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Download MBBS Burns and Plastic Surgery PPT 4 Disorders Of Melanocytes Lecture Notes

Download MBBS (Bachelor of Medicine, Bachelor of Surgery) Burns and Plastic Surgery PPT 4 Disorders Of Melanocytes Lecture Notes

This post was last modified on 07 April 2022




DISORDERS OF MELANOCYTES

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DISORDERS OF MELANOCYTES

? 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 NAEVI

Congenital 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 NAEVI

Epidermal 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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melanocytes

DISORDERS 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 MELANOMA

Clinical 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 MELANOMA

Superficial 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 MELANOMA

Staging (AJCC)?


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DISORDERS OF MELANOCYTES-

MALIGNANT MELANOMA

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Staging (AJCC)?

DISORDERS OF MELANOCYTES-

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MALIGNANT MELANOMA

The 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 MELANOMA

Surgical 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 Excision

Suggested 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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