I. Tumours of Epidermal Origin
A. BENIGN
1. Surface Epidermis a. Viral tumours
(1) Human papilloma virus
(2) Molluscum contagiosum b. Seborrheic keratosis c. Cutaneous cysts
(1) Epidermal inclusion cysts (eg sebaceous cyst)
(2) Dermoid cysts
(3) Milia d. Achrochordon (skin tag) e. Keratoacanthoma f. Epidermal naevi (naevus verrucosus)
2. Epidermal Appendages a. Pilar (hair) structures
(1) Pilar (trichilemmal) cysts
(2) Pilomatrixoma
(3) Trichoepithelioma b. Sebaceous glands
(1) Rhinophyma
(2) Sebaceous hyperplasia
(3) Naevus sebaceous c. Sweat glands
(1) Syringoma
(2) Eccrine poroma
(3) Hidradenoma papilliferum
(4) Cylindroma
B. PREMALIGNANT
1. Surface Epidermis

a. Bowen’s disease b. Actinic keratosis c. Leukoplakia d. Erythroplakia e. Paget’s disease
2. Epidermal Appendages a. Naevus sebaceous of Jadassohn
C. MALIGNANT –
1. Basal Cell Carcinoma
2. Squamous Cell Carcinoma
II. Tumours arising from the Melanocyte system
A. TUMOURS ARISING FROM NEVUS CELLS
B. TUMOURS ARISING FROM MELANOCYTES (epidermal / dermal)
C. MALIGNANT MELANOMA
III. Tumours of Mesodermal origin
A. CONNECTIVE TISSUE
B. VASCULAR
C. FAT / MUSCLE / BONE
D. LYMPHORETICULAR SYSTEM
IV. Cutaneous Endometriosis
V. Visceral Metastases to Skin

Malignant tumour arising from basal layer of the epithelium or from the external root sheath of the hair follicle
Greatest concentration in areas that have the highest concentration of pilosebaceous units
Does not possess cellular aplasia (required for a true carcinoma and (almost) never metastasizes
Basal cell carcinoma differs from squamous cell carcinoma in that it does not arise from malignant changes occurring in pre-existing mature epithelial structures
Jacob first described in 1827 – three cases of an ulcer in Celts from Dublin
Krompecher 1900 – pathological description
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Aetiology o Genetic

Gorlin-Golt Syndrome
 childhood onset.

Palmar pits, Calcification of the falx, bifid ribs,jaw keratocysts esp after puberty, other craniofacial
 autosomal dominant
 tumors have a benign clinical course until after puberty, when malignant degeneration

Xeroderma Pigmentosum
 incomplete sex-linked recessive gene.
 onset during early childhood
 extreme sensitivity to sunlight.

Initially, diffuse lentigos are noted, with progressive drying and thinning of the skin.

The primary deficiency is that of the enzyme endonuclease, which is needed to repair sunlightdamaged DNA.

Malignant degeneration into basal cell carcinoma, squamous cell carcinoma, or melanoma is noted during early adult life, with death due to metastatic disease. Prolongation of life is possible by absolute protection from sun exposure and continual aggressive treatment of all developing tumors. The prognosis is dismal. o Acquired

Sun

Fitzgerald Skin types I and II

Immune-suppression (x20)

Arsenic ingestion (Bell’s Asthma Mixture)

Scar

Smallpox vaccination scars

Burns scars

XRT

Viral infection (small pox vac, HZV, HPV)

Sebaceous naevus (10%)
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Classification o A Localised or diffuse o B Clinicopathological type

Papulonodular (45%)
 solid, cystic

Infiltrating (8%)
 primary (8%), secondary characteristic (16.6% total), 35% recurrent BCC’s

Multifocal (35%)
 superficial, centre-healing/field fire/cicatrising, multifocal in depth

Morphoeic / sclerosing (8.9%)

Metatypical / basisquamous(1.4%)
 rare metastatic BCC (1:50000) o C Secondary characteristics

Pigmented, naevoid, ulcerated, recurrent, arising in scar/XRT

Clinical manifestations o Papulonodular
 raised pearly edge, surface venules, depressed or ulcerated centre.

May be very well circumscribed.

Infiltrative component in ~15%. o Infiltrating


Diverse appearance, scaly red or grey with induration.

May lack the characteristic edge.

Invade deeply along tissue planes and nerves. o
Multifocal

Red scaly patch 5-10mm diameter with multiple foci, micropearly edge, field fire surface with multiple small ulcerations.

~10% infiltrative component. o
Morphoeic

Whitish grey plaque, may be hollowed.

May be a red ring with the pearly plaque only visible on tensing the skin.

Dangerous because poorly recognised and infiltrative in >50%. o
Metatypical

Characteristics of SCC & BCC.

More aggressive. o Other

Pigmented- can be any type.

Histology : o Nests or sheets of uniform basophilic cells o Peripheral palisading (basaloid cells in a single line at the periphery of the tumour) o High mitotic and apoptotic rates (Councilman bodies) o Acid mucopolysaccharide stroma- cysts o Pigment- Haemosiderin and melanin within stromal macrophages o Infiltrating components are thin strands, +/- spindle cells, palisading gone

Rx : o
Excision with margin: PN localised (? 1mm), infiltrating 5mm, recurrent infiltrating up to 10mm o Difficult recurrent tumour: horizontal histologically sectioned o Dermatological:

Cryotherapy (liquid nitrogen -195 degrees)

Topical 5-FU
 Moh’s microscopically controlled surgery o XRT

Outcome: o 5% recurrence at 5yrs o 10% recurrence if BCC < 1 hpf from margin o 33% if positive margin o
Re-excision for positive margin only 50% with residual BCC o DANGER ZONES: areas of embryonic cleavage (along the frontonasal prominence, eg alar base, nasolabial fold, inner canthus, nose-cheek angle; also the postauricular region, pinna, ear canal, ?forehead, and ?scalp)

Malignant tumour of epidermal keratinocytes characterised by invasive nests of prickle cells showing variable central keratinisation and pearl formation.
Arises from the stratum spinosum

Incidence 201/100000 (Aust 1 SCC: 4 BCC)
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Aetiology o Sunlight (stronger correlation with damage to skin by actinic radiation then BCC – occurs in areas of direct sunlight) o skin type o viral infection (VZV, HPV) o immunosuppression o scars (burn, trauma, vaccination, XRT) o chemical (tars, nitrogen mustard, polycyclic hydrocarbons, nitrosureas, arsenic, soot) o genetic (xeroderma pigmentosa)

Classification: Based on clinical features and is tempered by the knowledge that diagnostic accuracy for SCC <50% for Dermatologists/Surgeons and ~15% for GP’s o Site o Descriptive: superficial, proliferative, scar, recurrent, metastatic o Histology:
 Spindle cell: bundles of spindle cells

Adenoid: islands or columns with tubular differentiation

Verrucous: WD, slow growth, warty appearance o Differentiation: Well, moderate, poor

DDx o Hyperkeratosis o BCC o
KA o Amelanotic melanoma o Merkel Cell Ca o Leukaemic skin deposit o
Chronic ulcer o Fungal infection
 Histology : o consists of irregular masses of squamous epithelium that proliferate downward to the dermis o The degree of cellular differentiation determines the grade of the tumour and is measured in the ratio of atypical pleomorphic and anaplastic cells to normal epithelium o Changes in size and shape of the cells, hyperchromasia, keratinization, and the proportion of mitotic figures influence the determination of grade o Prickle cell o
Keratin pearl o Spindle cells o Majority arise in solar keratosis o Involve full thickness epidermis before dermis o
Invade dermis in large tongues vs strands (BCC) o Eosinophilic cells o Epidermal Cytokeratin Antibody is specific for squamous epithelium
 Natural History

Recurrence: adequate margins ~4%, total ~10% o Predictors of recurrence:

Degree of cellular differentiation

Depth of tumour invasion

Perineural invasion by the tumour

Clinical signs include parasthesia, pain, numbness, and paralysis, but frequently no symptoms


Metastasis: o Actinic SCC 0.5% o Acantholytic variety 2% o Non-sun exposed skin 2-3% o Lip 2-16%

Rx: o Marjolin’s ulcer 10-30% o Excision margin:

5-7(20) mm
 wider for proliferative, inflammatory, scar, recurrent, perineural spread or symptoms, poor differentiation, extensive. o Lymph Node Involvement

TLND (no place ELND or sentinel biopsy in actinic SCC) o Adjuvant Therapy

XRT

Tumour spill, PD, perineural spread, close/incomplete margin, extracapsular spread, extensive disease.
Aggressive cutaneous malignancy, cell of origin unproven, propensity for LN & distant spread.

Cell of origin o ?cutaneous stem cell capable of differentiation into both neuroendocrine and keratinocyte lineages (favoured) o ?neuroendocrine cell of non-neural crest origin o
?APUD less favoured now
 Normal Merkel Cell described 1875 = associated with a slow adapting mechanoreceptor o
Tumour described by Toker 1972 = trabecular ca skin
 Clinical manifestations. o Pink to violaceous, hard nodule with shiny epithelium, +/- telangiectasia, o 6th - 7th decades o
Sun exposed areas o 50% head and neck o
40% limbs o 10% trunk o Diagnosis is histological
 Histology: o eM: paranuclear aggregates of intermediate filaments, dense cytoplasmic core granules o
Cellular patterns a. trabecular “classical pattern” b. intermediate: most, solid nests, peripheral trabecular c. small cell- diffuse sheets o
Features: involved dermis, spared epidermis, round-oval cells, large nuclei, high mitotic rate, high apoptosis, perineural & lymphatic invasion

Immunohistochemistry: o juxtanuclear labelling for cytokeratins (8, 18, 19) o Widespread cytoplasmic positivity for neurone specific enolase (NSE) o Negative staining for S100 & leukocyte common antigen (LCA)
 Staging;
I Local disease only
II LN mets (mean <4/12 post Dx)
III Distant disease (mean <12/12 post Dx)

Natural History: o 1/3 develop recurrence o 1/2-2/3 develop LN spread o
1/3-1/2 develop distant spread (all die)
 Prognostic factors: o LN mets strongest predictor of death o Others:
 tumour >2 cm

Head and neck primary

Histology: LN or perineural spread, small cell type, mitotic rate


Rx: o Stage I: ?WLE 3cm margin, ?XRT o Stage II: WLE & TLND, ?XRT o Stage III: Palliative surg, XRT and CT

Adjuvant therapy: o MCC is radiosensitive and postop XRT imparts improved locoregional control but not a survival advantage

Areas of contention o Management of LN basins in stage I disease

Victor, Morton & Smith 1996: ELND in stage I disease improved locoregional control, 15 P

Messina, Reintgen et al 1997: 12 P sentinel LN biopsy, all alive at 10.5 months, only 2 with mets

Smith et al. Locoregional XRT in stage I disease had improved survival and locoregional controls local treatment only o Current management is WLE, TLND +/- XRT according to pathology
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Hair follicle tumours
 Sebaceous tumours o
Glands confined to hairy skin except eyelids (Glands of Zeus and Meibomian glands), lips (white roll), papillae of the breast, labia minora

Apocrine tumours o Sweat; open onto hair follicles on the areola, axilla, vulvogenital & eyelids.

Eccrine tumours o
Sweat, distributed throughout the body, most numerous on soles, palms and face
Hair Follicle Tumours

Infundibular Lesions: Epidermal Cyst/ Sebaceous cyst/ Infundibular Cyst o Common after puberty, cyst attached to epidermis, expands into subcutaneous fat, Central punctum o Histology: Laminated keratin (NOT sebaceous) o
Rx: EDC with a small skin ellipse including the punctum

Outer Root Sheath Tumours: Tricholemmal Cyst o
Pilar Cyst, equivalent to an infundibular cyst but involves the scalp

Hair Germ lesions: Trichoepithelioma : o Common, young patient, central face o
Histology: nests of basaloid cells, peripheral palisade, keratinous cyst, abortive dermal papilla o Rx: EDC
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Matrical Tumours: Pilomatrixoma o Calcifying Epithelioma of Malherbe o Common, 60% <20yrs (child) o head/neck/arms o
Solitary, firm nodule, chalky discharge o Histology: basophilic cells, eosinophilic keratinising cells, foreign body response with calcification in 2/3 o Rx: EDC
Sebaceous Tumours

Sebaceous Naevus (of Ja Dusscha) o Embryonic streak along fusion planes (developmental malformation) o Complex hamartoma of epidermal and adnexal structures o Malignant degeneration in adults - 10% (BCC mostly) o
Yellowish hairless warty plaque, forehead/face/scalp o Histology: Epidermal naevus, apocrine glands in 50%, sebaceous glands (age dependent activity in infants & puberty) o Rx: EDC

Sebaceous hyperplasia o Yellowish papule, often multiple especially the forehead/cheek o Histology: enlarged mature sebaceous gland with a central follicle o Rx: Cosmetic, Shave, dermabrade, laser
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Sebaceous adenoma o Solitary, head and neck, elderly o Histology: Gland less mature with lobules o Rx: Cosmetic, EDC

Apocrine Tumours
Markers are CEA – 180, BGP, NCA, multiple monoclonal antibodies (SKH1, ferritin AB, anti-IgA Ab, Dako-CK1 and Cam 5.2)
 Apocrine Cystadenoma /hidrocystoma o Adenomatous cystic proliferation of apocrine glands o Small, naevoid, dome-shaped, often translucent nodule on the face o Frequently pigmented o When cut contains brownish fluid o Histology: originate in Glands of Moll o Rx: EDC

Hidradenoma papilliferum o Female, vulva/perineum

Syringocystadenoma papilliferum o Commonly Scalp/forehead o
Verrucous o Frequently develops in within associated organoid naevus o 50% present at birth or childhood o 10% coexisting BCC

Apocrine adenoma

Tubular apocrine adenoma

Apocrine mixed tumor
Eccrine Tumours markers are lysozyme, Leu MI and GCDFP -15

Eccrine cystadenoma o Periorbital most common o DDx: Apocrine cystadenoma, Chalazion, Lacrimal cystitis, sebaceous carcinoma o Rx: EDC

Papillary eccrine adenoma

Aggressive digital papillary adenoma

Eccrine poroma

Eccrine spiradenoma

Eccrine acrospiroma

Syringoma o mainly multiple flesh coloured nodules 2-3mm o Adolescent female, multiple papules lower lids/face/genitals/trunk o clear cell variant associated with DM o more common in Downs syndrome o Histology: multiple small eccrine ducts with "comma-like" tail, actively secrete o removal for cosmetic purposes

Cylindroma o Usually single, head/neck, mid age-elderly female o occurs predominantly on scalp o solitary or multiple, firm smooth pink nodules o large variants form multiple, coalescent (turban) tumours o multiple variant inherited as AD trait o assoc with multiple, inherited form of trichoepitheliomas o simple excision usually adequate o Histology -poorly circumscribed, islands of basaloid cells surrounded by hyaline bands o Rx: EDC

Sebaceous carcinoma:

Head & neck, especially eyelids

Arise: glands of Zeiss or Meibomian glands

Mimic chalazion (“recurrent chalazion”)

Aggressive 1/3 mets

Local spread down NL duct

Rx: WLE & TLND
Extramammary Paget’s disease:

?insitu apocrine ca with 25% associated with adnexal ca

Axilla & anogenital slow growing erythematous plaque in elderly

50% pruritic

Rx: Biopsy, Excision
Sclerosing Sweat Duct Carcinoma:

Adult, upper lip/face or elsewhere

Slow growing, high recurrence, rare mets

Infiltrative growth, perineural invasion

Evidence of eccrine and pilar differentiation

Biology similar to BCC

Rx; Excision

Dermatofibroma

Dermatofibroma Sarcoma Protuberans (DFSP)

Atypical Fibroxanthoma (AFX)

Malignant Fibrous Histiocytoma (MFH)
Dermatofibroma

Benign (?post traumatic)

Cell of origin: Factor XIIIa positive dermal dendrocyte

Cx: young adult, legs, red/brown/purple/yellow

Histology: o proliferation fibroblast like cells in dermis o variable other elements: vessels, histiocytes, haemosiderin, collagen o Epidermal changes: acanthosis, basal hyperpigmentation, sebaceous glands, BCC (rare)
Dermatofibroma Sarcoma Protuberans
Low-grade locally infiltrative malignancy involving the dermis and subcutis, composed of spindle cells.
Marked tendency to recur and rarely metastasises.

Cell of origin: ?CD34 positive dermal dendrocyte o Cx:
Firm intradermal plaque, red/pink, 0.5-10cm, single or multiple coalescing nodules. o
With extended duration often with multiple recurrences may become a fibrosarcoma
 Histology: o Uniform plump cells: spindle shaped o Storiform pattern centred on dermis o Superficial grenz zone o Involve subcutis

Macro: o solid whitish whorled tissue with softer myxoid areas

Rx: o WLE with 5 cm margin and down to next fascial plane

Atypical Fibroxanthoma
Presumably benign neoplasm of unknown origin with sarcomatous histology.

Cx: o 1-2 cm papule/nodule, face/hands, elderly in sun damaged skin, recur 5%

Histology: o Sarcomatous (like MFH) o Spindle, polyhedral and giant cells o Aberrant mitoses o
Factor XIIIa positive
 Rx: Excision, diagnosis made retrospectively
Malignant Fibrous Histiocytoma
Sarcoma usually of deep tissues from pleuripotential mesenchymal cells with uncommon cutaneous involvement

Cx: o Prox limbs/retroperitoneum, later adult life

Histology: o Undifferentiated with various variants

Pleomorphic, angiomatoid, myxoid, giant cell

Rx: o WLE +/- amputation o CT & XRT may be useful