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MSS Pathology
SECTION VI
SKIN TUMORS
Dr. Mohammed Alorjani MD, EBP.
2015
 Tumors of skin:
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Epidermis
Dermis
Skin appendages
Melanocytic tumors
Mesenchymal: Vascular tumors… etc
SKIN TUMORS
Cell of Origin
Benign
Malignant
Keratinocyte
Seborrheic
keratosis
Melanocyte
Melanocytic
nevus
!Actinic keratosis
!Bowen disease
BCC & SCC
Melanoma
Merkel cell
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Merkel cell Ca.
SKIN TUMORS
Mesenchymal
Hemangioma
Dermatofibroma
Angiosarcoma
Kaposi sarcoma
Dermatofibrosarcoma
Lymphocyte
Neurofibroma
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MPNST.
Mycosis fungoides(T)
Lymphoma(B)
Mast cell
Urticaria pigm.
Systemic.
Mastocytosis
Dermal adnexa
Adenoma
Carcinoma
EPIDERMAL TUMORS
A. BENIGN:
 SEBORRHEIC KERATOSIS:
 Benign neoplasm most in elderly
 Raised, flat, soft, well-demarcated
(coin-like) brown lesion.
 Located mostly on the trunk, limbs &
head.
 Micro: proliferation of squamous
epithelium + cysts filled with keratin
 FGFR3 activating mutations
B. PREMALIGNANT:
 Actinic Keratosis:
 Due to excessive, chronic exposure to
sunlight
TP53 mutation
 Considered as “premalignant” prolif.
Micro:
 Stratum corneum w/parakeratosis &
atypical keratinocytes, may evolve to CA
 Typically seen as hyperkeratotic, scaly
plaques on the face, neck, limbs & trunk.
 Affects most commonly old patients.
 In situ Invasive Squamous Cell CA
AK: Red and rough to touch (sandpaperlike)
Hyperkeratosis
Parakeratosis
Dysplasia
CA in Situ
Actinic Keratosis
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C- Malignant Epithelial Skin Tumors
These include:
 Basal Cell Carcinoma**
 Squamous Cell Carcinoma**
 Skin Appendage Tumors
** Very common & majority present on
sun-exposed skin
 BASAL CELL CARCINOMA
 Most common malignant tumor due to sun
exposure in patients over 40´s with pale skin
 Mainly on face. Sun exposed skin, never mucosal
 Infiltrative but NO METASTASES!
 Pathogenesis:
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 Defects in DNA repair & TP53 mutations
 PTCH gene mutation – Hedgohog Pathway
Gorlin Syndrome
Rx: Surgical Excision;
40% of treated develop a new BCC in 5 years.
Picture:
 Superficial multifocal or Nodular growth
 Other variants:
 Ulcer (Rodent Ulcer)
 Pigmented
 Basosquamous …….etc
 Gross: Papule, rodent ulcer, pigmented lesion…etc
 Micro: nests of epithelial cells that resemble basal
cells forming palisades separated from surrounding
fibroblasts by a cleft-like space.
 Squamous Cell Carcinoma
 Commmon tumor but less common than BCC
 Develops in sun-exposed skin of fair patients with
light hair & freckles, non-exposed skin or mucosa
 Etiology:
Exposure to sunlight, UVB light & radiation
Arsenicals & industrial carcinogens (tar, oil…)
Actinic keratosis
Any chronic scarring processes, e.g. burn scars,
chronic ulcers
 Immunosuppression (HPV 16 & 18)
 Xeroderma pigmentosum
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 Genes involved: TP53, Notch receptors, HRAS
 Sites: dorsal surface of hands, face ,ears,
mucosal surfaces
 Gross features:
 Small lesion initially ulceration later
 Microscopic:
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 Full thickness epidermal dysplasia (CA in situ)
 Invasive carcinoma
 Variable degree of keratinization (differentiation)
It has an increased tendency to infiltrate and
metastasize locally to regional lymph nodes
Melanocytic Tumors of the Skin
 Melanocytic NEVUS (mole/ common nevus).
 Commonest benign tumor in the body
 Derived from dendritic melanocytes
present in basal layer of the epidermis
(nevus cells)
 Contain melanin pigment
 Immature at junction, but mature as
cells migrate down into dermis.
 BRAF or NRAS mutation identified
 There are several types: junctional,
compound and intradermal.
 Gross:
Uniform small tan/brown color with
sharp delineation & tendency to be stable
in size & shape.
 Microscopic picture:
Nests or cords of uniform nevus cells
± pigment.
 Malignant transformation is uncommon
Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 4 October 2009 10:13 AM)
© 2007 Elsevier
Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 4 October 2009 10:13 AM)
© 2007 Elsevier
Dysplastic Nevus
 Sporadic: low risk of transformation
 Familial: Autosomal dominant with melanoma risk
up to 100%
 Considered as a marker for development of
melanoma
 Usually multiple, on exposed or unexposed skin
 Activating BRAF or RAS mutations
 Features: Compound nevus with increased
melanocytes, junctional cytological &
architectural atypia & dermal fibrosis around
proliferating cells
Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 20 October 2009 09:05 AM)
© 2007 Elsevier
Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 20 October 2009 09:05 AM)
© 2007 Elsevier
Possible steps in Development of melanoma
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© 2007 Elsevier
 MALIGNANT MELANOMA
 Sunlight has an important role in the
development of this tumor in the skin
 Appears most frequently on the upper back
(men/women) or legs (women).
 White individuals have higher risk
 More in New Zealand & Australia
 Intense intermittent exposure at early age
 Sporadic OR Familial (5%-10%)
 Sites: Skin, mucosa, eye, meninges… etc
Predisposing factors:
 Sunlight
 Pre-existing lesions: Dysplastic nevus
 Exposure to carcinogens
 Hereditary conditions:
 Xeroderma Pigmentosum
 Retinoblastoma
 Familial melanoma (40% with p16 mutation)
 Many gene mutations (CDKN2A (p16),
BRAF, NRAS, PTEN, c-KIT)…
Type of Growth
 First Radial (Superficial)
 Later downward growth (Vertical/Nodular)
 Staging & prognosis depends on depth of
invasion
 Breslow Thickness: Depth of invasion in mm.s
 Clark Level Staging: Depth of invasion by
location
 Spread is by lymphatics & blood to any site
(liver, lung, brain...etc)
Clark Levels
 Level I: confined to the epidermis (topmost 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 subcutaneous
tissue
Clinical Diagnosis:
 Change in color or size of an existing lesion,
itching, pain, border irregularity, ulceration
 New pigmented lesion in an adult
 Main signs summarized by: ABCDE
A. Asymmetry of shape
B. Border is irregular
C. Color is uneven
D. Diameter is enlarged
E. Evolution (change of an existing nevus)
Microscopic features:
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Neoplastic melanocytes are much larger
Large nuclei with prominent nucleoli
Tumor cells grow horizontally & vertically
Loss of nesting pattern (sheets)
Loss of maturation
 Prognosis is good in radial growth but bad
in deeper vertical growth
Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 20 October 2009 09:05 AM)
© 2007 Elsevier
Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 20 October 2009 09:05 AM)
© 2007 Elsevier
Thank you