sparse lymphocytes are
    features. Cytologic atypia is usually mild.

Dysplastic Nevi
  • Treatment
  • Patients with dysplastic nevi and a positive
    family or personal history of melanoma, physician
    examination every 3 6 months
  • Excision of those nevi that change clinically or
    are located in difficult to monitor locations
    such as the scalp.
  • Photographs with measured scale is useful
  • Sunscreens and Pt self exam are critical.

Dysplastic Nevus Syndrome
  • Around 1978 Lynch et al recognized an autosomal
    dominant inheritance pattern in families with
    unusual nevi and multiple melanomas-initially
    described by Clark et al as B-K mole syndrome.
  • Now called dysplastic nevus syndrome (DNS).
  • Melanoma in 1st or 2nd degree relative
  • Often 50 melanocytic nevi some AN
  • DN on histologic exam.

Dysplastic Nevus Syndrome
  • Risk of melanoma
  • Normal 1 .
  • DN, no family with MM 6 lifetime risk.
  • DN, () family history of MM 15
  • DN, () two or more 1st degree relatives with MM,
    lifetime risk approaches 100.

Dysplastic Nevi
  • Originate from melanocytes at epidermal-dermal
  • 50 will develop in pre-existing nevi.
  • Prolonged, non invasive, horizontally oriented
    growth phase. When tumor nodule develops the
    vertical growth phase is occurring and the risk
    of metastatic disease increases dramatically.
  • One in 80 Americans will develop melanoma.
  • Incidence is low until after puberty.
  • During pregnancy pigmented nevi may enlarge in
    size uniformly 2nd to hormones. If changes of
    irregular pigmentation or asymmetrical growth
    occur ect, then a biopsy should be performed.

Melanoma Risk Factors
  • Light complexion, blonde or red hair, childhood
    blistering sunburns, heavy freckling.
  • Other factors 50 benign nevi or family history
    of melanoma, dysplastic nevi.
  • 50 benign nevi
  • Presence of large congenital nevus
  • Presence of clinically dysplastic nevus
  • Mutations in the p16-CDK4 (DNS)
  • Immunodeficiency syndromes-acquired or genetic
  • PUVA treatments
  • Xeroderma pigmentosum
  • Use of tanning lamps

Melanoma Types.
  • There are four recognized clinicohistologic
  • 1.) Lentigo maligna (melanoma in situ,
    noninvasive melanoma)
  • 2.) Superficially spreading melanoma
  • 3.) Acral-lentiginous melanoma
  • 4.) Nodular melanoma

Lentigo Maligna(melanoma in situ, noninvasive
  • Begins as a tan macule that extends peripherally,
    with gradual uneven darkening, over several
    years. At this stage called lentigo maligna
  • After a radial growth of 5 to 20 years, a
    vertically growing component melanoma usually
    develops within it. A palpable nodule within the
    original macule is the best evidence that a
    lentigo maligna melanoma has occurred.
  • 60-70 yrs. MF
  • Usually on chronically sun-damaged skin, most
    often on the face
  • Accounts for 5 of all melanomas.

Lentigo Maligna(melanoma in situ, noninvasive
Superficially Spreading Melanoma
  • Most common, 70 of melanoma.
  • Adults of all ages. Median age 50 yrs.
  • No preference for sun damaged skin..
  • Lesion has tendency for multicolored appearance
    with notched borders and areas of regression.
  • Faster growing than lentigo maligna.
  • In a study by Bolognia et al 5 of lesions with
    an eccentric foci of hyperpigmentation(a roundish
    area of brown or black 3mm or less and located
    peripherally) are melanomas arising from within a
    nevus . It is necessary to ensure that the
    pathologist sections through the black dot to
    make this early diagnosis

Superficially Spreading Melanoma
Acral-lentiginous melanoma
  • Subungual and mucosal lesions are in this
  • Account for 10 of all melanomas.
  • The most common type among Japanese, African
    American, Hispanics, and Native Americans.
  • Due to lower incidence of other melanoma types.
  • Most common site in blacks is the foot - 60.
  • Median age is 50 yrs with equal sex distribution.

Acral-lentiginous melanoma
Nodular Melanoma
  • 15 of melanomas.
  • Pigmented papule or nodule of varying size.
  • No apparent radial growth phase.
  • Histologically, lesion extends several rete
    ridges past the apparent margin.
  • Polypoid Variant Does not appear to extend into
    dermis yet behaves like clark level IV or V. 42
    vs 57 five year survival.

Nodular Melanoma
Other Melanoma Types.
  • Desmoplastic Melanoma
  • Deeply infiltratiing, spindle cell type. Most are
    amelanotic. Occur within lentigo maligna often.
    Neurotropic spread.
  • Inflammatory melanoma
  • Inflammation surrounding melanoma poor
  • Amelanocytic melanoma pink or flesh colored.
    Mistaken for PG. Seen in Albinos.

Diagnosis of Melanoma
  • Surgical excision is the best method.
  • A shave may be better for less suspicious or
    broad, thin lesions.
  • For larger lesions an incisional or punch biopsy
    is the standard.
  • When melanoma is suspected in a melanotic freckle
    or a giant pigmented nevus, biopsy should be done
    through the thickest and most atypical area and
    multiply sectioned to find thickest area of

Histologic Diagnosis of Melanoma
  • Pinkus criteria
  • Presence of mitoses
  • Inflammatory reaction composed of lymphocytes and
    possibly plasma cells
  • Dermoepidermal junctional activity. (Except in
    giant nevus)
  • Absence of dermal stroma

Histologic Diagnosis of Melanoma
  • Increased number of melanocytes with atypical
    nuclei not only in the basal zone, but also at
    the upper levels of the epidermis

Histologic Diagnosis
  • Inflammatory cells surrounding atypical

Histologic Diagnosis of Melanoma
  • Neoplastic melanocytes extend into the dermis.
    Absence of maturation at deeper levels of the

Melanoma Metastasis
  • Metastasis-usually manifested by pigmented
    nodules appearing around the site of the excision
  • Early remote metastases occur via lymphatics and
    regional lynphadenopathy may be the first sign
  • Sites of mets Skin most common. Lungs, CNS also
    common. Any organ possible.
  • Usually occurs with in 5 years of diagnosis.

Melanoma Workup and Treatment
  • Establish a family history, thorough review of
    systems and physical exam for all patients.
  • A consensus conference in 1992 concluded that a
    staging workup (including E.L.N.D.) was not
    indicated for melanomas below 1.0 mm thickness.
  • Many physicians obtain a CXR and an LDH.
  • Consultation with an oncologist is worthwhile for
    advanced cases.
  • Sentinel node / ELND. Still evolving criteria.
    Recommended for tumors 1.0 mm thick or with

Melanoma Excision Margins
Melanoma - Other Treatments
  • High-dose interferon alfa-2b therapy.
  • Efficacy is equivocal and toxicity high.
  • May diminish the occurrence of mets and prolong
    disease free survival with melanoma 1.5 mm
  • Chemotherapy is not effective.
  • Adoptive immunotherapy with lymphokine-activated
    killer cells interleukin-2, or high dose
    interleukin-2 alone. Some patients are
  • Perfusion chemotherapy has been used for
    extremity melanoma and has almost eliminated the
    need for amputation.
  • Aldara and Tazorac for M.I.S. recently published.

Survival Indicators
  • 5 Year Survival Rates Based on Lesion Thickness
  • In situ 100
  • 0.76 to 1.49 90
  • 1.50 to 3.99 70
  • 4 mm .. 50

Dermal Melanocytic Lesions
  • At birth, melanocytes may be present in the
    dermal portion of the skin of the scalp, the
    backs of the hands, and the sacrum.
  • These are large ameboid cells that normally
    disappear shortly after birth.

Mongolian Spot
  • Bluish gray macule of varying size from 2-8 cm.
  • Typically in the sacral area of the newborn.
  • 80-90 of Asians, Southern Europeans, American
    blacks, and Native Americans.
  • Multiple spots may be situated in other locations
    and if associated with a nevus flammeus called
    phakomatosis pigmentovascularis
  • Most resolve with by adulthood.

Nevus of Ota(Nevus Fuscocerulleus
  • Brown, slate gray, or blue-black macules grow
    slowly larger and deeper in color around eye.
  • May have involvement of the conjunctiva and the
    skin about the eye.
  • Usually present at birth, esp if the patient is
    going to have ocular involvement.
  • 80 occur in women 5 are bilateral
  • Usually benign. Malignant melanoma may occur
    with choroid most commonly.
  • Glaucoma may occur.

Nevus of Ito(Nevus Fuscoceruleus
  • Same features as nevus of Ota except that it
    occurs in the distribution of the posterior
    supraclavicular and lateral cutaneous brachial
  • It involves the shoulder, side of the neck, and
    supraclavicular areas
  • TX Q-switched ruby laser.

Blue Nevus
  • 2 types
  • Blue nevus of Jadassohn-Tiche (common blue nevus)
  • Cellular blue nevus

Blue Nevus of Jadassohn-Tiche
  • Common blue nevus or nevus ceruleus
  • Steel-blue nodule that begins early in life
  • Slow growing. Rarely reaches 2-10mm.
  • Occurs most frequently on the dorsal hands, feet,
    forearms, shins, face, and the buttocks.

Blue Nevus
  • Within the dermis there is a poorly defined but
    symmetric spindle cell proliferation that is dark
    brown in color
  • No significant change in the overlying dermis

Blue Nevus
  • The spindled, heavily pigmented cells encircle
    collagen bundles in the reticular dermis.
  • The lesion is composed of elongate cells that are
    heavily pigmented and show prominent pigmented

Cellular Blue Nevus
  • Large, firm, blue or blue-black nodule.
    Frequently seen on the buttock and sacrococcygeal
  • Multilobulated, well circumscribed tumor.
  • Women 2.5 times Men. Occasionally present at
  • Average age is 40.
  • Uncommonly, these invade underlying structure
    such as the skull in scalp lesions.

Cellular Blue Nevus
  • Frequently large and involve a good part of the
    dermis and extending deeply as tonguelike
    aggregates of tumor cells at the base of the
  • Involvement of the subcutaneous fat is common and
    does not imply a malignant diagnosis

Cellular Blue Nevus
  • The cellular areas are composed of uniform
    spindled melanocytic cells with more cytoplasm
    and larger nuclei than what is seen in common
    blue nevus.
  • There are irregularly distributed collections of
    course melanin pigment within the cells

Epithelioid Blue Nevus
  • Newly described lesion with strong association
    with Carneys complex (myxomas, spotty skin
    pigmentation, endocrine over activity, and
  • Occur frequently on the head and neck, and are at
    times multiple
  • They are darkly pigmented, domed, and less than 1

Malignant Blue Nevus
  • Cellular blue nevus may rarely undergo malignant
    transformation into malignant melanoma
  • Clinically sudden increase in size and
  • Histologically Pleomorphism of nuclei, mitotic
    figures, and invasion of clusters of malignant
    cells into the deep dermis and fatty tissue.
  • Treatment
  • Benign lesions - Excision has been mainstay of
    treatment. Q-switched ruby laser.
  • Malignant variety is the same as M.M.