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 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

 Solar or Actinic Keratosis is

characterized by small patches
of flesh-colored, pink, or slightly
darker areas of skin. These
occur on sun-exposed 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:
 fair skin,
 ionizing radiation,
 hydrocarbon or arsenic exposure,
 renal transplant
 Treatment:
 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
Actinic keratosis
(a precancerous condition):
B2 As a result of permanent
DNA damage,
the epidermal epithelium
exhibits nuclear
polymorphism ( B1) and
nuclear polychromasia
B1 accompanied by excessive
formation of keratinized
corneal scales
(parakeratosis; B2).
B3 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 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 seborrheic keratosis
or warts
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 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 non-
sentinel 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:
 nuclear and cytoplasmic, 90%+ sensitive but not specific (although
usually negative in tumors considered in the differential)
 HMB45:
 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 peripheral nerve sheath and neuroendocrine
tumors
 Microphthalmia transcription factor:
 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
Hutchinson’s 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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BOWEN’S DISEASE
 Bowen’s 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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 Bowen’s disease

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 Bowen’s 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:
 high molecular weight keratin,
 EMA,
 involucrin,
 p53 (50%),
 variable CEA
 Negative stains:
 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 Predominantly endophytic with no
central horn-filled crater horn-filled crater
Overhanging 'lips' of epithelium No epithelial 'lips'
Rarely ulcerated Commonly ulcerated
Abundant pale staining cytoplasm Less common
of keratinocytes
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 Indistinct
nests and stroma
Absence of stroma desmoplasia Present
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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 Negativeb 01(4.2) 0 (0)
Weakc 20(83.3) 06(35.3) 0.001
Strongd 03(12.5) 11(64.7)
COX-2 Negative 16(66.7) 04(23.5)
Weak 07(29.2) 04(23.5) 0.001
Strong 01(4.2) 09(52.9)
p53 Negative 10(41.7) 02(11.8)
Weak 13(54.2) 04(23.5) 0.000
Strong 01 (4.2) 11(64.7)

a Number of samples (percentage in brackets).

b Negative — no staining.
c Weak — Combined score of <= 3.
d Strong — Combined score of >3.
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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:
 fair skin, blue eyes,
 immunosuppression (higher incidence, more
aggressive tumors),
 xeroderma pigmentosum
 Also associated with
 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 3-

month 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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neurofibromatosis
Type I neurofibromatosis (skin)

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 S-100: neurofibroma
(IH) x 75

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