Skin Tumour - 01-03-04

KERATINOCYTES NEOPLASMS

1	Seborrheic keratosis: Benign tumours. Where: trunk, face, extremeties. Who: elderly
	Macroscopy: "coinlike" lesions that look like they can be peeled off, well demarcated, Microscopy: exophytic lesion composed of sheets of basaloid cells, hyperkeratosis of at the surface, horn and pseudo-horn cysts (filled with keratin). 
	
2.	Solar keratosis: Pre-malignant dysplastic lesion (assoc with sun exposure)
	Macroscopy: red/brown lesion (<1cm), Microscopy: Epidermis: 1) hyperkeratosis, 2) hyperplasia of basal epithelial cells + hyperchromasia + increased mitosis, Dermis: 1) dermal elastosis (elastic fibre aggregates produced by fibroblasts). 

BOWEN'S DISEASE
What is it?: This is carcinoma in situ, occurs in sun exposure --> Where: vulva, glans penis, oral mucosa, skin. 
Macroscopy: flattened plaque, looks like "rash/psoriasis", Microscopy: 1) epithelial maturation lost, 2) no invasion of stroma, 3) epithelial cell atypia (hyperchromasia, pleomorphic, dysplastic, prominent nucleoli). 

SQUAMOUS CELL CARCINOMA (Robbins pp 1185)

1.	General: Most common tumour of the skin, men more affected than woman
	Risk factors: UV exposure, tar/oils, chronic ulcers, draining osteomyelitis, burn scars, arsenicals, radiation, tobaccoa + betel nut chewing (oral mucosa), xeroderma pigmentosa, immunosuppresion. 
	Pathogenesis: UV sunlight has a direct damaging effect on the DNA of epidermal cells. It also inhibits the function of Langerhan cells, and the cells that suppress T lymphocyte activation pathways are immune to UV damage. All this favours tumourigenesis. Viral DNA (e.g.: HPV Type 36) has been extracted from pre-malignant lesions that lead to SCC. 
	Morphology Fig 27-14A: The morphology may vary depending on whether its in-situ or invasive. Macroscopy: In situ SCC appear as well demarcated raised plaques. Invasive SCC appears as hyperkeratotic, ulcerated, nodular lesion. Microscopy: In situ: cellular atypia in all layers of epidermis, does not invade stroma, Invasive: cells break through basement membrane, range from well differentiated to anaplastic cells, foci of necrosis may be present. Tumour cells have prominent nucleus / nucleoli with angulated contours. 
	Clinical Course: Rarely metasise. (5% mets rate). 

BASAL CELL CARCINOMA (Robbins pp 1186)

1.	General: Common tumour
	Risk factors: UV exposure, xeroderma pigmentosa, immunosuppresion, carcinogens
	Morphology (Fig 27-15): Macroscopy: nodules with telangiectasia (dilated subepidermal, Microscopy: Two patterns: 1) multifocal: originates from epidermis and extends over several cm2 of skin, 2) nodular: downward growth of cords/islands of basaloid cells, central tumor cells haphazardly arranged, peripheral palisading cells, and separation artifacts ("stromal shrinking"). 
	Clinical course: locally aggressive (invades bone) but rarely metastasize vessels)

MELANOCYTIC NEVI (Robbins pp 1174)
General: This is a common hamartomas of melanocytes. nevi = mole). There are various types of nevi depending on where they are found and the clinical/histological appearances. 

1.	Nevocellular nevi: Melanocytes are highly dendritic cells that are found interspersed among the basal keratinocytes. The melanocytes in this case have been transformed into oval cells, that grow in nests/aggregates. They have a very prominent nucleus with clearish cytoplasm. They beging to grow in dermoepidermal junction (junctional nevi). Then, they progress into the dermal layer as nests/cords of cells (compound nevi). Sometimes the epidermal nests disappear leaving only dermal nests (dermal nevi). Maturation occurs at the same time. That is: superficial nevisu cells are less mature, grow in nests, but produce melanin pigment, but deep nevus cells are more mature, grow in cords, and produce no melanin pigment (they are "in betweens"). This differentiation is important in identify some benign nevus from malignant melanoma. 

The above description can apply all of the following types of nevi:

	Spitz nevi - compound (spindle and epitheloid cell nevus): large cells with pink/blue cytoplasm, fusiform cells. Common in children.
	Blue nevi (dermal): highly dendritic heavily pigmented nevi cells. Does not grow in nests. 
	Halo nevi: central area of pigmentation with clear area around it, heavy lymphocytic infiltration surrounding nevi cells. 
	
2.	Dysplastic nevi (autosomal dominant): In 1978, it was discovered that there was a specific type of nevi that was a precursor to malignancy. Note that all of the above are benign. Macroscopy (Fig 27-6): These are slightly raised dark macules with flattened irregular border (less darker). Microscopy: Nests of nevi cells fuse together to form large nests and eventually the basal layer of epidermis is replaced by nevi cells (lentiginous hyperplasia). Individual cells have cytological atypia (hyperchromasia, angulated irregular contours. 

MALIGNANT MELANOMA (Robbins pp 1177)
General: Melanoma is a neoplasm that occurs whereever there are melanocytes. Melanocytes exists in: skin, oesophagus, GIT, anogenital mucous, meninges, eye. 
Risk factors: sunlight, lightly pigmented individuals, dysplastic nevus, genetics, certain carcinogens. 

Molecular genetics: Most data recorded is from melanomas that run in families. Those that dont, we do not understand the genetics of. Mutations in genes involved are: CMMI, tumour suppresor gene p16 (negatively regulate cell cycle), CDK4. 

Morphology: Macroscopy: heavily pigmented irregularly bordered lesions, Microscopy: 1) larger than nevus cells, 2) irregularly peripherally clumped chromatin within nuclear membrane + prominent red nucleoli, cells have all features of malignancy (i.e.: cytological atypia). 
Growth patterns: radial (grow horizontally within the epidermis and superfical dermal layers without metastasis) vs vertical (downward growth of nests of cells into deep dermal layers). Specific types of radial growth: lentigo maligna (malignant melanocytes forming the basal epidermal layer), superficial spreading malignant melanoma in situ (melanocytes grow in nests/scattered in epidermis without dermal invasion), invasive superficial spreading malignant melanoma (similar to insitu, but invades into superficial dermal layer), acral/mucosal lentiginous (in nail beds, quite rare). Specific types of vertical growth are: invasive nodular malignant melanoma (have initial radial growth and then become vertical). 

Clinical course: The most important clinical sign of disease is: change in colour of pigmentation (black, brown, dark blue, red, grey), irregular border, may be ulcerated. Watch out for disease if: 1) enlargement of mole, 2) itching of mole, 3) change in pigmentation, 4) irregularly bordered lesion. Frequently metastatises to lung, breast, bone, brain, prostate, kidney. 