? Stratum germinativum /basal layer.
? Also contains melanocytes
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? Stratum spinosum
? Stratum granulosum
? Stratum lucidum
? Stratum corneum
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DISORDERS OF MELANOCYTES
Melanocytes ?
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? Derived from the neural crest.
? Spindle-shaped clear cells with dendritic processes and dark nucleus.
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? Produce melanin packaged in melanosomes, delivered along dendrites to surrounding keratinocytes.DISORDERS OF MELANOCYTES
Melanin-
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? Synthesised within melanocytes from the amino acid tyrosine, via the intermediate Dopa.
? Accumulates in vesicles within melanocytes called melanosomes.
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? Cells around melanocytes usually contain more melanin than the melanocytes.? Increased pigmentation is due to increased basal production of melanin.
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DISORDERS OF MELANOCYTES
Naevus cells -
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? When melanocytes leave the epidermis and enter the dermis they become naevus cells.
? Naevus cells are round rather than spindle shaped and has no dendritic processes
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? Tend to congregate in nests.? Large with abundant cytoplasm
DISORDERS OF MELANOCYTES-
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NAEVUS CELL NAEVI
Congenital Melanocytic Naevus (CMN)-
? Brown or black lesions present at birth.
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? `Giant' if >20cm diameter in adulthood.? Sometimes called giant hairy naevi.
? Annual incidence of CMN is approximately 2%.
? Giant CMN is much rarer ? annual incidence 1 in 20,000.
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DISORDERS OF MELANOCYTES-
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NAEVUS CELL NAEVICongenital Melanocytic Naevus (CMN)-
? Significant risk of central nervous system (CNS) abnormalities with CMN :
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? Disorders of CNS development? Intracranial melanosis .
? Nonmelanotic intracranial abnormalities
? More recent prospective reports show risk of melanoma is 0.7?2.4%
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DISORDERS OF MELANOCYTES-
NAEVUS CELL NAEVI
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Congenital Melanocytic Naevus (CMN)-? Excision of the nevus is the treatment of choice
DISORDERS OF MELANOCYTES-
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NAEVUS CELL NAEVI
Acquired Nevus-
? Classified as junctional, compound, or dermal
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? Nevus cells? Accumulate in Epidermis (junctional),
? Migrate partially into the dermis (compound)
? Completely in the dermis (dermal).
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? Eventually most lesions undergo involution.
DISORDERS OF MELANOCYTES-
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NAEVUS CELL NAEVI
Acquired Nevus-
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Junctional nevus-? Flat, smooth, irregularly pigmented lesions.
? Usually found in the young.
? Nests of naevus cells clustered at the dermoepidermal junction
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DISORDERS OF MELANOCYTES-
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NAEVUS CELL NAEVI
Acquired Nevus-
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Compound naevus-? Round, well-circumscribed, slightly raised lesions.
? Nests of naevus cells clustered at the dermoepidermal junction extending into
dermis.
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DISORDERS OF MELANOCYTES-
NAEVUS CELL NAEVI
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Acquired Nevus-Intradermal naevus-
? Dome-shaped lesions; may be nonpigmented or hairy.
? Tend to occur more in adults. ?
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? Nests of naevus cells clustered solely within dermis.DISORDERS OF MELANOCYTES-
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MELANOCYTIC NAEVIEpidermal melanocytic naevi -
Ephelis -
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? Commonly known as a freckle.? Contains a normal number of melanocytes.
? Pigmentation is due to increased melanin production.
? Lesions are said to disappear in the absence of sunlight
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DISORDERS OF MELANOCYTES-MELANOCYTIC NAEVI
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Epidermal melanocytic naevi -Lentigo ?
? Contains an increased number of melanocytes.
? Persists in the absence of sunlight.
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? Different types of Lentigo:-? Lentigo simplex ? occurs in the young and middle aged
? Lentigo senilis ? occurs in the elderly
? Solar lentigo ? occurs after sun exposure.
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DISORDERS OF MELANOCYTES-
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MELANOCYTIC NAEVI
Epidermal melanocytic naevi -
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Caf?-au-lait patch ?? Pale brown macule.
? Histologically there are `macromelanosomes' in basal melanocytes.
? Six or more >5mm in children (>15mm in adults)
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required to support a diagnosis of NF1.DISORDERS OF MELANOCYTES-
MELANOCYTIC NAEVI
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Dermal melanocytic naevi -
Mongolian blue spot ?
? Characterised by blue-grey pigmentation over the sacrum.
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? Said to be present in 90% of Mongolian infants.? Can be mistaken for bruising and attributed to non accidental injury of children.
DISORDERS OF MELANOCYTES-
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MALIGNANT MELANOMA
? A melanoma ? or malignant melanoma (MM) ? is a malignant tumour of
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melanocytesDISORDERS OF MELANOCYTES-
MALIGNANT MELANOMA
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Epidemiology
? Fifth most common cancer in the United Kingdom.
? 4% of all new cancers.
? Annual incidence approximately 20 per 100,000 population.
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DISORDERS OF MELANOCYTES-
MALIGNANT MELANOMA
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Etiology:
? May develop de novo or arise within a pre-existing nevus
? Cumulative and prolonged UVB and/or UVA exposure
? UVA exposure from tanning beds increases risk for melanoma
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DISORDERS OF MELANOCYTES-
MALIGNANT MELANOMA
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Heredity ??
10 % of melanomas are familial and have a genetic basis
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DISORDERS OF MELANOCYTES-
MALIGNANT MELANOMA
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Risk factors -
Premalignant lesions
? Atypical naevi ?
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? FAMM syndrome (previously called atypical naevus syndrome) is defined as:? Patients with FAMM have a lifetime risk of melanoma close to 100%.
? Congenital melanocytic naevus has risk of 0.7?2.4%.
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DISORDERS OF MELANOCYTES-
MALIGNANT MELANOMA
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Clinical Manifestations ?? Usually asymptomatic
? May develop de novo or arise within a pre-existing nevus
? Majority located in sun-exposed areas, but also occur in non-sun-exposed areas
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? Also occur on mucous membranes (mouth, genitalia)DISORDERS OF MELANOCYTES-
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MALIGNANT MELANOMAClinical Manifestations ?
? Typically appears as a pigmented papule, plaque or nodule.
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? Demonstrates any of the ABCDEs? It may bleed, be eroded or crusted
? Patients may give history of change
DISORDERS OF MELANOCYTES-
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MALIGNANT MELANOMA
Suspicious moles may have any of the fol owing features
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DISORDERS OF MELANOCYTES-
MALIGNANT MELANOMA
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Types of Malignant Malenoma ?? Superficial spreading type-
? Nodular type-
? Lentigo maligna type-
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? Acral lentiginous type-? Amelanotic/Hypomelanotic type-
DISORDERS OF MELANOCYTES-
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MALIGNANT MELANOMASuperficial spreading type-
? Most common type
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? Involves back in men; back and legs in women? Growth of tumour is primarily horizontal rather than down into the dermis
DISORDERS OF MELANOCYTES-
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MALIGNANT MELANOMA
Nodular type-
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? Rapid growth? Growth is vertical, giving tumor an increased Breslow's depth
? Breslow's depth = thickness of the primary melanoma measured from the
granular layer of the epidermis to the deepest part of the tumour
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DISORDERS OF MELANOCYTES-
MALIGNANT MELANOMA
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Lentigo maligna type-? Occurs on chronically sun-damaged skin, more common in elderly patients
? Slow progression
? Growth of tumor is primarily horizontal, and not vertical
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DISORDERS OF MELANOCYTES-
MALIGNANT MELANOMA
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Acral lentiginous type-
? More common in people with darker skin color (Asians and persons of African
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ancestry)? Diagnosis is often delayed, so lesions tend to be many centimeters in diameter
DISORDERS OF MELANOCYTES-
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MALIGNANT MELANOMA
Diagnosis?
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Biopsy-? Excision (Golden standard)
? Incision biopsy
? Punch biopsy
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? Partial thickness or shaving biopsies are contraindicated? All dermis layers should be included in the biopsy
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DISORDERS OF MELANOCYTES-
MALIGNANT MELANOMA
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Staging (AJCC)?
DISORDERS OF MELANOCYTES-
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MALIGNANT MELANOMAStaging (AJCC)?
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DISORDERS OF MELANOCYTES-
MALIGNANT MELANOMA
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Staging (AJCC)?
DISORDERS OF MELANOCYTES-
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MALIGNANT MELANOMAThe histopathologic classification by Clark-
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DISORDERS OF MELANOCYTES-MALIGNANT MELANOMA
Prognostic Factors
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? Breslow thickness (most important)
? Clark invasion level
? Ulceration
? Age, sex, location
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? Size and surgical margins? Others (Mitotic index, growth phase, regression...)
DISORDERS OF MELANOCYTES-
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MALIGNANT MELANOMASurgical treatment-
? Biopsy
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? Wide Local Excision? Staging with Sentinel Lymph Node biopsy
? Therapeutic Lymph Node Dissection
? Treatment of Distant Metastasis
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DISORDERS OF MELANOCYTES-
MALIGNANT MELANOMA
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Wide Surgical ExcisionSuggested surgical margins: (according to Breslow thickness)
? In-situ MM:
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0.5-1 cm? Breslow thickness < 1mm :
1 cm
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? Breslow thickness 1-4 mm:
2 cm
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? Breslow thickness >4 mm:> 3 cm
DISORDERS OF MELANOCYTES-
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MALIGNANT MELANOMA
Sentinel Lymphadenectomy
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? Sentinel lymph node shows the regional node status? If sentinel lymph node negative, others lymph nodes in the basin are also negative
? If sentinel lymph node contains tumour cells, It means disease spread to the regional nodal
basin
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DISORDERS OF MELANOCYTES-
MALIGNANT MELANOMA
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Management of metastatic disease
Distant Metastasis-
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? Skin? Subcutaneous Tissue
? Distant Lymph Nodes
? Pulmonary
? Liver
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? Brain? Bone
? Intestine
DISORDERS OF MELANOCYTES-
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MALIGNANT MELANOMA
Management of Locoregional recurrent melanoma-
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Treatment options are palliative:? Surgical excision for solitary lesions.
? CO2 laser for multiple small (<1mm) dermal lesions.
? Extensive limb disease may benefit from regional chemotherapy by isolated limb
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infusion/ perfusion.
? Consider radiotherapy.
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DISORDERS OF MELANOCYTES-
MALIGNANT MELANOMA
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Management of Systemic metastatic disease? Signal transduction inhibitor Vemurafenib
? Given orally.
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? Targets a mutated form of the BRAF gene present in about half of MMs.? Resected MM tissue is first tested to confirm presence of the BRAF V600 mutation.
? Without a V600 mutation, vemurafenib stimulates growth of tumour cells.
? Immunotherapy
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? Monoclonal antibody( Ipilimumab )
? Inhibits cytotoxic T-lymphocyte antigen 4 (CTLA-4).
? CTLA-4 normally downregulates T-cell activation.
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? Inhibiting CTLA-4 therefore stimulates the immune system to attack the cancer.? Interleukin-2
? Arrests growth of metastatic MM for prolonged periods.
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DISORDERS OF MELANOCYTES-
MALIGNANT MELANOMA
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Management of Systemic metastatic disease? Chemotherapy
? The main drug for MM is dacarbazine, an alkylating agent.
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? Response rates are 10?20% and short-lived, usually <6 months.? Metastases to distant lymph node basins can be palliated by lymphadenectomy.
? Single metastases can be palliated with resection.
? MM is classically radioresistant, but radiotherapy may alleviate symptoms.
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