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SKIN HISTOLOGY AND FUNCTION

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Page 1: HISTOLOGY AND FUNCTION1).pdf · histology ¾nest of epidermal cells –mixture of normal and anaplastic ¾cells ¾well ... • skin, git, brain – adults • white population highest

SKIN

HISTOLOGY   AND  FUNCTION

Page 2: HISTOLOGY AND FUNCTION1).pdf · histology ¾nest of epidermal cells –mixture of normal and anaplastic ¾cells ¾well ... • skin, git, brain – adults • white population highest

THREE  LAYERS  : EPIDERMISBASEMENT  MEMBRANE DERMIS

EPIDERMIS : COMPOSED  OF  KERATINOCYTES• NO  MATRIX• DEEP  BASAL  LAYER  MITOTICALLY ACTIVE• SPINOUS  LAYER – MATURE –HYALIN• HORNY  LAYER – AGED CELLS –SHED• TRANSIT  TIME: 40 TO 56 DAYS• KERAINS  5 & 14

MELANOCYTES • ORIGIN  FROM  NEURA  CREST• 1:35• MELANIN – TYROSINE  &  CYSTEINE• MELANOSOME  – TO  KERATINOCYTES• DENSITY  OF  MELANOCYTES  CONSTANT• MELANIN  PRODUCTION  INFLUENCED  BY MSH,  ACTH,  UV RAYS etc

Page 3: HISTOLOGY AND FUNCTION1).pdf · histology ¾nest of epidermal cells –mixture of normal and anaplastic ¾cells ¾well ... • skin, git, brain – adults • white population highest

• BASEMENT   MEMBRANE 

• ZONE  ANCHOR  EPIDERMIS  TO  DERMIS  BY   PROTEIN STRUCTURES

DERMIS :

70%  OF   WEIGHT  COLLAGEN  TYPE  I  TENSILE  STRENGTH

ELASTIC  FIBRES

GROUND  SUBSTANCE  – POLYSACCHARIDE,  POLYPEPTIDES

FIBROBLASTS – THROUGHOUT  DERMIS – PROTEIN  MATRIX

NET WORK  OF  BLOOD VESSELS – PAPILLARY  DERMIS

GLOMUS  BODIES:

TORTUOUS   A‐V  SHUNTS – REGULATES   BODY  TEMPERATURE

SENSORY  NERVE ENDINGS – RECEPTORS,  PACINIAN,  MEISSNER, RUFFINI

FREE  NERVE  ENDINGS   MERKEL’S  CELLS,  HAIR  FOLLICLE

ADENEXCAL :  SWEAT  GLANDS – PALMS,  SOLE,  AXILLA

APPOCRINE  GLANDS – AXILLA,  PERINEUM  SCENT

Page 4: HISTOLOGY AND FUNCTION1).pdf · histology ¾nest of epidermal cells –mixture of normal and anaplastic ¾cells ¾well ... • skin, git, brain – adults • white population highest
Page 5: HISTOLOGY AND FUNCTION1).pdf · histology ¾nest of epidermal cells –mixture of normal and anaplastic ¾cells ¾well ... • skin, git, brain – adults • white population highest

MALIGNANT TUMOURS

• EPIDEMIOLOGY

• EXPOSURE  TO  UV RADIATION

• CHEMICAL  CARCINOGEN – TAR,  ARSENIC ,  NITROGEN  MUSTARD

• HPV – SQUAMOUS  CELL CA

• RADIATION  DERMATITIS

• CHRONIC  IRRITATION – MARJOLIN’S  ULCER   etc

• IMMUNO  SUPPRESSION

• HIV

BASAL  CELL  CARCINOMA

SLOW  GROWING

RARELY  METASTASIS

LOCALLY  DESTRUCTIVE

SITES – FACE,  SCALP,  NOSE,  CHEEK

Page 6: HISTOLOGY AND FUNCTION1).pdf · histology ¾nest of epidermal cells –mixture of normal and anaplastic ¾cells ¾well ... • skin, git, brain – adults • white population highest

PRE ‐ DISPOSING  FACTORS• FAIR  COMPLEXION• RADIOATION  EXPOSURE• SUN  BURNS• IMMUNO SURESSION

PATHOLOGYARISE  FROM  BASAL  LAYER  OF EPIDERMISPILOSEBACEOUS  ADENEXA

TYPES:a) NODULARb) SUPERFICIALc) MICRONODULARd) INFILTRATING e) SCLEROSINGINFILTRATING  AND  SCLEROSING  TYPES  MOST  AGGRESSIVE 10 %

Page 7: HISTOLOGY AND FUNCTION1).pdf · histology ¾nest of epidermal cells –mixture of normal and anaplastic ¾cells ¾well ... • skin, git, brain – adults • white population highest
Page 8: HISTOLOGY AND FUNCTION1).pdf · histology ¾nest of epidermal cells –mixture of normal and anaplastic ¾cells ¾well ... • skin, git, brain – adults • white population highest
Page 9: HISTOLOGY AND FUNCTION1).pdf · histology ¾nest of epidermal cells –mixture of normal and anaplastic ¾cells ¾well ... • skin, git, brain – adults • white population highest

CLINICAL  FEATURES

PEARLY,  TRANSLUCENT  MASSRAISED  BORDERSULCERATEERYTHMATOUS  PATCHES,  SCALYSCARING, (DD.PSORIASIS, EZEMA)ISLANDS  OF  TUMOUR  EXTENDING  SURROUNDING

DIAGNOSISBIOPSY – SHAVE , PUNCH,  INCISION,  EXCISION

TREATMENTELECTRO  DESICCATION CURETTAGENODULAR  TYPE  LESS  THAN  2 cmSUPERFICIAL  ANY  SIZE90 – 98 %  CURE  RATE

Page 10: HISTOLOGY AND FUNCTION1).pdf · histology ¾nest of epidermal cells –mixture of normal and anaplastic ¾cells ¾well ... • skin, git, brain – adults • white population highest

CRYOTHERAPY:

• LESION  2 cm ↓

• Scarring,  HYPOPIGMENTATION

• NO HISTELOGICAL  CONFIRMATION

• USED  ONLY  LESS  AGGRESSIVE  LESIONS

• NOT  USED  IN PERI ORAL, ORBITAL  AREAS

SURGICAL  EXCISION

CURE  RATE 90 %

MARGIN 2‐5 mm DEPEND  ON  SIZE

MOH’S  MICROGRAPHIC  SURGERY – PERI  ORAL  AREA

99 %  PRIMARY  96 %  RECURRENT  NASAL  ALA  LESIONS

Page 11: HISTOLOGY AND FUNCTION1).pdf · histology ¾nest of epidermal cells –mixture of normal and anaplastic ¾cells ¾well ... • skin, git, brain – adults • white population highest

SQUAMOUS  CELL  CARCINOMA

MORE  COMMON  THAN BCCARISE  FROM  KERATINOCYTES  EPIDERMISARISE  FROM  ACTINIC  KERATOSIS,  LEUKOPLAKIA,  RADIATION DERMATITIS,  SCARS,  CHRONIC  ULCER,  BOWEN  DISEASE – INSITUSKIN  PATCHES,  NODULE – CENTRAL  INFLAMATIONINDURATION,  NECROSIS – OOZINGMETASTASES – DIRECT  INFILTARTION,  LYMPHATICHAEMATOGENOUS

AUSTRALIA:  HIGH  UV  EXPOSURERACE         : WHITE  COMPLEXIONSEX            : MALE / FEMALE 2:1AGE           : ABOVE  60 years

RISK  FACTORS: IONIZING  RADIATION,  ARSENIC etc

Page 12: HISTOLOGY AND FUNCTION1).pdf · histology ¾nest of epidermal cells –mixture of normal and anaplastic ¾cells ¾well ... • skin, git, brain – adults • white population highest

DIFFERENTIAL   DIAGNOSIS• ACTINIC   KERATOSIS• BCC• MELANOMA• KERATOACANTHOMA• PYODERMA  GANGRENOSUM• WARTS

INVESTIGATIONS• CT,  MRI,  DEPTH  OF  INVASION• BIOPSY : PUNCH,  SHAVE,  INCISIONAL,  EXCISIONAL

HISTOLOGYNEST  OF  EPIDERMAL  CELLS – MIXTURE  OF  NORMAL  AND   ANAPLASTIC CELLSWELL   DIFFERENTIATED – EPITHELIAL  PEARL‐ CONCENTRIC  LAYERS  OFSQUAMOUS   CELLS  WITH  CENTRAL  KERANTINIZATIONPOORLY   DIFFERENTIATED  LACKS  HORN  PEARLSSPECIAL   STAINS :  S100 NEGATIVE  FOR   SCC

POSITIVE  FOR   MELANOMA

Page 13: HISTOLOGY AND FUNCTION1).pdf · histology ¾nest of epidermal cells –mixture of normal and anaplastic ¾cells ¾well ... • skin, git, brain – adults • white population highest

STAGING – TNM• PRIMARY   TUMOUR• Tx – PRIMARY   TUMOUR  CANNOT  BE   ASSESSED• To – NO  EVDIENCE   OF   PRIMARY   TUMOUR• T1  ‐ TUMOUR 2 cm• T2 – TUMOUR 2‐4 cm• T3 – TUMOUR   LARGER  THAN 4 cm• T4 – TUMOUR  INVADES  DEEPER  STRUCTURES

REGIONAL  NODES• NX – NODES  CANNOT  BE  ASSESSED• N0 – NO NODES• N1 – SINGLE  IPSILATERAL  NODE – 3 cm • N2 – a) SINGLE• b) MULTIPLE• c) BILATERAL

METASTASISMX  ‐ DISTANT  METASTASIS  CANNOT  BE  ASSESSED M0 – NO  DISTANT  METASTASISM1 – DISTANT  METASTASIS  PRESENT

Page 14: HISTOLOGY AND FUNCTION1).pdf · histology ¾nest of epidermal cells –mixture of normal and anaplastic ¾cells ¾well ... • skin, git, brain – adults • white population highest

TREATMENT :

• DRUG  THERAPY

• ACTINIC  KERATOSIS – 5‐FLUORORACIL TOPICAL

• ‐ DICLOFENAC GEL

• ‐ BIOPSY CONFIRMATION

• SCC/BCC                     ‐ IMIQUIMOD 5 % CREAM

• SUPERFICIAL                ‐ IMMUNE  MODIFIER  THROUGH  LESIONS  ONLY  INTERFERON,  CYTOKINES

PHOTODYNAMIC   THERPAY (PDT)

• PHOTOSENSITIZING  DRUGS

• LIGHT – ACTIVATES  OXYGEN,  FREE  RADICALS  DESTROY,  TARGETED TISSUE.

• ALA – AMINOLEVULINIC ACID – SKIN   TUMOURS – ACTIVE

• PROTOPORPHYRIN   IX

• ACTINIC KERATOSIS, FACIAL  LESION  90 %

Page 15: HISTOLOGY AND FUNCTION1).pdf · histology ¾nest of epidermal cells –mixture of normal and anaplastic ¾cells ¾well ... • skin, git, brain – adults • white population highest

SURGICAL   TREATMENT• CURETTAGE  AND   ELECTROSURGERY• REPEATED  SEVERAL   TIMES• NO  SPECIMEN  AVAILABLE   FOR  HPE• 96 % CURE

CRYOSURGERY• LIQUID  NITROGEN• CURE  97 %

• EXCISION• LOCAL   EXCISION – HPE – 92 %  CURE• 4 mm  MARGIN – RECURRENCE  5 ‐8 %• WELL  DIFFERENTIATED  LESIONS

MOH’S   MICROGRAPHIC   SURGERY

LESIONS   ARE   REMOVED IN STAGESHORIZONTAL   FROZEN   SECTIONING – PERIPHERAL   AND  DEEP MARGINS

Page 16: HISTOLOGY AND FUNCTION1).pdf · histology ¾nest of epidermal cells –mixture of normal and anaplastic ¾cells ¾well ... • skin, git, brain – adults • white population highest

CURE  RATE SCC 96 %  IN  5  YEARSFOR  RECURRENT  SCC  90 %  CURE RATETISSUE SPARING – DISFIGUREMENT  IN  DISTINCT  MARGIN, GENITALPENILE  SHAFTLOCAL  ANAESTHESIA,  SAY  CASE  OF  SURGERY  COST  EFFECTIVEMOH’S SURGERY  NOT  USEFUL  IN  INVASIVE  LESIONSSENTINEL  NODE  BIOPSY

LASER SURGERYRADIATION  THERAPYOLDER  PATIENT,  NO  HPE

PREVENTIONSPF – SUN PROTECTING  FACTORCLOTHING SUNSCREEN’S – SPR 30↑ZINC  OXIDE, TITANIUM  OXIDEAPPLIED EVERY 30 MINTS  DURING   EXPOSURE

Page 17: HISTOLOGY AND FUNCTION1).pdf · histology ¾nest of epidermal cells –mixture of normal and anaplastic ¾cells ¾well ... • skin, git, brain – adults • white population highest

MALIGNANT MELANOMA• MALIGNANT   TRANFORMATION  OF MELANOCYTES • MELANOCYTES  DERIVED  FROM  NEURAL CREST• SKIN, GIT,  BRAIN – ADULTS• WHITE  POPULATION   HIGHEST• ASIAN’S  LOWEST

ETIOLOGY

• FAMILY  HISTORY• POSITIVE  IN  5 – 10 %

PERSONAL

BLUE EYES,  FAIRSUN  BURNFRECKLINGNEVI ‐ DYSPLASTICIMMUNOSUPPRESSIVE   STATE

Page 18: HISTOLOGY AND FUNCTION1).pdf · histology ¾nest of epidermal cells –mixture of normal and anaplastic ¾cells ¾well ... • skin, git, brain – adults • white population highest

SUN EXPOSURE

HIGH  U‐V  RADIATIONLOW  LATITUDEBLISTERING  SUN BURNSDYSPLASTIC  NEVI  OVER  A  TIME  MELANOMA

CLINICAL PRESENTATION 

• ABCDE• A ‐ ASYMMETRY• B ‐ BORDER   IRREGULAR• C ‐ COLOUR  VARIATION• D ‐ DIAMETER  >  6 cm• E  ‐ ELEVATED   SURFACE

ITCHING,  BLEED,  ULCERATION,  SATELITE  LESIONS

BIOPSY:  EXCISION / INCISION, 2 mm   MARGINFULL   THICKNESS   SKIN

Page 19: HISTOLOGY AND FUNCTION1).pdf · histology ¾nest of epidermal cells –mixture of normal and anaplastic ¾cells ¾well ... • skin, git, brain – adults • white population highest

SAPPEY : LYMPHATIC   DRAINAGE   DEPEND  ONANATOMICAL  LOCATIONLYMPHATIC   OVER   LAP

HISTOLOGICAL  CLASSIFICATION

GROWTH   PATTERN

SUPERFICIAL SPREADING

70 %   OF   MELANOMACELLS   AT  DERMS – EPIDERAL   JUNCTIONMIGRATE   TO  S.GRANULOSUM  & CORNEUMPAPPILARY   DERMISFROM   DYSPLATIC  NEVUSFLAT,  ELEVATED  LATTER2 cm DIAMETER,  VARIGATED   COLOURS

NODULAR MELANOMAEXTENSIVE   VERTICAL   GROWTH   INTO   DERMIS  THAN   RADIAL

Page 20: HISTOLOGY AND FUNCTION1).pdf · histology ¾nest of epidermal cells –mixture of normal and anaplastic ¾cells ¾well ... • skin, git, brain – adults • white population highest
Page 21: HISTOLOGY AND FUNCTION1).pdf · histology ¾nest of epidermal cells –mixture of normal and anaplastic ¾cells ¾well ... • skin, git, brain – adults • white population highest
Page 22: HISTOLOGY AND FUNCTION1).pdf · histology ¾nest of epidermal cells –mixture of normal and anaplastic ¾cells ¾well ... • skin, git, brain – adults • white population highest
Page 23: HISTOLOGY AND FUNCTION1).pdf · histology ¾nest of epidermal cells –mixture of normal and anaplastic ¾cells ¾well ... • skin, git, brain – adults • white population highest
Page 24: HISTOLOGY AND FUNCTION1).pdf · histology ¾nest of epidermal cells –mixture of normal and anaplastic ¾cells ¾well ... • skin, git, brain – adults • white population highest
Page 25: HISTOLOGY AND FUNCTION1).pdf · histology ¾nest of epidermal cells –mixture of normal and anaplastic ¾cells ¾well ... • skin, git, brain – adults • white population highest
Page 26: HISTOLOGY AND FUNCTION1).pdf · histology ¾nest of epidermal cells –mixture of normal and anaplastic ¾cells ¾well ... • skin, git, brain – adults • white population highest
Page 27: HISTOLOGY AND FUNCTION1).pdf · histology ¾nest of epidermal cells –mixture of normal and anaplastic ¾cells ¾well ... • skin, git, brain – adults • white population highest
Page 28: HISTOLOGY AND FUNCTION1).pdf · histology ¾nest of epidermal cells –mixture of normal and anaplastic ¾cells ¾well ... • skin, git, brain – adults • white population highest

15‐30 %BLUE  BLACKOCCUR   WITHOUT   PRE EXISTING   LESION

LENTIGO  MALGNA   MELANOMA

4 – 10 %  MELANOMASPINDLE   SHAPE   HYPERCHROMATIC  CELLSEPIDERMIS   ATROPHICSIZE 3 cms, FLAT, FRECKLE,  FACE, NECKARISE   IN  HUTCHINSON’S   FRECKLE  (LENTIGO MALIGNA)

ACRAL  LENTIGINOUS   MELANOMA

• 2‐8%  IN   WHITE• 30 – 60% IN  DARK   SKINNED   PEOPLE• DERMO   EPIODERMAL   JUNCTION – INVASION   PAPILLAR   DERMIS• PALMS,   SOLES  , FLAT   IRREGULAR   BORDERS   ULCERATIONS

Page 29: HISTOLOGY AND FUNCTION1).pdf · histology ¾nest of epidermal cells –mixture of normal and anaplastic ¾cells ¾well ... • skin, git, brain – adults • white population highest

DESMOPLASTIC MELANOMA

1%  RAREPERI  NEURAL   INVASIONHIGHER   LOCAL   RECURRENCELOWER   REGIONAL   METASTASIS

CLASSIFICATION  AND  STAGING

BRESLOW’STHICKNESS  0.75 mm  or   LESSTHICKNESS  0.75  – 1.5 mmTHICKNESS   1.5 – 4 mmTHICKNESS   > 4 mm

Page 30: HISTOLOGY AND FUNCTION1).pdf · histology ¾nest of epidermal cells –mixture of normal and anaplastic ¾cells ¾well ... • skin, git, brain – adults • white population highest

• CLARK

LEVEL  I – INVOLVES    EPIDERMIS  ONLY   IN  SITU

LEVEL  II – INVADES  PAPILLARY  DERMIS  ONLY

LEVEL  II  ‐ INVADES PAPILLART  & INTERFACE

LEVEL  IV – INVADER  RETICULAR DERMIS  NOT  SUB –CUTANEOUS  TISSUE

LEVEL  V – INVADES  INTO  SUB  CUTAEOUS  TISSUE

TNM  STAGING

T X ‐ PRIMARY  TUMOUR  CANNOT  BE  ASSESSED

Page 31: HISTOLOGY AND FUNCTION1).pdf · histology ¾nest of epidermal cells –mixture of normal and anaplastic ¾cells ¾well ... • skin, git, brain – adults • white population highest
Page 32: HISTOLOGY AND FUNCTION1).pdf · histology ¾nest of epidermal cells –mixture of normal and anaplastic ¾cells ¾well ... • skin, git, brain – adults • white population highest

• T0 – NO  EVIDENCE  TUMOUR 

• T15 – IN SITU –INVOLVES  ONLY  EPIDERMIS

• T1  ‐ 1  mm LESS THICKNESS

• T2  ‐ 1‐1.2  mm  LESS  THICKNESS

• T3  ‐ 2‐4 mm  LESS  THICKNESS

• T4 ‐ > 4 mm , INVADES  SUB  CUTANEOUS   TISSUE 

SATELLITE  TUMOURS  WITHIN  2 cm

• a) TUMOUR > 4 mm

• b) WITHOUT  ULCERATION

• c) ULERATION 

REGIONAL  NODES

• NX – CANNOT  BE  ASSESSED

• N0 – NO REGIONAL  NODE  METS

Page 33: HISTOLOGY AND FUNCTION1).pdf · histology ¾nest of epidermal cells –mixture of normal and anaplastic ¾cells ¾well ... • skin, git, brain – adults • white population highest

• N1 – ONE NODE 

• N2 – 2‐3 NODES

• N3 – 4 OR MORE

DISTANT   METASTASIS

• MX – DISTANT  METASTASIS  CANNOT  BE  ASSESSED

• M0 – NO DISTANT  METS

• M1 – DISTANT  METASTASIS

• a) SUB‐ CUTANEOUS  TISSUE  , NODES

• b) METASTASIS  TO  LUNG

• c)  METASTASIS  TO  OTHER  ORGANS

Page 34: HISTOLOGY AND FUNCTION1).pdf · histology ¾nest of epidermal cells –mixture of normal and anaplastic ¾cells ¾well ... • skin, git, brain – adults • white population highest

MEDICAL MANAGEMENT

INTERFERON  (α 2BIFN)• STAGE  III  MELANOMA• TOXIC• RELAPSE   REDUCED

GM‐CSF (GRANULOCYTE STIMULATING FACTOR)

• STIMULATES  IMMUNE    SYSTEM• NOT   TOXIC   AND  OVER ALL  SURVIVAL ↑• STAGE   III &  IV• PALLIATION   ONLY

CYTOKINE  AND   VACCINE   THERAPY

TUMOUR   SPECIFIC  TARGETS – ONCOGENE

Page 35: HISTOLOGY AND FUNCTION1).pdf · histology ¾nest of epidermal cells –mixture of normal and anaplastic ¾cells ¾well ... • skin, git, brain – adults • white population highest

CDK4, TRP‐2, MART‐1AUTOLOGOUS (ALLOGENIC)

CHEMOTHERAPY

• TEMOZOLOMIDE• DACARBAZINE

SURGICAL  TREATMENT

STAGE – O :• 0.5 % TO 1.5 % cm MARGIN EXCISION IN‐SITU/OBSERVATION

STAGE – I : • T₁  LESION• 1  TO  2 cms MARGIN• SENTINEL  NODE   BIOPSY• CLOSURE – PRIMARY,   SKIN   GRAFTING

Page 36: HISTOLOGY AND FUNCTION1).pdf · histology ¾nest of epidermal cells –mixture of normal and anaplastic ¾cells ¾well ... • skin, git, brain – adults • white population highest

STAGE II

• 2 cms MARGIN  – NO  ADVANTAGE   IN 4 – 6 cms MARGINS• LYMPH ADENCTOMY• SENTINEL   NODE  BIOPSY  IN  NO  NODES  CLINICALLY• HYPERTHERMIC   ARTERIAL   LIMB   PERFUSION – MELPHALAN• ADJUVANT   THERPAY

STAGE III

• 2 cm MARGIN• REGIONAL   LYMPHADENOCTOMY

STAGE IV• REFRACTORY• CONSIDER  FOR   CLINICAL  TRIALS• DTC ,  BCNU• RADIATION

Page 37: HISTOLOGY AND FUNCTION1).pdf · histology ¾nest of epidermal cells –mixture of normal and anaplastic ¾cells ¾well ... • skin, git, brain – adults • white population highest
Page 38: HISTOLOGY AND FUNCTION1).pdf · histology ¾nest of epidermal cells –mixture of normal and anaplastic ¾cells ¾well ... • skin, git, brain – adults • white population highest
Page 39: HISTOLOGY AND FUNCTION1).pdf · histology ¾nest of epidermal cells –mixture of normal and anaplastic ¾cells ¾well ... • skin, git, brain – adults • white population highest

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