LMM arises from LM, a slowly growing and variably pigmented macule that almost exclusively develops on chronically sun-damaged skin of the head and neck region [1]. LM may be present for years before transforming into LMM; it is an indolent, rather small lesion that may not overly concern the patient [2]. There are no macroscopic features that would unequivocally confirm the transition from LM to LMM, although the loss of symmetry and regular borders, changes in pigmentation, the progressive elevation above surrounding skin, and an acceleration in growth may provide valuable hints to this end. Vertical growth giving rise to nodularity is a sign of dermal invasion. It is not to be expected in mere LM, but should neither be considered an exclusion criterion for LMM: The latter may remain in the radial growth phase for years. What's more, LMM may simultaneously grow and regress in a pattern that makes the lesion appear to move across the skin [3]. The spectrum of colors ranges from light to darker brown to black, though pink and amelanotic LMM have also been described [4].

• Pathologist

  The nomeclature is very confusing to both patients, dermatologists, and pathologists alike. Lentigo maligna is the non-invasive skin growth that some pathologists consider to be a melanoma-in-situ. [checkorphan.org]

  Zitelli Medicine Archives of dermatology 1991 Although some Mohs surgeons and pathologists are uncomfortable reading frozen sections for melanoma, it should be emphasized that examination of the margins by frozen section has been documented to be effective [semanticscholar.org]

  Lentigo maligna is the non-invasive skin growth that some pathologists consider to be a melanoma-in-situ.[3] A few pathologists do not consider lentigo maligna to be a melanoma at all, but a precursor to melanomas. [en.wikipedia.org]

  It is not uncommon for pathologists to receive partial or scouting biopsies to assess for LM. This makes the interpretation of symmetry and circumscription of the lesions challenging. [jcp.bmj.com]

  But in slow Mohs, rush permanent sections are sent off to the pathologist rather than the frozen sections integral to conventional Mohs. Dr. [mdedge.com]

• Inflammation

  Difference in overall inflammation score between the 2 groups was significant (mean difference (MD) 0.6, 95% CI 0.2 to 1, P value = 0.004), with the mean overall inflammation score being significantly higher in the combination group. [cochrane.org]

  591 per 1000 815 per 1000 (615 to 1000) RR 1.38 (1.04 to 1.84) 88 (1 study) ⊕⊕⊝⊝ low ¹ ‐ Secondary outcome: Inflammatory response (overall Inflammation score) for all participants Mean grade of inflammation in each group² ‐ The mean overall inflammation [cochranelibrary.com]

  We therefore advocate close examination of lentigo maligna with the use of appropriate immunohistochemical techniques if there are areas of dermal fibrosis or inflammation that might obscure invasion. [jaad.org]

  Patchy inflammation and fibrosis may be noted in the upper dermis associated with invasion into superficial dermis. [histopathology-india.net]

• Weakness

  Weak recommendations use "consider" or "suggested" phrasing. Recommendations are explicitly labeled as Strong recommendations or Weak recommendations when a qualified group has explicitly deliberated on making such a recommendation. [dynamed.com]

  Weakness increases as the disease gets worse. [medlineplus.gov]

  Read et al also reported that the evidence available for the effective use of laser therapy was weak. [wiki.cancer.org.au]

  Brain metastases may result in headaches, seizures, vision changes, or weakness on one side of the body. [verywell.com]

  Common signs and symptoms include: weight loss weakness fever that lasts for weeks or months enlarged spleen enlarged liver decreased production of blood cells bleeding other infections swollen lymph nodes It’s important to tell your doctor if you lived [healthline.com]

• Surgical Procedure

  The use of non-surgical interventions, such as imiquimod, as monotherapy may be effective and may be considered in selected cases where surgical procedures are contraindicated and used preferentially by experienced providers under close and adequate follow [cochrane.org]

  If the local lymph nodes are enlarged due to melanoma, they should also be completely removed, which entails a major surgical procedure under general anaesthetic. [dermnetnz.org]

  & procedural Modifiers Audits Quick coding guides Derm Coding Consult Coding webinars Coding products MIPS reporting guide MIPS quality measures Medicare fee schedule Prior authorization letter tool Prior authorization resources Drug pricing tool Compounding [aad.org]

• Swelling

  However, removal of these nodes may therefore lead to a build-up of lymph causing swelling (lymphedema) Chemotherapy: Drugs are used to kill the tumor cells, which may be given as oral pills, or injected into veins Side effects of chemotherapy may include [dovemed.com]

  When damage occurs to lymph nodes and vessels, the subsequent build-up of fluid can cause swelling and tightness of the skin. [verywell.com]

  People who develop clinical evidence of infection usually have fever, weight loss, enlargement (swelling) of the spleen and liver, and abnormal blood tests. [cdc.gov]

  Contact your doctor should you notice the following side effects: Ulcers forming Pustules Skin weeping Swelling of the eyelids If you think the application site has become infected. [myskincancercentre.com.au]

• Keratosis

  Pigmented basal cell carcinoma Pigmented actinic keratosis Pigmented Bowen disease Best Tests Subscription Required Management Pearls Subscription Required Therapy Subscription Required References Subscription Required Last Updated: 08/17/2016 [visualdx.com]

  Often actinic keratosis and lentigo maligna co-exist. Atypical keratinocytes in actinic keratosis may cause further problem in making histological diagnosis. It may be difficult to identify the microinvasive foci even after multiple levels. [histopathology-india.net]

  A benign lesion, evenly coloured Download Figure: 7 Dermoscopic appearance of figure 6 Grey granules uniformly distributed throughout the lesion Download Figure: 8 Lichenoid keratosis Download Figure: 9 Dermoscopic appearance of figure 8 Download Figure [pcds.org.uk]

• Skin Lesion

  METHODS: Four women and eight men aged 58-88 years presenting with facial skin lesions suspicious of LM/LMM were included. In total, 17 lesion areas were imaged by RCM before biopsy. [ncbi.nlm.nih.gov]

  […] small pigmented skin lesions that were diagnostically equivocal when examined with the naked eye. [typeset.io]

  Skin lesion, forehead Show diagnosis & comments Diagnosis: Lentigo maligna melanoma Comments: Any invasive melanoma associated with lentigo maligna is classified as lentigo maligna melanoma. [melanocytepathology.com]

• Hyperpigmentation

  […] melanoma Note: lentigo maligna (a subtype of melanoma in situ), by definition, does NOT infiltrate into dermis but lentigo maligna melanoma has at least single cell infiltration into papillary dermis Clinical features Flat, tan to black with irregular hyperpigmentation [pathologyoutlines.com]

  The cosmetic results of radiotherapy were good or excellent in the vast majority of patients, with only a few experiencing hypopigmentation or hyperpigmentation in the irradiated area. [ncbi.nlm.nih.gov]

  Malignant melanoma Benign freckle (ephelis)- very small, flat, uniformly brown spots with sharp borders that represent hyperpigmentation of the basal layer of the epidermis. [aao.org]

  Follicular openings were surrounded by a rim of hyperpigmentation. One asymmetric follicular opening and 1 rhomboidal structure were seen dermoscopically. The clinical diagnosis of LM seemed reasonable, and excision was recommended. [jamanetwork.com]

  Four patients with hyperpigmentation showed only basal epidermal hyperpigmentation with immunohistochemistry staining negative for melan-A (Fig. 3). Fig. 3. A 77-year-old woman with hyperpigmentation. (A) Ten-year follow-up with hyperpigmen-tation. [medicaljournals.se]

• Skin Disease

  As dermatopathologist Klaus Busam examines skin tissue under the microscope to provide clinical colleagues with information about the nature of their patients' skin disease. [amazon.in]

• Sweating

  […] keratoses (benign) Yellow opaque areas Fingerprint-like structures A well-demarcated, continuous, 'moth-eaten' border A symmetrical brown pseudonetwork with a broad 'rounded' mesh and holes created by the numerous pigment free hair follicles and openings of sweat [pcds.org.uk]

  Other symptoms of systemic visceral leishmaniasis may include: Abdominal discomfort Fever that lasts for weeks; may come and go in cycles Night sweats Scaly, gray, dark, ashen skin Thinning hair Weight loss Your health care provider will examine you and [medlineplus.gov]

  These holes correspond to hair follicle and sweat gland openings on the skin surface. This pseudonetwork is observed in melanocytic and nonmelanocytic pigmented lesions on the face. [actasdermo.org]

  Reapply every two hours or immediately after swimming or heavy sweating. Do not burn, tan or use tanning booths Keep newborns out of the sun. Use sun protection on babies age 6 months and older. [centexderm.com]

  […] minimum sun protection factor (SPF) of 30, preferably a physical blocker such as zinc oxide or titanium dioxide liberally applying sunscreen about half an hour before going outside in the sun reapplying sunscreen every 2 hours and after swimming or sweating [medicalnewstoday.com]

• Suggestibility

  Want to suggest a symptom? Please send suggestions to RareGuru! [rareguru.com]

  The significantly younger age group of patients with LMM at extrafacial compared with head and neck sites therefore suggests that the relationship between LMM and sunlight is not simply related to cumulative solar exposure. [ncbi.nlm.nih.gov]

  It is suggested that melanomas are tumors of the epidermal melanocytes and are not necessarily derived from melanocytic nevi. [typeset.io]

• Aggressive Behavior

  Discussion: - This is an uncommon case with extensively invasive follicular carcinoma, with very aggressive behavior, diffusely affecting the lungs, and presenting metastases to the dermis and subcutaneous, these latter two sites being infrequent for [endocrine-abstracts.org]

  In addition, LM has a potential to progress to an invasive tumor with potentially aggressive behavior: lentigo maligna melanoma (LMM).1,2 The lifetime risk of progression from LM to LMM ranges from 5% to 50% and increases with time.3 Overall, LM has a [dovepress.com]

• Seizure

  Brain metastases may result in headaches, seizures, vision changes, or weakness on one side of the body. [verywell.com]

The distinction of LMM, LM, and other lesions on sun-damaged skin may pose a major challenge. The presurgical diagnosis is based on a thorough clinical, dermoscopic, and confocal evaluation and the histopathological analysis of biopsy samples [1] [5] [6]. With regard to the latter, incisional biopsies involving more or less extensive parts of the lesions and a margin of clinically normal-appearing skin are most commonly performed. Complete excisional biopsies may provide even more reliable information as to the presence and distribution of atypical melanocytes, but they are more difficult to obtain. In the presence of high-risk features, additional biopsies of sentinel lymph nodes may be realized to detect subclinical metastases [2].

With regards to skin biopsies, the following may be expected [2] [7]:

• LMM consist of large atypical melanocytes initially proliferating along the lower layers of the epidermis and up to the hair follicles, but eventually invading the dermis. Melanocytic markers such as S100, MITF, Melan A, and HMB45 may be used to confirm the origin of degenerated cells.
• The abnormally high density of melanocytes, which tend to group in nests, may help to demarcate the tumor and to distinguish LM and LMM from non-malignant actinic lesions. This is particularly important because most LMM are embedded in chronically sun-damaged skin, which shares many features with the neoplasm. Increased pigmentation of basal keratinocytes, atrophy of the epidermis, and solar elastosis are frequent background features related to chronic sun exposure and skin damage.
• Both melanocytes and keratinocytes may contain giant granules filled with melanin, which are called macromelanosomes.
• Desmoplasia may be noted in adjacent regions.

Radical surgical removal is the first choice of treatment but may be impeded by the location of the tumor. Staged excision is thus preferred in many cases, i.e., the tumor is removed in two or more sessions [7]. After each surgery, the excision specimen is histopathologically examined. If surgical margins are not free of tumor cells, another intervention is scheduled for the following day. This procedure is associated with optimum preservation of healthy tissues and high rates of cure. Alternatively, Mohs micrographic surgery may be performed. The idea is similar, but instead of taking longer breaks between multiple interventions, the patient awaits for the results of tissue processing and evaluation, and the excision of LMM is concluded in a single procedure. A potential pitfall of this approach is the difficulty of identifying LMM using en face frozen sections [2]. Most studies show low rates of recurrence after Mohs micrographic surgery, in the range of 0.5 to 6.3% [7]. Once margins are histologically clear, both staged excision and Mohs micrographic surgery must be followed by skin reconstruction. Methods include healing by secondary intention, primary repair, skin grafts, local flaps, and distant flap.

Due to the advanced age of many LMM patients, non-surgical management is frequently considered. In this context, topical imiquimod may be combined with cryosurgery, laser ablation, or radiotherapy. Topical imiquimod has been shown to induce clinical and histological clearance in up to 74% of patients with LM [8], but the prognosis is likely to be less favorable in case of LMM - even if combined with additional therapeutic procedures. Recurrence rates in the range of 20 to 100% have been reported for non-surgical LMM therapy, and thus, it should be carefully revised whether or not a patient is truly "unfit for surgery" [7].

In any case, monitoring for disease clearance and recurrence is paramount and can be achieved using dermoscopy and confocal microscopy [2]. The mean time to local recurrence has been reported to be almost five years for LM and thin LMM, but more than a decade may pass until the relapse [9]. Hence, lifelong surveillance is recommended. Follow-ups should take place every 3 to 6 months for the first two years after therapy and annually thereafter [3].

LMM is a slowly-growing type of skin cancer, and most patients are diagnosed with in situ melanoma or stage 0 disease, which has an extremely positive effect on the outcome. Post-surgical recurrence rates are low, and cosmetic issues can generally be resolved. Even in case of recurrence, the incidence of invasive disease is low among patients who previously underwent surgery, and their prognosis remains favorable [9].

Notwithstanding, LMM may grow invasively and has metastatic potential [10] [11]. Advanced-stage LMM is associated with the same detrimental prognosis as other malignant melanoma, with maximum Breslow thickness being one of the most important prognostic factors [1].

The development of LM involves the proliferation of atypical melanocytes along the basal layer of the epidermis. Its transformation into LMM is characterized by the progression of degenerated cells beyond the epidermis, i.e., by the invasion of adjacent tissues [1]. The lifetime risk of LM patients to develop LMM decreases with age and ranges between 2-5% [8].

The molecular mechanisms behind LM and LMM development could not yet be clarified. Mutations, as induced by ultraviolet radiation, of stem cells in the hair follicle have recently been suggested as a possible starting point of tumorigenesis [12]. Other hypotheses refer to primitive melanoblasts as the cells of origin.

LMM accounts for 4–15% of cutaneous melanomas [7]. At the time of diagnosis, the vast majority of patients is older than 65 years, and the individual risk of developing LMM augments with age [2]. Rising life expectancy and the more frequent relocation of retirees to warmer locations with higher cumulative ultraviolet light exposure have been named as possible causes of the global increase of LMM incidence rates [7]. In detail, the annual incidence of LMM has recently been estimated at 1.2 and 4.7 per 100,000 inhabitants of the Netherlands and Australia, respectively [13] [14]. LMM incidence rates have been observed to increase by as much as 12.4% per year among the Dutch population [13]. Gender preference varies between distinct countries; in Australia, males are affected up to three times as often as females, while no differences between sexes were observed in Holland [13] [14].

Little is known about the pathogenesis of LMM. The study of differences in gene-expression patterns of LM and LMM revealed a downregulation of p53, p16, and Bax, which are all involved in the cellular stress response. At the same time, an upregulation of Bcl-2 may be observed. These changes imply a progressive loss of the cell's ability to respond to stress and reduced sensitivity towards apoptosis. Loss of function of PTEN may further disturb the regulation of cell proliferation and survival, but the triggers of these changes remain unclear. In sum, tumor cells may accumulate more than 100,000 somatic mutations, and primary oncogenic mutations tend to affect proto-oncogenes NRAS and KIT instead of BRAF [15].

Sun exposure, light skin with freckles, and propensity towards the development of lentigines have been identified as risk factors for LM and LMM [2]. Beyond that, LMM patients are more likely to have a history of non-melanoma skin cancers than comparable patient populations [7]. Among these factors, sun exposure is the easiest target of preventive actions. The general population should be educated accordingly, should be encouraged to use sunscreen, wear sunglasses and hats as well as long-sleeved clothes, and to avoid sunlight exposure during the peak hours of ultraviolet radiation. Such measures should be taken throughout life.

LMM is the most common presentation of cutaneous melanomas with cumulative sun-induced damage [15]. Here, a pigmented macule comprising a subtle proliferation of single intraepidermal melanocytes transforms into invasive melanoma with accelerated radial and vertical growth. It may take years or even decades until this transformation occurs. The primary lesion is LM, and both environmental and genetic factors may trigger profound changes in the tumor's growth characteristics. Further research is required to identify these factors and to understand their interactions, with current knowledge not allowing for reliable conclusions as to the individual risk and time of transformation, or the likelihood of aggressive growth and the formation of metastasis. Accordingly, close monitoring is recommended for all LM and LMM patients, both before and after treatment. If at all possible, the tumor should be removed in its entirety, and the clearance of excision margins should be confirmed histologically.

Lentigo maligna melanoma (LMM) is a type of skin cancer. It arises from lentigo maligna, a non-invasive lesion almost exclusively developing on chronically sun-damaged skin. Lentigo maligna typically corresponds to an indolent, pigmented macule in the head and neck region and is related to a favorable prognosis. It may be present for decades before transforming into invasive LMM, a tumor with metastatic potential. This transformation may be associated with evident changes of the lesion, e.g., more pronounced pigmentation, the progressive elevation above surrounding skin or invasion of deeper layers, and an acceleration in growth - or it may go unnoticed. Indeed, the distinction of lentigo maligna and LMM poses a major challenge even to experienced dermatologists. It is thus of major importance to seek medical advice and a thorough evaluation of anomalies of the skin, especially if their appearance is changing.

The surgical removal of LMM is the mainstay of therapy. Because it may be difficult to establish the margins of LMM, it is usually resected in multiple operations. After each intervention, the excision specimen is microscopically examined for the presence of tumor cells in the peripheral regions. This procedure is repeated until all margins are found to be clear from tumor cells. The post-surgical management of LMM involves measures of skin reconstruction and regular evaluations for possible recurrence. It is important to note that recurrence may occur years after the initial diagnosis and surgery, so patients and physicians need to remain alert to any changes of the scar or adjacent skin.

The causes of LMM are incompletely understood. Notwithstanding, prolonged exposure to sunlight is known to be a major risk factor for this type of skin cancer and a variety of other diseases. The best way to prevent the development of lentigo maligna and LMM thus is the consistent use of sun protection and the avoidance of sunlight exposure during the peak hours of ultraviolet radiation.

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