Chromoblastomycosis is a chronic fungal infection of the skin caused by certain dematiaceous fungi that form characteristic dark-colored sclerotic bodies in tissue. Microscopically, there is pseudoepitheliomatous hyperplasia and a mixed inflammatory infiltrate containing the sclerotic fungal bodies. Cultures grow darkly pigmented molds. Treatment involves thorough surgical excision or prolonged antifungal therapy.

1. PATHOLOGY
(DERMATOPATH)
BERNADETTE R. ESPIRITU, M.D. FPSP
Anatomic & Clinical Pathologist

2. FUNCTIONS:
 Protection
 Sensation
 Thermoregulation
 Metabolic functions
(Vitamin D is synthesized in the
epidermis and subcutaneous fat is a
major energy store)

3. NORMAL SKIN
 Epidermis
 Dermis
◦ Hair follicle
◦ Sebaceous glands
◦ Multiple bundles of collagen

4. NORMAL EPIDERMIS
● Outer layer of skin
● Inner layers are dermis and
subcutaneous tissue
● Superficial fascia marks deep boundary
between skin and underlying soft tissue
● Epidermis forms outer layer of keratin
that is protective and waterproof
● Cells present include melanocytes,
keratinocytes, Langerhans’ cells and
Merkel cells

5. The epidermis is composed of 5 sublayers and the dermis is
composed of 2 sublayers, the papillary layer and the reticular layer.

6. EPIDERMIS
● Stratified squamous epithelium
containing keratinocytes in 4 layers:
◦ inner basal
◦ squamous
◦ granular
◦ outer cornified
● Keratinization takes 30-45 days
◦ Alterations in pattern and speed cause
dermatoses, hyperkeratosis or
parakeratosis

7. EPIDERMIS
● Stratum Basalis or Stratum Germinatum)
Basal layer:
These cells are cuboidal and are separated from the
dermis by a basement membrane.
Merkel Cells Tactile cells of located in the basal layer
of the epidermis.
It is from the basal layer that cells emerge and change
morphology as they migrate to the upper layers of the
epidermis.
Basal cell carcinoma originates in this level.
Other cells within the epidermis include: Melanocytes to
provide pigmentation. They occur within the basal layer.
Langerhans cells and macrophages also occur within
skin.

8. EPIDERMIS
● Squamous layer
(stratum spinosum)
- Prickle Cell or Malpighian layer
- Has several layers of cells,
larger than basal layer, which
become flat and eosinophilic
as they approach the surface due to
an increase in keratin and reduction in
ribosomes
- May have clear vacuolated cytoplasm
- Cells are attached to each other by fine spiny
bridges with central dot-like desmosomes
(Bizzozero’s nodule)
- Loss of spiny bridges causes acantholysis

9. EPIDERMIS
● Stratum granulosum: Granular layer
- 1 to 3 layers of flattened cells with intensely basophilic
keratohyaline granules, which contain precursors of filaggrin
protein, which causes aggregation of keratin filaments
- These cells have multiple cytoplasmic granules that are
keratohyalin. In the outermost layer of the stratum
granulosum cell death occurs and keratinization is nearly
complete. This is not always present; it is seen only in thick
skin.
 Stratum lucidum: Translucent layer
- Homogenous eosinophilic zone
- flattened keratinocytes that are present only in soles
and palms and exists between the Granular layer and
the overlying keratinized or cornified layer

10. EPIDERMIS
Stratum Corneum
(Cornified layer)
 - Also called horny layer
- Basket weave pattern of multiple layers of polyhedral cells without
nuclei
- Region is thicker and more compact in acral region [peripheral
body-
limbs, fingers, ears]
 This is comprised of dead and dying cells that lack nuclei and are
filled with keratin. Ultimately the strong junctions between these cells
weaken and desquamation occurs.
● Rete ridges:
- Undulating forms of epidermis and dermal papillae at
dermoepidermal junction - Flattens with aging

11. epidermis

13. DERMIS :
 Collagen and elastic fibers within ground substance composed of
mucopolysaccharides and mucoproteins
 Adnexa, nerves and blood vessels
 Degenerates with age and sunlight and becomes basophilic
 Divided into superficial papillary dermis and deeper reticular dermis
 Papillary dermis contains rete pegs and periadnexal dermis
- Has thin and delicate collagen fibers compared to thicker fibers
in reticular dermis

14. DERMIS:
● Acral skin has Sucquet-Hoyel canals –
specialized arteriovenous anastomoses,
surrounded by glomus cells
● Glomus cells are modified smooth muscle cells
that are round with clear cytoplasm and well
defined cytoplasmic borders
● Papillary dermis of palms and soles contains
Wagner-Meissner corpuscles with a tactile
function
● Deep dermis and subcutis of weight bearing
areas contain Pacinian corpuscles, sensitive to
pressure
● Normal dermis contains a few fibroblasts, mast
cells, macrophages, lymphocytes and dermal
dendrocytes (Factor XIIIa+)

15. SKIN ADNEXAE
 Hair Growth is from a bulb. A small bundle of smooth muscle is
attached to the follicular sheath and the dermal papilla and contracts
to make the hair stand on end. This muscle is called erector pili.
 Sebaceous glands. These are associated with the hair follicle and
secrete an oily substance (sebum) that waterproofs and moisturizes
the skin and hair. Sebaceous glands are abundant and discharge
directly onto the skin surface at the nipples, lips, eyelids, labia
minora and glans penis.
 Merkel Cells Tactile cells of located in the basal layer of the
epidermis.

 Pacinian Corpuscle A nerve receptor located in the subcutaneous
fatty tissue that responds to pressure and vibration.

 Sweat glands. These are mostly simple coiled glands that secrete a
watery substance. They are important in thermoregulation, as
evaporation cools blood in peripheral vascular beds.

16. NORMAL SKIN ADNEXAE
 Hair follicles
 Sebaceous glands
- waterproofs & moisturizes the skin &
hair.
- abundant and discharge directly onto
the
skin surface at the nipples, lips, eyelids,
labia
minora and glans penis.
 Eccrine Sweat glands
- impt in thermoregulation: evaporation

17. FOLLICULAR UNIT
● Functional complex of terminal and vellus
hair follicle, sebaceous gland, erector pili
muscle and (depending on site) apocrine
gland
● Often contains Demodex folliculorum mites,
clumps of Staphylococcus epidermidis or
Pityrosporum yeasts
● Each follicle has an epithelial and
mesenchymal component
● Embryologically, the epithelial buds (hair
germs) derive from the fetal epidermis and
project downward, interacting with
mesenchymal cells which form the dermal
sheath and dermal papillae

18. Contains protected repositories of epithelial stem cells
Forms hair via cyclic process of
(a) anagen or growing phase
(b) catagen or involuting phase
(c) telogen or resting phase
Matrix (regenerative) cells line the dermal papillae, are mitotically
active, give rise to hair shaft and inner root sheath

19.  HP: demonstrating the deeply
pigmented hair shaft towards the
center, surrounded by the cells of the
hair sheath.

20. • inner and outer hair sheath.
•The two sebaceous glands are attached
to the hair follicle above the erector pili
muscle.

21.  Normal Sweat Glands
•Multiple sections of the ampullary region of the
normal sweat gland.
•The eccrine sweat gland is composed of
numerous acinar structures with a large central
lumen.
•These are multiple cuts across a single,
convoluted stucture.

23. Normal Sebaceous Gland
•Towards the periphery of this
single acinus of a sebaceous
gland is a single layer of
cuboidal cells that are
somewhat deeper staining.
•Towards the center are large
cells which are pale staining
cytoplasm and a central
pyknotic nucleus.
•At the very center is a dark
staining structure that
represents the duct of this
gland.
•The central, light-staining
cells are normally shed as
such into the hair shaft and
form the oily secretion that
coats the hair as well as the
overlying skin.

25. NORMAL SKIN ADNEXAE
Positive stains
● Eccrine and apocrine glands:
EMA, CEA, keratin, S100
● Myoepithelial cells: actin, calponin,
caldesmon, S100

26. Subcutaneous tissue
 Also called subcutis
 Contains lobules of mature adipose
tissue and thin connective tissue septa
 Pacinian Corpuscle : A nerve
receptor located in the subcutaneous
fatty tissue that responds to pressure
and vibration.

27. SUBCUTIS

28. ANTHRAX
 Etio: endospores of Bacillus anthracis, a
common soil organism
 Manifestations: Cutaneous, Pulmonary or
Gastrointestinal symptoms
Culture: nonhemolytic, nonmotile, ground-
glass colonies that retain their shape when
manipulated; grow readily on sheep red blood
cell agar (no special conditions needed)
Gram stain: gram positive, spore-forming rods
Treatment: antibiotics, reduces mortality from
20% to less than 1%

29. ANTHRAX: MICRO
ESCHAR
 Coagulative necrosis of epidermis and dermis
 Prominent edema of underlying viable dermis
 Frequent focal hemorrhages,
 Intense, reactive-appearing mononuclear
inflammatory infiltrates around small vessels and
some adnexae
 PMNs only around necrotizing sebaceous glands
 Sharp demarcation between superficial necrotic
and deeper edematous viable tissue (at
periphery)
 Islands of regenerating epidermis under necrotic
layer of eschar
 Vessels with degenerated endothelial cells and
focal thrombi
 No abscess, No granulation tissue

30. ANTHRAX
 Bacterial images: bacteria, in CSF
(inhalation anthrax)
 EM images: anthrax spores

31. SUBCUTIS : Carbuncle
 Painful localized bacterial infection of
skin and subcutis, usually with several
openings through which pus is
discharged
CMV (cytomegalovirus)
 Gross/clinical images: punched out
ulcers in immunocompromised
patients

32. CMV Infection of Skin
Numerous cleanly punched out ulcers
that occur in the case of an acute
CMV infection in an
immunocompromised individual.

33. ERYSIPELAS
Streptococcal infection causing upper dermal edema and “orange
peel” or peau d’orange appearance

34.  “orange peel” or peau d’orange
appearance

35. FOLLICULITIS
 Inflammation around
hair follicles, involving
follicular opening or adjacent skin
 Infectious cases are either superficial
(fungi, bacteria, syphilis, viral) or deep
(granulomatous, due to fungi or
bacteria)
 Fungal forms may be endothrix
(spores within hair shaft) or ectothrix
(spores on outer surface of hair shaft)

36. Infectious cases:
FOLLICULITIS
Superficial
◦ Fungi
◦ Bacteria
◦ Syphilis
◦ Viral
Deep
◦ granulomatous, due to fungi or bacteria
Fungal forms:
◦ endothrix (spores within hair shaft)
◦ ectothrix (spores on outer surface of hair
shaft)

37. Noninfectious cases:
FOLLICULITIS
Superficial / Suppurative
 Acne vulgaris
 Rosacea
 Follicular mucinosis
 Steroid-induced
Deep/Granulomatous
 Acne vulgaris-conglobate and keloidal
forms or perforating
 Spongiotic (Fox-Fordyce disease, atopic
dermatitis, pruritic folliculitis of
pregnancy)

38. FOLLICULITIS
Perifolliculitis forms:
 lymphocytic (lichen planopilaris,
pityriasis rubra pilaris)
 granulomatous (perioral dermatitis,
rosacea)
Pseudolymphomatous folliculitis: facial
lesion with dense, polymorphic, mixed
lymphocytes around hair follicles and
infiltrating follicular epithelium

39. SUBCUTIS:Fungi
 Fungi-Candida

40. FUNGAL:
CHROMOBLASTOMYCOSIS
 Clinically resembles carcinoma
 Color of lesion is due to brown spores
 Indolent cutaneous disease due to
Phialophora, Fonsecaea or Cladosporium
fungi, that multiply by cross wall formation
and splitting
Cultures (Phialophora): slow growing,
dark gray-black and hairlike
Gross: verrucous or nodular, resembling CA
Micro: marked pseudoepitheliomatous
hyperplasia and mixed granulomatous-
neutrophilic infiltrate; contains brown spores;
fungi have cross walls but no budding

41. CHROMOBLASTOMYCOSIS
 Chronic verrucous chromoblastomycosis of the
hand due to Cladophialophora carrionii
 tissue hyperplasia forming a white verrucoid
cutaneous lesion.
 In Australia, chromoblastomycosis due to C.
carrionii occurs mostly on the hands and arms of
timber and cattle workers in humid tropical
forests

42. CHROMOBLASTOMYCOSIS
Laboratory diagnosis:
1. Clinical Material: Skin scrapings
and/or biopsy.
2. Direct Microscopy: (a) Skin
scrapings should be examined using
10% KOH and Parker ink or calcofluor
white mounts; (b) Tissue sections
should be stained using H&E, PAS
digest, and Grocott's methenamine
silver (GMS).

43. CHROMOBLASTOMYCOSIS
 Direct microscopy of tissue is
necessary to differentiate between
chromoblastomycosis and
phaeohyphomycosis where the tissue
morphology of the causative organism
is mycelial

44. CHROMOBLASTOMYCOSIS
 Skin scrapings from a patient with
chromoblastomycosis mounted in 10%
KOH and Parker ink solution showing
characteristic brown pigmented,
planate-dividing, rounded sclerotic
bodies.

45. CHROMOBLASTOMYCOSIS
 H&E stained section showing
characteristic dark brown sclerotic cells
which divide by binary fission and not by
budding.
 Note all agents of chromoblastomycosis
form these sclerotic bodies in tissue.

46. CHROMOBLASTOMYCOSIS
 3. Culture: Clinical specimens should
be inoculated onto primary isolation
media, like Sabouraud's dextrose
agar.
 Cultures of the etiologic agents of
chromoblastomycosis are typically
olivaceous-black with a suede-like
surface.

47. CHROMOBLASTOMYCOSIS
 Culture identification is the only
reliable means of distinguishing these
fungi.

48. CHROMOBLASTOMYCOSIS
 4. Serology: There are currently no
commercially available serological
procedures for the diagnosis of
chromoblastomycosis.
 5. Identification: Culture characteristics
and microscopic morphology are
important, especially conidial
morphology, the arrangement of conidia
on the conidiogenous cell and the
morphology of the conidiogenous cell.
Cellotape flag and/or slide culture
preparations are recommended.

49. CHROMOBLASTOMYCOSIS
Causative agents:
 Cladophialophora carrionii, Fonsecaea pedrosoi,
Phialophora verrucosa
Management:
 The treatment of chromoblastomycosis has been
exceedingly difficult.
 Successful surgical excision requires the removal
of a margin of uninfected tissue to prevent local
dissemination.
 Flucytosine with or without thiabendazole has
been extensively used in the past.
 However both itraconazole [400 mg/day] and
terbinafine [500 mg/ day] for 6 to 12 months have
been used successfully for the treatment of
chromoblastomycosis.

50. Histoplasma capsulatum
 A dimorphic saprophytic fungus found in soil
contaminated with bird or bat feces
 Endemic to southeast US (80% of this population
may have positive intradermal histoplasmin skin
test), Mexico, Africa, Asia
 Via inhalation of spores, causing a primary
pulmonary pneumonia
 Pneumonia is self-limited in immunocompetent
patients, but disseminates in
immunocompromised (very young, very old,
HIV+) to liver, spleen, bone marrow, nodes, lung,
rarely to skin
 Disseminated disease: strongly associated with
AIDS; fever, weight loss, splenomegaly; variable
cutaneous lesions

51. H. CAPSULATUM
 Culture: tan-white-brown wooly mold
at 25-30C on Sabouraud dextrose
agar; organisms have delicate,
septate hyphae, 1-2 microns thick,
with large rough-walled macroconidia
5-15 microns; revert to yeast at 37C
on sheep blood agar; yeast is 2-4
microns, budding, single nuclei,
round/oval with thin rigid walls
 Treatment: antifungal drugs

52. H. CAPSULATUM
 Gross: cutaneous lesions are
nodules, papules, ulcers; less
commonly macules, pustules or
vesicles
 Micro: isolated intracellular
organisms, larger aggregates
surrounded by chronic inflammatory
cells and fibroblasts (but no
neutrophils or eosinophils) or
epithelioid granulomas with variable
caseation; may be narrow based

53.  Histoplasma capsulatum - a disseminated
infection, and the macrophages containing
small yeasts appear in multiple organs,
particularly those of the mononuclear
phagocyte system (lymph node, liver, spleen,
marrow).
 Liver with H and E stain

54. HISTOPLASMOSIS
 Histoplasma capsulatum organisms in
macrophages are seen in liver with
PAS stain.

55.  Histoplasma capsulatum yeast forms
fill phagocytes.

56. MADURAMYCOSIS
 Actinomadura is an aerobic
actinomycetes, a filamentous
bacterium found in soil
 Initially believed (incorrectly) to be a
fungi, so diagnostic procedures are
often performed in mycology
laboratories

57.  MADURA
 FOOT

58. ONCHOMYCOSIS
 Spread of fungi to nails
 Candida albicans, Scopulariopis
brevicaulis, others;
 often multiple fungal species

59.  ONYCHOMYCOSIS

60. SUPERFICIAL FUNGAL INFECTIONS
 Scalp and beard lesions may have
superimposed bacterial folliculitis /
perifolliculitis
 May also be found on neoplastic skin
lesions
 Infections of stratum corneum are
usually caused by dermatophytes
 Spores, hyphae and neutrophils usually
are present in stratum corneum or hair
shafts
 Associated with pseudoepitheliomatous
hyperplasia

61. SUPERFICIAL FUNGAL INFECTION
 Kerion celsi: superimposed bacterial
folliculitis on tinea of scalp
 Majocchi’s granuloma: nodular
granulomatous perifolliculitis; inflammation of
dermis and subcutis by dermatophytes,
usually Trichophyton rubrum
 Sycosis barbae: tinera barbae with
superimposed bacterial follicultis
 Tinea corporis: infection of trunk of children
and adults, associated with excessive heat
and humidity; scaly, red, annular plaques
(“ringworm”)
 Tinea cruris: "jock itch", infection of inguinal
area of obese men during warm weather

62.  Tinea pedis: "athletes foot", infection causing
diffuse erythema and scaling, initially in web
spaces, often with bacterial superinfection

64.  This photomicrograph reveals a number of macroconidia of
the dermatophytic fungus Epidermophyton floccosum.
 known to be a cause of dermatophytosis leading to tinea
corporis (ringworm), tinea cruris (jock itch), tinea pedis
(athlete’s foot), and onychomycosis or tinea unguium, a
fungal infection of the nail bed.

65.  Tinea capitis: infection causing
hairless patches of skin in scalp,
usually in children

66.  Tinea barbae: infection of beard area
of adult men

67. Tinea versicolor
 Infection by Malassezia furfur of upper
trunk
 Micro: variably pigmented macules of all
sizes, with orthokeratotic hyperkeratosis,
yeast spores and pseudohyphae within
stratum corneum; short hyphae and
spores (“spaghetti and meatballs”) with
GMS or PAS stains
 Presence of fungi does not rule out
coexisting inflammatory and neoplastic
disorders

68. Malasse

69.  Coccidioides immitis infection can often be
disseminated to multiple organs, though
pneumonia is often present because the
infection is acquired via the respiratory
tract.
 Spherules are seen here in lung with H and

70.  Spherules of Coccidioides immitis are seen
here in liver with H and E staining.
 Note the thick wall of the sperules containing
endospores. One spherule is rupturing to
release the endospores, the yeast phase
which grows at body temperature.

71. HERPES SIMPLEX / VARICELLA ZOSTER
 Painful diseases caused by herpes simplex virus
or varicella zoster virus (chickenpox)
 After primary infection, viral particles reside in
sensory ganglia and are dormant until they erupt
as recurrent herpes simplex virus or shingles
(zoster)
 Associated with leukemia and lymphoma
 Shingles has dermatomal distribution or severe
involvement of trigeminal nerve-first division with
corneal ulceration and herpetic keratitis
 The two viruses are differentiated by culture or
immunologic methods
 Gross: grouped vesicles on an erythematous
base, later become pustules, then crusts

72.  Here is the classic lesion of varicella zoster
following the dermatome T7 in this 12-year-
old boy

73. HIDRADENITIS SUPPURATIVA
 Due to bacterial infection around apocrine
glands of axilla, occasionally perineum or
vulva
 Usually due to anaerobes
 May produce fistulas and scarring
 Treatment: excision of involved skin if
medical therapy fails
 Gross: abscesses, sinuses, perianal fistulas
with scarring
 Micro: heavy neutrophilic or mixed
inflammatory infiltrate around apocrine glands
with dilated lumina

74. HIDRADENITIS SUPPURATIVA

75. HIV associated
 Dermatitis: interface dermatitis
occurs early in HIV infection, with
pronounced vacuolization of basal
keratinocytes, inflammatory infiltrate is
CD3+/CD8+ T cells expressing
granzyme B7 and TIA1, and
histiocytes; decreased Langerhans
cells

76. HIV ASSOCIATED
 Folliculitis: infants and adults;
perifollicular chronic inflammatory
infiltrate, often with follicular rupture,
often with marked eosinophils
 Infections: scabies, fungi,
mycobacteria, syphilis, bacterial
angiomatosis
 Maculopapular eruptions: in 25%, in
trunk with possible extension to
extremities; nonspecific perivascular
lymphocytes and histiocytes in upper
dermis, variable papulovesicular foci

77.  Papular neutrophilic xanthoma:
foamy macrophages, extracellular
nuclear dust, hyaline necrosis of
collagen fibers
 Papular pruritic eruptions:
anywhere on body; may wax and
wane; superficial and mid-dermal
perivascular lymphocytes with
eosinophils, acanthosis, parakeratosis

78.  Psoriasis
 Seborrheic dermatitis: common,
usually severe, involves trunk &
extremities

79.  Vasculitis:
leukocytoclastic, may be due to
HIV directly or CMV
 Viruses: herpes simplex (20%; painful
perianal or perioral ulcers with large
intranuclear inclusions), severe varicella-
zoster infection, CMV (ulcerative lesions
at mucocutaneous junctions), molluscum
contagiosum, hairy leukoplakia, anal
warts, bowenoid papulos

80.  A. widespread maculopapular HIV
exanthema.
 B. oral enanthema with ulceration.

81.  A. interface dermatitis with individual necrotic
keratinocytes, lymphocytic exocytosis.
 B. several lymphocytes surrounding one necrotic
keratinocyte ("satellite cell necrosis
 C. With necrosis and vacuolization of
keratinocytes

82. IMPETIGO
 Usually affects hands and face of
normal children or adults in poor
health
 Common, due to Staphylococcus or
Streptococcus infection
 Gross: erythematous macule
 Micro: neutrophils beneath stratum
corneum; may have subcorneal
pustule

83. LEPROSY
 Also called Hansen’s disease
 Most US cases from immigrants
 Diagnosis: PCR

84. LEPROMATOUS LEPROSY
 Micro: numerous foamy macrophages
(Virchow cells, lepra) stuffed with acid-
fast bacilli; granulomas in and around
cutaneous nerves or infiltrating and
destroying arrectores pilorum muscle;
may have subcutaneous nodules
(erythema nodosum leprorum)
 Positive stains: acid-fast (Ziehl-
Neelsen)
 DD: fibrous histiocytoma

85. TUBERCULOID LEPROSY
 Micro: bacilli are scanty; granulomas
in and around cutaneous nerves or
infiltrating and destroying arrectores
pilorum muscle

86. LEPROMATOUS
LEPROSY
LEPROMATOUS LEPROSY

87. LEPROMATOUS
LEPROSY – ACID
FAST

88. MALAKOPLAKIA
 Rare; may occur in HIV+ patients
 Micro:
Histiocytes have Michaelis-Gutmann
bodies, rarely contain gram negative
organisms

89. MOLLUSCUM CONTAGIOSUM
 Caused by human molluscum contagiosum poxvirus
 Multiple nodules on skin, trunk, anogenital region, due
to skin to skin contact; also sexually transmitted
Gross:
 multiple firm, pruritic, pink-tan nodules, up to 4 mm, with
central cores containing white keratinous material
 raised, firm, flesh colored nodules
Micro:
 characteristic findings of sharply delimited dermal lesion
containing proliferating epithelium
 molluscum bodies present (large cells with cytoplasmic,
faintly granular eosinophilic inclusions that displace
nuclei; contain viral particles)
 may have intense dermal inflammatory infiltrate; rarely
metaplastic ossification

90. MOLLUSCUM CONTAGIOSUM
 The features to look for are:
◦ epidermis acanthosis (hyperplasia) which
grows into the dermis to form multiple
lobule
◦ intracytoplasmic inclusion bodies which
are eosinophilic (stianed pink with H & E)
at the base but becomes more basophilic
(stained blue with H & E) at the superficial
layer
◦ central crater into which the inclusion
bodies discharge their content

91.  Lobules of epidermis with inclusion
bodies. Note the inclusion bodies are
pinker at the base and become
progressively darker and bluish towards
the crater

92.  c/s showing nestles of inclusion
bodies

93. MYCOBACTERIA,
ATYPICAL
 May cause ulcerations, abscesses,
rheumatoid-like nodules, histiocytic
reactions, panniculitis
 Most commonly due to M. kansasii, M.
marinum, M. ulcerans

94. GROSS DESCRIPTION:
 The specimens labelled "synovium, left fifth
toe" consisted of irregular portions of focally
hemorrhagic, fibrofatty tissue, up to 1.0 cm in
greatest dimension.
 From a 52 y.o.woman with foot infection

95. Histologic sections revealed fibrovascular and adipose tissue with granulation
tissue and focal prominent acute inflammation. Gram stain showed numerous
gram positive rods . Acid fast stain revealed several groups of rarely beaded
acid fast rods

96. Aerobic cultures showed rare coagulase negative
staphylococcus. Gram positive rods grew on 5%
sheep blood agar after four days. The gram positive
rods were acid fast positive. Growth of buff colored,
nonphotochromogenic, rounded, smooth colonies
without filamentous extensions was noted on
Lowenstein-Jensen agar at 28oC in four days .
Subculture onto Lowenstein-Jensen agar with 5%
NaCl and MacConkey agar without Crystal Violet
showed growth in 5 days. Growth on tap water agar
after 48 hours at 28oC lacked aerial hyphae and
showed morphology typical of mycobacterial species.
The 3-day arylsulfatase test was positive. The nitrate
reduction and iron uptake tests were negative. The
organism was identified as Mycobacterium abscessus

97. Parvovirus B19
 skin manifestations are petechial eruption in
a glove and stocking distribution, reticular
truncal erythema, and "slapped cheek" sign
 Manifestation: Fifth’s disease; atypical
presentations resemble asymptomatic
papular eruption, Sweet’s syndrome,
myopathic dermatomyosis, lupus, lower
extremity palpable purpura
 Due to delayed type hypersensitivity, antibody
dependent cellular immunity against microbial
antigens in epidermis or endothelium, or
circulating immune complexes

98.  Gross images: slapped cheek
appearance
 Micro: interstitial histiocytic infiltrate
with piecemeal fragmentation of
collagen and mononuclear cell-
predominant vascular injury pattern;
also interface dermatitis, eczematous
alterations, papillary dermal edema;
occasionally mesenchymal mucinosis,
leukocytoclastic vasculitis

99. PARVOVIRUS B19

100. SYPHILIS
 Secondary lesions are maculopapular,
and resemble drug eruption, lichen
planus, psoriasis
 May present as moth-eaten alopecia
on scalp, mucous patches on tongue
 Occur on face and trunk

101. syphilis
 Gross: scaly, flesh-colored to erythematous
papules or annular plaques; copper macules
on palms and soles
 Micro: dense perivascular or diffuse plasma
cell infiltrate with marked endothelial swelling
and proliferation in blood vessels is
characteristic; may have noncaseating
granulomas, vacuolar interface change,
acanthosis, spongiosis, lymphocyte
exocytosis

102.  PRIMARY SYPHILIS
 The epidermis is ulcerated, and the underlying tissue is infiltrated by
predominantly plasma cells, macrophages, and lymphocytes.
 Positive stains: Steiner stain (71% sensitive)

103. TB-SKIN: LUPUS VULGARIS
 Reactivation form of tuberculosis
 Chronic cases are associated with
squamous cell carcinoma
 Diagnosis: culture or PCR
 Gross: facial lesions with small, firm
nodules in underlying, irregular red patch
with elevated borders; nodules become
pale and tan when pressed with a glass
slide; variable ulceration
 Micro: sarcoid-like or necrotic
granulomas in dermis; rare acid-fast
bacilli

104.  Lupus vulgaris on the face of an 88 y-
o female (gross findings).
 The facial skin is the most common
site of reinfection tuberculosis of this
form.

105.  Histologic features of lupus vulgaris (HE).
 Caseous granuloma is observed in the
dermis in the biopsy specimen. Caseation is
a relatively rare event and bacilli are usually
sparse.

106.  Fibrosing epithelioid granuloma extends
into the subcutaneous tissue. The
cytoplasm of the epithelioid cells appears
to be foamy (HE). Necrosis is only focally
seen.

107.  A few acid-fast bacilli are identified within the
lesion (Ziehl-Neelsen). "Scrofuloderma" is a
form of skin tuberculosis showing secondary
fistulous extension from the lymph node or
bone.

108. WARTS
 Also called verrucae
 Cutaneous and mucosal lesions
caused by
various types of human
papillomaviruses
(HPV), a type of papova virus
 Usually resolve in 6-24 months

109. Micro:
 focal epidermal hyperplasia with
hyperkeratosis and parakeratosis,
papillomatosis (not verruca plana), may have
trichilemmal keratinization
 Koilocytes (keratinocytes in upper squamous
layer with vacuoles, large cytoplasmic
eosinophilic aggregates, pyknotic nuclei)
 Tangential sections may show squamous
cells surrounded by inflamed stroma
 Older lesions may lack cytoplasmic changes
 Viral nuclear inclusions are basophilic

110.  Verruca vulgaris:
 A tan rough sessile nontender
enlargement is present on the palmar
skin.

113. CAUSE:
 HPV
 130 known types of HPV
 HPV infects the Squamous epithelium,
usually of the skin or genitals, but each HPV
type is typically only able to infect only a few
specific areas on the body.
 Many HPV types can produce a benign
growth, often called a "wart" or "papilloma", in
the area they infect. Many of the more
common HPV and wart types are as follows:
 Common warts - HPV types 2 and 4 (most
common); also types 1, 3, 27, 29, and 57 and
others.

114. WART
 Cancers and Genital Dysplasia - "high-risk"
HPV types are associated with cancers, (
cervical cancer and can also cause some
vulvar, vaginal, penile, anal and some
oropharyngeal cancers.
 "low-risk" types are associated with warts or
other conditions
 High-risk: 16, 18 (cause the most cervical
cancer); also 58, 33, 45, 31, 52, 35, 39, 59,
and others.
 Plantar warts (myrmecia) - HPV type 1 (most
common); also types 2, 3, 4, 27, 29, and 57
and others.

115. WART
 Anogenital warts (condylomata
acuminata or venereal warts) - HPV
types 6 and 11 (most common); also
types 42, 44 and others.
 Low-risk: 6, 11 (most common); also 13,
44, 40, 43, 42, 54, 61, 72, 81, 89, and
others.
 Flat warts - HPV types 3, 10, and 28.
 Butcher’s warts - HPV type 7.
 Heck’s Disease (Focal epithelial
hyperplasia) - HPV types 13 and 32.

116. INFESTATIONS

117. INFESTATIONS
 Skin lesions due to direct irritant
effects, immediate or delayed
hypersensitivity or specific effects of
venom
 Bites: urticaria, inflamed papules or
nodules, variable ulceration
Body louse
 Causes hyperpigmentation and
scratch marks (excoriations)

118. BODY LOUSE
 This is a magnified view of a female body louse
with larvae. Lice cause itching and a
characteristic excoriated skin rash (looks like a
scrape). They may also transmit diseases,
including relapsing fever, typhus, and trench
fever. (Image courtesy of the Centers for Disease
Control and Prevention.)

119. PEDICULOSIS (LICE)
 Causes pruritis, enlarged local lymph
nodes
 Eggs are attached to hair shaft (nits)

121. PUBIC LOUSE (CRABS)
 A sexually transmitted disease
 Gross images:

122. PUBIC LICE: Phthirus pubis
Habitat:
Crab or pubic lice lay their eggs on coarse
body hair, particularly the hair associated with
the pubic regions, perianal region, thighs,
abdomen, and armpits, but they will also
infest a person's beard and eyelashes.
- Much less mobile than head or body lice, they
can remain attached with their mouthparts in
the skin for days
Pubic lice are typically found only on humans
and are most often transmitted directly from
person to person, particularly during sexual
contact.

123. PUBIC LICE
When crab lice feed they can inject saliva
into the host, causing pruritus and
itching.
Scratching the area can increase the
irritation. The area can become scaly
and hardened with oozing lesions.
Painless blue spots can appear after crab
lice feed.
Other evidence of crab lice includes the
occurence of rust-colored insect
exretions and darker spots in underwear
and flakes similar to dandruff in pubic
hair.

124. SCABIES (MITE)
 Produces burrows and extremely
pruritic erythematous papules on
interdigital skin, palms, wrists
 Micro: burrow appears as cleft in
upper epidermis containing mite body
parts; epidermis exhibits acanthosis,
parakeratosis, spongiosis, with dense
eosinophilic dermal infiltrate

125.  Scabies in the young adult - sexually transmitted infection.
 Cleaning and disinfection by hot water are needed for the
linen to avoid unnecessary transmission
 Within the cornified layer, a cut surface of Sarcoptes
scabiei hominis with the spiked cuticle and immature and
mature eggs is observed (HE)
 The epidermis is moderately acanthotic and the dermis is
actively inflamed.

126.  Another case of scabies in the aged (68 y-o M). Itchy papules are seen
on the interphalangeal area, focally with burrow formation. The mite
burrow formation is pathognomonic of scabies.
 Nosocomial infection of scabies is problematic, particularly in the ward of
neurosurgery and in the care stations for the aged.
 The female mite, Sarcoptes scabiei hominis, eggs and pigmented feces
in the unstained skin scratch preparation after potassium hydroxide
treatment.
 The mite, measuring 0.3-0.45 mm, has four pairs of legs. The mite eats
keratinocytes, so that the feces is pigmented by melanosomes and
mitochondria.

127. BLISTERING
DISORDERS

128. EPIDERMOLYSIS BULLOSA
 At least 12 genetic disorders with site of cleavage in
dermis, lower epidermis or at dermoepidermal junction
 Blisters form shortly after birth due to pressure, rubbing
or trauma
 Cause scarring or milia on dorsum of hands, elbows
and knees and oromucosal lesions
 Dystrophic types: blisters beneath lamina densa
(associated with anchoring fibrils), cause scarring
 Hallopeau-Siemens recessive dystrophic form
associated with aggressive squamous cell carcinoma
 Junctional: blisters at lamina lucida, skin appears
normal
 Simplex: degeneration of basal cell layer causes clinical
bullae
 Epidermolysis bullosa acquisita: rare autoimmune
disorder of antibodies to hemi-desmosomes; rarely
occurs following drug therapy, usually unkown cause

129.  JUNCTIONAL EPIDERMOLYSIS
BOLLUSA

130.  Micro: subepidermal blister with
variable inflammation; superficial
dermis is fibrotic
 Positive stains: linear C3 and IgG
deposits along epidermal basement
membrane
 EM: may be necessary for
classification

131. Epidermolysis Bullosa
 An uncommon disorder with a genetic pattern (three types),
presenting in children. There is also an acquired form of the
disease. Profound scarring of the skin leads to deformities. In the
mouth the children present with dental anomalies and fragile
blisters. Scarring usually follows.
Key Features
 Subepithelial separation of the epithelium from the underlying
corium
 Subepithelial vesicle
MICRO:
 formation of subepithelial vesicle
 subepithelial separation of the epithelium from the underlying
corium

132. ERYTHEMA MULTIFORME
 Acute, self limited, hypersensitivity reaction to
infections (herpes simplex, mycoplasma,
histoplasmosis, coccidioidomycosis, typhoid,
leprosy), drugs (penicillin, sulfa, salicylates,
phenytoin, phenylbutazone), carcinoma /
lymphoma, or collagen vascular disorders
 Affects skin (distal extremities, palms, soles)
and mucous membranes with target lesions;
also sore throat and malaise
 Any age
 Gross: variable (multiform) lesions –
papules, macules, vesicles, bullae, target
lesions; commonly in mucous membranes

133.  ERYTHEMA
MULTIFORM
E

134. ERYTHEMA MULTIFORME
 Micro: subepidermal bullae with basement
membrane in bullae roof due to dermal edema;
severe dermal inflammatory infiltrate (includes
cytotoxic T cells) with nuclear dust; overlying
epidermis often demonstrates liquefactive
necrosis and degeneration, dyskeratotic
keratinocytes; variable epidermal spongiosis and
eosinophils
 No microabscesses, no festooning of dermal
papillae
 Note: erythema multiforme may have variable
histologic changes from toxic epidermal
necrolysis to dermal disturbances; may also have
dermoepidermal bullae with basal lamina at floor
of bullae
 Positive stains: granular C3 and IgM at
basement membrane and in vessels

135. IMPETIGO CONTAGIOSA
 Also called bullous impetigo
 Affects face, trunk and extremities of
infants and children
 Contagious superficial infection of
skin, associated with staphylococci
 Gross: small vesicles or pustules that
rupture easily; may be covered by
yellow crust
 Micro: vesicles just below keratin
layer

136. STEVEN-JOHNSON
SYNDROME
 Systemic form of erythema multiforme
with fever
 Common in children, often involving lips,
oral mucosa or other mucosa with
erosions and hemorrhagic crusts
 Infection of affected areas may cause life
threatening sepsis
 Toxic epidermal necrolysis: variant
with full thickness epidermal necrosis but
intact cornified layer, subepidermal
bullae and sloughing of skin/mucosal
epithelium; analogous to severe burn

137.  Micro: full thickness epidermal
necrosis with separation of epidermis
from dermis; necrotic keratinocytes at
edge of bullae
 DD: staphylococcal scalded skin
syndrome (similar clinically, but plane
of cleavage is in granular layer),
necrolytic migratory erythema
(glucagonoma syndrome – has
superficial epidermal necrosis)

138.  Note early cutaneous slough with areas of violaceous
erythema.
 Extensive sloughing on the face
 Note the presence of both 2-zoned atypical targetoid
lesions and bullae.

139. OTHER
DERMATOSIS

140. ACANTHOSIS NIGRICANS
 80% are benign type, either autosomal
dominant or associated with tissue resistance
to insulin, including diabetes, obesity,
Cushing’s disease
 20% are associated with GI or other internal
malignancies; usually age 40+ years
Gross: brown, velvety, verrucous plaques in
axillae, back of neck and other skin folds
Micro: orthokeratotic hyperkeratosis (not
actually acanthosis) and papillomatosis of
stratum spinosum; hyperpigmentation of
basal cell layer, but no melanocytic
hyperplasia

141.  This photograph demonstrates the hyperpigmented,
brownish, velvety lesions of acanthosis nigricans.
 This skin condition may occur in skin folds such as the axilla
(armpit - pictured here), neck, and other areas.
 In adults, it may be associated with hormonal problems,
internal malignancy, obesity, and drugs.

142. ACNE ROSACEA
 Also called rhinophyma
 Erythema of central face, with
acneiform pustules and papules,
telangiectasia, blepharitis
 Micro: perinfundibular lymphocytic or
granulomatous inflammation

143.  Rosacea is a common condition characterized
by symptoms of facial flushing and a spectrum
of clinical signs, including erythema,
telangiectasia, coarseness of skin, and an
inflammatory papulopustular eruption
resembling acne.

144. ACNE VULGARIS
 Usually teenagers, either gender, although often more severe
in males
 Due to hormonal variations and alterations in hair follicle
maturation
 Worsens with drugs (steroids, testosterone, contraceptives),
oils/tars, heavy clothing, tropical climates
 Noninflammatory acne is due to open and closed comedones
 Open comedones: small follicular papules with central black
keratin plug (due to oxidation of melanin)
 Closed comedones: follicular papules with a deeper plug
below the surface
 Follicles may rupture and become inflamed
Treatment: antibiotics, isotretinoin
Micro: lipid (sebum) and keratin within hair follicle; variable
lymphocytes and histiocytes

145.  Severe Acne Vulgaris
involving the face &
back

146.  Acne, grade III; papulopustules.
 Acne, grade IV; multiple open comedones,
closed comedones, and papulopustules, plus
cysts.

147. CAUSES OF ACNE
VULGARIS Main underlying cause - a genetic predisposition.
- Inherited in an AD pattern with incomplete penetrance.
Acne vulgaris may skip a generation.
The following aggravating factors are recognized:
 Cosmetic agents and hair pomades may worsen acne.
 Medications that can promote acne development
include steroids, lithium, some antiepileptics, and
iodides.
 Congenital adrenal hyperplasia, polycystic ovary
syndrome
and other endocrinological disorders associated with
excess androgens may trigger the development of acne
vulgaris. Even pregnancy may cause a flare-up.
 Mechanical occlusion with headbands, shoulder pads,
back packs, or under-wire bras can be aggravating
factors
 Excessive sunlight may either improve or flare acne. In
any case, the ultraviolet exposure ages the skin

148. ACUTE ECZEMATOUS
DERMATITIS
 Allergic contact dermatitis:
 Atopic dermatitis: unknown cause (not allergic); may
be familial (hay fever, asthma, eczema); occurs on
flexural surfaces
 Drug-related: usually systemic (penicillin), eosinophils
present in deep dermis
 Eczema: red, papulovesicular, oozing, crusted lesions
(spongiotic dermatitis) which evolves to raised, scaling
plaques (epidermal hyperplasia and excessive scale)
 Irritant contact dermatitis
 Photo-dermatitis: due to UV light exposure
 Primary irritant dermatitis: due to repeated rubbing
 Micro: spongiosis, perivascular lymphocytic infiltrate
 DD: drug reaction (prominent eosinophilic infiltrate)

150.  ATOPIC DERMATITIS

151. Infancy
 Atopic dermatitis is usually noticed soon after
birth. Xerosis occurs early and often involves
the whole body; the diaper area is usually
spared.
 The earliest lesions affect the creases
(antecubital and popliteal fossae), with
erythema and exudation. Over the following
few weeks, lesions usually localize to the
cheeks, the forehead and scalp, and the
extensors of the lower legs; however, they
may occur in any location on the body,
usually sparing the diaper area. Lesions are
ill-defined, erythematous, scaly, and crusted
(eczematous) patches and plaques.
 Lichenification is seldom seen in infancy

152. Childhood
 Xerosis is often generalized. The skin is flaky
and rough.
 Lichenification is characteristic of childhood
atopic dermatitis. It signifies repeated rubbing
of the skin and is seen mostly over the folds,
bony protuberances, and forehead.
 Lesions are eczematous and exudative.
Pallor of the face is common; erythema and
scaling occur around the eyes. Dennie-
Morgan folds (ie, increased folds below the
eye) are often seen. Flexural creases,
particularly the antecubital and popliteal
fossae, and buttock-thigh creases are often
affected.

153. Adulthood
 Lesions become more diffuse with an
underlying background of erythema.
The face is commonly involved and is
dry and scaly.
 Xerosis is prominent.
 Lichenification may be present.
 A brown macular ring around the neck
is typical but not always present. It
represents localized deposition of
amyloid.

154. ERYTHEMA NODOSUM
 Red, painful, subcutaneous lesions on
anterior surface of legs that usually
involute in days/weeks, leaving
depressed pigmented lesions
 No ulceration
 Immune mediated, but precise
mechanism is unknown
 May be associated with streptococcus
infection, tuberculosis, sarcoidosis,
coccidioidomycosis, ulcerative colitis,
Behcet’s disease, drug reactions or
idiopathic

155.  Micro: inflammatory infiltrate at junction of
dermis and subcutis, extending along fibrous
septa separating fat lobules and in dermal
vessels; may be neutrophilic, lymphocytic,
histiocytic or granulomatous (noncaseating or
with occasional giant cells); variable vasculitis
 Miescher’s radial granuloma: cluster of
small histiocytes arranged around a central
cleft
 DD: nodular vasculitis or subacute nodular
migratory panniculitis (usually septal), Weber-
Christian disease associated panniculitis
(usually lobular inflammation)

156. Erythema Nodosum
 Deep dermal tissue with inflammatory cells in a
perivascular location, between collagen bundles.
 Infiltration of inflammatory cells between the adipocytes,
typical of a lesion of erythema nodosum.
 Represents a common reaction to a variety of insults to the
skin.

157. EXFOLIATIVE DERMATITIS &
ERYTHRODERMA
 Total body erythema and scaling
 Due to drug reaction, allergic contact
dermatitis, psoriasis, pityriasis rubra
pilaris, malignancy
 Associated with dermatopathic
lymphadenitis
 Micro: nonspecific changes; may
have lichenoid dermatitis
 DD: Sezary’s syndrome / mycosis
fungoides

158.  Diffuse skin involvement
 90% or more scaling of the cutaneous surface
 Exfoliative dermatitis onset usually occurs in persons
older than 40 years, except when the condition results
from atopic dermatitis, seborrheic dermatitis,
atphylococcal scalded skin syndrome a hereditary
ichthyosis.
 Age of onset primarily is related to etiology.

159. ICHTHYOSIS
 Disorder of epidermal maturation; skin
resembles fish scales
 Associated with excessive keratin
buildup due to desquamation defect,
leading to retention of abnormally formed
scale
 Usually apparent at birth; in adults, is
associated with malignancies
 Ichthyosis vulgaris: common type
 Lamellar ichthyosis: rare, inherited skin
condition of newborn with shedding of
plate-like layers of skin
 X linked variant: deficiency in steroid
sulfatase, which removes proadhesive

160.  Gross: skin resembles fish scales;
rough scaly patches and plaques
 Micro: increased stratum corneum
with loss of normal basket weave
pattern, little inflammation; loss of
granular layer in ichthyosis vulgaris

161. Lamellar ichthyosis
 The abnormal stratum
corneum has produced what
appears as very thick scale
on the skin, and with an
abnormal barrier layer these
patients commonly get
secondary staphylococcal
and yeast infections.
 Note that there are other
associated ectodermal
problems such as the teeth,
hair, and eyelids.
 X-LINKED

162. LICHEN PLANUS
 Purple, pruritic, polygonal papules of unknown
origin
 Usually flexor arms and legs, glans penis and
mucous membranes; may be confined to oral
mucosa
 Self limiting lasting 1-2 years, although longer for
oral lesions; may have zone of
hyperpigmentation after resolution
 Wickham straie: white dots or lines within
papules
 Koebner phenomenon: new lesions at sites of
trauma
 Lichen planopilaris: primary site of involvement
is epithelium of hair follicles, causing alopecia

163.  Micro: classic example of a lichenoid dermatitis;
hyperkeratosis and acanthosis; prominent
granular cell layer, sawtoothing of rete pegs,
band like chronic inflammatory infiltrate (T cells
and macrophages) that destroys the
dermoepidermal junction; Civatte bodies
(apoptotic basal cells, PAS+); artifactual cleft
formation between epidermis and papillary
dermis; occasional subepidermal bullae; no
atypia
 Variants: bullous, pemphigoid, hypertrophic,
atrophic, follicular
 Positive stains: immunoglobulins along
dermoepidermal junction
 DD: lichenoid dysplasia (atypia present),
lichenoid dermatitis

164.  hyperkeratosis and acanthosis; prominent granular cell layer,
sawtoothing of rete pegs, band like chronic inflammatory
infiltrate

165. SYSTEMIC LUPUS
ERYTHEMATOSUS (SLE)
 Due to anti-DNA antibodies
 Usually women
 Fatigue, fever, arthritis, erythematous
bilateral butterfly (malar) rash of face,
renal disease, lymphadenopathy,
serositis
 Exacerbated by sunlight
 Discoid lupus-type lesions in 1/3
 Gross images: Malar rash of the face

166.  Micro: fibrinoid necrosis at
dermoepidermal junction with
liquefactive degeneration and atrophy of
epidermis; more mucin deposition in
reticular dermis than discoid lupus
 Positive stains: IgG, IgM, C5b-C9 (by
direct immunofluorescence) in clinically
involved skin as irregular band at
dermoepidermal junction; IgG and IgM
only in 50% in normal skin
 DD: polymorphous light eruption,
Jessner’s lymphocytic infiltration of skin

167.  This is a picture of a systemic lupus
erythematosis rash on the face. Lupus
erythematosis often produces a "butterfly
rash" or malar rash.
 Typically, the rash also appears on the
nose.

169. MILIARIA
 Obstruction of sweat gland ducts
during high heat and humidity

170. MYXEDEMA
 Often in pretibial skin
 Due to accumulation of mucopolysaccharides
in dermis, similar to that in orbital tissues,
caused by excess TSH secretion or
hypothyroidism
 Skin is thick, dry, waxy
 Elephantiasis: extreme disease
 Gross: large nodular lesion in patients with
thyrotoxicity or euthyroid
 Micro: eccrine sweat glands contain
aggregates of mucoprotein that separates
collagen strands
 Positive stains: mucicarmine, Hale’s
colloidal iron, PAS+ diastase resistant

171.  Bilateral erythematous infiltrative plaques
in the pretibial areas.

172. NECROBIOSIS LIPOIDICA
 Usually on legs of diabetic patients
 Gross: atrophic, yellow depressed
plaques
 Micro: ill defined areas of disintegrating
dermal collagen, surrounded by
palisading lymphocytes and histiocytes,
with thick walled vessels, usually in
reticular dermis
 Negative stains: lysozyme, mucin
 DD: granuloma annulare (mucin+,
lysozyme+, no association with
diabetes), necrobiotic xanthogranuloma
(head and neck of patients with
paraproteinemia, not associated with

173. Necrobiosis lipoidica
diabeticorum
 is a chronic skin
disease characterized
by shiny plaques that
vary in color from light
yellowish to reddish-
tan.
 It is seen more
commonly in women.
 Although the name
implies diabetes and
the majority of cases
occur in diabetics, this
condition can occur in
individuals without
diabetes.

175. PITYRIASIS ROSEA
 Initially a single large “herald” patch, then
a generalized rash 1-2 weeks later,
lasting 2-6 weeks
 Self-limited, benign
 Children, young adults
 Micro: subacute spongiotic dermatitis
with papillary dermal microhemorrhage
and discrete mounts of parakeratosis
 DD: secondary syphilis (usually plasma
cells in dermis)

176.  Pityriasis rosea is a skin disease that
produces oval spots (papules) over the trunk.
The rash is frequently preceded by a "herald
patch" (pictured here) lasting 1 to 2 weeks.
The rash is usually rose red to brownish red
with fine scales and central clearing. Itching
(pruritus) occasionally occurs. Spontaneous
remission occurs in 2 to 8 weeks. It is
probably caused by an infectious agent, most
likely a virus.

177.  HERALD PATCH

178. PSORIASIS
 Also called psoriasis vulgaris
 Common, affects 1% of population, all
ages
 Chronic, bilaterally symmetric,
nonpruritic lesion of elbows, knees,
umbilicus, lower back, scalp, glans
penis; may be generalized
 Associated with arthritis, myopathy,
enteropathy, spondylitic heart disease,
AIDS
 30% have nail discoloration and
onycholysis

179.  Pustular psoriasis: rare; prominent small
pustules in plaque; either localized (hands/feet)
or generalized and life threatening with fever,
leukocytosis, diffuse infections, secondary
infections and electrolyte disturbances
 Auspitz sign: bleeding when scale is lifted from
the plaque
 Koebner phenomenon: new lesions form at site
of trauma
 Parapsoriasis: similar morphologically but no
pain or itching; small plaque variants are
considered benign; large plaque variants and
parapsoriasis variegata are consistered early
stages of cutaneous T cell lymphoma

180. PSORIASIS
 Treatment: photochemotherapy (psoralen) and
ultraviolet A light (PUVA) – associated with increased
risk of melanoma and squamous cell carcinoma
 Gross: well demarcated erythematous plaques covered
by fine, loosely adherent, silvery-white scales
 Micro: parakeratosis but usually no hyperkeratosis,
acanthosis with downward elongation of rete ridges
(resembles a comb), thin/no granular cell layer,
suprapapillary thinning (attenuated layer of epidermal
cells above tips of dermal papillae), Munro
microabscesses (neutrophils in parakeratotic scale);
increased mitotic figures above basal layer; prominent
dermal capillaries, mixed dermal infiltrate of
lymphocytes, macrophages and neutrophils
 DD: psoriasiform lesions - lichen simplex chronicus,
florid seborrheic dermatitis, pityriasis rubra pilaris,
mycosis fungoides, Reiter’s syndrome

181. PSORIASIS
 This is a picture of guttate (drop-
shaped) psoriasis on the arms and
chest.
 Guttate psoriasis is a rare form of
psoriasis.
 It frequently follows a streptococcal
infection, appears rapidly and
affects the face, chest, and nearest
limbs.
 The patches are small and round or
oval and have the typical
appearance of psoriasis.
 This photograph shows the diffuse
and widespread coverage on the
arm and chest

183. SEBORRHEIC DERMATITIS
 Nummular eczema (silver dollar-sized
patches) to generalized exfoliative
dermatitis (severe atopic dermatitis) to
large vesicles on palms and soles
(dyshidrosis)
 Not due to any known agents,
although associated with irritant
contact dermatitis
 Micro: acute, subacute or chronic
spongiotic dermatitis

184.  This is seborrheic dermatitis on the face. Note the
redness (erythema) and mild scaling. Individuals with
AIDS frequently develop seborrheic dermatitis or other
types of skin rashes, as seen in this person who is HIV
positive.
 his is a close-up of seborrheic dermatitis. Note the
redness (erythema) and mild scaling. Individuals with
AIDS frequently develop seborrheic dermatitis or other
types of skin rashes, as seen in this person.

186. NON-
MELANOCYTIC
LESION

187. FIBROEPITHELIAL POLYP
 Also called acrochordon, squamous
papilloma, skin tag, soft fibroma
 Common, non-neoplastic, no clinical
significance
 Ages 40+ years; usually face, neck,
trunk, intertriginous areas
 Associated with diabetes, intestinal
polyposis; increase during pregnancy
 May be a common endpoint of various
processes, including seborrheic
keratosis or warts

188. Gross: soft, flesh-colored, baglike
tumor, attached to skin by slender stalk
Micro: papillary, fibrovascular cores
covered by squamous epithelium; may have
ischemic necrosis due to torsion

189. SEBORRHEIC KERATOSIS
 Common; usually age 40+ years
 Benign, although may coexist with malignancy
 Usually affects trunk, head and neck, extremities;
only hair bearing skin
 Not HPV related, although HPV present in
morphologically similar cases of
epidermodysplasia verruciformis and bowenoid
changes
 Dermatosis papulosa nigra: in blacks
 Leser-Trelat sign: sudden appearance or
increase in number and size of seborrheic
keratoses, associated with internal malignancy
 Treatment: superficial curettage, freezing

190.  Gross: exophytic, sharply
demarcated, pigmented lesions that
protrude above surface of skin, appear
to be stuck to skin, single or multiple,
soft, tan-black
 Micro: basal keratinocyte
proliferations

191. SEBORRHEIC KERATOSIS
Patterns:
 acanthotic – most common, rounded verrucous surface; thick
layer of basal cells mixed with horn cysts (contain keratin)
and pseudohorn cysts (downgrowth of keratin into tumor
mass); no prominent granular layer; some cells contain
melanin due to transfer from neighboring melanocytes
 irritated – pronounced squamous metaplasia with abundant
eosinophilic cytoplasm and whorled squamous eddies; often
atypia and mitotic figures; resembles carcinoma
 inverted follicular keratosis – irritated seborrheic keratosis
that grows downward and involves hair follicles
 Also hyperkeratotic, adenoid, acantholytic and desmoplastic
patterns
 Positive stains: low molecular weight keratin
 Negative stains: high molecular weight keratin (usually),
HPV
 DD: squamous cell carcinoma (particularly desmoplastic
pattern)

192. VERRUCOUS
HYPERPLASIA
 Papillomatosis associated with hyperkeratosis
 Benign
 Nonspecific change, associated with various
entities
 Epidermal nevus: if present since birth or early
childhood; higher risk for basal cell carcinoma or
adnexal tumors
 Nevus sebaceous of Jadassohn: associated
with malformed adnexal structures
 Verruca vulgaris: exophytic growth with marked
hyperkeratosis, focal parakeratosis,
papillomatosis resembling church spires,
prominent granular layer, koilocytosis, dilated
vessels within papillary dermis

193. DERMOID CYST
 Resemble keratinous cysts of
epidermal type, but also have hair
adnexae
 Usually face of children along
embryonic closure lines

194. HIDROCYSTOMA
 Usually face, solitary or multiple
 Lined by two rows of sweat duct-like
epithelium which may have apocrine
features

196. ECCRINE ACROSPIROMA
 Also called solid-cystic or nodular
hidradenoma
 Arises from sweat gland distal excretory duct
 Gross: nodules with cystic foci high in dermis
 Micro: nests/lobules of cells resembling
eccrine poroma with either clear cytoplasm or
prominent squamous metaplasia; may have
marked vascularity; small and large lumina
are lined by cuboidal ductal cells or columnar
secretory cells; cystic spaces may be due to
degeneration of tumor cells
 Positive stains: keratin, EMA, CEA, S100,
vimentin
 DD: glomus tumor (different staining pattern)

198. BASAL CELL CARCINOMA
 The most common
cancer affecting
humans
 Slow growing
 At least 75% first
tumours are on the
face
 Relatively ‘benign’ in
most cases – but if
left untreated can be
disfiguring and life
threatening

199. ETIOLOGY
 The most important risk factor is solar
ultraviolet radiation
 Type 1 skin
 Episodes of painful sunburn in early life
 Mechanism of injury by UV radiation is
complex: direct
DNA damage
damage to repair mechanisms
immune dysregulation
mutations in p53 suppressor
genes

200. TYPES OF BCC (1)
NODULAR
 Usually begin as a
small pink ‘pearly’
papule
 Develop a
depression in the
centre
 Rolled edge
 Overlying
telangiectasia

201. TYPES OF BCC (2)
SUPERFICIAL
 Usually found on
the trunk
 May be multiple
 Flat red patches
 Usually have
typical beaded
edge

202. TYPES OF BCC (3)
MORPHOEIC
 White or waxy
 Always on face
 Presents as a
spontaneous ‘scar’
 Margins are usually
much wider than
what is clinically
visible

203. TYPES OF BCC (4)
 Multifocal
 Bowenoid – usually found on lower legs
of women with sun damaged skin.
Diagnosis by biopsy
 Poorly differentiated

204. MANAGEMENT
 Surgical excision – with 4mm margins –
complete excision of 98% tumours less than
2cm in diameter
 Moh’s micrographic surgery – immediate
histological analysis. If residual tumour –
further surgery. Ensures precise and
conservative tumour removal. Usually
reserved for high risk lesions – eyelids, nose,
lips, ears. 5 year cure rate 99%
 Photodynamic therapy
 Radiation therapy
 Topical therapy – imiquimod (aldara) –
immune modulator

205. FOLLOW UP POLICY
 Overall recurrence rate for BCC is around
5%
 Thus patients are followed up for 2 years –
at least 6 monthly
 However risk of second primary – 5 years
after excision 36% patients develop a
second primary and 20% develop multiple
new BCCs

206. SQUAMOUS CELL
CARCINOMA
 Less common than
BCC but more
aggressive
 The incidence is
rising
 Most important
aetiological agent
is UV radiation –
total life time
exposure

207. SCC: ETIOLOGY
 Sunlight exposure
 Therapeutic
radiation
 Chemical
carcinogens –
arsenic
 Immunosuppressio
n
 Viral infection
 Scars and chronic
inflammation
 Premalignant
lesions
 Genetic syndromes

208. CLINICAL FEATURES
 May be seen at any
body site
 Disorganised keratin
 Keratin horn on a
fleshy tumourous
base
 Surface tends to
ulcerate

209. CLINICAL FEATURES
 SCC on lower leg -
Marjolin’s ulcer
 Failure to respond
to nursing care
 Heaped up margin

210. METASTASES
SCC may spread in several ways:
 Local invasion
 Along tissue plains, between muscles,
over periosteum
 Along nerves and blood vessels
 Distant mets

211. RISK FACTORS FOR
METASTASES
 Most SCCs behave in a relatively benign
fashion
 SCC arising from sun-damages skin has a
low propensity to metastasize – 0.5%
compared to 2% of all SCCs
 SCCs arising in certain situations have a
much higher rate of spread:
>2cm
poorly differentiated
scars and ulcers
immunosuppression
perineural invasion
recurrent lesions

212. DIFFERENTIAL DIAGNOSIS
 Solar keratosis
 Bowen’s disease
 Viral warts
 Cutaneous horn
 Keratoacanthoma
 Basal cell carcinoma
 Leg ulcers

213. MANAGEMENT
 Intention to cure primary lesion and prevent
recurrences
 No one treatment has been shown to be
effective in all patients
 Thus treatment should be tailored to the
individual as much as possible
 Ideally – multidisciplinary oncology team –
clinical oncologist, dermatologist, pathologist,
appropriate surgeon

214. TREATMENT METHODS
 Excision – margins 2-10mm
 Moh’s micrographic surgery
 Curretage and cautery
 Cryotherapy
 Laser
 Photodynamic therapy
 Retinoids
 Radiation therapy

215. FOLLOW UP POLICIES
 75% SCCs recur within 2 years
 95% recurrences are within 5 years
 Most clinicians follow up for at least 4
years
 3 monthly for first year then every 6
months
 Close examination of the scar site and
draining lymph node areas is
recommended

216. MELANOCYTIC TUMORS
MELANOMA IN SITU
Definition
● Malignant melanocytes in epidermis,
without dermal invasion
● Variants include lentigo maligna,
superficial spreading, and acral
melanoma

217. MELANOMA IN SITU
Clinical
● Cases in sun damaged skin may resemble
benign lichenoid keratosis
● Characterized by pagetoid spread,
confluence, and nesting of atypical
melanocytes
● May be associated with invasive malignant
melanoma
● Hutchinson's sign: periungual extension of
brown-black pigmentation from longitudinal
melanonychia [pigmented stripe within length
of nail bed] onto the proximal and lateral
nailfolds
● Large, pigmented lesions, irregular margins,
irregular pigmentation

218. MELANOMA IN SITU
Treatment and prognosis
● Excision with negative margins
● Evaluation of entire margin is
recommended - not by classic Mohs
surgery, slow Mohs may be used
● Imiquimod cream 5% is a nonsurgical
alternative

219.  Figure 1.
Representative
images of
longitudinal
melanonychia prior
to biopsy.
 Note the positive
Hutchinson sign in
panel B. Scales
indicate millimeters

220. MELANOMA IN SITU
Micro description
● Atypical melanocytes in epidermis with
no dermal invasion
● Usually epidermal effacement (absences
of rete ridges in some foci
● Predominance of individual unit
melanocytes over nests
● Confluent growth of melanocytes along
the dermo-epidermal junction
● Pagetoid spread
● Involvement of the adnexal structures

221.  A 28-year-old man consulted for a pruritic
pigmented lesion of his right shoulder.
Dermoscopy revealed an asymetric pattern
with blue-gray globules and focal
structureless areas. The lesion was excised
and pathology revealed a melanoma in situ.

222. DERMOSCOPY
M-IS

223.  Case 2, an 80-year-old man. A Broad, irregularly pigmented macule
24 mm in maximum diameter on the sole of his foot.
 B. Dermoscopic image showing the typical parallel ridge pattern
 C. Histopathologic image showing proliferation of atypical
melanocytes in the epidermis, consistent with the diagnosis of
melanoma in situ.
 D. Fluorescence in situ hybridization image showing multiple red
CCND1 signals with 2 green reference signals in an atypical
melanocyte (white arrow).

224. Case 10, a 60-year-old woman.
A. Light brown macule on the sole of her foot. Maximal diameter of this lesion is only
6 mm.
B. Dermoscopic image showing the typical parallel ridge pattern
C. Histopathologic image showing a very slight increase of healthy-looking
melanocytes along the basal layer
D. Fluorescence in situ hybridization image showing the CCND1 amplification in a
melanocyte (white arrow) within the basal cell layer of the epidermis. Clustered
and multiple red CCND1 signals are seen (inset).

225.  Shave biopsy of mid-back shows usual
features of hyperkeratotic seborrheic
keratosis with co-existing melanoma in-
situ.

226.  High magnification of melanoma in-situ
component, with nests of atypical
melanocytes along dermal-epidermal
junction.

227. MELANOMA
 Third most common skin cancer
 Caused by severe intermittent bouts of
sun exposure
 Found on sun exposed and non-
exposed sites
 Second most common cancer to affect
young women
 High metastatic potential - local, lymph
nodes, lung, liver and brain

228. MELANOMA
 30% arise in a pre-existing mole
◦ Features to look out for are asymmetry of the
mole, irregular shape and irregular colour
 Most commonly arise in normal skin in
renal transplant patients

229. MELANOMA

230. Methods of Preventing Long
Term Skin Damage
 Avoid sun
 Avoid midday sun
 Use photo-
protective clothing,
hats etc
 Use sunblocks

231. MELANOMA, INVASIVE
Epidemiology
● Incidence increasing worldwide
● 48,000 cases and 9,200 deaths in US in 2000
● Usually due to sun (UV light) exposure
Populations at higher risk:
● Whites with fair skin, red hair, tendency to burn or freckle from
sun exposure, large number of melanocytic nevi, xeroderma
pigmentosum, familial dysplastic nevi, melanosis, vitiligo,
frequent sunburns at any age 5-10% familial, possibly
neurofibromatosis type I
● Blacks and Hispanics in US have low risk, their common
melanoma sites are palms, soles, nail beds or mucous
membranes; often poorer prognosis
● Usually occurs after puberty, occasionally children - all have
same morphology

232. MELANOMA, INVASIVE
Sites
● Head and neck, back, lower extremities (particularly in
women)
● Also oral and anogenital mucosa, esophagus,
meninges, eye
● Rarely subungual (“melanotic whitlow”), palm, sole
Clinical warning signs
● Change in color of pigmented lesion
● Enlargement of existing mole
● Itching or pain in preexisting mole
● Development of new pigmented lesion in adult life
● Irregular borders in pigmented lesion
● Variegation of color in pigmented lesion

233. MELANOMA, INVASIVE
Clinical features
● 5% are multiple, although prognosis is related to
type and stage of largest lesion, not number of
lesions
● Must distinguish multiple lesions from “hot nevi” /
nevus activation
● Self assessment often inaccurate
Physiology
● Cytotoxic T lymphocytes have difficulty killing
melanoma cells due to delayed or ineffective
apoptosis
Regression
● Partial regression is common, total regression
may occur

234. MELANOMA,INVASIVE
Metastases
● Regional lymph nodes, liver, lungs, GI tract,
bone, CNS, heart, skin (satellite tumors are
considered intralymphatic metastases within 2
cm of primary tumor, termed in transit
metastases if >2 cm from primary tumor but
before the first echelon of regional lymph nodes),
other sites
● Metastasis are occasionally S100 negative, but
can still be identified as melanoma due to (a)
negative workup for carcinoma, lymphoma and
sarcoma, (b) HMB45+, MART1+, (c) clinical
history of melanoma
● Metastases may arise from unrelated clones
● Molecular analysis can distinguish a second
primary from metastatic disease

235. MELANOMA, INVASIVE
Survival
● Overall 5 year survival is 60%, but behavior is variable, with
occasional late deaths or long survival even with widespread
satellite nodules
Poor prognostic factors
● Breslow (vertical) thickness in primary tumor
● Clark’s level
● Vascular invasion
● High stage (TNM)
● Male gender
● High mitotic rate
● Ulceration
● Microscopic satellites (tumor nests 50 microns or larger and
separated from main tumor mass)
● Deeper level of invasion for T1 tumors
● Higher % tumor area/volume in sentinel node
● Positive nonsentinel lymph nodes
● Regression
● Tumor-infiltrating lymphocytes

236. MELANOMA, INVASIVE
Possible poor prognostic factors:
● Patient age
● Site of primary melanoma
● Angiotropism (migration of melanoma cells along
external surface of blood vessels
● Tumor lymphangiogenesis
● Increased density of dendritic leukocytes in nodal
paracortex
● For patients with localized melanoma, most important
prognostic factors are tumor thickness and ulceration
● For patients with nodal metastases, most important
prognostic factors are number of metastatic nodes,
microscopic versus macroscopic tumor and presence or
absence of ulceration of primary melanoma
● Note: there is excellent agreement between pathologists
in assessing tumor thickness, ulcerative state and
tumor mitotic rate

237. MELANOMA, INVASIVE
Diagnosis and Treatment
● Initial biopsy should attempt to remove the entire
lesion
● Punch biopsies for diagnosis are discouraged,
since determination of depth may be inaccurate
but may be useful to define margins
● Initial excision is usually down to subcutis with
narrow margins, but then need wide local re-
excision with 1-2 cm margins
● Frozen sections for margins only
● Lymphatic mapping and sentinel node biopsy for
tumors with depth > 1mm
● Nodal block dissection

238. MELANOMA, INVASIVE
Note: minimal metastatic risk if radial
growth phase only; metastatic
behavior occurs with vertical growth
phase
Treatment for metastatic disease:
Interleukin-2 and dacarbazine;
possibly adoptive cell therapy with
autologous antitumor lymphocytes in
lymphodepleted hosts variable results
for adjuvant radiotherapy

239. MELANOMA, INVASIVE
 Scaly erythematous crusty pigmentation and
thickened plaques on the nipple, spreading to
surrounding areola

240. MELANOMA, INVASIVE
Micro description
● Features of melanoma in situ + dermal involvement of
atypical melanocytes with cytologic atypia and no
maturation
● Classic features are junctional activity with obscured
dermoepidermal junction and pagetoid spread
individually and in clusters throughout epidermis
● Prominent melanin pigmentation, invasion of
surrounding tissue
● Large cells with abundant eosinophilic and finely
granular cytoplasm
● Nuclear pseudoinclusions, folds or grooves
● Marked atypia with pleomorphic nuclei with large
eosinophilic nucleoli
● Frequent mitotic figures

241. MELANOMA, INVASIVE
4 major subtypes
● Acral lentiginous
● Lentigo maligna
● Nodular
● Superficial spreading (described
separately)

242. MELANOMA INVASIVE:
MICRO
● Lack of a junctional component suggests a
metastases, although epidermal component may
have regressed or not been sampled, or
melanoma may have developed from an
intradermal nevus
● Consumption of epidermis: usually (86%)
present; thinning of epidermis with attenuation of
basal and suprabasal layers and loss of rete
ridges in areas of direct contact with neoplastic
melanocytes; variable clefts separating epidermis
and dermis, edema, telangiectasias; is
associated with increased Breslow depth and
ulceration
● Lymphatic invasion identified in 5% on H&E but
33% using D2-40/podoplanin and S100

243. MELANOMA, INVASIVE
● Subepidermal cleft present in 24%
● Angiotropism is suggestive of
epidermotropic metastatic disease
versus recurrent disease
● Rarely paradoxical maturation occurs,
but still have areas of cells with
abundant cytoplasm and large nuclei,
more mitotic figures, more confluence,
high Ki-67 rate
● Rarely CD68+ osteoclast-like giant
cells, signet-ring cells, lipoblast like

244. MELANOMA, INVASIVE
Other microscopic features
● Growth patterns: pseudoglandular,
pseudopapillary, peritheliomatous (around blood
vessels), hemangiopericytoma-like, Spitz nevus-
like, trabecular, verrucous, nevoid
● Cell type: epithelioid, spindled or bizarre
● Size: lymphocytes to multinucleated giant cells
● Cytoplasm: eosinophilic, basophilic, foamy,
signet ring, rhabdoid, oncocytic or clear
● Stroma: desmoplastic, myxoid, bone or
cartilage, osteoclast-like giant cells
● Epithelium: pseudoepitheliomatous hyperplasia
● Other differentiation: Schwann cells, ganglion
cells, other neural structures

245.  Thin and thick melanoma

246.  VASCULAR INVASION
 ULCERATION

247. Satellite metastasis Tumor infiltrating lymphocytes

248. NIPPLE MELANOMA, NODULAR TYPE

250. Pagetoid extension

251. Follicular growth

252. POSITIVE STAINS
MELANOMA, INVASIVE
Distinguish melanocytes from non-
melanocytes, but not malignant cells from
benign cells:
● S100: nuclear and cytoplasmic staining,
90%+ sensitive but not specific (although
usually negative in tumors considered in the
differential)
● HMB45: cytoplasmic and weak nuclear
staining , less sensitive but more specific
than S100; negative in desmoplastic
melanoma
● MelanA/Mart1: sensitive, but also stains
steroid-producing cells in ovary, testis,
adrenal cortex
● Tyrosinase: sensitive, but also stains

253. MELANOMA, INVASIVE
● Microphthalmia transcription factor: sensitive, but
also stains dermatofibroma and smooth muscle
tumors; negative in spindle cell / desmoplastic
melanoma
● NKI-C3 and NSE: nonspecific
● PHH3 and Ki-67: may distinguish melanoma from
nevi ; another marker is SM5-1
● Azure blue counterstaining may be preferable to
bleaching
● Other positive stains: Fontana-Masson (detects
melanin granules), vimentin; variable staining for
Cam 5.2, CEA, EMA, alpha-1-antichymotrypsin,
CD68
● some melanomas, especially when metastatic,
may stain with simple keratins (CK8)

254. MELANOMA, INVASIVE
Electron microscopy
● Melanosomes and premelanosomes
● May be useful if stains are not
confirmatory
● May have well developed microvilli
similar to adenocarcinoma

255. MELANOMA-MOLECULAR / CYTOGENETICS
● Main altered pathways include RAS-RAF-
MEK-ERK, p16(INK4A)-CDK4-RB and ARF-
p53
● 20% of melanoma prone families have point
mutation in CDKN2A locus at 9p21 which
encodes p16(INK4a) and p14(ARF)
● 10% of cases may be familial due to CMM1
gene at 1p36
● Microsatellite instability seen in pediatric
melanoma (43%), adult melanoma (30%),
nevi (9%)
● Most melanomas have multiple chromosomal
gains and losses, features that can be used
to differentiate them from nevi, which do not
have chromosomal alteration

256. MELANOMA: DD
● Nevi - particularly Spitz nevi-desmoplastic type, halo
nevi, activated and dysplastic nevi, vulval nevi and
recurrent nevi after incomplete excision; features
relatively specific for melanoma include absence of
maturation, suprabasal melanocytes; also atypia, size
>6 mm, mitotic figures, dermal lymphocytes and
asymmetry, necrosis, asymmetrical melanin and
melanin in deep cells
● Benign fibrous histiocytoma
● Hemangioma
● Pigmented seborrheic keratosis
● Pigmented basal cell carcinoma
● Atypical fibroxanthoma - HMB45, MelanA and S100 are
usually negative
● Granular cell tumor - negative for HMB45 and MelanA
● Amelanotic tumors resemble pyogenic granuloma

257. Helpful features of melanoma that differentiate
from benign lesions
● Poor circumscription of intraepidermal component
● Lateral extension of individual melanocytes
● Transepidermal migration of melanocytes
● Pleomorphism of tumor cells
● Asymmetry
● Lack of maturation of dermal tumor cells
● Atypia
● Mitotic figures in melanocytes (particularly atypical
ones)
● Melanocytes with clear cytoplasm and finely dispersed
chromatin, individual melanocyte necrosis (compared to
eosinophilic hyaline bodies in Spitz nevi)
● Band like chronic inflammatory infiltrate in dermis
● Presence of chromosomal gains or losses