Dermatologic Diseases of the Male Genitalia: Malignant

Differential diagnosis:
1.Balanitis Circumscripta Plasmacellularis: History
The patient, a male of middle age or older, usually presents with a characteristic lesion of
the glans penis or prepuce, present for an average of 1-2 years before diagnosis.
Symptoms are minimal, but patients may complain of mild pruritus or tenderness. Some
patients present for evaluation because of cosmetic concerns or anxiety. Bloodstaining of
the underclothes for months prior to presentation has been reported in a patient with
!"B.
Physical
The !"B lesion is usually a solitary, glistening, shiny, red-to-orange pla#ue of the glans
or prepuce of an uncircumcised male. The lesions may exhibit a yellowish hue with
pinpoint purpuric $cayenne pepper$ spotting. %rosive and vegetative variants have been
reported. Bowen disease of the glans penis &erythroplasia of 'ueyrat( has been reported
in association with !"B) thus, attention must be given to possible neoplastic associations
with this condition.
*umar et al
+
studied 112 persons with a clinical diagnosis of !"B ranging in age from
2,--. years. /ost had been symptomatic for more than 12 months. !la#ues manifested
on the prepuce and glans in 0.122 of patients, in the prepuce only in 2+.212 of patients,
and on the glans only in 1-.02 patients.
Causes
The etiology of !"B is un3nown. 4mportantly, all confirmed cases have been in
uncircumcised males. 4t has been proposed that friction, trauma, heat, poor hygiene,
chronic infection with Mycobacterium smegmatis, a reactive response to an un3nown
exogenous or infectious agent, an immediate hypersensitivity response mediated by
immunoglobulin % class antibodies, and hypospadias may be predisposing or inciting
agents. There is no evidence of human papilloma virus infection in !"B.
2. erosive lichen planus(Cicatricial Pemphigoid): History
!atients with "! typically present with persistent, painful erosions on the mucous
membranes. The clinical manifestations are dependent on the sites involved.
!atients with ocular involvement may present with pain or the sensation of
grittiness in the eye and con5unctivitis. %rosions may be seen on the con5unctival
surface. %arly changes include 3eratini6ation of the con5unctiva and shortening of
the fornices. 7ater, patients develop entropion with subse#uent trichiasis.

o !atients often present after ocular surgery, especially for cataracts, with
severe inflammation of the eye or eyes and scar formation. 8ith
progressive scarring, patients develop symblepharon &fibrous tracts that
tether bulbar and con5unctival epithelium(, synechiae &adhesion of the iris
to the cornea or the lens(, and an3yloblepharon &a fixed globe(.
o 7acrimal gland and duct involvement leads to decreased tear and mucous
production. 9iminished tear formation leads to ocular dryness and further
trauma.
o The end result of ocular involvement is opacification and blindness. Some
patients with ocular disease may represent a subset of patients with "!
who do not develop oropharyngeal, other mucous membrane, or cutaneous
disease.
/outh involvement presents as recurrent, painful erosions. The gingivae are most
commonly involved, followed by the palate and the buccal mucosa) however, any
mucosal site in the mouth may blister. 4nvolvement of the oropharynx may
present with hoarseness or dysphagia. !rogressive scarring disease may lead to
esophageal stenosis re#uiring dilatation procedures. Supraglottic involvement
may lead to airway compromise re#uiring tracheostomy.
:asal involvement may manifest as epistaxis, bleeding after blowing the nose,
nasal crusting, and discomfort. ;ther mucosal sites, such as the perianal area or
the genitalia, may be involved.
S3in lesions develop in approximately one third of patients with "!, manifesting
as tense vesicles or bullae that may be hemorrhagic. Blisters may heal with
scarring or milia. Scalp involvement may lead to alopecia. !ruritus at the sites of
blisters or generali6ed pruritus may be present.
"utaneous "! involving the head and the nec3 without mucosal involvement is
3nown as the Brunsting-!erry variant of locali6ed B!. !atients are predominately
elderly and male. !atients present with a chronic, recurrent vesiculobullous
eruption on the head and the nec3 that heals with atrophic scarring. !atients with
this disorder have histologic immunofluorescent and immunoelectron microscopic
features similar to other patients with "!.
Physical
%arly ocular lesions may manifest as con5unctivitis, progressing to 3eratini6ation
of the corneal epithelium and shortening of the corneal sulcus. !rogressive ocular
disease leads to entropion and progressive corneal in5ury secondary to trichiasis.
8ith persistent disease activity, synchesis and symblepharon occur. 7ong term,
an3yloblepharon &a fixed globe( may occur. !atients with pure ocular involvement
may constitute a distinct subset of patients with "!. These patients are distinct
from patients with classic B! because they have a lower fre#uency of
immunoglobulin < &4g<( and "+ as depicted by 94=, and they are usually
negative for circulating autoantibodies as depicted by indirect
immunofluorescence &494=(. These patients do not have detectable reactivity to
B! antigens.
:asal involvement can be detected as erosions and crusting in the nasal vestibule,
best seen by nasal speculum examination.
;ral erosions often begin on the gingiva, particularly near the teeth. %rosions can
also be seen on the palate, the buccal mucosa, the lips, the posterior part of the
pharynx, the tongue, and the floor of the mouth. 4ntact blisters are rarely seen, but
they may appear flaccid or tense.
;n the genitalia, painful erosions involving the clitoris, the labia, the glans, or the
shaft of the penis may be seen. !erianal involvement manifests as perianal blisters
and erosions.
;n the s3in, tense blisters or erosions may be seen on either normal-appearing
s3in or erythematous pla#ues. "ommon sites include the scalp, the head, the nec3,
the distal extremities, or the trun3. 4n patients with active disease, erosions may be
persistent and difficult to heal. Scarring and milia fre#uently develop in this
condition and are helpful in clinically differentiating "! from B! and linear
immunoglobulin > &4g>( bullous dermatosis, both of which do not tend to scar.
7ocali6ed "! on the head and the nec3 is 3nown as Brunsting-!erry "!. This
disease heals with scarring and milia.
Causes
"! is an autoimmune blistering disease associated with autoantibodies directed
against basement membrane 6one target antigens. >utoantibodies of the 4g<
subclass, particularly 4g<,, are associated with "!) however, 4g> antibodies have
also been detected. The 2 ma5or antigens associated with "! are B!><2 and
epiligrin &laminin-(. !atients with clinical features of "! may have antibodies
directed against B!><1 or the %B> antigen &type ?44 collagen(. :o clinical
difference between patients with anti-B!><2 and antiepiligrin reactivity is
present.
B!><2 is also 3nown as collagen @?44. 4t is a 10.-3d hemidesmosomal protein
with multiple extracellular collagenous domains.
2
B!><2 is also a ma5or target
antigen for patients with B! and linear 4g> bullous dermatosis. !atients with "!
react with epitopes on B!><2 distinct from those associated with B! and linear
4g> bullous dermatosis. Aecent studies suggest that B!><2 is cleaved to form a
12.-3d fragment that contains the "! epitope. "irculating autoantibodies in
patients with autoantibodies specific for B!><2 bind to the epidermal side of
salt-split s3in as depicted by 494= study.
> subset of patients with "! reacts with laminin-. These patients have circulating
autoantibodies that bind to the dermal side of salt-split s3in as depicted by 494=
study. By immunoelectron microscopy, these autoantibodies deposit at the lower
lamina lucida, extending to the lamina densa. 7aminin- contains disulfide-lin3ed
alpha, beta, and gamma chains, of which the alpha subunit is the ma5or site of "!
reactivity. 7aminin- plays a ma5or role in the adhesion of human 3eratinocytes to
the dermis by binding alpha-B-beta-, integrin. Because defects in laminin- are
associated with 5unctional epidermolysis bullous, one group has suggested calling
"! associated with antiepiligrin autoantibodies ac#uired 5unctional %B) however,
most clinicians refer to this disease as antiepiligrin "!.
>utoantibodies specific for epiligrin and B!><2 are believed to be important in
blister formation. 7a6arova et al
+
have developed an animal model of antilaminin-
"! in which passive transfer of rabbit antilaminin- into neonatal mice leads to
a subepidermal blistering disease with features consistent with "!. !assive
transfer of antilaminin- antibodies to mast cell and complement deficient
neonatal mice can also induce blistering, suggesting a direct effect of the
circulating autoantibodies in inducing dermal-epidermal cleavage.
The incidence of the C7> haplotype C7>-9'B1D.+.1 is increased in patients
with ocular "!. This C7> haplotype may be important in the presentation of
specific epitopes on target antigens in the generation of an autoimmune response)
however, the precise events relevant in the initiation of autoantibody production
in patients with this disease are un3nown.
3. psoriasis:History
8orsening of a long-term erythematous scaly area

Sudden onset of many small areas of scaly redness

Aecent streptococcal throat infection, viral infection, immuni6ation, use of

antimalarial drug, or trauma

=amily history of similar rash

!ain

!ruritus

:o fever

?esicles

7ong-term rash with recent presentation of 5oint pain

Physical
=indings on physical examination depend on the type of psoriasis.
!la#ue psoriasis is characteri6ed by raised inflamed lesions covered with a silvery
white scale. The scale may be scraped away to reveal inflamed s3in beneath. This
is most common on the extensor surfaces of the 3nees, elbows, scalp, and trun3.

<uttate psoriasis presents as small red dots of psoriasis that usually appear on the
trun3, arms, and legs) the lesions may have some scale. 4t fre#uently appears
suddenly after an upper respiratory infection &EA4(.

4nverse psoriasis occurs on the flexural surfaces, armpit, groin, under the breast,
and in the s3in folds and is characteri6ed by smooth, inflamed lesions without
scaling.

!ustular psoriasis presents as sterile pustules appearing on the hands and feet or,
at times, diffusely, and may cycle through erythema, pustules, and scaling.

%rythrodermic psoriasis presents as generali6ed erythema, pain, itching, and fine

scaling.

Scalp psoriasis affects approximately .2 of patients, presenting as erythematous

raised pla#ues with silvery white scales on the scalp.

:ail psoriasis may cause pits on the nails, which may develop yellowish color and
become thic3ened. :ails may separate from the nail bed.

!soriatic arthritis affects approximately 1.2 of those with s3in symptoms. The
arthritis is usually in the hands, feet, and, at times, in larger 5oints. 4t produces
stiffness, pain, and progressive 5oint damage.

;ral psoriasis may present with whitish lesions on the oral mucosa, which may
appear to change in severity from day to day. 4t may also present as severe
cheilosis with extension onto the surrounding s3in, crossing the vermillion border.
Causes
7esions of psoriasis are caused by an increase in the turnover rate of dermal cells
from the normal 2+ days to +- days in affected areas.

Silver scale on the surface of lesions is a layer of dead s3in cells and may be
scraped away from most lesions even if the scale is not apparent on visual
inspection.

!atients with psoriasis have a genetic predisposition for the disease.

o <ene locus has been determined.

o The trigger event may be un3nown in most cases but is li3ely an
immunologic event.
o "ommonly, the first lesion appears after an upper respiratory infection,
such as streptococcal pharyngitis.
!erceived stress can cause exacerbation of psoriasis. Some authors suggest that
psoriasis is a stress-related disease and offer findings of increased concentrations
of neurotransmitters in psoriatic pla#ues.

>utoimmune function

o Significant evidence is accumulating that psoriasis is an autoimmune

disease.
o 7esions of psoriasis are associated with increased activity of T cells in
underlying s3in.
o <uttate psoriasis has been recogni6ed to appear following certain
immunologically active events, such as streptococcal pharyngitis,
cessation of steroid therapy, and use of antimalaria drugs.
Superantigens and T cells

o !soriasis is related to excess T-cell activity. %xperimental models can be

induced by stimulation with streptococcal superantigen, which cross-reacts
with dermal collagen. This small peptide has been shown to cause
increased activity among T cells in patients with psoriasis but not in
control groups.
o Some of the newer drugs used to treat severe psoriasis directly modify the
function of lymphocytes.
o >lso of significance is that 2.2 of those with C4? develop psoriasis
during the course of the disease.
4. Candidiasis, Cutaneous: History
"andidal vulvovaginitisF This common condition in women presents with itching,
soreness, and a thic3 creamy white discharge &see /edia =ile 1(. >lthough most
candidal infections occur more fre#uently with advancing age, vulvovaginitis is
unusual in older women. 4n the absence of estrogen stimulation, the vaginal
mucosa becomes thin and atrophic, producing less glycogen. "andidal
coloni6ation of vaginal mucosa is estrogen dependent and subse#uently decreases
sharply after menopause &see /edia =ile 2(. 4n contrast, the li3elihood of
coloni6ation increases during pregnancy &2-++2(. The widespread use of
hormone replacement for reduction of osteoporosis and heart disease may cause
an increasing trend in candidal vulvovaginitis among older women.

"andidal balanitisF Signs and symptoms of this candidal infection vary but may
include tiny papules, pustules, vesicles, or persistent ulcerations on the glans penis
&see /edia =ile +(. %xacerbations following intercourse are common.

"ongenital candidosisF This rarely reported candidal infection &-. cases during
the 111.s( may be ac#uired by the infant in utero or during delivery. !resumably,
congenital candidosis is an ascending intrauterine infection with cutaneous or
systemic manifestations that typically present within 12 hours after birth.
>lthough the congenital systemic form typically is fatal, congenital cutaneous
infections usually have a more benign course. !rematurity and the presence of an
intrauterine foreign body &intrauterine device( are associated with this condition.
Entreated, infants are at higher ris3 for systemic infection, which is associated
with a high mortality rate &-.2(. Some infants have respiratory distress and
pneumonia secondary to in utero aspiration of infected amniotic fluid.

;ropharyngeal candidiasis &;!"(F This form is 3nown more commonly as oral

thrush and is considered by many to be a minor problem of little significance that
may clear spontaneously. Cowever, without appropriate treatment this can lead to
a chronic condition that can result in discomfort and anorexia. Aarely,
oropharyngeal infection leads to systemic candidiasis.

o ;!" in the neonate most commonly is ac#uired from the infected

maternal mucosa during passage of the infant through the birth canal. ;!"
is + times more common in neonates of infected mothers compared to
uninfected mothers.
o
o ;!" is the most common type of clinical presentation in infants and
children. 4mmaturity of host defenses and incomplete establishment of the
normal orointestinal flora are li3ely reasons why C albicans often acts as a
pathogen in the neonate compared to a child aged several months who is
not nearly as susceptible. Beyond the neonatal age, C albicans is
considered a normal constituent of the oral and intestinal flora.
o
o "andidosis of the nipple in the nursing mother is associated with infantile
;!". :ipple candidosis almost always is bilateral, with the nipples
appearing bright red and inflamed, with the loo3 and feel of being
sunburned or on fire. Enli3e a painful-with-nursing cut or abrasion from
local trauma by the infant &incorrect latch-on(, nipple candidosis hurts
between feedings. /erely having the clothing brush against the nipples is
painful.
"andidal diaper dermatitis &"99(F 4nfants with ;!" invariably harbor C albicans
in the intestine and feces &0-1.2(. 4n most patients, ""9 is the result of
progressive coloni6ation from oral and gastrointestinal candidiasis. 4nfected stools
represent the most important focus for cutaneous infection. /oist macerated s3in
is particularly susceptible to invasion by C albicans. >dditional factors that
predispose infants to "99 include local irritation of the s3in by friction) ammonia
from bacterial brea3down of urea, intestinal en6ymes, and stool) detergents) and
disinfectants.

;ral candidiasis in adultsF Ese of broad-spectrum antibiotics and inhaled

corticosteroids, diminished cell-mediated immunity, and xerostomia are all ris3
factors for candidiasis &see /edia =ile ,(.

o @erostomia may be either primary resulting from the natural aging process
or secondary resulting from the anticholinergic effect of certain drugs
including psychoactive drugs such as phenothia6ines and tricyclic
antidepressants. > decrease in salivary production decreases both the
amount of available mucosal secretory antibody &immunoglobulin >
G4g>H( and the natural cleansing action provided by saliva.
o
o 4n older adults, the development of oral thrush in the absence of a 3nown
etiology should raise the clinicianIs index of suspicion for an underlying
cause of immunosuppression, such as malignancy or >49S.
o
o 8ith denture stomatitis, the areas of erythema may be painful and may
affect up to B2 of patients who wear dentures, especially those who wear
full sets. 9espite popular belief, denture stomatitis is not associated with
smo3ers or patients who are immunosuppressed.
4ntertrigoF /ost cases of cutaneous candidosis occur in s3in folds where occlusion
&by clothing or shoes( produces abnormally moist conditions. Sites such as the
perineum, mouth, and anus, in which Candida organisms normally may be
carried, are at further ris3 of infection. "andidal infection of the s3in under the
breasts or pannus occurs when those areas become macerated &see /edia =ile (.

9ecubital candidosis is a particular form of cutaneous candidosis that occurs on

the dorsal s3in of chronically bedridden patients.

!aronychiaF Candida organisms occasionally cause infection in the periungual

area and underneath the nailbed &see /edia =ile B(. Candida species &not always
C albicans( can be isolated from most patients with chronic paronychia. The yeast
is believed to play an etiologic role in this condition, but bacteria also may act as
co-pathogens. 4mmediate contact dermatitis to food allergens may play a role in
the pathogenesis of the condition as well. !rogression to total nail dystrophy has
been associated specifically with C albicans and usually has been limited to
women with 2 important predisposing conditions, ie, "ushing syndrome and
Aaynaud disease. 9isease is more common in people who fre#uently submerge
their hands in water and usually is not associated with the elderly population. ;ne
important exception to this generali6ation is the population of patients with
diabetes.

"andidosis and C4?F %pidemiologic studies indicate that a very high percentage
of patients infected with C4? contract some type of s3in disorder during the
course of the disease. /ore specifically, most patients with C4? infection have
some form of candidal infection during the illness. Aecurrent episodes of oral
candidiasis typically occur in patients in whom "9, counts are less than +..JK7,
an important mar3er of disease progression.

See "andidiasis, "hronic /ucocutaneous for discussion of that form of

candidiasis.

"utaneous hypersensitivity to C albicans has been reported in persons with

idiopathic vulvodynia.
Physical
"andidal vulvovaginitisF "linical examination reveals erythema of the vaginal
mucosa and vulval s3in with curdy white flec3s within the discharge. %rythema
may spread to include the perineum and groin, with satellite pustules.
>lternatively, the vaginal mucosa may appear red and gla6ed. > patient presenting
with symptoms of vulvovaginitis with identification of yeasts in the vaginal
discharge has a diagnosis of candidosis.

"ongenital candidosisF 4n 2..,, 9iana et al

reported that cutaneous congenital

candidiasis &"""( is a rare disease of term or premature infants. 4t typically
manifests as an erythematous maculopapular eruption affecting the trun3 and
extremities) it resolves after extensive des#uamation. !ustules and vesicles
usually are superficial and resolve spontaneously or with topical treatment &see
/edia =ile 0(. The presence of white microabscesses on the placenta and
umbilical cord of an infant with such an eruption must suggest the diagnosis of
""". 4t is always secondary to candidal chorioamnionitis, but it may pass
unrecogni6ed.

;!" in the infantF 7esions become visible as pearly white patches on the mucosal
surfaces. Buccal epithelium, gums, and the palate commonly are involved with
extension to the tongue, pharynx, or esophagus in more severe cases. 4f the lesions
are scraped away, an erythematous base is exposed. 7esions may progress to
symptomatic erosion and ulceration.

"andidal diaper dermatitisF The eruption of "99 usually starts in the perianal
area, spreading to involve the perineum and, in severe cases, the upper thighs,
lower abdomen, and lower bac3. /aceration of the anal mucosa and the perianal
s3in often is the first clinical manifestation. The typical eruption begins with scaly
papules that merge to form well-defined, weeping, eroded lesions with a scalloped
border. > collar of overhanging scales and an erythematous base may be
demonstrated. Satellite flaccid vesicopustules around the primary intertriginous
pla#ue also are characteristic of "99 and represent the primary lesions.

;ral candidiasis in elderly personsF The most common clinical appearance of

;!" &pseudomembranous candidosis or oral thrush( in the adult population
occurs as white pla#ues that are present on the buccal, palatal, or oropharyngeal
mucosa overlying areas of mucosal erythema. Typically, the lesions are removed
easily and may demonstrate areas with tiny ulcerations &see /edia =ile -(. 4n
addition, some patients may develop soreness and crac3s at the lateral angles of
the mouth &angular cheilitis(. 9enture stomatitis presents as chronic mucosal
erythema typically beneath the site of a denture.

4ntertrigoF 4ntertrigo typically presents with erythema, crac3ing, and maceration

with soreness and pruritic symptoms. 7esions typically have an irregular margin
with surrounding satellite papules and pustules. 8eb spaces of affected fingers or
toes are macerated and have the appearance of soft white s3in, which is a
condition termed erosio interdigitalis blastomycetica &interdigital candidosis(.

!aronychiaF The nailfold becomes erythematous, swollen, and tender, with an

occasional discharge. 7oss of the cuticle occurs, along with nail dystrophy and
onycholysis with discoloration around the lateral nailfold &see /edia =ile 1(. >
greenish color with hyponychial fluid accumulation may occur that results
entirely from Candida, and not Pseudomonas, infection. > potassium hydroxide
&*;C( preparation is helpful and is li3ely to show yeast organisms.
Causes
Cost factors that predispose patients to infections are numerous. 7ocal factors
such as tissue damage resulting from trauma, xerostomia, radiation-induced
mucositis, ulcerations, s3in maceration, or occlusion enhances adhesion and
predisposes patients to increased infection rates.

%ndocrine diseases such as diabetes mellitus, "ushing syndrome,

hypoparathyroidism, hypothyroidism, and polyendocrinopathy are associated with
increased susceptibility to infection. The mechanism by which diabetes mellitus is
believed to raise infection rates is through increased tissue glucose, altered yeast
adhesion, and decreased phagocytosis.

:utritional deficiencies may alter host defense mechanisms or epithelial barrier

integrity, allowing increased adherence or penetration. 4ron deficiency anemia and
deficiencies including vitamins B1, B2, BB, ", and folic acid are associated with
heightened infection rates.

T-lymphocyteLmediated immunity plays an important immunologic role against

infection through phagocytosis and 3illing by polymorphonuclear cells and
macrophages. 4ndividuals with deficient T-lymphocyte function, such as patients
with >49S, appear to be particularly vulnerable to mucosal or cutaneous
candidiasis but not to systemic infection. !atients with primary immune
deficiencies, such as lymphocytic abnormalities, phagocytic dysfunction, 4g>
deficiency, viral-induced immune paralysis, and severe congenital
immunodeficiencies, often are affected by ;!" and other fungal mycoses.

. /elanocytic :eviF History: /elanocytic nevi are common lesions that can be found
on the integument of almost all individuals. Some patients present with few lesions, while
others have hundreds. The number on a given individual increases in rough proportion to
the degree of s3in pigmentation.
:evi can be broadly divided into congenital and ac#uired types. 9etermining if a lesion is
congenital or ac#uired is generally easily accomplished by direct #uery of the patient,
although some small congenital melanocytic nevi are tardive and may be perceived by
the patient as ac#uired.
8hen evaluating the nature of a melanocytic lesion, a number of attributes must
be assessed. =urther commentary describing physical attributes can be found in
!hysical.
o 8hether a lesion has become symptomatic &eg, itchy, painful, irritated, or
bleeding( is important.
o :ot all melanocytic nevi that change are malignant, especially if change is
noted in a person younger than ,. years. Cowever, change that is
perceptible over a short time is an indicator of potential malignancy and
designates a lesion deserving of biopsy.
>c#uired melanocytic nevi are typically less than a centimeter in diameter and
evenly colored.
/elanocytic nevi most commonly are tan to brown, but coloration can be
variable, ranging from s3in-colored &nonpigmented( to 5et blac3.
Spit6 nevi are a distinctive variant of melanocytic nevi. 4n decades past, these
lesions were called 5uvenile melanomas, but now they are recogni6ed by specific
microscopical features and are 3nown to be benign. The outdated designation
5uvenile melanoma persists in some areas, but the term should be discarded
because of the dire prognosis it suggests and its potential for misconstrued
implications.
o >lthough Spit6 nevi tend to manifest as pin3 papules on the head of a
child, they can be clinically indistinguishable from conventional nevi in
some instances) they also can be heavily pigmented.
o /any Spit6 nevi exhibit considerable associated vascular ectasia and, thus,
display a hemangiomali3e clinical appearance.
Blue nevi are a form of melanocytic nevi that typically is heavily pigmented.
Because of the presence of deep pigmentation within a refracting colloidal
medium &namely, the s3in(, the brownish-blac3 pigment present contributes a
bluish cast to such lesions, thereby explaining the name. The optical effect that
accounts for clinical blueness is 3nown as the Tyndall phenomenon.
o :ot all blue nevi are blue, and some are various shades of gray, brown, or
blac3. The clinical appearance varies depending on the degree of clinical
pigmentation. 4ndeed, some blue nevi may be wholly amelanotic. Because
of the fact that the term blue nevus is not always reflective of the true
clinical appearance of the lesion, some dermatopathologists name blue
nevi based on the cellular morphology present &eg, dendritic melanocytic
nevi(.
o 9espite their variability in coloration, blue nevi are usually relatively
small and reasonably symmetric, as typically is the case in benign lesions.
Blue nevi typically occur on the distal extremities or scalp, but they can
occur anywhere.
Physical: !hysical examination involves, at a minimum, careful visual inspection of the
lesion in #uestion) in some instances, an examination of the entire s3in surface should be
performed. 4mportantly, document the dimensions and coloration of any lesion evaluated
and record its exact location. > simple drawing of the lesion and the overall topography
can be helpful. /any dermatologists use topographic charts to record the location of
multiple lesions that are monitored from visit to visit. Some dermatologists enumerate
individual lesions to facilitate follow-up. =or some patients, especially those with
multiple nevi, photographic documentation of lesions &including both distant views that
demonstrate topography and close views that capture subtle features of a particular
lesion( can be valuable. 8hen examining melanocytic nevi, the physician should examine
the scalp &possibly with the aid of a hair dryer(, the palms, the soles, between the toes,
and the genitalia.
"ongenital nevi vary considerably in si6e and are commonly classified as small
&M1 cm(, intermediate &1-+ cm(, or largeJgiant &N+ cm(.
o "ongenital nevi are generally relatively evenly pigmented and tan or
brown, especially those that are thin. 4n some congenital nevi, the cells
extend from the level of the epidermis to the subcutaneous fat. These
lesions can have an array of colors, and, at times, they cannot be easily
distinguished from melanoma based solely on findings from the clinical
evaluation.
o "ongenital melanocytic nevi are hamartomali3e) that is, they contain a
predominance of melanocytes but also seem to have simultaneous
accentuation of other cutaneous elements. Thus, an increase in the number
of hair follicles, the presence of follicles of increased si6e, or an increase
in other appendages may be observed.
"onventional or common ac#uired melanocytic nevi are generally less than 1 cm
in diameter and evenly pigmented. Some atypical melanocytic nevi &melanocytic
nevus of the so-called "lar3 or dysplastic type( exceed 1 cm in si6e, especially
those occurring on the trun3.
o Ounctional melanocytic nevi are macular or thinly papular. Ounctional
lesions typically range from brown to brownish-blac3. The dar3er
coloration of 5unctional melanocytic nevi stems from the fact that the
surface epidermis is often simultaneously hyperpigmented.
o "ompound and intradermal melanocytic nevi display elevation relative to
surrounding uninvolved s3in. "ompound melanocytic nevi are often
lighter in color than 5unctional nevi and range from tan to light brown.
Some compound melanocytic nevi have areas of dar3 pigmentation,
particularly those that have been recently irritated or traumati6ed. /any
wholly intradermal melanocytic nevi display no significant pigmentation.
o The development of a new area of pigmentation within a long-standing
nonpigmented or lightly pigmented compound or intradermal melanocytic
nevus is a cause for concern. 8hile pigmentary changes could be due to
incidental inflammation or recent irritation or trauma, the possibility of
evolving melanoma is also a consideration in the differential diagnosis.
<enerally, a biopsy for microscopic examination is warranted in this
context.
9ysplastic or atypical nevi &also 3nown as "lar3 nevi( are ac#uired variants that
are relatively flat, thinly papular, and relatively broad. ;ften, such lesions exhibit
targetli3e or fried eggLli3e morphology, with a central papular 6one and a macular
surrounding area with differing pigmentation.
o "lar3 nevi often occur in a familial fashion. >ffected individuals may
present with do6ens or hundreds of such lesions. >lmost invariably,
individuals with dysplastic nevi are of northern %uropean ancestry from
the Enited *ingdom, the :etherlands, <ermany, or, occasionally, !oland
or Aussia. /ost of these individuals have fair s3in and other "eltic
features. Some individuals have only a few atypical nevi, and their ris3 of
melanoma may not be much higher than those without such nevi. !ersons
with large numbers of nevi &N1..( have a high lifetime ris3 of melanoma
that approaches unity. !ersons with large numbers of nevi and a familial
history of melanoma &consisting of N2 members of the primary family
with melanoma( have an extremely high ris3 of developing melanoma and
deserve vigilant clinical monitoring.
o 9ysplastic nevi generally grow through lateral extension of the
intraepidermal component of the lesion) therefore, these lesions often
assume the clinical configuration of a fried egg, with a central papular
6one and a surrounding macular area of differing pigmentation. The
peripheral border is often perceived as blurred or fu66y because of this
lateral extension of superficial melanocytes.
o Some authorities have postulated that "lar3 &dysplastic( nevi are
precursors to melanoma. The designation dysplastic was chosen to suggest
that these lesions represent an intermediate &unstable( form between
conventional nevi and melanoma. 8hether or not they are precursor
lesions, dysplastic nevi are mar3ers for the ris3 of melanoma, and many of
the melanomas may occur de novo. 8hile the removal of all dysplastic
nevi from an individual with melanoma is generally not indicated, removal
of highly atypical appearing lesions is reasonable.
Spit6 nevi vary considerably in si6e, but they generally are smaller than 1 cm in
diameter.
o /any Spit6 nevi have a 3eratosisli3e #uality because of associated
epidermal hyperplasia and hyper3eratosis, and some have an angiomali3e
appearance because of associated vascular ectasia.
o The degree of pigmentation of Spit6 nevi also varies) a heavily pigmented,
small, spindle cell variant on the legs of women has been referred to as
pigmented spindle cell nevus or Aeed nevus because the pigmented
spindle cell variant was described by Aichard Aeed.
Blue nevi are not always blue, and they are not even always pigmented. The
designation blue nevus, although flawed, has been preserved for historical
reasons.
o Blue nevi are sometimes larger than other melanocytic nevi, occasionally
measuring 2 cm or greater in diameter. This is particularly true of cellular
lesions &cellular blue nevi( that occur at sun-protected sites, such as the
buttoc3s.
o Blue nevi are often firm because of associated stromal sclerosis, and they
often have a nodular #uality, a reflection of their deeper position within
the s3in.
o Ceavily pigmented blue nevi manifest clinically as blue, blac3, or gray
lesions, whereas blue nevi with lesser degrees of pigmentation may be tan
or brown or strictly the color of surrounding healthy s3in.
Causes: The etiology of melanocytic nevi remains un3nown. :o established genetic or
environmental influences are 3nown to contribute to the development of congenital nevi.
The specific genetic factors that contribute to the development of ac#uired melanocytic
nevi also remain un3nown. Cowever, reasonably reliable data suggest that the propensity
for developing large numbers of nevi &eg, multiple "lar3 nevi( might be inherited as an
autosomal dominant trait.
!atients with the familial atypical multiple mole and melanoma syndrome &also
3nown as the dysplastic nevus syndrome( develop do6ens to hundreds of
melanocytic nevi and have an elevated lifetime ris3 for the development of
melanoma. >s the name implies, this disorder is believed to have an inherited
basis.
Some evidence suggests that ultraviolet irradiation may trigger the development
of ac#uired melanocytic nevi. The number of melanocytic nevi in childhood is
inversely related to the degree of s3in pigmentation and is high in children with
poor sun tolerance. The mechanism of this induction has not been ade#uately
investigated, but such induction could represent an example of tumor promotion
by ultraviolet light.