SKIN: Tumors and Tumor-like

conditions
September 21 and 28, 2016
Aisa G. Mendoza, MD DPSP
 OBJECTIVES:
• Be familiar with some of the clinically
important epidermal, melanocytic and dermal
tumors
• Differentiate SCCA from BCCA
• Understand the pathophysiology of each
tumor and correlate it clinically
 OUTLINE:
• Epidermal Tumors
– Seborrheic Keratosis
– Acrochordion
– Squamous Cell Carcinoma
– Basal Vcell Carcinoma
• Melanocytic Tumors
– Nevus
– Malignant Melanoma
• Dermal Tumors
– Dermatofibroma
– Dermatofibroma protuberans
 SEBORRHEIC KERATOSIS
• Benign
• Pigmented
• Basal keratinocytic proliferation
• Trunk
• Laser-Trelat sign
LESION: round, flat, coin-like, waxy plaques
that vary in diameter; uniformly tan to dark
brown & usually have a velvety to granular
surface
MICRO: marked acanthosis of predominantly basaloid cells
with moderate papillomatosis and hyperkeratosis
- small keratin-filled cysts (horn cysts) and invaginations of
keratin into the main mass (invagination cysts)
 Hyperkeratotic type

Acanthotic type

Reticulated or Adenoid
type
Acantholytic subtype
• Immunohistochem:
– Keratinocytes
• express Low Molecular Weight Keratin
• Deficient in High Molecular Weight Keratin
• Irritated seborrheic keratosis
– Squamous metaplasia is pronounced
– Misdiagnosed as basosquamous ca
– NOT related to HPV
• INSTEAD, HPV CAN BE IDENTIFIED IN THE SEBORRHEIC
KERATOSIS-LIKE LESIONS OF PATIENTS WITH
EPIDERMODYSPLASIA VERRUCIFORMIS AND THOSE
EXHIBITING BOWENOID CHANGES
• Treatment:
– Superficial curettage
– Freezing
 FIBROEPITHELIAL POLYP
• A.K.A. acrochordon, squamous papilloma,
skin tag
• Generally detected as an incidental finding
in middle-aged and older individuals on
neck, trunk, face and intertriginous areas
• Often become more numerous or
prominent during pregnancy  related to
hormonal stimulation
• LESION: soft, flesh-colored, bag-like tumor often
attached to the surrounding skin by a slender
stalk
MICRO: tumors consist of fibrovascular cores
covered by benign squamous epithelium
• Acquired (digital) fibrokeratoma
– Collagenous protrusions covered by hyperkeratotic
epidermis
– Usually seen around interphalangeal joints
 Squamous cell carcinoma (SCCa)
• Actinic induced
• Induction of p53 mutation by ultraviolet light
• Sun exposure
• Lack of pigmentation in the skin
• Scca as a complication of the ff:

– Xeroderma pigmentosa – diminished capacity for

DNA repair following ultraviolet radiation
• BCCA
• Malignant melanoma
• Epidermoplasia verruciformis – generalized
virally induced dermatosis
• Cutaneous scars from various type:
– Marjolin’s ulcer (burn)
– X-ray
– Epidermolysis bullosa
– Chronic osteomyelitic sinuses
– Necrobiosis lipoidica
– Hidradenitis suppurativa or acne aggregata seu
conglobata
• Chemical exposure
• Organ transplanttaion
• PUV-treated psoriatic patients
• HIV infection
• Ichthyosis, epidermal nevus, porokeratosis
and congenital lympedema
scca
LPO
hpo
• Invasion of the dermis is sine qua non for
diagnosis
– Can be subjective
– But of no great practical importance, since
treatment and prognosis is the same
• Immunohistochem:
– Express :
• High molecular weight keratin
• Involucrin
• Epithelial membrane antigen (EMA)
• CEA
• Vimentin (poorly differentiated tumor)
• Laminin and type IV collage – can be seen surrounding
tumor nests
• Negative:
– BerEP4
 Other microscopic types
• Spindle SCCA (metaplastic carcinoma)
– Sun exposed area
– Lips
– Express vimentin
• Adenoid (pseudoglandular; acantholytic) SCCA
– lack of cell cohesiveness caused by a desmosomal
defect (acantholysis)
– Sun exposed
– Immunohistochem:
• Reduction of cell adhesion molecule syndecan-1
• Verrucous CA
– Extremely well differentiated type
– Carcinoma or epithelioma cuniculatum
– Ulcerated, fungating and polypoid mass with
openings of sinus tracts onto the skin surface
 Treatment scca
• Complete excision
• Alternative therapies:
– Curettage and electrodessication
– Cryotherapy
– Radiation therapy
• Prognosis:
– Excellent (actinic induced tumor)
– Best prognostic determinators are
• Staging
• Level of dermal invasion
• Vertical tumor thickness
 Basal cell carcinoma (BCCa)
• Most frequent form of skin cancer
• Sun exposed skin in direct proportion to the
number of pilosebaceous unit present therein
• May also develop in:
– sunlight protected skin
– Nevus sebaceous of jadassohn
– Lower leg in asso w/chronic venous stasis
– Arsenic ingestion
– X-ray exposure
– Skin injury
• May also develop in:
– Chicken pox scars
– Tattoos
– Hair transplantation scars
– Immune suppression
• Clinical appearance may be variable....
– Nodular
– Ulcerative
– Superficial
– Erythematous
– Sclerosing (morphea like)
• Basal cell nevus syndrome (Gorlin’s syndrome)
– Multiple basal cell ca
– Palmar pits
– Calcification of dura
– Keratinous cysts of the jaws
– Skeletal animalies
– Occasional abnormalities of the CNS, mesentery
and endocrine glands
Palmar pits
Multiple bcca
• Suspect when:
– BCCA are seen in young people
– Multiple tumor
– Superficial multicentric type
– Osteoid is a occasional finding
 Microscopic
• Arise from:
– Basally located cells of the epidermis and
pilosebaceous units
• DIFFERENTIATE INCOMPLETELY IN THE DIRECTION OF
ADNEXAL (PRIMARILY FOLLICULAR) STRUCTURES
• EPIDERMAL ATTACHMENT IS PRESENT
• Characteristics:
– Palisading
– Surrounded by a typical loose stroma
– Containing microblast
– Mucinous change
– Cleft like retraction spaces
– Melanin can accumulate in the dermal
macrophages
• May have the ff patterns:
– Solid
– Cystic
– Adenoid
– Keratotic
– Pigmented
– Infiltrating
– Sclerosing (morphea-like)
• May occur:
– Mitotic activity
– Marked atypia
– Bizarre (monster) tumor cells
– Giant cell formation
• Histochemical/immunohistochem:
• Positive:
– Keratin (low molecular weight type)

– BerEP4
• Negative :
– EMA
– CEA
– Involucrin
• Molecular
– Over expression of p53 protein
– Bcl-2 (differentiate with actinic keratosis)
• Genetic:
– Clonal chromosome abberation (numerical
changes +18, +9, +20, +7 and +5
– Loss of heterozygosity (9q22.3)
– Trisomy 6
 Other microscopic type
• Superficial BCCA
– Arises in thin epidermis (trunk), sparse, fine hairs
– High recurrence
• Basosquamous (metatypical) CA
– Also contain atypical squamous cells
– More aggressive than conventional BCCA
– High proportion metastasize
• Granular basal cell CA
– Tumor cells with cytoplasmic granules
• Clear cell basal cell ca
– Prominent cytoplasmic vacuoles
– Signet ring configuration
• Fibroepithelial tumor / Pinkus’ tumor/
Fibroepithelioma
– Polypoid variant
– Occur at the back
– Abundant stroma
• Infundibulocytic basal cell ca
– Hair follicle differentation
 Spread and metastasis
• Grow in slow, indolent fashion
• If untreated invade subcutaneous fat, skeletal
muscle and bone (“ulcus rodens”)
• Tumor in the face may invade the skull, nares,
orbit, temporal bone
• Distant metastasis is extraordinarily rare
– Regional LN, lungs, bones and liver
– Basosquamous type
• Treatment :
– Excision
– Curettage and desiccation
– Irradiation
• Recurrence :
– Radiation therapy
– Surgical re-excisison
– Mohs’ surgery
 Benign and Malignant Tumors of
Melanocytes
• Nevus (pl. Nevi)
• Malignant Melanoma
 Nevus (pl. Nevi)
• L. naevus, birthmark - any circumscribed
growth of the skin of congenital nature
• L. moles, a shapeless mass - localized benign
abnormality of the melanocytic system
• Melanocytic nevi – usually acquired
• Become clinically apparent after the first year
of life
• Appear 2nd to 6th years, nearly all by 20 years
• BRAF mutation
 Nevus (pl. Nevi)
• Most common location?
• What is the distribution in the body?
• Head, neck, trunk? or
• Lower extremities?
• Different size, shape, degree of pigmentation
• More or less hairy
• Types are best classified accdg to location in
relation to the major epidermal and dermal
landmarks
Junctional nevus
• is restricted to the basal
portion of the
epidermis (‘junctional’
area)
• palms and soles
• Gross:
• Microscopic:
• Malignant melanomas
may arise from this
lesion
Compound Nevus
• it has both an epidermal
and a dermal component
• The percentage of nevi
with junctional changes
decreases as the age of the
patient increases
• amount of melanin
deposition is concentrated
in the superficial half of the
lesion
• lymphocytes and other
mononuclear cells may be
seen at the base of the
lesion
Intradermal Nevus
• all the melanocytes are in the
dermis
• Most common adult type of
nevus
• papillomatous,
pedunculated, or flat, and it
is often hairy
• Microscopic:
• Malignant melanomas
practically never arise from
intradermal nevi
Blue Nevus
• small and located in the head,
neck, or upper extremity
• an ill-defined deep dermal
proliferation of elongated and/or
dendritic dermal melanocytes
• Melanin pigment is usually
abundant
• junctional activity is consistently
absent
• GNAQ mutation, no BRAF
• Diff Dx: Benign Fibrous
Histiocytoma, DFSP, MM
 Treatment
• Excision
• Definite indications
– appearance of a pigmented lesion in an adult
– chronic mechanical irritation of a nevus,
– appearance of any of the following changes in a
preexisting nevus:
• deepening of pigmentation or spread of the pigment
beyond the gross confines of the lesion
• appearance of flat areas of depigmentation within the
nevus,
• appearance of a red inflamed zone around the nevus
• rapid growth, ulceration, itching, oozing of serum, or
bleeding with trivial trauma.[
 Malignant Melanoma
• Majority associated with sunlight exposure
• most are found in the head and neck area and
on the (lower extremities females)
• Whites with fair complexion, red hair , and a
tendency to burn or develop freckles after
exposure to sunlight
• Blacks-palms, soles, nail beds, or mucous
membranes
• SKIN, other sites (oral and anogenital
mucosal surfaces, esophagus, meninges &
eye)
– Men - on upper back
– Women -both the back and legs
• RISK FACTORS
– Fair skin (blond or red hair, light-colored eyes, freckle
or sunburn easily)
– History of blistering sunburn
– Excessive UV light exposure (sun & tanning beds)
– Living closer to the equator or at a higher elevation
– Having many moles or unusual moles (>50 or unusual
mole >5mm)
– Family history of melanoma
– Weakened immune system
• Immunohistochemical Features:
positive for
– HMB-45
– vimentin
– S-100
– Melan-A
– tyrosinase
• Molecular genetic factors: genetic
abnormalities detected in melanoma
include:
– CDKN2A and PTEN inactivation
– RAS mutation
– BRAF mutation
Clark Model of Tumor Progression
Pathogenesis
 Dysplastic Nevus
• Precursor of melanoma
• Dysplastic nevus syndrome: probability that a
person will develop melanoma is over 50% by
age 60 and at-risk individuals sometimes develop
several melanomas at different sites
 Dysplastic Nevus
• larger than most acquired nevi (often >5 mm across)
• flat macules, slightly raised plaques
• variability in pigmentation (variegation)
• borders that are irregular in contour
• occur on non-sun-exposed as well as on sun-
exposed body surfaces
• probability of developing melanoma is 56% at age
59 years
LESION: flat macules, slightly rased plaques
with a “pebbly” surface, or target-like lesions
with a darker raised center and irregular flat
periphery
MICRO: Nevus cell nests within the epidermis may be enlarged
and often fuse or coalescence with adjacent nests
 Pathogenesis
• Dysplastic nevus syndrome is inherited in an
autosomal dominant pattern.
• Several mutated genes have been discovered
in affected families, including CDKN2A on
chromosome 9p21 and CDK4 (cyclin-
dependent kinase 4) on chromosome 12q14,
both of which are also associated with
familial forms of melanoma
 Dysplastic Nevus
May be <6mm in diameter, not often >10mm
Somewhat symmetrical
Uniformly elongated narrow, delicate rete
ridges
No alteration of stratum corneum
Nests predominate over single cells in the
epidermis
Little or no pagetoid spread of lesional cells
into epidermis
Scattered atypical epithelioid cells with dusty
melanin pigment, nucleoli, anisokaryosis
(random atypia)
Most cells are not atypical
No mitoses in epidermis or dermis
Cells in dermis, if any, are smaller than those in Cells in dermis are similar to those in
epidermis
Radial Growth-Phase Melanoma
Usually >6mm, often much >10mm
Often highly asymmetrical
Irregularly thickened epidermis, often with
effaced rete ridges
May be hyperkeratotic
Single cell predominate except in late lesion
Usually obvious pagetoid spread into
epidermis, extending to S. corneum
Epithelioid cells with dusty pigment, nucleoli,
anisokaryosis predominate (uniform atypia)
Most cells are atypical
Intraepidermal mitoses in abt 1/3 of cases; no
mitoses in epidermis
epidermis
Morphology (ABCDE of Melanoma)
Clinicopathologic Types
 Morphology
• Radial growth describes the horizontal spread of
melanoma within the epidermis and superficial
dermis.
• Vertical growth phase occurs when tumor cells invade
downward into the deeper dermal layers as an
expansile mass
– Heralded by the appearance of a nodule and correlates with
the emergence of a clone of cells with metastatic potential
– The probability of metastasis in such lesions correlates with
the depth of invasion, which by convention is the distance
from the superficial epidermal granular cell layer to the
deepest intradermal tumor cells (Breslow thickness)
Radial growth phase: irregular Vertical growth phase: Nodular
nested and single-growth of aggregates of infiltrating cells
melanoma cells within the
epidermis & an underlying
inflammatory response within
the dermis
MICRO: Melanoma cells contain large nuclei with irregular
contours chromatin clujped at the periphery of the nuclear
membrane and prominent red (eosinophilic) nucleoli
Breslow Thickness
• less than 1 mm: 5-year survival is 95% to 100%
• 1 to 2 mm: 5-year survival is 80% to 96%
• 2.1 to 4 mm: 5-year survival is 60% to 75%
• greater than 4 mm: 5-year survival is 37% to 50%

Clark Level
• Level I: confined to the epidermis (top-most layer of skin);
called "in situ" melanoma; 100% cure rate at this stage
• Level II: invasion of the papillary (upper) dermis
• Level III: filling of the papillary dermis, but no extension in
to the reticular (lower) dermis
• Level IV: invasion of the reticular dermis
• Level V: invasion of the deep, subcutaneous tissue
AJCC 2010 Staging
AJCC 2010 Staging
 Spread and Metastases
• melanoma spreads by growing along the
dermoepidermal junction and upper dermis
and later by invading the deep dermis and
eventually the subcutis and deeper structures
• Metastases in regional lymph nodes are
common even if the nodes appear clinically
negative
• Distant metastases-liver, lungs,
gastrointestinal tract, bone, and central
nervous system but can occur anywhere,
including within other tumors
 Treatment
• wide excision of the primary lesion (atleast 3.0
cm margin) with radical lymph node dissection
• Radiation therapy-Hutchinson freckle
(alternative)
• radiation therapy, chemotherapy, and
immunotherapy are ineffective in invasive or
metastatic melanoma
• Dacarbazine-drug of choice in disseminated
melanoma
• interleukin, biochemotherapy, and interferon
have given good results, but only in a small
percentage of patients
 Prognostic Factors
• Tumor stage-the most important prognostic
parameter
• Level of invasion and tumor thickness (Clark
and Breslow)
• Shape of the lesion-plypoid is poorer
• Sex-the 5 year survival rate was 50.5% for
males and 70.5% for females
• Age-younger is better in MALES but not in
females
 Prognostic Factors
• Anatomic location-scalp, mandibular area,
midline of trunk, upper medial thighs, hands,
feet, popliteal fossae, and genitalia, ungual

• Size. The diameter of the melanoma has no

independent prognostic significance once this
parameter has been corrected for tumor
thickness
 Prognostic Factors
• Clinicopathologic type-Hutchinson (best),
Nodular and Acral (worse), Superficial
(intermediate) Note:once depth of invasion is
entered into the equation, most of these
differences are erased
• Cytologic features and Degree of
pigmentation-no influence on prognosis
• Mitotic rate-higher rate, poorer prognosis
• Dermal inflammatory infiltrate- the denser the
better
 Prognostic Factors
• Ulceration-one of the most important
prognostic determinators of the primary
tumors
• Angiotropism-local recurrence and in-transit
metastasis
• Microscopic satellites-high association with
regional lymph nodes metastasis
• Preexisting benign nevus-better prognosis
 Tumors of the Dermis
• Dermatofibroma
• Dermatofibroma protuberans
 Benign Fibrous Histiocytoma
• subepidermal nodular fibrosis,
dermatofibroma, histiocytoma, and sclerosing
hemangioma
• firm, nodular, nonencapsulated, often
pigmented lesions that occur chiefly on the
extremities
• Clinically, single or multiple, and have a flat,
polypoid or depressed shape. Most of them
are less than 1 cm in diameter
 Benign Fibrous Histiocytoma
•usually seen in adults & often occur on the
legs of young to middle-aged women
• Indolent biologic behavior
• LESION: On transection, solid,well
circumscribed but not encapsulated
•color white to yellow to dark brown,
depending on the relative
amounts of fibrous tissue,
fat, and hemosiderin
MICRO: benign, spindle-shaped cells arranged in a well-
defined, non-encapsulated mass within the mid-dermis
 Dermatofibrosarcoma protuberans
• regarded as a well-differentiated, primary
fibrosarcoma of the skin
• slow-growing, nodular, polypoid neoplasms that
are found almost exclusively in the dermis, from
which they often invade the subcutaneous tissue
•locally aggressive and can recur
• rarely metastasize
• Molecular HALLMARK: t(17;22)(q22;q13)
balanced translocation between genes
encoding collagen 1A1 (COL1A1) and
PDGF-B
LESION: firm, solid nodules that arise most frequently
on the trunk
Dermatofibrosarcoma protuberans
• radial whorls of spindle cells
producing the storiform or
cartwheel pattern
• the high cellularity,
monomorphic appearance,
moderate-to-high mitotic
activity, lack or
inconspicuousness of foamy
or hemosiderin-laden
macrophages and/or
multinucleated giant cells
• entrapment of isolated fat
cells when the subcutis is
infiltrated
DFSP to Fibrosarcoma
 Pigmented DFSP (Bednar Tumor)
• Ordinary DFSP containing variable amounts of
melanin pigment
• Melanocytic markers are negative