Melanocytic Nevi and Neoplasms

Andrew’s chapter 30JoAnne M. LaRow, D.O.

Epidermal Melanocytic Lesions

Normal melanocte occurring at the epidermal-dermal Normal melanocte occurring at the epidermal-dermal junction is a dendritic secretory cell supplying all junction is a dendritic secretory cell supplying all normal melanin to skinnormal melanin to skin

These cells contain pigment granules (melanosomes)These cells contain pigment granules (melanosomes) Stain with dopa reaction and silver stainsStain with dopa reaction and silver stains Melanocytes of the epidermis transfer the Melanocytes of the epidermis transfer the

melanosomes through their thin dendritic processes melanosomes through their thin dendritic processes into surrounding keratinocytesinto surrounding keratinocytes

Size and number in keratinocytes determine Size and number in keratinocytes determine pigmentation of skin and hairpigmentation of skin and hair

Nevus Spilus

Pigmented, light brown or tan Pigmented, light brown or tan macule, varied diameter, macule, varied diameter, speckled with smaller, speckled with smaller, darker-colored macules or darker-colored macules or papulespapules

Lower extremity & trunk Lower extremity & trunk frequentlyfrequently

May be <1cm or largeMay be <1cm or largeMay follow a dermatomal May follow a dermatomal

distribution when largedistribution when largeUsually they do not cross the Usually they do not cross the

midlinemidline

Nevus SpilusWhen these nevi follow a When these nevi follow a dermatomal distribution they may dermatomal distribution they may be referred to as a zosteriform, or be referred to as a zosteriform, or sometimes a speckled lentiginous sometimes a speckled lentiginous nevusnevus

When nevus spilus is present with a When nevus spilus is present with a nevus flammeus = phakomatosis nevus flammeus = phakomatosis pigmentovascularis phakomatosis pigmentovascularis phakomatosis pigmentokeratotica= a syndrome pigmentokeratotica= a syndrome of organoid nevus with sebaceous of organoid nevus with sebaceous differentiation, hemiatrophy with differentiation, hemiatrophy with muscular weakness & other muscular weakness & other neurologic findings & speckled neurologic findings & speckled lentiginous nevuslentiginous nevus

Nevus Spilus

-The darker speckles usually contain nevus -The darker speckles usually contain nevus cellscells

-Due to this melanoma may arise in the with -Due to this melanoma may arise in the with greater frequency than in normal skingreater frequency than in normal skin

-However, removal is not necessary-However, removal is not necessary

-Removal by Q-switched ruby laser has been -Removal by Q-switched ruby laser has been reported effectivereported effective

Lentigo Simplex

Usually arise in childhood but can arise anytimeUsually arise in childhood but can arise anytime Sharply defined, rounded, brown or black macules Sharply defined, rounded, brown or black macules

found anywhere on body or mucosafound anywhere on body or mucosa Histologically shows elongation of rete ridges, Histologically shows elongation of rete ridges,

increase in number of melanocytes in basal layer, increase in number of melanocytes in basal layer, increase of melanin in both melanocytes, and basal increase of melanin in both melanocytes, and basal keratinocytes, and melanophages in the upper keratinocytes, and melanophages in the upper dermisdermis

No therapy is needed/ there is no predisposition to No therapy is needed/ there is no predisposition to neoplastic changeneoplastic change

Solar LentiginesCommonly called “liver spots”Commonly called “liver spots”Hyperpigmented maculesHyperpigmented maculesMay evolve into sk’s or lichenoid May evolve into sk’s or lichenoid

keratoseskeratosesTx=liquid nitrogen, laserTx=liquid nitrogen, laserMay recur, as a lentigo maligna or May recur, as a lentigo maligna or

lentigo maligna melanomalentigo maligna melanomaBe aware-oral methoxsalen Be aware-oral methoxsalen

photochemotherapy or frequent photochemotherapy or frequent tanning salons may develop tanning salons may develop lentigines on non-sun-exposed lentigines on non-sun-exposed areas and these may show areas and these may show cellular atypiacellular atypia

Penile and Vulvar Melanosis

Localized pigmentary Localized pigmentary alterationsalterations

Most often show basilar Most often show basilar hyperpigmentation hyperpigmentation

May appear in large May appear in large patches or in smaller, patches or in smaller, well-demarcated lesionswell-demarcated lesions

Present on the penis or in Present on the penis or in women on the labia women on the labia majora majora

Bannayan-Riley-Ruvalcaba Syndrome Rare, AD disorder that manifests in Rare, AD disorder that manifests in

childhoodchildhood 80% of the pts are male80% of the pts are male Characterized by genital lentiginosis, Characterized by genital lentiginosis,

macrocephaly, motor and speech delay, macrocephaly, motor and speech delay, mental retardation, lipomas, hemangiomas, mental retardation, lipomas, hemangiomas, verruca vulgaris, and many types of facial verruca vulgaris, and many types of facial papulespapules

Multiple Lentigenes Syndrome

Lentigines are dark Lentigines are dark brown macules 1-5 brown macules 1-5 mm.mm.

Preponderance on the Preponderance on the trunktrunk

Multiple generalized Multiple generalized lentigines may occur lentigines may occur with a number of with a number of associated signs as an associated signs as an dominantly inherited dominantly inherited syndromesyndrome

ll

LEOPARD Syndrome

Leopard syndrome = Leopard syndrome = acronym for lentigines, acronym for lentigines, electrocardiographic electrocardiographic abnormalities, ocular abnormalities, ocular hypertelorism, pulmonary hypertelorism, pulmonary stenosis, abnormalities of stenosis, abnormalities of genitalia, retardation of genitalia, retardation of growth, and deafnessgrowth, and deafness

Moynahan Syndrome

Multiple lentiginesMultiple lentigines Congenital mitral stenosisCongenital mitral stenosis DwarfismDwarfism Genital hypoplasiaGenital hypoplasia Mental deficiencyMental deficiency

Centrofacial Lentiginosis

Characterized by lentigines on the nose, and Characterized by lentigines on the nose, and adjacent cheeks adjacent cheeks

Sometimes associated with status Sometimes associated with status dysraphicus, multiple skeletal anomalies, dysraphicus, multiple skeletal anomalies, and CNS disordersand CNS disorders

Spares the mucous membranesSpares the mucous membranes Onset is first years of lifeOnset is first years of life

Inherited Patterned Lentiginosis in Blacks

AD- reportedly, 10 light-AD- reportedly, 10 light-complexioned black patients complexioned black patients who developed numerous who developed numerous lentigines in infancy or early lentigines in infancy or early childhoodchildhood

Distribution is central face, Distribution is central face, lips, with variable lips, with variable involvement of dorsal hands involvement of dorsal hands and feet, elbows, and and feet, elbows, and buttocksbuttocks

Sparing of mucous Sparing of mucous membranes and no internal membranes and no internal abnormalitiesabnormalities

Carney’s Syndrome

AKA NAME syndrome or LAMB AKA NAME syndrome or LAMB syndromesyndrome

Characterized by cardiocutaneous Characterized by cardiocutaneous myxomas, lentigines, blue nevi, and myxomas, lentigines, blue nevi, and endocrine anomaliesendocrine anomalies

Peutz-Jeghers Syndrome

AD AD Pigmented macules on Pigmented macules on

the lips, oral mucosa, the lips, oral mucosa, perioral acral areasperioral acral areas

Gastrointestinal Gastrointestinal polyps, especially polyps, especially prominent in the prominent in the jejunum are seenjejunum are seen

Melanoacanthoma

uncommon lesion, a benign epidermal uncommon lesion, a benign epidermal melanocytic neoplasm, occurring on the melanocytic neoplasm, occurring on the headhead

Resembles a pigmented sk or a pigmented Resembles a pigmented sk or a pigmented BCCBCC

Predominantly seen in white men > 60 yrsPredominantly seen in white men > 60 yrs

Cellular Nevi Begins to appear in first yrs of life, increase in prevalence and Begins to appear in first yrs of life, increase in prevalence and

number over the next two decades, after which there is a number over the next two decades, after which there is a steady declinesteady decline

Females tent to have more than malesFemales tent to have more than males Less common in sun-protected areasLess common in sun-protected areas Maximum number is at age 20- 25 yrs, the average number is Maximum number is at age 20- 25 yrs, the average number is

4040 Sun exposure increases the number of nevi in the exposed Sun exposure increases the number of nevi in the exposed

skinskin Eruptive nevi are rare, but may occur after severe bullous Eruptive nevi are rare, but may occur after severe bullous

disease such as TEN, EM, or severe sunburn, Addison’s disease such as TEN, EM, or severe sunburn, Addison’s disease or immunosuppresion disease or immunosuppresion

Junctional Nevi Nevi begin as small, flat, Nevi begin as small, flat,

pigmented macules = pigmented macules = junctional nevijunctional nevi

A smooth, hairless, light to A smooth, hairless, light to dark brown macule, dark brown macule, varying in size from 1 –6 varying in size from 1 –6 mmmm

Occurs on any site, Occurs on any site, especially on palms, soles, especially on palms, soles, scrotumscrotum

During adolescence some During adolescence some will become compound or will become compound or intradermal intradermal

It is characterized by single It is characterized by single melanocytes, or theques of melanocytes, or theques of them in the lower them in the lower epidermisepidermis

Compound Nevus

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

Junctional Nevi Nevi begin as small, flat, Nevi begin as small, flat,

pigmented macules = pigmented macules = junctional nevijunctional nevi

A smooth, hairless, light to A smooth, hairless, light to dark brown macule, dark brown macule, varying in size from 1 –6 varying in size from 1 –6 mmmm

Occurs on any site, Occurs on any site, especially on palms, soles, especially on palms, soles, scrotumscrotum

During adolescence some During adolescence some will become compound or will become compound or intradermal intradermal

It is characterized by single It is characterized by single melanocytes, or theques of melanocytes, or theques of them in the lower them in the lower epidermisepidermis

Compound Nevus

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

Compound Nevus

An 8-mm, well-An 8-mm, well-circumscribed, circumscribed, symmetric, uniformly symmetric, uniformly colored papulecolored papule

A lesion of this size A lesion of this size could be an acquired could be an acquired nevus or a small nevus or a small congenital pattern congenital pattern nevusnevus

Compound Nevus Nests of Nests of

nevus nevus cells in cells in the the epidermiepidermis s overlying overlying a dermal a dermal componecomponent of nt of orderly orderly nevus nevus cellscells

Compound Nevus Acral type-thickened basket Acral type-thickened basket

weave stratum corneum weave stratum corneum shows that it is an acral siteshows that it is an acral site

Nevus is small and Nevus is small and symmetric, and shows both symmetric, and shows both a junctional and superficial a junctional and superficial dermal componentdermal component

The nests in the papillary The nests in the papillary dermis are small, orderly, dermis are small, orderly, and lack atypia. The and lack atypia. The epidermal component may epidermal component may show a few pagetoid cellsshow a few pagetoid cells

Intradermal Nevus

a compound nevus in which junctional a compound nevus in which junctional activity- that is, theques of melanoctyes in activity- that is, theques of melanoctyes in the epidermis or at the dermal epidermal the epidermis or at the dermal epidermal junction- has ceased, and all the nevus cells junction- has ceased, and all the nevus cells are in the dermisare in the dermis

Intradermal Nevus Low power-as in Low power-as in

junctional nevi , dermal junctional nevi , dermal nevi contain nevus cells nevi contain nevus cells that are recognized at this that are recognized at this power by tendency to be power by tendency to be arranged in nestsarranged in nests

High power- at the base of High power- at the base of this dermal nevus the this dermal nevus the melanocytic cells melanocytic cells resemble neural resemble neural structures( neurotization)structures( neurotization)

Balloon Cell Nevus A pigmented nevus, varying in A pigmented nevus, varying in size from 1 –5 mm, usually size from 1 –5 mm, usually occurring on the head, neck, and occurring on the head, neck, and trunk.trunk.

They are clinically They are clinically indistinguishable from ordinary indistinguishable from ordinary pigmented or nonpigmented pigmented or nonpigmented nevusnevus

Histologically, the lesions are Histologically, the lesions are composed of peculiar vesicular composed of peculiar vesicular cells that appear to be foamy cells that appear to be foamy and form large pale polyhedral and form large pale polyhedral balloon cells that may be balloon cells that may be multinucleated giant cells in multinucleated giant cells in addition to nevus cells.addition to nevus cells.

Not considered potentially Not considered potentially malignant, and treatment is malignant, and treatment is same as other nevisame as other nevi

Halo Nevus AKA Sutton’s nevus, AKA Sutton’s nevus,

perinevoid vitilgo, & perinevoid vitilgo, & leukoderma acquisitum leukoderma acquisitum centrifugumcentrifugum

A pigmented nevus with A pigmented nevus with surrounding depigmented surrounding depigmented zonezone

Nevus is usually compound or Nevus is usually compound or intradermalintradermal

May be single or multipleMay be single or multiple Usually on the trunkUsually on the trunk Mostly develop in teenagersMostly develop in teenagers No tx indicated- central nevus No tx indicated- central nevus

disappears with time disappears with time leukodermic area will usually leukodermic area will usually repigment with timerepigment with time

Halo Nevus

The nevus architecture The nevus architecture is obscured by a dense is obscured by a dense lymphocytic infiltratelymphocytic infiltrate

Lymphocytes infiltrate Lymphocytes infiltrate among the dermal among the dermal nevus cells, which nevus cells, which eventually degenerate eventually degenerate and disappearand disappear

Congenital Nevocytic Nevus Giant Pigmented Nevus Giant Pigmented Nevus

(Giant hairy nevus, bathing (Giant hairy nevus, bathing trunk nevus)trunk nevus)

Characterized by a large, Characterized by a large, darkly pigmented hairy darkly pigmented hairy patch in which smaller, patch in which smaller, darker patches are darker patches are interspersed or present as interspersed or present as small satellite lesionssmall satellite lesions

Skin may be thickened or Skin may be thickened or verrucousverrucous

Has a tendency to follow a Has a tendency to follow a dermatome distributiondermatome distribution

Trunk favored siteTrunk favored site

Congenital Nevocytic Nevus Giant hairy nevi are present Giant hairy nevi are present

at birth and grow at birth and grow proportionally to the site of proportionally to the site of the body where they are the body where they are locatedlocated

By definition they are >20cmBy definition they are >20cm When a large congenital When a large congenital

nevus involves the axial skin, nevus involves the axial skin, there may be an associated there may be an associated neurocutaneous neurocutaneous melanocytosismelanocytosis

Incidence of melanoma Incidence of melanoma developing is 3% to 7%developing is 3% to 7%

CNN About 40% of the malignant About 40% of the malignant

melanomas seen in children occur in melanomas seen in children occur in large congenital nevi -risk is greatest large congenital nevi -risk is greatest for axial lesionsfor axial lesions

If neurocutaneous melanosis is If neurocutaneous melanosis is present (which can be detected by present (which can be detected by MRI), the risk of dying at a young MRI), the risk of dying at a young age is high secondary to age is high secondary to hydrocephalus or leptomeningeal hydrocephalus or leptomeningeal melanomamelanoma

Most recommend total surgical Most recommend total surgical excision and resurfacing autograftsexcision and resurfacing autografts

Alternative treatments-dermabrasion, Alternative treatments-dermabrasion, curettage, and laser ablation- are curettage, and laser ablation- are designed to eliminate some of the designed to eliminate some of the nevus cells, with theoretic lowering nevus cells, with theoretic lowering of the risk of melanomaof the risk of melanoma

Small and Medium-sized Congenital Nevocytic Nevus

Small - < 1.5 cm in greatest diameterSmall - < 1.5 cm in greatest diameter Medium- > 1.5 cm but < 20 cmMedium- > 1.5 cm but < 20 cm Found in 1% of newbornsFound in 1% of newborns Half eventually become hairyHalf eventually become hairy Data to determine the incidence of melanoma are still Data to determine the incidence of melanoma are still

being gatheredbeing gathered Excision is recommended for lesions of the hairy Excision is recommended for lesions of the hairy

scalp, or those of great cosmetic concern or nevi with scalp, or those of great cosmetic concern or nevi with unusual clinical featuresunusual clinical features

Epitheliod and Spindle-Cell Nevus(benign Juvenile Melanoma, Spitz Nevus)

Spitz Nevus

A smooth-surfaced, raised, round, slightly A smooth-surfaced, raised, round, slightly scaly, firm papule with distinctive pink, scaly, firm papule with distinctive pink, brownish red, or purplish red colorbrownish red, or purplish red color

Typically, firm,rosy papule on the face, Typically, firm,rosy papule on the face, especially on the cheekespecially on the cheek

3 – 10 mm in diameter3 – 10 mm in diameter Female predominanceFemale predominance Should be completely excised Should be completely excised

Spitz Nevus A variant of the compound A variant of the compound

nevusnevus Epidermal irregular Epidermal irregular

acanthosis, acanthosis, pseudoepitheliomatous pseudoepitheliomatous hyperplasia, and thinning hyperplasia, and thinning of the epidermisof the epidermis

Nevus cells are Nevus cells are pleomorphic, but mostly pleomorphic, but mostly spindle-shaped (fusiform), spindle-shaped (fusiform), or polygonal (epithelioid) or polygonal (epithelioid) cellscells

Spitz Nevus Giant cells with eosiophilic Giant cells with eosiophilic

cytoplasm and a large nucleus cytoplasm and a large nucleus may be seenmay be seen

Multinucleated giant cells are Multinucleated giant cells are seen less frequentlyseen less frequently

No difference between childhood No difference between childhood and adult lesionsand adult lesions

Eosinophilic globules with Eosinophilic globules with fibrillar microstructure (Kamino fibrillar microstructure (Kamino bodies) are found in 60% - 85% bodies) are found in 60% - 85% of SNof SN

May also be present in May also be present in melanomas (12&) and compound melanomas (12&) and compound nevi(8%), but are fewer and nevi(8%), but are fewer and smaller in SNsmaller in SN

Spitz Nevus

* Immunohistochemical staining for MIB-1 * Immunohistochemical staining for MIB-1 and bcl-2 will distinguish most Spitz nevi and bcl-2 will distinguish most Spitz nevi from melanoma;melanomas are from melanoma;melanomas are immunoreactive, whereas Spitz nevi are notimmunoreactive, whereas Spitz nevi are not

* Differential diagnosis-pyogenic granuloma, * Differential diagnosis-pyogenic granuloma, mastocytoma, juvenile xanthogranuloma, or mastocytoma, juvenile xanthogranuloma, or melanomamelanoma

Dysplastic Nevus

Variegated tan, brown, pink Variegated tan, brown, pink colorationcoloration

Pink hues seen in macular Pink hues seen in macular portion portion

Macular portion always Macular portion always present, may comprise present, may comprise entire lesion, but frequently entire lesion, but frequently surrounds a papular centersurrounds a papular center

Generally larger than are Generally larger than are common nevi, usually 5 – common nevi, usually 5 – 12mm, with irregular 12mm, with irregular bordersborders

Dysplastic Nevus Syndrome

Around 1978 Lynch et al recognized an autosomal Around 1978 Lynch et al recognized an autosomal dominant inheritance pattern in families with unusual dominant inheritance pattern in families with unusual nevi and multiple melanomas-initially described by nevi and multiple melanomas-initially described by Clark et al as B-K mole syndrome- then named Clark et al as B-K mole syndrome- then named familial atypical multiple mole-melanoma syndromefamilial atypical multiple mole-melanoma syndrome

Now termed dysplastic nevus syndrome (DNS)Now termed dysplastic nevus syndrome (DNS) Pts with dysplastic nevi send at least two blood Pts with dysplastic nevi send at least two blood

relatives with dysplastic nevi and melanoma have the relatives with dysplastic nevi and melanoma have the worst prognosis with possibly 100% lifetime risk of worst prognosis with possibly 100% lifetime risk of melanomamelanoma

Dysplastic Nevus Syndrome-Genetics 25% -33% of pts have germline mutations on 25% -33% of pts have germline mutations on

chromosome 9p in the CDKN2A tumor-chromosome 9p in the CDKN2A tumor-suppressor gene-which encodes for an inhibitor of suppressor gene-which encodes for an inhibitor of a cyclindependent kinase 4 (CDK4) that functions a cyclindependent kinase 4 (CDK4) that functions to suppress proliferationto suppress proliferation

In these pts with mutations that impair the In these pts with mutations that impair the function of the p16 suppressor protein, referred to function of the p16 suppressor protein, referred to as the p16M alleles, there is a concomitant as the p16M alleles, there is a concomitant predisposition to pancreatic cancerpredisposition to pancreatic cancer

Dysplastic Nevus Syndrome

Dysplasic nevi occur commonly in pts without a Dysplasic nevi occur commonly in pts without a personal or family history of melanoma-5% -20% personal or family history of melanoma-5% -20% of pts having at least one clinically dysplastic of pts having at least one clinically dysplastic nevusnevus

This is important for (1) histologic evaluation is This is important for (1) histologic evaluation is neede (2) a careful history and evaluation of neede (2) a careful history and evaluation of family members (3) they provide another risk family members (3) they provide another risk factor for melanoma predispositionfactor for melanoma predisposition

Dysplastic Nevus Syndrome

Histologic features as per an NIH consensus- Histologic features as per an NIH consensus- basilar melanocytic hyperplasia with elongation of basilar melanocytic hyperplasia with elongation of rete ridges; spindle-shaped or occasionally, rete ridges; spindle-shaped or occasionally, epithelioid melanocytes arranged horizontally and epithelioid melanocytes arranged horizontally and aggregating in nests that fuse with adjacent rete aggregating in nests that fuse with adjacent rete ridges; lamellar and concentric superficial dermal ridges; lamellar and concentric superficial dermal infiltrate; cytologic atypia, usually present but not infiltrate; cytologic atypia, usually present but not essential for diagnosisessential for diagnosis

Dysplastic Nevi

Patients with dysplastic nevi and a positive Patients with dysplastic nevi and a positive family or personal history of melanoma, family or personal history of melanoma, physician examination every 3 – 6 months physician examination every 3 – 6 months

Excision of those nevi that change clinicallyExcision of those nevi that change clinically Photographs with measured scale is usefulPhotographs with measured scale is useful

Melanoma Originate from melanocytes Originate from melanocytes

at epidermal-dermal junctionat epidermal-dermal junction Half will develop in Half will develop in

preexisting nevipreexisting nevi Prolonged, non invasive, Prolonged, non invasive,

horizontally oriented growth horizontally oriented growth phasephase

When tumor nodule develops When tumor nodule develops the vertical growth phase is the vertical growth phase is occurring and the risk of occurring and the risk of metastatic disease increases metastatic disease increases dramaticallydramatically

Melanoma

One in 80 Americans will One in 80 Americans will develop melanomadevelop melanoma

Incidence is low until after Incidence is low until after pubertypuberty

Children may present with Children may present with congenital melanoma or congenital melanoma or acquired melanomaacquired melanoma

Congenital melanoma may occur Congenital melanoma may occur because of transplacental because of transplacental transmission, as a primary transmission, as a primary intrauterine lesion, as a intrauterine lesion, as a melanoma from a congenital melanoma from a congenital nevus in utero, or as prenatal nevus in utero, or as prenatal metastatic lesions from metastatic lesions from neurocutaneous melanosis all of neurocutaneous melanosis all of these have a poor prognosisthese have a poor prognosis

Diagnosis of Melanoma

- surgical excision is the best method- surgical excision is the best method

-for larger lesions an incisional or punch biopsy, -for larger lesions an incisional or punch biopsy, deep enough is considered good practicedeep enough is considered good practice

-when melanoma is suspected in a melanotic freckle -when melanoma is suspected in a melanotic freckle or a giant pigmented nevus, biopsy should be done or a giant pigmented nevus, biopsy should be done through the thickest and most atypical area and through the thickest and most atypical area and multiply sectioned to find thickest area of multiply sectioned to find thickest area of involvementinvolvement

Histologic diagnosis:

-presence of mitoses-presence of mitoses-inflammatory reaction -inflammatory reaction

composed of composed of lymphocytes and lymphocytes and possibly plasma cellspossibly plasma cells

-dermoepidermal -dermoepidermal junctional activityjunctional activity

-absence of dermal -absence of dermal stromastroma

Histologic diagnosis:

-a moderately brisk tumor--a moderately brisk tumor-infiltrating lymphocyte infiltrating lymphocyte response is present around response is present around the nodulethe nodule

- the cells in the nodule are - the cells in the nodule are large epithelioid large epithelioid melanoma cells that have melanoma cells that have abundant cytoplasm and abundant cytoplasm and large irregular nuclei with large irregular nuclei with prominent nucleoli with prominent nucleoli with numerous mitosesnumerous mitoses

Melanoma

Metastasis-usually Metastasis-usually manifested by manifested by pigmented nodules pigmented nodules appearing around the appearing around the site of the excisionsite of the excision

Early remote metastases Early remote metastases occur via lymphatics occur via lymphatics and regional and regional lynphadenopathy may lynphadenopathy may be the first signbe the first sign

Melanoma

> 50 benign nevi> 50 benign nevi Presence of large congenital nevusPresence of large congenital nevus Presence of clinically dysplasic nevusPresence of clinically dysplasic nevus Mutations in the p16-CDK4Mutations in the p16-CDK4 Immunodefiency syndromes-acquired or geneticImmunodefiency syndromes-acquired or genetic PUVA treatmentsPUVA treatments Xeroderma pigmentosumXeroderma pigmentosum Use of tanning lampsUse of tanning lamps Levodopa therapy for Parkinson’s disease has been Levodopa therapy for Parkinson’s disease has been

implicated in 19 case reports by Rampenimplicated in 19 case reports by Rampen

Melanoma

There are four recognized clinicohistologic There are four recognized clinicohistologic types:types:

1.) Lentigo maligna (melanoma in situ, 1.) Lentigo maligna (melanoma in situ, noninvasive melanoma)noninvasive melanoma)

2.) Superficially spreading melanoma2.) Superficially spreading melanoma3.) Acral-lentiginous melanoma3.) Acral-lentiginous melanoma4.) Nodular melanoma4.) Nodular melanoma

Melanoma

*Pedunculated, polypoidal melanomas, *Pedunculated, polypoidal melanomas, inflammatory melanomas, amelanotic inflammatory melanomas, amelanotic melanomas, and hyperkeratotic and melanomas, and hyperkeratotic and verrucous melanomas are clinical findingsverrucous melanomas are clinical findings

*At a microscopic level-desmoplastic, *At a microscopic level-desmoplastic, neurotropic, myxoid, balloon cell, and neurotropic, myxoid, balloon cell, and signet cell patterns are seensignet cell patterns are seen

Lentigo maligna(melanoma in situ, noninvasive melanoma)

Begins as a tan macule that extends peripherally, with Begins as a tan macule that extends peripherally, with gradual uneven darkening, over several yearsgradual uneven darkening, over several years

After a radial growth of 5 to 20 years, vertically growing After a radial growth of 5 to 20 years, vertically growing melanoma usually develops within it melanoma usually develops within it

A palpable nodule within the original macule is the best A palpable nodule within the original macule is the best evidence that a lentigo maligna melanoma has occurredevidence that a lentigo maligna melanoma has occurred

Equal incidence in men and womenEqual incidence in men and women Usually 60-70 yrsUsually 60-70 yrs Usually on chronically sun-damaged skin, most often on Usually on chronically sun-damaged skin, most often on

the facethe face Accounts for 5% of all melanomasAccounts for 5% of all melanomas

Lentigo maligna(melanoma in situ, noninvasive melanoma)

Superficially spreading melanoma

In a study by Bolognia et al In a study by Bolognia et al 5% of lesions with an 5% of lesions with an eccentric foci of eccentric foci of hyperpigmentation(a hyperpigmentation(a roundish area of brown or roundish area of brown or black 3mm or< and located black 3mm or< and located peripherally) are peripherally) are melanomas arising from melanomas arising from within a nevuswithin a nevus

It is necessary to ensure that It is necessary to ensure that the pathologist sections the pathologist sections through the black dot to through the black dot to make this early diagnosismake this early diagnosis

Acral-lentiginous melanoma

Acral-lentiginous melanoma lies midway between Acral-lentiginous melanoma lies midway between the lentigo maligna and the superficially spreading the lentigo maligna and the superficially spreading melanoma in respect to speed of horizontal growth melanoma in respect to speed of horizontal growth into adjacent epidermisinto adjacent epidermis

Subungual and mucosal lesions are in this Subungual and mucosal lesions are in this categorycategory

Account for 10% of all melanomasAccount for 10% of all melanomas The most common type among Japanese, African The most common type among Japanese, African

American, Hispanics, and Native AmericansAmerican, Hispanics, and Native Americans Median age is 50 yrs with equal sex distributionMedian age is 50 yrs with equal sex distribution

Melanoma- workup and follow-up-establish a family history-establish a family history-thorough review of systems-thorough review of systems- physical examphysical exam- A consensus conference in 1992 concluded that a staging A consensus conference in 1992 concluded that a staging

workup was not indicated for melanomas below 1.0 mm workup was not indicated for melanomas below 1.0 mm thicknessthickness

- Many physicians obtain a CXR and an LDHMany physicians obtain a CXR and an LDH- As in the initial workup, more information and a As in the initial workup, more information and a

consensus statement would help to establish indications consensus statement would help to establish indications for testing for testing

- Consultation with an oncologist is worthwhileConsultation with an oncologist is worthwhile

Melanoma-treatment

-early diagnosis and excision-early diagnosis and excision-margin of 0.5 to 1.0 cm for melanoma in situ-margin of 0.5 to 1.0 cm for melanoma in situ-1.0 cm margin for melanomas < 2.0 cm thick-1.0 cm margin for melanomas < 2.0 cm thick-3.0 cm margin for those thicker than 2.0 mm -3.0 cm margin for those thicker than 2.0 mm -Zitelli et al recommended wider margins for -Zitelli et al recommended wider margins for

melanomas of the head, neck, hands, and feet- they melanomas of the head, neck, hands, and feet- they recommend a minimum surgical margin of 1.5 cm, recommend a minimum surgical margin of 1.5 cm, unless Mohs’ micrographic surgery is useunless Mohs’ micrographic surgery is use

- ELND is controversial and therefore intraoperative - ELND is controversial and therefore intraoperative lymphatic mapping is usedlymphatic mapping is used

Melanoma-treatment-high-dose interferon alfa-2b therapy has been used, however -high-dose interferon alfa-2b therapy has been used, however

efficacy is equivocal and toxicity highefficacy is equivocal and toxicity high-adjuvant interferon alfa-2a treatment has been reported to -adjuvant interferon alfa-2a treatment has been reported to

diminish the occurrence of mets and prolong disease free diminish the occurrence of mets and prolong disease free survival in pts with melanoma > 1.5 mm thicksurvival in pts with melanoma > 1.5 mm thick

-chemotherapy is not effective-chemotherapy is not effective-Adoptive immunotherapy with lymphokine-activated killer -Adoptive immunotherapy with lymphokine-activated killer

cells + interleukin-2, or high –dose into leukin-2 alone is cells + interleukin-2, or high –dose into leukin-2 alone is also toxic, some patients are responsivealso toxic, some patients are responsive

-perfusion chemotherapy has been used for extremity -perfusion chemotherapy has been used for extremity melanoma and has almost eliminated the need for melanoma and has almost eliminated the need for amputationamputation

Dermal Melanocytic Lesions

At birth, melanocytes may be present in the At birth, melanocytes may be present in the dermal portion of the skin of the scalp, the dermal portion of the skin of the scalp, the backs of the hands, and the sacrumbacks of the hands, and the sacrum

These are large ameboid cells that normally These are large ameboid cells that normally disappear shortly after birthdisappear shortly after birth

Mongolian Spot

Bluish gray macule of Bluish gray macule of varying size from 2-8 cmvarying size from 2-8 cm

Occurs typically in the Occurs typically in the sacral area of the newbornsacral area of the newborn

80-90% of Asians, 80-90% of Asians, Southern Europeans, Southern Europeans, American blacks, and American blacks, and Native AmericansNative Americans

Multiple spots may be Multiple spots may be situated in other locationssituated in other locations

Mongolian Spot

Multiple spots occurring in a widespread Multiple spots occurring in a widespread distribution have been termed generalized distribution have been termed generalized dermal melanocytosis or dermal dermal melanocytosis or dermal melanocytic hamartomasmelanocytic hamartomas

If associated with a nevus flammeus- If associated with a nevus flammeus- phakomatosis pigmentovascularis phakomatosis pigmentovascularis

Nevus of Ota

Aka nevus fuscocerulleus Aka nevus fuscocerulleus opthalmaomaxillarisopthalmaomaxillaris

Usually present at birth , especially if Usually present at birth , especially if the patient is going to have ocular the patient is going to have ocular involvementinvolvement

May have involvement of the May have involvement of the conjunctiva and the skin about the conjunctiva and the skin about the eyeeye

On the skin brown, slate gray, or On the skin brown, slate gray, or blue-black macules grow slowly blue-black macules grow slowly larger and deeper in colorlarger and deeper in color

80% occur in women; 5% are 80% occur in women; 5% are bilateralbilateral

Usually a benign lesion malignant Usually a benign lesion malignant melanoma may occurmelanoma may occur

Most common location is the choroidMost common location is the choroid Glaucoma may occurGlaucoma may occur

Nevus of Ito

Aka nevus fuscoceruleus acromiodeltoideusAka nevus fuscoceruleus acromiodeltoideus Has the same features as nevus of Ota Has the same features as nevus of Ota

except that it occurs in the distribution of except that it occurs in the distribution of the posterior supraclavicular and lateral the posterior supraclavicular and lateral cutaneous brachial nervescutaneous brachial nerves

It involves the shoulder, side of the neck, It involves the shoulder, side of the neck, and supraclavicular areasand supraclavicular areas

Tx –Q-switched ruby laser are dramaticTx –Q-switched ruby laser are dramatic

Blue Nevus

Two types:Two types: 1.) Blue nevus of Jadassohn-Tiche 1.) Blue nevus of Jadassohn-Tiche

(common blue nevus)(common blue nevus) 2.) Cellular blue nevus2.) Cellular blue nevus

Blue Nevus Within the dermis there is a Within the dermis there is a poorly defined but symmetric poorly defined but symmetric spindle cell proliferation that is spindle cell proliferation that is dark brown in colordark brown in color

No significant change in the No significant change in the overlying dermisoverlying dermis

The spindled heavily pigmented The spindled heavily pigmented cells encircle collagen bundles cells encircle collagen bundles in the reticular dermis, a pattern in the reticular dermis, a pattern also seen in dermatofibromasalso seen in dermatofibromas

The lesion is composed of The lesion is composed of elongate cells that are heavily elongate cells that are heavily pigmented and show prominent pigmented and show prominent pigmented dendritespigmented dendrites

Blue Nevus of Jadassohn-Tiche

The typical common blue The typical common blue nevus or nevus ceruleusnevus or nevus ceruleus

Steel-blue nodule that Steel-blue nodule that begins early in lifebegins early in life

Slow growing Slow growing Rarely reaches 2-10mmRarely reaches 2-10mm Occurs most frequently on Occurs most frequently on

the dorsal hands, feet, the dorsal hands, feet, forearms, shins, face, and forearms, shins, face, and the buttocksthe buttocks

Cellular Blue Nevus Large, firm, blue or blue-Large, firm, blue or blue-

black noduleblack nodule Frequently seen on the Frequently seen on the

buttock and sacrococcygeal buttock and sacrococcygeal regionregion

Occasionally present at birthOccasionally present at birth Seen in women 2.5 times as Seen in women 2.5 times as

frequently as menfrequently as men Average age is 40Average age is 40 Uncommonly these invade Uncommonly these invade

underlying structure such as underlying structure such as the skull in scalp lesionsthe skull in scalp lesions

Cellular Blue Nevus

Frequently large and Frequently large and involve a good part of the involve a good part of the dermis and extending dermis and extending deeply as tonguelike deeply as tonguelike aggregates of tumor cells aggregates of tumor cells at the base of the lesionat the base of the lesion

Involvement of the Involvement of the subcutaneous fat is subcutaneous fat is common and does not common and does not imply a malignant imply a malignant diagnosisdiagnosis

Cellular Blue Nevus

The cellular areas are The cellular areas are composed of uniform composed of uniform spindled melanocytic cells spindled melanocytic cells with mor cytoplasm and with mor cytoplasm and larger nuclei than what is larger nuclei than what is seen in common blue seen in common blue nevus. nevus.

There are irregularly There are irregularly distributed collections of distributed collections of course melanin pigment course melanin pigment within the cellswithin the cells

Epithelioid Blue Nevus

Newly described lesion Newly described lesion Strong association with Carney’s complex Strong association with Carney’s complex

(myxomas, spotty skin pigmentation, endocrine (myxomas, spotty skin pigmentation, endocrine over activity, and schwannomas)over activity, and schwannomas)

Occur frequently on the head and neck, and are at Occur frequently on the head and neck, and are at times multipletimes multiple

They are darkly pigmented, domed, and less than They are darkly pigmented, domed, and less than 1 cm1 cm

Malignant Blue Nevus -Cellular blue nevus may rarely undergo malignant -Cellular blue nevus may rarely undergo malignant

transformation into malignant melanomatransformation into malignant melanoma -clinically increase in size, suddenly and ulceration-clinically increase in size, suddenly and ulceration -histologically, pleomorphism of nuclei, mitotic -histologically, pleomorphism of nuclei, mitotic

figures, and invasion of clusters of malignant cells into figures, and invasion of clusters of malignant cells into the deep dermis and fatty tissuethe deep dermis and fatty tissue

-excision has been mainstay of treatment-excision has been mainstay of treatment -Q-switched ruby laser has been reported to be -Q-switched ruby laser has been reported to be

successfulsuccessful - treatment of the malignant variety is the same as MM- treatment of the malignant variety is the same as MM