Melanoma In Situ: Diagnosis And Management Strategies

  • Vishesh Asnani MSc. Biotechnology with Business Enterprise- University of Leeds, United Kingdom
  • Maha Ahmed MBBS, Intarnal Medicine and General Surgery, Cairo University, Egypt

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Introduction

Definition and overview

Have you ever wondered why it is always advised to pack sunscreen for a beach trip? The sun’s rays are rich in UV light- and this UV light has a very slim, but very real possibility of causing mutations in the cells that it penetrates that can turn them into tumour progenitor cells, or cells that can lead to tumours. If these tumours are malignant (that is, tend to spread and undergo metastasis) they can potentially lead to cancer via a series of events. 

The first line of defence of the human body against such radiations is the skin. The word “melanoma” is derived from “melanocytes” (cells on the skin that make the pigment melanin) and the suffix “oma” which denotes a tumorous growth. 1.7%.1 of the cancers diagnosed worldwide are a variety of melanoma. It might seem like a small number, but 1.7% when put against the millions of cancer diagnoses per year is a significant amount.

There are many stages a tumour progenitor cell has to go through before it can turn into a full-fledged melanoma. “Melanoma in-situ ” is one of the most important of these stages. It is a stage where cancerous cells are confined to the epidermis (the uppermost layer of the skin). In the medical world, “in-situ ” is generally shorthand for “locally restricted”. The melanoma at this point hasn’t spread to any other layer of the skin or any other body part, that is, it has not undergone metastasis. It is considered non-invasive cancer and is not a cause of death.2

Lentigo Maligna Melanoma in-situ accounts for 5% of all Melanomas according to the National Cancer Institute (USA)3, it is also called Hutcherson’s Melanotic Freckle. It can be frequently seen on the head and neck regions of fair-skinned elderly people. It was initially thought to be a benign (non-spreading) growth but instead was discovered to be invasive but incredibly slow. It might take as long as 28.3 years for a case of lentigo maligna to give rise to an invasive melanoma (in which case it is known as a lentigo maligna melanoma, or LMM for short).4

In appearance, it is common for Lentigo maligna in situ to be mistaken for a common lesion or a minor discolouration of the skin. There is just simple brown discolouration with no bulging out of the skin in most cases. The lesions may be brown, black, or both and it is typical of them to gradually develop over a larger area of the skin in patches.5

Importance of early diagnosis

Melanoma in-situ is also known as stage 0 melanoma. As the name suggests, it is a stage where the melanoma is non-invasive (that is, does not spread to other parts of the body via the lymph nodes or the bloodstream). The cancer cells are restricted to the epidermis. Even though less than 5% of melanoma in-situ and Lentigo maligna become invasive, it is a very significant number.

Melanoma in-situ is entirely curable and usually does not lead to recurrence. This cannot be said for fully-fledged melanomas. Minimally invasive treatment at this stage can eradicate the condition and prevent the development of higher stages of the disease and potentially prevent disfigurement.

Diagnosis

Clinical examination and history

The genetic history of the patient is reviewed. This involves simple questions like “Has any of your immediate family been diagnosed with melanoma or any other form of cancer throughout their lives?”. This is a part of holistic risk analysis where other factors like complexion and exposure to the sun are evaluated to calculate the overall risk of melanoma for the patient. 

This is accompanied by a physical examination of the lesion at risk of melanoma. This is usually a black or brown discoloured lesion that slowly expands to cover a larger area of the skin as time passes. Physical examinations alone are not enough to diagnose melanoma in-situ or Lentigo maligna.

Dermoscopy and biopsy

The presence of melanoma can be suspected based on dermoscopy reports. Dermoscopy, also known as skin-surface microscopy is a non-invasive procedure that is initially used to evaluate a lesion that is suspected of being a melanoma in-situ or Lentigo maligna.6 Specialised stains may also be used to evaluate cells. In certain cases like sun-damaged cells, or simply by pure chance, a dermoscopy alone cannot be used to diagnose melanomas, and histopathological evaluations are required to arrive at a final diagnosis.

Histopathological evaluation

This involves an examination of the suspected skin cells. The cells are analysed for biomarkers and other immunological signals typical of melanoma cells. Factors analysed collaborate with the hallmarks of cancer- the replication rate of the cells, the presence, and absence of certain growth factors, and certain antigens. A histopathological evaluation provides the complete picture of a mass of tissue and is finally used to arrive at a diagnosis.7

Management

Surgical options

Wide local excision

As the name suggests, a wide local excision removes the lesion of interest, as well as some of the surrounding tissue to make sure that any cells at risk of becoming a melanoma in-situ later are removed. Unlike Mohs micrographic surgery, it is comparatively imprecise and does not treat preservation of surrounding tissue is not a priority- a margin of .5 to 1 cm.8 of clear skin around the lesion is also removed. This is the most widely used treatment for melanoma in-situ with a high success rate, effectively curing melanoma in most patients.

Mohs micrographic surgery

Named after Frederick Mohs, the developer of this surgery, it is the leading option at the moment for the treatment of melanoma in-situ, Lentigo maligna, and Lentigo maligna melanomas. It involves the precise surgical removal of cancerous skin cells and aims to leave the rest of the tissue intact to the best of the surgeon’s ability. Thin margins of the cancerous tissue are removed from the melanoma site and examined sequentially for the presence of cancer cells. Once most of the cells are removed from the margin tissue, the procedure is stopped.9

Non-surgical approaches

A non-surgical approach towards the treatment of the various subtypes of melanoma in situ may be considered, especially in the case of lentigo maligna where the melanoma is present in the head or neck region. These methods may be used to reduce the chance of disfigurement of the patient or medical comorbidities as the patients are often elderly.10

Topical therapies

consist of medications that can be absorbed through the skin, usually in the form of creams and ointments. Topical treatments for Melanoma in-situ cases have been researched, and the leading candidate at the moment is imiquimod11, an immunomodulator. It has been successfully used in patients suffering from Lentigo maligna. However, the cure rates are comparatively lower than surgical alternatives, and frequent follow-up is required.

Photodynamic therapy

can be understood by the name, “photo” which involves anything to do with light. In this case, photodynamic therapy, also known as PDT, involves sensitisation of the skin to light using a collection of drugs and using high-energy light to destroy the melanoma cells. It is a promising treatment in the earlier stages, that is melanoma in situ. Unfortunately, most melanomas show resistance to PDT to the point that it is considered an ineffective12 approach.

Cryotherapy

The prefix “cryo” usually indicates the presence of extremely low temperatures. In this case, cryotherapy’s main aim is to kill melanoma cells via freezing temperatures. 

In this method, the lesions are frozen with liquid nitrogen, most frequently using the open spray method. Cryotherapy is often coupled with surgical methods, collectively known as “Cryosurgery” which has been successfully used for melanoma in-situ treatment on the face and neck13 for elderly patients with various comorbidities. This method prevents disfigurement in patients with Lentigo maligna on the face or neck with promising clinical trials.

Follow-up and surveillance

This differs from patient to patient and depends on various factors like the modality of treatment (surgical vs. non-surgical, level of invasiveness of the treatment, clinical outcomes, cutaneous melanoma vs. non-cutaneous melanoma), any comorbidities in 

the patient, the age of the patient and the genetic history concerning melanomas and other cancer types. It is recommended for one to undergo skin examinations every 3 months post-treatment for the first two years.14 After that, such check-ups may be carried out once a year, depending on the level of risk. No scans (CT scans, MRI, PET, etc.) are recommended for melanoma in-situ follow-ups.

It is recommended to avoid exposure to the sun as much as possible and practice protective measures such as application of sunscreen if going out. The skin needs to be closely monitored for the presence of any abnormal lesions or hyperpigmentation. The doctor may also instruct you on how to perform a self-examination of the skin post-follow-up.

Prognosis and education

Risk factors

  • Age

The elderly in general are more susceptible to melanomas due to cumulative exposure to the sun throughout life. As a person passes 50 years of age, it is advised to carry out routine skin examinations to rule out the possibility of an invasive melanoma in-situ.

  • Unprotected sun exposure

It is advised to always wear a sunscreen of SPF30 or above when anticipating high exposure to the sun, or in the case of tropical areas, applied in the summers when going out. This is to reduce the chance of incidence by preventing the exposure of the skin to UV radiation.

  • Tanning

People engaging in tanning, both indoors and outdoors, highly increase their risk of melanomas and other skin cancers as tanning involves exposure of skin to UV light. People who particularly use tanning beds and sun lamps have an increased risk as they tend to expose the skin to concentrated UV light.

  • Genetics

Around 10% of cutaneous melanoma patients can be traced to have a history of the disease through biological relatives. Any immediate family member having a history of melanoma increases one’s risk two to three-fold.15

Recurrence rates and monitoring

Melanoma in situ (stage 0) is the most curable stage of melanoma.16 At this point, melanoma is not invasive. Hence, if the condition is cured at a time using the options described above, there is almost no risk of recurrence. However, frequent follow-ups and self-examinations are still advised. In very few cases, the cancer cells may spread to the lymph nodes and lead to further complications.

Sun protection and self-examination

As described in the previous sections, exposure to the sun and similar UV sources like tanning beds is one of the largest risk factors for the development of melanoma and other skin cancers. Hence, patients with a history of melanoma should make sure to avoid exposure to the sun as much as possible to reduce the likelihood of recurrence. This can be done by applying sunscreen of a suitable SPF (Sun Protection Factor), wearing long-sleeved clothing, and avoiding deliberate tanning. Exposure to solar radiation can also be reduced by avoiding going out during times when sunlight is intense, like early afternoon. 

Patients who are currently suffering from, or have recovered from melanoma in-situ, lentigo maligna or any other associated conditions should learn how to do a self-examination. This can be taught by a medical professional. In general, they should keep a lookout for abnormal lesions, brown or black patches on the skin, and sudden discolourations, especially if they follow exposure to the sun.

Additional considerations

Genetic testing and counselling

Genetic Testing tests for mutations in particular genes that are linked to increased susceptibility to various types of cancer. This can prompt someone to take precautions to reduce the environmental factors resulting in these cancers. A genetic test is not a guarantee that a person will develop the associated type of cancer. It should only be used as a form of risk assessment and precaution rather than a scare or confirmation of disease. Not having genetic predispositions does not eliminate the risk of getting melanoma as well.

Mutations on the following genes are most frequently associated with melanomas:

  • Gene BAP1- Mutations on this gene are not just linked to cutaneous melanomas but other conditions like kidney cancer
  • Gene CDKN2A- Mutations here are linked to pancreatic cancer, cancer of the CNS (Central Nervous System) and melanomas as discussed17

Genetic tests should always be accompanied by a consultation with a qualified medical professional to study the implications of the result.

Sentinel lymph node biopsy

This is a diagnostic test carried out to isolate the first lymph nodes a cancerous tumour (in this case, melanoma) may spread to. It is at this point a melanoma in-situ undergoes metastasis (spreading to different parts of the body). After finding said lymph node, it is analysed to check for the presence of cancerous cells. This is usually not needed for stage 0 melanoma18, which an in-situ melanoma is.

However, it may be carried out as a preventative measure or if there is a risk of melanoma becoming invasive.

Collaborative care

Collaborative care, on the end of a medical professional, is of utmost importance in dealing with any type of cancer. Diagnosis of any type of cancer carries a huge emotional weight on the patient and their family, and a medical professional at all times must be conscious of the same. 

In the case of cutaneous melanoma, this is especially important as treatment is highly personalised. New modalities of treatment are continuously evolving for melanoma and the staff associated should be knowledgeable about the therapeutic options available to the patient. They should be able to explain the approach to the patient’s family in layman's terms with empathy and focus on the quality of life for the patient.

Difficult conversations like preventing disfiguration in the case of Lentigo maligna need to be carried out by specially trained nurses and staff with tenderness. The way medical personnel interacts with the patient and their family greatly influences the outcomes and their confidence in recovery.19

Summary

Melanoma in-situ, also called stage 0 melanoma, is one of the most frequent but curable forms of cancer alike. At this stage, the cancer cells have not reached the lymph nodes and remain restricted to the epidermis. It also happens to be the most preventable use of sunscreen of an appropriate SPF and practising proper sun protection and control alone eliminates a majority of the risk associated with melanoma in-situ.

The most common form of the disease is Lentigo maligna, which is the presence of discoloured lesions on the skin and neck. Melanoma in-situ is common among the elderly. The average age of diagnosis of the disease is 65, however, it is not uncommon among younger populations. It is diagnosed via histopathological analysis of the tissue and can be treated via surgical and non-surgical means.

The most common is the wide local excision, where some of the surrounding skin cells around the lesion are removed to eliminate the risk of recurrence. However, there are emerging methods undergoing clinical trials like Mohs Micrographic Surgery which offer a reduced risk of disfigurement for sensitive areas like the face, eyelids, and genital regions. Non-surgical methods, although less effective are being studied. Cryotherapy coupled with surgery is an emerging method of preference along with topical treatments. 

Post-treatment follow-ups are essential to prevent recurrence of the melanoma. A patient should educate themselves on self-examination from a qualified medical professional to look out for the warning signs of a returning melanoma or Lentigo maligna. It is nothing to be afraid of, as at the in-situ stage, melanoma is one of the most curable forms of cancer with minimal side effects, and novel treatments with further reduced risks are being developed as you read this!

References

  1. Saginala K, Barsouk A, Aluru JS, Rawla P, Barsouk A. Epidemiology of melanoma. Med Sci (Basel) [Internet]. 2021 Oct 20 [cited 2023 Jun 21];9(4):63. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8544364/
  2. Stage 0 Melanoma (In situ) [Internet]. AIM at Melanoma Foundation. [cited 2023 Jun 21]. Available from: https://www.aimatmelanoma.org/stages-of-melanoma/stage-0-in-situ-melanoma/
  3. Types of melanoma | seer training [Internet]. [cited 2023 Jun 21]. Available from: https://training.seer.cancer.gov/melanoma/intro/types.html
  4. Menzies SW, Liyanarachchi S, Coates E, Smith A, Cooke-Yarborough C, Lo S, et al. Estimated risk of progression of lentigo maligna to lentigo maligna melanoma. Melanoma Research [Internet]. 2020 Apr [cited 2023 Jun 21];30(2):193. Available from: https://journals.lww.com/melanomaresearch/Abstract/2020/04000/Estimated_risk_of_progression_of_lentigo_maligna.10.aspx
  5. Xiong M, Charifa A, Chen CSJ. Lentigo maligna melanoma. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2023 Jun 21]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK482163/
  6. Tzellos T, Kyrgidis A, Mocellin S, Chan AW, Pilati P, Apalla Z. Interventions for melanoma in situ, including lentigo maligna. Cochrane Skin Group, editor. Cochrane Database of Systematic Reviews [Internet]. 2014 Dec 19 [cited 2023 Jun 22]; Available from: https://doi.wiley.com/10.1002/14651858.CD010308.pub2
  7. Gheoca Mutu DE, Avino A, Balcangiu-Stroescu AE, Mehedințu M, Bălan DG, Brîndușe LA, et al. Histopathological evaluation of cutaneous malignant melanoma: A retrospective study. Exp Ther Med [Internet]. 2022 Jun [cited 2023 Jun 22];23(6):402. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9115627/
  8. Mohs surgery for melanoma in situ – where we stand [Internet]. Melanoma Research Alliance. [cited 2023 Jun 22]. Available from: https://www.curemelanoma.org/blog/article/mohs-surgery-for-melanoma-in-situ-where-we-stand
  9. Prickett KA, Ramsey ML. Mohs micrographic surgery. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2023 Jun 22]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK441833/
  10. Ellis LZ, Cohen JL, High W, Stewart L. Melanoma in situ treated successfully using imiquimod after non-clearance  with surgery: a review of the literature. Dermatologic Surgery [Internet]. 2012 Jun [cited 2023 Jun 22];38(6):937–46. Available from: https://journals.lww.com/00042728-201206000-00019
  11. Fan Q, Cohen S, John B, Riker AI. Melanoma in situ treated with topical imiquimod for management of persistently positive margins: a review of treatment methods. Ochsner J [Internet]. 2015 [cited 2023 Jun 22];15(4):443–7. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4679308/
  12. Huang YY, Vecchio D, Avci P, Yin R, Garcia-Diaz M, Hamblin MR. Melanoma resistance to photodynamic therapy: new insights. Biol Chem [Internet]. 2013 Feb 1 [cited 2023 Jun 22];394(2):239–50. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3545031/
  13. Huang YY, Vecchio D, Avci P, Yin R, Garcia-Diaz M, Hamblin MR. Melanoma resistance to photodynamic therapy: new insights. Biol Chem [Internet]. 2013 Feb 1 [cited 2023 Jun 22];394(2):239–50. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3545031/
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  17. Should I get genetic testing for melanoma? [Internet]. [cited 2023 Jun 22]. Available from: https://www.aad.org/public/diseases/skin-cancer/types/common/melanoma/genetic-testing
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  19. Kirkwood JM, Ribas A. Collaborative care in melanoma: the essential role of the nurse. Clin J Oncol Nurs. 2017 Aug 1;21(4 Suppl):4–6.

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Vishesh Asnani

MSc. Biotechnology with Business Enterprise- University of Leeds, United Kingdom

Vishesh is a professional in the Biotechnology industry and is well acquainted with research, leadership and management roles.

He is an experienced writer and editor for the healthcare sector with a particular interest in Molecular Biology, Genetics and Drug Development. His body of work is largely focused on making healthcare research accessible to the general population.

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Klarity is a citizen-centric health data management platform that enables citizens to securely access, control and share their own health data. Klarity Health Library aims to provide clear and evidence-based health and wellness related informative articles. 
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