LEUKOCYTES (THE WHITE BLOOD CELLS)
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Transcript LEUKOCYTES (THE WHITE BLOOD CELLS)
MSS Pathology
SECTION VI
SKIN TUMORS
Dr. Mohammed Alorjani MD, EBP.
2015
Tumors of skin:
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
----
Merkel cell Ca.
SKIN TUMORS
Mesenchymal
Hemangioma
Dermatofibroma
Angiosarcoma
Kaposi sarcoma
Dermatofibrosarcoma
Lymphocyte
Neurofibroma
----
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:
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
Genes involved: TP53, Notch receptors, HRAS
Sites: dorsal surface of hands, face ,ears,
mucosal surfaces
Gross features:
Small lesion initially ulceration later
Microscopic:
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
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© 2007 Elsevier
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© 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
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© 2007 Elsevier
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© 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:
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
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© 2007 Elsevier
Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 20 October 2009 09:05 AM)
© 2007 Elsevier
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