Lentigo Maligna Melanoma

Updated: Apr 01, 2016
  • Author: Winston W Tan, MD, FACP; Chief Editor: William D James, MD  more...
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The incidence of melanoma has increased steadily over the past 3 decades, and melanoma in situ has constituted a disproportionately high percentage of the rise in cases. [1] It is estimated that in 2015, 73,870 cases of invasive skin melanoma and 63,440 cases of melanoma in situ will be newly diagnosed. [2]

Lentigo maligna (LM) is a subtype of melanoma in situ, and it has a slight female preponderance. Lentigo maligna melanoma (LMM) is one of the four 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%). [3]

Lentigo maligna melanoma is most often found in the head and neck (see the image below). Approximately 10-30% of all cutaneous melanoma arise in this region. [4]

Photograph shows lentigo maligna melanoma on a pat Photograph shows lentigo maligna melanoma on a patient’s cheek. Lentigo maligna melanoma most commonly occurs on sun-exposed skin, especially of the face, in elderly persons. It is characterized by a highly irregular border, heterogeneous coloration, and—because of its long radial growth phase—a large diameter. Courtesy of CDC/Carl Washington, MD, Emory University School of Medicine, and Mona Saraiya, MD, MPH.


See Mole or Melanoma? Test Yourself With These Suspicious Lesions, a Critical Images slideshow, to help identify various skin lesions.

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.

For more information, see the following


Etiology and Pathophysiology

Risk factors for lentigo maligna melanoma include the following:

  • Ultraviolet radiation exposure: For people who live in Australia, the risk increases as the number of years spent in Australia increases, as well as with increased hours of exposure to sunlight, with the amount of actinic damage, and with a history of nonmelanoma skin cancer.

  • Increased number of melanocytic nevi, including large or giant congenital nevi

  • Fair skin

  • History of severe sunburn

  • Occupational risk

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

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. [5] The second gene that has been noted in melanoma prone families is CDK4, and germline mutations have been identified in this group.



The American Cancer Society estimates that 76,380 new melanomas (about 46,870 in men and 29,510 in women) will be diagnosed in the United States in 2016. The number of deaths from melanoma is estimated at 10,130 persons (about 6750 men and 3380 women). [6]

The incidence of lentigo maligna is greatest in Hawaii, intermediate in the central and southern states, and lowest in the northern states. The incidence of melanoma is highest in Australia, where lentigo maligna accounts for 10-15% of all melanomas. [7]

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 are associated with higher occupational exposure and lower recreational sun exposure.


Clinical Evaluation

As mentioned earlier, the risk of lentigo maligna melanoma increases as the number of years of residence in sunnier climates (eg, southern United States) increases, and the risk increases with increased hours of exposure to sunlight, [8] increased amount of actinic damage, and a history of nonmelanoma skin cancer. See the image below.

Photograph shows lentigo maligna melanoma on a pat Photograph shows lentigo maligna melanoma on a patient’s cheek. Lentigo maligna melanoma most commonly occurs on sun-exposed skin, especially of the face, in elderly persons. It is characterized by a highly irregular border, heterogeneous coloration, and—because of its long radial growth phase—a large diameter. Courtesy of CDC/Carl Washington, MD, Emory University School of Medicine, and Mona Saraiya, MD, MPH.

Therefore, it is important to elicit this information from the patient. In addition, associations have been reported between lentigo maligna melanoma and the following:

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).

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. [9]

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. The review of systems should focus on symptoms pertaining to metastatic disease. Melanoma usually metastasizes to lungs, liver, and brain.

Physical assessment

Patients with melanoma need a complete and thorough physical examination, especially with focus on the skin and lymph nodes.

The most frequent findings that suggest 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. 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.

Less common sites of involvement 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, as follows, 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

Clinical characteristics of lentigo maligna include the following:

  • Large size: >6 mm and often several centimeters in diameter at diagnosis
  • Irregular shape
  • Variable pigmentation – colors may include light brown or tan, dark brown, pink, red, or white
  • Smooth surface

Lentigo maligna, the precursor lesion, has been likened to a stain on the skin. The lesion is typically tan-brown, with differing shades throughout.

Assess the total number of all types of moles. More than 50 nevi 2 mm in diameter or larger indicate an increased risk for melanoma.

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.


Diagnostic Considerations

Distinguishing lentigo maligna from its invasive counterpart on a clinical basis continues to present diagnostic dilemmas, especially in patients who had previous therapeutic interventions such as cryotherapy. It is important to have a low threshold for biopsy of pigmented facial lesions. In a series of 85 excised lesions with a clinical diagnosis of lentigo maligna, more than 50% had invasive lentigo maligna melanoma.

The following conditions should also be considered when evaluating a patient for suspected lentigo maligna and lentigo maligna melanoma:

  • Common acquired nevi

  • Dysplastic nevi

  • Pigmented actinic keratosis

  • Seborrheic keratosis

  • Solar lentigo (see the image below)

Woman with solar lentigo. Common in sun-exposed sk Woman with solar lentigo. Common in sun-exposed skin, solar lentigines are benign lesions that must be distinguished from lentigo maligna melanoma.

Diagnostic Evaluation

Patients with low-risk melanomas, less than 1 mm thick, do not routinely need laboratory studies. Dermoscopy is the first step that is essential for diagnosis of this lesion. The use of a dermatoscope, by a dermatologist or other physician trained in its use, can be very helpful in distinguishing lentigo maligna from other types of skin lesion. However, the dermoscopic appearance of early lentigo maligna can be difficult to distinguish from that of other pigmented lesions, particularly on the face.

Confocal microscopy can sometimes be helpful. Confocal fluorescence microscopy is a microscopic technique that provides true three-dimensional (3D) optical resolution. In microscopy, 3D resolution is generally realized by designing the instrument so that it is primarily sensitive to a specimen’s response coming from an in-focus plane, or by subsequently removing the contributions from out-of-focus planes. [30]

However, most centers order liver function tests and lactate dehydrogenase (LDH) levels as part of the initial laboratory evaluation. Serum LDH is used as part of metastasis staging (see Staging).


Imaging Studies

Most institutions obtain chest radiographs in patients with low-risk disease.

To determine the extent of disease, positron emission tomography (PET) scanning, staging computed tomography (CT) scanning, or magnetic resonance imaging (MRI) can be performed for patients with node-positive disease or those with symptoms suggestive of metastasis.



Dermoscopy is a tool that helps the dermatologist distinguish benign from malignant lesions. [10] It is a hand-held instrument that magnifies the skin lesion 10 times to enable a more accurate diagnosis.


Skin Biopsy

Ideally, 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 (see Staging).

A better biopsy choice would be excisional biopsy with a narrow margin of normal-appearing skin, which can usually 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. This technique is indicated in all melanoma patients except those with stage 0 or stage 1A disease, that is, patients with a lesion thinner than 1 mm (see Staging).

If metastasis is present, a full nodal dissection is done to fully stage the disease.



Lentigo maligna is melanoma in situ; lentigo maligna melanoma is melanoma.

The American Joint Committee on Cancer (AJCC) Tumor, Node, Metastases (TNM) staging for melanoma uses tumor size, rather than invasion, and ulceration and number of mitoses per mm2 to stage the tumor. [11]

Tumor staging is as follows. For the stages below, the addition of “a” indicates without ulceration and of “b” indicates with ulceration, except for “T1a,” which indicates without ulceration and mitosis less than 1/mm2 and “T1b,” which indicates with ulceration or mitoses 1 or more per mm [210] :

  • Tx – Primary tumor cannot be assessed (eg, regressed primary).

  • T0 – No evidence of primary tumor

  • Tis – Melanoma in situ

  • T1 – 1 mm or less in thickness; T1a; T1b

  • T2 – 1.01-2.0 mm; T2a; T2b

  • T3 – 2.01-4.0 mm; T3a; T3b

  • T4 – Larger than 4.0 mm; T4a; T4b

Regional nodal staging is as follows. For the stages below, the addition of “a” indicates micrometastasis clinically occult, of “b” indicates macrometastasis clinically apparent, and of “c” indicates in transit metastasis(es)/satellite(s) without metastatic nodes [11] :

  • Nx – Nodes cannot be assessed (eg, previously removed).

  • N0 – No regional metastases detected.

  • N1 – 1 metastatic node; N1a; N1b

  • N2 - 2-3 metastatic nodes; N2a; N2b; N2c

  • N3 - 4 or more metastatic nodes, or matted nodes, or in transit metastasis(es)/satellite(s) with metastatic nodes.

M indicates distant metastasis and is staged incorporating serum lactate dehydrogenase (LDH) levels as follows [11] :

  • M0 – No detectable evidence of distant metastases

  • M1a – Metastases to skin, subcutaneous, or distant lymph nodes, normal LDH level

  • M1b – Metastases to lung, normal LDH level

  • M1c – Metastases to all other visceral sites with normal LDH level or distant metastases to any site combined with an elevated serum LDH level


Management Overview

Melanoma should be managed by a multidisciplinary team that includes a dermatologist, surgeon, and medical oncologist, as well as other allied health professionals.

Lentigo maligna is treated with surgery. The standard and preferred treatment is surgical excision. However, various nonsurgical modalities are available to patients in whom surgical therapy is not feasible, including cryotherapy and immune response therapy with topical imiquimod. [12, 13]

Melanoma in situ (MIS) is a noninvasive lesion. In a retrospective study of 2,121 patients treated for melanoma by Akhtar et al, [14] 192 patients with MIS were identified; those treated with narrow margins of excision are unlikely to recur; therefore, wider excision is not required.

Radiotherapy in the treatment of lentigo maligna was first described by Miescher in 1954. Other investigators have employed similar techniques with varying results. A primary risk of using radiation therapy for lentigo maligna is that it may miss focal lentigo maligna melanoma.

In one study, radiation therapy was an effective and safe treatment for lentigo melanoma. Radiation was given twice a week over three consecutive weeks in total doses of 100 to 160 Gy, Patients were followed for 2 to 5 years. [15]

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.

With metastatic or unresectable disease, National Comprehensive Cancer Network (NCCN) guidelines recommend choosing therapy on the basis of the tumor's BRAF mutation status (wild type versus mutated). An additional consideration is whether the patient is expected to remain clinically stable for more than 12 weeks (in which case the therapeutic intent is long-term survival) or clinical deterioration is expected in 12 weeks or less. [16]

Vaccines have been tested in various studies, but none have led to any significant survival advantage. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been found to prolong time to progression compared to historical control in both node-positive and metastatic stage of the disease.

Nonsurgical therapies have a recurrence rate of 20-100% at 5 years.

Special considerations

Potential medicolegal pitfalls include the following:

  • Failure to diagnose, which is often the case with skin lesions that were initially thought to be benign without a biopsy

  • Failure to provide adequate follow-up care



Cryotherapy is not standard for the management of lentigo maligna, but it is often used in patients who are not candidates for surgery. Temperatures of -4°C (24.8°F) to -7°C (19.4°F) selectively destroy melanocytes while preserving keratinocytes in skin and mucosal epithelia.

Most authors discourage using cryotherapy for lentigo maligna, because focal lentigo maligna melanoma cannot be detected clinically. In addition, cryotherapy can have complications that include hypopigmentation, infection, scarring, inability to detect invasive melanoma, and failure to treat periadnexal involvement.



Topical Imiquimod Therapy

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

A systematic review found that imiquimod monotherapy provides a 76% histologic and a 78% clinical clearance rate for lentigo maligna. The incidence of clinical recurrence was 2.3%. Both cumulative dose and treatment intensity affect tumor clearance; treatment with more than 60 total applications, or with more than five applications per week, was associated with a higher likelihood of histologic clearance. [17]


Surgical Intervention

Lentigo maligna is treated with definitive surgical therapy. The actual margins of atypia usually extend beyond the clinically apparent margin, so total removal may be difficult. National Comprehensive Cancer Network (NCCN) practice guidelines for melanoma in 2015 are as follows (tumor thickness, recommended clinical margin) [16] :

  • Tumor in situ – Margin size 0.5-1.0 cm

  • Tumor ≤1 mm – Margin size 1 cm

  • Tumor 1.01-2 mm – Margin size 1-2 cm

  • Tumor 2.01-4 mm – Margin size 2 cm

  • Tumor >4 mm – Margin size at least 2 cm

The NCCN notes that for large melanoma in situ of the lentigo maligna type, surgical margins wider than 0.5 cm may be necessary. [16] In a study by Kunishige and colleagues in 1120 patients with melanoma in situ treated with Mohs surgery, 6-mm margins removed 86% of melanomas while 9-mm margins removed 99%. [18]


Surgical Outcomes

Standard excisions have a recurrence rate of 8-20%. Mohs surgery and staged excision may offer better control and lower recurrence rates (up to 5%). [19, 20, 21, 22] A study of Mohs surgery using immunostaining of frozen sections with melanoma antigen recognized by T cells 1 (MART-1) reported a recurrence rate of less than 1%. [23]

Surgical excision with 5-mm margin is often inadequate for lentigo maligna on sun-damaged skin where a background of melanocytic hyperplasia obscures the true borders of the lesion. The cure rate is 80-94%, but staged margin excisions using frozen, or permanent, sections consistently provided much higher cure rates. [24]

A review of staged excision as treatment of lentigo maligna concluded that this technique provides a long disease-free survival of 95% with follow-up of 57 months. [21] The technique included vertical excision with initial 2- to 3-mm margins and examination of permanent sections within 24 hours. Further excisions took place as guided by the histologic findings. [21]

Hazan et al studied staged excision of lentigo maligna and lentigo maligna melanoma in the head and neck region of 117 cases and reported that the mean total surgical margin for excision of lentigo maligna was 7.1 mm and 10.3 mm for lentigo maligna melanoma. [25]


Systemic Therapy for Metastatic Disease

For patients with metastatic or unresectable disease whose tumor has wild-type BRAF V600, National Comprehensive Cancer Network (NCCN) options for first-line systemic therapy include the following [16] :

  • Pembrolizumab
  • Nivolumab (category 1)
  • Nivolumab/ipilimumab

For patients with wild-type BRAF V600 (preferred if clinically needed for early response), NCCN prefers the following combination regimens for first-line systemic therapy [16] :

  •  Dabrafenib + trametinib (category 1)
  • Vemurafenib + cobimetinib (category 1)

Singe agents with category 1 recommendations are as follows:

  • Vemurafinib
  • Dabrafenib

For patients who experience disease progression or maximum clinical benefit from BRAF-targeted therapy, NCCN recommendations for second-line or subsequent therapy vary by performance status. For patients with performance status 3-4, consideration of best supportive care is advised. For those with performance status of 0-2, with wild-type BRAF, recommended agents include the following [16] :

  • Pembrolizumab
  • Nivolumab
  • Nivolumab + ipilimumab
  • Ipiliumab (category 1)
  • High-dose interleukin-2
  • Biochemotherapy (category 2B)
  • Cytotoxic agents
  • Imatinib (for tumors with activating mutations of C-KIT)

For patients with mutated BRAF, recommended second-line or subsequent regimens include the following [16] :

  • Dabrafenib + trametinib (preferred)
  • Vemurafenib + cobimetinib
  • Vemurafinib
  • Dabrafenib



Outpatient Follow-up

Although early detection of a melanoma recurrence is a major concern, recommendations from different dermatological and oncological organizations vary with respect to who should provide follow-up, as well as duration and frequency of follow-up and the use of imaging and laboratory studies. However, all organizations agree that the physical examination is the cornerstone of follow-up care. [26]

The National Comprehensive Cancer Network (NCCN) recommends at least annual skin exams for life in all melanoma patients, along with patient education in self-examination of skin and lymph nodes. The follow-up schedule should be influenced by factors affecting risk of recurrence, such as family history and presence of atypical moles or dysplastic nevi. The NCCN does not recommend routine blood tests. [16]

For patients with stage 0 in situ through stage IIA melanoma with no evidence of disease, the NCCN recommends a history and physical examination with emphasis on nodes and skin every 6-12 months for 5 years, than annually as clinically indicated. The NCCN recommends against routine radiologic imaging to screen for asympomatic recurrent metastatic disease. [16]

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, strongly counsel patients to avoid excess sun exposure, to use sunblock liberally, and to wear protective clothing.

For patient education information, see Cancer and Tumors Center, as well as Skin Cancer and Skin Biopsy.


Prognosis and Prognostic Factors

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. [27] Lentigo maligna melanoma has a mortality rate similar to that of other melanoma types if depth of the tumor is taken into account. [28]

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 (see Staging).

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%.

Patients with neck and scalp melanoma have shorter survival compared with melanoma at other sites (extremities, face, trunk). [29] In an analysis of the Surveillance, Epidemiology, and End Results (SEER) program data, patients with scalp and neck had a 1.84 risk of dying compared with patients affected at other sites such as extremity melanoma. The 5- and 10-year Kaplan Meier survival probabilities for scalp and neck melanoma were 83.1% and 76.2%, respectively, compared with melanoma of other sites at 92.1% and 88.7%, respectively. [29]