NonMelanocytic dr.

Riesye Arisanty, SpPA(K)

Cutaneous Anatomical Pathology Department
FMUI
Neoplasm
 BENIGN :

• Epidermal Nevus* (hamartomas)

• Acanthoma :
• Seborrheic keratosis*
• Epidermolytic acanthoma
• Warty dyskeratoma
• Acantholytic acanthoma
• Pseudoepitheliomatous hyperplasia (reactive hyperplasia)

PREMALIGNANT :

Epidermal • Actinic Keratosis*

Tumor INTRAEPIDERMAL CARCINOMA :

• Bowen’s disease*
• Erythroplasia of Queyrat
• Bowenoid papulosis

MALIGNANT :

• Squamous cell carcinoma*

• Verrucous carcinoma
• Keratoacanthoma
• Basal cell carcinoma*
• Merkel cell carcinoma
 Broad range of Benign, Premalignant,
intraepidermal carcinoma and Malignant
lesion

Seborrheic keratosis, epidermal cyst, actinic

Keratinocytic keratosis, basal cell carcinoma and squamous
cell carcinoma → Large Presentation and
tumours routine in clinical and pathology Practice

Wide variety some rare tumors →

Pathologist needs to be aware
BENIGN KERATINOCYTIC
EPIDERMAL
NEVUS
(keratinocytes
epidermal nevus)
CLINICAL FEATURES
• Developmental malformation of the epidermis, an excess of
keratinocytes
• Present at birth or develop during childhood
• Generally present as yellowish-brown warty papules or plaques with
irregular margins.
• Papules may be solitary or arranged in clusters in linear configuration
→ follow Blaschko’s lines
• Epidermal nevus syndroms : autosomal dominant inheritance
extensive epidermal nevi with abnormality of CNS and CV systems,
eyes, skeleton, or other cutaneous findings.
• Variants :
• Nevus verrucosus (verrucous epidermal nevus) has been used for localized
wart-like variants
• Nevus unius lateris has been used for long, linear, usually unilateral lesions on
the extremities
• Ichthyosis hystrix refers to large, often disfiguring nevi with a bilateral
distribution on the trunk.
• acantholytic, dyskeratotic epidermal nevus: associated with mutations
affecting the sarcoendoplasmic reticulum calcium transport adenosine
triphosphate-2 (SERCA2) pump. Mutations in the encoding ATP2A2 gene are
also described in the microscopically similar Darier’s disease and acrokeratosis
verruciformis of Hopf
• epidermal nevus syndrome: epidermal nevi with neurological, ocular, and
skeletal abnormalities
• Inflammatory Linear Verrucous Epidermal Nevus (ILVEN) : occur on lower
extremities, typically inflamed and clinically resemble psoriasis
yellowish-brown warty papules or plaques with irregular margins.
Dermoscopy : verrucous epidermal nevus has shown large brown circles
• coalesce, lichenify and arrange in a linear
pattern
• Linear epidermal nevus: this is a more
extensive lesion involving the scapular
region, shoulder and upper arm
HISTOPATHOLOGICAL FEATURES
• At least 10 different histological patterns have been found in
epidermal nevi. More than 60% → common type :

• Hyperkeratosis, Acanthosis, Papillomatosis, sometimes

hypergranulosis
• Perivascular lymphocyte – often
• Achantolytic dyskeratosis and Epidermolytic hyperkeratosis --
rarely
Epidermal nevus: scanning view; note the hyperkeratosis, papillomatosis,
and acanthosis.
Medium power field with flattening of the epidermal papillations → “mesa – sign”
irregular papillomatosis, some flattening of the epidermal papillations
reminiscent of a seborrheic keratosis.
the keratin-filled pseudocysts, scattered lymphocytes in the superficial
dermis.
reminiscent of a seborrheic keratosis, with keratin-filled pseudocysts,
 Verrucae (vulgaris)

DIFFERENTIAL • “In-bowing” epithelial margin,

koilocyte cells with “raisinoid” nuclei
DIAGNOSIS
Seborrheic keratosis
(conventional
/ common • Hyperkeratotic type SK with marked
papillomatotic
type) • Not a diagnostic for children lesion
• Epidermal nevi show rete ridges with
flat bottom
SEBORRHEIC
KERATOSIS
 The importance of a familiarity with
microscopic appearance of SK and its variant

▪ Extremely common lesion among adult

▪ Clinically mimic premalignant & malignant lesion
▪ Sometimes show histologic features that raise concerns about
malignancy
▪ Occasionally malignant cutaneous tumor arise in association
with SK
CLINICAL FEATURES
Extremely common lesion among adult – begin to developed during the 4th or 5th

Synonims : senile warts, basal cell papillomas

often multiple and occur common on the face, chest, back,and any part of the body, except the
palms and soles

Sharply demarcated, rough-surfaced papule, nodule or plaque, gray-brown to black lesions, slightly
raised. Sometimes covered with greasy scales.

Most lesions are ≤1 cm in diameter, but larger and pedunculated sometimes even
Dermoscopy :
The classic criteria—milia-like cysts • Sharply demarcated, rough-surfaced papule, nodule or plaque, gray-brown
and comedo-like openings, fissures and ridges, to black lesions, slightly raised, ± 1cm in diameter
hairpin blood vessels, sharp demarcation,
moth-eaten borders, and “fat fingers,” may abe
present
• Fitzpatrick
SEBORRHEIC KERATOSIS
CLINICAL VARIANT
Common Reticulated
seborrheic seborrheic Stucco keratosis
keratosis keratosis

Melanoacanthoma
(pigmented Dermatosis Clonal seborrheic
seborrheic papulosa nigra keratosis
keratosis)

Seborrheic
Irritated seborrheic
keratosis with Leser–Trélat sign
keratosis
squamous atypia
 • COMMON (Acantothic) TYPE :
• sharply defined tumors that may be endophytic
or exophytic.
• composed of basaloid cells with a varying
admixture of squamoid cells.
HISTOPATHOLOGY • Keratin-filled invaginations and small cysts (horn
cysts) are a characteristic feature.
• Nests of squamous cells (squamous eddies) may
be present, particularly in the irritated type.
• one-third of seborrheic keratoses appear
hyperpigmented
 sharply defined tumor endophytic proliferation
composed of basaloid cells with a varying admixture of squamoid cells.
Keratin-filled invaginations and small cysts (horn cysts) are a
characteristic feature.
 HISTOPATHOLOGY VARIANT

hyperkeratotic (Papilomatotic) reticulated (adenoid) type : Clonal seborrheic keratoses :

type :
• exophytic, with varying degrees of
hyperkeratosis, papillomatosis, and
acanthosis.
• There are both basaloid and squamous cells.
• has interlacing thin strands of basaloid cells, • have intraepidermal nests of basaloid cells
often pigmented, enclosing small horn cysts resembling the Borst–Jadassohn
• This variant often evolves from a solar phenomenon (intraepidermal epithelioma)
lentigo.

irritated type : Pigmented type :

• a heavy inflammatory cell infiltrate, with • Increased keratinocytes pigmentation and
/without lichenoid features in the upper scattered melanophages
dermis.
• Apoptotic cells are present in the base of
the lesion and in areas of squamous
differentiation.
• Kamino bodies are rarely found in this type.
Hyperkeratotic type : exophytic, with varying degrees of hyperkeratosis,
papillomatosis, and acanthosis of basaloid and squamous cells
Reticulated type : interlacing thin strands of basaloid cells,
often pigmented, enclosing small horn cysts
Clonal type : intraepidermal nests of basaloid cells resembling the
Borst–Jadassohn phenomenon (intraepidermal epithelioma)
Irritated type SK with squamous eddies
• Actinic keratosis :
• limited to sun-damaged areas
atypical keratinocytes and
inflamed even when not
“irritated”, usually no string sign, DIFFERENTIAL
no horn pseudocysts, usually no
pigment. DIAGNOSIS
• Verruca vulgaris :
• mounds of parakeratosis,
hypergranulosis, koilocytosis, and
dilated vessels in papillae.
PRE-MALIGNANT EPIDERMAL TUMOR
• A precancerous or premalignant lesion is
one that has a strong likelihood of
transforming into a malignancy → “solar
keratotic intraepidermal squamous cell
carcinoma”
• precancerous lesions and SCC are
considered to represent a continum of
disease with dysplasia at one end of the
spectrum and invasive carcinoma at the
other.
• Rate of progression to invasive SCC is low :
0,1 to 10%
ACTINIC
KERATOSIS
• Actinic keratosis (solar keratosis, senile keratosis) →
cutaneous neoplasms consisting of proliferations of
cytologically abnormal epidermal keratinocytes
• prolonged exposure to ultraviolet (UV) radiation.
• PUVA therapy, exposes to arsenic
ETIOLOGY and PATHOGENESIS
• genetic and environmental factors (UV
exposure)
• it causes mutations (p53) in cellular DNA
→ ≠ repaired → unrestrained growth and
tumor formation
• induced immunosuppression but the
precise mechanisms are uncertain.
CLINICAL FEATURES
• Often multiple, flat to elevated, flesh-colored, pigmented or
erythematous, discrete to ill-defined borders,1 – 2 cm in diameter →
“Erythematous AK”
• pruritus, burning or stinging pain, bleeding, and crusting
• common in chronically sun- exposes site, incl Head and neck,
forearms, dorsa of the hand, lower legs
• Middle to older adults
CLINICAL VARIANT
• Hypertrophic AK
• Cornu cutaneum ( Cutaneous horn) :
• a reaction pattern and not a particular lesion
• a type of Hypertrophic AK that presents with a conical hypertrophic
protuberance emanating
• Actinic Cheilitis:
• confluent AKs on the lower lips,
Variant of Actinic Keratosis
erythematous AK, actinic cheilitis, cornu cutaneum
 • Basilar keratinocyte atypia with crowding and variability in
nuclear size
• May proliferate along the basilar layer of adnexal
epithelium
• The epidermis may be atrophic
HISTOPATOLOGY • Parakeratosis and hipogranulosis overlying epidermal
atypia
• Suprabasilar acantholysis
ALTERNATING PARAKERATOTIK (pink and blue sign), WITH CROWDED NUCLEI AT BASAL INC
ADNEXAL EPITHELIUM, THICK OF SOLAR KERATOSIS
 Commonly found in all types : Parakeratosis,
atypical suprabasal cells, hyperkeratosis, solar
elastosis
Atrophic:
Bowenoid : Acantholytic:
Atrophy of the
Hypertrophic : Findings Acantholysis Pigmented : Lichenoid :
epidermal
Mainly resembling immediately Increase in Marked
basal cell layer,
acanthosis and those of above the melanin lichenoid
loss of the
hyperkeratosis Bowen’s epidermal granules reaction
epidermal rete
disease basal cell laye
ridges
Bowenoid AK – full thickness of dysplasia
DIFFERENTIAL DIAGNOSIS
• acantholytic dermatoses (Darier’s disease or Grover’s disease)
• Benign lichenoid keratosis
• irritated seborrheic keratosis
• superficial basal cell carcinoma,
• Bowen’s disease

A key to the recognition of actinic keratosis is keratinocyte atypia that

involves the basilar layer of the epidermis
INTRAEPIDERMAL
CARCINOMA
BOWEN’S DISEASE
Bowen’s disease

adults, (rarely < 30 y.o ), M=F

Intraepidermal carcinoma

any body site (sun-exposed and non-sun-exposed); genital area as

Bowenoid Papulosis

predilection for sun-exposed surfaces : head and neck, lower legs

of women

usually solitary (multiple : 10%–20% of individuals)

ETIOLOGY
• Multifactorian
• significant sun exposure, arsenic exposure, ionizing radiation, immunosuppression
• HPV infection esp. periungual and anogenital (Up to 30% of extragenital BD lesions)
• HPV 16 is the most prevalent human papillomavirus,
• Periungual Bowen’s disease and vulvar intraepithelial neoplasia (VIN) concordant for
the same HPV types (HPV-34 and HPV-21) dan HPV 58 (high prevalent in Asia)
• 8% of cases develop an invasive component if untreated (13% have
metastatic potential)
CLINICAL FEATURES

• asymphtomatic sharply marginated round or oval plaque, flatly elevated,

reddish‐brown to blackish‐brown,underneath the scales and crusts that cover
the plaque, erosion and small nodules may be present.
• diameter of 1–10 cm
• Dermoscopy can be helpful for diagnosing Bowen’s disease → by glomerular
vessels and a scaly surface.
CLINICAL FEATURES
CLINICAL VARIANT • Bowen's disease of the
penis is also known as
erythroplasia of Queyrat.
• Term of Bowen’s disease at
gynecology is no longer
used and replaced in 1986
by the concept of VIN
• slightly scaly,
erythematous, velvety
plaques.
• in association with Zoon's
balanitis and may be
complicated by urethral
involvement
 Variably hyperkeratotic and parakeratotic and often
acanthosis

Full thickness of epidermis loss and disorderly

maturation of the epidermis ( WIND BLOW EPIDERMIS),
mitoses at different levels, multinucleate keratinocytes,
and dyskeratotic cells.
HISTOPATHOLOGY
Basal cells is normal → EYE LINER SIGN

sometimes with involvement of pilosebaceous unit

 The atypical
keratinocytes are
pale, with a pagetoid
appearance
• Pagetoid cells are often present at
the edge of Bowen’s disease. They
may simulate melanoma or Paget’s
disease in small (2 or 3 mm) punch
biopsies.
• Recurrences take place particularly
when adnexal structures are
involved
 actinic (solar) keratosis

seborrheic keratoses

DIFFERENTIAL Extra Mammary Paget’s disease

DIAGNOSIS
in situ superficial spreading melanoma

Verruca Vulgaris
 BD pagetoid type VS
BD VS Irritated type BD VS Clonal type SK
BD VS AK : EMP VS in-situ
SK : :
melanoma SS:
• full-thickness atypia • squamous eddies • lack of nuclear • Difficult to
of the epithelium and loss of crowding or distinguished
• sparing the cohesion of mitoses • IHC : S100 –
acrosyringium keratinocytes • IHC CK10 (-) BCl2 melanocyte cells ;
• the basal layer, (+) → CEA, CK7, CAM 5.2
which is always intraepidermal nest – EMP ;
atypical in actinic
keratoses.
• IHC – P16 →
sparing off Basilar
layer,
MALIGNANT
EPIDERMAL
TUMOR
• In most instances, the histopathological
diagnosis is straightforward
• occasionally tumors are difficult to classify
because of morphological overlap (ex.
various appendageal tumors or tumor
exhibits both basaloid and squamous
differentiation)
• immunohistochemistry may be of assistance
SQUAMOUS CELL CARCINOMA
Pre-existing
lesion of scc
CLINICAL FEATURES

• occurs in elderly people, M>F

• related to excessive exposure of UV B
• solitarily on directly sun‐exposed areas
of the body, such as the face and the
dorsum of the hands.
• Small papules and nodules appear on
preexisting lesions and extend to form
tumors with a cauliflower‐like
appearance.
 Nests/sheets and infiltrative cords of squamous epithelial
cells that arise from the epidermis and extend into the
dermis for a variable distance.

The cells have abundant eosinophilic cytoplasm and a large,

often vesicular nucleus.

variable central keratinization and horn pearl formation,

HISTOPATHOLOGY Individual cell keratinization is often present.

The degree of anaplasia in the tumor nests has been used to

grade SCC.

Recurrences are more likely in those tumors with aggressive

histological features such as deep invasion, poor
differentiation, perineural invasion, and acantholytic features
Well diff SCC
Multiple LOW-RISK VARIANTS include well-differentiated SCC arising in
variants of AK, KA, verrucous carcinoma, and tricholemmal (variant of clear
cell) carcinoma

differing INTERMEDIATE-RISK VARIANTS include acantholytic

(adenoid/pseudoglandular) and lymphoepithelioma-like
carcinoma of the skin
malignant HIGH-RISK VARIANTS include spindle cell/sarcomatoid, basaloid,
adenosquamous, and desmoplastic Also, radiation, burn scar,
potential and immunosuppression-related SCCs

described RARE VARIANTS of uncertain malignant potential include clear

cell SCC, signet ring cell SCC, follicular SCC, papillary SCC,
pigmented SCC, and SCC arising from adnexal ducts or cysts
DIFFERENTIAL
DIAGNOSIS
KERATOACANTHOMA
• = Well diff SCC- keratoacanthoma type
• Spontaneous regress
• Sun exposed and fair-skinned : face, dorsum of hand, legs, 6th – 7th decades, M>F
• UV radiation, photon radiation, trauma, infection, immunosuppression → Human
Polyomavirus (HPyV) 6, 19
• Symmetrical dome shape, capped with keratin, evolved rapidly, >5cm : giant
keratoacanthoma
 Natural history of keratoacanthoma (from onset to spontaneous resolution). a: Onset.
The lesion begins as a dome‐shaped tumor 1 cm in diameter. b: The tumor gradually grows. c: It grows
further. The center ruptures spontaneously. d: The lesion heals without treatment, with slight scarring
HISTOPATHOLOGY

Large squamous cells with

Scanning magnification shows
abundant, dense eosinophilic-
large, nodular, well- Prominent inflammatory
staining cytoplasm and
differentiated tumor, appears infiltrate, usually with many
enlarged, hyperchromatic to
symmetric with central eosinophils and neutrophils
vesicular-appearing nuclei
keratin-filled crater present
with prominent nucleoli

Regressing lesions often show

epidermal atrophy, dermal
fibrosis, and bland cytologic
features
Scanning Magnification of Keratoacanthoma Scanning magnification of a keratoacanthoma shows an endophytic-appearing atypical
squamous proliferation with prominent, central keratin-filled cavities . High Magnification of Keratoacanthoma High magnification
of an area with significant cytologic atypia is characterized by enlarged squamous cells with hyperchromatic nuclei and prominent
nucleoli . Note the inflamed papillary dermal stroma .
 • Verrucous carcinoma :
• Shows prominent endophytic and
exophytic architecture with deep,
bulbous rete ridges
DIFFERENTIAL • Lacks central crater of KA
DIAGNOSIS
VERRUCOUS CARCINOMA
• Rare, 6th – 7th decades, affect anogenital, feet, usually
soliter, some lesion related to viral warts (plantar)
• Exophytic papillary tumor, broad and pushing base
 Lesions are endophitic and exophytic, with papillomatosis and
a covering of hyperkeratosis and parakeratosis, and
endophytic composed of large well differentiated squamous
epithelial cells with benign appearance.
They are blunted downgrowth projections with intact
basement membrane with very low mitotic activity, and this is
confined to the basal layer

HISTOPATHOLOGY burrows in the surface filled with parakeratotic horn

Absence of koilocytosis
Acanthotic
papillae with
orange
keratin,blunted
downgrowth
DIFFERENTIAL DIAGNOSIS

Verruca vulgaris → well

Pseudoepitheliomatous
defined deep boundaries,
hyperplasia → uneven,
acanthosis, papilomatosis,
sharply pointed and
hypergranulosis and
jagged downgrowths
koilocytosis
BASAL CELL
CARCINOMA
the most common cutaneous tumors (70%),

predominantly on areas of skin exposed to the sun, particularly in fair-skinned individuals – head
and neck (80%)
M>F, mostly elderly – Children : Xeroderma pigmentosum

The 5-year recurrence rate is approximately 5%

Rare metastases → regional lymph nodes

usually arise from the lowermost layers of the epidermis, although a small percentage may originate
from the outer root sheath of the pilosebaceous unit.
 • small, firm, waxy, glossy,
blackish‐brown (pearly)
nodules at the periphery of
the skin lesion
• Telangiectasia often occurs
in and at the periphery of
the lesion.
• The lesion appears
blackish‐brown in most cases
in Asians; however, it is
usually normal skin color in
Caucasians
• The accuracy rate in the
clinical diagnosis of BCC is
CLINICAL FEATURES still 60% to 70%.
NODULAR
• more than 80% of BCCs
• Small, firm, black nodules coalesce, accompanied by epidermal
telangiectasia. The center of the lesion often ulcerates (rodent ulcer).

SUPERFICIAL BCC
• a flatly elevated, infiltrative plaque ranging in color from red to
blackish‐brown gradually expands.
• This type often affects the trunk.

MORPHEAFORM
• this is an oval, infiltrative plaque with an atrophic, slightly concave
center.
• It resembles morphea
 Nodule, nest and / or infiltrative cords

• Overlying ulceration and serum crusting

HISTOPATHOLOGY
Proliferation of small basaloid cells with
peripheral palisading

Stromal retraction artefact

Mucinous material in stroma

Numerous mitotic and apoptotic figures

BCC
Nodular BCC with origin from
the underlying epidermis
 a peripheral
palisade and
retraction artifact
as seen in this field
is a characteristic
feature.
 • Varian nodular BCC :
• KERATOTIC BCC → tumor nest with central mature keratinization
NODULAR BCC • NODULOCYSTIC / CYSTIC BCC → cystic degeneration within tumor island
• ADENOID BCC → cribriform nests
• Trabecular pattern
SUPERFICIAL BCC

• BCC variant with epidermal

connection
• Confined to papillary dermis
• Superficial lobules of basaloid
cells that project from epidermis
/ the sides of follicles into
dermis
• Surrounded by loose myxoid
stroma
MICRONODULAR
BCC
• Small nest often scattered
throughout the dermis and
subcutis
• Perineural involvement
• Frequently mixed with others
variant
Micronodular with perineural invasion
INFILTRATING BCC

• Variably size basaloid tumor

infiltrate in the normal dermal
kolagen stroma
• >5 – 8 cells thick
• 30% admixed with others variant
(low risk subtypes)
• Perineural invasion is common
SCLEROSING/MORPHEIC
BCC

• Very thin / narrow cords of

tumor ( 1 – 5 cells thick)
• Sclerotic collagenous stroma
• Retraction artefact is uncommon
•
Basosquamous
carcinoma
• Both features of BCC and SCC, as well with
transition zone in between
• Cellular fibrotic stroma
• Distinguishing from :
• keratotic BCC by present of cytological
atypia of SCC.
• Collision tumor by clearly delineated from
one another
FIBROEPITHELIAL
BCC
• Fibroepithelioma of pinkus
• Delicate interanastomosing
strands of basaloid cells
downward from epidermis and
surrounded by abundant
fibroblastic stroma
• Trunk and back, Rarely multiple
• DD/ eccrine
syringofibroadenoma → ductal
epithelium and cuticle
 DIFFERENTIAL DIAGNOSIS
Squamous cell carcinoma : basosquamous type of BCC
• prominent squamous differentiation with areas of more typical BCC, especially at periphery. Overlying AK
or BD often seen in association with SCC

Actinic keratosis (on superficial shave biopsy) : superficial type of BCC

• AK shows basilar budding of atypical squamous cells and overlying parakeratosis, No mucinous stroma,
peripheral palisading, or tumor-stromal retraction artifact should be seen Numerous apoptotic and
mitotic figures favor BCC

Follicular neoplasms (trichoepithelioma and trichoblastoma) : Nodular type of BCC

• Dermal-based basaloid adnexal neoplasms, may be large and nodular symmetric and well circumscribed,
peripheral palisading, lack degree of cytologic atypia, mitoses, mucinous stroma and tumor-stromal
retraction artifact typically lacking,
• Broad connections to the epidermis are uncommon
• Surgical methods remain the preferred treatment for basal
cell carcinoma with surgical excision 4 mm clinical and
histological margin assessment is suitable for low-risk
• Reporting :
• the histological type (growth pattern),
• type of differentiation (the presence of a squamous
component),
• presence of perineural invasion
• distance to the nearest peripheral margin and to the
deep margin.
THANK YOU
FOR YOUR
ATTENTION