Basal Cell Carcinomas

BASAL CELL CARCINOMA

• Malignant epithelial neoplasm• Chronic sun exposure • Slow growing • Metastasis• Local tissue destruction

EPIDEMIOLOGY

• Australia –Highest incidence • BCC 788/100,000• SCC 321/100,000

• Fitzpatrick Types I and II

EPIDEMIOLOGY

• Oily skin offers some protection

• History of sunburn

• Cumulative sun exposure • Incidence increases towards the North

DISTRIBUTION

• sun exposed areas and areas of bioembryological fusion

• Rare on the hand, penis, lower lip

DISTRIBUTION

• Upper lip BCC, Lower lip SCC

• Ext. ear SCC 60%, BCC 40%

HISTOGENESIS• UVA Light 95 % (315-400nm)• UVB Light 5 % ----

sunburn, malignant degeneration

(290-315nm)• UVA enhances the

carcinogenic effect

• UV induced mutation of the p53 tumor suppressor gene

• 56 % mutation occurs in both p53 alleles

• Aggressiveness of the tumor relates to the presence of p53 protein

• Mutation in the patched gene PTCH is responsible for BCC in Gorlin's, XP

Carcinogenesis

Initiation - Genetic mutation , DNA changes

Promotion – Changes in cellular environment

Progression – Further genetic alteration.

If erroneous sequences are not repaired propagation continues during DNA replication.

• UV induced immunosuppression – depletion of Langerhans cells and stimulation of suppressor T cells – hindering the detection and destruction of the tumor cells.

Non UV

• < 1% • Arsenic• Non ionizing radiation• Immunosuppression• Tobacco • Human papilloma virus • Scars

Spread

• BCC’s are stromal dependant

• Do not survive transplantation

• Rarely metastasize – 0.1 %

Spread

• Aggressive local growth - following the path of least resistance

• Spreads along:• periosteum• Perichondrium• Fascia• tarsal plate

Spread

• Can spread deeply between nasal cartilages

• Embryonic fusion planes

PREDISPOSING CONDITIONS

• Xeroderma Pigmentosum • Gorlin’s Syndrome - Basal Cell Nevus

Syndrome• Bazex Syndrome • Nevus Sebaceous of Jadassohn• Porokeratosis• Linear unilateral Basal cell Nevus

Xeroderma Pigmentosum• Autosomal recessive defect • DNA repair – skin intolerant of UV light • Skin normal as infant- becomes

dry,pigmented,cutaneous,s/c atrophy

• Xerodermic idiocy – progressive neurological deterioration• BCC,SCC,Melanomas• Usually die in second decade

Gorlin’s Syndrome

• Basal cell nevus syndrome • Autosomal dominant with low penetrance • Mutation in tumor suppressor gene located

on 9q23-q31

Multiple Nevi Reddish Brown, Papular andVariously sized Appear after puberty several to thousands76% become invasive BCCs

Porokeratosis

Hereditary conditions Disseminated annular plaques with sharply

raised horny borders13% BCCs and SCCs2/5 types of porokeratosis premalignantMibelli PorokeratosisDisseminated superficial actinic porokeratosis

ORIGIN

Germinative layers of the skin

• Basal Cells of the Epidermis• Epithelial cells of the Adenexa

CLASSIFICATION

• Emmett and Rourke• Papulonodular• Infiltrating• Multifocal• Morphoeic / Sclerosing• Metatypical• Others – Pigmented , NBCC

Papulonodular Bcc

• Commonest - 45%

• PN Solid 38% Smooth, raised, waxy Translucent, NODULE, thin epithelial cover,Minute vessels in the periphery, surface shows fine venules, Pearly edge, central depression

• PN Cystic 6.9% Pale, pearly pink

Lucid gray with a well defined margin Acid mucopolysaccharide gel

Multifocal Bcc• 35%

• Multifocal SuperficialOften merely red areas with a patchily adherent Parakeratotic scalesPattern with small areas of epithelial discontinuityMargin ill defined Pearly edge defined on stretch

• Superficial Early stage of MFS – small red patch with a localizedsuperficial cluster of BCC cells

• Cicatrizing, Field Fire Red irregular scaly rim round a whitish healing centre

Morphoeic / Sclerosing

• 8.9%• Flat whitish plaques

• Fine pearly edge Noticed on stretching the skin at the edge of the Plaque

• Central regression- skin pitOn stretching the skin the white plaque becomes Evident may be localized or infiltratingSynthesize type IV collagenase Discontinuous basement membrane

Infiltrating Bcc

• Primary Infiltrating 8%No characteristic clinical appearanceRed or gray scaling area Induration, Ulceration, Whitish plaqueMicroscopic examination diagnostic

• Secondary InfiltratingParts of the lesion of bcc develops anInfiltrative character

• Recurrent InfiltratingRecurrent bcc develops into an

infiltrativetypeD/D Solar Keratoses

Squamous cell ca.

Metatypical

• Irregular mammilated pale pink flesh colored lesion

• Without marginal light reflex

• Without any superficial vv.

• May stay like this for years

• Ulceration

Pigmented Type

• Variation in pigment

• Scant flecks to deeper pig.

• Edge - pearly translucence

• Fine superficial venules

• Stromal melanophages

• Central regression

• D/D Melanoma

HISTOLOGY

• Cutaneous epithelial tumors

• Nests and sheets of basal type cells with a large oval nucleus

• Intercellular bridges not seen

• Peripheral layer is arranged like a palisade

• Central haphazard arrangement

• Abundant connective tissue stroma rich in acid mucopolysaccharides mucinuous appearance

• Amyloid in 65% bccs

Morphological Types • Solid • Micronodular• Cystic• Multifocal• Infiltrating• Sclerosing• Pigmented• Metatypical• Adenoid• Keratotic• Infundibulocystic• Fibroepithelioma

Solid, Micronodular• 70%• Islands of Cells • Peripheral palisading• Central haphazard • Retraction spaces

• Smaller nests• Palisading less • Infiltration into dermis

and subcutis• Increased rec.

Cystic, Keratotic• Similar to solid• Cystic spaces present

towards the centre dt degeneration of tumor cells

• Similar to solid • Keratinization towards

the centre • Very little stroma

Infiltrating, Multifocal• Elongated strands of

basiloid cells between collagen bundles

• Fibroblasts• Focal infiltration in rec.

Solid in scar

• Discreet nests of tumor cells apparently interconnected

• Multiple small islands of basiloid cells attached to the extending to the papillary dermis

Sclerosing, Metatypical• Thin strands and nests

of cells embedded in a dense fibrous stroma

• Eosinophillic areas - Morphoeic

• Plump squamous cells with loss of peripheral palisading

• Represents basiloid and squamous features

Invasive Histological Features

• Microfilaments located on the periphery of the individual cells with the highest density at the tumor borders

• Increased type IV collagenase • Focal gaps in the basement membrane• Loss of intercellular bridges • Increased cytokines which stimulate fibroblast

glycosamineglycans synthesis • Increased peri tumor stroma

Differential Diagnosis

• Squamous cell carcinoma

• Solar Keratoses• Keratoacanthoma• Melanoma • Merkel Cell Tumor• Appendegeal tumors• Dermatofibroma

• Non pigmented naevus

• Chondrodermatitis Nodularis Helicis

• Seborrhoeic keratoses• Bowens disease• Pyogenic grannuloma • AFX• Cutaneous sarcoid

Differentials• Noduloulcerative Bcc• Slow growing • Pearly edge• Fine venules

• Ulcerated Scc• Fleshy rapidly growing• indurated

TREATMENT

• Goals :Total lesion removal

Preservation of normal tissue

Preservation of function

Optimal cosmesis

• Biopsy: • Excisional• Punch• Incisional• Shave

• Does not affect the natural history

• Variables:

Patient Age Number of lesions Lesion sizeTumor bordersPrimary Vs RecurrentAnatomic location – sub clinical spread

Treatment Modalities

• Curettage and Electrodessication

• 2 mm – 100%, 2-5 mm – 85%

• Cryosurgery

• lesions up to 2 cm 97% high morbidity• lack of microscopic evaluation• Edema• hypo pigmentation• atrophic scars• Neuropathy• sub clinical spread• unpredictable cosmesis

• Surgical Excision • 90% overall success rate• Nodular lesions <1cm - 2mm margin• Lesions < 2cm 3-4 mm• Lesions > 2cm, subclinical spread, aggressive

histology, multifocal - may require margins up to 10mm

• Mohs micrographic surgery:recurrent bccs, morphoeaform or arising from scar, anatomic sites with relatively high rates of treatment failure, critical locations – eyelid 99% primary, 95% recurrent

• Frozen Sections• Delayed primary repair temporary grafting

ADJUNCTS• Topical Chemotherapy

5 FU with retinoids

Imiquimod – immune response modifier that induces cytokines including interferons

Radiation Therapy - older patients, adjuvant therapy where negative margins are difficult to obtain – nasal, periorbital, periauricular 92%

Others• Alpha-interferon Therapy

• Laser excisions

• Photodynamic Therapyincludes the administration of Dihaematoporphyrine or its derivative followed by exposure to 630 nm light with a tunable dye laser .It localizes to the tumor cells and absorption of light by dihaematoporphyrin ether has a cytotoxic effect

Follow up

• Follow up for 5 yrs

• Recurrence is defined as the reappearance of a bcc within or contiguous to a scar resulting from an initial attempt at definitive treatment

Increased Risk

• Long time presence of the lesion

• Location in a high risk area

• Aggressive clinical and histological features

• 20% will develop a new lesion within 1 yr of having been treated

• 36% will develop another lesion by 5 years

• Overall recurrence rate of 2.9 % - 9 %

• 82% recurrence occurs in first 5 years ,18% in 6-10 yrs

Incomplete Resection

• 35% recurrence if one margin is involved

• 12% recurrence when tumor within one high power field of margin