MALIGNANT MELANOMA
Introduction
-Melanoma is a tumor that develops as a result of the
malignant transformation of melanocytes.
-Melanocytes cells are derived from the neural crest.
-Melanomas usually occur on the skin but can arise in
other locations where neural crest cells migrate, such as in the
gastrointestinal tract, eye or brain.
-Melanoma predominantly is an adult disease with a
peak incidence in the 4th decade
and no sex prevalence.
A patient's risk of developing a second primary
melanoma after diagnosis of the first one is 3-5%.
Incidence
-The
incidence is estimated to be rising rapidly by almost 6% per year.
Morbidity and Mortality
-Early
diagnosis and treatment before metastasis most important in management.
While only 5%
of skin cancers are melanomas, about two-thirds of all deaths from skin
cancer are due to melanomas
Etiology/risk factors
1.Family history
Positive
family history in 5-10% of patients
With
at least one affected relative, 2.2-fold higher risk
2.Personal characteristics
-Blue
eyes, fair and/or red hair, pale complexion
-Skin
reaction to sunlight - Easily sunburned
-Freckling
3.Benign and/or dysplastic melanocytic nevi
- Number rather than size has better correlation
4.Immunosuppressive states - Transplant
patients, hematologic malignancies
5.Sun exposure during adolescence
Ø High UV-B radiation
Ø Low latitude
Ø Number of blistering sunburns
6.Atypical mole syndrome (formerly
termed B-K mole syndrome, dysplastic nevus syndrome, familial atypical
multiple mole melanoma)
Pathophysiology
Benign
melanocytic nevi are markers of melanoma risk rather than direct precursors;
however, dysplastic nevi are believed to degenerate over time into melanoma.
Lentigo
maligna is believed to be a pre-invasive precursor of lentigo maligna
melanoma, and at least 5% progress to malignancy
Clinical
presentation
Patients
usually present with skin lesions that have changed in size, color, contour,
or configuration. The acronym "ABCDE" is the hallmark of
international public awareness campaigns and may be used to remember the
physical characteristics suggestive of malignancy. ABCDE stands for
A-Asymmetry of shape
B-Border irregular
C-Color
variations (especially red, white, and blue tones in a brown or black lesion)
or deepening of pigmentation
D-Diameter
greater than 6 mm(size),or recent increase in size
E-Elevated
surface, erosions or ulcerations, bleeding ,crusting
Other
symptoms of the lessions
Ø Itching, pain,ulcerate, Bleed, Develop satellites
Biopsy
-Perform biopsy on all
lesions suggestive of melanoma in the thickest part.
-If the resection will not
result in a disfiguring defect, excisional biopsy with a 2-cm skin margin and
extending to the subcutaneous tissue is suggested for lesions less than 1.5
cm in diameter.
-If the lesion is large or
located in an anatomic area where skin removal would cause disfigurement, an
incisional biopsy may be performed.
-A full-thickness core punch
biopsy in the most raised or irregular area is suggested with the
understanding that this area may not be the thickest area.
Skin anatomy
Four major types of melanomas exist based on growth pattern.
1.
Superficial spreading melanoma
2.
Nodular melanoma
3.
Lentigo maligna melanoma
4.
Acral lentiginous melanoma
Other more unusual types include mucosal lentiginous
melanoma, desmoplastic melanoma, and verrucous melanoma.
1.Superficial spreading melanoma
Commonest up to 70% of melanomas in white population. Histologically
Ø Appear singly or in nests along the dermal-epidermal
junction
Ø May migrate
into the stratum granulosum or stratum corneum
Ø These cells
can invade the papillary dermis with an inflammatory lymphocytic infiltrate.
Clinically
Ø Usually arise in a preexisting dysplastic nevus.
Ø Typically, this lesion changes slowly over several
months to years.
Ø They are usually flat but may become irregular and
elevated in later stages.
Ø The lesions average 2 cm in diameter with variegated
colors and peripheral notches and/or indentations.
2,Nodular melanoma
They comprise approximately 15-30% of melanoma
Histology
Ø Characterized by extensive vertical growth into the
dermis with a minimal radial component.
Clinical
Ø These tumors typically are blue-black but may lack
pigment in some circumstances.
Ø They are known to arise without a preexisting lesion.
May develop at the site of a preexisting nevus and rapidly becomes a
palpable, elevated, firm nodule
Breslow classification -Thickness of
lesion
Stage 1Thickness of 0.75 mm or less
Stage 2
Thickness of 0.76-1.50 mm
Stage 3
Thickness of 1.51-4.00 mm
Stage 4
Thickness greater than 4.00 mm
Clark classification
Level I -
Involves only epidermis (in situ melanoma); no invasion
Level II -
Invades papillary dermis
Level III – Papillary-reticular
dermis interface
Level IV - Invades reticular dermis
Level V -
Invades into subcutaneous tissue
TNM classification
Primary tumor (pT)
pTX - Primary
tumor cannot be assessed
pT0 - No
evidence of primary tumor
pTis - Melanoma
in situ (Clark level [CL] I)
pT1 - Tumor 0.75
mm or less in thickness; invades papillary dermis (CL II)
pT2 - Tumor
0.76-1.50 mm in thickness and/or invades to papillary-reticular dermal
interface (CL III)
pT3 - Tumor
1.51-4.00 mm in thickness and/or invades reticular dermis (CL IV)
pT3a - Tumor 1.51-3.00 mm in thickness
pT3b - Tumor 3.01-4.00 mm in thickness
pT4 - Tumor
greater than 4.00 mm in thickness and/or invades subcutaneous tissue (CL V)
and/or satellite(s) within 2 cm of the primary tumor
pT4a - Tumor
greater than 4.00 mm in thickness and/or invades subcutaneous tissue
pT4b -
Satellite(s) within 2 cm of primary tumor
Regional lymph nodes (N)
NX - Regional
lymph nodes cannot be assessed
N0 - No regional lymph node metastasis
N1 - Metastasis
3 cm or less in greatest dimension in any regional lymph node
N2 - Metastasis
more than 3 cm in greatest dimension in any regional lymph node(s) and/or
in-transit metastasis N2a - Metastasis more than 3 cm in greatest dimension
in any regional lymph node(s)
N2b - In-transit
metastasis
N2c - Both N2a
and N2b
Distant metastasis (M)
MX - Distant
metastasis cannot be assessed
M0 - No distant metastasis
M1 - Distant
metastasis
M1a - Metastasis
in skin or subcutaneous tissue or lymph node(s) beyond the regional lymph
nodes
M1b - Visceral metastasis.
Stage III
-Wide local excision of the primary tumor with 2-cm
margins remains the first-line therapy.
-. Skin grafting or other
tissue-transfer technique may be necessary to close the defect.
-Perform regional lymph node
dissection, since a stage III melanoma represents nodal disease.
- If the nodal status is
unknown, consider a sentinel lymph node biopsy to determine if the disease is
stage I, II, or III.
-As in stage II disease, a
higher rate of treatment failure exists with wide local excision alone in
this group compared to stages 0 and I. Many clinical trials currently are
exploring similar options as adjuvant therapy.
Stage IV
Advanced metastatic melanoma
usually is refractory to standard therapy; thus, consider these patients for
clinical trials.
Some treatments have
reported various objective responses, although they usually are short lived.
Dacarbazine (DTIC) and the nitrosoureas, carmustine (BCNU) and lomustine
(CCNU), produced a 20% objective response rate.
Response rates for
interferon alfa and interleukin-2 range from 8-22% and 10-20%, respectively.
Currently, other studies in progress are comparing other cytotoxic and biologic
drug regimens.
Prognosis
1) Size of the tumor and the depth of invasion. Small
tumors with minimal invasion (< 0.7 mm) are usually curable by wide local
excision.
2) The prognosis is usually favorable in lentigo maligna
melanoma and in superficial spreading melanomas without deep invasion. Most nodular
melanomas, particularly if ulcerated and associated with deep invasion, have
a poor prognosis.
3) Lesions of the extremities have a more
favorable prognosis than those of the trunk, and
4) women with malignant
melanoma have better survival statistics at 5 and 10 years than
men.
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Pigmented Lesions
-The appearance of a new pigmented nevus should arouse
suspicion of melanoma.
-About one-third of all melanomas arise
from pigmented nevi.
-Since the average white adult has 15-20 nevi, a clear idea of the indications for biopsy or
excision should be developed. Recognition and early excision of atypical
pigmented lesions are potentially lifesaving, since
surgery is the only effective treatment.
Benign
/common naevi
Junctional
nevi
-Are usually small, circumscribed, light
brown or black, flat or only slightly elevated, and rarely contain hair. They
are found on all areas f the body, and moles of the mucous membranes,
genitalia, soles, and palms are usually of this type.
-The nevus cells are located in the
epidermis and at the dermal-epidermal junction.
Intradermal
nevi
-Range from
small spots to extensive areas covering much of the body.
-Have variable shape and surface configuration, are
usually brown or black, and often are slightly elevated.
-Nevus cells are confined to the dermis, and the
lesions are basically benign.
Compound
nevi have both junctional and intradermal elements.
Blue
nevi
-Are circumscribed, flat or dome-shaped,
bluish-black lesions, usually on the hands, face, or arms.
-Although benign, they may closely
resemble nodular melanoma and require diagnostic excisional biopsy.
Premalignant
lesions
Dysplastic nevi
Are larger (5-12 mm) than common nevi.
-They have macular and papular
components, are variegated in color (tan-brown) on a pink base, and have
indistinct, irregular edges.
-Unlike common nevi, dysplastic nevi are
most prevalent on covered body areas, though they can appear anywhere. Any
suspicious lesions should be excised. An accurate family history should be
obtained in such cases, and first-degree relatives should be examined.
Congenital
nevi
-Occur in about 1% of newborns, and most lesions are
small.
-Along with dysplastic nevi, these lesions are now
classified as precursors of melanoma.
-Lifetime risk of melanoma developing in large congenital
nevi (> 20 cm) is 5-20%, with some increased risk in smaller lesions as
well.
-Prophylactic excision is cosmetically
prohibitive in many cases, and these lesions must be carefully monitored for
suspicious change.
Other pigmented lesions, including basal
cell carcinomas, seborrheic keratoses, and actinic keratoses, occasionally resemble
melanoma and require biopsy for diagnosis.
3..Lentigo maligna
melanoma
-4-10% of melanomas. Show dermal and epidermal
changes from sun exposure.
Clinical.
Ø Larger than 3 cm
Ø Flat, tan, and begin as small, freckle-like lesions.
Ø They occur in sun-exposed areas (eg, face and neck of
older individuals).
Ø Marked notching of the borders is present.
-Lentigo maligna melanoma usually arises within a Hutchinson freckle
(lentigo maligna).
The histologic appearance
Ø Irregularly shaped hyperchromatic cells that form
spindle-shaped nests.
Ø The epidermis is atrophic
Ø The dermis contains solar elastosis with chronic
inflammatory infiltrates.
5.Acral lentiginous melanoma
This tumor comprises 2-8% of melanomas in whites and
35-60% of melanomas in dark-skinned people.
Histology
Ø Occur in dermal-epidermal junction with microinvasion
into the papillary dermis.
Ø The cells have increased melanin granule production,
which fills their dendritic extensions.
Clinical
Ø Occur on the palms of the hands, beneath the
nailbeds, and on the soles of the feet.
Ø They may appear as flat, tan, or brown stains with
irregular borders on the palms and soles
Ø Subungual lesions can be brown or black, with
ulcerations in later stages.
No correlation with a worse prognosis is demonstrated
for these lesions when tumor thickness is considered.
6.Desmoplastic melanoma
-These lesions account for approximately 1% of
melanoma cases; they are fairly rare.
- They demonstrate a tendency for perineural
invasion, especially in the head and neck.
Classification
and staging
Two classification schemes have been developed, based
on either:
1.The vertical
thickness of the lesion in millimeters (Breslow classification)
2. The anatomic
level of invasion of the layers of skin
(Clarks
staging)
Breslow classification scheme is used almost
exclusively now since it more accurately predicts future tumor behavior.
The TNM (tumor, node, metastasis) system is used for
clinical staging
Management
Surgical therapy-wide margin excision. If the lesion
has not spread beyond the primary site, it is potentially curable.
Stage
I
For a T1
lesion, 1-cm excision margins are adequate, but lesions greater than 1 mm
require 2-cm margins. Studies demonstrate no improvement in recurrence or
survival rates with larger margins of resection. Attempt primary closure and
perform skin grafting or flap closure if necessary. For lesions with a depth
greater than 1 mm, many recommend sentinel lymph node biopsy at the time of
wide local excision (see "Stage II," below).
Stage
II
Perform
a 2-cm surgical resection on stage II lesions. No recurrence or survival
advantage exists when 2-cm margins are compared to wider margins (4-6 cm).
Smaller
resection decreases the need for skin grafting and inpatient hospital stay.
-Perform
a complete therapeutic lymphadenectomy on patients with suspected lymph node
metastases based on physical examination. This consists of excision of all
lymph nodes in the affected regional lymph node basin.
-Consider
sentinel lymph node biopsy if no clinically positive nodes are present. Using
blue dye and/or radioisotope injected at the site of the primary melanoma,
the first-echelon node can be identified within the regional lymph node
basin. Send this sentinel node to the pathologist for analysis using routine
stains, immunohistochemistry, and even polymerase chain reaction in some
centers.
-If the
sentinel node is positive, then predictive importance exists of regional
lymph node metastases; perform a complete lymph node dissection.
-The correlation is based on the thickness of the
primary tumor. If the sentinel lymph node is negative, a 99% chance exists
that all others are negative. This procedure is becoming the standard of care
for tumors greater than 1 mm in depth.
-Hyperthermic
arterial limb perfusion with melphalan for extremity melanomas has been
studied as an adjuvant therapy. One study found it to be beneficial in that
it produced higher response rates and overall survival rates than those for
surgery alone. Other studies do not demonstrate benefit.
-Adjuvant
chemotherapy and/or biological therapy also are under clinical evaluation.
One study demonstrated that high-dose
interferon alfa-2b resulted in prolonged relapse-free survival and
overall survival compared to no adjuvant therapy. A follow-up study by the
same group demonstrated in preliminary results that high-dose interferon
offered patients a relapse-free survival benefit over patients who did not
receive adjuvant treatment but not over those who received low-dose interferon.
-Neither
high-dose nor low-dose interferon had a significant overall survival
advantage compared to observation alone. High-dose interferon can be
associated with significant toxic side effects (ie, liver toxicity), and some
patients require dose reduction since it may not be well tolerated.
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doctors notes
medical notes for university students pursuing a medical and clinical career.
Sunday, 10 June 2012
MALIGNANT MELANOMA
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