Developmental defects, Nevi & benign Developmental defects, Nevi & benign epithelial tumorsepithelial tumors

Dr Mesfin Hunegnaw,Dr Mesfin Hunegnaw,

Consultant dermatologist and Consultant dermatologist and venerologist, AAU, Medical venerologist, AAU, Medical faculty, Dept. of faculty, Dept. of DermatovenerologyDermatovenerology

Developmental defects are errors in morphogenesis. Developmental defects are errors in morphogenesis. They largely arise during intrauterine life; most are They largely arise during intrauterine life; most are

congenital, i.e. present at birth. congenital, i.e. present at birth. The term embraces malformations, deformations and The term embraces malformations, deformations and

disruptions. disruptions.

1-Malformations1-Malformations:: are primary anatomical defects are primary anatomical defects that occur during the development of an organ or that occur during the development of an organ or tissue.tissue.

Such malformations are most commonly single, or Such malformations are most commonly single, or isolated, usually occurring in normal children, or isolated, usually occurring in normal children, or multiple, affecting several body systems. multiple, affecting several body systems.

When multiple malformations occur in a recognizable When multiple malformations occur in a recognizable pattern, they constitute a pattern, they constitute a multiple malformation multiple malformation syndromesyndrome, and are the frequently accompanied by , and are the frequently accompanied by mental retardation. mental retardation.

2-Deformations2-Deformations reflect abnormal moulding of the reflect abnormal moulding of the growing fetus by intrauterine mechanical forces.growing fetus by intrauterine mechanical forces.

Deformations are most commonly musculoskeletal, Deformations are most commonly musculoskeletal, and generally affect fetuses with neuromuscular and generally affect fetuses with neuromuscular problems. problems.

For example, paralysis in fetuses with spina bifida For example, paralysis in fetuses with spina bifida characteristically results in positional deformation of characteristically results in positional deformation of the legs and feet. the legs and feet.

Oligohydramnios, whatever the cause, may result in a Oligohydramnios, whatever the cause, may result in a characteristic combination of congenital abnormalities, characteristic combination of congenital abnormalities, usually referred to as Potter's syndrome. usually referred to as Potter's syndrome.

3-Disruptions3-Disruptions: : Occur when the fetus is subject to a Occur when the fetus is subject to a destructive intrauterine influence, such as infection, destructive intrauterine influence, such as infection, circulatory compromise or amniotic bands.circulatory compromise or amniotic bands.

There is clearly considerable overlap between these There is clearly considerable overlap between these three categories.three categories.

• A chimeraA chimera is an individual formed from two different is an individual formed from two different zygotes. zygotes.

• Chimeras can result from the fertilization of an ovum Chimeras can result from the fertilization of an ovum containing a polar body by two spermatozoa, or from containing a polar body by two spermatozoa, or from the fusion of dizygotic twin embryos.the fusion of dizygotic twin embryos.

• MosaicismMosaicism is a term that denotes the presence of two is a term that denotes the presence of two or more genetically distinct cell populations in an or more genetically distinct cell populations in an individual derived from a single zygote. individual derived from a single zygote.

• The differences can be between single genes, groups of The differences can be between single genes, groups of genes or entire chromosomes. genes or entire chromosomes.

Mosaicism most commonly appears to arise from post-Mosaicism most commonly appears to arise from post-zygotic chromosomal non-dysjunction during mitosis or zygotic chromosomal non-dysjunction during mitosis or somatic mutation during embryogenesis. somatic mutation during embryogenesis.

A number of patients with cutaneous pigmentary A number of patients with cutaneous pigmentary abnormalities reflecting mosaicism are now being abnormalities reflecting mosaicism are now being reported. reported.

Congenital malformations may be caused by genetic or Congenital malformations may be caused by genetic or environmental factors, or combinations of the two, environmental factors, or combinations of the two, although, in practice, the aetiology is often obscure. although, in practice, the aetiology is often obscure.

Skin lesions that occur in the linear configurations Skin lesions that occur in the linear configurations originally described by Blaschko appear to reflect originally described by Blaschko appear to reflect genetic mosaicism.genetic mosaicism.

Environmental factors provoking congenital Environmental factors provoking congenital malformations (i.e. teratogens) include:-malformations (i.e. teratogens) include:-

Intrauterine infections, Intrauterine infections, Ionizing radiation,Ionizing radiation, Drugs taken during pregnancy: sp. anti-cancer agents…Drugs taken during pregnancy: sp. anti-cancer agents… Alcohol abuse during pregnancy,Alcohol abuse during pregnancy, Trace metal excesses or deficiency during pregnancy, Trace metal excesses or deficiency during pregnancy,

particularly mercury exposure, Zn def.particularly mercury exposure, Zn def. Maternal diseases, such as DM and phenylketonuria.Maternal diseases, such as DM and phenylketonuria.

Classification of benign epithelial tumors based Classification of benign epithelial tumors based on histologyon histology

Classification….Classification….

ClassificationClassification … …

NEVUS:NEVUS: A nevus, or mole, is a benign proliferation of normal A nevus, or mole, is a benign proliferation of normal

skin constituents. skin constituents. Melanocytic nevus is a benign proliferation of Melanocytic nevus is a benign proliferation of

melanocytes or melanocytic nevus cells that appears in melanocytes or melanocytic nevus cells that appears in childhood. childhood.

The number of nevi peaks in early adulthood and The number of nevi peaks in early adulthood and decreases thereafter. decreases thereafter.

Indicate circumscribed lesions of the skin and/or Indicate circumscribed lesions of the skin and/or neighbouring mucosae, which are permanent or at least neighbouring mucosae, which are permanent or at least very long-lasting, & which are not neoplastic.very long-lasting, & which are not neoplastic.

NEVUS…NEVUS… It has been proposed that the definition should include It has been proposed that the definition should include

a requirement that lesions must be caused by genetic a requirement that lesions must be caused by genetic mosaism.mosaism.

Lesions resembling naevi but not fulfilling all the Lesions resembling naevi but not fulfilling all the criteria should be called naevoid.criteria should be called naevoid.

Naevi are classified according to whether they arise Naevi are classified according to whether they arise from epidermal or dermal structures, and from epidermal or dermal structures, and

In the second, according to the presumed organ of In the second, according to the presumed organ of origin or to the predominant cell type. origin or to the predominant cell type.

Classification of naevi Classification of naevi According to Rook)According to Rook)

I-Epidermal naeviI-Epidermal naevi

1- Keratinocyte naevi1- Keratinocyte naevi

Verrucous epidermal naevusVerrucous epidermal naevus

Linear porokeratosisLinear porokeratosis

Inflammatory epidermal naeviInflammatory epidermal naevi

2- Follicular naevi 2- Follicular naevi

Hairy malformation of palms & solesHairy malformation of palms & soles

3- Eccrine naevi3- Eccrine naevi

Eccrine naeviEccrine naevi

Pure eccrine naevusPure eccrine naevus

Eccrine angiomatous hamartomaEccrine angiomatous hamartoma

4- Becekers nevus4- Becekers nevus

II-Dermal and subcutaneous naevi -II-Dermal and subcutaneous naevi - 1- Connective tissue naevi1- Connective tissue naevi

- Collagen nevi: Familial cutaneous collagenoma, TSC…- Collagen nevi: Familial cutaneous collagenoma, TSC… - Elastic naevi- Elastic naevi 2- Smooth-muscle naevi2- Smooth-muscle naevi - Comedo naevus- Comedo naevus - Congenital smooth-muscle hamartoma- Congenital smooth-muscle hamartoma - Linear basal cell naevus- Linear basal cell naevus - Diffuse smooth-muscle hamartoma- Diffuse smooth-muscle hamartoma 3-Vascular naevi3-Vascular naevi - Haemangiomas- Haemangiomas - Verrucus haemangioma- Verrucus haemangioma - Hamartoma- Hamartoma - Vascular (capillary) malformations- Vascular (capillary) malformations - Port wine’s stain- Port wine’s stain 4- Fat nevi4- Fat nevi:: Congenital lipoma, Fibrolipoma…Congenital lipoma, Fibrolipoma…

BENIGN EPITHELIAL TUMORS BENIGN EPITHELIAL TUMORS (Classification according to FITZPATRIK):(Classification according to FITZPATRIK):

1-Seborrheic keratosis1-Seborrheic keratosis• Common seborrheic keratosis,Common seborrheic keratosis,• Reticulated seborrheic keratosis,Reticulated seborrheic keratosis,• Stucco keratosis,Stucco keratosis,• Clonal seborrheic keratosis,Clonal seborrheic keratosis,• Irritated seborrheic keratosis,Irritated seborrheic keratosis,• Seborrheic keratosis with squamous atypia,Seborrheic keratosis with squamous atypia,• Melanoacanthoma (pigmented seborrheic keratosis),Melanoacanthoma (pigmented seborrheic keratosis),• Dermatosis papulosa nigra,Dermatosis papulosa nigra,• Sign of Leser-Trelat,Sign of Leser-Trelat,

2- Epidermal nevi2- Epidermal nevi Linear verrucous epidermal nevusLinear verrucous epidermal nevus

- Localized, - Localized,

- Systematized,- Systematized, Nevus unius lateris, Nevus unius lateris, Ichthyosis hystrix, Ichthyosis hystrix, Inflammatory linear verrucous epidermal nevus (ILVEN), Inflammatory linear verrucous epidermal nevus (ILVEN), Nevus sebaceous of Jadassohn, Nevus sebaceous of Jadassohn, Nevus comedonicus, Nevus comedonicus, Eccrine nevus, Eccrine nevus, Apocrine nevus, Apocrine nevus, Becker's nevus, Becker's nevus, White sponge nevus, White sponge nevus, Epidermal nevus syndrome. Epidermal nevus syndrome.

3- Clear cell acanthoma3- Clear cell acanthoma

4- Warty dyskeratoma4- Warty dyskeratoma

5- Acanthoma fissuratum5- Acanthoma fissuratum

6- Cysts of epithelial origin6- Cysts of epithelial origin

- Epidermoid cyst- Epidermoid cyst - Trichilemmal cyst - Trichilemmal cyst - Milium - Milium - Steatocystoma multiplex - Steatocystoma multiplex - Dermoid cyst - Dermoid cyst - Branchial cyst - Branchial cyst - Preauricular cyst and sinus - Preauricular cyst and sinus

Nevi…Nevi…

I-Epidermal NevusI-Epidermal Nevus Epidermal nevus is a developmental (hamartomatous) Epidermal nevus is a developmental (hamartomatous)

disorder xcd by hyperplasia of epidermal structures disorder xcd by hyperplasia of epidermal structures (surface epidermis and adnexal structures) in a (surface epidermis and adnexal structures) in a circumscribed area of the skin. circumscribed area of the skin.

The term nevus is used here to denote a The term nevus is used here to denote a developmental defect; developmental defect;

There is no proliferation of nevocellular nevus cells There is no proliferation of nevocellular nevus cells (melanocytes) in the lesion.(melanocytes) in the lesion.

Epidemiology:Epidemiology: The incidence:1 per 1000 live births.The incidence:1 per 1000 live births. The majority occur sporadically; familial cases have been The majority occur sporadically; familial cases have been

described.described. Sex: equal. Sex: equal. Most epidermal nevi are present at birth or infancy, rarely lesions Most epidermal nevi are present at birth or infancy, rarely lesions

appear as late as puberty. appear as late as puberty. Over 80 % of the cases have onset of their epidermal nevi in the Over 80 % of the cases have onset of their epidermal nevi in the

first year of life; first year of life; The remainder develop b/n the ages 1 & 7 years.The remainder develop b/n the ages 1 & 7 years. Late-developing lesions probably represent lesions that have Late-developing lesions probably represent lesions that have

always been present, but new inspection of recent growth resulted always been present, but new inspection of recent growth resulted in their recognition. in their recognition.

Everyone has at least one nevus. Everyone has at least one nevus.

Classification of Epidermal NeviClassification of Epidermal Nevi

Classification…Classification…

Verrucus epidermal Verrucus epidermal nevus:nevus:

- Localized,- Localized,

-Systematized,-Systematized, Nevus unis lateralis,Nevus unis lateralis, Ichthyosis hysterix,Ichthyosis hysterix, ILVEN.ILVEN.

Nevus sebaceus,Nevus sebaceus, Eccrine nevus,Eccrine nevus, Apocrine nevus,Apocrine nevus, Nevus comedonicus,Nevus comedonicus, Becker's nevus,Becker's nevus, Spongiform nevusSpongiform nevus

1.1-Verrucous Epidermal Nevus1.1-Verrucous Epidermal NevusSynonyms:linear verrucous epidermal nevus, linear epidermal nevus.Synonyms:linear verrucous epidermal nevus, linear epidermal nevus.

Clinical featuresClinical features The lesion consists of closely set verrucous papules that may The lesion consists of closely set verrucous papules that may

coalesce to form well-demarcated papillomatous plaques. coalesce to form well-demarcated papillomatous plaques. It may be skin-colored, brown, or gray-brown. It may be skin-colored, brown, or gray-brown. A linear configuration is common, sp. limb lesions. A linear configuration is common, sp. limb lesions. Such lesions may appear to follow skin tension lines, or Blaschko's Such lesions may appear to follow skin tension lines, or Blaschko's

lines.lines. Verrucous epidermal nevi may be localized or diffuse. Verrucous epidermal nevi may be localized or diffuse.

An epidermal nevus with diffuse or extensive An epidermal nevus with diffuse or extensive distribution is called distribution is called systematized epidermal nevus.systematized epidermal nevus.

When the lesions are distributed on one-half of the When the lesions are distributed on one-half of the body, it is termed body, it is termed nevus unius laterisnevus unius lateris..

Ichthyosis hystrixIchthyosis hystrix refers to an epidermal nevus refers to an epidermal nevus with extensive bilateral distributionwith extensive bilateral distribution. .

In these systematized nevi, the lesions on the limbs are In these systematized nevi, the lesions on the limbs are usually linear in configuration,usually linear in configuration,

Those on trunk tend to form wavy, transverse bands.Those on trunk tend to form wavy, transverse bands.

Inflammatory linear verrucous epidermal Inflammatory linear verrucous epidermal nevusnevus ( (ILVENILVEN), ), is an inflammatory variant of is an inflammatory variant of epidermal nevus. epidermal nevus.

The lesion is pruritic and clinically shows The lesion is pruritic and clinically shows erythema, scaling, and crusting.erythema, scaling, and crusting.

ILVENILVEN

Extensive epidermal nevusExtensive epidermal nevus

Epidermal nevusEpidermal nevus

LVENLVEN

Epidermal nevusEpidermal nevus

Epidermal nevusEpidermal nevus

Epidermal nevusEpidermal nevus

Epidermal nevusEpidermal nevus

NB: Linear psoriasisNB: Linear psoriasis

Linear LPLinear LP

Course and complicationsCourse and complications A verrucous epidermal nevus may enlarge slowly during childhood. A verrucous epidermal nevus may enlarge slowly during childhood. By adolescence, the lesion usually reaches a stable size and By adolescence, the lesion usually reaches a stable size and

further extension is unlikely. further extension is unlikely. In Rogers' series of 131 cases, only 16 % of the epidermal nevi In Rogers' series of 131 cases, only 16 % of the epidermal nevi

present at birth showed extension, compared with 65 % of lesions present at birth showed extension, compared with 65 % of lesions of later onset; extension rarely lasts for more than 2 years. of later onset; extension rarely lasts for more than 2 years.

Epidermal nevus, especially if extensive, may be associated with Epidermal nevus, especially if extensive, may be associated with developmental abnormalities in other systems developmental abnormalities in other systems (“Epidermal (“Epidermal Nevus Syndrome”). Nevus Syndrome”).

Course…Course…

Rarely, BCC & SCC have been reported to develop in a Rarely, BCC & SCC have been reported to develop in a verrucous epidermal nevus; verrucous epidermal nevus;

This malignant transformation should be suspected This malignant transformation should be suspected when sudden localized growth, nodules, or ulcers when sudden localized growth, nodules, or ulcers appear. appear.

Epidermal nevi in intertriginous areas may become Epidermal nevi in intertriginous areas may become macerated and secondarily infected.macerated and secondarily infected.

PathologyPathology There is hyperkeratosis, acanthosis, & papillomatosis. There is hyperkeratosis, acanthosis, & papillomatosis. The rete ridges are elongated. The histologic picture is essentially The rete ridges are elongated. The histologic picture is essentially

that of a benign papilloma. that of a benign papilloma. Epidermolytic hyperkeratosis may be seen. Epidermolytic hyperkeratosis may be seen.

This is characterized by compact hyperkeratosis, vacuolization of This is characterized by compact hyperkeratosis, vacuolization of the upper and middle prickle cell layer, and large keratohyaline the upper and middle prickle cell layer, and large keratohyaline granules within or outside the cells. granules within or outside the cells.

Epidermolytic hyperkeratosis is most frequently seen in ichthyosis Epidermolytic hyperkeratosis is most frequently seen in ichthyosis hystrix but may also be found in localized epidermal nevi. hystrix but may also be found in localized epidermal nevi.

The ILVEN lesion shows a dermal chronic inflammatory infiltrate in The ILVEN lesion shows a dermal chronic inflammatory infiltrate in the dermis in addition to above findings. the dermis in addition to above findings.

Furthermore, the characteristic feature of alternatingFurthermore, the characteristic feature of alternatingareas of hyperkeratosis with a thickened granular layer and areas of hyperkeratosis with a thickened granular layer and parakeratosis without a granular area may be present.parakeratosis without a granular area may be present.

Differential diagnosis:Differential diagnosis:

Verrucous epidermal nevi should be differentiated from Verrucous epidermal nevi should be differentiated from other linear hyperkeratotic or verrucous lesions: other linear hyperkeratotic or verrucous lesions:

Incontinentia pigmenti (verrucous stage),Incontinentia pigmenti (verrucous stage), Lichen striatus, Lichen striatus, Linear porokeratosis, Linear porokeratosis, Linear lichen planus,and Linear lichen planus,and Linear psoriasis. Linear psoriasis.

The latter two conditions are considered by some The latter two conditions are considered by some authors as lichenoid & psoriasiform variants of authors as lichenoid & psoriasiform variants of linear epidermal nevus. linear epidermal nevus.

Linear porokeratosis is distinguished by its Linear porokeratosis is distinguished by its pathognomonic cornoid lamellae. pathognomonic cornoid lamellae.

The history of an antecedent vesicular stage and the The history of an antecedent vesicular stage and the transient nature of the linear verrucous lesions of transient nature of the linear verrucous lesions of incontinentia pigmenti allow differentiation of this incontinentia pigmenti allow differentiation of this condition from an epidermal nevus;condition from an epidermal nevus;

Histologically, incontinentia pigmenti shows Histologically, incontinentia pigmenti shows eosinophilic exocytosis, dyskeratosis, basal layer eosinophilic exocytosis, dyskeratosis, basal layer vacuolization, and pigment incontinence that are vacuolization, and pigment incontinence that are absent in an epidermal nevus.absent in an epidermal nevus.

Lichen striatus may be difficult to exclude clinically and Lichen striatus may be difficult to exclude clinically and histologically fromhistologically from ILVEN ILVEN. .

Their differentiation is important from a prognostic Their differentiation is important from a prognostic point of view as lichen striatus is self-limited, whereas point of view as lichen striatus is self-limited, whereas ILVEN persist indefinitely. ILVEN persist indefinitely.

Clinically, lichen striatus is asymptomatic, whereas Clinically, lichen striatus is asymptomatic, whereas ILVEN is usually pruritic;ILVEN is usually pruritic;

Histologically,lichen striatus shows little or no Histologically,lichen striatus shows little or no acanthosis & may have lichenoid inflammatory acanthosis & may have lichenoid inflammatory infiltrateinfiltrate..

TreatmentTreatment Excision is the most reliable treatment.Excision is the most reliable treatment. However, this may not be practical or advisable if the epidermal However, this may not be practical or advisable if the epidermal

nevus is very extensive or at sites not amenable to simple surgery. nevus is very extensive or at sites not amenable to simple surgery. The excision should extend to the deep dermis; otherwise the The excision should extend to the deep dermis; otherwise the

lesion may recur.lesion may recur. Alternative treatments include: Alternative treatments include: laser, Cryotherapy, laser, Cryotherapy,

electrofulguration, dermabrasion, or chemical peels with electrofulguration, dermabrasion, or chemical peels with trichloroacetic acid or phenol. trichloroacetic acid or phenol.

These treatment modalities usually remove only the superficial These treatment modalities usually remove only the superficial portion of the nevus and recurrence is common.portion of the nevus and recurrence is common.

Topical treatment include:Topical treatment include:podophyllin,retinoic acid,anthralin,alpha-hydroxy acids podophyllin,retinoic acid,anthralin,alpha-hydroxy acids and is relatively ineffective.and is relatively ineffective.

Systemic retinoids can produce a partial but usually Systemic retinoids can produce a partial but usually temporary response in some patients with extensive temporary response in some patients with extensive disease. disease.

Since epidermal nevus is associated with a small risk of Since epidermal nevus is associated with a small risk of malignancy, suspect areas of any lesion should be malignancy, suspect areas of any lesion should be biopsied. biopsied.

If malignancy is confirmed, the entire lesion should be If malignancy is confirmed, the entire lesion should be excised if possible.excised if possible.

1.2-1.2-Nevus SebaceousNevus SebaceousSynonym:Synonym: nevus sebaceous of Jadassohn. nevus sebaceous of Jadassohn.

Clinical featuresClinical features This usually presents as a solitary lesion at birth or in This usually presents as a solitary lesion at birth or in

early childhood.early childhood. There is a predilection for the scalp, where it manifests There is a predilection for the scalp, where it manifests

as a patch or slightly elevated yellowish plaque with as a patch or slightly elevated yellowish plaque with alopecia.alopecia.

Less commonly, nevus sebaceous may be found on the Less commonly, nevus sebaceous may be found on the face, neck, or trunk. face, neck, or trunk.

Nevus sebaceous occurring exclusively in the oral Nevus sebaceous occurring exclusively in the oral cavity has also been reported.cavity has also been reported.

The well-developed lesion with its characteristic yellow The well-developed lesion with its characteristic yellow or yellow-brown color, linear configuration, and or yellow-brown color, linear configuration, and verrucous surface is quite distinctive.verrucous surface is quite distinctive.

However, in early childhood, the lesion may be flat and However, in early childhood, the lesion may be flat and inconspicuous; the characteristic appearance may not inconspicuous; the characteristic appearance may not develop until puberty. develop until puberty.

Nevus sebaceous occurs sporadically; familial nevus Nevus sebaceous occurs sporadically; familial nevus sebaceous has been described but is exceedingly rare.sebaceous has been described but is exceedingly rare.

Course and complicationsCourse and complications Nevus sebaceous appears to be under some hormonal Nevus sebaceous appears to be under some hormonal

control.control. The lesion can be raised at birth, flatten in childhood, The lesion can be raised at birth, flatten in childhood,

and become raised again during puberty. and become raised again during puberty. Further extension after puberty is uncommon. Further extension after puberty is uncommon. Systemic abnormalities may occur in association with a Systemic abnormalities may occur in association with a

nevus sebaceous (“Epidermal Nevus Syndrome,”). nevus sebaceous (“Epidermal Nevus Syndrome,”). This is more common in patients with multiple or This is more common in patients with multiple or

extensive lesions. extensive lesions. Another significant complication is the development of Another significant complication is the development of

secondary tumors that may be benign or malignant.secondary tumors that may be benign or malignant.

It is believed that nevus sebaceous arises from It is believed that nevus sebaceous arises from pleuripotential primary epithelial germ cells and that pleuripotential primary epithelial germ cells and that these cells have the capacity to dedifferentiate into these cells have the capacity to dedifferentiate into various epithelial tumors, of which the most frequent various epithelial tumors, of which the most frequent are syringocystadenoma papilliferum (8 to 19 %) and are syringocystadenoma papilliferum (8 to 19 %) and BCC (5 to 7 %).BCC (5 to 7 %).

Less common associations include sebaceous Less common associations include sebaceous epithelioma, hidradenoma, syringoma, chondroid epithelioma, hidradenoma, syringoma, chondroid syringoma, trichilemmoma, desmoplastic syringoma, trichilemmoma, desmoplastic trichilemmoma, proliferating trichilemmal tumor, and trichilemmoma, proliferating trichilemmal tumor, and metaplastic synovial cysts.metaplastic synovial cysts.

The development of squamous cell carcinoma, apocrine The development of squamous cell carcinoma, apocrine carcinoma, and malignant eccrine poroma has been carcinoma, and malignant eccrine poroma has been reported but is rare.reported but is rare.

Syringocystadenoma papilliferumSyringocystadenoma papilliferum

PathologyPathologyThe epidermis shows papillomatous hyperplasia. In the The epidermis shows papillomatous hyperplasia. In the

dermis, there are increased numbers of mature dermis, there are increased numbers of mature sebaceous glands.sebaceous glands.

Apocrine glands are often found in the deep dermis.Apocrine glands are often found in the deep dermis. Frequently, small hair follicles and buds of basaloid cells Frequently, small hair follicles and buds of basaloid cells

that may represent malformed hair germs are present.that may represent malformed hair germs are present.In childhood, the sebaceous glands in nevus sebaceous In childhood, the sebaceous glands in nevus sebaceous

areareunderdeveloped and the histologic finding may consist underdeveloped and the histologic finding may consist of only immature hair structures.of only immature hair structures.

Differential diagnosisDifferential diagnosis In a well-developed lesion, nevus sebaceous is easy to In a well-developed lesion, nevus sebaceous is easy to

diagnose and should not be confused with other diagnose and should not be confused with other conditions. conditions.

Although some authors make a distinction between an Although some authors make a distinction between an epidermal nevus with a predominant sebaceous epidermal nevus with a predominant sebaceous component and a nevus sebaceous, this may well be a component and a nevus sebaceous, this may well be a matter of semantics. matter of semantics.

In childhood, when the lesion may not be well In childhood, when the lesion may not be well developed, the differential diagnosis should include developed, the differential diagnosis should include other congenital causes of localized alopecia, such as other congenital causes of localized alopecia, such as aplasia cutis and congenital triangular alopecia.aplasia cutis and congenital triangular alopecia.

TreatmentTreatment Surgical excision of a nevus sebaceous is Surgical excision of a nevus sebaceous is

recommended because of the high potential for recommended because of the high potential for development of basal cell carcinoma and other tumors.development of basal cell carcinoma and other tumors.

The lesion should preferably be excised before puberty The lesion should preferably be excised before puberty because it may enlarge and the risk of malignancy because it may enlarge and the risk of malignancy increases after puberty.increases after puberty.

1.3-Nevus comedonicus1.3-Nevus comedonicus

1.4-Becker's Nevus1.4-Becker's NevusSyn.:Syn.:Becker's pigmented hairy nevus,Becker's melanosis.Becker's pigmented hairy nevus,Becker's melanosis.

First described by Becker in 1949, this lesion is fairly First described by Becker in 1949, this lesion is fairly common and is found in all races. common and is found in all races.

Becker's… Becker's…

Clinical features:Clinical features: It appears to be more common in men. It appears to be more common in men. Prevalence of 0.52 % in men.Prevalence of 0.52 % in men. The lesion may be present at birth or may develop in The lesion may be present at birth or may develop in

early childhood, but the majority of cases are first early childhood, but the majority of cases are first noticed shortly before, at, or after puberty.noticed shortly before, at, or after puberty.

Familial cases have been described.Familial cases have been described.

Becker's nevus is sharply demarcated hyperpigmented Becker's nevus is sharply demarcated hyperpigmented patch that is characteristically situated over the patch that is characteristically situated over the shoulder, anterior chest, or scapula.shoulder, anterior chest, or scapula.

Typically, coarse dark hairs are seen within the lesion, Typically, coarse dark hairs are seen within the lesion, but this may not be evident in early lesions or in fair-but this may not be evident in early lesions or in fair-complexioned individuals. complexioned individuals.

Sometimes, the skin texture may be slightly thickened.Sometimes, the skin texture may be slightly thickened.

Occasionally, Becker's nevus may appear onOccasionally, Becker's nevus may appear on atypical atypical sitessites such as the face, arms, low back & legs. such as the face, arms, low back & legs.

The patch enlarges slowly and in an irregular fashion to The patch enlarges slowly and in an irregular fashion to give a geographic configuration; the ultimate size give a geographic configuration; the ultimate size ranges from a few to the usual 10-20 cm in diameter. ranges from a few to the usual 10-20 cm in diameter.

The hyperpigmentation may vary from light brown to The hyperpigmentation may vary from light brown to dark brown. dark brown.

Several months to years after the appearance of pigmentation, Several months to years after the appearance of pigmentation, thick brown-to-black hairs develop both within and in close thick brown-to-black hairs develop both within and in close proximity to the patch.proximity to the patch.

Hair density is highly variable and Hair density is highly variable and occasionally, occasionally, hypertrichosis does not occur.hypertrichosis does not occur.

The central area in the patch may thicken, and acne vulgaris The central area in the patch may thicken, and acne vulgaris may develop.may develop.

Once present, the patch remains indefinitely, although minimal Once present, the patch remains indefinitely, although minimal pigmentary fading may occur in adulthood.pigmentary fading may occur in adulthood.

Pathophysiology: Pathophysiology: • The pathogenesis of Becker nevus remains uncertain. The pathogenesis of Becker nevus remains uncertain. • Androgens may play a role as evidenced by:Androgens may play a role as evidenced by:

- Peripubertal development, - Peripubertal development,

- Male preponderance, - Male preponderance,

- Hypertrichosis, - Hypertrichosis,

- Occasional development of acneform lesions within the patch - Occasional development of acneform lesions within the patch

- Rare association with accessory scrotum in genital region. - Rare association with accessory scrotum in genital region. • In addition, a significant increase in the number of androgen In addition, a significant increase in the number of androgen

receptors in lesional skin has been reported. receptors in lesional skin has been reported.

Course and complicationsCourse and complications A Becker's nevus may enlarge slowly for a year or two A Becker's nevus may enlarge slowly for a year or two

after presentation.after presentation. It then stabilizes and appears to persist indefinitely, It then stabilizes and appears to persist indefinitely,

although there may be some fading of the lesion in late although there may be some fading of the lesion in late adulthood. adulthood.

It is usually asymptomatic. It is usually asymptomatic. A benign asymptomatic smooth muscle hamartoma A benign asymptomatic smooth muscle hamartoma

may underlie a Becker's nevus.may underlie a Becker's nevus.

Rarely, Becker's nevus may be associated Rarely, Becker's nevus may be associated with hypoplasia of underlying structures, with hypoplasia of underlying structures, e.g., hypoplasia of the breast or e.g., hypoplasia of the breast or shortening of the arm.shortening of the arm.

Other associations seen with Becker nevus include:Other associations seen with Becker nevus include: Unilateral or ipsilateral pectoralis major aplasia, Unilateral or ipsilateral pectoralis major aplasia, Ipsilateral limb shortening, Ipsilateral limb shortening, Ipsilateral foot enlargement, Ipsilateral foot enlargement, Spina bifida, Spina bifida, Scoliosis, Scoliosis, Pectus carinatum, Pectus carinatum, Localized lipoatrophy, Localized lipoatrophy, Congenital adrenal hyperplasia, Congenital adrenal hyperplasia, Polythelia, and Polythelia, and Accessory scrotum.Accessory scrotum.

Becker nevus is considered a benign process; however, an Becker nevus is considered a benign process; however, an association with melanoma was discussed in a series of 9 association with melanoma was discussed in a series of 9 patients in whom both Becker nevus and melanoma developed. patients in whom both Becker nevus and melanoma developed.

In this series, 5 patients developed melanoma on the same In this series, 5 patients developed melanoma on the same body site as the Becker nevus, but in 1 patient only did body site as the Becker nevus, but in 1 patient only did melanoma develop within the Becker nevus.melanoma develop within the Becker nevus.

PathologyPathology The epidermis shows slight acanthosis and papillomatosis. The epidermis shows slight acanthosis and papillomatosis. There is hyperpigmentation of the basal layer. There is hyperpigmentation of the basal layer. The number of melanocytes is usually normal or only slightly The number of melanocytes is usually normal or only slightly

increased. increased. The hair follicles appear normal. The hair follicles appear normal. There is variable increase in dermal smooth muscle fibers. There is variable increase in dermal smooth muscle fibers. Ultrastructural studies reveal an increased number of Ultrastructural studies reveal an increased number of

melanosomes in the melanocytes and increased number and size melanosomes in the melanocytes and increased number and size of melanosome complexes in the keratinocytes.of melanosome complexes in the keratinocytes.

There is an increased expression of testosterone receptors, and There is an increased expression of testosterone receptors, and this hormonal feature may account for the expression of the lesion this hormonal feature may account for the expression of the lesion around puberty.around puberty.

Differential diagnosisDifferential diagnosis A congenital Becker's nevus may be confused with a A congenital Becker's nevus may be confused with a

congenital nevocellular nevus. congenital nevocellular nevus. The latter is usually raised, more corrugated, and may The latter is usually raised, more corrugated, and may

show variegation of pigment. show variegation of pigment. Histologically, there is no difficulty differentiating the Histologically, there is no difficulty differentiating the

two conditions, as Becker's nevus does not have two conditions, as Becker's nevus does not have nevocellular nevus cells.nevocellular nevus cells.

TreatmentTreatment Because a Becker's nevus does not have any malignant Because a Becker's nevus does not have any malignant

potential, excision is usually not practical or advisable. potential, excision is usually not practical or advisable. The skin hyperpigmentation may respond to therapy The skin hyperpigmentation may respond to therapy

with a pigmented lesion laser with a pigmented lesion laser

(e.g.,Q-switched ruby laser), but the results are (e.g.,Q-switched ruby laser), but the results are unpredictable and recurrences common.unpredictable and recurrences common.

Nevus SpilusNevus Spilus Nevus spilus is a congenital, isolated benign lesion Nevus spilus is a congenital, isolated benign lesion

characterized by a CALM sprinkled with flat melanotic characterized by a CALM sprinkled with flat melanotic macules or with pigmented papules. macules or with pigmented papules.

The clustering of 1- to 2-mm pigmented lesions is The clustering of 1- to 2-mm pigmented lesions is usually apparent, but a Wood's lamp may be required usually apparent, but a Wood's lamp may be required to identify the underlying CALM.to identify the underlying CALM.

Histologic studies of the background CALM show a Histologic studies of the background CALM show a slight increase in the number of dopa-positive slight increase in the number of dopa-positive melanocytes and epidermal hyperplasia. melanocytes and epidermal hyperplasia.

The darkly pigmented macules and papules are The darkly pigmented macules and papules are junctional or compound nevi.junctional or compound nevi.

MMG have been described in this entity.MMG have been described in this entity.

The relationship of nevus spilus to NF is unresolved. The relationship of nevus spilus to NF is unresolved. Nevus spilus may be observed in patients with multiple Nevus spilus may be observed in patients with multiple

neurofibromas. neurofibromas. Melanoma has been seen in fewer than a dozen cases Melanoma has been seen in fewer than a dozen cases

of nevus spilus.of nevus spilus.

Seborrheic KeratosisSeborrheic Keratosis Synonyms: senile wart, senile keratosis, seborrheic Synonyms: senile wart, senile keratosis, seborrheic

verruca, verruca seborrhica, basal cell papilloma.verruca, verruca seborrhica, basal cell papilloma. Seborrheic keratoses are benign skin tumors.Seborrheic keratoses are benign skin tumors.

Classification of benign epithelial tumorsClassification of benign epithelial tumors

They are very common & most people will develop at They are very common & most people will develop at least one such tumor in their lifetime, with many least one such tumor in their lifetime, with many developing hundreds of these lesions.developing hundreds of these lesions.

Seborrheic keratoses are most commonly found in the Seborrheic keratoses are most commonly found in the over-30 age group.over-30 age group.

These lesions can appear on any part of the body These lesions can appear on any part of the body except the mucous membranes.except the mucous membranes.

When they occur on the trunk & are multiple, When they occur on the trunk & are multiple, seborrheic keratoses can be seen in a “Christmas seborrheic keratoses can be seen in a “Christmas tree” pattern, lying with their long axes along tree” pattern, lying with their long axes along

skin folds, or Blaschko's linesskin folds, or Blaschko's lines..

Seborrheic keratoses typically begin as flat, sharply Seborrheic keratoses typically begin as flat, sharply demarcated, brown macules. demarcated, brown macules.

As they progress, they become polypoidal,with uneven As they progress, they become polypoidal,with uneven surface. surface.

The surface usually shows “warty” topography with The surface usually shows “warty” topography with multiple plugged follicles and fronds and is usually dull multiple plugged follicles and fronds and is usually dull or lack luster.or lack luster.

Follicular prominence is one of the hallmarks of Follicular prominence is one of the hallmarks of seborrheic keratosesseborrheic keratoses. .

This can be due either to pale follicular plugs within a This can be due either to pale follicular plugs within a darker lesion or to black or brown plugs within a pale darker lesion or to black or brown plugs within a pale lesion. lesion.

Seborrheic keratoses typically have a “stuck-on” Seborrheic keratoses typically have a “stuck-on” appearance secondary to their somewhat polypoidal appearance secondary to their somewhat polypoidal morphology. morphology.

Colors of these lesions can vary from a pale brown with Colors of these lesions can vary from a pale brown with pink tones to dark brown or black. pink tones to dark brown or black.

Some seborrheic keratoses can be almost whiteSome seborrheic keratoses can be almost white..

A clinical variant of the typical seborrheic A clinical variant of the typical seborrheic keratosis described is a variant of small keratosis described is a variant of small polypoidal lesions commonly called “skin tags.”polypoidal lesions commonly called “skin tags.”

Distinct from smooth skin tags, these small, furrowed, Distinct from smooth skin tags, these small, furrowed, rough-surfaced polyps appear most commonly around rough-surfaced polyps appear most commonly around the neck, under the breast, or in the axillae. the neck, under the breast, or in the axillae.

They seem to have a predilection for points of They seem to have a predilection for points of chronic traumachronic trauma. .

They show a surface morphology similar to that of the They show a surface morphology similar to that of the classic seborrheic keratosis, but their diameter is classic seborrheic keratosis, but their diameter is frequently only 1 to 2 mm, with a height above the skin frequently only 1 to 2 mm, with a height above the skin of sometimes more than 3 mm. of sometimes more than 3 mm.

These lesions may disappear spontaneously by These lesions may disappear spontaneously by dropping off.dropping off.

Lesions around the neck can catch on clothing, as can Lesions around the neck can catch on clothing, as can lesions around the waist. lesions around the waist.

Others can grow to become cosmetically undesirable. Others can grow to become cosmetically undesirable. Many can cause concern to the patient because of Many can cause concern to the patient because of

confusion with nevi and the thought that the lesion is confusion with nevi and the thought that the lesion is becoming a malignant melanoma. becoming a malignant melanoma.

Conversely, dysplastic nevi or malignant melanomas Conversely, dysplastic nevi or malignant melanomas can lurk in a forest of seborrheic keratoses and be can lurk in a forest of seborrheic keratoses and be undetected till a late stage,posing significant danger.undetected till a late stage,posing significant danger.

EtiologyEtiology The etiology of seborrheic keratoses is not known. The etiology of seborrheic keratoses is not known. In patients with a great number of lesions, it is In patients with a great number of lesions, it is

sometimes noted that there is a family history. sometimes noted that there is a family history. This may well reflect a genetic propensity.This may well reflect a genetic propensity. Are blamed, usually by the patient, to sun exposure. Are blamed, usually by the patient, to sun exposure. There is little to support this other than a propensity for There is little to support this other than a propensity for

the large type of seborrheic keratoses to develop in the large type of seborrheic keratoses to develop in areas of intermittent sun exposure, such as the back areas of intermittent sun exposure, such as the back and anterior chest.and anterior chest.

There does not seem to be a relationship with There does not seem to be a relationship with skin type or with areas of sun exposure.skin type or with areas of sun exposure.

B/c of the verrucous appearance of, HPV is suggested B/c of the verrucous appearance of, HPV is suggested as a possible cause,but despite repeated searches,viral as a possible cause,but despite repeated searches,viral involvement has not been confirmed. involvement has not been confirmed.

Epidermal growth factorsEpidermal growth factors have been implicated in have been implicated in the development of seborrheic keratoses. the development of seborrheic keratoses.

Melanocytic hyperplasia is commonly seen in Melanocytic hyperplasia is commonly seen in seborrheic keratoses. seborrheic keratoses.

It has been suggested that It has been suggested that melanocytes or melanocytes or melanocyte-derived growth factorsmelanocyte-derived growth factors may have a may have a role in the dvt of seborrheic keratoses.role in the dvt of seborrheic keratoses.

However,causal relationship has not been determined.However,causal relationship has not been determined.

The eruptive appearance of multiple seborrheicThe eruptive appearance of multiple seborrheickeratoses (keratoses (the sign of Leser-Trelatthe sign of Leser-Trelat)) in association in association with various internal malignancies and with with various internal malignancies and with concomitant ANconcomitant AN, suggests the possibility that:, suggests the possibility that:

A A tumor-derived circulating growth factortumor-derived circulating growth factor may be may be involved in the pathogenesis of these lesions. involved in the pathogenesis of these lesions.

Such factor has not yet been identified with certainty, Such factor has not yet been identified with certainty, although although transforming growth factortransforming growth factor has been has been implicated.implicated.

Clinicopathologic Variants:Clinicopathologic Variants:1-Common Seborrheic Keratosis1-Common Seborrheic KeratosisSynonyms: basal cell papilloma, solid seborrheic keratosis.Synonyms: basal cell papilloma, solid seborrheic keratosis. This is considered the classic lesion. This is considered the classic lesion. The configuration is mushroom-like with sharply The configuration is mushroom-like with sharply

demarcated hyperplastic epidermis overhanging the demarcated hyperplastic epidermis overhanging the surrounding skin. surrounding skin.

The tumor consists of uniform basaloid cells. The tumor consists of uniform basaloid cells.

Keratin cysts are often prominent and may be follicular Keratin cysts are often prominent and may be follicular or extrafollicular. or extrafollicular.

Melanocytes are often present in considerable numbers Melanocytes are often present in considerable numbers and their pigment production results in the color of the and their pigment production results in the color of the darker lesions. darker lesions.

Pigment transfer to the keratinocytes appears to be Pigment transfer to the keratinocytes appears to be normal.normal.

2-Reticulated Seborrheic 2-Reticulated Seborrheic KeratosisKeratosis

Synonym:Synonym: adenoid seborrheic keratosis. adenoid seborrheic keratosis. Thin cords of basaloid cells descend from the base of Thin cords of basaloid cells descend from the base of

the epidermis. the epidermis. Keratin cysts are embraced by these thin strands of Keratin cysts are embraced by these thin strands of

cells. cells. A fine eosinophilic collagen stroma wraps around these A fine eosinophilic collagen stroma wraps around these

cords and can form much of the lesion. cords and can form much of the lesion.

3-Clonal Seborrheic Keratosis3-Clonal Seborrheic Keratosis Nests, usually but not always well defined, of round, Nests, usually but not always well defined, of round,

loosely packed cells are present within the epidermis.loosely packed cells are present within the epidermis. Although the predominant cell is the keratinocyte, the Although the predominant cell is the keratinocyte, the

nests may contain large numbers of melanocytes.nests may contain large numbers of melanocytes. The keratinocytes vary in size.The keratinocytes vary in size.

4-Stucco Keratosis4-Stucco KeratosisSynonyms: hyperkeratotic seborrheic keratosis,acanthotic Synonyms: hyperkeratotic seborrheic keratosis,acanthotic

seborrheic keratosis, verrucous seborrheic keratosis.seborrheic keratosis, verrucous seborrheic keratosis. Stucco keratoses are typically gray-white in color. Stucco keratoses are typically gray-white in color. They tend to be multiple, about 3- to 4-mm, and They tend to be multiple, about 3- to 4-mm, and

located on the legs. located on the legs. Church spire–like projections of the epidermal cells Church spire–like projections of the epidermal cells

around a collagen core thrust upward into a around a collagen core thrust upward into a basketweave type of hyperkeratosis. basketweave type of hyperkeratosis.

The vacuolated keratinocytes seen in verruca vulgaris The vacuolated keratinocytes seen in verruca vulgaris are not seen in this lesion, although clinically it can are not seen in this lesion, although clinically it can resemble a small viral wart.resemble a small viral wart.

5-Irritated Seborrheic Keratosis5-Irritated Seborrheic Keratosis• Synonyms:Synonyms: inflamed seborrheic keratosis, inflamed seborrheic keratosis,

basosquamous cell acanthoma.basosquamous cell acanthoma.• Eczematous changes can occur in and around an Eczematous changes can occur in and around an

otherwise typical seborrheic keratosis. otherwise typical seborrheic keratosis. • The cause of this eczematous reaction is unknown.The cause of this eczematous reaction is unknown.• Trauma may play a role, but in most instances there is Trauma may play a role, but in most instances there is

no apparent antecedent event. no apparent antecedent event. • Histologically, an irritated seborrheic keratosis shows, Histologically, an irritated seborrheic keratosis shows,

apart from inflammatory changes, many whorls or apart from inflammatory changes, many whorls or eddies of eosinophilic flattened squamous cells eddies of eosinophilic flattened squamous cells arranged in onionskin fashion.arranged in onionskin fashion.

These resemble poorly differentiated keratin pearls in These resemble poorly differentiated keratin pearls in squamous cell carcinoma but can be distinguished by squamous cell carcinoma but can be distinguished by their large number, small size, and circumscribed their large number, small size, and circumscribed configuration.configuration.

Keratinocytes within an irritated seborrheic keratosis Keratinocytes within an irritated seborrheic keratosis show a higher degree of keratinization or more show a higher degree of keratinization or more complete maturation as compared with the common complete maturation as compared with the common seborrheic keratosis; the mechanism for this seborrheic keratosis; the mechanism for this phenomenon is unknown.phenomenon is unknown.

6-Seborrheic Keratosis with Squamous Atypia6-Seborrheic Keratosis with Squamous Atypia Cellular atypia and dyskeratosis can be seen in some Cellular atypia and dyskeratosis can be seen in some

seborrheic keratoses.seborrheic keratoses. These lesions can closely mimic Bowen's disease or These lesions can closely mimic Bowen's disease or

invasive squamous cell carcinoma. invasive squamous cell carcinoma. It is not known what causes these changes, whether It is not known what causes these changes, whether

they are due to irritation/activation or whether they are they are due to irritation/activation or whether they are precursors of SCC. precursors of SCC.

It seems prudent to remove these lesions completely.It seems prudent to remove these lesions completely.

7-Melanoacanthoma7-MelanoacanthomaSynonym:Synonym: pigmented seborrheic keratosis. pigmented seborrheic keratosis. Melanoacanthoma is more than a darkly pigmented Melanoacanthoma is more than a darkly pigmented

seborrheic keratosis. seborrheic keratosis. Within the lesion there is striking proliferation of Within the lesion there is striking proliferation of

dendritic melanocytes. dendritic melanocytes. These melanocytes are engorged with melanin, but the These melanocytes are engorged with melanin, but the

surrounding keratinocytes contain hardly any melanin.surrounding keratinocytes contain hardly any melanin. The melanocytes may proliferate as nests. The melanocytes may proliferate as nests. This lesion has no malignant potential.This lesion has no malignant potential.

8-Dermatosis Papulosa Nigra8-Dermatosis Papulosa Nigra These small facial papules, originally described in These small facial papules, originally described in

African Americans but seen in darker-skinned persons African Americans but seen in darker-skinned persons of many other races, of many other races,

Appear to be a variant of seborrheic keratosis. Appear to be a variant of seborrheic keratosis. They resemble tiny melanoacanthomas.They resemble tiny melanoacanthomas.

Skin Cancer AssociationsSkin Cancer Associations• BCC and other common skin cancers have been BCC and other common skin cancers have been

reported, rarely, in association with seborrheic reported, rarely, in association with seborrheic keratoses.keratoses.

• In a study of 4310 tumors clinically diagnosed as In a study of 4310 tumors clinically diagnosed as seborrheic keratoses,60 (1.4 %) proved to be SCSIsitu.seborrheic keratoses,60 (1.4 %) proved to be SCSIsitu.

• In another study of 108 seborrheic keratoses, a 4.6 % In another study of 108 seborrheic keratoses, a 4.6 % incidence of associated SCC was reported.incidence of associated SCC was reported.

• Such lesions may represent a collision phenomenon. Such lesions may represent a collision phenomenon. • Prudence, though, dictates that seborrheic keratoses Prudence, though, dictates that seborrheic keratoses

that have undergone rapid growth or are clinically that have undergone rapid growth or are clinically atypical be biopsied and that lesions demonstrating atypical be biopsied and that lesions demonstrating cellular atypia be completely removed.cellular atypia be completely removed.

The Sign of Leser-TrelatThe Sign of Leser-Trelat Multiple eruptive seborrheic keratoses, also known as Multiple eruptive seborrheic keratoses, also known as

the the sign of Leser- Trelat,sign of Leser- Trelat, have been mentioned in have been mentioned in association with multiple internal malignancies. association with multiple internal malignancies.

The frequent associations are The frequent associations are adenocarcinomas of adenocarcinomas of the stomach, colon, and breast. the stomach, colon, and breast.

This sign has also been reported with a variety of other This sign has also been reported with a variety of other tumors, including lymphomas, leukemias, & melanoma.tumors, including lymphomas, leukemias, & melanoma.

It has also been mentioned in association with It has also been mentioned in association with hyperkeratosis of the palms and soles associated with hyperkeratosis of the palms and soles associated with malignant disease and with acanthosis nigricans.malignant disease and with acanthosis nigricans.

A hallmark of many patients with so-called eruptive A hallmark of many patients with so-called eruptive seborrheic keratoses is a cutaneous eruption that is seborrheic keratoses is a cutaneous eruption that is also inflammatory.also inflammatory.

It may well be that the inflammatory dermatosis is It may well be that the inflammatory dermatosis is centering on skin papillomas and seborrheic keratoses, centering on skin papillomas and seborrheic keratoses, making them suddenly “appear.”making them suddenly “appear.”

It is common clinical experience to see an increase in It is common clinical experience to see an increase in the prominence of seborrheic keratoses in patients with the prominence of seborrheic keratoses in patients with generalized dermatitis from any cause.generalized dermatitis from any cause.

If there is a relationship with cancer, it could be If there is a relationship with cancer, it could be explained via growth factor or hormone effects on explained via growth factor or hormone effects on keratinocytes, perhaps a mechanism similar to that keratinocytes, perhaps a mechanism similar to that involved in the production of acanthosis nigricans.involved in the production of acanthosis nigricans.

The true relationship of multiple eruptive seborrheic The true relationship of multiple eruptive seborrheic keratoses to internal malignant disease remains to be keratoses to internal malignant disease remains to be defined.defined.

TreatmentTreatment• Lesions that are bothering the patient functionally or Lesions that are bothering the patient functionally or

cosmetically can be treated. cosmetically can be treated. • Cryotherapy is the RX of choice for majority of lesions. Cryotherapy is the RX of choice for majority of lesions. • Following cryotherapy, postinflammatory Following cryotherapy, postinflammatory

hypopigmentation or hyperpigmentation may develop. hypopigmentation or hyperpigmentation may develop. • Although usually temporary, these pigmentary changes Although usually temporary, these pigmentary changes

may persist in darker-skinned patients and can be most may persist in darker-skinned patients and can be most disturbing. disturbing.

• Other treatment modalities include electrodesiccation Other treatment modalities include electrodesiccation followed by the removal of the lesion with a curette or followed by the removal of the lesion with a curette or curettage followed by light electrodesiccation. curettage followed by light electrodesiccation.

Laser therapy using a pigmented lesion laser such as Laser therapy using a pigmented lesion laser such as the Q-switched ruby laser is also effective, and when the Q-switched ruby laser is also effective, and when used to treat flat seborrheic keratoses, it may carry a used to treat flat seborrheic keratoses, it may carry a lower risk of post-inflammatory pigmentation or lower risk of post-inflammatory pigmentation or scarring compared with cryotherapy or scarring compared with cryotherapy or electrodesiccation.electrodesiccation.

Surgical excision is also effective but is usually not the Surgical excision is also effective but is usually not the treatment of choice in view of the certainty of scarring.treatment of choice in view of the certainty of scarring.

One of the greatest dangers posed by treating a One of the greatest dangers posed by treating a “seborrheic keratosis” other than by surgical excision “seborrheic keratosis” other than by surgical excision and histologic revision is that the treated lesion could and histologic revision is that the treated lesion could be a dysplastic nevus or a malignant melanoma. be a dysplastic nevus or a malignant melanoma.

It is strongly recommended that if the lesion is not It is strongly recommended that if the lesion is not absolutely typical of seborrheic keratosis, it should be absolutely typical of seborrheic keratosis, it should be submitted for histologic examination.submitted for histologic examination.

Disorders of MelanocytesDisorders of Melanocytes

ACQUIRED MELANOCYTIC NEVOCELLULAR NEVIACQUIRED MELANOCYTIC NEVOCELLULAR NEVI Melanocytic nevocellular nevi are small (<1.0 cm), Melanocytic nevocellular nevi are small (<1.0 cm),

circumscribed, acquired pigmented macules or papules circumscribed, acquired pigmented macules or papules composed of groups of melanocytic nevus cells located composed of groups of melanocytic nevus cells located in the epidermis, dermis, and rarely, subcutaneous in the epidermis, dermis, and rarely, subcutaneous tissue.tissue.

EpidemiologyEpidemiology One of the most common acquired new growths in One of the most common acquired new growths in

Caucasians (most adults have about 20 nevi), less Caucasians (most adults have about 20 nevi), less common in blacks or pigmented peoples.common in blacks or pigmented peoples.

Dysplastic nevi, which are putative precursor lesions of Dysplastic nevi, which are putative precursor lesions of malignant melanoma, occur in 30 % of patients with malignant melanoma, occur in 30 % of patients with primary melanoma and in 6 % of their family members.primary melanoma and in 6 % of their family members.

Risk of melanoma is related to the numbers of nevi.Risk of melanoma is related to the numbers of nevi.

HistoryHistory Duration of Lesions Duration of Lesions These lesions, which are These lesions, which are

commonly called commonly called moles, moles, appear in early childhood and appear in early childhood and reach a maximum in young adulthood. reach a maximum in young adulthood.

There is a gradual involution of lesions, and most There is a gradual involution of lesions, and most disappear by age 60 (the dermal melanocytic disappear by age 60 (the dermal melanocytic nevocellular nevus does not disappear). nevocellular nevus does not disappear).

Dysplastic nevi continue to appear throughout life and Dysplastic nevi continue to appear throughout life and are believed not to involute.are believed not to involute.

Skin Symptoms Skin Symptoms Nevocellular nevi are asymptomatic, and if a lesion Nevocellular nevi are asymptomatic, and if a lesion

persistently itches or is tender, it should be followed persistently itches or is tender, it should be followed carefully or excised, since pruritus, may be an early carefully or excised, since pruritus, may be an early indication of malignant change.indication of malignant change.

Classification:Classification:1-Junctional Melanocytic NCN1-Junctional Melanocytic NCN Cells at the dermal-epidermal junction above the Cells at the dermal-epidermal junction above the

basement membrane. (on the epidermal site of the basement membrane. (on the epidermal site of the basement membrane, they are intraepidermal.)basement membrane, they are intraepidermal.)

2-Compound Melanocytic NCN2-Compound Melanocytic NCN A combination of the A combination of the histologic features of the junctional and dermal. histologic features of the junctional and dermal.

Nevus cells invade the papillary dermis, and nevus cell Nevus cells invade the papillary dermis, and nevus cell nests are found both intraepidermally and dermally.nests are found both intraepidermally and dermally.

3. 3. Dermal melanocytic NCNDermal melanocytic NCN: :

These represent the last stage of the evolution of NCN.These represent the last stage of the evolution of NCN.

Cells exclusively in the dermisCells exclusively in the dermis. .

““Dropping off” (Dropping off” (AbtropfungAbtropfung) into the dermis is now ) into the dermis is now completed, and the nevus grows or rests intradermally. completed, and the nevus grows or rests intradermally.

Evolution:Evolution: Melanocytic NCN develop during childhood and usually Melanocytic NCN develop during childhood and usually

have reached their final number by adolescence, have reached their final number by adolescence, Though some NCN may arise during adulthood (note Though some NCN may arise during adulthood (note

the difference with Clark’s nevi,). the difference with Clark’s nevi,). All NCN undergo a predetermined evolution, which All NCN undergo a predetermined evolution, which

usually results in involution and fibrosis in time.usually results in involution and fibrosis in time. With progressive age, there will be gradual fibrosis.With progressive age, there will be gradual fibrosis.

Since common melanocytic NCN lose their capacity for Since common melanocytic NCN lose their capacity for melanization, the further the nevus cells penetrate into melanization, the further the nevus cells penetrate into the dermis, the lesser is the intensity of pigmentation the dermis, the lesser is the intensity of pigmentation with the increase in the dermal proportion of the nevus. with the increase in the dermal proportion of the nevus.

Purely dermal NCN are therefore almost always Purely dermal NCN are therefore almost always without pigment.without pigment.

I-Junctional Melanocytic Nevocellular I-Junctional Melanocytic Nevocellular NeviNevi

Skin Lesions: Skin Lesions: Macule, or only very slightly raised.Macule, or only very slightly raised. SIZE SIZE If If ..1.0 cm, the mole is a congenital nevomelanocytic 1.0 cm, the mole is a congenital nevomelanocytic

nevus or a dysplastic melanocytic nevus.nevus or a dysplastic melanocytic nevus. COLOR COLOR Uniform tan, brown, or dark brownUniform tan, brown, or dark brown SHAPE SHAPE Round or oval with smooth, regular bordersRound or oval with smooth, regular borders ARRANGEMENT ARRANGEMENT Scattered discrete lesionsScattered discrete lesions DISTRIBUTION: DISTRIBUTION: RandomRandom SITES OF PREDILECTION SITES OF PREDILECTION Trunk, upper extremities, Trunk, upper extremities,

face, lower extremities, occasionally palmar and plantar.face, lower extremities, occasionally palmar and plantar.

Differential DiagnosisDifferential Diagnosis Tan/Brown/Black Macule Tan/Brown/Black Macule Solar lentigo, lentigo Solar lentigo, lentigo

maligna.maligna.

Junctional NMNJunctional NMN

II-Compound Melanocytic Nevocellular NeviII-Compound Melanocytic Nevocellular Nevi

Compound melanocytic nevocellular nevi represent a Compound melanocytic nevocellular nevi represent a combination of junctional and dermal NCN and are combination of junctional and dermal NCN and are usually usually darkly pigmented (junctional component darkly pigmented (junctional component of NCN),elevated, and often papillomatous due to of NCN),elevated, and often papillomatous due to their dermal component.their dermal component.

Skin Lesions: Skin Lesions: Papules or nodules.Papules or nodules. COLOR COLOR Dark brown, sometimes even black; color may Dark brown, sometimes even black; color may

become mottled as progressive conversion into dermal become mottled as progressive conversion into dermal NCN occurs.NCN occurs.

SHAPE SHAPE Round, dome-shaped, smooth, occasionally Round, dome-shaped, smooth, occasionally papillomatous or hyperkeratotic, often associated with papillomatous or hyperkeratotic, often associated with bristle-like terminal hairs.bristle-like terminal hairs.

DISTRIBUTION DISTRIBUTION Face, scalp, trunk, extremities.Face, scalp, trunk, extremities.

Differential DiagnosisDifferential Diagnosis Tan/Brown/Black Papule :Tan/Brown/Black Papule : Seborrheic keratosis, Seborrheic keratosis, Dermatofibroma, Dermatofibroma, Dysplastic nevus,Dysplastic nevus, Spitz nevus, blue nevus, and nodular melanoma must Spitz nevus, blue nevus, and nodular melanoma must

be considered.be considered.

Compound NMNCompound NMN

III-Dermal Melanocytic Nevocellular III-Dermal Melanocytic Nevocellular NeviNevi

Skin Lesions: Skin Lesions: Papule or Nodule,Papule or Nodule, COLOR COLOR Skin-colored, tan, brown, or flecks of brown, Skin-colored, tan, brown, or flecks of brown,

often with telangiectasia.often with telangiectasia. SHAPE SHAPE Round, dome-shaped.Round, dome-shaped. DISTRIBUTION DISTRIBUTION More common on the face and neck More common on the face and neck

but can occur on the trunk or extremitiesbut can occur on the trunk or extremities OTHER FEATURES OTHER FEATURES Usually present in the second or Usually present in the second or

third decade. Older lesions, mostly on the trunk, may third decade. Older lesions, mostly on the trunk, may become papillomatous or pedunculated and do not become papillomatous or pedunculated and do not disappear spontaneously.disappear spontaneously.

Differential Diagnosis:Differential Diagnosis:

Skin-Colored Papule Skin-Colored Papule Basal cell carcinoma, Basal cell carcinoma, Neurofibroma, Neurofibroma, Trichoepithelioma, Trichoepithelioma, Sebaceous hyperplasia, Sebaceous hyperplasia, Dermatofibroma.Dermatofibroma.

HALO NEVOMELANOCYTIC NEVUSHALO NEVOMELANOCYTIC NEVUS This lesion is a nevomelanocytic nevus that is encircled This lesion is a nevomelanocytic nevus that is encircled

by a halo of leukoderma or depigmentation. by a halo of leukoderma or depigmentation. The leukoderma is based on a decrease of melanin in The leukoderma is based on a decrease of melanin in

melanocytes or disappearance of melanocytes at the melanocytes or disappearance of melanocytes at the DEJ. DEJ.

Halo nevi often undergo spontaneous involution and Halo nevi often undergo spontaneous involution and often with regression of the centrally located often with regression of the centrally located pigmented nevus.pigmented nevus.

Synonym: Synonym: Sutton’s leukoderma acquisitum centrifugumSutton’s leukoderma acquisitum centrifugum..

Epidemiology and EtiologyEpidemiology and Etiology Age Age First three decades,First three decades, Race and Sex Race and Sex All races, both sexes,All races, both sexes, Incidence Incidence Occurs in patients with vitiligo, 18 % to 26 Occurs in patients with vitiligo, 18 % to 26

%. May herald vitiligo.%. May herald vitiligo. Family History Family History Halo nevi occur in siblings and with Halo nevi occur in siblings and with

history of vitiligo in family.history of vitiligo in family. Associated Disorders Associated Disorders Vitiligo, metastatic melanoma Vitiligo, metastatic melanoma

(around lesions and around nevus cell nevi).(around lesions and around nevus cell nevi).

HistoryHistory

Three StagesThree Stages1-Development (in months) of halo around preexisting 1-Development (in months) of halo around preexisting

nevus cell nevus. nevus cell nevus.

Halo may be preceded by faint erythema,Halo may be preceded by faint erythema,

2. Disappearance (months to years) of nevus cell nevus2. Disappearance (months to years) of nevus cell nevus

3. Repigmentation (months to years) of halo.3. Repigmentation (months to years) of halo.

Physical Examination:Physical Examination:

Skin Lesions: - Skin Lesions: - Papular brown nevus (5.0mm) with halo, Papular brown nevus (5.0mm) with halo,

- Sharply marginated hypomelanosis. - Sharply marginated hypomelanosis.

- The nevus is centrally located.- The nevus is centrally located.

SHAPE SHAPE Oval or round hypomelanosisOval or round hypomelanosis

ARRANGEMENT ARRANGEMENT Scattered discrete lesions (1- 90),Scattered discrete lesions (1- 90),

DISTRIBUTION DISTRIBUTION Trunk (same as distribution of nevus cell Trunk (same as distribution of nevus cell nevus).nevus).

Differential DiagnosisDifferential Diagnosis ““Halo” Depigmentation around Other Lesions Halo” Depigmentation around Other Lesions Can Can

occur around blue nevus,congenital garment nevus cell occur around blue nevus,congenital garment nevus cell nevus, Spitz’s juvenile nevus, verruca plana, primary nevus, Spitz’s juvenile nevus, verruca plana, primary melanoma, dermatofibroma, and neurofibroma.melanoma, dermatofibroma, and neurofibroma.

DermatopathologyDermatopathology Nevus Cell Nevus Nevus Cell Nevus Junctional dermal or compound nevus Junctional dermal or compound nevus

surrounded by lymphocytic infiltrate (lymphocytes and surrounded by lymphocytic infiltrate (lymphocytes and histiocytes) around and between nevus cells.histiocytes) around and between nevus cells.

Nevus cells develop evidence of cell damage & disappear.Nevus cells develop evidence of cell damage & disappear. Halo (Epidermis) Halo (Epidermis) Decrease or total absence of melanin Decrease or total absence of melanin

and melanocytes (as shown by electron microscopy)and melanocytes (as shown by electron microscopy)

DiagnosisDiagnosis If clinical findings atypical, confirm histologicallyIf clinical findings atypical, confirm histologically

PathophysiologyPathophysiology Immunologic phenomena are responsible for the Immunologic phenomena are responsible for the

dynamic changes through the action of circulating dynamic changes through the action of circulating cytotoxic antibodies and/or cytotoxic lymphocytes.cytotoxic antibodies and/or cytotoxic lymphocytes.

This disease awaits a reevaluation using newer This disease awaits a reevaluation using newer techniques.techniques.

CourseCourse The lesions undergo spontaneous resolution. The lesions undergo spontaneous resolution. Nevus cell nevi within the halo always must be Nevus cell nevi within the halo always must be

evaluated for clinical criteria of malignancy evaluated for clinical criteria of malignancy (variegation of pigment & irregular borders)(variegation of pigment & irregular borders) because a halo can and does occasionally develop because a halo can and does occasionally develop around primary malignant melanoma. around primary malignant melanoma.

ManagementManagement Reassurance.Reassurance. Excision Excision If clinical findings are atypical, diagnosis If clinical findings are atypical, diagnosis

uncertain, lesion should be exciseduncertain, lesion should be excised..

BLUE NEVUS:BLUE NEVUS: A blue nevus is an acquired, benign, firm, dark-blue to A blue nevus is an acquired, benign, firm, dark-blue to

gray-to-black, sharply defined papule or nodule gray-to-black, sharply defined papule or nodule representing a localized proliferation of melanin-representing a localized proliferation of melanin-producing dermal melanocytes.producing dermal melanocytes.

Synonyms: Synonyms: Blue neuronevus, dermal melanocytoma.Blue neuronevus, dermal melanocytoma.

Epidemiology:Epidemiology: Age Age Onset in late adolescence,Onset in late adolescence, Sex Sex Equal distribution,Equal distribution, Variants Variants Cellular blue nevus, combined blue nevus–Cellular blue nevus, combined blue nevus–

nevomelanocytic nevus.nevomelanocytic nevus.

HistoryHistory Nearly always asymptomatic, occasionally of cosmetic Nearly always asymptomatic, occasionally of cosmetic

concern.concern. Appearance gradual and often not observed by patient Appearance gradual and often not observed by patient

or parents.or parents.

Physical ExaminationPhysical ExaminationSkin LesionsSkin Lesions Papules to nodules usually <10.0 mm in Papules to nodules usually <10.0 mm in

diameter.diameter.

COLORCOLOR - - Blue, blue-gray, blue-black. Blue, blue-gray, blue-black.

- Occasionally has target-like pattern of - Occasionally has target-like pattern of pigmentation.pigmentation.

SHAPE SHAPE Usually round to oval.Usually round to oval.

PALPATIONPALPATION Firm.Firm.

SITE:SITE: - - Most common on dorsa of hands or feet;Most common on dorsa of hands or feet;

- May occur at any site.- May occur at any site.

Differential DiagnosisDifferential DiagnosisBlue/Gray Papule: Blue/Gray Papule: Dermatofibroma, Dermatofibroma, Glomus tumor, Glomus tumor, Primary (nodular) or metastatic melanoma, Primary (nodular) or metastatic melanoma, Pigmented spindle cell (Spitz) nevus, Pigmented spindle cell (Spitz) nevus, Traumatic tattoo.Traumatic tattoo.

DermatopathologyDermatopathology Melanin-containing fibroblast-like dermal melanocytes Melanin-containing fibroblast-like dermal melanocytes

grouped in irregular bundles admixed with melanin-grouped in irregular bundles admixed with melanin-containing macrophages; excessive fibrous tissue containing macrophages; excessive fibrous tissue production in upper reticular dermis. Epidermis normal.production in upper reticular dermis. Epidermis normal.

DiagnosisDiagnosis Usually made on clinical findings including Usually made on clinical findings including

epiluminescence microscopy, at times confirmed by epiluminescence microscopy, at times confirmed by excision and dermatopathologic examination to rule out excision and dermatopathologic examination to rule out nodular melanomanodular melanoma

PathogenesisPathogenesis Probably represents ectopic accumulations of melanin-Probably represents ectopic accumulations of melanin-

producing melanocytes in the dermis during their producing melanocytes in the dermis during their migration from neural crest to sites in the skin.migration from neural crest to sites in the skin.

Course and PrognosisCourse and Prognosis Most remain unchanged. Most remain unchanged. Malignant melanoma rarely develops in blue nevi.Malignant melanoma rarely develops in blue nevi.

ManagementManagement Blue nevi smaller than 10.0 mm in diameter and stable Blue nevi smaller than 10.0 mm in diameter and stable

for many years usually do not need excision. for many years usually do not need excision. Sudden appearance or change of an apparent blue Sudden appearance or change of an apparent blue

nevus warrants surgical excision and nevus warrants surgical excision and dermatopathologic examination.dermatopathologic examination.

SPITZ NEVUSSPITZ NEVUS Spitz nevus is a benign, dome-shaped, hairless, Spitz nevus is a benign, dome-shaped, hairless,

small (1.0 cm in diameter) nodule, most often small (1.0 cm in diameter) nodule, most often pink or tan. pink or tan.

About half the patients are children. About half the patients are children. The clinical presentation is distinctive, and there is The clinical presentation is distinctive, and there is

often a history of recent rapid growth. often a history of recent rapid growth. However, the pathology of Spitz nevus is misleading, However, the pathology of Spitz nevus is misleading,

consisting of spindle and epithelioid nevus cells, some consisting of spindle and epithelioid nevus cells, some of which may be atypical.of which may be atypical.

Differentiation from nodular malignant melanoma may Differentiation from nodular malignant melanoma may require an experienced dermatopathologist.require an experienced dermatopathologist.

Synonyms: Synonyms: Spitz tumor, formerly also juvenile melanoma, Spitz tumor, formerly also juvenile melanoma, epithelioid cell–spindle cell nevomelanocytic nevus.epithelioid cell–spindle cell nevomelanocytic nevus.

EpidemiologyEpidemiology Incidence Incidence 1.4 : 100,000 (Australia)1.4 : 100,000 (Australia) Age:Age: Occurs at all ages. Occurs at all ages. A third of the patients are children under 10 years of A third of the patients are children under 10 years of

age, a third are 10 to 20 years old, and a third are older age, a third are 10 to 20 years old, and a third are older than 20; rarely seen in persons 40 years of age or than 20; rarely seen in persons 40 years of age or older.older.

HistoryHistory Onset of Lesions Onset of Lesions Recent (within months). The large Recent (within months). The large

majority of the lesions (majority of the lesions (..90 %) are acquired.90 %) are acquired. Skin Symptoms Skin Symptoms NoneNone Family History Family History NoneNone

Physical ExaminationPhysical Examination Skin LesionsSkin Lesions Papule or nodule, smooth-topped, Papule or nodule, smooth-topped,

hairless.hairless. COLORCOLOR Uniform pink , tan , brown, dark brownUniform pink , tan , brown, dark brown SHAPE OF INDIVIDUAL LESIONSHAPE OF INDIVIDUAL LESION Round, dome-Round, dome-

shaped, well-circumscribed nodule.shaped, well-circumscribed nodule. DISTRIBUTIONDISTRIBUTION Head and neck.Head and neck.

Spitz nevusSpitz nevus

Nevus spilusNevus spilus

Spitz nevusSpitz nevus

Differential DiagnosisDifferential Diagnosis Pink or Tan Papule Pink or Tan Papule Pigmented spindle cell Pigmented spindle cell

nevus of Reed is considered by many to be a nevus of Reed is considered by many to be a variant of Spitz nevus. variant of Spitz nevus.

The tumor is dome-shaped, deeply pigmented, The tumor is dome-shaped, deeply pigmented, and often surrounded by a lighter brown regular and often surrounded by a lighter brown regular rim; epiluminescence is particularly helpful; the rim; epiluminescence is particularly helpful; the tumor cells are not “diffusely infiltrating,” as in tumor cells are not “diffusely infiltrating,” as in the Spitz nevus, but grow in a compact nodular the Spitz nevus, but grow in a compact nodular pattern. pattern.

Other lesions in the differential diagnosis are Other lesions in the differential diagnosis are pyogenic granuloma, hemangioma, molluscum pyogenic granuloma, hemangioma, molluscum contagiosum, juvenile xanthogranuloma, contagiosum, juvenile xanthogranuloma, mastocytoma, dermatofibroma, atypical mastocytoma, dermatofibroma, atypical melanocytic nevi, nodular melanoma,and dermal melanocytic nevi, nodular melanoma,and dermal melanocytic nevus.melanocytic nevus.

DermatopathologyDermatopathology

LIGHT MICROSCOPYLIGHT MICROSCOPY Site Site Reticular dermis and epidermis Reticular dermis and epidermis Process Process

Hyperplasia of epidermis, neoplasm of Hyperplasia of epidermis, neoplasm of melanocytes, dilatation of capillariesmelanocytes, dilatation of capillaries

Cell Types Cell Types Admixed large epithelioid cells, Admixed large epithelioid cells, large spindle cells with abundant cytoplasm, large spindle cells with abundant cytoplasm, occasional mitotic figures; there are sometimes occasional mitotic figures; there are sometimes bizarre cytologic patterns; nests of large cells bizarre cytologic patterns; nests of large cells extend from the epidermis (“raining down”) extend from the epidermis (“raining down”) into the reticular dermis as fascicles of cells into the reticular dermis as fascicles of cells form an “inverted triangle,” with the base lying form an “inverted triangle,” with the base lying at the dermal-epidermal junction and the apex at the dermal-epidermal junction and the apex in the reticular dermis.in the reticular dermis.

DiagnosisDiagnosis Although the clinical appearance and recent Although the clinical appearance and recent

growth are characteristic of a Spitz nevus, growth are characteristic of a Spitz nevus, histologic examination must be done to confirm histologic examination must be done to confirm the clinical diagnosis.the clinical diagnosis.

..

SignificanceSignificance Excision in its entirety is important because the Excision in its entirety is important because the

condition recurs in 10 % to 15 % of all cases in lesions condition recurs in 10 % to 15 % of all cases in lesions that have not been excised completely. that have not been excised completely.

This tumor poses some special problems in cytologic This tumor poses some special problems in cytologic diagnosis. Atypical lesions are worrisome. diagnosis. Atypical lesions are worrisome.

While the majority of Spitz nevi are benign, there can While the majority of Spitz nevi are benign, there can be a histologic similarity between Spitz nevi and be a histologic similarity between Spitz nevi and melanoma. Also, atypical Spitz nevi can occur and even melanoma. Also, atypical Spitz nevi can occur and even have occasional “metastases” from such lesions. have occasional “metastases” from such lesions. Melanoma has been reported to arise rarely in Spitz Melanoma has been reported to arise rarely in Spitz nevi.nevi.

Course and PrognosisCourse and Prognosis Spitz tumors probably do not involute, as do common Spitz tumors probably do not involute, as do common

acquired nevomelanocytic nevi. acquired nevomelanocytic nevi. However, some lesions have been observed to However, some lesions have been observed to

transform into common compound NMC, some undergo transform into common compound NMC, some undergo fibrosis and in late stages may resemble fibrosis and in late stages may resemble dermatofibromas.dermatofibromas.

ManagementManagement Excision with a border of 5 mm. Excision with a border of 5 mm. Follow-up in 6 to 12 months is advised, especially for Follow-up in 6 to 12 months is advised, especially for

atypical lesions.atypical lesions.

Congenital neviCongenital nevi Congenital nevi are present at birth & result Congenital nevi are present at birth & result

from a proliferation of from a proliferation of benign melanocytes in benign melanocytes in the dermis, epidermis, or both. the dermis, epidermis, or both.

Occasionally, nevi that are not present at birth Occasionally, nevi that are not present at birth but are histologically identical to congenital nevi but are histologically identical to congenital nevi may develop during the first 2 years of life.may develop during the first 2 years of life.

This is referred to as This is referred to as congenital nevus congenital nevus tardive.tardive.

Pathophysiology: Pathophysiology: The etiology of congenital melanocytic nevi remains unclear. The etiology of congenital melanocytic nevi remains unclear. The melanocytes of the skin originate in the neuroectoderm, The melanocytes of the skin originate in the neuroectoderm,

although the specific cell type from which they derive remains although the specific cell type from which they derive remains unknown. unknown.

One hypothesis is that pluripotential nerve sheath precursor One hypothesis is that pluripotential nerve sheath precursor cells migrate from the neural crest to the skin along paraspinal cells migrate from the neural crest to the skin along paraspinal ganglia and peripheral nerve sheaths and differentiate into ganglia and peripheral nerve sheaths and differentiate into melanocytes upon reaching the skin. melanocytes upon reaching the skin.

Congenital melanocytic nevi is that an external insult results in Congenital melanocytic nevi is that an external insult results in a mutation that affects the morphogenesis of the embryonic a mutation that affects the morphogenesis of the embryonic neuroectoderm and migration of precursor cells to the skin. neuroectoderm and migration of precursor cells to the skin.

Stratified into 3 groups according to size: Stratified into 3 groups according to size:

1-Small nevi are less than 1.5 cm in greatest diameter, 1-Small nevi are less than 1.5 cm in greatest diameter,

2-Medium nevi are 1.5-19.9 cm in greatest diameter, and 2-Medium nevi are 1.5-19.9 cm in greatest diameter, and

3-Large or giant nevi are > 20 cm in greatest diameter3-Large or giant nevi are > 20 cm in greatest diameter. .

Giant nevi are often surrounded by several smaller satellite nevi. Giant nevi are often surrounded by several smaller satellite nevi. An alternate definition is that a small congenital nevus is one for An alternate definition is that a small congenital nevus is one for

which primary closure is possible after excision. which primary closure is possible after excision. Congenital nevi may also be seen as a component of Congenital nevi may also be seen as a component of

neurocutaneous melanosisneurocutaneous melanosis, a rare congenital syndrome , a rare congenital syndrome characterized by the presence of congenital melanocytic nevi characterized by the presence of congenital melanocytic nevi and melanotic neoplasms of the central nervous system. and melanotic neoplasms of the central nervous system.

The current diagnostic criteria for The current diagnostic criteria for neurocutaneous melanosis are:neurocutaneous melanosis are:

1-Large (>20 cm) or multiple (>3) congenital nevi in association 1-Large (>20 cm) or multiple (>3) congenital nevi in association with meningeal melanosis or melanoma, with meningeal melanosis or melanoma,

2-No evidence of meningeal melanoma except in patients in 2-No evidence of meningeal melanoma except in patients in whom cutaneous lesions are histologically benign, and whom cutaneous lesions are histologically benign, and

3-No evidence of cutaneous melanoma except in patients in 3-No evidence of cutaneous melanoma except in patients in whom meningeal lesions are histologically benign . whom meningeal lesions are histologically benign .

Neurocutaneous melanosis may result from an error in the Neurocutaneous melanosis may result from an error in the morphogenesis of the neuroectoderm, which gives rise to morphogenesis of the neuroectoderm, which gives rise to the melanotic cells of both the skin and meninges. the melanotic cells of both the skin and meninges.

Clinically, patients may present with increased intracranial Clinically, patients may present with increased intracranial pressure due to hydrocephalus or a mass lesion. pressure due to hydrocephalus or a mass lesion.

The prognosis of patients with symptomatic neurocutaneous The prognosis of patients with symptomatic neurocutaneous melanosis is very poor, even in the absence of malignancy. melanosis is very poor, even in the absence of malignancy.

In one review of 39 reported cases of symptomatic In one review of 39 reported cases of symptomatic neurocutaneous melanosis, death occurred in more than half neurocutaneous melanosis, death occurred in more than half the patients within 3 years of the onset of neurological the patients within 3 years of the onset of neurological symptoms, and most deaths were in patients younger than 10 symptoms, and most deaths were in patients younger than 10

years.years.

Frequency: Frequency: Internationally: Internationally: present in 1-2% of newborn infants. present in 1-2% of newborn infants. Race: Race: No No

racial predilection is recognized. racial predilection is recognized. Sex: Sex: Congenital nevi occur in both sexes, with no known Congenital nevi occur in both sexes, with no known

predilection. predilection. Age: Age: To be considered congenital nevi, lesions must be To be considered congenital nevi, lesions must be

present at birth.present at birth.

Mortality/Morbidity: Mortality/Morbidity: For giant congenital melanocytic nevi, the risk of For giant congenital melanocytic nevi, the risk of

developing melanoma has been reported to be as high developing melanoma has been reported to be as high as 5-7% by age 60 years.as 5-7% by age 60 years.

Risk of melanoma may be greater in those with giant Risk of melanoma may be greater in those with giant congenital melanocytic nevi with congenital melanocytic nevi with more satellite more satellite lesions or a larger diameter.lesions or a larger diameter.

However, while the general consensus regarding However, while the general consensus regarding smaller nevi is that they pose a greater risk for the smaller nevi is that they pose a greater risk for the development of melanoma than normal skin, this risk development of melanoma than normal skin, this risk has not been quantified. has not been quantified.

DDx:DDx: Becker nevusBecker nevus Spitz nevus,Spitz nevus, Seborrheic keratosis, Seborrheic keratosis, Pagets disease,mammary,Pagets disease,mammary, Nevus sebacus,Nevus sebacus, Melanocytic nevi,Melanocytic nevi, Nevi of ito & ota,Nevi of ito & ota, Neurofibromatosis,Neurofibromatosis, Malignant melanoma,Malignant melanoma, Halo nevus,Halo nevus, Epidermal nevus syndrome,Epidermal nevus syndrome, Epidermal nevusEpidermal nevus Nevus spilusNevus spilus Pigmented non-melanoma carcinomaPigmented non-melanoma carcinoma

Mx;Mx;

Ageminated nevusAgeminated nevus

Nevomelanocytic nevi Nevomelanocytic nevi Etiology and PathogenesisEtiology and Pathogenesis Congenital and acquired nevomelanocytic nevi are Congenital and acquired nevomelanocytic nevi are

presumed to occur as the result of a developmental presumed to occur as the result of a developmental defect in neural crest-derived melanoblasts. defect in neural crest-derived melanoblasts.

This defect probably occurs after 10 weeks in utero but This defect probably occurs after 10 weeks in utero but before the sixth uterine month; the occurrence of the before the sixth uterine month; the occurrence of the “split” nevus of the eyelid is an indication that “split” nevus of the eyelid is an indication that nevomelanocytes migrating from the neural crest were nevomelanocytes migrating from the neural crest were in place in this site before the eyelids split (24 weeks).in place in this site before the eyelids split (24 weeks).

Course and PrognosisCourse and Prognosis By definition, CNN appear at birth, but varieties of CNN By definition, CNN appear at birth, but varieties of CNN

may arise during infancy (so-called tardive CNN). may arise during infancy (so-called tardive CNN). The life history of CNN is not documented, butThe life history of CNN is not documented, but CNN have been observed in elderly persons, an age CNN have been observed in elderly persons, an age

when acquired nevomelanocytic nevi have when acquired nevomelanocytic nevi have disappeared.disappeared.

Very large or giant CNN: Very large or giant CNN: The lifetime risk for The lifetime risk for development of melanoma in largedevelopment of melanoma in large

CNN has been estimated to be at least 6.3 %; in 50 % CNN has been estimated to be at least 6.3 %; in 50 % of patients who develop melanoma in large CNN, the of patients who develop melanoma in large CNN, the diagnosis is made between the ages of 3 and 5 years. diagnosis is made between the ages of 3 and 5 years.

Melanoma that develops in a large CNN has a poor Melanoma that develops in a large CNN has a poor prognosis.prognosis.

Small CNN: Small CNN: The lifetime risk of developing malignant The lifetime risk of developing malignant melanoma is 1 % to 5 %.melanoma is 1 % to 5 %.

Congenital nevomelanocytic neviCongenital nevomelanocytic nevi

Congenital nevomelanocytic neviCongenital nevomelanocytic nevi

Very Large (“Giant”) CNNVery Large (“Giant”) CNN

Giant CNN of the head and neck may be Giant CNN of the head and neck may be associated with involvement of the associated with involvement of the leptomeninges with the same pathologic leptomeninges with the same pathologic process; this presentation may be process; this presentation may be asymptomatic or be manifested by seizures, asymptomatic or be manifested by seizures, focal neurologic defects, or obstructive focal neurologic defects, or obstructive hydrocephalus.hydrocephalus.

Differential DiagnosisDifferential Diagnosis Common acquired nevomelanocytic nevi, dysplastic Common acquired nevomelanocytic nevi, dysplastic

melanocytic nevi, congenital blue nevus, nevus spilus, melanocytic nevi, congenital blue nevus, nevus spilus, Becker’s nevus, pigmented epidermal nevi, and caféau-Becker’s nevus, pigmented epidermal nevi, and caféau-lait macules should be considered in the differential lait macules should be considered in the differential diagnosis of CNN. diagnosis of CNN.

Small CNN are virtually indistinguishable clinically from Small CNN are virtually indistinguishable clinically from common acquired nevomelanocytic nevi except for common acquired nevomelanocytic nevi except for size, and lesions >1.5 cm may be presumed to be size, and lesions >1.5 cm may be presumed to be either CNN or dysplastic melanocytic nevi. either CNN or dysplastic melanocytic nevi.

Without a good history or photographs, it may not be Without a good history or photographs, it may not be possible to ascertain the age of onset of a possible to ascertain the age of onset of a nevomelanocytic nevus <1.5 cm in diameter.nevomelanocytic nevus <1.5 cm in diameter.

BirthmarksBirthmarks

BirthmarksBirthmarks Birthmarks represent an excess of one or more of the Birthmarks represent an excess of one or more of the

normal components of skin per unit area: normal components of skin per unit area: blood blood vessels, lymph vessels, pigment cells, hair vessels, lymph vessels, pigment cells, hair follicles, sebaceous glands, epidermis, collagen, follicles, sebaceous glands, epidermis, collagen, or elastinor elastin. .

Birthmarks are collections of highly differentiated cells Birthmarks are collections of highly differentiated cells in tissue.in tissue.

Congenital malformations’r most frequently observed in Congenital malformations’r most frequently observed in skin. skin.

Birthmarks…Birthmarks…

The vascular birthmarks are the most common.The vascular birthmarks are the most common. The two most commonly seen birthmarks are flat The two most commonly seen birthmarks are flat

capillary malformations of a faint red color, the so- capillary malformations of a faint red color, the so- called called salmon patch, & Mongolian spots.salmon patch, & Mongolian spots.

They are observed at least 100 times more frequently They are observed at least 100 times more frequently than any other skin birthmark. than any other skin birthmark.

Salmon patches are observed with high frequency in Salmon patches are observed with high frequency in infants, both in white infants (703 per 1000 live births) infants, both in white infants (703 per 1000 live births) and black infants (592 per 1000 live births). and black infants (592 per 1000 live births).

Mongolian spots are more frequently observed in Mongolian spots are more frequently observed in Asians (910 per 1000 live births) and black infants (880 Asians (910 per 1000 live births) and black infants (880 per 1000 live births), but are less common in white per 1000 live births), but are less common in white infants (48 per 1000 live births).infants (48 per 1000 live births).

Flat Capillary MalformationsFlat Capillary Malformations Flat capillary malformations can be divided into: Flat capillary malformations can be divided into:

--Those that are light red or pink in color [salmon patch (nevus Those that are light red or pink in color [salmon patch (nevus flammeus)] and flammeus)] and

-Those that are deep red or purple-red (port-wine stain).-Those that are deep red or purple-red (port-wine stain). A salmon patch is present over the back of the neck in over 40% of A salmon patch is present over the back of the neck in over 40% of

infants,% over glabella or eyelids in 20%. infants,% over glabella or eyelids in 20%. Portwine stains are seen in 0.5% of newborns.Portwine stains are seen in 0.5% of newborns.

Clinical manifestationsClinical manifestations The salmon patch appears as a light red macule over the nape of The salmon patch appears as a light red macule over the nape of

the neck, the upper eyelids,& the glabella.the neck, the upper eyelids,& the glabella. Over the nape of the neck they may become inflamed and develop Over the nape of the neck they may become inflamed and develop

overlying dermatitis. overlying dermatitis. Port-wine stains appear as deep red or purple-red macules over Port-wine stains appear as deep red or purple-red macules over

the face or extremities; they are usually unilateral.the face or extremities; they are usually unilateral. Occasionally, they are extensive and cover large areas of skin. Occasionally, they are extensive and cover large areas of skin. Port-wine stains over the face or an extremity may be associated Port-wine stains over the face or an extremity may be associated

with soft tissue and bony hypertrophy.with soft tissue and bony hypertrophy.

A port-wine stain over the face may be a clue to the A port-wine stain over the face may be a clue to the Sturge-Weber syndrome.Sturge-Weber syndrome.

Overall, 8 % of infants with facial port-wine stains will Overall, 8 % of infants with facial port-wine stains will develop Sturge-Weber syndrome, but the incidence is develop Sturge-Weber syndrome, but the incidence is higher if the lesion covers the upper and lower eyelid or higher if the lesion covers the upper and lower eyelid or is bilateral.is bilateral.

The Sturge-Weber syndrome is characterized by The Sturge-Weber syndrome is characterized by seizures,mental retardation,glaucoma, & hemiplegia.seizures,mental retardation,glaucoma, & hemiplegia.

Calcification of the capillary malformation in the brain Calcification of the capillary malformation in the brain in Sturge-Weber syndrome may be detected in in Sturge-Weber syndrome may be detected in childhood by skull x-ray.childhood by skull x-ray.

Identification of cerebral vascular abnormalities and Identification of cerebral vascular abnormalities and early calcification can be detected in infancy by early calcification can be detected in infancy by computed tomography or magnetic resonance imaging. computed tomography or magnetic resonance imaging.

When port-wine stains are found over an extremity and When port-wine stains are found over an extremity and are associated with soft tissue or bony hypertrophy of are associated with soft tissue or bony hypertrophy of that extremity, the condition is called the Klippel-that extremity, the condition is called the Klippel-Trenaunay-Weber syndrome.Trenaunay-Weber syndrome.

Elongation of an extremity can cause orthopedic Elongation of an extremity can cause orthopedic deformity. deformity.

Arteriovenous fistulas are present in 25% of such pts.Arteriovenous fistulas are present in 25% of such pts. Absence of the deep venous channels in the affected Absence of the deep venous channels in the affected

limb may be detected by venography.limb may be detected by venography.

PathologyPathology Numerous dilated capillaries W/O endothelial change Numerous dilated capillaries W/O endothelial change

are seen on a skin biopsy of lesions in an adolescent or are seen on a skin biopsy of lesions in an adolescent or adult.adult.

The capillaries are mature and represent a The capillaries are mature and represent a developmental malformation. developmental malformation.

In infants and children, the skin biopsy may be In infants and children, the skin biopsy may be indistinguishable from normal skin.indistinguishable from normal skin.

Diagnosis and differential diagnosisDiagnosis and differential diagnosis In an older infant, capillary vascular malformations are In an older infant, capillary vascular malformations are

so characteristic that they are seldom confused with so characteristic that they are seldom confused with other skin conditions, but other skin conditions, but

In the first weeks of life the raised hemangioma may be In the first weeks of life the raised hemangioma may be flat and look like a port-wine stain.flat and look like a port-wine stain.

After several weeks of life, the raised hemangioma will After several weeks of life, the raised hemangioma will begin to elevate the skin and be distinguished from a begin to elevate the skin and be distinguished from a port-wine stain. port-wine stain.

Port-wine stain lesions usually cover a larger surface Port-wine stain lesions usually cover a larger surface area and are unilateral.area and are unilateral.

TreatmentTreatment ppulsed dye laser, which selectively causes thermal ulsed dye laser, which selectively causes thermal

damage to cutaneous vasculature while sparing damage to cutaneous vasculature while sparing surrounding epidermal and dermal structures.surrounding epidermal and dermal structures.

This therapy is best initiated during early infancy, and This therapy is best initiated during early infancy, and clearing is dependent on the size of the capillary clearing is dependent on the size of the capillary malformation and the age when therapy is begun.malformation and the age when therapy is begun.

Therapy for the cutaneous lesion may reverse Therapy for the cutaneous lesion may reverse underlying soft tissue overgrowth, but bonyunderlying soft tissue overgrowth, but bonyhypertrophy or the neurologic progressions in Sturge-hypertrophy or the neurologic progressions in Sturge-Weber syndrome are not affected. Weber syndrome are not affected.

Flat hemangiomas may be covered with make-up. Flat hemangiomas may be covered with make-up.

If features of Sturge-Weber syndrome are present, If features of Sturge-Weber syndrome are present, ophthalmologic evaluation and follow-up should be ophthalmologic evaluation and follow-up should be obtained immediately.obtained immediately.

Measurements of the length and girth of the Measurements of the length and girth of the extremities should be carefully recorded every 3 to 6 extremities should be carefully recorded every 3 to 6 months if a port-wine stain is found over an extremity. months if a port-wine stain is found over an extremity.

Since leg length differences can induce scoliosis, Since leg length differences can induce scoliosis, orthopedic evaluations and assistance may be required orthopedic evaluations and assistance may be required if one leg is longer than the other.if one leg is longer than the other.

Course and prognosisCourse and prognosis Flat vascular malformations tend to persist. Flat vascular malformations tend to persist. Salmon patches may fade somewhat with time, but Salmon patches may fade somewhat with time, but

remnants persist well into adult life. remnants persist well into adult life. Generally, the eyelid lesions fade by 6 to 12 months of Generally, the eyelid lesions fade by 6 to 12 months of

age. age. Lesions on the nape of the neck are likely to persist into Lesions on the nape of the neck are likely to persist into

adulthood.adulthood.

Raised Hemangiomas (Superficial and DeepRaised Hemangiomas (Superficial and DeepHemangiomas)Hemangiomas)

Capillary malformation & nevus anemicusCapillary malformation & nevus anemicus

PhakomatosisPhakomatosis

PWS:Sturge-weber syndrome?PWS:Sturge-weber syndrome?

Klipple terunaneyKlipple terunaney

SyndromeSyndrome

Mongolian SpotsMongolian Spots Mongolian spots are blue-black macules found on the Mongolian spots are blue-black macules found on the

skin of dark-skinned newborns. skin of dark-skinned newborns. Infants' skin is always light at birth,& becomes Infants' skin is always light at birth,& becomes

progressively darker with increasing age. progressively darker with increasing age. Hyperpigmentation of the scrotum and of theHyperpigmentation of the scrotum and of the

linea alba is common in dark-skinned infants at birth. linea alba is common in dark-skinned infants at birth. The most commonly observed pigmentary abnormality The most commonly observed pigmentary abnormality

of infants is the Mongolian spot.of infants is the Mongolian spot. Mongolian spots are found over the lumbosacral area in Mongolian spots are found over the lumbosacral area in

up to 90 % of Asian, black, & American Indian babies. up to 90 % of Asian, black, & American Indian babies.

Etiology and pathogenesisEtiology and pathogenesis Mongolian spots consist of spindle-shaped pigment cells Mongolian spots consist of spindle-shaped pigment cells

located deep within the dermis.located deep within the dermis. The precise mechanism of this condition is not known.The precise mechanism of this condition is not known.

Clinical manifestationsClinical manifestations Mongolian spots are blue-black macules usually found Mongolian spots are blue-black macules usually found

in lumbosacral skin.in lumbosacral skin. They are occasionally noted over the shoulders and They are occasionally noted over the shoulders and

back and may extend over the buttocks & extremities.back and may extend over the buttocks & extremities.

Course and prognosisCourse and prognosis Mongolian spots fade somewhat with time, and the Mongolian spots fade somewhat with time, and the

difference in pigmentation from normal skin pigment difference in pigmentation from normal skin pigment becomes less obvious as the newborn's pigment becomes less obvious as the newborn's pigment darkens. darkens.

Some traces of Mongolian spots may persist into adult Some traces of Mongolian spots may persist into adult life. life.

ABCDEABCDE

Cutis Marmorata Telangiectatica Cutis Marmorata Telangiectatica CongenitaCongenita

Cutis marmorata is a rare, persistent mottling pattern Cutis marmorata is a rare, persistent mottling pattern due to a vascular birthmark.due to a vascular birthmark.

Etiology and pathogenesisEtiology and pathogenesis The disorder is considered to be a vascular ectasia of The disorder is considered to be a vascular ectasia of

veins and, possibly,of capillaries.veins and, possibly,of capillaries. Tortuous, dilated veins are found in the dermis and Tortuous, dilated veins are found in the dermis and

subcutaneous tissue on biopsy.subcutaneous tissue on biopsy.

Clinical manifestationsClinical manifestations In cutis marmorata telangiectatica congenita, a mottled pattern of In cutis marmorata telangiectatica congenita, a mottled pattern of

blue or dusky-red erythema is seen from birth.blue or dusky-red erythema is seen from birth. It is unresponsive to skin warming. It is unresponsive to skin warming. Often a single extremity is involved, but the lesions may occur Often a single extremity is involved, but the lesions may occur

bilaterally on the extremities or on the trunk.bilaterally on the extremities or on the trunk. The skin surface overlying such areas may be depressed. The skin surface overlying such areas may be depressed. A gradual increase in the size of lesions is expected over the first A gradual increase in the size of lesions is expected over the first

few years of life, but most fade by adult life.few years of life, but most fade by adult life. Rigorous natural history studies of cutis marmorata telangiectatica Rigorous natural history studies of cutis marmorata telangiectatica

congenita are not available. congenita are not available. Associations with musculoskeletal or vascular abnormalities occur.Associations with musculoskeletal or vascular abnormalities occur.

Diagnosis and differential diagnosisDiagnosis and differential diagnosis In contrast to cutis marmorata telangiectatica congenita, mottling In contrast to cutis marmorata telangiectatica congenita, mottling

of newborn skin is a transient vasodilation and is relieved by of newborn skin is a transient vasodilation and is relieved by rewarming the skin. rewarming the skin.

The livedo reticularis pattern of collagen vascular disease is flat, The livedo reticularis pattern of collagen vascular disease is flat, not depressed over the discolored areas, always bilateral, and not depressed over the discolored areas, always bilateral, and associated with systemic signs and symptoms.associated with systemic signs and symptoms.

TreatmentTreatment There is no reliable treatment, but some lesions will respond to There is no reliable treatment, but some lesions will respond to

pulsed dye laser therapy.pulsed dye laser therapy. Routine evaluations should include close inspection of the Routine evaluations should include close inspection of the

extremities for possible orthopedic deformity. extremities for possible orthopedic deformity. It should be emphasized that it is an unusual disorder and that few It should be emphasized that it is an unusual disorder and that few

data are available for predicting the course. data are available for predicting the course. Associated deformities should be treated as necessary.Associated deformities should be treated as necessary.

Diffuse Neonatal Hemangiomatosis and Blue Diffuse Neonatal Hemangiomatosis and Blue Rubber Bleb SyndromeRubber Bleb Syndrome

These are vascular syndromes consisting of multiple These are vascular syndromes consisting of multiple raised hemangiomas.raised hemangiomas.

Both diffuse neonatal hemangiomatosis and blue Both diffuse neonatal hemangiomatosis and blue rubber bleb syndrome are rare.rubber bleb syndrome are rare.

Etiology and pathogenesisEtiology and pathogenesis In diffuse neonatal hemangiomatosis, proliferating In diffuse neonatal hemangiomatosis, proliferating

endothelial cells and numerous capillary lumens are endothelial cells and numerous capillary lumens are observed within the middermis. observed within the middermis.

This syndrome has been reported in twins, but This syndrome has been reported in twins, but insufficient data are available to determine whether it is insufficient data are available to determine whether it is hereditary. hereditary.

The blue rubber bleb nevus syndrome lesions are more The blue rubber bleb nevus syndrome lesions are more similar to cavernous hemangiomas, with numerous similar to cavernous hemangiomas, with numerous dilated vascular channels.dilated vascular channels.

Clinical manifestationsClinical manifestations Diffuse neonatal hemangiomatosis consists of multiple, Diffuse neonatal hemangiomatosis consists of multiple,

small, raised cutaneous hemangiomas, which may or small, raised cutaneous hemangiomas, which may or may not be associated with hemangiomas in the liver, may not be associated with hemangiomas in the liver, lungs, gastrointestinal tract, and lungs, gastrointestinal tract, and central nervous central nervous system (CNS)system (CNS)..

The raised hemangiomas may be present at birth, and The raised hemangiomas may be present at birth, and more develop with time. The hemangiomas vary from 2 more develop with time. The hemangiomas vary from 2 to 15 mm in diameter. to 15 mm in diameter.

Spontaneous involution of the lesions has beenSpontaneous involution of the lesions has beenreported. reported.

Bleeding may occur into the gastrointestinal tract. Bleeding may occur into the gastrointestinal tract. The blue rubber bleb nevus syndrome is a rare disorder The blue rubber bleb nevus syndrome is a rare disorder

consisting of multiple cavernous hemangiomas of the consisting of multiple cavernous hemangiomas of the skin and bowel.skin and bowel.

The lesions are blue and 3 to 4 cm in diameter.The lesions are blue and 3 to 4 cm in diameter.

Diagnosis and differential diagnosisDiagnosis and differential diagnosis The presence of skin hemangiomas is so characteristic The presence of skin hemangiomas is so characteristic

that little difficulty in differential diagnosis is there. that little difficulty in differential diagnosis is there. The lesions of blue rubber bleb nevus syndrome are The lesions of blue rubber bleb nevus syndrome are

compressible and may be painful or associated with compressible and may be painful or associated with excessive sweating.excessive sweating.

Monitoring stool samples for occult blood is helpful in Monitoring stool samples for occult blood is helpful in identifying presence of intestinal lesions.identifying presence of intestinal lesions.

TreatmentTreatment Infants with diffuse neonatal hemangiomatosis who Infants with diffuse neonatal hemangiomatosis who

develop complications may respond to prednisone at a develop complications may respond to prednisone at a dose of 2 to 6 mg/kg per day, with appropriate dose of 2 to 6 mg/kg per day, with appropriate attention to side effects.attention to side effects.

The duration of treatment may exceed 8 to 12 weeks. The duration of treatment may exceed 8 to 12 weeks. The blue rubber bleb lesions are not responsive to The blue rubber bleb lesions are not responsive to

systemic therapy and may require surgical resection. systemic therapy and may require surgical resection. Frequent stool examinations for blood will identify Frequent stool examinations for blood will identify

intestinal bleeding.intestinal bleeding.

Nevus sebaceousNevus sebaceous

Lymph Vessel Birthmarks:Lymph Vessel Birthmarks:

LymphangiomasLymphangiomas Lymphangiomas may be circumscribed, superficial skin Lymphangiomas may be circumscribed, superficial skin

papules or deep,cavernous nodules, uncommon in the papules or deep,cavernous nodules, uncommon in the newborn period.newborn period.

Etiology and pathogenesisEtiology and pathogenesis Dilated, tortuous lymph vessels appear within the Dilated, tortuous lymph vessels appear within the

dermis and subcutaneous fat. dermis and subcutaneous fat. Most often, many channels are found spreading from Most often, many channels are found spreading from

the original lesion, so that the skin surface change the original lesion, so that the skin surface change reflects only the tip of a tetrahedral lesion. reflects only the tip of a tetrahedral lesion.

Cavernous lymphangiomas may involve the muscle as Cavernous lymphangiomas may involve the muscle as well.well.

Clinical manifestationsClinical manifestations Circumscribed lymphangiomas appear as a solitary group of 2- to Circumscribed lymphangiomas appear as a solitary group of 2- to

4-mm,gelatinous skin-colored papules limited to a skin area less 4-mm,gelatinous skin-colored papules limited to a skin area less than 10 cm2.than 10 cm2.

They are often connected to underlying venous channels, and They are often connected to underlying venous channels, and hemorrhage into one or more papules may occur, producing hemorrhage into one or more papules may occur, producing sudden darkening.sudden darkening.

They may be present at birth but are often not noticed until late They may be present at birth but are often not noticed until late infancy or childhood.infancy or childhood.

Cavernous lymphangiomas are rubbery, skin-colored nodules that Cavernous lymphangiomas are rubbery, skin-colored nodules that may result in grotesque enlargement of soft tissues. may result in grotesque enlargement of soft tissues.

They are usually solitary and involve the face, trunk, and They are usually solitary and involve the face, trunk, and extremities.extremities.

They are particularly common over the parotid area, where they They are particularly common over the parotid area, where they are called are called cystic hygromascystic hygromas..

They may have a rapid growth phase similar to that of raised They may have a rapid growth phase similar to that of raised hemangiomas.hemangiomas.

Diagnosis and differential diagnosisDiagnosis and differential diagnosis Circumscribed lymphangioma may be mistaken for a Circumscribed lymphangioma may be mistaken for a

disorder with grouped vesicles, such as herpes simplex, disorder with grouped vesicles, such as herpes simplex, herpes zoster, or dermatitis herpetiformis.herpes zoster, or dermatitis herpetiformis.

However, there is no erythematous base in However, there is no erythematous base in circumscribed lymphangioma,and the lesions appear circumscribed lymphangioma,and the lesions appear gelatinous, not fluid-filled. gelatinous, not fluid-filled.

Hemorrhage into such lesions results in darkening, Hemorrhage into such lesions results in darkening, which may be confused with malignant melanoma. which may be confused with malignant melanoma.

Cavernous lymphangiomas may be confused with Cavernous lymphangiomas may be confused with lipomas, neurofibromas, and other soft subcutaneous lipomas, neurofibromas, and other soft subcutaneous masses.masses.

TreatmentTreatment There is no satisfactory treatment.There is no satisfactory treatment. Surgical excision can result in defects two or three Surgical excision can result in defects two or three

times larger than the observed skin lesion, and the times larger than the observed skin lesion, and the recurrence rate is high. recurrence rate is high.

Often, the lymph channels are found to surround vital Often, the lymph channels are found to surround vital subcutaneous structures, such as major arteries or subcutaneous structures, such as major arteries or nerves. nerves.

The lesions are not responsive to radiotherapy or The lesions are not responsive to radiotherapy or systemic steroids. systemic steroids.

Monthly or bimonthly visits in which photographs of the Monthly or bimonthly visits in which photographs of the lesions are taken & careful measurements made are lesions are taken & careful measurements made are indicated initially. indicated initially.

Eventually, semiannual or annual visits are sufficient to Eventually, semiannual or annual visits are sufficient to evaluate the lesions & commence therapy for evaluate the lesions & commence therapy for complications.complications.

Café au Lait SpotsCafé au Lait Spots

Aplasia Cutis CongenitaAplasia Cutis Congenita Aplasia cutis congenita is the failure to form certain Aplasia cutis congenita is the failure to form certain

layers of skin. layers of skin. This condition occurs in 1 per 3000 live births.This condition occurs in 1 per 3000 live births. It may be seen as an autosomal dominant trait in some It may be seen as an autosomal dominant trait in some

families or associated with a variety of other families or associated with a variety of other malformations.malformations.

Etiology and pathogenesisEtiology and pathogenesis Aplasia cutis congenita is a developmental failure of Aplasia cutis congenita is a developmental failure of

skin fusion. skin fusion. Dermis,epidermis, and fat may all be missing, or single Dermis,epidermis, and fat may all be missing, or single

layers may be absent.layers may be absent.

Clinical manifestationsClinical manifestations In aplasia cutis congenita, oval, sharply marginated, 1- In aplasia cutis congenita, oval, sharply marginated, 1-

to 2-cm depressed areas are seen primarily in the to 2-cm depressed areas are seen primarily in the midline of the posterior scalp.midline of the posterior scalp.

They are hairless, may appear as an ulcer, or are They are hairless, may appear as an ulcer, or are covered by a smooth, finely wrinkled epithelial covered by a smooth, finely wrinkled epithelial membrane. membrane.

Ulcerated defects heal with scar formation. Ulcerated defects heal with scar formation. Aplasia cutis congenita may be found as an isolated Aplasia cutis congenita may be found as an isolated

lesion or associated with other developmental defects, lesion or associated with other developmental defects, such as cleft palate or lip, syndactyly, absence of digits, such as cleft palate or lip, syndactyly, absence of digits, eye anomalies, and congenital heart disease.eye anomalies, and congenital heart disease.

Although the majority of lesions appear on the scalp, Although the majority of lesions appear on the scalp, lesions may be found on the trunk, face, or proximal lesions may be found on the trunk, face, or proximal extremities.extremities.

Diagnosis and differential diagnosisDiagnosis and differential diagnosis Scalp ulcers at birth may be mistaken for obstetric Scalp ulcers at birth may be mistaken for obstetric

trauma, although a careful history will distinguish trauma, although a careful history will distinguish between the two. between the two.

Other forms of congenital circumscribed hair loss Other forms of congenital circumscribed hair loss should be considered.should be considered.

TreatmentTreatment If the lesion is small, surgical excision, with mobilization If the lesion is small, surgical excision, with mobilization

of the scalp andof the scalp andsimple closure, will correct the hairless defect.simple closure, will correct the hairless defect.

Hair transplantation successful is 4 large defects. Hair transplantation successful is 4 large defects. Convincing the parents that this is not the result of Convincing the parents that this is not the result of

obstetric trauma is critical.obstetric trauma is critical.

Connective Tissue BirthmarksConnective Tissue Birthmarks Connective tissue nevi are skin lesions consisting Connective tissue nevi are skin lesions consisting

predominantly of the elements of extracellular collagen predominantly of the elements of extracellular collagen tissue and products of fibroblasts, such as collagen, tissue and products of fibroblasts, such as collagen, elastin, and proteoglycans.elastin, and proteoglycans.

All connective tissue nevi are quite rare, although the All connective tissue nevi are quite rare, although the precise incidence is not known.precise incidence is not known.

Etiology and pathogenesisEtiology and pathogenesis The etiology is unknown.The etiology is unknown.

Clinical manifestationsClinical manifestations Connective tissue nevi are localized areas of thickened Connective tissue nevi are localized areas of thickened

skin appearing as multiple skin-colored papules and skin appearing as multiple skin-colored papules and plaques.plaques.

Stretching the overlying skin will give a yellowish Stretching the overlying skin will give a yellowish discoloration to the areas. discoloration to the areas.

They may occasionally have increased vascularity and They may occasionally have increased vascularity and appear red. appear red.

Collagenomas are localized areas of thickened Collagenomas are localized areas of thickened skin with multiple skin-colored papules or skin with multiple skin-colored papules or plaquesplaques. .

They may be solitary or appear in a zosteriform They may be solitary or appear in a zosteriform segmental pattern. segmental pattern.

Elastomas are solitary plaques that are present at birth and Elastomas are solitary plaques that are present at birth and contain increases in both elastic tissue and proteoglycans.contain increases in both elastic tissue and proteoglycans.

Elastomas may be solitary or they may be multiple inElastomas may be solitary or they may be multiple inthe Buschke-Ollendorff syndrome. the Buschke-Ollendorff syndrome.

This autosomal dominant syndrome appears as symmetrically This autosomal dominant syndrome appears as symmetrically distributed skin-colored papules or nodules with a predilection for distributed skin-colored papules or nodules with a predilection for the lower trunk or for the extremities.the lower trunk or for the extremities.

Lesions may assume a thickened appearance of skin and develop Lesions may assume a thickened appearance of skin and develop a lacy pattern over the trunk.a lacy pattern over the trunk.

X- rays may show sclerotic densities of the ends of long bones, X- rays may show sclerotic densities of the ends of long bones, pelvis, and hands, although such lesions are often asymptomatic. pelvis, and hands, although such lesions are often asymptomatic.

The shagreen patch of tuberous sclerosis is a connective tissue The shagreen patch of tuberous sclerosis is a connective tissue nevus. nevus.

The nevi are subtle at birth and may go unnoticed. The nevi are subtle at birth and may go unnoticed. They tend to persist throughout life.They tend to persist throughout life.

PathologyPathology Connective tissue nevi show thickened abundant Connective tissue nevi show thickened abundant

collagen bundles, with or without associated increases collagen bundles, with or without associated increases in elastic tissue.in elastic tissue.

Such histologic changes are difficult to appreciate Such histologic changes are difficult to appreciate unless the skin biopsy includes adjacent normal skin for unless the skin biopsy includes adjacent normal skin for comparison.comparison.

Diagnosis and differential diagnosisDiagnosis and differential diagnosis The lesions are so characteristic that they are seldom The lesions are so characteristic that they are seldom

misdiagnosed.misdiagnosed. Examinations for possible associated systemic disease Examinations for possible associated systemic disease

may be necessary.may be necessary.