Early Detection of Malignant Melanoma:The Roleof PhysicianExaminationand Self-Examinationof the Skin

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1 Early Detection of Malignant Melanoma:The Roleof PhysicianExaminationand Self-Examinationof the Skin Robert J. Friedman, M.D. Darrell S. Rigel, M.D. Alfred W. Kopf, M.D. Introduction Malignant melanoma is the leading cause of death from diseases of the skin. In 1985, about 22,000 people will develop newly recognized malignant melanomas; 5,500 people will die of the disease.' This ac counts for about 74 percent of all deaths from cutaneous cancers. The mortality rate from malignant melanoma is increasing faster than that of any other cancer except lung cancer.2 In the United States, about one in 150 people will develop a malignant melanoma during his or her lifetime, and this rate is esti mated to increase to one in 100 by the year Dr. Friedman is Clinical Instructor in the De partment of Dermatology of New York Univer sity School of Medicine, and Co-Director of the Pigmented Lesions Section, Oncology Section, of the Skin and Cancer Unit of New York Uni versity Medical Center, in New York, New York. Dr. Rigel is Clinical Instructor in the Department of Dermatology of New York University School of Medicine, and Co-Director of the Pigmented Lesions Section, Oncology Section, of the Skin and Cancer Unit of New York University Medi cal Center, in New York, New York. Dr. Kopf is Clinical Professor in the Department of Dermatology of New York University School of Medicine in New York, New York. This article was prepared in conjunction with the Task Force on Preventive Dermatology of the American Academy of Dermatology, and the American Cancer Society. There are two principal ways to reduce the morbidity and mortality from cuta neous malignant melanomas. The most di rect method would be to reduce the number of new tumors by identifying, eliminating, or counteracting the many factors that promote the development of malignant melanomasâ e.g., genetic influence, ex cessive exposure to ultraviolet light, im munologic defects, oncogenic viruses, and chemical carcinogens. Despite the many important research efforts designed to identify causal and promoting factors, however, this preventive strategy does not hold great promise for the short run. Thus, in 1985 and in the immediate future, the most important method of at tacking malignant melanoma is diagnosis at an early stage when the prognosis for cure by surgical removal is excellent. By performing careful, periodic, complete cu taneous examinations, by teaching patients the technique of routine self-examination of the skin, and by proper and timely use of diagnostic aids (particularly biopsy of the skin), physicians can improve the chances for early diagnosis and prompt eradication of malignant melanoma. Importance of Early Diagnosis The early diagnosis of malignant mela noma cannot be overemphasized.3-9 There is much evidence that thin malignant mel anomas have an excellent prognosis.3-'â 130 CA-A CANCERJOURNALFORCLINICIANS

2 C a U a Years Fig. 1. Ten-yearsurvival rate of patients with malignant melanoma (all stages), by lesion thick ness. Source: New York University Melanoma Cooperative Group, Breslow, in his fundamental study pub lished in 1970, showed that metastases did not develop in patients with malignant mel anomas less than 0.76 mm thick.â The excellent prognosis for patients who have such thin lesions excised has been repeat edly confirmed by others.'2â 9 Our experience with patients regis tered in the New York University Mela noma Cooperative Group2Â has been a 10-year survival rate of 99.5 percent for all stages of malignant melanoma less than 0.76 mm thick. In contrast, the rate was only 48 percent for those with malignant melanomas three mm and more in thick ness (Fig. I). There are, of course, rare exceptions, but the earlier the diagnosis â that is, the thinner the malignant melanomaâ and the earlier the surgical treatment, the greater the survival rate. Therefore, although we currently do not have the ability to prevent the development of malignant melanoma, we do have the ability to reduce the death rate from ma lignant melanoma to near zero through the recognition of such lesions when they are thin and virtually 100 percent curable by surgery. Patients can also participate in the identification of early malignant melano mas by using a thorough, easily taught method of cutaneous self-examination (de scribed on pages 141 and 146 to 150). Basic Factors in Early Diagnosis To make an early diagnosis, the physician must have a high index of suspicion for VOL.35,NO.3 MAY/JUNE

3 history of sunburns, and susceptible age. CommonBenignPigmentedLesions The most frequently encountered pig mented lesions are simple lentigines, â œ common molesâ (i.e., melanocytic nevi junctional, compound, intradermal), solar lentigines, and seborrheic keratoses. Fig. 2. Simple lentigo. Sharply defined, black reticulated, macular lesion with sharp jagged borders. â..â.. â œ 4 - lili@llflilfpfiirliif@ill@l1ltlijlfii1i.,,i1 SPECIMEN â _@_ DATE Fig. 3. Junction nevus. Sharply defined tan to brown macule. this tumor and thorough knowledge of: e The clinical characteristics of early ma lignant melanomas. â The clinical features of the common types of pigmented lesions that must be dif ferentiated from malignant melanomas. â The characteristics of precursor le sionsâ e.g., dysplastic nevi and certain congenital melanocytic nevi â thatmay give rise to malignant melanoma. â Other factors that increase the risk of developing a malignant melanoma e.g., familial history of malignant mel anoma, many melanocytic nevi, exces sive sun exposure, light complexion, Simple Lentigo (Fig. 2) A simple lentigo is a small (one to five mm), pigmented lesion. It is the initial stage of development of a common mole. The simple lentigo is a sharply defined, round, brown to black, macular lesion with smooth or jagged edges that may appear anywhere on the surface of the skin. The pigmen tation often has a reticulated (net-like) pat tern. Such a lesion generally arises in childhood but may appear later. Some sim ple lentigines are clinically indistinguish able from junctional nevi. Junctional Nevus (Fig. 3) A junctional nevus is generally a small (less than six mm, about 0.25 inch), macular, well-circumscribed, pigmented lesion with a smooth surface and relatively uniform pigmentation that ranges from light brown to very dark brown to black. It may appear at any site on the surface of the body, but occurs most often on areas exposed to the sun. A junctional nevus usually arises in childhood, but may lescence and young adulthood. It may per sist throughout adulthood in a junctional position or may develop into a compound or intradermal nevus as its cells proliferate and extend into the dermis (Fig. 4). Rarely do junctional nevi develop in people over the age of 40. The development of a mac ular, pigmented lesion in someone older than 40 years should alert the physician and patientâ to the possibility that it is an early malignant melanoma (Figs. 5a and Sb). Compound Nevus (Fig. 6) A compound nevus is generally a well 132 CA-ACANCERJOURNALFORCLINICIANS

4 Fig. 4. Progression of Melanocytic Nevi (a) Junctional: nevus cells present both singly and in uniform nests at the dermoepidermal junction. (b) Compound: nevus cells present both singly and in uniform nests at the dermoepidermal junction; and nests, cords, and strands of nevus cells in the dermis. (c) Intradermal: nests, cords, and strands of nevus cells in the Fig. 5. (a) Macular pigmented lesion on sole with some features of both an early malignant melanoma and an unusual junction nevus. (b) Progressionof the lesion two years later. Typical features of a thick malignant melanoma. VOL35,NO.3 MAY/JUNE

5 circumscribed, small (less than six mm), raised papule that is uniformly pigmented with a range of color from skin-colored to tan to shades of brown and a smooth or rough surface. It may have an excess of hair. It usually develops in late childhood, adolescence, or early adulthood. Fig. 6. Compound nevus. Small, well-circum scribed, uniformly pigmented, raised papule.,,.@.,; ii.*@, â œ â Iâ ; â..@ â œ â â â III.*@ Intradermal Nevus (Fig. 7) An intradermal nevus is generally a small (up to six mm) well-circumscribed papule that is usually uniform in pigmentation from skin-colored to tan or various shades of brown. The surface may be smooth or rough. Intradermal nevi may have an ex cess of hair. Solar Lentigo (Fig. 8) A solar lentigo is generally a uniform tan to brown macule, known to the lay pub lic as a â œ liver spot.â It is found on sun exposed skin in people with significantly sun-damaged skin. Common sites include the face, chest, and dorsa of the â P / â â â Fig. 7. Intradermal nevus. Small, well-circum scribed papule with minimal pigmentation. Seborrheic Keratosis (Fig. 9) A seborrheic keratosis is generally a ver rucous, round or ovoid, variably raised, light brown to black, sharply demarcated papule or plaque that ranges in diameter from a few millimeters to several centimeters. The sur face is generally â œ dullâ or â œ warty.â It often has a â œ stuck onâ appearance. Seborrheic keratoses are most commonly situated on the face, neck, and trunk. They are composed predominantly of proliferating keratino cytes (epidermal cells) and are not primarily of melanocytic origin. Fig.8. Solarlentigo.Tan,sharplydefined patch. Age as a Factor in the Onset and Diagnosis of Pigmented Lesions of the Skin The age of the patient is important to consider in making a differential diagno sis of pigmented lesions of the skin. Ma lignant melanomas rarely develop in childhood.2'-23 When they do occur in pre adolescents, they may develop de novo or 134 CA-ACANCERJOURNALFORCLINICIANS

6 Fig. 9. Seborrheic keratoses. Multiple, tan to darker brown, raised verrucous papules. Fig. 10. Asymmetry of early malignant mela noma. may originate in congenitally determined lesions like large congenital melanocytic nevi.212â 2'The most common benign pig mented lesions in children are ephelides (freckles), simple lentigines, and junc tional nevi. Compound nevi generally begin in childhood or adolescence; intra dermal nevi predominate in adulthood. The other common benign pigmented lesions (solar lentigines and seborrheic keratoses) usually begin later in adult life, generally from the 40s onward. The inci dence of malignant melanoma is very low in childhood and then increases with age.29'3â The mean age of presentation overall is approximately SO. However, any new pigmented lesion on the skin that de velops after age 403 and does not meet the criteria set forth for benign p'igmented lesions should be suspected of being a ma lignant melanoma or a precursor/marker lesion of a malignant melanoma (e.g., a dysplastic nevus). Clinical Characteristics ofearly MalignantMelanoma The clinically diagnostic features of early malignant melanoma (malignant mela noma in situ) are similar regardless of the anatomical site.4632 It is essential that physicians recognize these features. Un like benign pigmented lesions, which are generally round and symmetrical, early malignant melanomas are usually asym Fig. 11. Asymmetry of early malignant mela noma. metrical (Figs. 10 and 11). Unlike benign pigmented lesions, which generally have regular margins, the borders of early ma lignant melanomas are usually irregular (Figs. 12 and 13). Unlike benign pig mented lesions, which are generally uni form in color, macular malignant melanomas are variegated, ranging from various hues of tan and brown to black, and sometimes intermingled with red and white (Figs. 14â 17). Unlike most benign pigmented lesions, which generally have diameters less than six mm, the diameters of macular malignant melanomas when first identified are often more than six mm (Figs. 18â 20). These characteristic clinical features of early malignant melanoma can be easily VOL35.NO.3 MAY/JUNE

7 or the development of a new pigmented lesion, particularly after the age of 40, is of importance in alerting the physician to the possibility of a malignant melanoma. A malignant melanoma should be consid ered if any of the changes shown in Table 1 are Fig. 12. Border irregularity of early malignant melanoma. Fig. 13. Border irregularity of early malignant melanoma. remembered by thinking of ABCD: â A = Asymmetry. â B = Border irregularity. â C = Color variegation. â D = Diameter generally greater than six mm. Several clinical examples of the pro gression of malignant melanomas are il lustrated in Figures 21 to 24 for comparison with the early malignant melanomas de scribed above. The goal is to significantly reduce the number of these more advanced malignant melanomas, because they are associated with higher mortality rates. The diagnosis of malignant melanoma is based not only on clinical appearance, but also on history and symptomatology. Change in a preexisting melanocytic nevus PrecursorLesionsof Malignant Melanoma Recent evidence suggests that certain pig mented cutaneous lesions may give rise to malignant melanomas. These lesions in clude acquired abnormal melanocytic nevi known as dysplastic nevi, which are es pecially prevalent in certain melanoma prone families, but can also occur in the general population; and certain congenital melanocytic nevi. Dysplastic Nevus Dysplastic nevi are acquired pigmented le sions of the skin. Clinical and histological definitions of dysplastic nevi are evolv ing.@' In general, dysplastic nevi differ from common, acquired benign melanocytic nevi in several respects (Table 2). Some, how ever, cannot be distinguished clinically from malignant melanomas. Dysplastic nevi may occur in both familial and sporadic (non familial) settings. The clinical features of dysplastic nevi are similar, however, in both settings. Dysplastic nevi are typically larger than ordinary nevi, generally ranging from six to 12 mm or more in diameter (Fig. 25). They usually have both macular and ele vated (â œpebbly,â papular, nodular, or plaque) components (Fig. 26). The bor ders of dysplastic nevi, unlike those of common nevi, are often irregular and frequently so ill-defined that they fade imperceptibly into the surrounding skin (Fig. 27). Dysplastic nevi usually are variegated in color, ranging from tan to dark brown, at times with a prominent pink component (Fig. 28). These lesions may appear any where on the body, especially on the sun exposed areas of the trunk and extremities. However, they may also occur on sun-pro 136 CA-A CANCER JOURNAL FOR CLINICIANS

8 Fig. 14. Color variegation of early malignant melanoma. Note nuances of tans and browns. Fig. 15. Color variegation of early malignant melanoma. tected areas like the breasts, pubic area, buttocks, and scalp.35-4' Young adults generally have an aver age of 25 common melanocytic nevi, whereas individuals with dysplastic nevi may have more than 100 lesions. Common melanocytic nevi usually do not develop after the age of 40,31 whereas dysplastic nevi generally begin in adolescence and continue to appear throughout life.35-4' Dysplastic nevi may be familial or sporadic. Familial dysplastic nevi may be inherited as an autosomal dominant trait.35-4' The sporadic variant occurs in people who have no family history of either liiiiii.1iiiifitii I III It Fig. 16. Color variegation of malignant mela noma. Note the pink-red component at lower margin of lesion. The mortality rate from malignant melanoma is increasing at a rate faster than that from any other cancer except for lung cancer. dysplastic nevi or malignant melanomas. Overall, patients with dysplastic nevi have a reported lifetime risk for malignant mel anoma of approximately five to 10 percent, compared with the risk of about 0.7 percent for the general population.@â 4' The risk of developing malignant mel anoma is greater for those with one or more relatives with this tumor.4â The lifetime ;@i@i'i Fig. 17. Color variegation of early malignant melanoma. Irregularly marginated pigmented lesion and prominent central pinkish white components are indicative of spontaneous partial regression. VOL35,NO.3 MAY/JUNE

9 â I of malignant melanoma approaches a re ported 100 percent for those patients with dysplastic nevi who have both two or more first-degree relatives with cutaneous ma lignant melanomas and two or more with dysplastic Malignant melano mas in such individuals may arise either within the dysplastic nevi or apparently de novo in normal-appearing Fig. 18. Early malignant melanoma, approxi mately six mm in <â ;4i - FIg 19 Early malignant melanoma, approxi mately eight mm in diameter. Congenital Melanocytic Nevus By definition, a congenital melanocytic nevus is a lesion that contains nevus cells and is present at birth. Congenital melano cytic nevi can be categorized by size as follows:27@ â Smallâ less than 1.5 cm in diameter. â Mediumâ 1.5 to 19.9 cm in diameter. â Largeâ 20 cm or more in diameter. Congenital melanocytic nevi occur in about one percent of newborns;26 most of these nevi are small or medium-sized. The lifetime risk of malignant melanoma in pa tients with large congenital melanocytic nevi has been estimated to be about six percent,28 again, compared with a risk of 0.7 percent for the general population. The risk of a malignant melanoma developing in small and medium-sized congenital mel anocytic nevi has also been reported to be increased according to some investiga tors.42-40the magnitude of that risk, how ever, has not been established and is, therefore, still controversial. In sum, it has been found that malig nant melanomas may arise de novo as well as in association with preexisting melano cytic nevi. Dysplastic nevi may be both markers for malignant melanomas (i.e., identifying melanoma-prone individuals) or precursors of malignant melanomas (i.e., the dysplastic nevi themselves give rise to malignant melanomas). Again, large con genital melanocytic nevi (Fig. 29) also have a substantially greater risk of giving rise to malignant melanomas. Fig 20. Malignant melanoma in situ on sun damaged skin of cheek, approximately 18mm in largest diameter. Risk Factors for Development of Malignant Melanoma Epidemiologic data suggest that malignant melanomas may also be related to addi 138 CA-A CANCER JOURNAL FOR CLINICIANS

10 Fig. 21. Progression of malignant melanoma. plaque. 5_,JllIIJHhIJ IIlifi 111,11 1IIIUIIIIIIIIII I1J â PZCJME@ Fig. 22. Progression of malignant melanoma: plaque with nodule tional risk factors. Those at risk include: â People with light-colored eyes (blue, green, grey), light complexions, and light-colored hair, and those who are more easily sunburned.45 â Patients with xeroderma pigmentosum.40 â People who live near the equator.4' â People who have had severe sunburns, especially in childhood through their early teens to 20s.48 â People who work indoors and have pri marily outdoor recreational habits.49 â People with an increased number of mel anocytic nevi in childhood.5â Examination of the Skin: The First Step towards Diagnosis Unlike other cancers, which are generally hidden from view, malignant melanoma, as Dr. Neville Davis has said so inci sively,5' â œ writes its message in the skin with its own ink and it is there for all of us to see. Some see but do not compre hend.â It is our intent to make everyone see, understand, comprehend, and act. It has been demonstrated that there is a strong association between the length of survival of patients with malignant melanoma and the thickness of the lesion. Patients who have thin (less than 0.76 mm) malignant melanomas have a cure rate of close to 100 percent following surgical removal of the primary tumor. Fig. 23. Progression of malignant melanoma plaque with amelanotic nodule Ill.! I,I1@I'I@j1i1 CI@.4IN :,._..:..,_, :...) _â œ - -1)@II Fig 24. Progression of malignant melanoma with ulcerated nodule. VOL 35, NO. 3 MAY/JUNE

11 :cr.n Fig. 25. Dysplastic nevus measuring nine mm in diameter. Fig. 28. Dysplastic nevus with color variega tion from tan to IiIt,Ifl sf111.1 Fig. 26. Dysplastic nevus with features of a dark-target cm I@ I; 2j Fig. 27. Dysplastic nevus with papillated sur face and tan macular border fading into the surrounding skin (so-called â papillatedâ var iant). Early detection of breast cancer is fa cilitated by examinations by physicians and frequent self-examinations by women.52 Similarly, if malignant melanomas are to be identified when they are curable, complete and thorough examinations by physicians should be encouraged and taught, supplemented by frequent self examinations of the skin by patients. The following section describes a technique of systematic and thorough physician-examination of the skin and offers guidelines on teaching self examination of the skin. Examinationof the Skin by Physicians The equipment needed for complete ex amination of the skin is simple: examina tion table, source of bright light, and, occasionally, a magnifying lens (2 x â 4 x). The patient should lie on an exami nation table and the entire anterior surface of the body (including intertriginous areas) should be closely scrutinized for pig mented lesions. The next step is to look at the entire posterior aspect of the body (in cluding intertriginous areas). The scalp should also be thoroughly examined. An ordinary inexpensive blow dryer can be used, especially if hair is plentiful. All pigmented lesions should be care fully studied. Any lesion even remotely suggestive of a malignant melanoma should be given special attention.this includes 140 CA-A CANCER JOURNAL FOR CLINICIANS

12 obtaining an in-depth history and a biopsy. Remember the ABCDs (Asymmetry, Border irregularity, Color variegation, Di ameter â enlargement). A completeannualexaminationof the skin by a physician is recommended for everyone, supplemented by monthly self examinations by the patient. Patients with a personal or family history of malignant melanoma, as well as those with dysplastic nevi or any of the other risk factors, should have more frequent examinations by both their physicians and Self-Examination of the Skin Routine self-examination of the skin is in expensive, noninvasive, and free of danger. The patient takes part of the re sponsibility for identifying early malignant melanomas of the skin at a time when such lesions are curable. A thorough self-examination of the skin requires the patient to undress completely and have a full-length mirror, hand-held mirror, hand-held blow dryer, two chairs, and a well-lighted room. Right after bath ing is a good time for the examination. The first few times, the patient should spend a good deal of time inspecting the en â j Fig. 29. Giant congenital melanocytic nevus. By performing periodic complete cutaneous examinations, by teaching patients the technique of routine self-examination of the skin, and by proper use of diagnostic aids (particularly skin biopsy), physicians can improve the chances for early diagnosis and prompt eradication of malignant melanoma. tire surface of the skin. With experience, however, the self-examination should take only a few minutes. To look at parts of the skin surface that may be hard to seeâ for example, some areas of the back, scalp, and buttocksâ the patient may find it helpful to ask for the help of a spouse, relative, or friend. The self-examination should be carried out step by step as shown in the illustrations on pages 146 to 149. These pages can be photocopied and given to patients to en courage and facilitate their learning this critically important technique. Educational pamphlets for the public are also avail able through the American Academy of Dermatology or the American Cancer Society. It may be useful to measure unusual pigmented lesions and pinpoint their loca tions and sizes on body charts (Figs. 30 and 31). The blank body charts also may be photocopied and given to patients. The patient should see a physician if there are any newly discovered pigmented [Text continued on page 150/ VOL35,NO.3 MAY/JUNE

13 Fig. 30. Body chartsâ anteriorview and posterior view. 142 CA-A CANCER JOURNAL FOR CLINICIANS

14 â A Fig. 31. Photograph of patient with multiple dysplastic nevi. Body chart shows how these nevi are mapped. VOL 35, NO. 3 MAY/JUNE

15 144 CA-A CANCER JOURNAL FOR CLINICIANS

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17 / Ij Step2 Hold your hands with the palms face up, as shown in the drawing. Look at your palms, fingers, spaces between the fingers and forearms. Then turn your hands over and ex amine the backs of your hands, fin gers, spaces between the fingers, fingernails, and forearms. Step 1 Make sure the room is well-lighted, and that you have nearby a full length mirror, a hand-held mirror, a hand-held blow dryer, and two chairs or stools. Undress com pletely. Step 3 Now position yourself in front of the full-length mirror. Hold up your arms, bent at the elbows, with your palms facing you. In the mirror, look at the backs of your forearms and elbows. Â 1985,AmericanCancer Society Inc., New York, N.Y. 146 CA-ACANCERJOURNALFORCLINICIANS

18 (Pt IF I Step Again using the full-length mirror, observe the entire front of your body. In turn, look at your face, neck, and arms. Turn your palms to face the mirror and look at your upper arms. Then look at your chest and abdomen; pubic area; thighs and lower legs. Step5 Still standing in front of the mirror, lift your arms over your head with the palms facing each other. Turn so that your right side is facing the mirror and look at the entire side of your bodyâ your hands and arms, underarms, sides of your trunk, thighs, and lower legs. Then turn, and repeat the process with your left side. VOL 35, NO. 3 MAY/JUNE

19 A. With your back toward the full length mirror, look at your buttocks and the backs of your thighs and lowerlegs. Step7 Now pick up the hand-held mirror. With your back still to the full-length mirror, examine the back of your neck, and your back and buttocks. Also examine the backs of your arms in this way. Some areas are hard to see, and you may find it helpful to ask your spouse or a friend to assist you. Â AmericanCancerSociety,Inc.,New York,N.Y. 148 CA-A CANCER JOURNAL FOR CLINICIANS

20 St 9 Sit down and prop up one leg on a chair or stool in front of you as shown. Using the hand-held mirror, examine the inside of the propped-up leg, beginning at the groin area and moving the mirror down the leg to your foot. Repeat the procedure for your other leg. Step 8 Use the hand-held mirror and the full-length mirror to look at your scalp. Because the scalp is diffi cult to examine, we suggest you also use a hand-held blow dryer turned to a cool setting, to lift the hair from the scalp. While some people find it easy to hold the mir ror in one hand and the dryer in the other, while looking in the full-length mirror, many do not. For the scalp examination in particular, then, you might ask your spouse or a friend to assist you. Ste 10Still sitting, cross one leg over the other. Use the hand-held mirror to examine the top of your foot, the toes, toenails, and spaces be tween the toes. Then look at the sole or bottom of your foot. Repeat the procedure for the other foot. VOL 35, NO. 3 MAY/JUNE

21 lesions or any significant changes in a preexisting pigmented lesion. Most early malignant melanomas are macular and grow in diameter for some time before they be come elevated. Flat lesions are almost al ways curable, whereas lesions that develop plaques, papules, or nodules have a greater risk for metastases.'6 The goal is to recog nize early malignant melanomas when they are flat and curable. In Summary The combination of routine physician examination of the skin coupled with self-examination provides a realistic op portunity for the identification of early malignant melanomas. Removal of such thin lesions can significantly reduce the mortal ity rate from this potentially serious form of cutaneous cancer. References 1. Silverberg E: Cancer statistics, CA 35:19â 35, KopfAW, Rigel DS, Friedman RJ: The rising incidence and mortality rate of malignant mela noma. J Dermatol SurgOncol 8:760â 761, Mihm MC Jr. Fitzpatrick TB, Brown MML, et al: Early detection of primary cutaneous ma lignant melanoma. A color atlas. N Engl J Med 289:989â 996, Ackerman AB: Clinical diagnosis of malig nant melanoma in situ, in Ackerman AB (ed): Pa thology of Malignant Melanoma. New York, Masson Publishing USA, Inc. 1981, pp 57â Sober AJ, Fitzpatrick TB, Mihm MC, et al: Early recognition of cutaneous melanoma. JAMA 242:2795â 2799, Ackerman AB: Malignant melanoma: A unifying concept. Hum Pathol 11:591â 595, Breslow A: Prognostic factors in the treat ment of cutaneous melanoma. J Cutan Pathol 6:208â 212, Fitzpatrick TB: Early recognition of primary cutaneous melanoma. Hosp Pract 17:67â 75, Clark WH Jr: Clinical diagnosis of cutaneous malignant melanoma (editorial). JAMA 236:484â 485, Clark WHir, From L, Bernardino EA, et al: The histogenesis and biologic behavior of pri mary human malignant melanomas of the skin. Cancer Res 29:705â 727, Breslow A: Thickness, cross-sectional areas, and depth of invasion in the prognosis of cuta neous melanoma. Ann Surg 172:902â 908, Balch CM, Murad TM, Soong SJ, et al: A multifactorial analysis of melanoma: Prognostic histopathological features comparing Clark's and Breslow's staging methods. Ann Surg 188:732â 742, McGovern Vi, Shaw HM, Milton GW, et al: Prognostic significance of the histological fea tures of malignant melanoma. Histopathology 3:385â 393, Day CL Jr. Mihm MC Jr, Lew RA, et al: Cu taneous malignant melanoma: Prognostic guide lines for physicians and patients. CA 32:113â 122, Breslow A, Cascinelli N, van der Esch EP, et al: Stage I melanoma of the limbs: Assess ment of prognosis by levels of invasion and maximum thickness. Tumori 64: , Funk W, Schmoeckel C, HÃ lzeld, et al: Prognostic classification of malignant melanoma by clinical criteria. BrJ Dermatol 111:129â 138, Wick MM, Sober AJ, Fitzpatrick Ti, et al: Clinical characteristics of early cutaneous mel anoma. Cancer 45:2684â 2686, Roses DF, Harris MN, Ackerman AB: Di agnosis and Management of Cutaneous Malig nant Melanoma. Philadelphia, WB Saunders Co. 1983, pp 126â BalchCM, MiltonGW, Shaw HM, etal: Cu taneous Melanoma: Clinical Management and Treatment Results Worldwide. Philadelphia, JB Lippincott Co, 1985, pp 63â NYU Melanoma Cooperative Group, un published observations, KopfAW, Ban RS, Rodrlguez-Sains RS, et al (eds): Malignant Melanoma. New York, Mas son Publishing USA, mc, 1979, pp 152â Lyall D: Malignant melanoma in infancy (letter). JAMA 202:1153, Trozak Di, Rowland WD, Hu F: Metastatic malignant melanoma in prepubertal children. Pediatrics 55:191â 204, Kaplan EN: The risk of malignancy in large congenital nevi. PlastReconstr Surg 53:42 lâ 428, Mark GJ, Mihm MC, Liteplo MG, et al: Congenital melanocytic nevi of the small and garment type. Clinical, histologic, and ultra 150 CA-A CANCER JOURNAL FOR CLINICIANS

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