1. MSS Pathology SECTION VI SKIN TUMORS Dr. Mohammed Alorjani MD, EBP. 2015

2.  Tumors of skin: Epidermis Dermis Skin appendages Melanocytic tumors Mesenchymal: Vascular tumors… etc

3. SKIN TUMORS Cell of OriginBenignMalignant KeratinocyteSeborrheic keratosis !Actinic keratosis !Bowen disease BCC & SCC MelanocyteMelanocytic nevus Melanoma Merkel cell ----Merkel cell Ca.

4. SKIN TUMORS MesenchymalHemangioma Dermatofibroma Neurofibroma Angiosarcoma Kaposi sarcoma Dermatofibrosarcoma MPNST. Lymphocyte ----Mycosis fungoides(T) Lymphoma(B) Mast cellUrticaria pigm.Systemic. Mastocytosis Dermal adnexaAdenomaCarcinoma

5. 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

8. 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

9. AK: Red and rough to touch (sandpaper- like)

10. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 4 October 2009 10:13 AM) © 2007 Elsevier Hyperkeratosis Parakeratosis Dysplasia CA in Situ Actinic Keratosis

11. C- Malignant Epithelial Skin Tumors

12. These include:  Basal Cell Carcinoma**  Squamous Cell Carcinoma**  Skin Appendage Tumors ** Very common & majority present on sun-exposed skin

13.  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.

14. 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.

17.  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

18.  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

22. Melanocytic Tumors of the Skin

23.  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.

24. 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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29.  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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33. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 20 October 2009 09:05 AM) © 2007 Elsevier Possible steps in Development of melanoma

34.  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

35. 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)…

36. 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)

37. Clark Levels  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 subcutaneous tissue

38. 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)

40. 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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44. Thank you