W8L2 - Neoplastic Disorders of the Skin

Question 1

Divisions of Primary Skin Tumours

Answer 1

Those arising from epithelial cells
Those arising from melanocytes
Those arising within the dermal and subcutaneous tissues

Question 2

Non-Melanocytic Tumours

Answer 2

Tumours of epidermis
- keratosis, acanthosis
- SCC in situ
- invasive SCC
- basal cell carcinoma
Tumour of cutaneous appendages
- hair follicle tumours e.g. tricho-folliculoma, epithelioma, adenoma, pilomatrixoma
- eccrine tumours syringoma, cylindroma
Sebaceous and apocrine hyperplasia/adenoma

Question 3

SCC in situ and Invasive SCC

Answer 3

Typically in older people especially on sun exposed skin and in immunocompromised individuals
CIS
- Bowen’s disease
- produces scaly lesions on face and legs
SCC
- firm erythematous nodules forming ulcers over time sometimes with crust metastatic potential
- microscopic shows acanthosis, hyperkeratosis, invasion of the dermis, acantholysis

Question 4

Bowen’s Disease

Answer 4

Can be single/multiple may be rounded/irregular/scaly
May be crusty, hairless and well demarcated
Usually 1-5cm in size
More common in women > men 
Exposed and non-exposed areas equally affected
Risks 
- exposure to sunlight
- irradiation
- sunbeds
- arsenic
- Fowlers solution (used to tx asthma)
- HPV-16
- HIV etc.
Considered a pre-cancerous lesion

Question 5

Histology of Bowen’s Disease

Answer 5

Full epidermal thickness dysplasia
Hyperkeratosis, parakeratosis, acanthosis
Hypo or hypergranulosis
Chronic inflammatory infiltrate
Loss epidermal polarity

Question 6

Solar Keratosis

Answer 6

Usually multiple and erythematous
Yellow/brown in appearance, scaly and dry looking
Middle-aged to elderly
Males > females
< 10mm in size
Surrounding skin shows features of sun damage
(atrophy, pigment changes, telangiectasia)
Face, neck dorsal aspects of hands and forearms

Question 7

SCC Clincal

Answer 7

Typically presents in older adults and elderly especially on sun damaged skin
Occ seen in assoc with burn scars, melanoma, porokeratosis, keratosis
2nd most common skin cancer with the 1st being BCC
SCC is variably growing (fast/slow) red, or tan papules or plaques on sun exposed skin that may develop into hyperkeratotic scale or ulcerative lesions
Fair skinned individuals are more commonly affected than dark skinned individuals
Men > women
Recurrence and mets range from 3 to 10%
Poorly differentiated SCC has a worse prognosis but many well differentiate SCC also have a poor outcome

Question 8

Most Common Sites for Mets in SCC

Answer 8

Lymph nodes
Lung
Bone
Brain

Question 9

Histology of SCC

Answer 9

SCC is composed of tumour cells that resemble the epidermal stratum spinosum
SCC originates from epidermal keratinocytes and usually develop from Bowen’s disease or Actinic keratosis
The edges of many tumours show a variably thickened epidermis with parakeratosis and significant atypia of the basal keratinocytes
Dyskeratotic or clear cytoplasm and large, variable vesicular or basophilic nuclei with visible nucleoli and mitoses are seen
The keratinocytes are smaller with more basophilic cytoplasm and mitotic activity
Parakeratotic keratinised eosinophilic pearls are seen in well differentiated tumours
May see inflammatory cells

Question 10

Basal Cell Carcinoma

Answer 10

A group of malignant cutaneous (skin) tumours characterised by the presence of lobules, columns, bands or chords of basaloid cells (‘germinative cells’).
Most common malignant tumour in caucasians
While it can be locally aggressive, metastasis are extremely rare
Arises from the interfollicular or follicular epithelium

Question 11

Pathogenesis of BCC

Answer 11

Somatic mutations seen in PTCH gene
Usually develops on sun damaged skin of fair skinned individuals
BCC arises on areas not exposed to intense sunlight
Unusual to find BCC on fingers and dorsal surfaces of the hands
Tumour derives from the pluripotential cells in the basale and the bulge regions of the hair follicle

Question 12

BCC Clincal

Answer 12

Pearly papule, named because it resembles a 2-3mm pearl
It is covered by tightly stretched epidermis and is laced with small, delicate branching vessels (telangiectasia)
Rodent ulcer - is a small appearing crater in the centre of the pearl
Superficial BCC - appears as a scaly, red, sharply demarcated plaque

Question 13

BCC Variants/Subtypes - Superficial, Nodular and Pigmented

Answer 13

Superficial BCC
- shows multifocal nests of atypical basaloid epithelium arising as buds from the basale
- these nests remain confined to the papillary dermis
Nodular BCC
- forms a solid tumour nodule or nodules which may extend into subcutaneous tissues
- cartilaginous invasion is unusual
Pigmented BCC
- focal deposits of melanin are evident
- increased number of melanocytes can be seen within the tumour
- scattered melanophages may be present in the stroma

Question 14

BCC Variants/Subtypes - Micronodular, Basosquamous, Infiltrating

Answer 14

Micronodular BCC
- forms nodular architecture and the tumour is composed of multiple small nests
- may exhibit extensive infiltration into the surrounding tissue
- associated with a poor prognosis with increased risk of local recurrence
Basosquamous carcinoma
- shows large pale squamoid looking cells that lack keratinisation
- stain +ve with BerEP4 while negative for EMA
Infiltrating BCC
- an aggressive subtype
- shows extensive infiltration of strands and cords of atypical basaloid cells

Question 15

BCC Variants/Subtypes - Metatypical, Infundibulocystic, Sclerosing, Sebaceous

Answer 15

Metatypical BCC
- progression into the typical BCC into areas with large pale cells
- peripheral palisading and clefting is lost
Infundibulocystic BCC
- shows multiple small cysts containing cornified material with differentiation towards the infundibulum
- lacks mesenchymal bodies, but may retain stroma
Sclerosing BCC
- tumour shows strands of atypical basaloid epithelial cells in a densely fibrotic stroma
Sebaceous differentiation
- BCC can occasionally show areas of significant sebaceous differentiation

Question 16

Melanocytic Lesions

Answer 16

Can be divided into 2 main lesions:
- benign and malignant
Benign pigmented skin lesions are very common and are known as ‘moles’
This term encompasses a large group of benign lesions called nevi, which are characterised histologically by aggregates of melanocytic cells at various sites within the skin

Question 17

Benign Melanocytic Lesions

Answer 17

Common tan to brown birthmarks
Present at birth or in first ten years of life
Typically on trunk or extremities
Histology - normal epidermis with increased basal keratinocyte melanin pigment without increased melanocytes

Question 18

Benign Melanocytic Lesion - Solar Lentigo

Answer 18

Occurs as multiple brown macules often due to sun damaged exposed areas involving face and dorsal hands
Slowly increase in size and number over the years
Common variant ‘inkspot’

Question 19

Benign Melanocytic Lesion - Nevus Spilus

Answer 19

Present at birth or early childhood

A tan/brown macule or patch containing speckled darkly pigmented smaller macules

Question 20

Benign Melanocytic Lesion - Junctional Nevus

Answer 20

Well circumscribed light brown to dark brown macules that occur anywhere in the body
Arise in childhood
Histology
- epidermis has variable thickness but with melanocytic nests occurring at the tips of epidermal rete
- melanocytes can range in size with oval to epithelioid shapes with clear cytoplasm containing melanin

Question 21

Benign Melanocytic Lesion - Intradermal

Answer 21

Are often skin coloured papules occasionally dome shaped or polypoid and occur anywhere, but freq on head and neck or trunk on adults
Histology - melanocytes are confined to the dermis where they are organised into nests and cords, often showing neurotized cells deepest zones in the lesion

Question 22

Benign Melanocytic Lesion - Congenital

Answer 22

Present at birth and appear as a solitary tan to dark brown papule/plaque typically present on the trunk
Most measure close to 1cm and may contain mature terminal hairs
- larger nevi are called giant congenital nevi
- 5% increased risk of developing melanoma
Histology
- variable forms presenting as junctional, compound or dermal have been reported
- melanocytes are bland in appearance, with involvement around adnexal structures, vessels and nerves
- deeper portion of the lesion tends to disperse into single cell cords
- variable lymphohistiocytic inflammation in and around the melanocytes

Question 23

Malignant Melanoma

Answer 23

Malignant neoplasms derived from melanocytes
Most commonly encountered types:
- superficial spreading melanoma: 30-60%
- nodular melanoma: 10-35%
- lentigo malignant melanoma: 10-40%
- acral lentiginous melanoma: 5-10%
- desmoplastic and nevoid: rare
Mean age for dx is 63yrs among men and 60 yrs for women
Melanoma is the most common cancer dx in young Australians aged 15-24yrs

Question 24

Risk Factors of Malignant Melanoma

Answer 24

Most significant risk factor include the number of nevi, both typical and atypical, cutaneous and pigmented phenotypes
Other factors include; eye colour, hair colour, skin colour, freckling and skin phototype, family and personal history of melanoma and non melanoma skin cancer
Significant sun exposure
Non solar UV radiation
Immunosuppression

Question 25

Melanoma Progression (Clark Model)

Answer 25

1. Benign melanocytic nevi
   - controlled proliferation of normal melanocytes to produce a benign nevus
2. Atyp/dysplastic nevi
   - abnormal growth of melanocytes in a pre existing nevus or new location resulting in a pre-malignant lesion with random cytologic atypia
   - these may be flat macules >5mm in size with irreg borders and variable pigmentation
3. Radial growth
   - melanocytes acquire ability to proliferate horizontally in the epidermis and histologically show continuous atypia (melanoma in situ)
4. Vertical growth
   - numerous biochemical events including the loss of E-Cadherin and expression of N-cadherin allow malignant cells to invade BM and proliferate vertically in the dermis with metastatic potential
5. Mets (metastasis)
   - malignant melanocytes spread to other sites usually LNd then to skin, subcutaneous, soft tissue, lungs and brain

Question 26

Signs and Symptoms of Malignant Melanoma - A, B, C, D, E

Answer 26

A = asymmetry
- benign is symmetrical while malignant isn’t
B = border
- benign border is even and malignant is uneven
C = colour
- benign is 1 colour, malignant 2 or more colours
D = diameter
- benign is < 6mm, malignant > 6mm
E = evolution
- benign is an ordinary mole, malignant shows changing in size, shape, colour etc.

Question 27

Staging of Invasive BCC and SCC

Answer 27

Stage 1 - tumour diameter < 20mm
Stage 2 - tumour diameter > 20mm
Stage 3 - lymph node involvement
Stage 4 - distant metastasis