Disorders of Melanocytes
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Melanoma
Nevus
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Histopathology:Main cell is nevus cell
These are large ovoid cells with vesiculated nuclei, and pale cytoplasm
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They are derived from neural crest cells
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Congenital nevi
Rarer , 1% of neonates
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larger and may contain hair
Congenital giant lesions (giant hairy nevus) most often occur in a bathing
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trunk distribution or on the chest and backDevelop malignant melanoma in 1 to 5% of the cases
Excision of the nevus is the treatment of choice
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Giant cel nevus
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Acquired melanocytic nevi
Classified as junctional, compound, or dermal, depending on the location of the nevus cells.
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Nevus cells accumulate in the epidermis (junctional), migrate partially into the dermis (compound), and
finally rest completely in the dermis (dermal).
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Eventually most lesions undergo involution.Melanocytes in Normal epithelium
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Compound Nevus
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- Shows junctional activity & nestsof nevus cells in connective
tissue.
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Dysplastic Nevus
Multicolored
Asymmetric pigment
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deposition
Asymmetric contour-macular
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and papularIndistinct margins
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Atypical mole syndrome-(Dysplastic nevus
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syndrome)>100 melanocytic nevi
1 or more nevi >8mm in
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diameter
1 or more dysplastic nevi on
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exam10 year risk of developing melanoma of 14%
Management
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Close monitoring- full body exams every 6 months
Dermoscopy of all atypical appearing nevi
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The magnified visualization of pigmented skin lesions beyond what would be visible bythe physician
Increases diagnostic accuracy by 10-20%
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Excision of any changing or markedly atypical nevi
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MelanomaMelanoma: Pathogenesis
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Cell of origin: melanocyte
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Etiology:? Cumulative and prolonged UVB and/or UVA exposure
? UVA exposure from tanning beds increases risk for melanoma
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Risk Factors
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? Individual risk factors for development of melanoma? Increasing age
? Fair skin; blue eyes, red or blond hair; freckling
? Greater than 100 acquired nevi
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? Atypical nevi? Immunosuppression
? Personal or family history of melanoma (two or more 1st degree relatives)
? Ultraviolet exposure: Risk directly related to # of severe blistering sunburns
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before puberty; tanning booth use? Genetic syndromes
Heredity of Melanoma
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? 10 % of melanomas are familial and have a genetic basis
? The genes CDKN2A and CDK4 together make up 50% of all
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inherited familial cases? Other identified genes include p53, BRCA2
? 50% of familial melanoma patients have no identified mutation ?
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i.e., their genes have not been identified yet
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Clinical Manifestations
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? May cause symptoms, but 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
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areas, such as the buttock? Also occur on mucous membranes (mouth, genitalia)
? 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
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The ABCDEs of MelanomaSuspicious moles may have any of the following features:
ASYMMETRY
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? With regard to shape or color
BORDER
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? Irregular or notchedCOLOR
? Very dark or variegated colors
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? Blue, Black, Brown, Red, Pink, White
DIAMETER
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? >6 mm, or "larger than a pencil eraser"? Diameter that is rapidly changing
EVOLVING
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? Evolution or change in any of the ABCD features
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Superficial Spreading
17
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? Superficial spreading type
? Most common type
? Involves back in men; back and
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legs in women
? Growth of tumor is primarily
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horizontal rather than down into thedermis
Nodular
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? Nodular type
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? Rapid growth? Growth is vertical, giving tumor an
increased Breslow's depth
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? Breslow's depth = thickness of the primarymelanoma measured from the granular
layer of the epidermis to the deepest part of
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the tumor
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Lentigo Maligna
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? Lentigo maligna type
? Occurs on chronically sun-damaged
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skin, more common in elderlypatients
? Slow progression
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? Growth of tumor is primarilyhorizontal, and not vertical
Acral Lentiginous
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? Acral lentiginous type
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? More common in people with darkerskin color (Asians and persons of
African ancestry)
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? Diagnosis is often delayed, so
lesions tend to be many centimeters
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Amelanotic
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? Amelanotic type? Morphologic appearance is variable, and the clinical
appearance of pigment is subtle or often absent
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? As such, the lesion may be confused with a variety of
benign lesions, such as psoriasis or dermatitis
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? This lesion may also be confused with a variety ofmalignant lesions, such as squamous cel carcinoma in
situ or basal cel carcinoma
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? This is a difficult diagnosis to make, which is why it isimportant to biopsy when unsure of the diagnosis
Diagnosis
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Biopsy
Excision (Golden standard)
*ncision biopsy
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*Punch biopsyPartial thickness or shaving biopsies are contraindicated
*All dermis layers should be removed
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Balch CM, Houghton AN, Sober AJ, Soong S.
Cutaneous Melanoma. St Louis QMP 1998
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Staging (AJCC 7th Edition)--- Content provided by FirstRanker.com ---
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Clark Classification
Level I -- the atypical melanocytes are confined to the epidermis (in situ melanoma);
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Level II -- the atypical melanocytes have extended into the papil ary dermis but have notreached the reticular dermis;
Level III -- the atypical melanocytes have penetrated to the interface between the papil ary
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dermis and the reticular dermis but do not extend into the reticular dermis;
Level IV -- the atypical melanocytes have extended into the reticular dermis;
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Level V -- the atypical melanocytes have reached into the subcutaneous fat.--- Content provided by FirstRanker.com ---
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The histopathologic classification of the Melanoma by Clark
Breslow Classification
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Level 1: less than 0.76 mm thickLevel 2: between 0.76? 1.50 mm
Level 3: between 1.50 - 4.00 mm
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Level 4: exceed 4.00 mm in thickness
According to the thickness of the lesion as measured by an ocular micrometer from the top of
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the granular zone of the epidermis to the base of the neoplasm--- Content provided by FirstRanker.com ---
Prognostic Factors
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n Breslow thickness (most important)
n Clark invasion level
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n Ulcerationn Age, sex, location
n Size and surgical margins
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n Others (Mitotic index, growth phase, regression.. )
Surgical Treatment
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n Biopsyn Wide Local Excision
n Staging with Sentinel Lymph Node biopsy
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n Therapeutic Lymph Node Dissection
n Treatment of Distant Metastasis
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Wide Surgical Excision
Suggested surgical margins:
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(according to breslow thickness)
In-situ MM:
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0.5-1 cmBreslow thickness < 1mm : 1 cm
Breslow thickness 1-4 mm: 2 cm
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Breslow thickness >4 mm: > 3 cm
Sentinel Lymphadenectomy
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Sentinel Lymphadenectomy
Sentinel lymph node shows the regional node status
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If sentinel lymph node negative, others lymph nodes in the basin are also
negative
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If sentinel lymph node contains tumor cel s, It means disease spread to theregional nodal basin
Sentinel Lymphadenectomy
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Sentinel node negative
no additional treatment, follow the patient
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Sentinel lymph node positiveTherapeutic lymph node dissection
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Advantages of Sentinel Lymphadenectomy
n Provides staging
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n Prevention of Elective Lymph node dissection morbiditySites of Distant Metastasis
n Skin
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n Subcutaneous Tissuen Distant Lymph Nodes
n Pulmonary
n Liver
n Brain
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n Bonen Intestine
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Chemotherapeutic agents
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? Melphalan? Interferon
? Interleukin-2
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? Dacarbazine