AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

The overall incidence of cutaneous melanoma is increasing faster than that of any other neoplasm. In 2006, an estimated 62,200 patients will have melanoma, and 7,900 will die of the disease (Jemal, 2006). The annual lifetime risk of an American developing invasive melanoma was estimated as 1 in 71 in 2005.

Lentigo maligna melanoma is one of the 4 main subtypes of invasive melanoma and represents 5-15% of cases. The other types are superficial spreading (70%), nodular (10-15%), and acral lentiginous melanoma (5%) (Liu, 2003).

Sir John Hutchinson first described lentigo maligna in 1890; the disease continues to be called Hutchinson melanotic freckle on occasion. The Hutchinson melanotic freckle was originally thought to be infectious because of its slow yet progressive growth. The lesion has subsequently been characterized as malignant lentigo of elderly people, junctional nevus, and melanoma in situ. Most authors currently refer to it as lentigo maligna when it is confined to the epidermis and lentigo maligna melanoma when it violates the dermis.

Pathophysiology

Many authors consider lentigo maligna to be a preinvasive lesion induced by long-term cumulative ultraviolet injury. Conceptually, the term melanoma is used when atypical melanocytes invade the rich vascular and lymphatic networks of the dermis, thereby establishing metastatic potential.

Most malignant melanoma arise as superficial tumors confined to the epidermis, which is often known as horizontal growth. At some point there is a stepwise accumulation of genetic abnormalities leading to proliferation and progression to the vertical growth phase leading to dermal and deeper involvement and subsequently nodal metastases.

Frequency

United States

The incidence of lentigo maligna is greatest in Hawaii, intermediate in the central and southern states, and lowest in the northern states.

International

The incidence of melanoma is highest in Australia, where lentigo maligna can be found at an annual rate of 1.3 cases per 100,000 population (Holman, 1980).

Mortality/Morbidity

Melanoma is second only to adult leukemia in years of potential life lost in young adults. The disease is responsible for death in a disproportionately high number of young and middle-aged adults.

Lentigo maligna melanoma has mortality rate similar to that of other melanoma types if depth of the tumor is taken into account.

About 10% of melanomas are familial. A first-degree relative has an 8-12 times increased risk of melanoma. The major gene resides on chromosome arm 9p and encodes a tumor suppressor gene called CDKN2A or MTS1. The second gene that has been noted in melanoma prone families is CDK4 and germline mutations have been identified in this group.

Race

Melanoma is the most frequent cancer in white women aged 25-29 years and the second most frequent (after breast cancer) in white women aged 24-30 years with fair skin.

Sex

A slight female preponderance is seen among patients with lentigo maligna.

Age

Patients with lentigo maligna tend to be older than those with superficial spreading malignant melanoma or nodular melanoma.

• Generally, patients with lentigo maligna are older than 40 years, with a mean age of 65 years.
• The peak incidence occurs in the seventh to eighth decades of life.
• Lentigo maligna and lentigo maligna melanoma have higher occupational exposure and lower recreational sun exposure.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

The risk of lentigo maligna melanoma increases as the number of years of residence in sunnier climates (eg, southern United States) increases, and risk increases with increased hours of exposure to sunlight, increased amount of actinic damage, and a history of nonmelanoma skin cancer.

• Associations have been reported with the following:
• • Basal cell carcinoma
  • Light skin color (especially people who have red hair)
  • History of severe sunburn
  • Porphyria cutanea tarda
  • Werner syndrome
  • Tyrosine-positive oculocutaneous albinism
  • Xeroderma pigmentosa
• Lentigo maligna most commonly affects the sun-exposed skin of the head and neck, with a predilection for the nose and cheek. In fact, in Australia, the lesions occur more commonly on the right side (driver's side) of the head and neck in men and on the left side (passenger's side) in women. According to the Australian road traffic database, most Australian drivers are men, and most passengers in the front seat are women.
• Suspect the possibility of melanoma if a patient reports a new pigmented lesion or changes in an existing mole. About 50% of melanomas can arise from normal skin with no preexisting lesions.

Physical

Patients with melanoma need a complete and thorough physical examination, especially with focus on skin and lymph nodes. Review of systems should focus on symptoms pertaining to metastatic disease. Melanoma usually metastasizes to lungs, liver, and brain.

The most frequent findings suggesting early melanoma are changes in size or color of a new pigmented lesion or an existing mole. Lentigo maligna most commonly affects the sun-exposed skin of the head and neck, with a predilection for the nose and cheek. Less common sites include the arm, leg, and trunk. The conjunctivae and oral mucosa may become involved when a cutaneous lentigo maligna spreads onto mucosal surfaces. Signs suggestive of a more locally advanced lesion include elevation, burning, itching, pain, or bleeding.

• The simple ABCDE rule of melanoma helps patients as well as physicians to suspect and make an early diagnosis.
• • A - Asymmetry
  • B - Border irregularity
  • C - Color variegation
  • D - Diameter greater than 6 mm (tip of pencil head), although melanoma can occur in lesions less than 6 mm
  • E - Enlargement
• Lentigo maligna, the precursor lesion, has been likened to a stain on the skin. The lesion typically is tan-brown, with differing shades throughout.
• Lentigo maligna can be present for long periods (5-15 y) before invasion occurs, although rapid progression within months has been described. The percentage of lentigo maligna that progress to lentigo maligna melanoma remains unknown, but estimates of the lifetime risk of developing lentigo maligna melanoma in patients diagnosed with lentigo maligna at age 45 years appears to be 5%. The risk for progression to lentigo maligna melanoma appears to be proportional to the size of the lesion of lentigo maligna
  (Weinstock, 1987).
• • Distinguishing lentigo maligna from its invasive counterpart on a clinical basis continues to present diagnostic dilemmas, especially in patients who had prior therapeutic interventions like cryotherapy. It is important to have a low threshold for biopsy of pigmented facial lesions.
  • In one series of 85 excised lesions with a clinical diagnosis of lentigo maligna, more than 50% had invasive lentigo maligna melanoma.
• A strong correlation exists between patients who report finding a nodule and diagnosis of melanoma. Although palpability usually indicates dermal invasion, clinical examination may be unreliable in early invasive lentigo maligna melanoma (lesions <1 mm).
• Assess the total number of all types of moles. More than 50 nevi 2 mm in diameter or larger indicate increased risk.
• Search for dysplastic (clinically atypical) melanocytic nevi. Irregular pigment patterns, such as variegation, central dark areas, or halos of pigment, may indicate the presence of dysplasia. Atypical nevi tend to be larger than common acquired neomelanocytic nevi, which rarely exceed 5 mm.
• Search for congenital melanocytic nevi. People with very large or giant congenital nevi have an increased lifetime risk (>6%) of developing melanoma. Intermediate sized (>0.5 cm), raised, pigmented lesions, with or without hair, that do not have the features of clinically atypical nevi have an uncertain but elevated risk for development of melanoma.

Causes

• Ultraviolet radiation exposure: For people who live in Australia, risk increases as the number of years spent in Australia increases, and risk increases with increased hours of exposure to sunlight, with the amount of actinic damage, and with history of nonmelanoma skin cancer.
• Increased number of melanocytic nevi, including large or giant congenital nevi
• Fair skin
• History of severe sunburn
• Occupational risk

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Solar lentigo
Pigmented actinic keratosis
Seborrheic keratosis
Common acquired nevi
Dysplastic nevi

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Patients with low risk melanomas, less than 1 mm thick, routinely do not need laboratory studies. Most centers order liver function tests and lactose dehydrogenase (LDH) as part of the initial laboratory evaluation.

Imaging Studies

• Chest radiograph is done by most institutions in patients with low-risk disease.
• A PET scan, staging CT scans, or MRI can be performed for patients with node positive disease or symptoms suggestive of metastasis, to determine extent of disease.

Other Tests

• Dermoscopy is a newer tool available to help the dermatologist distinguish benign from malignant lesions. It is a hand held instrument that magnifies the skin lesion ten times to enable more accurate diagnosis.

Procedures

• Skin biopsy
• • Ideal biopsy of lesions should include full thickness skin extending to the subcutaneous fat.
  • Avoid superficial skin biopsy by shaving, scissors excision, or curettage because these techniques do not allow for assessment of tumor thickness, which is important for prognostication and treatment planning.
  • A better choice would be excisional biopsy with a narrow margin of normal-appearing skin, which usually can be performed on lesions unless the result would be disfiguring, in which case incisional biopsy is considered reasonable. Incisional biopsy is also indicated for lesions that are too large for complete excision.
  • The type of biopsy does not influence patient survival or rate of metastasis. Previous concerns that incision into a melanoma promotes its dissemination have been allayed. The excisional biopsy specimen may be obtained by elliptical excision, saucerization, or punch biopsy, if the lesion is small enough. The specimen should include a portion of subcutaneous fat to ensure that accurate microstaging can be determined.
• Lymph node biopsy
• • Sentinel lymph node biopsy is done to assess regional lymph node involvement and to decide on adjuvant therapy. It is indicated in all melanoma patients except Stage 0 or Stage 1A, that is, patients with a lesion less than 1 mm.
  • If metastasis is present, a full nodal dissection is done to fully stage the disease.

Staging

Lentigo maligna is melanoma in situ.

Lentigo maligna melanoma is melanoma.

The American Joint Committee on Cancer (AJCC) 2002 Tumor, Node, Metastases (TNM) staging for melanoma uses tumor size, rather than invasion, and ulceration to stage the tumor.

• Tumor staging is as follows (for the stages below, a indicates without ulceration, and b indicates with ulceration):
• • Tx - Primary tumor cannot be assessed (eg, regressed primary)
  • Tis - Melanoma in situ
  • T1 - Less than 1 mm
  • T2 - 1.01-2.0 mm
  • T3 - 2.01-4.0 mm
  • T4 - Greater than 4.0 mm
• Nodal staging is as follows (for the stages below, a indicates micrometastasis [clinically occult], and b indicates macrometastasis [clinically apparent]):
• • N - Nodal involvement
  • N1 – One node
  • N2 - 2-3 nodes
  • N3 - 4 nodes or more
• M indicates metastasis.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

Various nonsurgical modalities are available to patients in whom surgical therapy is not feasible.

• Cryotherapy is not standard but is often used in patients who are not candidates for surgery.
• • Temperatures of -4°C to -7°C selectively destroy melanocytes while preserving keratinocytes in skin and mucosal epithelia.
  • The first report of cryotherapy for lentigo maligna was published in 1975.
  • Most authors discourage cryotherapy for lentigo maligna because focal lentigo maligna melanoma cannot be detected clinically.
  • Risks include hypopigmentation, infection, scarring, inability to detect invasive melanoma, and failure to treat periadnexal involvement.
• Radiation therapy
• • Miescher first described radiation therapy in treatment of lentigo maligna in 1954. Others have employed similar techniques with varying results.

    Like cryotherapy, radiation therapy may miss focal lentigo maligna melanoma

• Topical Imiquimod 5% cream has recently been described in many studies to be effective, especially in patients who are not surgical candidates. Imiquimod is an immune response modifier that is offering encouraging results, but further studies are needed to identify ideal treatment protocols.

Surgical Care

Lentigo maligna is treated with definitive surgical therapy. The actual margins of atypia usually extend beyond the clinically apparent margin; total removal may be difficult. National Comprehensive Cancer Network (NCCN) practice guidelines for melanoma in 2006 are as follows (tumor thickness, recommended clinical margin):

• Tumor in situ, margin 0.5 cm
• Tumor less than 1 mm, margin 1 cm
• Tumor 1-2 mm, margin 1-2 cm
• Tumor 2-4 mm, margin 2 cm
• Tumor > 4 mm, margin at least 2 cm

But a study by Agarwal and colleagues in 2002 suggests that 5 mm margins are not sufficient in lentigo maligna, given that only 42% of tumors were cleared after a 5 mm excision in this study.

• Standard excisions have a recurrence rate of 8-20%. Mohs surgery and staged excision may offer better control and lower recurrence rates (4-5%)(Stevenson, 2005; Mckenna, 2006).
• Nonsurgical therapies such as cryosurgery, radiotherapy, electrodissection, curettage laser surgery, and topical medications have a recurrence rate of 20-100% at 5 years.

Consultations

Melanoma should be managed by a multidisciplinary team

that includes a dermatologist, surgeon, and medical oncologist.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

In the presence of nodal disease, multiple chemotherapy and immunotherapy drugs have been tested. High-dose alpha-interferon remains the standard adjuvant option, especially with stage III cancer, in which it results in a 9-month increase in disease-free survival and a 1-year increase in overall survival. In the presence of metastases, the options include high-dose interleukin-2, dacarbazine, and temozolomide.

Vaccines have been tested in various studies, but none have lead to any significant survival advantage. GM-CSF has been

found to prolong time to progression compared to historical

control in both node-positive and metastatic stage of the disease.

Drug Category: Biological response modulators

These agents have antiviral, antitumor, and immunomodulatory actions. They are used as adjuvant treatment.

Drug Category: Antineoplastic agents

These agents inhibit cell growth and proliferation.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Outpatient Care

• Follow-up consists of examination of the skin, the primary site, and the regional nodal basin.
• The National Cancer Institute recommends follow-up every 6 months for the first 2 years after surgical therapy in patients without atypical moles and without a family history of melanoma. If the patient is disease-free at 2 years, conduct yearly follow-up visits.
• For patients with atypical moles or a positive family history, follow up every 3-6 months.
• Base the decision to extend the interval after 2 years on the stability and characteristics of the atypical moles.

Deterrence/Prevention

• Avoidance of sun exposure and use of sunscreen is highly recommended.

Prognosis

• The overall prognosis is good for patients with localized melanoma and no nodal or distant metastases. An overall 5-year survival rate of 79% has been reported for patients with stage I or stage II lesions.
• In patients with regional nodal disease (ie, stage III), the 3 dominant prognostic variables are the number of nodal metastases, the patient's age, and ulceration in the primary tumor.
• • Numerous studies have shown that the number of nodes with metastases has significant prognostic value in patients with stage III disease. Patients with 1 positive node fared the best; 40% remained alive at 10 years. Those with 2-4 positive nodes had an intermediate 10-year survival rate of 26%. Patients with 5 or more positive nodes had the lowest 10-year survival rate, at 15%.
  • In both men and women with stage III melanoma, patients older than 50 years tend to do worse. In studies evaluating tumor ulceration as a prognostic factor in lentigo maligna melanoma, the 3-year survival rate for patients with an ulcerated primary tumor was 20%, compared with 35% for those with nonulcerated primary lesions.
• Patients with stage IV melanoma generally have a poor prognosis. From the time the metastasis is diagnosed, the median survival is 6-7.5 months, with a 5-year survival rate of approximately 6%.

Patient Education

• Education plays an integral role in the follow-up care of patients with melanoma.
• Instruct patients on self-examination for new and locoregional recurrences. Teach them to recognize the classic characteristics of cutaneous melanoma in friends and family. In addition, during every follow-up visit, counsel patients to avoid excess sun exposure, to use sunblock liberally, and to wear protective clothing.
• For excellent patient education resources, visit eMedicine's Cancer and Tumors Center. Also, see eMedicine's patient education articles Skin Cancer and Skin Biopsy.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to diagnose, which is often the case of skin lesions that were initially thought to be benign without a biopsy
• Failure to provide adequate follow-up care
• • Melanoma should be managed by a multidisciplinary team.
  • The team should include a dermatologist, surgeon, medical oncologist, and other allied health workers.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• NCCN practice guidelines in oncology for melanoma. v.2.2006.
• Abeldano AM, Saadi ME, Brea P. Amelanotic lentigo maligna melanoma. Skinmed. Jan-Feb 2004;3(1):41-4. [Medline].
• Agarwal-Antal N, Bowen GM, Gerwels JW. Histologic evaluation of lentigo maligna with permanent sections:implications regarding current guidelines. J Am Acad Dermatology. 2002;47:743-8.
• Albert VA, Koh HK, Geller AC. Years of potential life lost: another indicator of the impact of cutaneous malignant melanoma on society. J Am Acad Dermatol. Aug 1990;23(2 Pt 1):308-10. [Medline].
• Bastian BC. Understanding the progression of melanocytic neoplasia using genomic analysis: from fields to cancer. Oncogene. May 19 2003;22(20):3081-6.
• Cohen LM. Lentigo maligna and lentigo maligna melanoma. J Am Acad Dermatol. Dec 1995;33(6):923-36; quiz 937-40. [Medline].
• Goldstein AM, Dracopoli NC, Engelstein M. Linkage of cutaneous malihnant melanoma / dysplastic nevi to chromosome 9p and evidence for genetic heterogeneity. Am J Hum Genet. 1994;54:489.
• Gross EA, Andersen WK, Rogers GS. Mohs micrographic excision of lentigo maligna using Mel-5 for margin control. Arch Dermatol. Jan 1999;135(1):15-7. [Medline].
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• Jemal A, Siegel R, Ward E. Cancer statistics, 2006. CA Cancer J Clin. Mar-Apr 2006;56(2):106-30.
• Koh HK, Michalik E, Sober AJ. Lentigo maligna melanoma has no better prognosis than other types of melanoma. J Clin Oncol. Sep 1984;2(9):994-1001. [Medline].
• Langford FP, Fisher SR, Molter DW. Lentigo maligna melanoma of the head and neck. Laryngoscope. May 1993;103(5):520-4. [Medline].
• Liu V, Mihm MC. Pathology of malignant melanoma. Surg Clin North Am. Feb 2003;83(1):31-60, v.
• McKenna JK, Florell SR, Goldman GD. Lentigo maligna/lentigo maligna melanoma: current state of diagnosis and treatment. Dermatol Surg. Apr 2006;32(4):493-504.
• Rigel DS, Friedman RJ, Kopf AW. The incidence of malignant melanoma in the United States: issues as we approach the 21st century. J Am Acad Dermatol. May 1996;34(5 Pt 1):839-47. [Medline].
• Schiffner R, Schiffner-Rohe J, Vogt T. Improvement of early recognition of lentigo maligna using dermatoscopy. J Am Acad Dermatol. Jan 2000;42(1 Pt 1):25-32.
• Stevenson O, Ahmed I. Lentigo Maligna: prognosis and treatment options. Am J Clin Dermatology. 2005;6[3]:151-164.
• Su LD, Fullen DR, Lowe L. Desmoplastic and neurotropic melanoma. Cancer. Feb 1 2004;100(3):598-604. [Medline].
• Weinstock MA, Sober AJ. The risk of progression of lentigo maligna to lentigo maligna melanoma. Br J Dermatol. Mar 1987;116(3):303-10. [Medline].
• Whiteman DC, Stickley M, Watt P. Anatomic site, sun exposure, and risk of cutaneous melanoma. J Clin Oncol. Jul 1 2006;24(19):3172-7.

Article Last Updated: Dec 21, 2006