IV.7.1 Definition
Lentigo maligna and lentigo maligna melanoma represent a characteristic, histogenetic subclass of melanocytic malignancies. They are found on chronically light-exposed skin, usually the face of middle-aged and elderly people. During the long preinvasive period, called lentigo ma- ligna, a very slow horizontal growth can be ob- served. After a variable period of time, invasion into the underlying dermis will occur. Other names for the preceding horizontal or in-situ growth phase are Hutchinson’s melanotic freck- le and premalignant melanosis of Dubreuilh.
Once obvious dermal invasion is present, the name lentigo maligna melanoma is appropri- ate.
Chapter IV.7
Melanoma of the Face
Ulrike Weigert and Wilhelm Stolz
IV.7
Contents
IV.7.1 Definition . . . .233
IV.7.2 Clinical Features . . . .233
IV.7.3 Dermoscopic Criteria . . . .233
IV.7.4 Relevant Clinical Differential Diagnoses . . . .234
IV.7.5 Histopathology . . . .234
IV.7.6 Management . . . .234
IV.7.7 Case Study . . . .235
References . . . .236
IV.7.2 Clinical Features
Lentigo maligna occurs at an average age of 63 years and lentigo maligna melanoma at 73 years. Lentigo maligna melanomas are more common in women than men, at a ratio of 1.7:1.0. Most lesions develop on the face, fre- quently on the upper cheek, temple or forehead.
About 10% of lentigo maligna melanomas are observed on extrafacial sites such as trunk and limbs [1].
Initially the lentigo maligna is a flat brown or black, irregularly shaped lesion which often gradually thins out toward the periphery. These lesions grow very slowly over months or years and there may be central regression while the peripheral margin continues to extend. In time, a raised nodule will develop indicating transi- tion to the vertical growth phase; therefore, pa- tients usually present with a history of an in- crease in diameter of the pigmented lesion, and the perception that it has changed in some way.
IV.7.3 Dermoscopic Criteria
According to the clinical course of lentigo ma- ligna and lentigo maligna melanoma, Schiffner et al. [2] developed a progression model (Fig. IV.7.1) for lentigo maligna. Slate-grey ag- gregated dots around the hair follicles are an early feature of lentigo maligna. Then short dark-brown or black streaks can be detected which can progress to very specific dark-brown or black rhomboidal structures around the fol- licles, resulting in a characteristic annular–
granular pattern. Dark-brown or black asym- metrical pigmented follicular openings can also be an early sign of lentigo maligna and represent
234 U. Weigert, W. Stolz
IV.7
the irregular proliferation of atypical melano- cytes within the follicles. In the final stage, ho- mogeneous areas are present and the hair folli- cles are now obliterated, and the development of milky red areas correlates with invasive mela- noma.
IV.7.4 Relevant Clinical Differential Diagnoses
Three relevant differential diagnoses of early le- sions are solar (actinic) lentigo (flat seborrheic keratosis), pigmented actinic keratosis and pig- mented basal cell carcinoma. Dermoscopically solar lentigines often present with horn pseudo- cysts, fingerprint-like structures, a moth-eaten border and the jelly sign [3]. Actinic keratoses tend to have more surface scaling and their rough surface often gives a clue to the diagnosis. Der- moscopy also may be helpful in diagnosing a pig- mented basal cell carcinoma. Often typical crite- ria, such as gray-blue ovoid nests and globules, maple leaf-like areas, spoke-wheel structure, ul- ceration and arborizing vessels, are present.
IV.7.5 Histopathology
The histology of lentigo maligna is character- ized by an increased number of atypical mela- nocytes in the basal epidermis, which are ar- ranged as single cells or in small nests. The
lesion is poorly circumscribed and periadnexal extension is common [1]. There is no downward invasion into the underlying dermis. Solar dam- age is always noted as evidenced by atrophic epi- dermis, with effacement of rete ridges, and by marked underlying dermal elastosis. In lentigo maligna melanoma an invasion of the underly- ing dermis can be seen.
IV.7.6 Management
Surgical excision is the treatment of choice for lentigo maligna and lentigo maligna melanoma to obtain clinical and histological clearance [4].
There are three surgical options including con- ventional surgery, staged surgery and Mohs mi- crographic surgery.
In conventional surgery the recommended margins for lentigo maligna are 0.5 cm, the same as for in-situ melanoma [5]. The surgical margins for lentigo maligna melanoma are in principle the same as for invasive melanoma (1 cm for lesions up to 2 mm in thickness, 2 cm- margins for tumor thickness >2 mm) [6], but the margin of excision can be limited on the face to obtain acceptable cosmetic results. Because histological margins can extend beyond the clinically visible lesion, routinely wider margins sometimes might be necessary. Nevertheless, aggressive surgical management is not always considered appropriate on the head and neck, where there may be considerable cosmetic con-
Fig. IV.7.1. Progression model for lentigo maligna
Melanoma of the Face Chapter IV.7 235
straints. To ensure complete clearance and best cosmetic results with the smallest margin pos- sible, excision with 3D histology is used. It al- lows confirmation of negative margins with de- layed repair or, in case of Mohs micrographic surgery, completion in a single patient visit.
Studies have shown a high cure rate with sur- gery followed by a careful histological work-up in all directions compared with other treatment modalities [7, 8].
Other treatment options for lentigo maligna include cryotherapy, radiotherapy, azelaic acid, laser therapy or imiquimod.
Liquid nitrogen cryotherapy is reported to be as effective as conventional surgery as long as treatment times are sufficiently long [9]. It is recommended for use in elderly or ill patients. A major disadvantage is that is does not allow as- sessment of whether the lesion has been com- pletely destroyed.
Superficial X-ray therapy for lentigo maligna is also convenient and well tolerated, but there are significant time and cost considerations.
Clearance rates are comparable to those of con- servative surgery and cryotherapy, but possible subclinical disease may be left untreated [10].
The suggested mechanism of action of azelaic acid 20% cream or 15–35% ointment is selective cytotoxicity for abnormal melanocytes by re- versible inhibition of tyrosinase and inhibition of mitochondrial enzymes. It has to be applied twice daily for 2 weeks to 12 months, depending on response. Studies on the use of topical azelaic acid have reported variable results [11, 12]. Nev- ertheless, this convenient and well-tolerated therapy may be worth considering in patients who are unable or unwilling to undergo surgery, or in those with serious coexisting disease.
Although there have been some encouraging results with use of various lasers (Argon, CO2, Ruby, Q-switched Neodymium:Yttrium-Alu- minium-Garnet) in the treatment of lentigo maligna, there are insufficient data to support the routine use of this approach [13].
The immune response modifier imiquimod is licensed for the treatment of external genital warts and superficial basal cell carcinomas. Suc- cessful treatment of lentigo maligna was first reported by Ahmed and Berth-Jones in 2000 [14]. Since then, there have been larger studies
with promising results, although there is confu- sion about which treatment strategy offers the best results with few complications [15, 16].
Treatment has been used daily for 6 weeks or 3 months, and five times weekly for 9 months.
Local effects, such as erythema and crusting, are frequent. Further studies are necessary to identify ideal treatment protocols.
The major limitation of all these non-surgi- cal procedures is that the whole specimen is never examined histologically, and so invasive malignancy may be missed. In every case the advantages and disadvantages of various treat- ment options should be considered and therapy should be tailored to the patient.
IV.7.7 Case Study
A 40-year-old woman presented with a brown lesion on the right cheek. The lesion existed for many years and did not change in color or size.
The patient has the skin phototype II.
236 U. Weigert, W. Stolz
IV.7
The diameter of the lesion was 8 mm. Der- matoscopically, asymmetrical pigmented follic- ular openings in the upper part of the lesion could be detected.
Lentigo senilis and lentigo maligna have to be taken into account as differential diagnoses.
The correct diagnosis was lentigo maligna and the management was excision.
C
Core Messages
■ Lentigo maligna and lentigo maligna melanoma are found on chronically light-exposed skin, mostly on the face of the elderly.
■ Lentigo maligna melanoma is charac- terized by invasion into the dermis.
■ Dermoscopic criteria for lentigo maligna include asymmetrical pig- mented follicular openings, and slate- grey aggregated dots around the hair follicles proceeding to dark-brown or black streaks.
■ Differential diagnoses include lentigo senilis (flat seborrhoeic keratosis), pigmented actinic keratosis and pigmented basal cell carcinoma.
■ Surgery is the treatment of choice for lentigo maligna and lentigo maligna melanoma. Other treatment modalities for lentigo maligna include cryothera- py, radiotherapy, azelaic acid and imiquimod.
References
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2. Schiffner R, Schiffner-Rohe J, Vogt T, et al. Im- provement of early recognition of lentigo maligna using dermatoscopy. J Am Acad Dermatol 2000;
42:25–32
3. Stolz W, Braun-Falco O, Bilek P, Burgdorf WHC, Landthaler M. Colour atlas of dermatoscopy, 2nd edn. Blackwell, London, 2002
4. Mahendran R, Newton-Bishop JA. Survey of UK current practice in the treatment of lentigo maligna.
Br J Dermatol 2001; 144:71–76
5. National Institute of Health Consensus Conference.
Diagnosis and treatment of early melanoma. NIH Consensus development panel on early melanoma.
J Am Med Assoc 1992; 268:1314–1319
6. Balch CM, Soong S, Smith T, et al. Long-term results of a prospective surgical trial comparing 2cm vs 4cm excision with margins for intermediate-thick- ness melanomas. Ann Surg Oncol 2001; 8:101–108 7. Bub JL, Berg D, Slee A, et al. Management of lentigo
maligna nd lentigo maligna melanoma with staged excision: a 5-year follow-up. Arch Dermatol 2004;
140:552–558
8. Cohen LM, McCall MW, Zax RH. Mohs micro- graphic surgery for lentigo maligna melanoma: a follow-up study. Dermatol Surg 1998; 24:673–677 9. Collins P, Rogers S, Goggin M, et al. Cryotherapy of
lentigo maligna. Clin Exp Dermatol 1991; 16:433–
10. Farshad A, Burg G, Panizzon R, et al. A retrospec-435 tive study of 150 patients with lentigo maligna and lentigo maligna melanoma and the efficacy of radio- therapy using Grenz or soft X-rays. Br J Dermatol 2002; 146:1042–1046
11. Prieto MAR, Lopez PM, Gonzalez IR, et al. Treat- ment of lentigo maligna with azelaic acid. Int J Der- matol 1993; 32:353–364
12. Doherty VR. Azelaic acid in lentigo maligna. Br J Dermatol 1987; 116:606
13. Iyer S, Goldman M. Treatment of lentigo maligna with combination laser therapy: recurrence at 8 months after initial resolution. J Cosmet Laser Ther 2003; 5:49–52
14. Ahmed I, Berth-Jones J. Imiquimod: a novel treat- ment for lentigo maligna. Br J Dermatol 2000;
143:843–845
15. Naylor MF, Crowson N, Kuwahara R, et al. Treat- ment of lentigo maligna with topical imiquimod. Br J Dermatol 2003; 149 (Suppl):66–70
16. Powell AM, Russell-Jones R, Barlow RJ. Topical imiquimod immunotherapy in the management of lentigo maligna. Clin Exp Dermatol 2004; 29:15–21
