Lentigo Maligna 

Lentigo Maligna 

Introduction

• Lentigo maligna (LM) is a type of melanoma in situ, characterized by a slowly spreading, usually pigmented skin patch or macule that typically appears on chronically sun-exposed skin of the head or neck in older patients; LM is^(1,2)
  • estimated to account for 79%-83% of melanoma in situ cases⁽³⁾
  • is a precursor to lentigo maligna melanoma (LMM), a type of cutaneous invasive melanoma characterized by spread of atypical melanocytic cells to dermis^(1,2,3)
  • estimated risk for transformation to LMM ranges from 5% to 50% and increases over time⁽³⁾
  •  distinct from acral lentiginous melanoma, which is another type of cutaneous invasive melanoma^(1,2)

Synonyms

•  lentigo melanosis⁽²⁾
•  Hutchinson freckle⁽²⁾
•  Hutchinson’s melanotic freckle⁽²⁾
•  senile freckle⁽²⁾
•  precancerous non-nevoid melanocytoma⁽²⁾
•  circumscribed precancerous melanosis⁽²⁾

Epidemiology

Who Is Most Affected

• lentigo maligna is typically seen in adults aged 60-80 years with sun-damaged skin, and may be more common in male patients^(1,2,3)
• lentigo maligna incidence reported to be higher in male patients and persons ≥ 80 years old (compared to ages 18-49 years) in Olmsted County, Minnesota, United States from 1970 to 2007
  •  based on medical record review of residents of Olmsted County, Minnesota, United States from 1970 to 2007 (as part of the Rochester Epidemiology Project)
  • incidence of lentigo maligna per 100,000 person-years from 1970 to 2007
    •  9.9 (95% CI 7.8-12) in male patients and 3.8 (95% CI 2.7-4.8) in female patients (p < 0.05)
    •  21.9 (95% CI 14.2-32.4) for persons ≥ 80 years old and 1 (95% CI 0.6-1.5) for ages 18-49 years (p < 0.05)
  •  Reference – J Am Acad Dermatol 2014 Mar;70(3):443full-text

Incidence/Prevalence

• lentigo maligna and lentigo maligna melanoma are estimated to account for 4%-15% of all melanoma cases and 10%-26% of head and neck melanoma cases⁽³⁾
• incidence of lentigo maligna is reported to be
  • increasing over the last few decades, potentially due to increased chronic sun exposure, increasing age of affected populations, and growing awareness of lentigo maligna as a distinct diagnosis⁽³⁾
  • higher among people living in southern geographic regions compared to northern regions⁽³⁾
• lentigo maligna incidence 6.3 per 100,000 person-years reported in Olmsted County, Minnesota, United States from 1970 to 2007, with higher incidence from 2004 to 2007
  •  based on medical record review of residents of Olmsted County, Minnesota, United States from 1970 to 2007 were assessed (as part of the Rochester Epidemiology Project)
  • incidence of lentigo maligna per 100,000 person-years in age- and gender-adjusted analysis (p < 0.05 for each pairwise comparison)
    •  overall 6.3 (95% CI 5.3-7.4) from 1970 to 2007
    •  2.2 (95% CI 1.2-3.2) from 1970 to 1989
    •  13.7 (95% CI 9.8-17.5) from 2004 to 2007
  •  Reference – J Am Acad Dermatol 2014 Mar;70(3):443full-text
•  incidences of melanoma and melanoma in situ in general are also reported to be increasing over the past decade, with the fastest rate increase in persons aged 20-49 years (J Am Acad Dermatol 2015 Aug;73(2):181)
• lentigo maligna/lentigo maligna melanoma (LM/LMM) reported to account for 6.9% of melanoma cases in Catalonia, Spain in 2000 and 13.1% of cases in 2007 based on population-based surveillance study (Int J Dermatol 2019 May;58(5):577); mean age at LM/LMM diagnosis was 73 years

Risk Factors

• lentigo maligna risk factors include^(1,2,3)
  •  older age (> 60 years)
  •  lighter-toned skin
  •  chronic sun exposure, particularly on sun-damaged skin
  • increasing number of solar lentigines and/or actinic keratoses
  • history of sunburns (particularly intermittent sunburns)
  • history of skin cancers, including
    • melanoma
    • keratinocyte carcinomas (cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma of the skin)
  • genetic conditions such as
    • xeroderma pigmentosum
    • oculocutaneous albinism; see also Congenital Disorders of Pigmentation
    • Werner syndrome
    • porphyria cutanea tarda
• mutations in specific genes appear associated with increased risk of lentigo maligna/lentigo maligna melanoma, with affected genes including NF1, BRAFV600K, NRAS, and KIT; and possibly CCND1, MITF, and TP53⁽³⁾

Etiology and Pathogenesis

Causes

• lentigo maligna is thought to result from a combination of sun exposure and genetic mutations; specific genes that have been implicated in development of lentigo maligna/lentigo maligna melanoma (LM/LMM) include
  • NF1
  • BRAF V600K
  • NRAS
  • KIT
  • CCND1, MITF, and TP53 (gain- or loss- of function mutations on these genes are associated with sun damage-related melanomas)
  • References – ³, Lancet 2014 Mar 1;383(9919):816
• BRAF V600E (implicated in superficially spreading melanoma) does not appear associated with LM/LMM⁽³⁾

Pathogenesis

• mechanism of sunlight exposure in pathogenesis of lentigo maligna is thought to involve the ultraviolet radiation increasing melanocyte proliferation through melanocyte photomodulation and DNA mutation (Arch Pathol Lab Med 2011 Jul;135(7):838full-text)
• lentigo maligna growth is typically progressive, with initial expansion confined to radial or centrifugal growth within the epidermis, and later vertical growth and dermal invasion (progression to lentigo maligna melanoma)^(1,2)

History and Physical

Clinical Presentation

• lentigo maligna (LM) most commonly presents as a slowly progressing, darkly pigmented skin patch or macule found on the head and neck, or the cheeks^(1,2,3)
  • lesion is typically asymmetrical with irregular borders; the color is typically variegated tan-brown and may also have net-like black pigmentation (amelanotic/hypomelanotic lesions are also possible, particularly in patients with light skin)
  •  lesion may be subtle with indistinct margins, especially in early stages; in later stages lesion may progress to papules, nodules, or thick plaques (suggesting an invasive foci)
  •  diameter may vary from few millimeters to centimeters depending on age of lesion; >10 mm diameter is commonly reported at diagnosis due to delayed recognition
  •  appearance may be novel or arising from an existing freckle or solar lentigo
  • repigmentation of previously white or gray hair has been reported as a presentation of LM of the scalp
•  palpate for induration which may suggest desmoplastic invasion (Dermatol Surg 2006 Apr;32(4):493)
• lentigo maligna reported to present on face in 81%-95% of patients
  •  based on 2 cohort studies
  • 200 patients (mean age 70 years, 60% female) with 201 histopathologically defined lentigo maligna were assessed for lesion location
    •  facial location in 192 (95%)
    •  solitary lesion in 51% and lesion with surrounding freckles in 49%
    •  lesion > 10 mm at largest diameter in 51%
    • specific anatomical locations
      •  cheeks in 54% (63% of female patients and 40% of male patients, p < 0.001)
      •  front upper face in 10%, periocular in 8.5%, scalp in 2%
      •  cartilaginous area of nose in 13%
      •  boney area of nose in 2%
      •  perioral area in 1%
      •  cartilaginous area of ear in 2% (0% of female patients and 4.9% of male patients, p = 0.025)
      •  earlobe and periauricular area in 3% (0.8% of female patients and 6.2% of male patients, p = 0.04)
      •  neck in 4.5%
      •  arm in 0%
    •  Reference – J Am Acad Dermatol 2015 May;72(5):801
  • 410 adults (mean age 69 years, 52% female) with melanoma in situ (79% with lentigo maligna) were reviewed for lesion location:
    •  face in 67% (81.4% of patients with lentigo maligna)
    •  scalp and neck in 8% (5.9% of patients with lentigo maligna)
    •  upper limb in 9%
    •  trunk in 8%
    •  lower limb in 8%
    •  Reference – Plast Reconstr Surg Glob Open 2015 Feb;3(2):e301full-text
• amelanotic lentigo maligna case reports
  •  case report of 85-year-old female patient with amelanotic lentigo maligna can be found in Acta Derm Venereol 2016 Mar 1;96(3):406full-text
  •  case report of 58-year-old female patient with amelanotic lentigo maligna on leg can be found in Int Wound J 2016 Oct;13(5):1034
• spontaneous black hair repigmentation in 3-cm lock which developed over 1 year reported as presenting feature of lentigo maligna of the scalp in 80-year-old male patient with gray hair in case report (Am J Dermatopathol 2019 Sep;41(9):671)

History

• ask about history of chronic sun exposure and sun burns^(1,2,3)
• ask about past/look for dermatological conditions such as
  • solar lentigines or actinic keratosis^(1,2,3)
  • skin cancer, including^(1,2,3)
    • melanoma
    • keratinocyte carcinomas such as squamous cell carcinoma (SCC) or basal cell carcinoma of the skin⁽³⁾
• ask about history of genetic conditions such as⁽³⁾
  • xeroderma pigmentosum
  • oculocutaneous albinism; see also Congenital Disorders of Pigmentation
  • Werner syndrome
  • porphyria cutanea tarda

Dermoscopy

•  consider dermatoscope to examine lesion with or without polarized light, usually at 10 × magnification^(1,2,3)
•  may help differentiate lentigo maligna from other lesions, but diagnostic performance depends on clinical expertise⁽¹⁾
• during dermoscopy, facial skin features (such as terminal hair follicle, sweat gland ostia, and attenuated rete ridges) may present a pseudo-network appearance (structureless pigment area with nonpigmented adnexal opening)⁽³⁾
• dermoscopic scoring systems such as facial integrated dermoscopic score (iDScore) may aid in determining the risk of an atypical pigmented facial lesion, such as lentigo maligna, of being malignant (J Eur Acad Dermatol Venereol 2023 Nov;37(11):2301)
• dermoscopic findings of lentigo maligna and dermoscopic findings of differential diagnoses for lentigo maligna

Table

Table 2: Dermoscopic Features of Lentigo Maligna

Dermoscopic Feature	Considerations
Annular-granular pattern of brown to blue-gray dots	May be seen throughout lesion or at arranged adnexal openingsBrown dots are indicative of clusters of melanocytes between dermoepidermal follicle junctionBlue-gray areas indicate melanophages in the upper dermis
Polygons, rhomboids, zig-zag pattern (angulated lines)	Seen as gray-brown lines connected at an angle or forming polygonsRhomboids and zig-zag lines are typically seen on the face or upper face and represent gray-brown angulated lines near adnexal ostial openingsPolygons are typically seen on nonfacial areas
Asymmetric pigmented follicular opening	Typically seen on lower faceMay be seen as a fine circle, semicircle, or ring-like circle
Circle within a circle	Concentric pigmented circles around follicular openingsSeen in 5%-25% of cases

Citation: Reference – Am J Clin Dermatol 2013 Dec;14(6):473, Clin Cosmet Investig Dermatol 2020;13:837.

Table

Table 3: Dermoscopic Features of Differential Diagnoses for Lentigo Maligna

Skin Lesion	Dermoscopic Feature
Solar lentigo	“Moth-eaten” bordersPseudonetworkComedo-like openingDiffuse solid brown pigmentLight brown fingerprint-like structuresMilia-like cysts
Seborrheic keratosis	Milia-like cystsComedo-like openingHairpin vesselsSharp demarcation”Moth-eaten” borders”Fat fingers”
Lichen planus like keratosis	Localized or diffused annular-granular pattern
Pigmented actinic keratosis	Annular patternGray colored short strikes and granulesPseudoreticular structuresGray-brown dots and globulesEvident white folliclesScalesBrown to gray rhomboidal lines not invading follicular openingBackground erythema
Melanoma	Irregular or atypical pigment networkNegative pigment networkStreaks (pseudopods and radial streaming)Off-centered blotch around boundariesDots/globules in varying size, shape, colorRegression structures (scar-like depigmentation and peppering)Overlying blue-white veil may vary in color and be asymmetrically organized or diffuse (also seen with lentigo maligna melanoma)Atypical vascular structures (dotted vessels over milky-red backgrounds, serpiginous vessels or polymorphous vessels)Crystalline structuresPeripheral brown structureless areasRhomboidal structures (seen with lentigo maligna melanoma)
Dysplastic nevus	Irregular ill-defined bordersAsymmetryPigmented network/meshNumerous globules or dotsHomogeneous brown pigmentation

Citation: Reference – Clin Cosmet Investig Dermatol 2020;13:837, Am Fam Physician 2013 Oct 1;88(7):441, Arch Dermatol 2001 Dec;137(12):1575.

• dermoscopic findings in retrospective cohort of 201 patients (mean age 70 years, 60% female) with histopathologically defined lentigo maligna
  •  gray color (including gray globules) in 89%
  •  asymmetric pigmented follicles (gray circle around follicle opening) in 44%
  •  annular granular pattern (gray globules and/or dots) in 24%
  •  circle within a circle in 25% (18% of female patients and 36% of male patients, p = 0.009)
  •  target pattern (dot within a circle) in 19% (12% of female patients and 31% of male patients, p = 0.001)
  •  pigmented (brown to gray) rhomboid structures in 18%
  •  increased vascular density in 15%
  •  white-gray scar-like structures in 14%
  •  damaged hair follicles in 12%
  •  red rhomboid structures formed by vessels in 2%
  •  darker colors visible during dermoscopic exam (but not to naked eye) in 1.5%
  •  Reference – J Am Acad Dermatol 2015 May;72(5):801

Wood’s Lamp (Wood’s Light)

• Wood’s lamp exam shows epidermal melanin as darker than surrounding epidermis, and is useful for estimating size of lentigo maligna lesion and detecting areas of subclinical disease not visible to the naked eye^(1,2,3)
  • Wood’s lamp is particularly useful for margin assessment before biopsy and surgical excision⁽³⁾
  • uses a wavelength of 320-400 nm with peak irradiance 365 nm⁽³⁾
  • presence of other benign lesions (such as seborrheic or pigmented keratoses) may limit Wood lamp ability to delineate lentigo maligna margins⁽³⁾
  • Wood’s lamp does not detect dermal melanin, so is not useful for assessment of deeper atypical melanocytes⁽³⁾
•  also consider Wood’s lamp exam for assessment of possible recurrence in scars from previous lentigo maligna excisions; see Follow-Up in Management for more information⁽¹⁾
• Wood’s lamp exam reported to help determine surgical margins of lentigo maligna in case series of 5 patients (Dermatol Pract Concept 2020;10(1):e2020018full-text)

Diagnosis

Making the Diagnosis

• lentigo maligna diagnosis may be suspected clinically based on
  •  a pigmented macule or patch on face, head, neck, or other chronically sun-exposed skin on older adults
  • Wood’s lamp finding of increased concentration of epidermal melanin
  • dermoscopic findings of an atypical pigment network, such as hyperpigmented follicular openings, grey coloration, and rhomboidal structures (zig-zag, polygons, and other angulated lines are seen); an annular-granular pattern is seen and circles-within-circles
• lentigo maligna diagnosis is confirmed with biopsy and histopathology showing an atypical melanocytic proliferation at epidermal–dermal junction restricted to epidermis
  • excisional biopsy is preferred for histologic diagnosis, but often is not possible due to the size and/or location of the lesion, so smaller “scouting” biopsies including shave or punch biopsy may be used
  • broad shave biopsy, which extends deep into papillary dermis may be helpful to visualize breath of pigmented lesion
  •  invasion of the papillary dermis is consistent with diagnosis of invasive melanoma; see also Melanoma

Differential Diagnosis

• benign nevus^(1,2)
• dysplastic nevus^(1,2)
• melanoma
•  pigmented actinic keratosis^(1,2,3)
• solar lentigo^(1,2,3)
•  lentigo simplex⁽²⁾
• lichen planus-like keratosis^(1,2,3)
•  pigmented and sessile seborrheic keratosis^(1,2,3)
• dermoscopic findings of differential diagnoses for lentigo maligna

Table

Table 4: Dermoscopic Features of Differential Diagnoses for Lentigo Maligna

Skin Lesion	Dermoscopic Feature
Solar lentigo	“Moth-eaten” bordersPseudonetworkComedo-like openingDiffuse solid brown pigmentLight brown fingerprint-like structuresMilia-like cysts
Seborrheic keratosis	Milia-like cystsComedo-like openingHairpin vesselsSharp demarcation”Moth-eaten” borders”Fat fingers”
Lichen planus like keratosis	Localized or diffused annular-granular pattern
Pigmented actinic keratosis	Annular patternGray colored short strikes and granulesPseudoreticular structuresGray-brown dots and globulesEvident white folliclesScalesBrown to gray rhomboidal lines not invading follicular openingBackground erythema
Melanoma	Irregular or atypical pigment networkNegative pigment networkStreaks (pseudopods and radial streaming)Off-centered blotches around boundariesDots/globules in varying size, shape, colorRegression structures (scar-like depigmentation and peppering)Overlying blue-white veil may vary in color and be asymmetrically organized or diffuse (also seen with lentigo maligna melanoma)Atypical vascular structures (dotted vessels over milky-red backgrounds, serpiginous vessels or polymorphous vessels)Crystalline structuresPeripheral brown structureless areasRhomboidal structures (seen with lentigo maligna melanoma)
Dysplastic nevus	Irregular ill-defined bordersAsymmetryPigmented network/meshNumerous globules or dotsHomogeneous brown pigmentation

Citation: Reference – Clin Cosmet Investig Dermatol 2020;13:837, Am Fam Physician 2013 Oct 1;88(7):441, Arch Dermatol 2001 Dec;137(12):1575.

Testing Overview

•  for more detailed exam of suspicious lesions, consider Wood’s lamp or dermoscopy
• reflectance confocal microscopy may help noninvasively visualize quasi-histologic features of lentigo maligna
• obtain biopsy for diagnosis of lentigo maligna
  •  excisional biopsy preferred, but often not possible due to size and/or location of lesion
  •  consider smaller “scouting” biopsies including shave or punch biopsy, if excision not possible, but risk of sampling error increased
  •  broad shave biopsy may improve diagnostic sampling for melanoma in situ
• guideline organizations consistently do not recommend baseline imaging or lab studies for patients with newly diagnosed lentigo maligna, unless symptoms of metastases are present

Recommendations From Professional Organizations

• National Comprehensive Cancer Network (NCCN) recommendations for initial biopsy assessment of a suspicious pigmented lesion and preliminary workup of confirmed lentigo maligna
  • consider excisional/complete biopsy (elliptical, punch, saucerization/deep shave removal) for suspicious skin lesions with 1-3 mm margin (NCCN Category 2A)
  • full-thickness incision or punch biopsy may be considered for certain locations such as palm/sole, digits, face, or for very large lesions (NCCN Category 2A)
  • multiple scouting lesions may be considered to guide treatment of very large lesions (NCCN Category 2A)
  • consider superficial/tangential shave biopsy only in cases where index of suspicion is low due to risk of interfering with pathology and Breslow thickness assessment (NCCN Category 2A)
  • consider broad shave biopsy for patients with for histology of melanoma in situ or lentigo maligna melanoma (NCCN Category 2A)
  • for patients with suspected subungual melanoma, consider biopsy of nail matrix (NCCN Category 2A)
  • after diagnosis of lentigo maligna (stage 0 in situ melanoma)
    • obtain history and physical, with focus on loco-regional area and draining lymph nodes (NCCN Category 2A), including a complete skin exam (NCCN Category 2A)
    • routine imaging and lab tests not recommended (NCCN Category 2A)
    • consider imaging only for specific signs or symptoms (NCCN Category 2A), or is needed for surgical planning (NCCN Category 2A)
    • if needed, recommended cross-sectional imaging modalities are chest/abdominal/pelvic computed tomography (CT) with contrast or whole-body, fluorodeoxyglucose (FDG) PET/CT, and brain magnetic resonance imaging (MRI) with contrast (if indicated, also obtain neck CT with IV contrast) (NCCN Category 2A)
  • Reference – NCNN Version 2.2023 guideline on cutaneous melanoma can be found at NCCN website (free registration required)
• American Academy of Dermatology does not recommend baseline imaging studies and laboratory tests for patients who are asymptomatic with newly diagnosed stage 0-II melanoma (AAD Strength of recommendation A, Level of evidence I/II) (J Am Acad Dermatol 2019 Jan;80(1):208)

Reflectance Confocal Microscopy

• reflectance confocal microscopy (RCM) uses a near infrared laser light to noninvasively visualize quasi-histologic features with 100× magnification by physical exam^(1,3)
• RCM may be particularly helpful for lesions located on the head and neck, and amelanotic/hypomelanotic or recurrent lesions⁽³⁾
• benefits of RCM include⁽³⁾
  • ability to visualize microscopic amounts of melanin that can not be detected on dermoscopy to differentiate lentigo maligna from other benign macules or solar damage
  • assessing margins of poorly defined lesions prior to surgical excision
  • can be used to assess large lesions on curved body areas (such as the face) in conjunction with video mosaics (static mosaics from dynamic videos)
• findings reported with lentigo maligna include
  •  increased large hyperreflectile cells (melanocytes) at dermal-epidermal junction (J Am Acad Dermatol 2016 Jun;74(6):1114)
  •  discrete nests and pagetoid spread of atypical melanocytes leading to epidermal disarray^(1,3)
  •  melanocytes have large angulated nuclei (including high nuclear to cytoplasmic ratio)⁽¹⁾
  •  intraepidermal increase of dendritic cells (with folliculotropism)⁽¹⁾
  •  “medusa head-like structures” may be seen, characterized by long buds of dendritic or pleomorphic cells extending from hair follicle and junctional swelling^(1,3)
•  difficult to assess invasive melanoma or lentigo maligna melanoma due to maximum depth to upper reticular dermis⁽¹⁾
• reflectance confocal microscopy may have high sensitivity and specificity for diagnosis of lentigo maligna (level 2 [mid-level] evidence)
  •  based on systematic review limited by heterogeneity
  • systematic review of 7 diagnostic studies evaluating reflectance confocal microscopy and dermoscopy in 498 patients with lentigo maligna
  • reference standard was histopathology in all studies
  • diagnostic performance of reflectance confocal microscopy for detection of lentigo maligna in analysis of all studies
    • sensitivity 93% (95% CI 85%-97%), results limited by significant heterogeneity
    • specificity 89% (95% CI 81%-94%), results limited by significant heterogeneity
    • positive likelihood ratio 8.5
    • negative likelihood ratio 0.08
  • Reference – Skin Res Technol 2020 Jul;26(4):494
• reflectance confocal microscopy might have higher sensitivity and specificity compared to dermoscopy for detecting lentigo maligna (level 2 [mid-level] evidence)
  •  based on systematic review limited by heterogeneity
  • systematic review of 6 diagnostic cohort studies comparing RCM to dermoscopy in 479 patients with suspected lentigo maligna
  • 294 patients (61.4%) had lentigo maligna
  • in 6 included studies: sensitivity ranged from 91.7% to 100% with RCM and 60% to 95% with dermoscopy, and specificity ranged from 77.7% to 94% with RCM and 37.5% to 92% with dermoscopy
  • RCM associated with
    • higher sensitivity (mean difference 14.6%, 95% CI 0.29%-28.8%), results limited by significant heterogeneity
    • higher specificity (mean difference 19.1%, 95% CI 0.93%-37.3%), results limited by significant heterogeneity
  • Reference – Int J Clin Pract 2021 Aug;75(8):e14346
• reflectance confocal microscopy has high sensitivity but low specificity for detection of residual melanoma in tumor debulk from adults with lentigo maligna/lentigo maligna melanoma (level 1 [likely reliable] evidence)
  •  based on diagnostic cohort study
  • 72 adults aged 38-89 years (69% male) with biopsy-proven stage 0 or IA lentigo maligna/lentigo maligna melanoma presenting for dermatologic surgery evaluation were assessed with RCM imaging
  • 97.2% of lesions were located on the head and neck and had mean largest clinical diameter of 1.3 cm
  • for each patient, noninvasive RCM imaging included examination of central residual clinical lesion and of surgical margin by quadrants
  • imaging of 72 central lesions and 282 margins were evaluated
  • reference standard was histopathology performed after tumor excision
  • 83.3% had residual melanoma in tumor debulk by histopathology
  • diagnostic performance of RCM imaging for detection of residual melanoma in tumor debulk
    • sensitivity 96.7%
    • specificity 66.7%
    • positive predictive value 93.6%
    • negative predictive value 80%
  • assessment of surgical margins by reflectance confocal microscopy imaging had overall agreement of 85.8% with histopathology
  • Reference – J Am Acad Dermatol 2023 Feb;88(2):371

Biopsy and Pathology

• skin biopsy used for definitive diagnosis of lentigo maligna (LM)⁽³⁾
• biopsy techniques may vary based on lesion size, location, cosmetic outcomes, and patient preference⁽³⁾
  • excision of entire clinically defined lesion preferred if possible^(1,2,3)
    •  excise down to subcutaneous fat and with 1-3 mm margin
    •  increases ability to assess depth and peripheral involvement
    •  may not be possible due to size and/or location of lesion
  • if excisional biopsy not possible, consider smaller “scouting” biopsies with shave biopsy, punch biopsy, or fusiform incisional biopsy, but risk of sampling error increased compared to excisional biopsy^(1,2)
    •  consider scouting biopsy or multiple biopsies from darkest or “most concerning” areas of lesion, and any area of induration^(1,2)
    •  consider sample from periphery also to aid in delineation of margin⁽¹⁾
    •  also consider excisional biopsy from sun-damaged skin that does not appear to contain lentigo maligna for comparison of severity of sun damage (Dermatol Surg 2006 Apr;32(4):493)
    •  multiple biopsies may reduce sampling error⁽¹⁾
  • broad shave biopsy, which extends deep into papillary dermis may be helpful to visualize breath of pigmented lesion⁽³⁾
  • reflectance confocal microscopy can aid in identifying areas to biopsy limiting sampling bias associated with blind mapping biopsies⁽³⁾
  •  upstaging is reported to occur in 5%-29% of melanoma in situ cases; shave biopsy may lead to higher risk of upstaging than punch or excisional biopsies (J Am Acad Dermatol 2015 Aug;73(2):193)
• histological features do not differ between lentigo maligna of the face or extrafacial region⁽³⁾
• histologic findings of LM involve atypical melanocytic hyperplasia in small nests or single cells at epidermal-dermal junction within a background of solar damage such as solar elastosis, necrosis, and melanocyte atypia; other typical findings include^(1,2,3)
  •  effacement of rete ridges
  •  single cells of atypical melanocytes predominate over nests of cells
  •  variable pagetoid spread
  •  epidermal atrophy
  •  extension of atypical melanocytes into periadnexal structures
  •  inflammatory dermal infiltrate
  • hyperpigmentation of basal keratinocytes
  • multinucleated melanocytes with prominent dendritic processes (starburst giant cell; not specific to LM and may also be present in benign melanocytic nevi)
•  histologic diagnosis may be difficult to distinguish from melanocytic hyperplasia due to sun damage, but presence of melanophages may help suggest LM^(1,2,3)
• if atypical melanocytes are found in the dermis, then the diagnosis is melanoma; histologic features of lentigo maligna melanoma include^(1,2,3)
  • rows of melanocytes⁽³⁾
  • subepidermal clefts⁽³⁾
  • solar elastosis and nests (less common)⁽³⁾
  • neurotropism with deeply invasive lentigo maligna melanoma⁽³⁾
• immunohistochemical staining techniques^(1,2)
  •  may help differentiate lentigo maligna from benign melanocyte proliferation within sun-damaged skin or within postexcisional scarring
  •  may be used with frozen sections during Mohs micrographic surgery or permanent sections with staged excision surgical techniques
  • stains may include
    • MART-1 / Melan-A
      •  stains cytoplasm of malignant and benign melanocytes, dendritic processes, and keratinocytes
      •  associated with high sensitivity, but poor specificity, which may lead to removal of normal tissue
    • microphthalmia transcription factor (MiTF)
      •  stains within nucleus of benign and malignant melanocytes
      •  may help distinguish lentigo maligna from pigmented actinic keratosis
    • soluble adenylyl cyclase antibody (R21)
      •  stains soluble adenylyl cyclase in lentigo maligna, where it is overexpressed, but not native melanocytes
      •  consider as adjunct to MART-1 / Melan-A to help differentiate from benign melanocytic lesions
    •  HMB-45
    •  Mel-5
    •  S-100
    •  Sox10

Management

Management Overview

• surgical excision is the preferred treatment for lentigo maligna
  • consider surgical techniques that allow for an extensive histologic examination of margins, such as Mohs micrographic surgery or staged excision techniques with en-face sections or thin step sectioning for the excision of lentigo maligna
  • for wide excision of melanoma in situ, consider surgical margins of 0.5-1.0 cm to clear a possible subclinical extension beyond visible margins
  • as lentigo maligna commonly occurs in cosmetically sensitive areas, delayed reconstruction after final margin histology should be considered
  • if tissue transfer is needed for repair, consider delayed repair until histologic clearance obtained
  •  larger lesions, particularly those on the head and neck, may need larger surgical margins to clear subclinical extension
  • evaluation of tumor debulking is necessary to assess for subclinical invasion or high-risk features, such as subclinical invasion or high melanocyte count
  • see Recommendations From Professional Organizations section for detailed recommendations on surgical excision of lentigo maligna
• consider nonsurgical management with imiquimod 5% topically for 5 nights/week for 2-3 months (off-label) or radiation therapy for patients with
  • contraindications for surgery such as anticoagulation or significant comorbidities, very large lesions, or those who may have problematic reconstruction due to lesion location
  • positive margins after surgical excision
• consideration of a “wait-and-see” strategy has been suggested for selected patients with limited life expectancy and numerous comorbidities⁽³⁾
•  destructive treatments such as cryotherapy, electrodessication and curettage, or laser therapy do not allow for histologic exam, have limited evidence for management of lentigo maligna, and are reported to have high recurrence rates
•  azelaic acid and 5-fluouracil 5% cream are not recommended due to limited evidence⁽¹⁾
• at least annual follow-up physical and skin exams are recommended by professional organizations, with an emphasis on looking for local recurrence of lentigo maligna; the initial follow-up after treatment is typically every 6-12 months for 2-5 years then annually thereafter

Recommendations From Professional Organizations

National Comprehensive Cancer Network (NCCN)

• wide surgical excision is recommended as the primary treatment for melanoma in situ (NCCN Category 2A)
  • recommend surgical excision margin is 0.5-1 cm for melanoma in situ; wider margins may be needed for lentigo maligna melanoma (which usually occurs on face or head and neck) due to possible subclinical extension (NCCN Category 2A)
  • if Mohs microsurgery is performed, consider 9 mm margin to increase rate of complete histological clearance (NCCN Category 2A)
  • Reference – NCCN Version 2.2023 guideline on cutaneous melanoma can be found at NCCN website (free registration required)
• for some patients with lentigo maligna and positive margins after surgical excision, topical imiquimod or radiotherapy may be considered as alternative options (NCCN Category 2B) (NCCN Version 2.2023 guideline on cutaneous melanoma can be found at NCCN website [free registration required])
• NCCN recommendations for follow-up
  • recommendations for follow-up of melanoma in situ
    • perform annual history and physical with emphasis on the skin examination (NCCN Category 2A)
    •  provide patient education in self skin and lymph node exam (NCCN Category 2A)
    • routine blood tests not recommended (NCCN Category 2A)
    • routine imaging of asymptomatic recurrence or metastatic diseases not recommended (NCCN Category 2A)
  • Reference – NCCN Version 2.2023 guideline on cutaneous melanoma can be found at NCCN website (free registration required)

American Academy of Dermatology (AAD)

• AAD recommends wide excision for treatment of cutaneous melanoma, including melanoma in situ, to ensure complete lesion removal (AAD Strength of recommendation A, Level I)
  • recommended clinical surgical margins for excision of melanoma in situ are 0.5-1 cm, where margins > 0.5 cm may be necessary for melanoma in situ, lentigo maligna type to achieve negative margins because of subclinical extension (AAD Strength of recommendation B, Level II/III)
  • Mohs micrographic surgery (MMS) or staged excision with paraffin-embedded permanent sections may be utilized for melanoma in situ, lentigo maligna type, on the face, ears, or scalp for tissue-sparing excision and exhaustive histologic assessment of peripheral margins (AAD Strength of recommendation B, Level II/III)
  • insufficient evidence to support use of MMS for melanoma in situ elsewhere on the body
  • sub-1 cm margins by either wide excision or Mohs micrographic surgery (MMS) for primary invasive melanomas at anatomically constrained sites (such as. head, neck, and acral sites) generally not recommended until further studies are available (AAD Strength of recommendation C, Level III)
  • Reference – American Academy of Dermatology (AAD) 2019 clinical practice guidelines for the management of primary cutaneous melanoma (J Am Acad Dermatol 2019 Jan;80(1):208)
• AAD 2019 recommendations for alternative and adjuvant therapies
  • topical imiquimod 5% cream is a second-line treatment for melanoma in situ, lentigo maligna if resection is not possible or as an adjuvant therapy after resection (AAD Strength of recommendation B, Level of evidence II/III)
  • rarely, radiation therapy may be an option for patients with unresectable melanoma in situ, lentigo maligna (AAD Strength of recommendation C, Level of evidence II/III)
  • use of brachytherapy for melanoma in situ, lentigo maligna is not recommended (AAD Strength of recommendation C, Level of evidence III)
  • Reference – American Academy of Dermatology (AAD) 2019 clinical practice guidelines for the management of primary cutaneous melanoma (J Am Acad Dermatol 2019 Jan;80(1):208)
• AAD suggested surveillance for melanoma in situ is follow-up every 6-12 months for 1-2 years then annually thereafter; visits should include physical exam with an emphasis on local recurrence (especially for lentigo maligna subtype) (AAD 2019 clinical practice guidelines for the management of primary cutaneous melanoma J Am Acad Dermatol 2019 Jan;80(1):208)

Surgical Excision

Options and Considerations

•  surgical excision is the preferred treatment for lentigo maligna^(1,2,3)
•  consider exam with Wood’s lamp, dermoscopy, and/or reflectance confocal microscopy as supplementary method to physical exam to clinically define lesion, if possible prior to excision
• surgical options for lentigo maligna melanoma

Table

Table 5: Surgical Options for Excision of Lentigo Maligna

Option	Procedure Considerations	Reported Recurrence Rate*
Standard wide local excision	Standard excision with 5 mm margins reported to miss subclinical invasive melanoma in 16%-50% of casesPositive margins on histopathologic analysis require follow-up surgical excision	8%-20%
Mohs micrographic surgery with horizontal en face frozen sectioning	Staged excision technique involving histopathologic margin assessment prior to wound repairImmunohistochemical stains (MART-1 or MITF) commonly used to improve accuracyTissue sparing technique which is preferred for cosmetically sensitive areas such as the face	0%-6% is most commonly reported, but recurrence of up to 33% has been reported in 1 study
Staged excision with permanent sections	Allows for histopathologic margin assessment prior to wound repair, and generally involves tumor debulking and staged excision of marginsAnalysis of tumor debulking can be used to detect invasion and upstaging to lentigo maligna melanomaCommon techniques include geometric staged excision and spaghetti technique	0%-7%

Citation: * Surgical cure typically assessed at 5 years.

• as lentigo maligna commonly occurs in cosmetically sensitive areas, delayed reconstruction after final margin histology should be considered (Adv Ther 2021 Jul;38(7):3506full-text)
• if tissue transfer is needed for repair, consider delayed repair until histologic clearance obtained (Adv Ther 2021 Jul;38(7):3506full-text)

Standard Wide Local Excision

• standard wide local excision
  •  positive margins on histopathologic analysis require follow-up surgical excision
• excision of lentigo maligna with 5-mm margin reported to be associated with no recurrence up to 7 years in adults with lesions on low-risk body sites (level 3 [lacking direct] evidence)
  •  based on case series
  • 292 adults (mean age 60 years, 55% female) with total of 351 melanomas in situ had excision with confirmed 5-mm margin in single dermatology clinic
    • melanoma subtypes were superficial spreading melanoma (50.4%), lentigo maligna (30.5%), and lentiginous melanoma in situ (19.1%)
    • median length of lesions 6 mm (< 10 mm in 78%) and median width 5 mm (< 10 mm in 89%)
    • lesion locations were trunk (48%), upper limb (27%), lower limb (17%), neck (4%), face (3.4%), and scalp (0.6%)
    • biopsy type was excised sample for 71% of lesions and shaved sample for 29%
  • median follow-up of 7 years (all had > 5 years of follow-up)
  • recurrence rate 0.9% among all 351 lesions (all had local recurrence with no metastatic spread)
  • specific recurrence rates
    • 0% among 107 lentigo maligna lesions
    • 1.1% among 177 superficial spreading melanomas
    • 1.5% among 67 lentiginous melanomas in situ
  • Reference – JAMA Dermatol 2024 Aug 1;160(8):874, editorial can be found in JAMA Dermatol 2024 Aug 1;160(8):803
• among adults with lentigo maligna who were treated with adjuvant topical imiquimod 5%, residual lentigo maligna reported in 18% of patients after stage 1 excision, and recurrence reported in 3.9% at 5 years (level 3 [lacking direct] evidence)
  •  based on case series
  • 334 adults (mean age 67 years, 70% male, 99% White) with 345 lentigo maligna lesions were treated with imiquimod 5% applied 5 nights per week for 2-3 months prior to staged surgical excision and followed for mean 5.5 years
    • tazarotene 0.1% gel administered to adults with no inflammatory response
    • frequency of imiquimod 5% application reduced for patients with grade 3 (red with surface erosion) inflammatory response
    • surgical excision performed ≥ 2 months after completion of imiquimod regimen; first-stage excision performed with 2-mm margin with subsequent stages with 4-mm margin performed as needed
  • 10.7% of adults loss to follow-up; 89% included in analyses
  • residual lentigo maligna noted in 18% of lesions after first excision, of these 32 patients (67%) had been noted to have complete clinical response to imiquimod 5% cream prior to excision
  • recurrence in 3.9% of adults; mean time to recurrence 4.3 years
  • in subgroup analysis of 262 patients not included in previous trial evaluating addition of tazarotene to imiquimod, recurrence in 7.6% of adults who had combination imiquimod plus tazarotene vs. 2.9% with imiquimod alone (not significant)
  • Reference – JAMA Dermatol 2018 Aug 1;154(8):885full-text

Mohs Micrographic Surgery

• Mohs micrographic surgery (MSS) with horizontal en face frozen sectioning is a staged excision technique that allows for histopathologic margin assessment prior to wound repair, potentially allowing entire staged excision to be completed within 1 day
  •  requires Mohs training
  •  involves repeated excision and microscopic analysis of en face fresh frozen sections until margins are tumor-free at surgery
  • immunohistochemical stains (MART-1 or MITF) may be used for freezing samples to improve accuracy
  •  time constraint may limit use of immunohistochemical staining that enhances ability to distinguish lentigo maligna from melanocyte hyperplasia
  • for details on appropriate use criteria of Mohs surgery for melanoma in situ, lentigo maligna see Indications in Mohs Micrographic Surgery
  • References – ^1,2,3, Dermatol Surg 2006 Apr;32(4):493
• slow Mohs micrographic surgery is similar to MMS, but uses permanent methods for section fixation (such as with paraffin wax or formalin) instead of frozen sections⁽¹⁾
  • slow Mohs excision reported associated with 0% recurrence at ≥ 5 years for well-defined primary lesions or excisions of incomplete excisions, 13.6% recurrence of poorly defined primary lesions, and 57% recurrence following excisions of recurrent lesions in patients with lentigo maligna (level 3 [lacking direct] evidence)
    •  based on case series
    •  74 adults (mean aged 68 years) with lentigo maligna had slow Mohs micrographic surgery with sections fixed with formalin
    •  ≤ 2 stages until histologic clearance in 78%
    • mean margins required for histologic clearance
      •  4.6 mm for well-defined primary lesions
      •  6.2 mm for poorly defined primary lesions (p < 0.05 vs. well-defined primary lesion)
      •  8.4 mm for excisions of remaining lesion from prior incomplete excision (p < 0.01 vs. well-defined primary lesion)
      •  15 mm for excisions of recurrent lesion from prior excision (p < 0.01 vs. well-defined primary lesion)
    • recurrence after excision in 12% of 56 patients who were followed for ≥ 5 years, including in
      •  0% of well-defined primary lesions
      •  13.6% of poorly defined primary lesion
      •  0% of excisions of remaining lesion from prior incomplete excision
      •  57% of excisions of recurrent lesion from prior excision
    •  Reference – Br J Dermatol 2014 Aug;171(2):298

Staged Excision Technique

• staged excision with permanent sections allows for histopathologic margin assessment prior to wound repair, and generally involves tumor debulking and staged excision of margins
  • analysis of central tumor debulking specimen can be used to detect invasion and lentigo maligna melanoma upstaging
  • staged excision procedures may include
    •  geometric staged excision using a geometric shape (sometimes called “square” excision) with at least 3 sides at a 3-5 mm margin around lesion, and margin analysis by vertical (“bread-loaf”) or en face horizontal sectioning
    •  spaghetti technique using a circumferential excision of 2 mm strip of skin at 3-5 mm margin around lesion with margin analysis by vertical or en face horizontal sectioning
    • collarette technique, identical to spaghetti technique with additional use of dermoscopy to delineate tumor border
  •  margin evaluation may involve vertical (“bread-loaf”) sectioning of margin tissue or en face horizontal sectioning for histopathologic analysis depending on choice of surgeon and histopathologist
  •  recurrence of 0%-7% reported after staged excision
  • References – ^1,2,3, Dermatol Surg 2006 Apr;32(4):493, Dermatol Pract Concept 2023 Jul 1;13(3)full-text
• EVIDENCE SYNOPSIS: Recurrence rates after staged excision may vary based on procedure used but appear to be ≤ 5%.
  • recurrence following staged excision reported in 2.4%-4% of patients with lentigo maligna (level 3 [lacking direct] evidence)
    •  based on 2 case series
    • 124 patients with lentigo maligna and 146 patients with lentigo maligna melanoma had staged excision
      •  > 1 excisions required in 48%
      • at follow-up of median 55 months (range 5-151 months)
        •  local recurrence in 2.4% with lentigo maligna and 2.1% with lentigo maligna melanoma
        •  disease-related death in 0 with lentigo maligna and 1 with lentigo maligna melanoma
      •  Reference – Br J Dermatol 2014 Dec;171(6):1605
    • 100 patients with lentigo maligna (97% on face or scalp) had staged surgical excision with mean follow-up 58 months
      •  procedure involved excision of lesion with 3 mm margin and histopathologic analysis, if margins positive then excision repeated with 5 mm margins until clear (surgical wound left open and covered until margins clear)
      •  clear margins after 1 stage in 49%
      •  recurrence in 4
      •  Reference – Br J Dermatol 2016 Mar;174(3):588
  • geometric staged excision reported associated with 2% recurrence in patients with lentigo maligna or lentigo maligna melanoma (level 3 [lacking direct] evidence)
    •  based on case series
    •  225 patients (mean aged 67 years) with lentigo maligna and 68 with lentigo maligna melanoma had geometric staged excision (with Wood’s lamp used to clinically define lesion)
    •  67.6% lesions located on face
    •  mean margin to clearance 6.6 mm for lentigo maligna and 8.2 mm for lentigo maligna melanoma
    •  mean follow-up 32.3 months (range 2-96 months) with 18.4% lost to follow-up
    •  recurrence at mean 32.3-month follow-up in 1.7%
    •  Reference – Arch Dermatol 2012 May;148(5):599
  • collarette (“spaghetti”) staged excision reported to be associated with 1.4%-5% recurrence in patients with lentigo maligna (level 3 [lacking direct] evidence)
    •  based on 3 case series
    • 31 adults with lentigo maligna of head or neck had collarette (also called “spaghetti” staged excision)
      •  initial skin biopsy showed lentigo maligna in all patients
      •  procedure involved strips excised at 5 mm margin of clinically defined lesion with perpendicular incisions, with additional strips if needed excised at 5 mm margins
      •  invasive melanoma detected at surgery in 15 patients
      •  ≥ 2 stages to margin clearance needed in most patients
      •  final excision margins of 10 mm in 71%, with mean final margins of 13.2 mm
      •  recurrence at mean 31-month follow-up in 1 (3%) patient
      •  Reference – Int J Dermatol 2014 Jul;53(7):899
    • 16 patients with lentigo maligna and 5 patients with acral lentiginous melanoma had spaghetti technique excision of lesions with median follow-up of 25.36 months
      •  mean operative defect size 27.5 cm² (range 1.97-108.4 cm²)
      •  mean steps needed 1.55 (range 1-4)
      •  1 (5%) recurrence at follow-up
      • Reference – J Am Acad Dermatol 2011 Jan;64(1):113
    • 102 patients with lentigo maligna of the head or neck had staged excision with circumferential margin control (spaghetti technique) and were followed for median 3.8 years
      • > 1 excision required in 22% of patients
      • 21% of patients needed excision margin > 5 mm to achieve histological clearance
      • infection in 6%
      • recurrence in 3.9% of patients
      • 5-year cumulative recurrence rate 1.4% (95% CI 0.2%-9.6%)
      • Reference – J Cutan Med Surg 2021 Jan;25(1):18
  • Johnson staged excision reported to clear most lesions in patients with poorly defined lentigo maligna or lentigo maligna melanoma (level 3 [lacking direct] evidence)
    •  based on case series
    •  18 adults with poorly defined lentigo maligna and 3 with lentigo maligna melanoma lesions had Johnson staged excision
    •  margins around clinically defined lesion (using Wood’s lamp) excised in a square shape leaving “picture frame” defect around lesion while permanent section histopathology obtained
    •  ≤ 2 stages needed in 16 patients
    •  recurrence within 5 years in 1 patient (4.8%) (who was unable to achieve histologic clearance due to lesion extension into mucosal surface of inner canthus)
    •  Reference – Clin Exp Dermatol 2014 Jul;39(5):570

Comparison of Surgical Techniques

• Mohs micrographic surgery and wide local excision appear associated with similar cancer-specific and overall survival in patients with melanoma in situ (level 2 [mid-level] evidence)
  •  based on retrospective cohort study
  • 28,637 patients (mean age 58 years) with melanoma in situ (MIS) treated with Mohs micrographic surgery (MMS) (4,122 cases) or wide local excision (WLE) (24,515 cases) and followed for up to 15 years from the Surveillance, Epidemiology, and End Results (SEER) cancer registry (National Cancer Institute)
  • comparing Mohs micrographic surgery vs. wide local excision
    • aged ≥ 75 years 23.3% vs. 15.3% (p < 0.001)
    • facial tumors 56.2% vs. 15.8% (p < 0.001)
    • not ulcerated 88.8% vs. 43.6% (p < 0.001)
    • tumor < 1 cm 35% vs. 13.1% (p < 0.001)
    • 5 year survival 92% vs. 94% (no p value reported)
    • 10 year survival 81% vs. 86% (no p value reported)
    • 15 year survival 73% vs. 76% (no p value reported)
  • comparing Mohs vs. wide local excision, no significant difference in
    • cancer-specific survival (hazard ratio [HR] 0.928, 95% CI 0.596-1.446)
    • adjusted overall survival (HR 1.006, 95% CI 0.896-1.129)
  • Reference – Int J Dermatol 2019 Jun;58(6):697
• EVIDENCE SYNOPSIS: There is mixed evidence comparing Mohs micrographic surgery (MMS) to wide excision for treatment of lentigo maligna in observational studies, but mean 3-5 year recurrence rates are generally reported as 0%-4.5% with MMS and 4%-24% with wide local excision.
  • among patients with lentigo maligna, recurrence at mean 3 years reported in 1.9% who received Mohs surgery and 5.9% who received wide excision (level 2 [mid-level] evidence)
    •  based on retrospective cohort study
    •  407 patients with 423 lentigo maligna lesions had surgical excision with MMS (in 36%) or nonstaged excision with 5 mm margin around clinical lesion (determined with Wood’s lamp) (in 64%)
    •  recurrence at mean 3.2 years in 1.9% with MMS and 5.9% with nonstaged excision (no p value reported)
    •  Reference – Dermatol Surg 2015 Feb;41(2):211
  • Mohs micrographic surgery and wide local excision may be associated with similar recurrence rates in patients with melanoma in situ, with 5-year recurrence reported in 1.1% with Mohs and 4.1% with wide local excision (level 2 [mid-level] evidence)
    •  based on retrospective cohort study
    • 662 patients (mean age 58 years) with melanoma in situ treated with MMS or wide local excision (WLE) and followed for mean of 8.6 years (range 0.2-37 years)
      • 277 patients had MMS and 385 patients had WLE for treatment of melanoma in situ
      • head or neck tumors in 62% overall
      • patients with invasive disease excluded
    • comparing MMS vs. WLE
      • 5-year recurrence 1.1% vs. 4.1% (p < 0.07)
      • melanoma-specific survival 99.3% vs. 96.6% (not significant)
      • overall survival 86.6% vs. 80.5% (not significant)
    • Reference – JAMA Dermatol 2017 May 1;153(5):436full-text
  • among patients with lentigo maligna, Mohs technique associated with lower recurrence than wide excision; 5-year recurrence reported in 0%-4.5% of patients who received usual MMS or MMS with videodermoscopy, and 24% of patients who received wide excision (level 2 [mid-level] evidence)
    •  based on cohort study
    •  54 patients with lentigo maligna on head or neck removed by videodermoscopy-assisted MMS or usual MMS or surgical excision with follow-up for 5 years
    • recurrence in
      •  6 (24%) with surgical excision (p = 0.04 compared to usual MMS and videodermoscopy-assisted MMS)
      •  1 (4.5%) with usual MMS
      •  0 with videodermoscopy-assisted MMS
    •  Reference – J Eur Acad Dermatol Venereol 2016 Aug;30(8):1440

Imiquimod

• topical imiquimod may be appropriate as monotherapy for patients with contraindications to surgery (such as anticoagulation or significant comorbidities), very large lesions, or potentially problematic reconstruction due to lesion location; also consider imiquimod as adjunctive therapy or for patients with positive margins after excision^(1,2,3)
  • off-label dosage for lentigo maligna: apply imiquimod 5% cream to an area of at least 2 cm beyond outlined tumor margins 5 nights/week for 2-3 months; allow a recuperation period of at least 2 months after completion of topical therapy before excision
  • evidence for imiquimod is mixed due to the varying regimens and follow-up durations among studies; 50%-93% complete histopathologic clearance and 7%-50% recurrence rates have been reported⁽³⁾
  • topical imiquimod does not penetrate the skin deep enough to treat atypical melanocytes within hair follicles⁽³⁾
  • adverse effects may include⁽³⁾
    • inflammatory reactions (may be severe, but are typically dose dependent and subside with cessation)
    • postinflammatory pigmentation changes
    • systemic effects, such as flu-like symptoms (rare)
  • topical imiquimod may also be used as a neoadjuvant therapy to decrease margin size prior to surgical resection or in combination with cryosurgery (see Cryosurgery and Immunocryosurgery for more information)⁽³⁾
• efficacy of imiquimod monotherapy
  • imiquimod 5% cream monotherapy for > 60 applications, or about 12 weeks, associated with improved clearance in patients with lentigo maligna (level 3 [lacking direct] evidence)
    •  based on systematic review without comparative data
    •  systematic review of 45 observational studies (28 case reports, 11 case series, and 6 cohort studies) evaluating imiquimod 5% cream monotherapy in patients (347 tumors) with lentigo maligna
    •  mean treatment duration 12.6 weeks with mean follow-up 27 months
    • in tumor-level analyses
      •  clinical clearance in 78.3% of 304 tumors
      •  histologic clearance in 76.2% of 303 tumors
      •  clinical recurrence in 2.3% of 256 tumors
    •  no significant difference in clearance or recurrence rates comparing primary tumors to recurrent tumors
    • increased clinical and histologic clearance rates associated with imiquimod monotherapy for
      •  > 60 total applications (odds ratio 8.4, 95% CI, 2.9-24.1)
      •  > 5 applications/week (odds ratio 6.0, 95% CI, 2.4-14.7)
    •  Reference – J Am Acad Dermatol 2015 Aug;73(2):205
  • among patients with lentigo maligna clearance after topical imiquimod 5% treatment, 20% recurrence reported at 10 years (level 3 [lacking direct] evidence)
    •  based on case series
    • 114 adults (median age 72 years, 61.3% female) with lentigo maligna and were treated with imiquimod 5% applied 1-2 times daily until weeping erosion seen on treated skin (median 4 week treatment duration) and followed for median 8 years
    • 60% of patients had Fitzpatrick skin type II, 30.9% type III, and 9.1% type I
    • 97.4% of adults had lesion clearance after imiquimod 5% cream and were included in analyses
    • relapse in 20% of adults over 10 years
    • lentigo maligna disease free survival rates
      • at 3 years 87.4% (95% CI 81%-94%)
      • at 5 years 76.5% (95% CI 68%-85%)
      • at 10 years 74.3% (95% CI 65%-84%)
    • no lentigo maligna-related mortality reported
    • adverse events include erosions, oozing, eschars (in 85.6% of patients), and erythema or inflammation (in 12.6%)
    • Reference – Cancers (Basel) 2023 Feb 28;15(5)full-text
• efficacy of imiquimod combination therapies (surgical excision, other topical treatments, cryotherapy)
  • among adults with lentigo maligna who were treated with adjuvant topical imiquimod 5% residual lentigo maligna reported in 18% of patients after stage 1 excision, and recurrence reported in 3.9% at 5 years (level 3 [lacking direct] evidence)
    •  based on case series
    • 334 adults (mean age 67 years, 70% male, 99% White) with 345 lentigo maligna lesions were treated with imiquimod 5% applied 5 nights per week for 2-3 months prior to staged surgical excision and followed for mean 5.5 years
      • tazarotene 0.1% gel administered to adults with no inflammatory response
      • frequency of imiquimod 5% application reduced for patients with grade 3 (red with surface erosion) inflammatory response
      • surgical excision performed ≥ 2 months after completion of imiquimod regimen; first-stage excision performed with 2-mm margin with subsequent stages with 4-mm margin performed as needed
    • 10.7% of adults loss to follow-up; 89% included in analyses
    • residual lentigo maligna noted in 18% of lesions after first excision, of these 67% (32 patients) had been noted to have complete clinical response to imiquimod 5% cream prior to excision
    • recurrence in 3.9% of adults; mean time to recurrence 4.3 years
    • in subgroup analysis of 262 patients not included in previous trial evaluating addition of tazarotene to imiquimod, recurrence in 7.6% of adults who had combination imiquimod plus tazarotene vs. 2.9% with imiquimod alone (not significant)
    • Reference – JAMA Dermatol 2018 Aug 1;154(8):885full-text
  • imiquimod 5% cream reported to help clear persistent lentigo maligna after incomplete surgical resection (level 3 [lacking direct] evidence)
    •  based on 2 case series
    • 61 patients with lentigo maligna or lentigo maligna melanoma after biopsy or after incomplete surgical resection were treated with imiquimod 5% cream for mean 11.7 weeks (range 2-60 weeks)
      • at mean follow-up 42.1 months, clinical clearance in
        •  72.7% with imiquimod as primary treatment
        •  94.4% with imiquimod as adjuvant treatment after surgical excision
    • Reference – J Am Acad Dermatol 2015 Jun;72(6):1047
  • addition of tazarotene 0.1% gel to imiquimod 5% cream may not increase clearance rates in patients with lentigo maligna (level 2 [mid-level] evidence)
    •  based on randomized trial without blinding
    • 90 patients with 91 lesions of lentigo maligna were randomized to tazarotene 0.1% gel 2 days weekly plus imiquimod 5% cream 5 days weekly vs. imiquimod alone for 3 months followed by staged surgical excision
      •  shave excision to remove visible signs of lentigo maligna in all patients before treatment
      •  lesion delineated with Wood’s lamp and template of original lesion created before topical treatment
    •  clearance assessed with Melan-A immunostaining of frozen sections of excised lesion
    • comparing patients with tazarotene plus imiquimod vs. imiquimod alone
      •  complete clearance in 78% vs. 64% (not significant)
      •  dropout due to adverse events in 13.6% vs. 2.2% (no p value reported)
    •  Reference – Arch Dermatol 2012 May;148(5):592
    •  no additional randomized trials found assessing imiquimod or any other treatment for lentigo maligna in Cochrane review (Cochrane Database Syst Rev 2014 Dec 19;(12):CD010308, comment in J Am Acad Dermatol 2022 Sep;87(3):e115)
  • imiquimod 5% cream once daily for 3 weeks plus cryotherapy (2 cycles of 20 seconds), followed by imiquimod 5% cream 3 times per week for 6 months, reported to clear lentigo maligna for in 3 patients with comorbid medical conditions in case series (J Dermatol 2018 May;45(5):564)
  •  imiquimod 5% cream plus cryotherapy for periorbital lentigo maligna and topical interferon-alpha-2b for conjunctival primary acquired melanosis with atypia reported to resolve lesions for 21 months in case report (Cornea 2015 Jan;34(1):90)
  • see also Cryosurgery and Immunocryosurgery

Other Procedures

Laser Therapy and Photodynamic Therapy

• photodynamic therapy (PDT) is used for management of precancerous and cancerous skin lesions, and has been proposed as an alternative treatment for lentigo maligna but has limited evidence for efficacy⁽³⁾
• ablative fractional lasers may be added to PDT, and help provide deeper penetration of photosensitizer precursor to reach all atypical melanocytes⁽³⁾
• other types of lasers that have been reported in case reports/series of lentigo maligna include carbon dioxide, Q-switched ruby, argon, neodymium-doped yttrium aluminium garnet, alexandrite laser or combinations lasers; all were reported to be associated with poor results and high recurrence rates⁽³⁾
• laser therapy reported with to be associated with mean 34.4% recurrence rate of lentigo maligna (level 3 [lacking direct] evidence)
  •  based on systematic review of observational studies
  •  systematic review of 29 studies of nonsurgical treatments for lentigo maligna
  •  9 case series reviewed laser therapy for lentigo maligna in 61 patients
  •  mean recurrence rate 34.4% (range 0%-100%)
  •  Reference – J Eur Acad Dermatol Venereol 2016 May;30(5):748
• recurrence following ablative laser therapy plus imiquimod reported to be associated with 20% recurrence rate in patients with lentigo maligna (level 3 [lacking direct] evidence)
  •  based on case series
  •  35 patients with lentigo maligna had erbium-doped yttrium aluminium garnet (Er:YAG) or carbon dioxide ablative laser therapy until complete pigment clearance and punctuate bleeding followed after 1 day by topical imiquimod once daily 5 days weekly for 6 weeks
  •  6 (23.5%) recurrences at median 19-month follow-up
  •  Reference – Br J Dermatol 2016 May;174(5):1134
• lack of clinical or histologic clearance following photodynamic therapy reported in 21% of patients with lentigo maligna (level 3 [lacking direct] evidence)
  •  based on case series
  •  15 adults with lentigo maligna had photodynamic therapy (40-90 Joules/cm² with wavelength 635 nanometers) every 3 weeks for 9-27 weeks (total 3-9 sessions) with follow-up for ≤ 50 months
  •  lack of clinical or histologic clearance immediately after therapy in 3 patients (21%)
  •  Reference – Pigment Cell Melanoma Res 2013 Mar;26(2):275

Cryosurgery and Immunocryosurgery

• cryosurgery refers to cryotherapy with liquid nitrogen, and has been proposed as a potential alternative therapy for some patients with lentigo maligna, but there is limited evidence for efficacy⁽³⁾
  • depth ≥ 3 mm is needed to achieve destruction of atypical melanocytes that are extended into hair follicles⁽³⁾
  • recurrence rates of lentigo maligna with cryosurgery are reported to range from 0% to 40%⁽³⁾
  • limited evidence available to evaluate cryosurgery for treatment of lentigo maligna^(1,2,3)
• immunocryosurgery refers to a combination of cryosurgery plus topical imiquimod, and has been proposed as an alternative management strategy for lentigo maligna, but has limited evidence⁽³⁾
  • immunocryosurgery is thought to potentially increase the efficacy of imiquimod therapy by inciting increased inflammation⁽³⁾
  • imiquimod 5% cream once daily for 3 weeks plus cryotherapy (2 cycles of 20 seconds), followed by imiquimod 5% cream 3 times per week for 6 months, reported to clear lentigo maligna for in 3 patients with comorbid medical conditions in case series (J Dermatol 2018 May;45(5):564)
  •  imiquimod 5% cream plus cryotherapy for periorbital lentigo maligna and topical interferon-alpha-2b for conjunctival primary acquired melanosis with atypia reported to resolve lesions for 21 months in case report (Cornea 2015 Jan;34(1):90)

Radiation Therapy

• radiation therapy may be considered as first-line therapy if surgery is contraindicated (such as for patients with anticoagulation or comorbidities, very large lesions, or lesions in problematic locations), or as an adjuvant therapy if positive margins after surgical resection remain⁽³⁾
• use of appropriate dose, volume, and fractionation pattern for radiation therapy is necessary to avoid adverse effects such as hypopigmentation, telangiectasia, or cicatrization (Dermatol Res Pract 2018;2018:7439807full-text)
• superficial radiation therapy (Grenz ray or Miescher technique) has minimal dermal penetration (1 mm deep) resulting in a lack of adnexal treatment and the risk of residual melanocytes, and so is reported to not be preferred for lentigo maligna⁽³⁾
• a meaningful depth reported to be 5 mm or to the oncological barrier (such as the skull); changes to appropriate depth may be needed based on location of lesion such as near the lacrimal gland (Dermatol Res Pract 2018;2018:7439807full-text)
• radiation therapy with deeper penetration has reported cure rates of 86%-91%, but is associated with risk of scarring and pigmentation changes which may inhibit ability to assess for recurrence⁽³⁾
• pooled recurrence rate 11.5% reported with radiation therapy for lentigo maligna (level 3 [lacking direct] evidence)
  •  based on systematic review of observational studies
  •  systematic review of 29 studies of nonsurgical treatments for lentigo maligna
  •  10 case series reviewed radiation therapy for lentigo maligna in 454 patients
  • recurrence 11.5% (range 0%-31.3%) in overall pooled data
    •  recurrence 10.8% with Grenz Ray therapy in pooling of case series with total 342 patients, results limited by statistical heterogeneity
    •  recurrence rate 13.4% with superficial radiation therapy techniques in pooling of case series with total 112 patients, results limited by statistical heterogeneity
  •  Reference – J Eur Acad Dermatol Venereol 2016 May;30(5):748
  • similar results reported in narrative systematic review of 14 case series assessing radiation therapy in 1,243 lentigo maligna lesions (Radiat Oncol 2020 Jul 14;15(1):174full-text)
• Grenz radiation as monotherapy or adjunct to excision reported to sustain complete clearance of lentigo maligna or lentigo maligna melanoma in 97% of patients with 10-year follow-up (level 3 [lacking direct] evidence)
  •  based on follow-up of case series
  • 159 patients (161 lesions) out of 593 patients who had Grenz radiation (GR) for lentigo maligna or lentigo maligna melanoma between 2005 and 2007 were included in a 10 year follow-up
  • 69 patients (mean age 74 years, 70% female) with total 70 lesions (83% facial) completed the 10-year follow-up and were included in analysis
  • of the included 69 patients, 46.4% had GR as primary treatment, 30.4% had GR as adjunct to radical excision, and 23.2% had GR as adjunct to nonradical excision
  • 10-year outcomes in 69 included patients
    • complete clearance in 97% (lentigo maligna recurrence reported in 2 cases)
    • 13% of patients had new cases of lentigo maligna, lentigo maligna melanoma, or other melanoma
  • Reference – Acta Derm Venereol 2020 Oct 6;100(17):adv00282full-text
• evidence assessing radiation therapy for management of lentigo maligna is ongoing (Dermatol Res Pract 2018;2018:7439807full-text)
• review of treating lentigo maligna with definitive radiotherapy can be found in Dermatol Res Pract 2018;2018:7439807

Follow-Up

• at least annual follow-up physical and skin exams are recommended by professional organizations, with an emphasis on looking for local recurrence of lentigo maligna
  • following treatment of lentigo maligna, consider a follow-up visit every 6-12 months for first 1-2 years (and thereafter annually)
  • provide patient education on self exam of the skin and lymph nodes
  • see Recommendations from Professional Organizations for details
• mean 4.5 years is the reported time to local lentigo maligna recurrence; see also Prognosis⁽³⁾
• surgical and nonsurgical management methods may cause inflammation and scarring that can interfere with assessment of recurrent lesions; tools such as dermoscopy and reflectance confocal microscopy (RCM) may help with follow-up evaluations⁽³⁾
  • presence of “dust-like dots” on dermoscopy is reported to suggest treatment failure following imiquimod or radiation therapy for lentigo maligna melanoma
  • waiting ≥ 3 months after surgical resection prior to RCM use is advised to avoid inflammation and early scarring changes; handheld RCM may be particularly useful for monitoring treatment outcomes of large, amelanotic, or poorly pigmented lentigo maligna lesions
•  limited evidence to guide surveillance of melanoma, and recommended follow-up intervals vary among organizations; see Follow-up in Melanoma for additional information

Complications

• lentigo maligna (LM) complications may include ⁽³⁾
  • progression to lentigo maligna melanoma
  • change to patient appearance if LM is present in visible area (such as the face); both the primary lesion and potential scarring from removal may affect appearance

Prognosis

Progression and Cancer Risk

• lentigo maligna (LM) has an estimated 5%-50% lifetime risk of progression to lentigo maligna melanoma (LMM), and risk may increase with age⁽³⁾
  • true progression risk is unclear due to limited prospective evidence, and likely nonreporting of mild or slowly progressing cases^(1,2)
  • larger lentigo maligna may increase risk for progression to LMM⁽³⁾
  • presence of papules, nodules, or thick plaques suggest progression to LMM⁽³⁾
  • estimated 3.53% risk of progression to lentigo maligna melanoma per year that lentigo maligna is present among adults in Australia
    •  based on population-based surveillance
    • 682 adults with newly diagnosed, nonrecurrent confirmed lentigo maligna or lentigo maligna melanoma of the head an neck identified in the Australian New South Wales Cancer Registry were sent a survey to assess when the lesion initially presented, when/if the patient noticed skin changes, and when the lesion was removed (survey sent at median 4.6 months after diagnosis)
    • estimated progression of lentigo maligna to lentigo maligna melanoma was calculated as: (total number of lentigo maligna melanoma diagnosed during study period) / (estimated total number of years lentigo maligna and lentigo maligna melanoma on skin prior to biopsy)
    • 53.5% of patients responded to surveys and were included in analysis; 88% had lentigo maligna (median age 67 years) and 12% had lentigo maligna melanoma (median age 70 years)
    • LM was present on the skin for median 18 months (range 0-690 months) and lentigo maligna melanoma (LMM) for median 18 months (range 0-665 months)
    • estimated risk of progression of LM to LMM was 3.53% per year (95% CI 2.5%-5%) that LM was present
    • mean time for LM to progress to LMM was 28.3 years (95% CI 20-40.5 years)
    • Reference – Melanoma Res 2020 Apr;30(2):193
• melanoma in situ (including lentigo maligna) is not reported to increase mortality, but may be associated with developing second primary cancer, including
  •  primary melanoma
  •  tumors of lip
  •  lymphocytic leukemia
  •  non-Hodgkin lymphoma
  •  hematologic malignancies
  •  Reference – J Am Acad Dermatol 2015 Aug;73(2):181
• 2.3% 15-year mortality reported among patients with LM in population-based surveillance study of 137,872 patients with melanoma in situ (24% with LM); LM subtype was not associated with increased risk of melanoma-specific mortality (JAMA Dermatol 2023 Jul 1;159(7):703)

Recurrence

• recurrent or persistent lentigo maligna (LM) or lentigo maligna melanoma (LMM) is defined as onset of a papule, nodule, or change in skin of treated area, often presenting as amelanotic or lightly pigmented with nonspecific clinical/dermoscopic features⁽³⁾
  • surgical cure rate typically assessed 5 years after treatment⁽³⁾
  • mean 4.7 years reported as time to recurrence for treated lentigo maligna or thin lentigo maligna melanoma
    •  based on case series
    • 649 adults with LM or stage 1 LMM received surgical or staged excision between 2000 and 2015 and were reviewed for biopsy-proven recurrence
    • 41 adults (6%) had locally recurrent LM or LMM
    • of the 41 adults with recurrence, 29 adults (70%) had previous pathology report/excision slides to confirm date of initial treatment to assess time to tumor recurrence
      • mean time to initial recurrence 4.7 (range 7 months to 16 years)
      • LM was primary lesion in 21 patients, and LMM in 8; of the 21 patients with LM, 7 recurred as LMM
      • 69% of recurrences were on the face, 21% on the ear, and 3.4% each on the neck, scalp, and trunk
      • mean size of locally recurrent lesion 1.7 cm (range 0.3-7 cm)
    • Reference – Dermatol Surg 2017 Jun;43(6):792
• reported recurrence rates vary according to treatment type and follow-up duration, but are generally reported to be lowest with surgical excision with complete histologic assessment of lesion margins; reported recurrence rates for standard therapies⁽¹⁾
  • surgical excision techniques
    • 0%-7% recurrence with staged excision with permanent sections (including geometric staged excision technique and the spaghetti technique)^(1,2,3)
    • 0%-6% recurrence with Mohs micrographic surgery (though recurrence of up to 33% has been reported in 1 study)^(1,2,3)
    • 8%-20% recurrence with standard wide local excision⁽²⁾
    • see also Surgical Excision in Management
  • 7%-50% recurrence rates have been reported with topical imiquimod; see also Imiquimod in Management⁽³⁾
  • 0%-31% recurrence reported with radiation therapy in systematic review, with rates varying based on penetration depth and technique (Radiat Oncol 2020 Jul 14;15(1):174full-text); see also Radiation Therapy in Management
• risk factors for recurrence
  • risk factors for recurrence may include⁽¹⁾
    •  smaller size of excisional margin
    •  incomplete margin control, with positive margins on pathologic assessment
    •  increased melanocyte count
  • melanocyte count > 20 cells per 0.5 mm diameter of most affected margin tissue associated with moderate-to-high risk of recurrence following surgical excision of lentigo maligna (level 2 [mid-level] evidence)
    •  based on retrospective cohort study
    •  99 patients with lentigo maligna were followed for ≥ 18 months for recurrence
    •  histologic assessment including melanocyte count of most affected margin tissues performed by dermatopathologists blinded to recurrence
    • predicted risk of recurrence for melanocyte count per 0.5 mm diameter in regression analysis
      •  0-20 cells, 1.4% (95% CI 0.2%-5%)
      •  21-30 cells, 45.8% (95% CI 20.6%-72.5%)
      •  ≥ 31 cells, 99.1% (95% CI 93.8%-100%)
    •  Reference – J Plast Reconstr Aesthet Surg 2014 Oct;67(10):1322
  • increased melanocytes in epidermis appear to increase risk for recurrence after imiquimod for lentigo maligna (level 2 [mid-level] evidence)
    •  based on cohort study
    •  89 patients (median age 72.5 years) with lentigo maligna treated with imiquimod 5% topically once or twice daily until weeping erosion developed
    •  recurrence in 16 at median of 1.89 years
    •  recurrence associated with greater number total melanocytes/mm (hazard ratio [HR] 1.03, 95% CI 1.02-1.05), basal and suprabasal melanocytes/mm (HR 1.06, 95% CI 1.03-1.1), and pagetoid spreading melanocytes/mm of epidermis (HR 1.05, 95% CI 1.01-1.1)
    •  Reference – J Am Acad Dermatol 2016 Jan;74(1):81
• lentigo maligna may be more likely to persist after complete excisional biopsy than other primary cutaneous melanoma (level 2 [mid-level] evidence)
  •  based on retrospective cohort study
  •  807 specimens from wide local excision (WLE) for primary cutaneous melanomas diagnosed by complete excisional biopsy with clinical and histologically clear margins were reviewed
  •  location of melanomas, trunk in 39%, lower extremity in 25.2%, upper extremity in 21.9%, and head and neck in 13.9%
  •  primary melanoma detected in WLE in 33 (4%), including 22 melanoma in situ and 12 invasive melanoma
  •  locally metastatic melanoma detected in 1 (0.1%)
  •  compared to other subtypes (superficial spreading, desmoplastic, nodular, or other), lentigo maligna associated with persistent melanoma in WLE (odds ratio 2.7, 95% CI 1.0-7.3, p = 0.04)
  •  Reference – J Am Acad Dermatol 2016 Jan;74(1):102

Prevention and Screening

Prevention

•  consider limiting sun exposure due to association of ultraviolet radiation with increased risk for lentigo maligna (see Risk Factors for additional information)
•  efficacy of sunscreen use in preventing lentigo maligna is not known (J Am Acad Dermatol 2015 Aug;73(2):181)
• for prevention of melanoma
  • United States Preventive Services Task Force (USPSTF) recommendations on behavioral counseling to prevent skin cancer:
    • Counsel patients aged 6 months to 24 years and parents of young children who have fair skin about minimizing exposure to ultraviolet (UV) radiation to reduce risk of skin cancer (USPSTF Grade B).
      • Fair skin can be defined by:
        • Light eye and hair color
        • Freckles
        • Historical factors (such as usually burning or infrequently tanning after sun exposure)
      • Effective counseling interventions were:
        • Generally low intensity
        • Accomplished within primary care visit
        • Cancer prevention or appearance-focused messages (aging effect of UV radiation) to target specific populations
    • Consider counseling on minimizing UV radiation exposure for patients > 24 years old with fair skin if other risk factor(s) for skin cancer are present (USPSTF Grade C). Other risk factors for skin cancer include:
      •  History of sunburns or use of indoor tanning beds
      •  Personal or family history of skin cancer
      •  Higher number of nevi and atypical nevi
      •  Compromised immune system (such as in patients with HIV infection or those who have received an organ transplant)
    •  Reference – JAMA 2018 Mar 20;319(11):1134, editorial can be found in JAMA 2018 Mar 20;319(11):1101

Screening

• insufficient evidence to recommend skin cancer screening of general population based on synthesis of guidelines from United States Preventive Services Task Force (USPSTF) and Australian Cancer Network/New Zealand Guidelines Group (ACN/NZGG) (USPSTF 2023 Apr 18, NHMRC 2008 Oct:CP111 PDF)
  • similar findings in Cochrane review of trials evaluating screening of general population for malignant melanoma (Cochrane Database Syst Rev 2019 Jun 3;6:CD012352)
  • no randomized trials directly assessing benefits or harms of skin cancer screening with visual skin examination in asymptomatic persons ≥ 15 years old found in systematic review evaluating evidence to inform recommendation by USPSTF (JAMA 2023 Apr 18;329(15):1296, editorial can be found in JAMA 2023 Apr 18;329(15):1259)
• increased skin monitoring generally recommended by expert guidelines for groups at increased risk of skin cancer, such as those with light skin prone to sun burn, personal history of nonmelanoma skin cancer, or family history of melanoma; see Screening in Melanoma for details

Guidelines and Resources

Guidelines

United States Guidelines

•  American Academy of Dermatology (AAD) guideline on management of primary cutaneous melanoma can be found in J Am Acad Dermatol 2019 Jan;80(1);208
•  National Comprehensive Cancer Network (NCCN) guideline on cutaneous melanoma can be found at NCCN website (free registration required)
• American Society of Plastic Surgeons/American Society for Dermatologic Surgery/American Academy of Dermatology/American Academy of Facial Plastic and Reconstructive Surgery/American Academy of Otolaryngology-Head and Neck Surgery Foundation/American College of Mohs Surgery/American Society for Mohs Surgery/American Society of Ophthalmic Plastic and Reconstructive Surgery (ASPS/ASDS/AAD/AAFPRS/AAO-HNSF/ACMS/ASMS/ASOPRS) clinical practice guideline on reconstruction after skin cancer resection can be found in J Am Acad Dermatol 2021 Aug;85(2):423
•  United States Preventive Services Task Force (USPSTF) recommendation statement on screening for skin cancer can be found in JAMA 2023 Apr 18;329(15):1290full-text, supporting systematic review can be found in JAMA 2023 Apr 18;329(15):1296full-text, summary for patients can be found in JAMA 2023 Apr 18;329(15):1324
•  United States Preventive Services Task Force (USPSTF) recommendation statement on behavioral counseling to prevent skin cancer can be found at USPSTF 2018 Mar 20 or in JAMA 2018 Mar 20;319(11):1134, editorial can be found in JAMA 2018 Mar 20;319(11):1101, commentary can be found in JAMA Intern Med 2018 May 1;178(5):609full-text

United Kingdom Guidelines

•  British Association of Dermatologists (BAD) clinical practice guideline on identification, screening, and follow-up of individuals at high risk of primary cutaneous melanoma can be found in Br J Dermatol 2015 Jan;172(1):33
• National Institute for Health and Care Excellence (NICE) guideline on recognition and referral of suspected cancer can be found at NICE 2015 Jun 23:NG12, last updated 2023 Aug 24PDF

Canadian Guidelines

• Cancer Care Ontario (CCO) guidelines on
  • screening for skin cancer can be found at CCO 2007 Jun PDF
  • surveillance of patients with stage I, II, III, or resectable iv melanoma who were treated with curative intent can be found at CCO 2023 Mar
  • use of adjuvant radiation therapy for curatively resected cutaneous melanoma can be found at CCO 2016 Jan
•  Alberta Health Services Provincial Tumour Teams (PTT) guideline on biopsy of suspicious pigmented lesion can be found at AHS 2021 Aug PDF

European Guidelines

• European Dermatology Forum/European Association of Dermato-Oncology/European Organization for Research and Treatment of Cancer (EDF/EADO/EORTC) consensus guideline for melanoma
  • part 1: diagnostics can be found in Eur J Cancer 2020 Feb;126:141full-text
  • part 2: treatment can be found in Eur J Cancer 2022 Jul;170:256full-text

Australian and New Zealand Guidelines

• Cancer Council Australia clinical practice guideline on diagnosis and management of melanoma can be found at Cancer Council Australia accessed 2023 Jun 1

Review Articles

• reviews can be found in
  • Actas Dermosifiliogr 2023 May;114(5):413full-text
  • Clin Plast Surg 2021 Oct;48(4):669
  • Clin Cosmet Investig Dermatol 2020;13:837full-text
  • G Ital Dermatol Venereol 2020 Apr;155(2):179full-text
• review of dermoscopic features of pigmented macules on the head and neck can be found in Dermatol Pract Concept 2022 Nov;12(4):e2022194full-text
• review of surgical techniques for management of lentigo maligna can be found in J Am Acad Dermatol 2023 Jun 10;
• review of treating lentigo maligna with definitive radiotherapy can be found in Dermatol Res Pract 2018;2018:7439807
•  review of epidemiology, screening, and clinical features of melanoma in situ can be found in J Am Acad Dermatol 2015 Aug;73(2):193-203; quiz 203
•  review of histopathology, treatment, and clinical management of melanoma in situ can be found in J Am Acad Dermatol 2015 Aug;73(2):193-203; quiz 203
• review of 9 subtypes of melanoma in 2018 World Health Organization classification system can be found in Arch Pathol Lab Med 2020 Apr;144(4):500full-text

MEDLINE Search

•  to search MEDLINE for (Lentigo Maligna) with targeted search (Clinical Queries), click therapy, diagnosis, or prognosis

Patient Information

• handouts from
  • British Association of Dermatologists PDF
  • American Osteopathic College of Dermatology
  • European Society for Micrographic Surgery

References

General References Used

1. Kasprzak JM, Xu YG. Diagnosis and management of lentigo maligna: a review. Drugs Context. 2015;4:212281full-text.
2. Kallini JR, Jain SK, Khachemoune A. Lentigo maligna: review of salient characteristics and management. Am J Clin Dermatol. 2013 Dec;14(6):473-80.
3. Iznardo H, Garcia-Melendo C, Yélamos O. Lentigo Maligna: Clinical Presentation and Appropriate Management. Clin Cosmet Investig Dermatol. 2020;13:837-855full-text.