ICD-9: 172 ○ ICD-10: C43
Classification of Melanoma
Four Important Messages Concerning Cutaneous Melanoma
1. Melanoma of the Skin Is Approaching Epidemic Proportions
In 2009, it was estimated that in the United States roughly 122,000 men and women were diagnosed with melanoma of which 69,000 were invasive. Melanoma is a common malignancy and its incidence is on the rise. In the United States, the lifetime risk of invasive melanoma in 2010 was 1 in 50. The US surveillance epidemiology and end results (SEER) estimated 8,650 deaths due to melanoma in the United States. The number of melanomas in the United States continues to increase by 7% per year. Cutaneous melanoma currently represents 5% of newly diagnosed cancer in men and 6% in women. It is the leading fatal illness arising in the skin and is responsible for 80% of deaths from skin cancer. US cancer statistics show that melanoma had the second highest mortality rate increase among men ≥65 years old. On the other hand, deaths from melanoma occur at a younger age than deaths from most other cancers, and melanoma is among the most common types of cancer in young adults.
2. Early Recognition and Excision of Primary Melanoma Result in Virtual Cure
Current cutaneous melanoma education stresses the detection of early melanoma, with high cure rates after surgical excision. Of all the cancers, melanoma of the skin is the most rewarding for detection of early curable primary tumors, thereby preventing metastatic disease and death. Curability is directly related to size and depth of invasion of the tumor. At present, the most critical tool for conquering this disease is, therefore, the identification of early “thin” melanomas by clinical examination. Total skin examination for melanoma and its precursors should be done routinely.
About 30% of melanomas arise in a preexisting melanocytic lesion; 70% arise in normal skin. Almost all melanomas show an initial radial growth phase followed by a subsequent vertical growth phase. Since metastasis occurs only infrequently during the radial growth phase, detection of early melanomas (i.e., “thin” melanomas) during this phase is essential.
There is the paradox that even with a rising mortality rate, there has been an encouraging improvement in the overall prognosis of melanoma with very high 5-year survival rates (approaching 98%) for thin (<0.75 mm) primary melanoma and an 83% rate for all stages. The favorable prognosis is entirely attributable to early detection.
3. All Physicians and Nurses Have the Responsibility of Detecting Early Melanoma
Early detection of primary melanoma ensures increased survival. The seriousness of this disease thus places the responsibility on the health-care provider in the pivotal role: not to overlook pigmented lesions. Therefore, it is recommended that in clinical practice, no matter what is the presenting complaint, total examination of the body should be requested of all Caucasian patients at the time of the first encounter and that all body regions, including the scalp, toe webs, and orifices (mouth, anus, vulva), be examined.
4. Examination of All Acquired Pigmented Lesions According to the ABCDE Rule
This rule analyzes pigmented lesions according to symmetry, border, color, diameter, growth, and elevation (see Cyclosporine and Table 12-1). While it does not apply to all types of melanoma, it permits differential diagnostic separation of most melanomas from common nevi and other pigmented lesions.
Etiology and Pathogenesis
The etiology and pathogenesis of cutaneous melanoma are unknown. Epidemiologic studies demonstrate a role for genetic predisposition and sun exposure in melanoma development. The major genes involved in melanoma development reside on chromosome 9p21. Twenty-five to forty percent of members of melanoma-prone families have mutations in cyclin-dependent kinase inhibitor 2A (CDKN2A) and a few families in cyclin-dependent kinase 4 (CDK4). These are tumor-suppressor genes that provide a rational basis for the link to susceptibility to melanoma. Sixty-six percent of melanomas have a mutation of the BRAF gene, others of MC1R.
There is convincing evidence from epidemiologic studies that exposure to solar radiation is the major cause of cutaneous melanoma. Cutaneous melanoma is a greater problem in light-skinned whites (skin types I and II), and sunburns during childhood and intermittent burning exposure in fair skin seem to have a higher impact than cumulative UV exposure over time. Other predisposing and risk factors are the presence of precursor lesions (dysplastic melanocytic nevi and congenital NMN) and a family history of melanoma in parents, children, or siblings. Risk factors for melanoma are listed in Table 12-2.
TABLE 12-2RISK FACTORS FOR THE DEVELOPMENT OF MELANOMA |Favorite Table|Download (.pdf) TABLE 12-2 RISK FACTORS FOR THE DEVELOPMENT OF MELANOMA
Genetic markers (CDKN2a), BRAF, MC1R
Photo skin type I/II
Family history of dysplastic nevi or melanoma
Personal history of melanoma
Ultraviolet irradiation, particularly sunburns during childhood and in termittent burning exposures
Number (>50) and size (>5 mm) of melanocytic nevi
Number of dysplastic nevi (>5)
Dysplastic melanocytic nevus syndrome
Almost all melanomas show an initial radial growth phase followed by a subsequent vertical growth phase. Radial growth phase refers to a mostly intraepidermal, preinvasive, or minimally invasive growth pattern; vertical growth refers to growth into the dermis and thus into the vicinity of vessels that serve as avenues for metastasis. Since most melanomas produce melanin pigment, even preinvasive melanomas in their radial growth phase are clinically detectable by their color patterns. The prognostic difference among the clinical types of melanoma relates mainly to the duration of the radial growth phase, which may last from years to decades in LMM, from months to 2 years in SSM, and 6 months or less in NM.
Six Signs of Malignant Melanoma (ABCDE Rule)
(does not apply to nodular melanoma)
Asymmetry in shape—one-half unlike the other half.
Border is irregular—edges irregularly scalloped, notched, sharply defined.
Color is not uniform; mottled—haphazard display of colors; all shades of brown, black, gray, blue, red, and white.
Diameter is usually large—greater than the tip of a pencil eraser (6.0 mm); others use D for “ugly duckling” sign: lesion is different from other pigmented lesions (nevi) on the body with respect to change in size, shape, and color.
Elevation is almost always present and is irregular—surface distortion is assessed by side lighting. MIS and acral lentiginous lesions initially macular; others use E for Evolving. A history of an increase in the size of lesion is one of the most important signs of malignant melanoma.
Clinical Presentations of Melanoma
The clinical characteristics of the four major types of melanoma are summarized in Table 12-3. Frequency of melanoma by type of tumor: SSM, 70%; NM, 15%; LMM, 5%; and acral and unclassified melanoma, 10%. Also discussed in this section are MIS and desmoplastic melanoma.
TABLE 12-3FOUR MAJOR TYPES OF MELANOMA |Favorite Table|Download (.pdf) TABLE 12-3 FOUR MAJOR TYPES OF MELANOMA
|Type ||Frequency (%) ||Site ||Radial Growth ||Vertical Growth |
|Superficial spreading ||70 ||Any site, lower extremities, trunk ||Months to 2 years ||Delayed |
|Nodular ||15 ||Any site, trunk, head, neck ||No clinically perceptible radial growth ||Immediate |
|Lentigo maligna melanoma ||5 ||Face, neck, dorsa of hands ||Years ||Much delayed |
|Acral lentiginous melanoma ||5–10 ||Palms, soles, subungual ||Months to years ||Early but recognition delayed |
ICD-9: 232 ○ ICD-10: D02
The clinical features of MIS are not always clearly presented. MIS is primarily a histopathologic definition, and the term is used when melanoma cells are confined to the epidermis, above the basement membrane; basilar melanocytic atypia, hyperplasia, and spread occur either in single-file alignment along the basal membrane or are distributed throughout the epidermis (pagetoid spread). Every melanoma starts as an in situ lesion, but MIS is clinically diagnosable only when the radial growth phase is long enough for it to become visually detectable. Such lesions are flat, within the level of the skin, and thus a macule (Fig. 12-7) or a macule with barely perceptible elevation (Fig. 12-8), with irregular borders and marked variegation of color: brown, dark brown, and black or reddish tones but without gray or blue, as this occurs only when melanin (within macrophages) or melanocytes or melanoma cells are located in the dermis. The clinical distinction between MIS and severely atypical DN may not be possible.
The clinical correlations of MIS are lentigo maligna (Fig. 12-7) and flat SSM (Fig. 12-8) and these are discussed in the respective sections below.
Melanoma in situ: lentigo maligna A large, very irregular, and asymmetric macule on the preauricular region of a 78-year-old male. There is striking variegation of pigmentation (tan, brown, dark brown, black).
Melanoma in situ, superficial spreading type (A) Barely elevated plaque on the arm of a 75-year-old white male was first noted 5 years previously, gradually increasing in size. The lesion is asymmetric and there is also asymmetry in the distribution of color that is variegated and shows dark-brown specks against a tan background. Dermatopathology of the lesion showed a superficial spreading melanoma in situ. (B) An almost oval, barely elevated small plaque that has a relatively regular border but is striking with regard to the variegation in color: tan, dark brown, and even black with an orange portion on the right. Dermatopathology again showed MIS with a pagetoid growth pattern of intraepidermal melanoma cells.
Lentigo Maligna Melanoma (LMM)
ICD-9: 232 ○ ICD-10: D02
The least common (<5%) of the four principal melanoma types of white persons (Table 12-3).
It occurs in older persons on the most sun-exposed areas—the face and forearms.
Sunlight is the most important pathogenic factor.
LMM always starts as lentigo maligna (LM), which represents a macular intraepidermal neoplasm and is an MIS (Figs. 12-7 and 12-10). LM is thus not a precursor but an evolving lesion of melanoma.
Focal papular and nodular areas signal a switch from the radial to the vertical growth phase and thus invasion into the dermis; the lesion is now called LMM (Fig. 12-9).
For the most important clinical characteristics, see Table 12-3.
Lentigo maligna melanoma Illustrated on the right of the lesion is a large, variegated, freckle-like macule (not elevated above the plane of the skin) with irregular borders; the tan areas show increased numbers of melanocytes, usually atypical and bizarre, and are distributed single file along the basal layer; at certain places in the dermis, malignant melanocytes have invaded and formed nests (radial growth phase). At the left is a large nodule that is heavily pigmented and composed of epithelioid cells that have invaded the dermis (vertical growth phase); the nodules of all four main subtypes of melanoma are indistinguishable from each other.
Lentigo maligna (A) A very large lentigo maligna on the right cheek with the typical variegation in color (tan, brown, black) and highly irregular shape. The lesion is flat, macular, and thus represents an in situ melanoma. (B) The classically macular lentigo maligna is highly irregular in shape and variegated in color. However, there is a bluish component and a large pink nodule in the infraorbital region, indicating a switch from the radial to the vertical growth phase and thus invasiveness: the lesion is now called lentigo maligna melanoma.
Equal incidence in males and females.
Rare in brown-skinned persons (e.g., Asians, East Indians) and extremely rare in black-skinned (African Americans and Africans) persons. Highest incidence in whites, skin phototypes I, II, and III.
5% of primary cutaneous melanomas.
Same factors as in sun-induced nonmelanoma skin cancer: older population, outdoor occupations (farmers, sailors, construction workers).
In contrast to SSM and NM, which appear to be related to intermittent high-intensity sun exposure and occur on the intermittently exposed areas (back and legs) of young or middle-aged adults, LM and LMM occur on the face, neck, and dorsa of the forearms or hands (Table 12-3); furthermore, LM and LMM occur almost always in older persons with evidence of heavily sun-damaged skin (dermatoheliosis). The evolution of the lesion most clearly reveals the transition from the radial to the vertical growth phase and from a clinically recognizable MIS to invasive melanoma (Fig. 12-9).
LMM very slowly evolves from LM over a period of several years, sometimes up to 20 years. There is practically always a background of dermatoheliosis.
Lentigo Maligna. Uniformly flat, macule (Fig. 12-7); 0.5 cm or larger, up to 20 cm (Fig. 12-10A). Usually well defined, in some areas also blurred borders or highly irregular borders, often with a notch; “geographic” shape with inlets and peninsulas (Fig. 12-10B). Early lesions tan, advanced lesions: striking variations in hues of brown and black (speckled), appears like a “stain” (Fig. 12-7); haphazard network of black on a background of brown (Fig. 12-10A). No hues of red and blue.
Lentigo Maligna Melanoma. The clinical change that indicates the transition of LM to LMM is the appearance of variegated red, white, and blue and of papules, plaques, or nodules (Fig. 12-10B). Thus, LMM is the same as LM plus (1) gray areas (indicate focal regression) and blue areas [indicating dermal pigment (melanocytes or melanin)] and (2) papules or nodules, which may be blue, black, or pink (Fig. 12-10B). Rarely, LMM may be nonpigmented. It is then skin colored and patchy red and clinically not diagnosable (see Fig. 12-18A).
Distribution. Single isolated lesion on the sun-exposed areas: forehead, nose, cheeks, neck, forearms, and dorsa of hands; rarely on lower legs.
Other Skin Changes in Areas of Tumor
Sun-induced changes: solar keratosis, freckling, telangiectasia, thinning of the skin, i.e., dermatoheliosis.
General Medical Examination
Check for regional lymphadenopathy.
LM shows increased numbers of atypical melanocytes distributed in a single layer along the basal layer and above the basement membrane of an epidermis that shows elongation of rete ridges. Atypical melanocytes are usually singly dispersed but may also aggregate to small nests and extend into the hair follicles, reaching the middermis, even in the preinvasive stage of LM. In LMM, they invade the dermis (vertical growth phase) and expand into the deeper tissues (Fig. 12-9).
Variegate Tan-Brown Macule/Papule/Nodule
Seborrheic keratoses may be dark but are exclusively papules or plaques and have a characteristic stippled surface, often with a verrucous component, i.e., a “warty” but greasy surface that, when scratched, exhibits fine scales. Solar lentigo, although macular, does not exhibit the intensity or variegation of brown, dark brown, and black hues seen in LM. Dermoscopy is essential.
Summarized in Table 12-5.
Very early LM lesions: Imiquimod.
Excise with 1 cm beyond the clinically visible lesion where possible and provided the flat component does not involve a major organ. Use of Wood lamp and dermoscopy help in defining borders.
Sentinel node to be done in lesions >1.0 mm in terms of thickness.
Superficial Spreading Melanoma
ICD-9: 232 ○ ICD-10: D02
SSM is the most common melanoma (70%) type in persons with white skin.
It arises most frequently on the upper back and occurs as a moderately slow-growing lesion over a period of up to 2 years.
SSM has a distinctive morphology: an elevated, flat lesion (plaque). The pigment variegation of SSM is similar to, but more striking than, the variety of color present in most LMM. The color display is a mixture of brown, dark brown, black, blue, and red, with slate-gray or gray regions in areas of tumor regression.
For most important clinical characteristics, see Tables 12-1 and 12-3.
30–50 (median, 37) years of age.
Slightly higher incidence in females.
White-skinned persons overwhelmingly predominate. Only 2% brown or black skinned. Furthermore, brown and black persons have melanomas usually occurring on the extremities; half of brown and black persons have primary melanomas arising on the sole of the foot (see below).
SSM constitutes 70% of all melanomas arising in white persons.
Predisposing and Risk Factors
In order of importance, these are presence of precursor lesions (DN, CNMN; p. 252 and p. 256); family history of melanoma in parents, children, or siblings; light skin color (skin phototypes I and II); and sunburns, especially during preadolescence. Especially increased incidence in young urban professionals, with a frequent pattern of intermittent, intense sun exposure (“weekenders”) or winter holidays near the equator.
In the early stages of growth, there is an intraepidermal, or radial, growth phase during which tumorigenic pigment cells are confined to the epidermis and thus cannot metastasize. At this stage, SSM is an MIS (Figs. 12-8 and 12-11). This “grace period” of the radial growth phase, with potential for cure, is followed by the invasive vertical growth phase, in which malignant cells consist of a tumorigenic nodule that vertically invades the dermis with potential for metastasis (Fig. 12-11).
Superficial spreading melanoma The border is irregular and elevated throughout its entirety; biopsy of this plaque surrounding the large nodule shows a pagetoid distribution of large melanocytes throughout the epidermis in multiple layers, occurring singly or in nests, and uniformly atypical (radial growth phase). On the left is a large nodule, and scattered throughout the surrounding portion of the plaque are smaller papular and nodular areas (vertical growth phase). The nodules may also show epithelioid, spindle cells, or small malignant melanocytes as in lentigo maligna melanoma and NM.
The pathophysiology of SSM is not yet understood. Certainly, in some considerable number of SSMs, sunlight exposure is a factor, and SSM is related to occasional bursts of recreational sun exposure during a susceptible period (<14 years). About 10% of the SSMs occur in high-risk families. The rest of the cases may occur sporadically among persons without a specific genetic risk.
The usual history of SSM is a change in a previously existing pigmented lesion (mostly a DN). It should be noted, however, that 70% of melanomas arise in “normal” skin, but since initial growth is slow and melanomas often occur in persons with many nevi, an early SSM may be mistaken for a preexisting nevus by the patient.
The patient or a close relative may note a gradual darkening in one area of a “mole” (see Figs. 12-3 and 12-8) or a change in shape; and as the dark areas increase, there will develop variegation of color with mixes of brown, dark brown, and black. Also, the borders of a previously regularly shaped lesion may become irregular with pseudopods and a notch.
With the switch from the radial to a vertical growth phase (Fig. 12-11), and thus invasion into the dermis, there is the clinical appearance of a papule and later nodule on top of the slightly elevated plaque of an SSM. Since many SSMs initially have the potential for a tumor-infiltrating lymphocyte (TIL)-mediated regression, albeit only partial, other areas of the SSM plaque may sink to the level of surrounding normal skin and the color mixes of brown to black are expanded by the addition of red, white, and the tell-tale blue and blue-gray.
(Figs. 12-12 and 12-13). SSM is the lesion to which the ABCDE rule (p. 261) best applies. Initially a very flat plaque 5–12 mm or smaller (Fig. 12-8); older lesions, 10–25 mm (Fig. 12-12). Asymmetric (one-half unlike the other) (Figs. 12-12A–C) or oval with irregular borders (Fig. 12-12D) and often with one or more indentations (notches) (Figs. 12-12 and 12-13). Sharply defined. Dark brown, black, with admixture of pink, gray, and blue-gray hues—with marked variegation and a haphazard pattern. White areas indicate regressed portions (Figs. 12-12C and D). An SSM is thus a flat plaque with all shades of brown to black plus the American flag or the tricolore (red, blue, white) (Fig. 12-12D). No benign pigmented lesion has these characteristics. As the vertical growth phase progresses, nodules appear (Fig. 12-13B); eventually, erosions and even superficial ulceration develop (Figs. 12-13C and D).
Superficial spreading melanoma, radial growth phase (A) A flat-topped, elevated, asymmetric, and irregular plaque with variegated color (brown, black) on the trunk with sharply demarcated margins. The surface is also irregular with a cobblestone pattern (see also Fig. 12-3). (B) An asymmetric, flat plaque with irregular and sharply defined margins and a cobblestone-like surface. The melanin pigmentation ranges from light brown to dark brown, black, and there are lighter areas interspersed. (C) A highly irregular lesion with dark-brown to bluish-black papules forming a ring around a white macular area with a central brownish to bluish papule. This white area marks spontaneous regression. (D) A relatively symmetric but large (8 cm) plaque with sharply defined and notched border and a considerable variegation of color: black, blue, red, and white.
Superficial spreading melanoma, vertical growth phase (A) An only minimally irregular plaque with variegate color (brown, black). In the center, there is a small black, dome-shaped nodule. This is the switch to the vertical growth phase. (B) An irregular very flat plaque with notched borders and highly variegated color (tan, brown, black, and red). Slightly off center there is a large partially crusted nodule (vertical growth phase). (C) A highly irregular and asymmetric plaque with a cobblestone-like surface and variegated color (black, brown). On the right there is an excentric, eroded black to blue nodule representing the vertical growth phase. (D) A highly irregular, asymmetric bluish to black plaque with brown, red, and white (regression). Off center is an eroded black nodule (vertical growth).
Distribution. Isolated, single lesions; multiple primaries are rare. Back (males and females); legs (females, between knees and ankles); anterior trunk and legs in males; relatively fewer lesions on covered areas, e.g., buttocks, lower abdomen, bra area.
Increases diagnostic accuracy by more than 50%.
Always search for enlarged regional nodes.
Malignant melanocytes expand in a pagetoid pattern, i.e., in multiple layers within the epidermis (if confined to the epidermis, the lesion is an MIS) and superficial papillary body of the dermis—the radial growth phase. They occur singly and in nests (see Fig. 12-11) and are S-100 and HMB-45 positive. In the vertical growth phase, presenting clinically as small nodules, they expand further into the reticular dermis and beyond (Fig. 12-11). For microstaging, see Table 12-4 and p. 282.
TABLE 12-4MELANOMA TNM CLASSIFICATION |Favorite Table|Download (.pdf) TABLE 12-4 MELANOMA TNM CLASSIFICATION
|T Classification ||Thickness (mm) ||Ulceration Status/Mitoses |
|T1 ||≤1.0 || |
a: Without ulceration and mitosis <1/mm2
b: With ulceration or mitosis ≥1/mm2
|T2 ||1.01–2.0 || |
a: Without ulceration
b: With ulceration
|T3 ||2.01–4.0 || |
a: Without ulceration
b: With ulceration
|T4 ||>4.0 || |
a: Without ulceration
b: With ulceration
|N Classification ||No. of Metastatic Nodes ||Nodal Metastatic Mass |
|N1 ||1 node || |
|N2 ||2–3 nodes || |
c: In-transit met(s)/satellite(s) without metastatic nodes
|N3 ||4 or more metastatic nodes, or matted nodes, or in-transit met(s)/satellite(s) with metastatic node(s) || |
|M Classification ||Site ||Serum Lactate Dehydrogenase |
|M1a ||Distant skin, subcutaneous, or nodal metastases ||Normal |
|M1b ||Lung metastases ||Normal |
|M1c ||All other visceral metastases ||Normal |
| ||Any distant metastasis ||Elevated |
If left untreated, SSM develops deep invasion (vertical growth) over months to years. Prognosis is summarized in Table 12-5.
TABLE 12-5SURVIVAL RATES FOR MELANOMA TNM STAGES I–III* |Favorite Table|Download (.pdf) TABLE 12-5 SURVIVAL RATES FOR MELANOMA TNM STAGES I–III*
|Stage ||Tumor ||Node State ||Node Tumor Burden ||5-Year Survival Rate (%) |
|IA ||T1a ||No ||— ||97 |
|IB ||T1b ||No ||— ||94 |
|ÎB ||T2a ||No ||— ||91 |
|IIA ||T2b ||No ||— ||82 |
|IIA ||T3a ||No ||— ||79 |
|IIB ||T3b ||No ||— ||68 |
|IIB ||T4a ||No ||— ||71 |
|IIC ||T4b ||No ||— ||53 |
|IIIA ||T1–T4a ||N1a/N2a ||Microscopic ||78 |
|IIIB ||T1–T4b ||N1a/N2a ||Microscopic ||55 |
|IIIB ||T1–T4a ||N1b/N2b ||Macroscopic ||48 |
|IIIC ||T1–T4b ||N1b/N2b/N3 ||Macroscopic or 4 + nodes ||38 |
|IIIC ||T1–T4a ||N3 ||4 + any nodes ||47 |
Clinically according to the ABCDE rule, verified by dermoscopy. In case of doubt, biopsy; total excisional biopsy with narrow margins is optimal biopsy procedure. Incisional or punch biopsy acceptable when total excisional biopsy cannot be performed or when lesion is large, requiring extensive surgery to remove the entire lesion. Shave biopsy should not be done, as it does not allow assessment of the level of invasion.
ICD-9: 232 ○ ICD-10: D02
NM is second in frequency after SSM.
Occurring largely in middle life in persons with white skin and, as in SSM, on the less commonly exposed areas.
The tumor from the beginning is in the vertical growth phase (Fig. 12-14).
NM is uniformly elevated and presents as a thick plaque or an exophytic, polypoid, or dome-shaped lesion.
The color pattern is usually not variegated, and the lesion is uniformly blue or blue-black or, less commonly, can be very lightly pigmented or nonpigmented (amelanotic melanoma).
NM is the one type of primary melanoma that arises quite rapidly (a few months to 2 years) from normal skin or from a melanocytic nevus as a nodular (vertical) growth without an adjacent epidermal component, as is always present in LMM and SSM.
Note: For the most important clinical characteristics, see Table 12-3.
Nodular melanoma This arises at the dermal–epidermal junction and extends vertically in the dermis (vertical growth phase). The epidermis lateral to the areas of this invasion does not demonstrate atypical melanocytes. As in lentigo maligna melanoma and superficial spreading melanoma, the tumor may show large epithelioid cells, spindle cells, small malignant melanocytes, or mixtures of all three.
Equal incidence in males and females.
NM occurs in all races, but in the Japanese it occurs nine times more frequently (27%) than SSM (3%).
NM constitutes 15% (up to 30%) of the melanomas in the United States.
Predisposing and Risk Factors
Both NM and SSM occur in approximately the same sites (upper back in males, lower legs in females), and presumably the same pathogenetic factors are operating in NM as were described in SSM. For the growth pattern of NM, see Fig. 12-14. The reason for the high frequency of NM in the Japanese is not known.
This type of melanoma may arise in a preexisting nevus, but more commonly arises de novo from normal skin. In contrast to SSM, NM evolves over a few months and is often noted by the patient as a new “mole” that was not present before.
Uniformly elevated “blueberry-like” nodule (Figs. 12-15A and B) or ulcerated or “thick” plaque; may become polypoid. Uniformly dark blue, black, or “thundercloud” gray (Figs. 12-15A and B); lesions may appear pink with a trace of brown or a black rim (amelanotic NM, see Fig. 12-18C). Surface smooth or scaly, eroded (Fig. 12-15C) or ulcerated (Fig. 12-15D). Early lesions are 1–3 cm in size but may grow much larger if undetected. Oval or round, usually with smooth, not irregular, borders, as in all other types of melanoma. Sharply defined, may be pedunculated (Fig. 12-15D).
Nodular melanoma (A) A 9-mm dome-shaped smooth nodule with a flatter brownish rim arising on the back of a 38-year-old male. (B) A 1-cm black papule on the posterior thigh of a 60-year-old female. The lesion had been present for less than 1 year. (C) An eroded, bleeding, brown nodule having a mushroom-like configuration giving it a stuck-on appearance. Such lesions can be mistaken for a vascular lesion such as a pyogenic granuloma. (D) Large (5 cm) irregular, black, bleeding nodule sitting on the skin like a mushroom. The lesion had grown for over a half year and the 56-year-old male patient had not seen a physician out of fear “it might be melanoma.”
Distribution. Same as SSM. In the Japanese, NM occurs on the extremities (arms and legs).
General Medical Examination
Malignant melanocytes, which appear as epithelioid, spindle, or small atypical cells, show little lateral (radial) growth within and below the epidermis and invade vertically into the dermis and underlying subcutaneous fat (see Fig. 12-14). They are S-100 and usually HMB-45 positive. For microstaging, see Staging of Melanoma.
Serum levels of S-100 beta and melanoma-inhibiting activity, S-cysteinyldopa, and lactate dehydrogenase (LDH) levels are markers for advanced melanoma patients. LDH is to date the only statistically significant marker for progressive disease.
Clinical and with the help of dermoscopy. However, dermoscopy may fail in uniformly black lesions. In case of doubt, biopsy. Total excisional biopsy with narrow margins is optimal biopsy procedure, where possible. If biopsy is positive for melanoma, reexcision of site will be necessary (see Management, p. 282). Incisional or punch biopsy acceptable when total excisional biopsy cannot be performed or when lesion is large, requiring extensive surgery to remove the entire lesion.
NM can be confused with hemangioma (long history) and pyogenic granuloma (short history—weeks) (see Fig. 12-15C) and is sometimes almost indistinguishable from pigmented basal cell carcinoma, although it is usually softer. However, any “blueberry-like” nodule of recent origin (6 months to 1 year) should be excised or, if large, an incisional biopsy is mandatory for histologic diagnosis.
Summarized in Table 12-5.
Desmoplastic Melanoma (DM)
The term desmoplasia refers to connective tissue proliferation and, when applied to malignant melanoma, describes (1) a dermal fibroblastic component of melanoma with only minimal melanocytic proliferation at the dermal–epidermal junction; (2) nerve-centered superficial malignant melanoma with or without an atypical intraepidermal melanocytic component; or (3) other lesions in which the tumor appears to arise in lentigo maligna or, rarely, in ALM or superficial spreading melanoma.
Also, DM growth patterns have been noted in recurrent malignant melanoma.
DM may be a variant of LMM in that most lesions occur on the head and neck in patients with dermatoheliosis.
DM is more likely to recur locally and metastasize than LMM, however. DM is rare and occurs more frequently in women and persons >55 years old.
At diagnosis, DM lesions have been present from months to years. DM is asymptomatic, usually not pigmented and is therefore overlooked by the patient. Early lesions may appear as variegated lentiginous macules or plaques, at times with small blue-gray specks of color. Later lesions may appear as dermal nodules, and although they commonly lack any melanin pigmentation, they may have gray to blue papular elevations (Fig. 12-16). Borders, when discernible, are irregular as in LM.
The diagnosis requires an experienced dermatopathologist; S-100 immunoperoxidase-positive spindle cells need to be identified in the matrix collagen. HMB-45 staining may be negative. A typical junctional melanocytic proliferation, either individual or focal nests, occurs, resembling LM. S-100-positive spindle-shaped cells are embedded in matrix collagen that widely separates the spindle cell nuclei. Small aggregates of lymphocytes are commonly seen at the periphery of DM. Neurotropism is characteristic, i.e., fibroblast-like tumor cells around or within endoneurium of small nerves. Often, DM is seen with a background of severe solar damage to the dermis.
There are mixed views about the prognosis of DM. In one series, approximately 50% of patients experienced a local recurrence after primary excision of DM, usually within 3 years of excision; some patients experienced multiple recurrences. Lymph node metastasis occurs less often than local recurrence. In one series, 20% developed metastases, and DM was regarded as a more aggressive tumor than LMM.
For management, see Staging of Melanoma.
Desmoplastic melanoma A bluish-black very hard nodule on the cheek of an 85-year-old woman. It recurred 1 year after primary excision: histopathologically, it was a desmoplastic melanoma with a thickness of greater than 3.4 mm and showed neural invasion.
Acral Lentiginous Melanoma
ICD-9: 232 ○ ICD-10: D02
ALM is a special presentation of cutaneous melanoma arising on the sole, palm, and fingernail or toenail bed.
ALM occurs most often in Asians, sub-Saharan Africans, and African Americans, comprising 50–70% of the melanomas of the skin found in these populations.
It occurs most often in older males (≥60 years) and often grows slowly over a period of years.
The delay in development of the tumor is the reason these tumors are often discovered only when nodules appear or, in the case of nail involvement, the nail is shed; therefore, the prognosis is poor.
7–9% of all melanomas; in whites, 2–8% and in Asians, Africans, African Americans, 50% of melanomas.
ALM is the principal melanoma in the Japanese (50–70%) and in American and sub-Saharan African blacks.
The pigmented macules that are frequently seen on the soles of African blacks could be comparable with DN. ALM has a similar growth pattern as LMM.
ALM is slow growing (about 2.5 years from appearance to diagnosis). The tumors occur on the volar surface (palm or sole) and in their radial growth phase may appear as a gradually enlarging “stain.” ALM as subungual (thumb or great toe) melanoma appears first in the nail bed and involves, over a period of 1–2 years, the nail matrix, eponychium, and nail plate. In the vertical growth phase, nodules appear; often there are areas of ulceration, and nail deformity and shedding of the nail may occur.
Skin Lesions Acral and Palm/Sole
Macular or slightly raised lesion in the radial growth phase (Fig. 12-17), with focal papules and nodules developing during the vertical growth phase. Marked variegation of color including brown, black, blue, depigmented pale areas (Fig. 12-17). Irregular borders as in LMM; usually well defined but not infrequently ill defined. This type of ALM occurs on soles, palms, dorsal, and palmar/plantar aspects of fingers and toes (Fig. 12-17).
Acral lentiginous melanoma (A) An ALM arising on the thumb. Lentiginous component on the dorsal skin of the thumb: macular, sharply and ill-defined brown and gray-bluish spots. Subungual and distal ulcerated nodular component. (B) The tumor has replaced the entire nail bed and surrounding skin: macular and of variegated color resembling a lentigo maligna. The nail has been shed. This is ALM that has led to destruction of the nail matrix and was first diagnosed as nail dystrophy. (C) ALM on the heel. There is a highly variegated macular component—brown to gray and black; the nodular component is hyperkeratotic, reddish, and ulcerated. (D) Lentigo maligna melanoma on the sole. This is an advanced lesion with a macular component and a reddish, ulcerated nodule. The lesion measured 10 mm in depth, and there were enlarged inguinal lymph nodes.
Subungual macule beginning at the nail matrix and extending to involve the nail bed and nail plate. Papules, nodules, and destruction of the nail plate may occur in the vertical growth phase (Fig. 12-17B). Dark brown or black pigmentation that may involve the entire nail and surrounding skin looking like LM (Figs. 12-17A and B). As the lesion switches to the vertical growth phase, a papule or nodule appears and the nail is shed (Figs. 12-17A and B). Often the nodules or papules are unpigmented. Amelanotic ALM is often overlooked for months and, since there are no pigmentary changes, may first present as nail dystrophy.
ALM (plantar type) is not infrequently regarded as a “plantar wart” and treated as such. Dermoscopy is of decisive help. Also, often misdiagnosed as tinea nigra.
ALM (subungual) is usually considered to be traumatic bleeding under the nail, and subungual hematomas may persist for over 1 year; however, usually the whole pigmented area moves gradually forward. Distinction of ALM from subungual hemorrhage can easily be made by dermoscopy. With the destruction of the nail plate, the lesions are most often regarded as “fungal infection.” When nonpigmented tumor nodules appear, they are misdiagnosed as pyogenic granuloma.
The histologic diagnosis of the radial growth phase of the volar type of ALM may be difficult and may require large incisional biopsies to provide for multiple sections. There is usually an intense lymphocytic inflammation at the dermal–epidermal junction. Characteristic large melanocytes along the basal cell layer may extend as large nests into the dermis, along eccrine ducts. Invasive malignant melanocytes are often spindle shaped, so that ALM frequently has a desmoplastic appearance histologically.
The volar type of ALM can be deceptive in its clinical appearance, and “flat” lesions may be quite deeply invasive. Five-year survival rates are <50%. The subungual type of ALM has a better 5-year survival rate (80%) than does the volar type, but the data are probably not accurate. Poor prognosis for the volar type of ALM may be related to inordinate delay in the diagnosis.
In considering surgical excision, it is important that the extent of the lesion be ascertained by viewing the lesion with dermoscopy. Subungual ALM and volar-type ALM: amputation [toe(s), finger(s)]; volar and plantar ALM: wide excision with split skin grafting. Sentinel lymph node procedure necessary in most cases (see “Management of Melanoma”).
ICD-9: 232 ○ ICD-10: D02
All types of melanoma can be amelanotic.
Since they do not have the characteristic pigment marker, they are a diagnostic challenge (Fig. 12-18).
However, often there are pigmented clones in the tumor, which reveal its nature as a melanoma (Figs. 12-18B and C).
In most cases, only biopsy will reveal the correct diagnosis (Figs. 12-18A and D).
Amelanotic melanoma (A) Amelanotic LMM. The red nodule was soft and diagnosed as pyogenic granuloma and was excised. Histopathology revealed melanoma and subsequent punch biopsies performed in the erythematous skin of the cheek revealed lentigo maligna (LM). The outlines of the LM lesion as determined by further punch biopsies are marked with green circles. Note that over the mandible lesion is also nodular (vertical) growth. (B) Amelanotic superficial spreading melanoma. The true nature of this red nodule is revealed by the blue crescent at its base and the variegated brown-red plaque with which it is contiguous. (C) Amelanotic nodular melanoma. This cherry-red nodule has a brown, macular extension at 4, 6, 9 and 12 o’clock, giving away the correct diagnosis. (D) Amelanotic ASM on the heel. This cherry-red lesion was clinically diagnosed as eccrine poroma. Biopsy revealed deeply invading ALM.
Malignant Melanoma of the Mucosa
ICD-9: 232 ○ ICD-10: D02
Malignant melanomas arising in the mucosal epithelial lining of the respiratory tract and gastrointestinal and genitourinary tracts are very rare, with an annual incidence of 0.15% per 100,000 individuals.
Major sites of the mucosal melanomas are the vulva and vagina (45%) and the nasal and oral cavity (43%).
Mucosal melanomas are so rare that there are no large databases compared with those for cutaneous melanoma.
Therefore, pathologic microstaging has not been possible, and the fine-tuning of the prognosis that has been useful in cutaneous melanoma (Breslow thickness) has so far not been possible in mucosal melanoma.
Melanomas of the Oral Cavity
There is a delay in diagnosis of melanoma of the oral and nasal surfaces. Although melanosis of the mucosa is common in blacks and East Indians, it involves the buccal and gingival mucosa bilaterally (see Section 33); when there is a single area of melanosis, a biopsy should be performed to rule out melanoma; this is also true of pigmented nevi in the oral cavity, which should be excised.
Melanomas in the Genitalia
These melanomas mostly arise on the glans or prepuce (see Section 36) and the labia minora; there are fewer on the clitoris and the labia majora. Most tumors extend to the vagina at the mucocutaneous border. They look and evolve like LM and LMM (see Section 34). Vulva melanomas are often flat like LMM with large areas of MIS, and this is important to ascertain in planning excision of all the lesions to prevent recurrence. Dermoscopy should be used to outline the periphery of the lesion, as is done in LMM.
Often presents with a localized, often polypoid or nodular primary tumor, but it may also present similarly to LMM.