Chapter IV.2 Acral Melanoma Toshiaki Saida, Hiroshi Koga, Yoriko Yamazaki, Masaru Tanaka IV.2 Contents thickness, biological behavior is not different among the four histogenetic types [16]. More- IV.2.1 Definition . .196 over, cutaneous melanomas not infrequently IV.2 IV.2.2 Clinical Features . .197 show overlapping histopathological features of IV2.3 Dermoscopic Criteria. 198 the four types [36]. Ackerman repeatedly criti- cized the validity of the Clark’s classification IV.2.4 Relevant Clinical Differential and proposed the unifying concept of melano- Diagnosis. 198 ma [1]. IV.2.5 Histopathology. .199 Recently, Bastian and co-workers defined ac- ral melanoma as melanoma occurring on the IV.2.6 Management. .200 non-hair-bearing skin of the palms or soles or IV.2.7 Case Study. .200 under the nails and found that this type of mel- References. .202 anoma was unique in frequent amplifications of chromosomes 5p15, 5p13, 11q13, and 12q14 [4, 7]. Particularly, amplification of 11q13 was de- tected in ~50% of this type of melanoma. Cyclin D1 is the most important candidate gene located in this chromosome region. It is noteworthy IV.2.1 Definition that 5 of 36 acral melanomas defined by Bastian and co-workers were superficial spreading mel- Acral melanoma is a melanoma that affects ac- anoma according to Clark’s classification [7]. ral areas of the skin, which is the most prevalent Another characteristic of acral melanoma is site of melanoma in non-Caucasians [5, 10]. very low rate of mutation of the BRAF onco- Strictly speaking, acral lentiginous melanoma is gene, which is commonly found in superficial not a synonym for acral melanoma. Acral len- spreading melanoma [8, 18]. These findings tiginous melanoma, originally described by suggest that molecular pathogenesis of melano- Reed in 1976 [21], is one of the four histogenetic ma is different depending on anatomical loca- types defined by Clark et al. [6]. Almost all acral tions and/or degrees of sun exposure, irrespec- lentiginous melanomas occur on glabrous (non- tive of Clark’s types. In this chapter we use the hair-bearing) acral skin. Superficial spreading term acral melanoma according to the defini- melanomas also occur on acral skin, but they tion by Bastian and co-workers [7]. are mostly seen on non-glabrous portions such Proportions of acral melanoma in all mela- as dorsal aspects of the hands and feet; however, nomas are quite different among races [5, 10, superficial spreading melanomas can occur also 17]: more than 80% in black persons, ~40% in on glabrous skin [12]. Furthermore, nodular Asians, and ~5% in Caucasian; however, there melanomas are seen on both glabrous and non- seems to be no significant difference in absolute glabrous acral skin. If stratified by the tumor incidence of acral melanoma among races [35]. Chapter IV.2 Acral Melanoma Chapter IV.2 197 Fig. IV.2.1. Clinical, dermo- Acral Melanoma scopic (a), and histopatho- logical (b) features of acral Toshiaki Saida, Hiroshi Koga, Yoriko Yamazaki, Masaru Tanaka IV.2 melanoma. This lesion was from the right heel of an 83- year-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 a is detected in the lower epi- dermis. 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) b IV.2.2 Clinical Features sion increases in size, and becomes irregular in shape and variegated in color (Fig. IV.2.1a, in- Acral melanomas occur in older patients. In a set), permitting differentiation from benign me- recent study of acral melanoma in Japan, a peak lanocytic nevus of the junctional type [23, 25]. of age distribution was in the seventh decade, Duration of this horizontal growth phase is and slight male preponderance was recognized variable: very long in some cases and transient [10]. Acral melanomas are most commonly seen in others. This macular stage is followed by the on the soles, followed by finger nails and then by vertical growth phase, which is characterized by toe nails. Palms are least frequently affected. appearance of indurated portions or elevated Clinically, most acral melanomas first appear nodules. In more advanced lesions, the indu- as a brownish macule on glabrous skin. The ini- rated or nodular portions are partly ulcerated tial stage may be difficult to recognize clinically [13]. Even in these advanced stages, macular because the lesion is small in size and is not so components are usually detected within or sur- irregular in shape and color [11]. In time, the le- rounding the lesions. Occasionally, small pale 198 T. Saida, H. Koga, Y. Yamazaki, M. Tanaka brownish macules not continuous to the main nomas, and thus this pattern is very much help- lesion are detected in the periphery (skip mac- ful in detecting early lesions of acral melanoma ules), which may be explained by the “field cell” [11]. Irregular diffuse pigmentation is another theory by Bastian [3]. dermoscopic finding of acral melanoma Most melanomas affecting nail apparatus are (Fig. IV.2.1a), which is detected in more ad- initially seen as longitudinal pigmented bands vanced macular portions [15, 29]. Moreover, of the nail plate (see Chap. IV.11) [24, 27]. In dermoscopic patterns observed in melanocytic time, the pigmented band of the nail plate in- nevus on acral volar skin, such as the parallel creases in width and becomes variegated in col- furrow pattern, the lattice-like pattern, or the or from tan to black. Later, pigmented macules fibrillar pattern, could be also detected in acral on the nail folds (Hutchinson’s sign) may devel- melanoma (see Chap. III.2) [28, 31]; however, op [32]. Still later, deformity of the nail plate is they are just focally detected within the lesion of recognized, and finally, the nail plate is de- acral melanoma, in contrast to overall regular stroyed, producing nodular lesions often ac- distribution of the patterns in melanocytic ne- IV.2 companied by ulceration. vus. Acral melanomas are not infrequently hy- Characteristic dermoscopic findings of pig- popigmented; 10~20% of acral melanoma in mented bands of the nail-apparatus melanoma Japanese was reported to be partly or completely have not yet been fully clarified [22] (see amelanotic [13]. Clinical diagnosis of amelanot- Chap. IV.11). If hyponychial volar skin is in- ic melanoma is difficult and often misdiagnosed volved by nail apparatus melanoma, the charac- as other neoplastic or non-neoplastic lesions teristic parallel ridge pattern is detected there, (see Chap. IV.3) [34]. which helps us to determine the diagnosis [14, 28]. In addition, dermoscopy enables us to rec- ognize tiny pigmentation on the cuticle not dis- IV2.3 Dermoscopic Criteria cernible with the naked eye (micro-Hutchinson sign) [14, 22]. This sign strongly suggests evolv- Dermoscopic features of advanced primary le- ing lesions of melanoma of nail apparatus sions of acral melanoma are common to those (Fig. IV.2.2); however, even by use of dermosco- affecting other anatomical sites: diffuse pig- py, it is still difficult for us to differentiate pig- mentation with variegated shades of brown mented bands of the nail plate caused by early from tan to black; abrupt edge; blue whitish veil; melanoma from those due to benign condi- and regression structures with whitish or gray- tions. ish color. In addition to irregular streaks found at the periphery, dots/globules of variable sizes are randomly distributed within a lesion [30, IV.2.4 Relevant Clinical Differential 31]. Ulceration is also common in advanced le- Diagnosis sions. In macular portions of acral melanoma, a Differentiation of early acral melanoma from very unique dermoscopic finding, termed the melanocytic nevus on glabrous skin is impor- parallel ridge pattern, is frequently detected tant. Melanocytic nevus is not uncommon on (Fig. IV.2.1a). This pattern is characterized by the glabrous skin: about 7% of Japanese general band-like pigmentation on the ridges of the skin populations have melanocytic nevi on their markings, which run in a parallel fashion on soles [25]. In general, melanocytic nevus on gla- glabrous skin [20, 31]. More importantly, the brous skin is regular in shape, usually oval or parallel ridge pattern is also frequently detected spindle-shaped, up to 7 mm in maximum di- in the lesions of melanoma in situ [28]. The sen- ameter, and homogeneous in color. In contrast, sitivity and specificity of the parallel ridge pat- most acral melanomas are seen as large, irregu- tern to acral melanoma are 86 and 99%, respec- lar lesions; however, we often encounter diffi- tively [29]. The sensitivity and specificity are culties in clinical differentiation of the two bio- almost same between invasive and in-situ mela- logically distinct entities. Dermoscopy is Acral Melanoma Chapter IV.2 199 Fig. IV.2.2. Dermoscopic and histopathological features cuticle and proximal nail fold (withe asterisk) was well of early melanoma in situ affecting nail apparatus. This -le recognized (Hutchinson’s sign). These findings prompted sion was from the right little finger of a 28-year-old Japa- us to excise this lesion. Histopathologically, random pro- nese woman. She had noticed the nail pigmentation more liferation of solitary arranged atypical melanocytes was than 10 years before. The longitudinal pigmented bands detected in the lower epithelium of the nail matrix and were 4.1 mm in width.