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Lentigo maligna is where
melanocyte Melanocytes are melanin-producing neural crest-derived cells located in the bottom layer (the stratum basale) of the skin's epidermis, the middle layer of the eye (the uvea), the inner ear, vaginal epithelium, meninges, bones, and heart. ...
cells have become
malignant Malignancy () is the tendency of a medical condition to become progressively worse. Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not s ...
and grow continuously along the
stratum basale The ''stratum basale'' (basal layer, sometimes referred to as ''stratum germinativum'') is the deepest layer of the five layers of the epidermis, the external covering of skin in mammals. The ''stratum basale'' is a single layer of columnar or ...
of the skin, but have not
invaded An invasion is a military offensive in which large numbers of combatants of one geopolitical entity aggressively enter territory owned by another such entity, generally with the objective of either: conquering; liberating or re-establishing con ...
below the
epidermis The epidermis is the outermost of the three layers that comprise the skin, the inner layers being the dermis and hypodermis. The epidermis layer provides a barrier to infection from environmental pathogens and regulates the amount of water rele ...
.
Lentigo A lentigo () (plural lentigines, ) is a small pigmented spot on the skin with a clearly defined edge, surrounded by normal-appearing skin. It is a harmless (benign) hyperplasia of melanocytes which is linear in its spread. This means the hyperplasi ...
maligna is not the same as
lentigo maligna melanoma Lentigo maligna melanoma is a melanoma that has evolved from a lentigo maligna, as seen as a lentigo maligna with melanoma cells invading below the boundaries of the epidermis. Last Update: May 18, 2019. They are usually found on chronically sun d ...
, as detailed below. It typically progresses very slowly and can remain in a non-invasive form for years. It is normally found in the elderly (peak incidence in the 9th decade), on skin areas with high levels of sun exposure like the face and forearms. Incidence of evolution to lentigo maligna melanoma is low, about 2.2% to 5% in elderly patients. It is also known as "Hutchinson's melanotic freckle". This is named for
Jonathan Hutchinson Sir Jonathan Hutchinson (23 July 1828 – 23 June 1913), was an English surgeon, ophthalmologist, dermatologist, venereologist, and pathologist. Life He was born in Selby, Yorkshire, of Quaker parents and educated in the local school. Then he ...
. The word lentiginous comes from the
latin Latin (, or , ) is a classical language belonging to the Italic branch of the Indo-European languages. Latin was originally a dialect spoken in the lower Tiber area (then known as Latium) around present-day Rome, but through the power of the ...
for
freckle Freckles are clusters of concentrated melaninized cells which are most easily visible on people with a fair complexion. Freckles do not have an increased number of the melanin-producing cells, or melanocytes, but instead have melanocytes that ...
.


Relation to melanoma

Lentigo maligna is a histopathological variant of
melanoma Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye ( ...
''
in situ ''In situ'' (; often not italicized in English) is a Latin phrase that translates literally to "on site" or "in position." It can mean "locally", "on site", "on the premises", or "in place" to describe where an event takes place and is used in ...
''. Lentigo maligna is sometimes classified as a very early melanoma, and sometimes as a precursor to melanoma. When malignant melanocytes from a lentigo maligna have
invaded An invasion is a military offensive in which large numbers of combatants of one geopolitical entity aggressively enter territory owned by another such entity, generally with the objective of either: conquering; liberating or re-establishing con ...
below the
epidermis The epidermis is the outermost of the three layers that comprise the skin, the inner layers being the dermis and hypodermis. The epidermis layer provides a barrier to infection from environmental pathogens and regulates the amount of water rele ...
, the condition is termed
lentigo maligna melanoma Lentigo maligna melanoma is a melanoma that has evolved from a lentigo maligna, as seen as a lentigo maligna with melanoma cells invading below the boundaries of the epidermis. Last Update: May 18, 2019. They are usually found on chronically sun d ...
. Last Update: May 18, 2019.


Signs and symptoms

Characteristics include a blue/black stain of skin initially. Skin is thin, about 4-5 cell layers thick, which is often related to aging. Histological features include
epidermal The epidermis is the outermost of the three layers that comprise the skin, the inner layers being the dermis and hypodermis. The epidermis layer provides a barrier to infection from environmental pathogens and regulates the amount of water relea ...
atrophy and increased number of
melanocyte Melanocytes are melanin-producing neural crest-derived cells located in the bottom layer (the stratum basale) of the skin's epidermis, the middle layer of the eye (the uvea), the inner ear, vaginal epithelium, meninges, bones, and heart. ...
s.


Diagnosis

First dilemma in diagnosis is recognition. As lentigo malignas often present on severely sun-damaged skin, it is frequently found amongst numerous pigmented lesions – thin seborrheic keratoses, lentigo senilis, lentigines. It is difficult to distinguish these lesions with the naked eye alone, and even with some difficulty using
dermatoscopy Dermatoscopy also known as dermoscopy or epiluminescence microscopy, is the examination of skin lesions with a dermatoscope. It is a tool similar to a camera to allow for inspection of skin lesions unobstructed by skin surface reflections. The de ...
. As the lentigo maligna is often very large, it often merges with, or encompasses other skin tumors – such as lentigines, melanocytic nevi, and seborrheic keratosis. Second dilemma is the biopsy technique. Even though excisional biopsy (removing the entire lesion) is ideal, and advocated by pathologists; practical reason dictates that this should not be done. These tumors are often large and presenting on the facial area. Excision of such large tumor would be absolutely contraindicated if the lesion's identity is uncertain. The preferred method of diagnosis is by using a punch biopsy, allowing the physician to sample multiple full thickness pieces of the tumor at multiple sites. While one section of the tumor might show benign melanocytic nevus, another section might show features concerning for severe cellular atypia. When cellular atypia is noted, a pathologist might indicate that the entire lesion should be removed. It is at this point that one can comfortably remove the entire lesion, and thus confirm the final diagnosis of lentigo maligna. The size of the punch biopsy can vary from 1 mm to 2 mm, but it is preferable to use a punch 1.5 mm or larger. Representative samples of the most atypical parts of the nevus should be biopsied, often guided by
dermatoscopy Dermatoscopy also known as dermoscopy or epiluminescence microscopy, is the examination of skin lesions with a dermatoscope. It is a tool similar to a camera to allow for inspection of skin lesions unobstructed by skin surface reflections. The de ...
. Image:Lentigo maligna - very high mag.jpg,
Light microscopy Microscopy is the technical field of using microscopes to view objects and areas of objects that cannot be seen with the naked eye (objects that are not within the resolution range of the normal eye). There are three well-known branches of micr ...
of lentigo maligna showing the characteristic atypical epidermal melanocytes.
H&E stain Hematoxylin and eosin stain ( or haematoxylin and eosin stain or hematoxylin-eosin stain; often abbreviated as H&E stain or HE stain) is one of the principal tissue stains used in histology. It is the most widely used stain in medical diagnos ...
. File:SOX10 immunohistochemistry of lentigo maligna.jpg,
Immunohistochemistry Immunohistochemistry (IHC) is the most common application of immunostaining. It involves the process of selectively identifying antigens (proteins) in cells of a tissue section by exploiting the principle of antibodies binding specifically to an ...
with
SOX10 Transcription factor SOX-10 is a protein that in humans is encoded by the ''SOX10'' gene. Function This gene encodes a member of the SOX gene family, SOX (Testis-determining factor, SRY-related HMG-box) family of transcription factors involved ...
(staining the cell nuclei of
melanocytes Melanocytes are melanin-producing neural crest-derived cells located in the bottom layer (the stratum basale) of the skin's epidermis, the middle layer of the eye (the uvea), the inner ear, vaginal epithelium, meninges, bones, and heart. ...
) facilitates diagnosis of lentigo maligna, in this case showing an increased number of melanocytes along
stratum basale The ''stratum basale'' (basal layer, sometimes referred to as ''stratum germinativum'') is the deepest layer of the five layers of the epidermis, the external covering of skin in mammals. The ''stratum basale'' is a single layer of columnar or ...
of the skin, and nuclear pleumorphism. The changes are continuous with the
resection margin A resection margin or surgical margin is the margin of apparently non-tumorous tissue around a tumor that has been surgically removed, called " resected", in surgical oncology. The resection is an attempt to remove a cancer tumor so that no portio ...
(inked in yellow, at left), conferring a diagnosis of a not radically removed lentigo maligna. File:Lentigo Maligna Melanoma Left Central Malar Cheek.jpg, Lentigo Maligna Melanoma, Left Central Malar Cheek marked for biopsy


Treatment

The best treatment of lentigo maligna is not clear as it has not been well studied. Standard excision is still being done by most surgeons. Unfortunately, the recurrence rate is high (up to 50%). This is due to the ill-defined visible surgical margin, and the facial location of the lesions (often forcing the surgeon to use a narrow surgical margin). The use of
dermatoscopy Dermatoscopy also known as dermoscopy or epiluminescence microscopy, is the examination of skin lesions with a dermatoscope. It is a tool similar to a camera to allow for inspection of skin lesions unobstructed by skin surface reflections. The de ...
can significantly improve the surgeon's ability to identify the surgical margin. The narrow surgical margin used (smaller than the standard of care of 5 mm), combined with the limitation of the standard bread loafing technique of fixed tissue histology - result in a high "false negative" error rate, and frequent recurrences. Margin controlled (peripheral margins) is necessary to eliminate the false negative errors. If breadloafing is utilized, distances from sections should approach 0.1 mm to assure that the method approaches complete margin control. Where the lesion is on the face and either large or 5mm margins are possible, a skin flap or
skin graft Skin grafting, a type of graft (surgery), graft surgery, involves the organ transplant, transplantation of skin. The transplanted biological tissue, tissue is called a skin graft. Surgeons may use skin grafting to treat: * extensive wounding o ...
may be indicated/required. Grafts have their own risks of failure and poor cosmetic outcomes. Flaps can require extensive incision resulting in long scars and may be better done by plastic surgeons (and possibly better again by those with extensive LM or "suspicious of early malignant melanoma" experience.
Mohs surgery Mohs surgery, developed in 1938 by a general surgeon, Frederic E. Mohs, is microscopically controlled surgery used to treat both common and rare types of skin cancer. During the surgery, after each removal of tissue and while the patient waits, t ...
has been done with cure rate reported to be 77%. The "double scalpel" peripheral margin controlled excision method approximates the Mohs method in margin control, but requires a pathologist intimately familiar with the complexity of managing the vertical margin on the thin peripheral sections and staining methods. Some melanocytic nevi, and melanoma-in-situ (lentigo maligna) have resolved with an experimental treatment,
imiquimod Imiquimod, sold under the brand name Aldara among others, is a medication that acts as an immune response modifier that is used to treat genital warts, superficial basal cell carcinoma, and actinic keratosis. Scientists at 3M's pharmaceuticals ...
(Aldara) topical cream, an immune enhancing agent. In view of the very poor cure rate with standard excision, some surgeons combine the two methods: surgical excision of the lesion, then three months treatment of the area with
imiquimod Imiquimod, sold under the brand name Aldara among others, is a medication that acts as an immune response modifier that is used to treat genital warts, superficial basal cell carcinoma, and actinic keratosis. Scientists at 3M's pharmaceuticals ...
cream. Studies seem to conflict about the level of certainty associated with using imiquimod. Another treatment to be considered where standard margins cannot be achieved or cosmetics are a major consideration is ultra-soft x-ray/grenz-ray radiation. In the very elderly or those with otherwise limited life expectancy, the impact of major day surgery for excision with 5mm margins and large skin flap could be worse than doing nothing or the possibility of failed treatments with imiquimod or Grenz ray.


References


External links

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External links

{{Skin tumors, nevi and melanomas Melanoma