TUMOR KULIT

Epidermis

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Epidermis

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Epidermis

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BENIGN SQUAMOUS
KERATOSIS

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SEBORRHEIC KERATOSIS

Seborrheic keratosis

A seborrheic keratosis is one of the most

common growths that occur on the skin. In
general terms these are often referred to as
"barnacles of time or age spots" I prefer to
call them wisdom spots.
Seborrheic keratoses are most frequently
seen in adults over thirty, and they can occur
almost anywhere on the skin. Looking a lot
like waxy lumps they are typically brown or
black in color, and appear like they have been
stuck on the skin. When they are very flat
they can look like large liver spots/lentigo
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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
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Seborrheic keratosis

Treatment: superficial curettage,

freezing
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

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Seborrheic keratosis

before
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after
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Seborrheic
keratosis

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Seborrheic keratosis

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ACTINIC KERATOSIS

Actinic keratosis

Also called solar keratosis, senile

keratosis
Buildup of excessive keratin due to
chronic exposure to sunlight
On sun-exposed sites (face, arms,
dorsum of hands)
Called actinic cheilitis in lips
May become invasive with only a single
layer of atypical keratinocytes
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Actinic keratosis

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Solar or Actinic Keratosis is

characterized by small
patches of flesh-colored,
pink, or slightly darker areas
of skin. These occur on sunexposed areas of the body
(face, scalp, back of hands,
neck, and chest) and have a
sandpaper feel.
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Actinic keratosis

Risk factors:

Treatment:

fair skin,
ionizing radiation,
hydrocarbon or arsenic exposure,
renal transplant
curettage,
cryotherapy,
topical chemotherapeutic agents

Gross: tan-brown, red or skin colored,

circumscribed lesions, sandpaper texture,
may have cutaneous horn (due to
excessive production of parakeratotic scale)
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Actinic keratosis

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Actinic keratosis

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Actinic keratosis
(HE) x 100
B2

B1

B3

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Actinic keratosis
(a precancerous condition):
As a result of permanent
DNA damage,
the epidermal epithelium
exhibits nuclear
polymorphism ( B1) and
nuclear polychromasia
accompanied by excessive
formation of keratinized
corneal scales
(parakeratosis; B2).
However, these changes
do not penetrate the
basement membrane ( B3).
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FIBROEPITHELIAL POLYP

Fibroepithelial polyp

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
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desmoplastic
pattern)

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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
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seborrheic
keratosis or warts

Fibroepithelial polyp

Acquired (digital) fibrokeratoma:

collagenous protrusions covered by
hyperkeratotic epithelium, often at
interphalangeal joints; dermis lacks adnexae
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
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Fibroepithelial Polyp of the

Ureter
A 73-year-old woman presented with
asymptomatic gross hematuria. Her physical
examination was unremarkable. A complete
blood cell count, levels of serum electrolytes
and creatinine, and results of cytologic
evaluation of voided urine were normal.
Urinalysis showed 0 to 2 white blood cells
and 25 to 50 red blood cells per high-power
field. Urine culture was negative.
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An excretory urogram and left retrograde

ureteropyelogram demonstrated a filling
defect within the distal left ureter

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branching polyp is observed in the distal left

ureter adjacent to a guidewire.

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One of the lobulated projections of the fibroepithelial polyp

shows benign urothelium covering a broad-based edematous
fibrovascular stroma (hematoxylin-eosin, 10).

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Fibroepithelial polyp

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PAPILLOMA

Squamous cell papilloma

(HE) x 25

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PAPILLOMA

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PAPILLOMA

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INTRADERMAL
PIGMENTED NEVI

Nevus Pigmentosus

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Nevus Pigmentosus
Junctional type

Small lesion, somewhat flat,

symmetric, and uniform

Rounded nest of nevus cells originating at the tips of

rete ridges along the dermo-epidermal junction
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Junctional nevus
(HE) x 25

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Nevus Pigmentosus
compound type

More raised than junctional nevus, Combination of features of junctional nevi

dome shaped. The symmetri and uniform (intraepidermal nevus cells nest) with nest
pigment suggest a benign process
of nevus cells in the underlying dermis
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Nevus Pigmentosus
dysplastic nevus

More pigmented and raised central zone (A: compound nevus component) and an
assymetric shoulder (B:junctional nevus component cytologic atypia: irregularly
shaped, dark staining nuclei). The dermis underlying atypical cells
linear or lamellar fibrosis desmoplasia.
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PIGMENTED NEVI

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MALIGNANT MELANOMA

Melanoma

Incidence increasing worldwide - 48,000 cases

and 9,200 deaths in US in 2000
Usually due to sun (UV light) exposure
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
Head and neck, lower extremities (particularly
in women); rarely subungual (melanotic
whitlow), palm, sole. Also oral and anogenital
mucosa, esophagus, meninges, eye
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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, possibly neurofibromatosis type I
Up to 10% may be familial due to CMM1 gene at
1p36
Blacks have low risk, their common melanoma sites
are palms, soles, nail beds or mucous membranes
Usually after puberty, occasionally children - all have
same morphology
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
Achilles tendon tumors are often spindled
Tend to grow laterally and deep; common metastases
to regional lymph nodes, also liver, lungs, GI tract,
bone, CNS, heart (50% at autopsy), skin (satellite
tumors within 2 cm of primary tumor), other sites
Overall
5 year survival is 60%
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Poor prognostic factors:

increased Breslow (vertical) thickness in primary

tumor,
high stage (TNM),
males (do worse than females),
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,
increased density of dendritic leukocytes in nodal
paracortex (associated with risk of tumor in nonsentinel nodes, recurrence and death,
Mod Path 2004;17:747 )

Overall behavior is variable, with occasional

late deaths or long survival even with
widespread satellite nodules
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Melanoma

S100:

HMB45:

sensitive, but also stains peripheral nerve sheath and

neuroendocrine tumors

Microphthalmia transcription factor:

sensitive, but also stains steroid-producing cells in ovary, testis,

adrenal cortex

Tyrosinase:

less sensitive but more specific than S100; negative in

desmoplastic melanoma

MelanA/Mart1:

nuclear and cytoplasmic, 90%+ sensitive but not specific

(although usually negative in tumors considered in the
differential)

sensitive, but also stains dermatofibroma and smooth muscle

tumors; negative in spindle cell / desmoplastic melanoma

NKI-C3 and NSE: nonspecific

Negative stains: p53
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Nevus Pigmentosus Melanoma

steps of tumor progression in dysplastic nevi

A. Melanocytic hyperplsia, B. Junctional nevus, C. Dysplastic nevus (compound

nevus with abnormal architectural and cytologic freatures, D. early melanoma
(radial growth phase melanoma large dark cells in epidermis), E.advanced
melanoma (vertical growth phase)
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Malignant Melanoma

Lesions are irregular in contour and pigmentation. Macular areas correlated

with the radial growth phase, while raised areas usually correspond to
nodular aggregation of malignant cells in the vertical cell growth
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Malignant Melanoma

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Malignant Melanoma
radial growth phase of melanoma

Irregular nested and single cell growth of melanoma cells within the
epidermis and an underlying inflammatory response within the dermis
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Malignant Melanoma
vertical phase growth

Nodular aggregates of infiltrating cells

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Malignant Melanoma

High-power view of malignant melanoma cells

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Nodular malignant
melanoma
(HE) x 10

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Superficial spreading
melanoma

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Superficial spreading
melanoma
(HE) X 100

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MALIGNANT MELANOMA

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LENTIGO

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Lentiginous melanocytic
nevus

Often benign mole with increase in size, formation

of irregular borders or peripheral change in color
May be due to reactivation of radial proliferation
Benign, but complete excision is recommended
Micro: shoulder area of lentiginous junctional
melanocytic proliferation beyond lateral border of
underlying dermal nevus; no atypia
DD: dysplastic nevi, superficial spreading
melanoma

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Lentigo maligna

Also called melanoma arising in

Hutchinsons freckle, actinic melanosis
Consisted the melanocytic equivalent
of actinic keratosis
Slow growing lesion of sun exposed
skin of elderly whites, often cheek
Unusual to die of disease
Partial regression is common
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Lentigo maligna

lentigo maligna, by definition, does NOT infiltrate into

dermis, but lentigo maligna melanoma has single cell
infiltration into papillary dermis
Treatment: excision, radiation
Gross: flat, tan to black with irregular hyperpigmentation, > 2 cm
Micro: atypical melanocytes in basal layer, individually and
in nests (theques); cells are often spindled, pleomorphic and
have cytoplasmic retraction; dermis shows solar elastosis;
also epidermal atrophy, actinic damage, basilar keratinocyte
hyperpigmentation
DD: invasive melanoma (clear cut dermal infiltration, not
just atypical melanocytes in deep rete ridges), desmoplastic
melanoma (may arise secondary to lentigo maligna)
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Lentigo maligna

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Lentigo maligna melanoma in

situ
(IH; HMB-45) x 25

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BOWENS DISEASE

Bowens disease

Usually on skin NOT exposed to

sunlight, such as trunk
Called erythroplasia if at glans penis,
vulva, oral cavity
Often considered as carcinoma in situ
or squamous intraepidermal
neoplasia
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Gross: slightly raised, large scaly

erythematous plaque with irregular border;
usually single patch or verrucous growth
Micro:

atypia is prominent and throughout epidermis;

includes nuclear hyperchromasia and
multinucleation, individual cell dyskeratosis,
increased mitotic figures, atypical mitotic figures;
also cytoplasmic vacuoles, markedly altered
maturation, but usually still some surface
keratinization;
may extend into eccrine sweat glands (not
considered invasive disease);
intercellular bridges present;
rarely pagetoid cells or ground glass cytoplasm
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Micro images: - Positive stains:

p53, HPV, high molecular weight
cytokeratin
Molecular: aneuploid
DD: bowenoid actinic keratosis
(circumscribed, in sun-exposed areas
with clinical appearance of actinic
keratosis), chronic arsenic ingestion
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Bowens disease

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Bowens disease

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SQUAMOUS CELL
CARCINOMA

SQUAMOUS CELL
CARCINOMA

Common, derived from keratinocytes in

epidermal layer
Usually men, associated with

sun exposure (UV light may induce p53

mutations and diminish surveillance function of
Langerhans cells in epidermis),
PUVA treatment for psoriasis, arsenic, tars/oils,
chronic ulcers,
draining osteomyelitis,
old burn scars,
necrobiosis lipoidica,
hidradenitis suppurativa,
ionizing radiation
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Risk factors:

immunosuppression (post-transplant or HIV),

xeroderma pigmentosa (disorder with diminished
capacity for DNA repair after UV light exposure, due to
gene at 9q22.3; associated with squamous cell, basal
cell carcinoma and melanoma),
lack of pigmentation in skin,
actinic keratosis (precursor lesion),
epidermodysplasia verruciformis;
very rare in blacks

5% are node positive at diagnosis; metastatic

rate is 5-10% in transplant patients, who do
poorly with metastatic disease
Slow growing, locally invasive but rarely
metastasizes outside nodes (but see above); most
common site is lung
Metastases more likely in tumors that originate in
scars or ulcers
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SQUAMOUS CELL
CARCINOMA

Prognosis: excellent; metastases uncommon if

tumor < 1.5 cm deep; 5% metastasize if 2 cm or
more and definite dermal invasion
Good prognostic factors:

low stage,
no/superficial dermal invasion, small vertical tumor
thickness (< 4 mm),
well differentiated,
short duration,
location other than scalp, ears, lips, nose, eyelids or soft
tissue (which readily invade subcutaneous tissue)

Treatment: surgical excision with adequate

margins; also currettage, electrodesiccation,
cryotherapy, radiation therapy
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Gross: often white plaque (leukoplakia); may have

induration, ulceration, hemorrhage
Micro: atypia at all levels of epidermis; 80% are well
differentiated with keratin pearls, intercellular bridges
and no/rare keratohyaline granules; invade dermis by
definition;

may contain non-neoplastic melanocytes that transfer

melanin to tumor cells; occasionally clear cells, rarely signet
ring cells
Spindle, adenoid and verrucous variants are described
separately
Other variants are acantholytic (pseudoglandular, tumor clefts
produed by acantholysis of tumor cells) and
pseudoangiosarcomatous (clefts separate neoplastic lobules)

Low grade (well differentiated): cell

differentiation, uniform cell size, intact intercellular
bridges, no/rare mitotic figures, no/mild pleomorphism
High grade (poorly differentiated): little cell
differentiation, pleomorphism with spindle cells,
necrosis, marked mitotic activity, deep invasion
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SQUAMOUS CELL
CARCINOMA

Positive stains:

Negative stains:

high molecular weight keratin,

EMA,
involucrin,
p53 (50%),
variable CEA
Ber-EP4, usually CK7 and CK20 (head and neck
tumors, Mod Path 2004;17:407)

DD: keratoacanthoma (for well

differentiated tumors)
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Squamous Cell Ca

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Squamous Cell Ca

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Squamous cell carcinoma

(HE) x 75

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Squamous cell carcinoma

(HE) x 150

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Selected cases of squamous cell carcinoma: (a) a

representative case of moderately differentiated squamous
cell carcinoma (H&E, X 40); (b) intranuclear staining for
human telomerase reverse transcriptase activity (X 200); (c)
intracytoplasmic COX-2 stain (X 200); (d) strong intranuclear
p53 expression (X 400).

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Selected cases of keratoacanthoma: (a) a representative case

of early keratoacanthoma with overhanging lips and central
horn-filled crater (H&E, 40); (b) negative for telomerase
activity ( 400); (c) basal staining for p53 ( 100); (d) negative
COX-2 stain ( 200).

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Histopathologic criteria to
differentiate early
keratoacanthoma from a well to
moderately differentiated
squamous cell carcinoma (Ackerman et
al and Cribier et al)

TABLE ..

Keratoacanthoma

Squamous cell
carcinoma

Exoendophytic lesion with a

central horn-filled crater

Predominantly endophytic
with no horn-filled crater

Overhanging 'lips' of
epithelium

No epithelial 'lips'

Rarely ulcerated

Commonly ulcerated

Abundant pale staining

cytoplasm of keratinocytes

Less common

Intraepithelial abscesses within the

lesion

Rare

Acantholytic cells within the

Acantholytic cells form without
intraepithelial abscesses often associated neutrophils
Gland-like formations rare

Pseudoglandular formations
often

Lack of anaplasia

Common

Sharp outline between tumor

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nests and stroma

Indistinct

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Immunohistochemical expression of
telomerase activity, COX-2, and p53
in keratoacanthoma (KA) and
squamous cell carcinoma (SCC).
TABLE ..

KA a
SCC a 'P' value
(n=24 (n=17)
)
Telomerase

COX-2

p53

Negativeb
Weakc
Strongd
Negative
Weak
Strong
Negative
Weak
Strong

01(4.2)
20(83.3)
03(12.5)
16(66.7)
07(29.2)
01(4.2)
10(41.7)
13(54.2)
01 (4.2)

0 (0)
06(35.3)
11(64.7)
04(23.5)
04(23.5)
09(52.9)
02(11.8)
04(23.5)
11(64.7)

a Number of samples (percentage in

brackets).
b Negative no staining.
c Weak
Combined score of <= 3.
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d Strong Combined score of >3.

0.001

0.001

0.000

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BASAL CELL CARCINOMA

BASAL CELL CARCINOMA

Most frequent form of skin cancer

Usually sun exposed skin (not mucosal surfaces), in
proportion to number of pilosebaceous units present
Rosai claims these tumors attempt to differentiate
toward pilosebaceous units, but often this is not
readily apparent
Often multiple tumors
Usually older adults
Slow and indolent, untreated cases may invade
subcutis, skeletal muscle and bone; facial tumors
may invade skull, nares, orbit or temporal bone; only
100 metastatic cases described, often associated
with basal cell nevus syndrome or basosquamous
histology, on sunlight-protected skin
Metastases are rare; 60% to regional lymph nodes,
also lung, liver, bone
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Risk factors:

Also associated with

fair skin, blue eyes,

immunosuppression (higher incidence, more
aggressive tumors),
xeroderma pigmentosum
nevus sebaceus of Jadassohn,
chronic venous stasis of lower leg,
arsenic, X rays,
skin injury, chickenpox scars,
tattoos, hair transplant scars,
immunosuppression

Less common in children or young adults,

sunlight-protected skin; rarely coexists
with benign nevus
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Basal cell carcinoma

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Basal cell carcinoma

(HE) x 75

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QUIZ

Miniquiz

A 14-year-old girl presented with a 3month history of multiple upper

extremity nodules. Physical examination
revealed multiple erythematous
pigmented nodules, 0.5 to 1 cm in
diameter, slightly pruritic, involving the
upper limbs (Figure 1). A skin biopsy of a
nodular lesion was performed (Figure 2).
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Figure 1 : Erythematous
pigmented
nodules of
forearms

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Figure 3 (toluidine blue stain x

40): Mast cell dermal infiltrate
with specific granulations
Figure 2 : (HES x 20):
Mononuclear cell infiltrate
of reticular dermis
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Question :
What is the diagnosis of this
case ?

Answer:

Mastocytosis

Mastocytosis

Mastocytosis (MC) is a rare,

heterogeneous disorder,
characterized by a marked increase in mast
cells in the skin and occasionally in the bone
marrow, liver, spleen, gastrointestinal tract,
and other various organ systems.
Mast cells are produced in the bone marrow
and contain mediators for inflammatory and
allergenic responses. When these cells are
triggered, a degranulation event occurs in
which mediators such as histamine,
prostaglandins, leukotrienes, heparin,
tryptase, and other chemicals are released
from the mast cell and into the systemic
circulation
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Mastocytosis

cutaneous mastocytosis is generally

benign in children
urticaria pigmentosa (UP) is the most
common clinical form though
descriptions of this entity should be
expanded to include nodular forms.
In childhood, in the absence of clinical
symptoms suggesting systemic
involvement, detailed laboratory
investigations are not recommended.
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Mast cell, Toluidine Blue,

Systemic mastocytosis marrow

One positive mast cell

(numerous large dark
granules filling cytoplasm),
1 negative blast and one
negative band neutrophil.
Toluidine Blue stain.
Systemic mastocytosis
marrow -100X

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Mastocytosis

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neurofibromatosi
s

Type I neurofibromatosis
(skin)

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S-100: neurofibroma
(IH) x 75

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