Download Malignant Melanoma Update 1993

VOLUME 26, No. 2 SUMMER 1994
JOURNAL OF INSURANCE MEDICINE
MALIGNANT MELANOMA UPDATE 1993
CHARLES W. LYNDE, MD, FRCP(C)
Acting Head of Dermatology
Toronto Western Hospital
Assistant Professor of Medidne
University of Toron to
President
Lynde Center for Dermatology
Introduction: Statistics
There has been a dramatic increase in the incidence of
melanoma throughout the world.
of incidence among women. Malignant melanoma is the
number one cancer in white women age 25-29, second
most prevalent in women age 30-35, second only to
breast cancer. This rate of increase in the incidence of
this disease is not just a specific flare or matter of more
cases suddenly being reported.
In the United States the incidence of melanoma has
almost tripled in the past four decades growing faster
than that of any other cancer. It now ranks number eight Melanoma counts for only 5% of the cases of skin canto all types. No major change in diagnostic criteria can cers but counts for the majority of skin cancer deaths.
explain this rapid increase. Approximately 32,000
Americans developed melanoma in 1991 and 6,500 died While the numbers of people getting melanoma has yet
of it. In terms of the life time risk, in 1935 it was one in to show much positive change, there are changes in the
1,500 and it is now felt that by the year 2,000, 1 to 75 to 5-year survival rate for those who have the illness. In
90 Americans will develop melanoma of which I in 300 British Columbia, between 1970-74 for example, the
will die.
5-year survival rate for men was 65%, by 1984 it increased to 82%. The survival rate for women during the
In terms of Canadian statistics, they are comparable, our same period increased to 88% from 80%. Similarly, in
population being approximately a tenth of the U.S. the U.S., while the death rate has continued to increase
population. Approximately 3,100 new cases of malig- with increased incidence 5 years, survival has more
nant melanoma will be diagnosed in 1993 in Canada than doubled from 40% in the 1940’s to over 80% in the
with 540 deaths resulting from this condition.
1980’s.1’2 The increase in survival is felt to be attributable to early diagnosis on the part of physicians and the
Overall the incidence of malignant melanoma (Canada) public.
is now 9 per 100,000 population although incidence
varies from a high of 14 per 100,000 in British Columbia Unlike many other forms of cancer which affect primarto I per 100,000 in Newfoundland. (By comparison, the ily older people, melanoma frequently affects young
incidence of lung cancer is now 73 per 100,000.) While people. The median age for patients with melanoma is
the mortality rate for melanoma is increasing, it is hold- in the low 40’s. Thus, diagnosis and cure of cutaneous
ing steady and even appears to be decreasing among
melanoma in young individuals can lead to dramatiwomen. In the U.S., of the 6,800 deaths in 1993, 4,200 cally increased life extension unachievable in cancers
(62%) will be in men and 2,600 (38%) will be in women.that primarily affect older individuals.
This is felt to be partly as result of women being more
health conscious and taking better overall care of them- Epidemiology
selves.
The precise causation of melanomas is unknown, alThis tells us that men are still one of the main groups though epidemiologic and case control studies suggest
we have to address to let them know that they are the
sunlight is the most important environmental factor in
ones who are dying disproportionately from this dis- the pathogenesis of melanoma with radiation in the
ease.
ultraviolet B range proposed to be the critical component.
Malignant melanoma has the fastest growing incidence
rate of all cancers among men, the third fastest increase
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MALIGNANT MELANOMA UPDATE 1993
The incidence of melanoma in whites generally corre- compounded by the phenotype of the population. Rates
lates inversely with latitude; i.e., rates are higher closer of melanoma are relatively low in persons with outdoor
to the equator and progressively lower in areas near the occupations, but much higher in middle class people
poles. In the Eastern Australia Mole Stud~ Jason Rivers, with high recreational exposure. Except for lentigo maet al,3 recruited a total of 1,123 caucasian children be-ligna; melanoma does not regularly occur on skin most
tween the ages of 6-15 years old in three cities along a exposed to the sun, such as the face. One would also
latitude gradient Melbourne 38 S, Sydney 34 S, Towns- have to explain mucosal melanoma. Equally aside from
ville 19 S. For each child the age, sex, eye and hair color, one single report, studies using ultraviolet light alone
skin reflectance, response to sun exposure, ability to tan,
have failed to induce melanoma regularly in animals.
and place of residence were determined. Each student The body of evidence supports the risk of melanoma
was examined by one of three trained medical ob- depends more on the intermittent exposure to the sun,
servers, and the total number of moles greater than 2 especially earl in life than on simple cumulative expomm were recorded for all body sites excluding the sure. One has to think about the increased recreational
genitalia and scalp. The average number of moles for exposure to the sun, the depletion of the earth’s ozone
the entire cohort was 44. Older children and those with layer increasing ultraviolet penetration to the earth and
blue eyes, light hair, fair skin, many freckles, and a the increased use of sunbeds and tanning parlors.
tendency to painful burns with peeling, and an inability
to tan had significantly more moles than children with- Loraine Marrett, et al4 in 583 case controls in southern
out these features. As well, the number of moles in- Ontario have further identified that people with a large
creased as one lived closer to the equator. This latter number of nevi, who have red or blond hair, having a
factor remained a significant independent risk factor history of freckling in response to sun exposure and
after controlling for age and phenotypic characteristics. burn with no tan after repeated sun exposure are parThese results indicate that in the Australian population ticularly at high risk. Interestingl)~ in their study it was
at very high risk for melanoma, school children have also suggested that exposure to fluorescent lighting
very large numbers of melanocytic nevi. The geo- may also be a risk factor. Other studies have found this,
graphic variation in mole counts would support a solar but dismissed it as a confounding factor.
ultraviolet radiation role in the causation of these leIn the past, melanoma was notorious for its poor progsions. The phenotypic characteristics that predispose
one to the development of moles in childhood are simi- nosis. The current 5-year survival rate of 80% is a great
lar to those that increase one’s risk for melanoma in later improvement over the 50% rate in 1950. Nevertheless,
life.
the overall mortality rate has increased by 150%, driven
up by the rising incidence rate.
Other investigators have linked blistering sunburns in
childhood or adolescence with increased rates of mela- We Wish to Win the War on Melanoma
noma in later life. Whites, especially those with a tenSeveral advances have dramatically improved our abildency to bum rather than tan when exposed to sunlight,
have higher rates of melanoma than nonwhites. Migra- ity to diagnose and treat melanoma.
tion studies by other investigators suggest that childhood or adolescence represents a critical period for
1) Recognition of Melanoma
ultraviolet burn. Australian children less than age 15
who migrated to Britain maintained high rates of ma- The first was to recognize that melanoma has distinct
lignant melanoma, whereas children from England who clinical features: The great physician Hippocrates reccame to Australia after age 15 had low rates of malig- ognized and described melanoma, and since then varinant melanoma.
ous names, including melano sarcoma, melano
carcinoma, Kaposis melano sarcoma, have been used to
Xeroderma pigmentosa, a rare autosomal recessive dis- describe this tumor.
order characterized by deficient repair of ultraviolet B
damaged DNA shows a greater than 100-fold higher It really wasn’t until the 1960"s or 70"s that we began to
rate of skin cancer and, in particular, primary melano- understand this tumor, recognizing its melanocytic orinlas.
gin and began to classify it and recognize its distinct
clinical features.
Not all evidence readily links ultraviolet light to melanoma, however. In some countries the incidence of ma- Cutaneous melanoma is a visible tumor and therefore
lignant melanoma, i.e. Europe, does not rise with perhaps more easily discovered in an asymptomatic
increasing proximity to the equator, but this may be phase than any other type of cancer. The early detection
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JOURNAL OF INSURANCE MEDICINE
and recognition of malignant melanoma is the key to
possible cure!
Lentigo Maligna
This often starts as a tan macule that extends peripherMelanoma writes its message in the skin with its own ally and darkens and eventually develops a black nodink and is there for all to see.
ule. The growth is extremely slow and insidious and
often occurs over 5-20 years. It is found equally in men
The ABCD rule has been established for the possible and women usually in their 60/70 decade, most frediagnosis of melanoma in any pigmented lesion. The A quently on the face and particularly on sun damaged
stands for asymme~t, B for border irregularity, C for skin. It represents 5% of all melanomas.
color variegation, often in a dark blue color, D for diNodular Melanoma
ameter being greater than 0.6 cm.
The rapid enlargement of a mole, the development of
raised areas on a previously fiat lesion, scaling, ulceration, crusting, bleeding, itching, burning, or pain should
alert the physician to possible change within the nevus
and the possibility of melanoma.5’6
This presents a very pigmented papule or dome-shaped
nodule that grows rapidly over a few months and arises
without a radial growth phase. It represents 15% of all
melanomas, is two times more frequent in men and
occurs in sun exposed head, neck and trunk areas. This
tumor arises de novo and the ABCD rule does not apply
However, most melanomas are completely asympto- in this case, as the growth is so rapid.
matic. Visual examination is the most reliable means of
identification. Melanoma can occur anywhere on the Acral Lenfiginous Melanoma
surface of the skin. It is often found on the back and
other areas that are difficult for a person to inspect This presents as an irregularly enlarging macule parthemselves. Patients with melanoma may thus be un- ficularly on the tips of the toes, fingers subungually and
aware that a lesion exists. Early detection by the physi- on the mucosa of the vagina, orally in the palate, on the
cian is exceedingly important.
glans penis or the anal canal. It represents 10% of all
melanomas. In Japanese (particularly the soles), in
2) Melanoma Subtypes
Blacks, Hispanics, and American Indians, it is the commonest type.
The second advance was the recognition that melanoma
can be classified into four major subtypes. Superficial Melanoma Look-Alikes
spreading melanoma, Lentigo maligna melanoma,
nodular melanoma and the newly described acral len- It is important to note that there are a number of skin
tigenous melanoma. These subtypes are useful in offer- lesions that are seen by physicians that can mimic melaing prognosis and therapy.
nomas. These include seborrheic keratoses, solar lentigines, pigmented basal ceils, pyogenic granulomas,
and angiokeratomas to name but a few. With the use of
Superficial Spreading Melanoma
oil and a magnifying lens on one’s ophthalmascope, one
This is the commonest type of melanoma representing creates an epi or dermatoscope and can improve one’s
over 70% of all the melanomas. The title is actually a ability to distinguish benign and malignant lesions.
misnomer as this does not always stay superficial; after However, the old surgical dictum holds that, "When in
a horizontal growth phase, it eventually develops a doubt, cut is out." Upon providing patholog~ one can
vertical growth phase and potential metastases. It af- have a definite answer.
fects adults of all ages, the median being in the fifth
decade. We see this particular type of melanoma tend- 3) Precursor Lesions
ing to occur at earlier and earlier ages. There is no
preference for sun damaged skin; the upper back is a The third advance was the recognition of precursor
favorite site in both sexes, and shin and calves in fe- lesions -- dysplastic nevi. Dysplastic nevi were first
males is an extremely common site also. These melano- described in 1978.7 Dysplastic nevi are both markers for
mas are often multicolored, showing many different an increased risk of melanoma and potential precursor
lesions from which melanoma may develop.
shades of pigmentation, and patients often present because their mole appears "ugly." The horizontal growth
phase is often over a year, then followed by a vertical Disagreements and precise reproducible definitions
growth phase. These tumors can have extremely rapid and dinpathical correlations of dysplastic nevi have
growth and metastases.
hindered efforts to determine their prevalence and
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MAL~G~hrr M~A~O~ UPOA’r~ 1993
proper management. In general, dysplastic nevi are
larger than common nevi and have clinical features of
haphazard pigmentation, irregular borders that are
quantitatively not as extreme as a melanoma.
4) Tumor Thickness = Prognosis
Dysplastic nevi were initially described in family pedigree studies. Persons with a familial dysplastic nevus
syndrome have a high risk of melanoma. In fact, ff you
have dysplastic nevus syndrome and two or more first
degree relatives with melanoma, your lifetime risk of
melanoma is 100%.8,9 Characteristics of familial dysplastic nevus syndrome include a family history of
melanoma or dysplastically acquired moles with characteristic pathologic dysplasia, moles present in unusual places, such as a breast or pubic area, and the
occurrence of new moles throughout life. Between 510 % of the population without a family history of melanoma have multiple dysplastic nevi. Their risk for
melanoma is unknown, although it has been estimated
at 18% over lifetime, as compared to the general population’s risk of less than 1%. The diagnosis of dysplastic
nevus is not difficult; the mole shows variation of outline and color and contrasts the dermal nevi which are
well circumscribed and evenly depigmented. It is really
fiat, although elevated areas in the center may occur.
In 1969, Clark and From were the first to link poorer
prognosis with increasing levels of microinvasion into
the dermis or subcutaneous tissue. They described five
levels of invasion, so called Clark’s Levels 1-5. Since
then, in 1970, Breslow has found a better predicator with
the vertical tumor thickness. With this, one can prognosticate a 5-year survival rate with those thin lesions less
than .76 mm having a 96% 5-year survival rate, and
those over 4 mm having a survival rate of only 47%, i.e.,
the thicker lesions would be more likely to develop
metastatic disease.
The fourth advance was the ability to predict patient
outcome from measurements of the primary tumor.
In addition to tumor thickness, which is felt to be the
best prognosticator, anatomical site also seems to play
a role, although which sites are at highest risk is somewhat a matter of debate. For an equivalent thickness,
those on the scalp, hand and feet seem to have a poorer
prognosis.
Older patients have a worse prognosis than younger.
Women better prognosis than men, although this probA dysplastic nevi patient should be followed, particuably reflects difference in the thickness site. Histologilarly, one with a family history of melanoma or dysplas- cally, a high mitotic rate, ulceration, large tumor
tic nevi. When dysplastic nevi are found on one patient volume, DNA aneuploidy all produce a poorer prognoand another family member has had a melanoma, all sis.
members of the immediate family should be thoroughly
examined for lesions.
Overall, in stage I, the 5-year survival rate if 79% and
decreases rapidly with state II (nodal mets) being 36%
The dysplastic nevus syndrome has now been called the
and stage HI (distant mets) 5%. State II disease at the
"atypical mole syndrome," and there have been various present time is felt to be incurable with the median
classifications made in an attempt to prognosticate survival rate being less than 6 months.
those at higher risk. One such recent classification is that
of group ) dysplastic nevus with no family history or 5) Less Surgery Necessary
personal history of melanoma, group I with a personal
history of melanoma, group 2 with a family history of The fifth advance was the demonstration that less mumelanoma and group 3 where two or more family mem- tilating surgery for melanomas is as curative as the more
bers have had melanoma.
radical procedures used in the past. This improvement
has been helped by the prognostic system by which low
Many physicians feel that only by paying particular risk patients can be treated with relatively narrow exciattention to the subsets of patients and following them
sion margins (one cm).11
closely will we be able to make some inroads in decreasing mortality from melanoma.
Melanoma is a multidisciplinary disorder that brings
together practitioners of many medical specialties: derGiant congenital melanocytic nevi rarely can transform matologists, oncologic surgeons, plastic surgeons,
into melanoma, although some people put the risk at medical oncologists, radiation medicine physicians,
6-7% lifetime risk of transformation. Others feel the risk epidemiologists, geneticists, pathologists, immunolois much smaller than this, and particularly in smaller gists, molecular biologists, public health officers, genlesions the risk is felt to be quite low.
eral physicians, pediatricians, and gynecologists, all of
whom bring their own unique approach to the problems. Each of these groups has a role to play in the
JOURNAL OF INSURANCE ME~ICINE
VO~.UME 26, NO. 2 SUMMER 1994
evaluation of causation, early detection, prevention, nately, efforts in immunotherapy or chemotherapy to
and treatment, and it is through synergistic multidisci- present have not been useful.
plinary interaction that many of these advances have
Melanomas are not likely to decrease in the next decade.
been achieved.12
Melanoma is not a disease to be feared but one that can
How to Win the War
be detected early and cured...The war can be won.
Areas of attack to reduce melanoma mortality include
several strategies.
1) Professional Education
The first is professional educational awareness about
the nature of the problem and the clinical features for
diagnosis.
Recent research has shown that, as a screening tool,
cutaneous examination by a dermatologist has a semitivity for melanoma detection that is at least as high as
that of the Pap smear, the stool guaiac test, and mammography for cervical, colorectal,a nd breast cancers,
respectively.13
2) Public Awareness
Individuals likewise should be aware of the problem
and taught self examination. Twenty percent of melanomas are being detected by individuals other than the
patient, such as spouses, friends, and physicians.
3) Prevention
This is a critical focus. The Canadian Dermatology Association, American Academy of Dermatology and
Cancer Societies are sponsoring several sun safety programs particularly aimed at young children.
REFERENCES
1. Boring CC, Squires TS, Tong T. Cancer statistics, 1991. CA
1991;41:19-36.
2. Cutler SJ, Myers MI-I, Green SB. Trends in survival rates of
patients with cancer. N Engl J Med 1975;293:122-124.
3. Rivers J, Kelly J, MacLennan R. Eastern Australia Mole Study.
Melanoma Letter 193;Vl1(2):1.
4. Marrett L, King W, Waiters S, From L. Use of host factors to
identify people at high risk for cutaneous melanoma. Can Med Assoc
11992;147(2):445-453.
5. Mihm MC Jr, Fitzpatrick TB, Brown MM, et al. Early detection
of primary cutaneous malignant melanoma" A color atlas. N Engl ]Med
1973;289:989-996.
6. Friedman RJ, Rigel DS, Silverman MK, et al. Malignant melanoma in the 1990s: The continued importance of early detection and
the role of physician examination and self-examination of the skin. CA
1991;41:201-226.
7. Reimer RR, Clark WH Jr, Green MH, et al. Precursor lesions in
familial melanoma" A new genetic preneoplastic syndrome. JAMA
1978;239:744-746.
8. Tiersten AD, Grin CM, Kopf AW, et al. Prospec~_ive follow-up
for malignant melanoma in patients with atypical-mole (dyspiasticnevus) syndrome. J Dermatol Surg Oncol 1991;17:44-48.
9. Albert I~q, Rhodes AR, Sober AJ. Dysplastic melanocytic nevi
and cutaneous melanoma: Markers of increased melanoma risk for
affected persons and blood relatives. ] Am Acad Dermatology
1990;22:69-75.
10. Breslow A. Thickness, cross-sectional areas and depth of invasion in the prognosis of cutaneous melanoma. Ann Surg 1970;17~’902908.
11. Veronesi U, Cascinelli N, Adamus J, et al. ~ stage I primary
cutaneous malignant melanoma: Comparison of excision with margins of I or 3 cm. N Engl J Med 1988;318:1159-1162.
It is hoped by developing good sun safety habits early
12. Sober A. Cutaneous melanoma" Opportunity for cure. CA-A
in life, these habits will carry through into adolescence Cancer l fvr clinicians 1991;V41(4):197-198.
13. Koh HK, Caruso A, Gage I, et al. Evaluation of melanoma/skin
and adult life.
cancer screening in Massachusetts. Preliminary results. Cancer
1990;65:375-379.
4) Research
Only by ongoing research into all aspects of melanoma
will we further understand this "black tumor." Unfortu-
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