Download MBBS (Bachelor of Medicine, Bachelor of Surgery) Burns and Plastic Surgery PPT 4 Disorders Of Melanocytes Lecture Notes
DISORDERS OF MELANOCYTES
DISORDERS OF MELANOCYTES
? Stratum germinativum /basal layer.
? Also contains melanocytes
? Stratum spinosum
? Stratum granulosum
? Stratum lucidum
? Stratum corneum
DISORDERS OF MELANOCYTES
Melanocytes ?
? Derived from the neural crest.
? Spindle-shaped clear cells with dendritic processes and dark nucleus.
? Produce melanin packaged in melanosomes, delivered along dendrites to surrounding keratinocytes.
DISORDERS OF MELANOCYTES
Melanin-
? Synthesised within melanocytes from the amino acid tyrosine, via the intermediate Dopa.
? Accumulates in vesicles within melanocytes called melanosomes.
? Cells around melanocytes usually contain more melanin than the melanocytes.
? Increased pigmentation is due to increased basal production of melanin.
DISORDERS OF MELANOCYTES
Naevus cells -
? 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
? Tend to congregate in nests.
? Large with abundant cytoplasm
DISORDERS OF MELANOCYTES-
NAEVUS CELL NAEVI
Congenital Melanocytic Naevus (CMN)-
? Brown or black lesions present at birth.
? `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.
DISORDERS OF MELANOCYTES-
NAEVUS CELL NAEVI
Congenital Melanocytic Naevus (CMN)-
? Significant risk of central nervous system (CNS) abnormalities with CMN :
? Disorders of CNS development
? Intracranial melanosis .
? Nonmelanotic intracranial abnormalities
? More recent prospective reports show risk of melanoma is 0.7?2.4%
DISORDERS OF MELANOCYTES-
NAEVUS CELL NAEVI
Congenital Melanocytic Naevus (CMN)-
? Excision of the nevus is the treatment of choice
DISORDERS OF MELANOCYTES-
NAEVUS CELL NAEVI
Acquired Nevus-
? Classified as junctional, compound, or dermal
? Nevus cells
? Accumulate in Epidermis (junctional),
? Migrate partially into the dermis (compound)
? Completely in the dermis (dermal).
? Eventually most lesions undergo involution.
DISORDERS OF MELANOCYTES-
NAEVUS CELL NAEVI
Acquired Nevus-
Junctional nevus-
? Flat, smooth, irregularly pigmented lesions.
? Usually found in the young.
? Nests of naevus cells clustered at the dermoepidermal junction
DISORDERS OF MELANOCYTES-
NAEVUS CELL NAEVI
Acquired Nevus-
Compound naevus-
? Round, well-circumscribed, slightly raised lesions.
? Nests of naevus cells clustered at the dermoepidermal junction extending into
dermis.
DISORDERS OF MELANOCYTES-
NAEVUS CELL NAEVI
Acquired Nevus-
Intradermal naevus-
? Dome-shaped lesions; may be nonpigmented or hairy.
? Tend to occur more in adults. ?
? Nests of naevus cells clustered solely within dermis.
DISORDERS OF MELANOCYTES-
MELANOCYTIC NAEVI
Epidermal melanocytic naevi -
Ephelis -
? 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
DISORDERS OF MELANOCYTES-
MELANOCYTIC NAEVI
Epidermal melanocytic naevi -
Lentigo ?
? Contains an increased number of melanocytes.
? Persists in the absence of sunlight.
? 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.
DISORDERS OF MELANOCYTES-
MELANOCYTIC NAEVI
Epidermal melanocytic naevi -
Caf?-au-lait patch ?
? Pale brown macule.
? Histologically there are `macromelanosomes' in basal melanocytes.
? Six or more >5mm in children (>15mm in adults)
required to support a diagnosis of NF1.
DISORDERS OF MELANOCYTES-
MELANOCYTIC NAEVI
Dermal melanocytic naevi -
Mongolian blue spot ?
? Characterised by blue-grey pigmentation over the sacrum.
? 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-
MALIGNANT MELANOMA
? A melanoma ? or malignant melanoma (MM) ? is a malignant tumour of
melanocytes
DISORDERS OF MELANOCYTES-
MALIGNANT MELANOMA
Epidemiology
? Fifth most common cancer in the United Kingdom.
? 4% of all new cancers.
? Annual incidence approximately 20 per 100,000 population.
DISORDERS OF MELANOCYTES-
MALIGNANT MELANOMA
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
DISORDERS OF MELANOCYTES-
MALIGNANT MELANOMA
Heredity ?
?
10 % of melanomas are familial and have a genetic basis
DISORDERS OF MELANOCYTES-
MALIGNANT MELANOMA
Risk factors -
Premalignant lesions
? Atypical naevi ?
? 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%.
DISORDERS OF MELANOCYTES-
MALIGNANT MELANOMA
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
? Also occur on mucous membranes (mouth, genitalia)
DISORDERS OF MELANOCYTES-
MALIGNANT MELANOMA
Clinical Manifestations ?
? Typically appears as a pigmented papule, plaque or nodule.
? Demonstrates any of the ABCDEs
? It may bleed, be eroded or crusted
? Patients may give history of change
DISORDERS OF MELANOCYTES-
MALIGNANT MELANOMA
Suspicious moles may have any of the fol owing features
DISORDERS OF MELANOCYTES-
MALIGNANT MELANOMA
Types of Malignant Malenoma ?
? Superficial spreading type-
? Nodular type-
? Lentigo maligna type-
? Acral lentiginous type-
? Amelanotic/Hypomelanotic type-
DISORDERS OF MELANOCYTES-
MALIGNANT MELANOMA
Superficial spreading type-
? Most common type
? Involves back in men; back and legs in women
? Growth of tumour is primarily horizontal rather than down into the dermis
DISORDERS OF MELANOCYTES-
MALIGNANT MELANOMA
Nodular type-
? 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
DISORDERS OF MELANOCYTES-
MALIGNANT MELANOMA
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
DISORDERS OF MELANOCYTES-
MALIGNANT MELANOMA
Acral lentiginous type-
? More common in people with darker skin color (Asians and persons of African
ancestry)
? Diagnosis is often delayed, so lesions tend to be many centimeters in diameter
DISORDERS OF MELANOCYTES-
MALIGNANT MELANOMA
Diagnosis?
Biopsy-
? Excision (Golden standard)
? Incision biopsy
? Punch biopsy
? Partial thickness or shaving biopsies are contraindicated
? All dermis layers should be included in the biopsy
DISORDERS OF MELANOCYTES-
MALIGNANT MELANOMA
Staging (AJCC)?
DISORDERS OF MELANOCYTES-
MALIGNANT MELANOMA
Staging (AJCC)?
DISORDERS OF MELANOCYTES-
MALIGNANT MELANOMA
Staging (AJCC)?
DISORDERS OF MELANOCYTES-
MALIGNANT MELANOMA
The histopathologic classification by Clark-
DISORDERS OF MELANOCYTES-
MALIGNANT MELANOMA
Prognostic Factors
? Breslow thickness (most important)
? Clark invasion level
? Ulceration
? Age, sex, location
? Size and surgical margins
? Others (Mitotic index, growth phase, regression...)
DISORDERS OF MELANOCYTES-
MALIGNANT MELANOMA
Surgical treatment-
? Biopsy
? Wide Local Excision
? Staging with Sentinel Lymph Node biopsy
? Therapeutic Lymph Node Dissection
? Treatment of Distant Metastasis
DISORDERS OF MELANOCYTES-
MALIGNANT MELANOMA
Wide Surgical Excision
Suggested surgical margins: (according to Breslow thickness)
? In-situ MM:
0.5-1 cm
? Breslow thickness < 1mm :
1 cm
? Breslow thickness 1-4 mm:
2 cm
? Breslow thickness >4 mm:
> 3 cm
DISORDERS OF MELANOCYTES-
MALIGNANT MELANOMA
Sentinel Lymphadenectomy
? 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
DISORDERS OF MELANOCYTES-
MALIGNANT MELANOMA
Management of metastatic disease
Distant Metastasis-
? Skin
? Subcutaneous Tissue
? Distant Lymph Nodes
? Pulmonary
? Liver
? Brain
? Bone
? Intestine
DISORDERS OF MELANOCYTES-
MALIGNANT MELANOMA
Management of Locoregional recurrent melanoma-
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
infusion/ perfusion.
? Consider radiotherapy.
DISORDERS OF MELANOCYTES-
MALIGNANT MELANOMA
Management of Systemic metastatic disease
? Signal transduction inhibitor Vemurafenib
? Given orally.
? 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
? Monoclonal antibody( Ipilimumab )
? Inhibits cytotoxic T-lymphocyte antigen 4 (CTLA-4).
? CTLA-4 normally downregulates T-cell activation.
? Inhibiting CTLA-4 therefore stimulates the immune system to attack the cancer.
? Interleukin-2
? Arrests growth of metastatic MM for prolonged periods.
DISORDERS OF MELANOCYTES-
MALIGNANT MELANOMA
Management of Systemic metastatic disease
? Chemotherapy
? The main drug for MM is dacarbazine, an alkylating agent.
? 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.
This post was last modified on 07 April 2022