INTEGUMENTARY SYSTEMTHE INTEGUMENTARY IS THE LARGEST ORGAN OF THE BODY.

IT CONSISTS OF TWO COMPONENTS:(1) THE SKIN, AND (2)THE EPIDERMAL DERIVATIVES, SUCH AS THE HAIR, NAILS

AND GLANDS.THE SKIN IS OF PARTICULAR SIGNIFICANCE IN A CLINICAL

EXAMINATION. FOR EXAMPLE, THE COLOR OFTHE SKIN MAY INDICATE THE EXISTENCE OF A PATHOLOGIC CONDITION: A

YELLOW COLOR INDICATES JAUNDICE; A BLUE-GRAY COLOR MAY INDICATE CYANOSIS, REFLECTING A PATHOLOGIC

CONDITION OF CARDIOVASCULAR AND RESPIRATORY FUNCTION S; A PALE COLOR IS INDICATIVE OF ANEMIA; LACK OF SKIN PIGMENTATION SUGGESTS ALBINISM, A

GENETIC TRAIT CHARACTARIZED BY LACK OF THE ENZYME TYROSINASE, INVOLVED IN THE CONVERSION OF THE AMINO

ACID TYROSINE TO MELANIN.

THE SKIN HAS SEVERAL FUNCTIONS: (1)PROTECTION, (2)AS A WATER BARRIER,(3) REGULATION OF BODY TEMPERATURE (CONSERVATION AND DISSIPATION OF HEAT ),(4) NON SPECIFIC DEFENSE( BARRIER OF MICRO-ORGANISMS);(5)EXCRETION OF SALTS (6) SYNTHESIS OF VITAMIN D; (7) AS A SENSORY ORGAN AND (8)SEXUAL SIGNALING (9)ECONOMIC VALUE(COSMETICS)--

SKIN TYPES AND GENERAL ORGANIZATION

THE SKIN CONSIST OF THREE LAYERS FIRMLY ATTACHED TO ONE ANOTHER : (1)THE OUTER EPIDERMIS –DERIVED FROM ECTODERM (2) THE DEEPER DERMIS DERIVED FROM MESODERM ; AND (3) THE HYPODERMIS OR SUBCUTANEOUS LAYER – CORRESPONDING TO THE SUPERFICIAL FASCIA OF GROSS ANATOMY.

SKIN IS GENERALLY CLASSIFIED INTO TWO TYPES

SKIN TYPES CONT............

(1) THICK SKIN (GLOBUS), AND (2) THIN SKIN (HAIRY). THICK SKIN (MORE THAN 5 MM THICK) COVERS THE PALMS OF THE HANDS AND THE SOLES OF THE FEET AND HAS A THICK EPIDERMIS AND DERMIS. THIN SKIN (1-2 MM IN THICKNESS) LINES THE REST OF THE BODY; THE EPIDERMIS IS THIN.

THE SURFACE OF THE SKIN HAS NARROW EPI-DERMAL RIDGES SEPARATED BY FURROWS .

SKIN TYPES CONT...................IN THE FINGER TIPS , RIDGES FORM COMPLICATED

CONFIGURATIONS. IMPRESSIONS RESULT FINGERPRINTS, CHARACTERISTICS FOR EACH INDIVIDUAL. THE POSITION OF THE EPIDERMAL RIDGES CORRELATES WITH THE PROJECTION OF THE EPIDERMIS ON THE DERMAL SIDE, CALLED THE PRIMARY DERMAL RIDGE . AN INTERPAPILLARY PEG DIVIDES THE PRIMARY DERMAL RIDGE INTO 2 DERMAL RIDGES. THE DERMAL PAPPILLA BETWEEN PRM&SEC DERMAL RIDGES. DERMAL PAPILLAE ARE NUMEROUS AND BRANCHED. IN THIN SKIN PAPILLAE ARE LOW AND THEIR NUMBER ARE REDUCED.

EPIDERMISTHE STRATIFIED SQUAMOUS EPITHERIAL LAYER OF THE

EPIDERMIS CONSISTS OF FOUR DISTINCT CELL TYPES 1. THE PREDOMINANT CELL TYPE IS THE

KERATINOCYTE, SO CALLED BACAUSE ITS MAJOR PRODUCT IS KERATIN, AN INTERMEDIATE FILAMENT PROTEIN .

MELANOCYTES-NEURAL CREST- DERIVED CELLS RESPONSIBLE FOR THE PRODUCTION OF MELANIN .

LANGERHANGS CELLS-DENDRITIC CELLS DERIVED FROM A BONE MARROW PRECURSOR,ACTING AS AN ANTIGEN-TRAPPING CELLS INTERACTING WITH

EPIDRM CONT..................

CELLS.MERKEL,S CELLS-NEURAL CREST DERIVED CELLS

INVOLVED IN TACTILE SENSATION. KERATINOCYTES ARE ARRANGED IN FIVE LAYERS OR STRATA: (1)THE STRATUM BASALE; (2)THE STRATUM SPINOSUM; (3) THE STRATUM GRANULOSUM;(4)THE STRATUM LUCIDUM;(5) THE STRATUM CORNEUM.

THE STRATUM BASALE AND STRAUM SPINOSUM FORM THE STRATUM OF MALPIGHI /OR GERMINITIVUM.

CLINICAL SIGNIFICANCE: WOUND REPAIR AND PSORIASIS

DEJTHE BASAL LAMINA OR BASMENT MEMBRANE CONSIST OF:

(1)LAMINA LUCIDA(2)LAMINA DENSA

(3)ANCHORING FIBRILS

DIFFERENTIATION OF A KERATINOCYTE.KERATINOCYTES OF THE STRATUM HAVE A FLATTENED

POLYGONAL SHAPE WITH A DISTINCT OVOID NUCLEUS. THE CYTOPLASM DISPLAYS SMALL GRANULES WITH A LAMELLAR CORE, CALLED MEMBRANE-COATING GRANULES, OR LAMELLAR BODIES. BUNDLES OF INTERMEDIATE FILAMENTS-TONOFIBRILS-EXTEND INTO THE CYTOPLASMIC SPINOUS-LIKE PROCESSES AND ATTACH TO THE DENSE PLAQUE OF A DESMOSOME.

THE STRATUM GRANULOSUM CONSIST OF MULTILAYERED ASSEMBLY OF FLATTENED NUCLEATED KERATINOCYTES WITH CHARACTERISTIC IRREGULARLY SHAPED KERATOHYALIN GRANULES WITHOUT A LIMITING MEMBRANE AND ASSOCIATED WITH THE TONOFILAMENTS.

DIFFERENTIATION CONT..................

THE LAMELLAR, WHICH FIRST APPEAR IN KERATINO CYTES OF THE STRATUM SPINOSUM, INCREASE IN NUMBER IN THE STRATUM GLANULOSUM, AND THE LAMELLAR MATERIAL PRODUCT, THE GLYCOLIPID ACYLGLUCOSYLCERAMIDE, IS REALIZED INTO THE INTERCCELLULAR SPACES .

IN THE INTERCELLULAR SPACE, THE LAMELLAR MATERIAL FORMS A STRUCTURE ARRANGED IN WIDE SHEETS, COATING THE SURFACE OF KERATINOCYTES OF THE UPPER LAYER,THE STRATUM LUCIDUM. THE GLYCOLIPID COATING PROVIDES THE WATER BARRIER OF THE EPIDERMIS.

DIFFERENTIATION CONT.........THE STRATUM LUCIDUM IS RECOGNIZED BY SOME

HISTOLOGISTS AS AN INTERMEDIATE LAYER ABOVE THE STRATUM GRANULOSUM AND BENEATH THE STRATUM CORNEUM. HOWEVER, NO DISTINCTIVE CYTOLOGIC FEATURES ARE SIGNIFICANTLY APPARENT. BOTH THE STRATUM LUCIDUM AND STRATUM CORNEUM CONSIST OF SEVERAL LAYERS OF KERATINOCYTES WITHOUT NUCLEI AND A CYTOPLASM CONTAINING AGGREGATED INTERMEDIATE FILAMENTS OF KERATIN CROSS-LINKED WITH FILAGGRIN CATALYZED BY TRANSGLUTAMINASES.

DIFFERENTIATION CONT..........

THE KERATIN-FILAGGRIN COMPLEX IS DEPOSITED ON THE INSIDE OF THE PLASMA MEMBRANE, FORMING A CORNIFIED STURUCTURE CALLED THE CELL ENVELOPE. ON THE OUTSIDE OF THE CELL, LIPIDS RELEASED FROM LAMELLAR BODIES CROSSLINK THE CELL ENVELOPE, FORMING THE COMPOUND CELL ENVELOPE.

MELANOCYTESMELANOCYTES ARE BRANCHING CELLS LOCATED IN THE

STRATUM BASALE OF THE EPIDERMIS. MELANOCYTES DERIVED FROM MELANOBLASTS, A CELL PRECURSOR MIGRANT FROM THE NEURAL CREST.

MELANOBLAST DEVELOPMENT INTO MELANOCYTES IS UNDER THE CONTROL OF THE LIGAND STEM CELL FACTOR INTERACTING WITH THE C-KIT RECEPTOR, A MEMBRANE-BOUND TYROSINE KINASE. RECALL THAT THE DEVELOPMENT OF MAST CELLS , PRIMORDIAL GERMINAL CELLS, AND HEMATOPOIETIC STEM CELLS IS ALSO DEPENDENT ON THE INTERACTION OF STEM CELLS FACTOR WITH THE C-KIT RECEPTOR

MELANOCYTES CONT......................MELANIN IS PRODUCED BY OXIDATION OF THYROSINE

3,4-DIHYDROXYPHENYLALANINE(DOPA) BY THE ENZYME TYROSINASE. DOPA IS THEN TRANSFORMED TO MELANIN, WHICH ACCUMULATES IN MELANOSOMES , THE MATURE MELANIN= GRANULES THAT ARE DISTRIBUTED ALONG THE CYTOPLASMIC PROCESSES OF THE MELANOCYTES. KERANOCYTES TAKE UP THE RELEASED INSOLUBLE AND DARK MELANIN GARANULES . IN ADDITION TO MELANO CYTES, MELANIN-PRODUCING CELLS ARE PRESENT INTHE CHOROID PLEXUS, RETINA AND CILIARY-BODY OF THE EYE. ALBINISM FROM THE INABILITY OF CELLS TO FORM MELANIN

LANGERHANS CELLS LANGERHANS CELLS ARE BONE MARROW-DERIVED

CELLS PRESENT IN THE EPIDERMIS AND INVOLVED IN IMMUNE RESPONSES, IN PARTICULAR THE PRESENTATION OF ANTIGENS TO T- CELLS DURING THE INITIATION OF CUTANEOUS HYPER-SENSITIVE REACTIONS . LANGERHANS CELLS MIGRATE FROM THE EPIDERMIS TO THE LYMPH NODE WHERE THEY DIFFERENTIATE INTO ACTIVATED DENDRITIC CELLS AFTER EXPRESSING CLASS I MHC (MAJOR HISTOCOMPATIBILITY COMPLEX), CLASS II MHC, AND B-CELLS SURFACE ANTIGENS. ACTIVATED DENDRITIC CELLS STIMULATE THE ACTIVITY OF T- CELLS.

LANGERHANS CONT....................

LIKE MELANOCYTES, LANGERHANS CELLS HAVE CYTOPLASMIC PROCESS (DENDRITIC CELLS) EXTENDING AMONG KERANOCYTES OF THE STRATUM SPINOSUM WITHOUT ESTABLISHING DESMOSOMAL CONTACT BUT ASSOCIATING WITH KERATINOCYTES THROUGH E-CADHERIN.

THE NUCLEUS OF A LANGERHANS CELL IS INDENTED, AND CYTOPLASM CONTAINS CHARACTERISTIC ROD-SHAPED GRANULES (BIRBECKS OR VERMFORM GRANULES).

MERKEL CELLS.MERKEL CELLS RESEMBLE MODIFIED KERANOCYTES, ARE FOUND

IN THE STRATUM BASALE, AND ARE NUMEROUS IN THE FINGERTIPS. MERKEL CELLS ARE MECHANORECEPTOR CELLS. LINKED TO ADJACENT KERATINOCYTES BY DESMOSOME AND IN CONTACT WITH AN AFFERENT MYELINATED NERVE FIBER PROJECTING FROM THE DERMIS INTO THE EPIDERMIS. THE NERVE FIBER BECOMES UNMYELINATED AFTER PASSING THROUGH THE BASAL LAMINA OF THE EPIDERMIS AND EXPANDS INTO A PLATELIKE SENSORY ENDING, THE NERVE PLATE, IN CONTACT WITH THE MERKEL CELL. THE NUCLEUS IS IRREGULARY SHAPED AND THE CYTOPLASM CONTAINS ABUNDANT GRANULES,PRESUMABLY NEUROTRANSMITTERS.

DERMIS

THE DERMIS IS FORMED BY TWO LAYERS WITHOUT DISTINCT BOUNDARIES:(1)THE PAPILLARY LAYER,CONSISTING OF LOOSE CONNECTIVE TISSUE (FIBROBLASTS, COLLAGEN FIBERS AND THIN ELASTIC FIBERS) IN CLOSE CONTACT WITH THE EPIDERMIS; AND (2) THE RETICULAR LAYER, CONTAINING THICK BUNDLES OF COLLAGEN FIBERS AND COARSE ELASTIC FIBERS. HAIR FOLLICLES AND SWEAT AND SEBACEOUS GLANDS ARE EPIDERMAL DERIVATIES PRESENT AT VARIOUS LEVELS OF THE DERMIS.

DERMIS CONT....................

HEMIDESMOSOMES ON THE BASAL DOMAIN OF KERATINOCYTES OF THE STRATUM BASALE ATTACH THE EPIDERMIS TO THE BASEMENT MEMBRANE AND THE PAPILLARY LAYER OF THE DERMIS BY ANCHORING FILAMENTS AND FIBRILS, RESPECTIVELY.THE MOLECULAR AND STRUCTUAL COMPONENTS OF THE HEMIDESMOSOME ARE OF CONSIDERABLE IMPORTANCE FOR UNDERSTANDING THE CAUSE OF BLISTERING DISEASES OF THE SKIN, THE EPITHELIUM, THE CLINICAL SIGNIFICANCE OF HEMIDESMOSOME AND INTERMEDIATE FILAMENTS.

BLOOD SUPPLYTHREE INTERCONECTED NETWORK ARE RECOGNIZED IN THE

SKIN :1.THE SUBPAPILLARY PLEXUS, RUNING ALONG THE PAPILLARY

LAYERS OF THE DERMIS.2.THE CUTANEOUS PLEXUS, OBSERVED AT THE BOUNDARY OF

THE PAPILLARY AND RETICULAR LAYERS OF THE DERMIS.3.THE HYPODERMIC OR SUBCUTANEOUS PLEXUS, PRESENT

IN THE HYPODERMIS OR SUBCUTANEOUS ADIPOSE TISSUE.THE SUBPAPILLARY PLEXUS GIVES RISE TO SINGLE LOOPS OF

CAPILLARIES WITHIN EACH DERMAL PAPILLA. VENOUS BLOOD FROM THE SUBPAPILLARY AND RECTICULAR LAYERS OF THE DERMIS.

SENSORY RECEPTORSTHREE CATEGORIES OF SENSORY RECEPTORS ARE

PRESENT INTHE SKIN AND OTHER ORGANS : (1)EXTEROCEPTORS, (2)PROPRIOCEPTORS AND (3) INTEROCEPTORS. EXTEROCEPTORS PROVID INFORMATION ABOUT THE EXTENAL INVIRONMENT. PROPRIOCEPTORS ARE LOCATED IN MUSCLES (MUSCLE SPINDLE), TENDONS, AND JOINT CAPSULES AND PROVIDE IFORMATIONS ABOUT THE POSITION AND MOVEMENT OF THE BODY. ANOTHER CLASSFICATION OF SENSORY RECEPTORS IS BASED ON THE TYPE OF STIMULUS TO WHICH A RECEPTOR RESPONDES: (1) MECHANORECEPTORS, (2) THERMORECEPTORS, AND (3) NOCICEPTORS

SENSORY RECEPTORS CONT..........MECHANORECEPTORS RESPOND TO MECHANICAL

DEFORMATION OF THE TISSUE OR THE RECEPTOR ITSELF (FOR EXAMPLE; STREACH, VIBRATION, PRESSURE AND TOUCH). THE MECHANORECEPTORS INCLUDE BOTH EXTEROCEPTORS AND PROPRIOCEPTORS. THERMORECEPTORS RESPONDS TO WARMTH AND COLD. NOCICEPTORS (OR PAIN RECEPTORS) RESPOND TO PAINFUL STIMULI. THE SKIN AND THE SUBCUTANEOUS TISSUE CONTAIN RECEPTORS THAT RESPOND TO STIMULI SUCH AS TOUCH, PRESSURE, HEAT AND PAIN.THE SIMPLEST MECHANORECEPTOR IS THE NAKED NERVE ENDING, WHICH LACKS MYELIN COVERING.

SENSORY RECEPTORS CONT..........NAKED NERVE ENDINGS ARE FOUND IN THE EPIDERMIS OF

THE SKIN AND CORNEA OF THE EYE.NAKED NERVE ENDINGS RESPOND TO LIGHT PRESSURE AND TOUCH STIMULI. THE SECOND TYPE OF MECHANORECEPTOR IS THE MERKEL DISK. THE NERVE ENDING OF THIS RECEPTOR DISCRIMINATES TOUCH AND FORMS A FLATTENED DISCOID STRUCTURE ATTACHED TO THE MERKEL CELLS FOUND IN THE STRATUM BASALE OF THE EPIDERMIS. THE THIRD TYPE OF MECHANOCEPTOR INCLUDES TWO ENCAPSULATED RECEPTORS: (1) THE MEISSNER CORPUSCLE AND (2) THE PACINIAN CORPUSCLE.

SENSORY RECEPTORS CONT..........THE MEISSNER CORPUSCLE IS FOUND IN THE DERMAL

PAPILLAE AND ACCOUNTS FOR HALF THE TACTILE RECEPTORS OF THE DIGITS AND HAND. THIS RECEPTER IS WELL SUITED FOR THE DETECTION OF SHAPE AND TEXTURE DURING ACTIVE TOUCH. THE PACINIAN CORPUSCLE IS FOUND IN THE HYPODERMIS, OR DEEP DERMIS. IT RESPONDS TO TRANSIENT VIBRATORY STIMULI AND IS THE RECEPTOR FOR DEEP PRESSURE. THE FOURTH TYPE IS THE VERY SENSITIVE PERITRICHIAL NERVE ENDING WRAPED AROUND THE BASE AND SHAFT OF THE HAIRY FOLLICLE. THE MOVEMENT OF THE HAIRY SUFFICIENT TO STIMULATE THE NERVE ENDING OF THIS RECEPTOR.

HYPODERMIS

THE HYPODERMIS, OR SUBCUTANEOUS LAYER OF THE SKIN, IS THE DEEPER CONTINUATION OF THE DERMIS. IT CONSIST 0F LOOSE CONNECTIVE TISSUE AND ADIPOSE CELLS FORMING A LAYER OF VARIABLE THICKNESS DEPENDING ON ITS LOCATION IN THE BODY. NO ADIPOSE TISSUE IS FOUND IN THE SUBCUTANEOUS PORTION OF THE EYELIDS, CLITORIS OR PENIS.

SKIN APPENDAGESSKIN APPENDAGES INCLUDES: HAIRS, GLANDS,AND

NAILS.HAIRS:DURING DEVELOPMENT THE EPIDERMIS AND DERMIS INTERACT TO DEVELOP SWEAT GLANDS AND

APPENDAGES, SUCH AS HAIRS. A HAIR FOLLICLE PRIMORDIUM FORMS AS A CELL AGGREGATE IN THE

BASAL LAYER OF THE EPIDERMIS, INDUCED BY SIGNALING MOLECULES DERIVED FROM FIBROBLASTS

OF THE DERMAL MESODERM. MELANOCYTES PRESENT IN THE HAIR GERM PRODUCE AND

TRANSFER MELANIN INTO THE SHAFT. A BULBULLOUS SWELLING ON THE SIDE OF THE HAIR

PILI MUSCLE.

GERM CONTAINS STEM CELLS– CLONOGENIC KERATINOCYTE– THAT CAN MIGRATE AND REGENERATE THE HAIR SHAFT, THE EPIDERMIS AND SEBACEOUS GLANDS IN RESPONSE TO MORPHOGENETIC SIGNALS. THE FIRST HAIR IN THE HUMAN EMBRYO IS THIN , UNPIGMENTED, AND SPACED, AND IS CALLED LANUGO. LANUGO IS SHED BEFORE BIRTH AND REPLACED BY SHORT COLORLESS HAIR CALLED VELLUS. TERMINAL HAIR REPLACE VELLUS, WHICH REMAINS IN THE SO- CALLED HAIRLESS PARTS OF THE SKIN (FOREHEAD OF THE ADULT)..

HAIR FOLLICLES ARE CONSTANTLY RENEWING ALTERNATING PHASES OF GROWTH (ANAGEN) WITH REGRESSION (CATAGEN) AND REST (TELOGEN).THE HAIR HAS TWO PARTS : THE HAIR FOLLICLE AND THE HAIR SHAFT. THE HAIRS ARE FILAMENTOUS KERATINIZED STRUCTURES PRESENT ALL OVER THE BODY SURFACE, EXCEPT ON THICK SKIN,NIPPLES, GLANS PENIS AND CLITORIS..EACH HAIR HAS: HAIR BULB,HAIR FOLLICLE( EXTERNAL ROOT SHEATH, INTERNAL ROOT SHEATH 3PARTS,) ARRECTOR PILI MUSCLE,

SKIN APPEN. CONT

• GLANDS• THE GLANDS OF THE SKIN ARE: (1) THE SEBACEOUS

GLANDS, (2)THE SWEAT GLANDS (ECCRINE AND APOCRINE SWEAT GLANDS) (3)THE MAMMARY GLANDS

• THE SEBACEOUS GLAND IS A HOLOCRINE SIMPLE SACCULAR GLAND EXTENDING OVER THE ENTIRE SKIN EXCEPT FOR THE PALMS AND SOLES. THE SECRETORY PORTION OF THE SEBACEOUS GLAND LIES IN THE DERMIS, AND THE EXCRETORY DUCT OPENS INTO THE NECK OF THE HAIR FOLLICLE.

SKIN APPEN. CONT• SWEAT GLANDS• THERE ARE TWO TYPES OF SWEAT GLANDS: (1)

ECCRINE (MEROCRINE) SWEAT GLANDS AND (2) APOCRINE SWEAT GLANDS.

• ECCRINE– IS TUBULAR GLAND WITH A ROLE IN THE CONTROL OF BODY TEMPERATURE INNERVATED BY CHOLLINERGIC NERVES. THE SECRETORY PORTION HAS THREE CELLS,(a) CLEAR CELLS, (b) DARK CELLS AND, AND(c) MYOEPITHELIAL CELLS.

• APOCRINE– ARE COLLED AND OCCUR IN THE AXILLA, MONS PUBIS, AND CIRCUMANAL AREA. THE DUCT OPENS, TOGETHER WITH DUCTS OF

SEBACEOUS GLANDS, INTO THE HAIR FOLLICLES (INSTEAD OF INTO THE EPIDERMIS AS IN THE ECCRINE GLANDS).

FINGER NAILSTHE NAILS ARE HARD KERATIN PLATES ON THE DORSAL SURFACE OF THE TERMINAL PHALANGES OF THE FINGERS AND TOES. NAIL PLATES COVER THE NAIL BED, THE SURFACE OF THE SKIN WHICH CONSIST OF THE STRUTUM BASALE AND STRUTUM SPINOSUM. THE PROXIMAL EDGE OF THE PLATE IS THE ROOT OR MATRIX OF THE NAIL. THE PROXIMAL EDGE OF THE NAIL PLATE IS COVERED BY THE EPONYCHIUM.

THE HYPONYCHIUM REPRESENTS THE UNION BETWEEN THE NAIL BED AND THE NAIL PLATE AT THE FINGERTIP. ITS FUNCTION IS TO RENDER THE NAIL BED IMPERMEABLE FOR PROTECTION PURPOSES. IF THIS STRUCTURE IS DISRUPTED, FUNGAL INVASION PRODUCES ONYCHOMYCOSIS. NORMAL NAIL GROWTH IS 0.1-I.2mm per DAY. FINGER FASTER THAN TOES.

SUMMARY

THE SKIN IS IMPORTANT TO YOU ALL. FROM IT’S SIZE, PART AND THE APPENDANGES. WHAT MAKES THE ORGAN MUCH

INTERESTING, SURPRISINGLY EVERY CELL TYPE CAN DEVELOP A PATHOLOGICAL LESSION. IE. KERATINOCYTE CELL CAN LEAD TO

SQUAMOUS CELL CARCINOMA. MELANOCYTE CELL – MELANOMA, SEBOCYTE- SEBACIOUS ADENOMA

THANK YOU !!!