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Case Report

Lentigo maligna mimicking invasive melanoma in Mohs surgery: a case report

[version 1; peer review: 2 approved]
PUBLISHED 24 Jan 2014
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Abstract

Lentigo maligna is a lentiginous proliferation of atypical melanocytes confined to the epidermis, typically on chronically sun-damaged skin. Following biopsy and exclusion of invasive disease, therapy may involve Mohs surgery, topical treatment or radiotherapy. However, lentigo maligna often involves adnexal structures, creating histological difficulty in distinguishing these foci from invasive melanoma. We present a case in which, during Mohs excision, a nodule of severely atypical melanocytes appeared to lie within the dermis, potentially altering treatment and prognosis. The use of laminin-5 provided a means of resolving this diagnostic dilemma, facilitating continuation of Mohs surgery until tumour clearance was achieved.

Introduction

Lentigo maligna is a form of melanoma in-situ that may be present in up to 1.17% of Caucasians aged 65–74 years1. The most significant risk factor is lifetime UV radiation exposure; accordingly, lentigo maligna often presents as an irregularly pigmented macule at sun-damaged sites in elderly individuals – particularly the head and neck. Left untreated, reported rates of progression to invasive melanoma vary between 2.2–50%2, and the prognosis of invasive disease is similar to that of other melanoma types after adjusting for tumour thickness3. However, controversy remains regarding the best therapeutic modality for lentigo maligna.

Report

A 76 year old British seaman presented in April 2010 with an unevenly pigmented brown macule on the left side of his neck, measuring 31 × 26 mm. This was at the site of a previous lentigo maligna that had been excised with a 5 mm margin.

6d6f4ee5-6e21-4bc0-a335-4368fb0e4022_figure1.gif

Figure 1. Lesion on left side of neck.

A diagnostic biopsy showed a lentiginous proliferation of atypical melanocytes tracking down adnexae, confirming recurrence. The patient was referred for Mohs surgery.

In addition to lentigo maligna in the epidermis, one Mohs section revealed a large nodule of severely atypical melanocytes, apparently lying mid-dermis.

6d6f4ee5-6e21-4bc0-a335-4368fb0e4022_figure2.gif

Figure 2. Nodule of atypical melanocytes (H&E ×20).

This presented a significant interpretational problem. Lentigo maligna commonly involves hair follicle epithelia; thus, the nodule may reflect complete replacement of the follicular epithelial cells still confined by basement membrane (in-situ disease). Alternatively, it could represent a focus of invasive melanoma, in which case Mohs surgery would have to be aborted.

To clarify this important distinction, immunocytochemical staining was performed for laminin-5 (Dako, Z0097, 1:100), a component of basement membrane. This revealed immunopositivity of the basement membrane of the follicular epithelium, confirming that the atypical melanocytes were confined to the hair follicle.

6d6f4ee5-6e21-4bc0-a335-4368fb0e4022_figure3.gif

Figure 3. Nodule with laminin 5 staining (×20).

Mohs surgery was therefore completed in a 2-stage, 10-section procedure. Following confirmation of negative margins, the defect measured 45 × 35 mm – substantially larger than the original lesion. This was closed using a rhombic transposition flap, which healed well. To date there has been no recurrence.

Discussion

Lentigo maligna presents several challenges in terms of diagnosis and management. Firstly, clinical and dermoscopic features may be strikingly similar to solar lentigo4. It is also prone to significant subclinical extension beyond the visible limits of the tumour. Following initial tumour debulk, single atypical melanocytes scattered irregularly along the dermo-epidermal junction may be the only histological feature of residual lentigo maligna5. This difficulty is compounded by the presence of single mildly atypical melanocytes in chronically sun-damaged skin6. Finally, lentigo maligna often spreads into deep adnexal structures, confounding both diagnosis and treatment6.

There are various management options for lentigo maligna. Excision is accepted as the gold standard and can consist of conventional excision with a 5 mm margin, or some form of Mohs surgery. Other therapies are destructive, including radiotherapy and imiquimod (Aldara), a topical immunomodulator.

An evidence-based comparison of treatment modalities supports Mohs surgery as first-line, with recurrence rates as low as 0.3% compared to up to 20% for standard excision6. The follow-up periods of these trials varied from 18 months to almost five years, but it is notable that the most favourable study for Mohs surgery included 625 patients and measured recurrence over 58 months7.

The impressive statistics for Mohs surgery are in part attributable to the superior histological margin control afforded by this technique. Traditional surgical excision uses ‘bread-loafing’ to check for residual tumour, but this allows visualization of less than 1% of the margin. By contrast, in Mohs surgery, tissue is excised tangentially before being processed into horizontal sections. This method – combined with precise mapping and orientation of tissue by the Mohs surgeon reading the pathology – allows all tumour extensions to be traced. The end benefits are two-fold: recurrence rates are significantly improved, as tumour clearance is optimised; and healthy tissue is conserved, preserving cosmesis and function – important considerations on the face. The significance of visualising the entire tumour is underscored by evidence showing that almost 25% of biopsy-proven melanoma in-situ lesions are found to contain invasive melanoma upon pathological examination after complete surgical removal6.

Follicular involvement by lentigo maligna is a widely recognised phenomenon, and is a characteristic of lentiginous spread. Indeed, a key dermoscopic feature of lentigo maligna is asymmetrical pigmentation of follicular openings, reflecting uneven descent of melanoma cells into individual hair follicles. Over time the slate-grey dots and streaks surrounding the follicle progress into a rhomboidal pattern, and then to eventual obliteration of the follicle, visible on dermoscopy as black blotches highly specific for malignant growth.

Follicular melanoma has been reported as a rare variant of melanoma, to be distinguished from lentigo maligna melanoma by its significantly smaller surface area (typically < 0.5 cm), the relative symmetry of the lesion and its similarity in appearance to a comedo or pigmented cyst8. A recent study investigating the growth characteristics of melanoma in-situ in relation to hair follicle microanatomy has suggested that the follicle itself represents a physiological barrier, restricting the intraepithelial spread of melanoma tumour cells at or beyond the level of the hair follicle bulge9.

The present case posed an interesting diagnostic dilemma – the difficulty in distinguishing between dermal invasion and melanoma in-situ within a hair follicle. To resolve this, we used immunocytochemistry for laminin-5 to delineate normal basement membrane surrounding the hair follicle, indicating in-situ disease and therefore justifying continuation of the Mohs procedure.

Laminin-5 is a component of the adhesion complex in basement membrane10. It is thought to act as a ligand for the attachment of normal melanocytes to the basement membrane. Conversely, loss of laminin production by melanoma cells is thought to be a marker for malignant transformation10. To our knowledge, the use of laminin-5 staining during Mohs has not been previously reported.

Learning points

  • Lentigo maligna presents significant challenges in diagnosis and treatment

  • Mohs surgery can be effective as long as disease remains in-situ, but this may be difficult to ascertain

  • Almost 25% of biopsy-proven melanoma in-situ lesions are upstaged to invasive melanoma upon pathological investigation, highlighting the importance of visualising the entire tumour

  • Surgeons using the Mohs technique require a thorough understanding of histopathology using horizontal sections to achieve meaningful margin control

Consent

Written informed consent for publication of clinical details and clinical images was obtained from the patient.

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how to cite this article
Tsakok T, Sheth N, Robson A et al. Lentigo maligna mimicking invasive melanoma in Mohs surgery: a case report [version 1; peer review: 2 approved]. F1000Research 2014, 3:25 (https://doi.org/10.12688/f1000research.3-25.v1)
NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article.
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Open Peer Review

Current Reviewer Status: ?
Key to Reviewer Statuses VIEW
ApprovedThe paper is scientifically sound in its current form and only minor, if any, improvements are suggested
Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.
Not approvedFundamental flaws in the paper seriously undermine the findings and conclusions
Version 1
VERSION 1
PUBLISHED 24 Jan 2014
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Reviewer Report 30 May 2014
Rajiv Kumar, Germany Cancer Research Center, Helmholtz Association, Heidelberg, Germany 
Approved
VIEWS 8
Well defined report. I ... Continue reading
CITE
CITE
HOW TO CITE THIS REPORT
Kumar R. Reviewer Report For: Lentigo maligna mimicking invasive melanoma in Mohs surgery: a case report [version 1; peer review: 2 approved]. F1000Research 2014, 3:25 (https://doi.org/10.5256/f1000research.3409.r4667)
NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.
Views
9
Cite
Reviewer Report 10 Feb 2014
Eduardo Nagore, Department of Oncology, Valencian Institute of Oncology, Valencia, Spain 
Approved
VIEWS 9
A nice case report ... Continue reading
CITE
CITE
HOW TO CITE THIS REPORT
Nagore E. Reviewer Report For: Lentigo maligna mimicking invasive melanoma in Mohs surgery: a case report [version 1; peer review: 2 approved]. F1000Research 2014, 3:25 (https://doi.org/10.5256/f1000research.3409.r3331)
NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.

Comments on this article Comments (0)

Version 1
VERSION 1 PUBLISHED 24 Jan 2014
Comment
Alongside their report, reviewers assign a status to the article:
Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested
Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.
Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions
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