• 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 Gorlins, XP
CarcinogenesisInitiation - Genetic mutation , DNA changesPromotion – Changes in cellular environmentProgression – Further genetic alteration.If erroneous sequences are not repaired propagationcontinues 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
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 and Variously sized Appear after puberty several to thousands 76% become invasive BCCs
PorokeratosisHereditary conditionsDisseminated annular plaques with sharply raised horny borders13% BCCs and SCCs2/5 types of porokeratosis premalignantMibelli PorokeratosisDisseminated superficial actinic porokeratosis
ORIGINGerminative layers of the skin• Basal Cells of the Epidermis• Epithelial cells of the Adenexa
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 pinkLucid gray with a well defined marginAcid mucopolysaccharide gel
Multifocal Bcc• 35%• Multifocal SuperficialOften merely red areas with a patchily adherentParakeratotic scalesPattern with small areas of epithelial discontinuityMargin ill defined Pearly edge defined on stretch• SuperficialEarly stage of MFS – small red patch with a localizedsuperficial cluster of BCC cells• Cicatrizing, Field FireRed irregular scaly rim round a whitish healing centre
Morphoeic / Sclerosing• 8.9%• Flat whitish plaques• Fine pearly edgeNoticed on stretching the skin at the edge of thePlaque• Central regression- skin pitOn stretching the skin the white plaque becomesEvident may be localized or infiltratingSynthesize type IV collagenaseDiscontinuous basement membrane
Infiltrating Bcc• Primary Infiltrating 8%No characteristic clinical appearanceRed or gray scaling areaInduration, 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
Solid, Micronodular• 70% • Smaller nests• Islands of Cells • Palisading less• Peripheral palisading • Infiltration into dermis• Central haphazard and subcutis• Retraction spaces • Increased rec.
Cystic, Keratotic• Similar to solid • Similar to solid• Cystic spaces present • Keratinization towards towards the centre dt the centre degeneration of tumor • Very little stroma cells
Infiltrating, Multifocal• Elongated strands of • Discreet nests of tumor cells basiloid cells between apparently interconnected collagen bundles • Multiple small islands of basiloid cells attached to• Fibroblasts the extending to the• Focal infiltration in rec. papillary dermis Solid in scar
Sclerosing, Metatypical• Thin strands and nests • Plump squamous cells of cells embedded in a with loss of peripheral dense fibrous stroma palisading• Eosinophillic areas - • Represents basiloid and Morphoeic 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
• 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 Chemotherapy5 FU with retinoidsImiquimod – immune response modifier that induces cytokines including interferonsRadiation Therapy - older patients, adjuvant therapy where negative margins are difficult to obtain – nasal, periorbital, periauricular 92%
Others• Alpha-interferon Therapy• Laser excisions• Photodynamic Therapy includes 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