Акральная меланома

Chapter IV.2. Acral melanoma. Color Atlas of Melanocytic Lesions of the Skin. H. P. Soyer, G. Argenziano, R. Hofmann-Wellenhof, R. H. Johr (Eds.)


Acral melanoma is a melanoma that affects acral areas of the skin, which is the most prevalent site of melanoma in non-Caucasians [5, 10]. Strictly speaking, acral lentiginous melanoma is not a synonym for acral melanoma. Acral lentiginous melanoma, originally described by Reed in 1976 [21], is one of the four histogenetic types defined by Clark et al. [6]. Almost all acral lentiginous melanomas occur on glabrous (nonhair-bearing) acral skin. Superficial spreading melanomas also occur on acral skin, but they are mostly seen on non-glabrous portions such as dorsal aspects of the hands and feet; however, superficial spreading melanomas can occur also on glabrous skin [12]. Furthermore, nodular melanomas are seen on both glabrous and nonglabrous acral skin. If stratified by the tumor thickness, biological behavior is not different among the four histogenetic types [16]. Moreover, cutaneous melanomas not infrequently show overlapping histopathological features of the four types [36]. Ackerman repeatedly criticized the validity of the Clark ’s classification and proposed the unifying concept of melanoma [1].

Recently, Bastian and co-workers defined acral melanoma as melanoma occurring on the non-hair-bearing skin of the palms or soles or under the nails and found that this type of melanoma was unique in frequent amplifications of chromosomes 5p15, 5p13, 11q13, and 12q14 [4, 7]. Particularly, amplification of 11q13 was detected in ~50% of this type of melanoma. Cyclin D1 is the most important candidate gene located in this chromosome region. It is noteworthy that 5 of 36 acral melanomas defined by Bastian and co-workers were superficial spreading melanoma according to Clark ’s classification [7]. Another characteristic of acral melanoma is very low rate of mutation of the BRAF oncogene, which is commonly found in superficial spreading melanoma [8, 18]. These findings suggest that molecular pathogenesis of melanoma is different depending on anatomical locations and/or degrees of sun exposure, irrespective of Clark ’s types. In this chapter we use the term acral melanoma according to the definition by Bastian and co-workers [7].

Proportions of acral melanoma in all melanomas are quite different among races [5, 10, 17]: more than 80% in black persons, ~40% in Asians, and ~5% in Caucasian; however, there seems to be no significant difference in absolute incidence of acral melanoma among races [35].

Acral Melanoma 1a



Acral Melanoma 1b

Fig. 1. Clinical, dermoscopic (a), and histopathological (b) features of acral melanoma. This lesion was from the right heel of an 83year-old Japanese man. Seven years previously, he noticed a small brown macule on his left heel. At his first visit to us, this lesion was 58×46 mm in size, and irregular and random in shape and color (a, inset), accompanied by ulcerated crusted areas (arrow). Dermoscopically, the parallel ridge pattern was well recognized along with diffuse irregular pigmentation and the fibrillar pattern (circle). Histopathologically, random proliferation of melanocytes is detected in the lower epidermis. It is noteworthy that the degree of proliferation is more prominent in the crista profunda intermedia (arrows) underlying the surface ridge of the skin marking (b)

Клинические черты

Acral melanomas occur in older patients. In a recent study of acral melanoma in Japan, a peak of age distribution was in the seventh decade, and slight male preponderance was recognized [10]. Acral melanomas are most commonly seen on the soles, followed by finger nails and then by toe nails. Palms are least frequently affected.

Clinically, most acral melanomas first appear as a brownish macule on glabrous skin. The initial stage may be difficult to recognize clinically because the lesion is small in size and is not so irregular in shape and color [11]. In time, the lesion increases in size, and becomes irregular in shape and variegated in color (Fig. IV.2.1a, inset), permitting differentiation from benign melanocytic nevus of the junctional type [23, 25]. Duration of this horizontal growth phase is variable: very long in some cases and transient in others. This macular stage is followed by the vertical growth phase, which is characterized by appearance of indurated portions or elevated nodules. In more advanced lesions, the indurated or nodular portions are partly ulcerated [13]. Even in these advanced stages, macular components are usually detected within or surrounding the lesions. Occasionally, small pale brownish macules not continuous to the main lesion are detected in the periphery (skip macules), which may be explained by the “field cell” theory by Bastian [3].

Most melanomas affecting nail apparatus are initially seen as longitudinal pigmented bands of the nail plate (see Chap. IV.11) [24, 27]. In time, the pigmented band of the nail plate increases in width and becomes variegated in color from tan to black. Later, pigmented macules on the nail folds (Hutchinson’s sign) may develop [32]. Still later, deformity of the nail plate is recognized, and finally, the nail plate is destroyed, producing nodular lesions often accompanied by ulceration.

Acral melanomas are not infrequently hypopigmented; 10~20% of acral melanoma in Japanese was reported to be partly or completely amelanotic [13]. Clinical diagnosis of amelanotic melanoma is difficult and often misdiagnosed as other neoplastic or non-neoplastic lesions (see Chap. IV.3) [34].

Дермоскопические критерии

Dermoscopic features of advanced primary lesions of acral melanoma are common to those affecting other anatomical sites: diffuse pigmentation with variegated shades of brown from tan to black; abrupt edge; blue whitish veil; and regression structures with whitish or grayish color. In addition to irregular streaks found at the periphery, dots/globules of variable sizes are randomly distributed within a lesion [30, 31]. Ulceration is also common in advanced lesions.

In macular portions of acral melanoma, a very unique dermoscopic finding, termed the parallel ridge pattern, is frequently detected (Fig. IV.2.1a). This pattern is characterized by band-like pigmentation on the ridges of the skin markings, which run in a parallel fashion on glabrous skin [20, 31]. More importantly, the parallel ridge pattern is also frequently detected in the lesions of melanoma in situ [28]. The sensitivity and specificity of the parallel ridge pattern to acral melanoma are 86 and 99%, respectively [29]. The sensitivity and specificity are almost same between invasive and in-situ melanomas, and thus this pattern is very much helpful in detecting early lesions of acral melanoma [11]. Irregular diffuse pigmentation is another dermoscopic finding of acral melanoma (Fig. IV.2.1a), which is detected in more advanced macular portions [15, 29]. Moreover, dermoscopic patterns observed in melanocytic nevus on acral volar skin, such as the parallel furrow pattern, the lattice-like pattern, or the fibrillar pattern, could be also detected in acral melanoma (see Chap. III.2) [28, 31]; however, they are just focally detected within the lesion of acral melanoma, in contrast to overall regular distribution of the patterns in melanocytic nevus.

Characteristic dermoscopic findings of pigmented bands of the nail-apparatus melanoma have not yet been fully clarified [22] (see Chap. IV.11). If hyponychial volar skin is involved by nail apparatus melanoma, the characteristic parallel ridge pattern is detected there, which helps us to determine the diagnosis [14, 28]. In addition, dermoscopy enables us to recognize tiny pigmentation on the cuticle not discernible with the naked eye (micro-Hutchinson sign) [14, 22]. This sign strongly suggests evolving lesions of melanoma of nail apparatus (Fig. IV.2.2); however, even by use of dermoscopy, it is still difficult for us to differentiate pigmented bands of the nail plate caused by early melanoma from those due to benign conditions.

Релевантный клинический дифференциальный диагноз

Differentiation of early acral melanoma from melanocytic nevus on glabrous skin is important. Melanocytic nevus is not uncommon on the glabrous skin: about 7% of Japanese general populations have melanocytic nevi on their soles [25]. In general, melanocytic nevus on glabrous skin is regular in shape, usually oval or spindle-shaped, up to 7 mm in maximum diameter, and homogeneous in color. In contrast, most acral melanomas are seen as large, irregular lesions; however, we often encounter difficulties in clinical differentiation of the two biologically distinct entities. Dermoscopy is immensely helpful in this differentiation; the parallel ridge pattern is unique to acral melanoma and the parallel furrow and the latticelike patterns are characteristic of melanocytic nevus (see Chap. III.2) [29]. Regularly distributed fibrillar pattern also strongly suggests melanocytic nevus.

Acral Melanoma 2

Fig. 2. Dermoscopic and histopathological features of early melanoma in situ affecting nail apparatus. This lesion was from the right little finger of a 28-year-old Japanese woman. She had noticed the nail pigmentation more than 10 years before. The longitudinal pigmented bands were 4.1 mm in width. Dermoscopically (inset), the pigmented bands were not so irregular, but the nail plate was partly destroyed at the distal tip (arrowhead). Moreover, proximal to the pigmented bands, pigmentation on the cuticle and proximal nail fold (withe asterisk) was well recognized (Hutchinson’s sign). These findings prompted us to excise this lesion. Histopathologically, random proliferation of solitary arranged atypical melanocytes was detected in the lower epithelium of the nail matrix and nail bed, confirming the diagnosis of melanoma in situ. In addition, solitary melanocytes were detected in the epidermis corresponding to the cuticle (circle)

Pigmented macules seen in Peutz–Jeghers syndrome and Laugier–Hunziker syndrome show the parallel ridge pattern [28, 31], but these conditions are easily diagnosed clinically: multiple tiny macules on the fingers and toes as well as on the lips. In our evaluation, brown macules induced by cytotoxic drugs such as 5-f luorouracil also show the parallel ridge pattern on dermoscopy. But this condition also can be clinically diagnosable, as multiple lesions on the background of grayish red atrophic skin. Volar melanotic macules commonly seen in black persons may show the parallel ridge pattern. Socalled black heel, i.e., calcaneal petechiae induced by ill-fitted shoes of athletes, is included in clinical differential diagnosis of acral melanoma. This condition is definitely diagnosed by the unique dermoscopic findings termed the reddish black “pebbles on the ridges” [31] and homogeneous pigmentation [38].


Histopathologically, in macular portions of acral melanoma, melanocytes randomly proliferate in the lower epidermis, which shows acanthosis and is often accompanied by elongated rete ridges [23]. Preferential proliferation of melanocytes in the crista profunda intermedia, an epidermal rete ridge underlying the surface ridge, can be recognized (Fig. IV.2.1b). The proliferating melanocytes are usually round or oval in shape but occasionally spindle-shaped or dendritic. The nuclei are often large and hyperchromatic. Near the invasive portions, the degrees of melanocytic proliferation become more pronounced: atypical melanocytes are often distributed throughout the entire epidermis [17]. In the invasive areas, growth of atypical melanocytes is seen in the dermis, usually arranged in densely packed nests or in sheets, often accompanied by lymphocytic infiltration. In more advanced lesions, epidermis is destroyed by infiltration of atypical melanocytes, producing necrotic, ulcerated areas.

Histopathological features of melanoma in situ affecting glabrous skin are similar to those of macular portion of acral melanoma. It is noteworthy that, corresponding to the dermoscopic parallel ridge pattern, proliferation is prominent in crista profunda intermedia, an epidermal rete ridge underlying the surface ridge [11, 20, 21, 26, 28]. This is in contrast to histopathological findings of melanocytic nevus showing the parallel furrow pattern, in which proliferation of melanocytes (nevus cells) are mostly confined to crista profunda limitans, an epidermal rete ridge underlying the surface sulcus [19]. To recognize these important findings, excised tissues must be cut perpendicularly to the skin markings [9, 11]. If the tissue of melanocytic nevus is cut parallel to the skin markings, continuous, irregular proliferation of melanocytes is seen in the lower epidermis, which mimics the features of melanoma in situ [33].

We occasionally see acral pigmented lesions which exhibit the parallel ridge pattern on dermoscopy, but their histopathological features are too subtle to diagnose as melanoma in situ: only slight increase of melanocytes in the basal layer of the crista profunda intermedia [11]. In about 40% of these subtle lesions, we have found amplification of cyclin D1 by f luorescent in-situ hybridization analysis, which strongly supports that these subtle lesions are evolving melanoma in situ [37].


Primary lesions of acral melanoma without metastatic lesions should be surgically excised with the free margin of 1–2 cm. Acral melanoma in situ is cured by simple excision with only 5 mm free margin. Suspicious lesions whose diagnosis cannot be definitely determined, even with dermoscopy, should be excised and evaluated histopathologically. In this case, the tissue specimen should be cut perpendicularly to the skin markings.

If nail-apparatus melanoma is detected early in the in-situ stage, amputation of the digit is not necessary. Such an early nail-apparatus melanoma can be cured with total excision of the nail apparatus, and the tissue defect is easily covered with skin grafting, preserving the function of the digit [27].

In a recent study of a total of 801 acral melanomas in Japan, 5-year survival rates according to the present UICC/AJCC staging were as follows: stage IA, 98.1%; stage IB, 95.8%; stage IIA, 93.8%; stage IIB, 73.4%; stage IIC, 64.2%; stage IIIA, 48.0%; stage IIIB, 39.4%; stage IIIC, 44.1%; and stage IV, 16.0% (unpublished data).

The survival rates in stages IIA, IIB, IIC and IIIC seem to be better than those reported by Balch et al. [2], whose patients were mainly Caucasians suffering from superficial spreading melanoma.

Изучение случаев

A 56-year-old Japanese woman noticed a brownish macule on her left sole 6 years previously. At her first visit to us, the pale brown macule was 21×16 mm in size, and not so irregular in shape and color (Fig. IV.2.3a, inset). These findings suggested benign melanocytic lesions such as lentiginous nevus or volar melanotic macule. Dermoscopically, however, this lesion exhibited the typical features of the parallel ridge pattern (Fig. IV.2.3a), strongly suggesting that this was melanoma in situ, and we excised the lesion totally.

Histopathologically, in tissue sections cut perpendicularly to the skin markings, random proliferation of melanocytes was recognized in the lower epidermis, which was more prominent in the crista profunda intermedia underlying the surface ridge of the skin marking (Fig. IV.2.3b, arrows).

Acral Melanoma 3a

Acral Melanoma 3b

Fig. 3. Case Study


Using conventional clinical and histopathological criteria, we diagnosed this case as possible lentiginous melanocytic nevus; however, if we consider all the findings, including dermoscopic features of the typical parallel ridge pattern, we could diagnose this lesion as an early lesion of acral melanoma in situ [11, 29, 30]. This case demonstrates that dermoscopy is very helpful in detecting early melanoma on glabrous skin. Preferential proliferation of melanocytes in the epidermal rete ridges underlying the surface ridges, which corresponds to the dermoscopic parallel ridge pattern, strongly suggests the diagnosis of early acral melanoma.

Центральные мессенджи

The parallel ridge pattern is a highly sensitive and specific dermoscopic pattern of acral melanoma, including early evolving lesions, and thus, using this dermoscopic finding, we can effectively detect acral melanoma in early, curable stages.

In addition, recent studies suggest that acral melanoma is unique in molecular pathogenesis, which could be used in developing molecular diagnosis and molecular targeting therapy.


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