IV.9 Cutaneous Metastatic Melanoma

IV.9

IV.9.1 Introduction

In patients with melanoma, the most common sites of initial relapse are the skin and/or subcu- taneous tissues, lymph nodes and lung [1]. Skin and/or subcutaneous loco-regional metastases occur in about 2–10% of all melanoma patients, whereas distant metastases of the skin, includ- ing those of the lymph nodes, representing the most common site of distant metastases, arise in about 42–59% of metastatic cases [1, 2]. The de- velopment of melanoma metastases depends on (a) the tumor thickness, which also influences the site of first recurrence because thicker mela- nomas tend to recur locally at first, whereas

Chapter IV.9

Cutaneous Metastatic Melanoma

Maria Antonietta Pizzichetta

IV.9

Contents

IV.9.1 Introduction . . . .260

IV.9.2 Clinical Features . . . .260

IV.9.3 Relevant Clinical Differential Diagnosis . . . .261

IV.9.4 Dermoscopic Patterns . . . .261

IV.9.4.1 Homogeneous Pattern . . . .261

IV.9.2 Saccular Pattern . . . .261

IV.9.4.3 Multicomponent and Non-specific Patterns . . . .261

IV.9.4.4 Vascular Patterns . . . .261

IV.9.5 Additional Dermoscopic Features . . . .262

IV.9.5.1 Histopathology . . . .262

IV.9.5.2 Management . . . .262

References . . . .264

thinner ones have a greater tendency to develop as first distant metastases; (b) its ulcerative state;

(c) the time of the first definitive surgical treat- ment; (d) the histological evidence of lymphatic invasion in the primary melanoma; and (e) the site of the primary melanoma, the proximal ex- tremity being least likely to have a local recur- rence, followed by the trunk, distal extremity, and head and neck [1, 2].

IV.9.2 Clinical Features

Different types of cutaneous metastatic mela- noma have been described: satellite type, which occurs within 5 cm of the primary melanoma;

in-transit type, localized beyond 5 cm of the primary melanoma but in the same regional lymph node drainage area; and distant metasta- ses, which occur beyond the regional lymph nodes [3]. Both the satellite and in-transit types result from loco-regional lymphatic spread.

They appear as blue-to-black or pink-to-red nodules that may be single or multiple, spread out or arranged in patches near the surgical scar [1]. Distant metastases of the skin often repre- sent the first sign of hematogenous spread, can be single or multiple and can occur anywhere on the body, and if diffuse, may be associated with metastases of the heart [1, 4]. They may be flat-like small papules, elevated with a nodular or fungating appearance, and are usually firm, round or oval with a diameter of 0.5–2.0 cm and with a uniform blue-black pigmentation and regular margins; alternatively, they may lack pigmentation appearing as skin-coloured, pink or reddish [1, 5].

Cutaneous Metastatic Melanoma

Maria Antonietta Pizzichetta

IV.9

Diagnosis

The clinical differential diagnosis includes blue nevi, haemangiomas, primary melanoma and cutaneous metastases from carcinoma. In rare cases, cutaneous metastases may have a zosteri- form appearance [6].

IV.9.4 Dermoscopic Patterns

A series of patterns have been identified for metastatic melanoma that are helpful in the der- moscopic diagnosis, but in some cases, the diag- nosis cannot be definitely defined by dermos- copy.

IV.9.4.1 Homogeneous Pattern

A diffuse homogeneous or non-homogeneous bluish-brown, blue-grey to blue-black pigmen- tation without a pigment network or any other recognizable local features has been described [7, 8]. In these cases, the differentiation from blue nevus can be extremely difficult. The pres- ence of additional colours and features, such as a peripheral reddish halo, globules/dots and surrounding grey streaks, greatly help to distin- guish them from blue nevus.

IV.9.2 Saccular Pattern

Some metastatic melanomas present with a sac- cular pattern that consists of clusters of round and ovoid shape, sized up to 0.45 mm sacculi, reddish, reddish-blue, red-brown and blue-grey in colour [5]. Like those found in angioma and angiokeratoma, they have a hint of a purple or reddish pigmentation and may be separated by whitish-opaque areas of fibrosis, but in meta- static melanoma sacculi are not well demarcated [9]. Some authors have described a globular pat- tern characterized by aggregations of irregular brown-black, brown-red, blue-grey, bluish-red and milky red globules [10–12]. In these cases, the differential diagnosis includes nevus with a globular pattern, but these globules are usually

symmetrical, well-demarcated, homogeneous in size, shape and pigmentation, more frequent- ly brown and smaller in diameter [5].

IV.9.4.3 Multicomponent

and Non-specific Patterns Multicomponent and non-specific patterns have also been reported, and the differential diagno- sis includes primary melanoma [10, 12].

IV.9.4.4 Vascular Patterns

Amelanotic/hypomelanotic metastatic melano- ma may have a dermoscopically visible poly- morphous vascular pattern characterized by the simultaneous presence of more types of vascu- lar structures with different morphological as- pects [5, 13, 14]. These aspects include linear ir- regular vessels, which in metastatic melanoma appear even more irregular in shape, size (rang- ing from very subtle to dilated to aneurysmatic) and distribution, often running horizontally at the periphery of the lesion [5]. Irregular hairpin vessels, defined in primary melanoma as long vascular loops, sometimes twisted and bending [15], have also been seen in metastatic melano- ma where their characteristic twists and bends are more accentuated, forming longer convolu- tions of irregularly distributed vessels. During their growth, these vessels elongate, change their shape and give origin to glomerular-like vessels found also in metastatic melanoma [16].

Dotted vessels and milky-red globules/areas [10–15] may also appear in metastatic melano- ma, and may be scattered throughout the lesion.

Furthermore, in metastatic melanoma, micro- scopic ovoid blood lakes corresponding to spon- taneous microhaemorrhages can be found next to irregularly shaped and aneurysmatic blood vessels [5]. All these vessels caused by neovascu- larization can be seen both in primary melano- ma and metastatic melanoma, but in metastatic melanoma they are positioned prevalently pe- ripherally, are more irregularly distributed and are intermixed, thus determining a more pro- nounced polymorphism.

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IV.9.5 Additional Dermoscopic Features

Other features to consider in addition to the global pattern include perilesional light brown halo, peripheral reddish halo, irregularly local- ized peripheral greyish patches and surround- ing grey streaks [5, 17], and can be seen in both metastatic melanoma and primary melanoma, with the exception of surrounding grey streaks corresponding to streaky melanoma cell infarcts of lymphatic and/or blood vessels, which have been found only in metastatic melanoma [5].

IV.9.5.1 Histopathology

Metastatic melanomas consist of nodules of atypical melanocytes that usually involve the subcutaneous fat or dermis without involve- ment of the overlying epidermis. In some cases, however, they may exhibit epidermotropism in- vading the overlying epidermis and, in such in- stances, simulate a primary melanoma [18, 19].

The microscopic features that suggest the meta- static nature of lesions include: small zones of epidermal involvement compared with the der- mal component, thinning of the epidermis by aggregates of atypical melanocytes within the dermis often associated with widening of the dermal papillae [18, 20], the presence of atypical melanocytes within blood and lymphatic ves- sels [20] and the absence of, or a limited, junc- tional activity [18, 19]. Metastatic melanoma can also occur with only an epidermal pattern and pagetoid spread, making the differentiation from a melanoma in situ very difficult [12, 21].

Other features in favour of cutaneous metastatic melanoma include small size (<3 mm in diame- ter), symmetry and a multiple lesion presenta- tion [3, 19].

IV.9.5.2 Management

When metastases of the skin and subcutaneous tissue are solitary or few in number and repre- sent the only metastatic site, surgical excision may be the most effective treatment [2]. When the interval of the appearance of new lesions is short, or in the presence of numerous or bulky lesions, hyperthermic isolated limb perfusion (ILP) with melphalan is the most effective treat- ment [2]. Combination therapy, using melpha- lan and tumor necrosis factor alpha, seems su- perior to melphalan alone in very large metastatic melanoma [22]. Systemic chemother- apy or immunotherapy should be considered for patients with widespread metastases also in- volving the skin and subcutaneous tissues.

C Core Messages

■ The diagnosis of metastatic melanoma may be difficult not only clinically but also dermoscopically and histopatho- logically.

■ The dermoscopic patterns of metastatic melanoma includes numerous different dermoscopic patterns, such as homoge- neous pattern, saccular pattern, multicomponent, non-specific pattern as well as vascular pattern.

■ The correlation with the evolution of the lesion and clinical history is crucial for diagnosis.

Case Study 1.4. The dermoscopic image shows a poly- morphous vascular pattern characterized by the simul- taneous presence of linear irregular vessels (arrow) ir- regularly sized (ranging from very subtle to dilated to aneurismatic) running horizontally at the periphery of the lesion; irregular hairpin, forming a long convolution of vessels (open arrow), glomerular like (arrow head) and dotted vessels (number sign) irregularly distributed.

(original magnification ¥ 10)

Case Study 1.3.  a The clinical image shows an asymmet- ric blue to black macule with a reddish peripheral halo.

b In the dermoscopic image, a multicomponent pattern can be observed characterized by irregular black dots/

globules, (white arrow) gray-blue pigmentation in the centre of the lesion and blue-grey sacculi (open arrow).

(original magnification ¥ 10) Case Study 1.1.  a The clinical image shows a-blue-black

nodule with a scaly skin surface. b In the dermoscopic image a diffuse non-homogeneous blue-grey pigmenta- tion, additional red-black color in the left lower periph- ery of the lesion, brown-black globules /dots ( arrow )and a light peripheral reddish halo (arrow head) can be ob- served. (original magnification ¥ 10)

Case Study 1.2.  In this dermoscopic image a saccular pattern consisting of cluster of round and ovoid reddish, reddish-blue and red brown sacculi separated by whitish opaque areas can be observed. (original magnification ¥ 10)

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References

1. Meyers ML, Balch CM. Diagnosis and treatment of metastatic melanoma. In: Balch CM, Houghton AN, Sober AJ et al. (1988) Cutaneous melanoma, 3rd edn. Quality Medical Publishing, St. Louis 2. Lotze MT, Dallal RM, Kirkwood JM et al. (2001)

Cutaneous melanoma. In: DeVita VT, Hellman S, Rosenberg SA (eds) Cancer principles and prac- tice of oncology, 6th edn. Lippincott Williams and Wilkins, Philadelphia

3. Elder DE (1987) Metastatic melanoma. Pigment Cell 8:182–204

4. Gupta TD, Brasfield R (1964) Metastatic melanoma.

Cancer 17:1323–1339

5. Schulz H (2000) Epiluminescence microscopy fea- tures of cutaneous malignant melanoma metasta- ses. Melanoma Res 10:273–280

6. Itin P, Lautenschlager S, Buechner SA (1995) Zos- teriform metastases in melanoma. J Am Acad Der- matol 32:854

7. Ferrari A, Peris K, Piccolo D et al. (2000) Dermo- scopic features of cutaneous local recurrent mela- noma. J Am Acad Dermatol 43:722–724

8. Argenziano G, Soyer HP, Giorgi V de et al. (2000) Interactive atlas of dermoscopy. Edra Medical Pub- lishing and New Media, Milan

9. Kenet RO, Kang S, Barney JK et al. (1993) Clinical diagnosis of pigmented lesions using digital epilu- minescence microscopy. Arch Dermatol 129:158–

10. Stolz W, Braun-Falco O, Bilek P et al. (1988) Color 174 atlas of dermatoscopy, 2nd edn. Blackwell, London 11. Pang BK, Kossard SS (1992) Surface microscopy in

the diagnosis of micropapular cutaneous metastatic melanoma. J Am Acad Dermatol 27:775–776 12. Pizzichetta MA, Canzonieri V, Gatti A et al. (2002)

Dermoscopic features of metastases from cutane- ous melanoma mimicking benign nevi and primary melanoma. J Clin Oncol 20:1411–1418

13. Argenziano G, Zalaudek I, Corona R et al. (2004) Vascular structures in skin tumors. Arch Dermatol 140:1485–1489

14. Pizzichetta MA, Talamini R, Stanganelli I et al.

(2004) Amelanotic/hypomelanotic melanoma: clin- ical and dermoscopic features. Br J Dermatol 150:

1117–1124

15. Kreusch JF. (2002) Vascular patterns in skin tu- mors. Clin Dermatol 20:248–254

16. Kreusch JF (2005) Diagnosis of amelanotic mela- noma by dermoscopy: the importance of vascular structures. In: Marghoob AA, Braun RP, Kopf AW (eds) Atlas of dermoscopy. Taylor and Francis, Lon- don and New York

17. Bono R, Giampetruzzi AR, Concolino F et al. (2004) Dermoscopic patterns of cutaneous melanoma me- tastases. Melanoma Res 14: 367–373

18. Mehergan DA, Bergeon MT, Meheregan DR (1995) Epidermotropic metastatic melanoma. Cutis 55:225–227

19. Heenan PJ, Clay CD (1991) Epidermotropic meta- static melanoma simulating multiple primary mela- nomas. Am J Dermatopathol 13: 396–402

20. Kornberg R, Harris M, Ackerman AB (1987) Epi- dermotropically metastatic malignant melanoma:

differentiating malignant melanoma metastatic to the epidermis from malignant melanoma primary in the epidermis. Arch Dermatol 114:67–69 21. Abernethy JL, Soyer HP, Kerl H et al. (1994) Epider-

motropic metastatic melanoma simulating mela- noma in situ. Am J Surg Pathol 18:1140–1149 22. Grunhagen DJ, Brunstein F, Graveland WJ et al.

(2004) One hundred consecutive isolated limb per- fusions with TNF-a and melphalan in melanoma patients with multiple in-transit metastases. Ann Surg 240:939–948