Mohs micrographic surgery

MMS is an extremely effective method for the removal of non-melanoma skin cancers.¹ The technique is most commonly used when it is preferable to remove basal cell carcinoma (BCC) without removing excessive unnecessary margins of normal tissue. It creates a skin specimen that can be processed to histopathologically assess all of the margins.

It is also used for squamous cell carcinoma and many rarer skin cancers. It is not generally used for melanoma, however, where guidelines recommend wide margins.²

History of MMS 

The origins of the technique date back to the 1930s, when Dr Frederic Mohs, a physician and surgeon at the University of Wisconsin, pioneered a surgical method for removing skin cancers, which he called ‘chemosurgery’. 

This method permitted the creation of specimens where all of the surgical margins, both peripheral and deep, could be visualised directly under the microscope. This allowed precise documentation by drawing on a diagram the locations of tumour extensions at the edge of the specimen. 

Direct clinicopathological correlation could take place, with the surgeon examining the histopathological slides, then excising further tissue only from the areas required. 

Before histopathology slides can be created, the skin tissue needs to undergo a process known as fixation. This preserves the tissue from decay and allows the preparation of thin sections, which can be stained and placed on a microscope slide. 

The original chemosurgery method used a zinc chloride paste applied to the area to fix the tissue in vivo, before excision and histopathological sectioning. This method was slow, with delays while the tissue was fixed. It was also painful and the resulting wounds, with fixed, hardened edges, were not amenable to closure, often having to heal by granulation.

The technique was refined over the following decades into the modern method known as MMS. This applies the same principles of creation of specimens, permitting histopathological visualisation of all of the margins, clinicopathological correlation and re-excision. Tissue fixing can now, however, be achieved painlessly ex vivo, usually using very rapidly fresh frozen sections, or if necessary, rushed paraffin sections (known as ‘slow’ MMS). Wounds can be closed immediately, once the surgeon is confident the entire tumour has been removed.

MMS requires specific attention to detail as to how the skin tissue is excised, orientated and processed. To understand the difference in this technique, it is necessary to consider first how standard skin excisions are performed and processed. 

Standard excision of skin lesions

Standard excision is performed using vertical incisions around a lesion, which creates a specimen with, essentially, a rectangular cross-section. The two peripheral margins of the specimen sit at 90° to the deep margin. 

The margins are not all in the same plane, so cannot be visualised together on the same histopathology slide. The specimen created from standard skin excision is therefore normally processed by cutting cross-sections through it, a process known as bread-loafing.

Bread-loafing of the skin specimen produces a histopathology slide which normally demonstrates the tumour centrally, hopefully with no tumour extending to the peripheral and deep edges of the slide. If this is the case, it will be reported as such, with usually a measurement in millimetres of the closest extension of tumour to the edge of the slide. 

However, when interpreting the report, it is important to understand that this method only directly visualises a very small proportion of the actual edges of the skin specimen. 

Only several microscopically thin slices have been taken through the specimen, which may be several centimetres in size. Imagine removing several thin slices of bread from a loaf – the vast majority of the loaf’s crust will not be assessed. This can explain why we sometimes see tumours recur, despite apparently clear margins demonstrated on bread-loafed sections. 

To have the confidence to assume complete removal, we need the tumour-free margin in the slides to be large, so we must take wide clinical margins of normal-appearing tissue, typically 4mm for BCC. 

We also need to be confident that the tumour is roughly spherical in shape. If it has undulating, rough edges, this increases the risk that the tumour will be at the edge of the specimen, but may not be demonstrated in the slides processed. 

In theory, the pathology laboratory could cut serial sections throughout the entire specimen, but with each section being only four microns thick, this would produce approximately 5,000 sections for a specimen only 2cm long – clearly not a practical solution. Bread-loafing is therefore always going to demonstrate a small sample of the margin.

Mohs micrographic surgery

MMS is fundamentally different from routine histopathological assessment. The slides created show all of the outer aspect of the specimen, rather than cross-sections through it.

MMS is performed by first marking the apparent visible edges of the lesion with pen, before infiltration of local anaesthetic. Clinically apparent diseased tissue is removed, usually using a curette, without any additional margin of normal-appearing tissue. This central debulk specimen may be processed to provide a ‘positive control’ of what the tumour looks like, and to aid interpretation of subsequent slides.

The defect created is then excised, using a bevelled 45° angle sloping beneath it, normally using a 1-2mm margin. The process has been described in more detail previously in this publication.³

The excised tissue is placed on gauze and orientated relative to the patient. A map is drawn of the excised tissue in relation to the patient. The tissue and map are then transported to the laboratory, and the tissue is divided into pieces that can be frozen in a cryostat machine. Orientation is maintained by inking the edges and recording on the detailed map.

The sloped edges, absence of interior skin tissue and thinness of the specimen permit this bowl-shaped tissue specimen to be pressed flat against a hard surface.

Downward pressure is placed on the edges of the tissue, to help provide a flat plane to allow a seamless transition from epidermis/dermis/fat; this allows the tissue to provide visualisation of its entire undersurface when cut. This is an essential procedure performed by a suitably trained histopathology technician.

The flat surfaces can then be sectioned in a horizontal plane, demonstrating the entire margin. If the tissue is not properly flattened, there is a risk that a large number of tissue sections will be obtained before the entire section is visualised, which runs the risk of producing an incorrect positive margin.

The tissue sections are placed on a glass slide, stained and cover slips applied. These can now be examined under the microscope. The locations of any tumour are recorded on the map and a further thin layer of tissue is excised from the patient, only from these areas. This tissue is again processed in a similar fashion to demonstrate the entire margin. If necessary, several such stages can be taken to demonstrate a complete tumour-free plane of tissue around the site of the tumour.

Figure 1 shows the appearance of a typical BCC. The apparent clinical edges are marked under good illumination, often with the aid of a handheld dermatoscope.

Figure 1: Typical basal cell carcinoma (Image: Dr John Mckenna)

Figure 2 shows the post-MMS defect created in this case. The irregular wound edges result from several
re-excisions (stages), tracking tumour extensions peripherally and deeply. 

Figure 2: Defect after MMS (Image: Dr John Mckenna)

BCC with infiltrative and perineural invasion (as in this case), or micronodular histopathology patterns are more likely to have asymmetric extensions into surrounding clinically normal tissue. This can also occur in tumours that have persisted after other failed treatments. 

Figure 3 shows the immediate postoperative appearance after reconstruction, with temporary swelling from local anaesthetic infiltration, and multiple sutures in place. Skin tissue reserve has been mobilised from the central forehead and nasal dorsum to reconstruct the defect. This avoids distortion of the upper eyelid. There was an excellent long-term cosmetic result.

Figure 3: After reconstruction (Image: Dr John Mckenna)

Figure 4 shows a Mohs map, which documents the locations of tumour seen at the edge of the specimen, along with landmarks that allow the Mohs surgeon to re-excise tissue only from those areas required. Each re-excision specimen is processed with horizontal sections, allowing tumour extensions to be tracked. 

Figure 4: Mohs map documents locations of tumour (Image: Dr John Mckenna)

This case required five stages before a complete tumour-free specimen edge was demonstrated. In this case, it is unlikely that tumour clearance would have been achieved with standard excision and bread-loafing histology. 

Very wide excision would have sacrificed unnecessary areas of healthy tissue around the eyelid, making reconstruction more complicated and increasing morbidity. Even if bread-loafing had shown clear margins in the sections examined, confidence of complete removal would be lower, given the infiltrative and perineural histology patterns. This could have led to persistence of the tumour and clinical recurrence in subsequent years.

Availability of MMS

The availability of MMS in the UK has increased significantly since NICE guidance in 2006 recommended that there should be an MMS service available in every skin cancer network. 

A 2011 survey of members of the British Society of Dermatological Surgery and the British Association of Dermatologists recorded 72 respondents stating that they performed MMS.⁴ 

Of these, 62% had been taught the technique in a dedicated Mohs fellowship of at least 12 months in the US or the UK, 11% had been taught in fellowships of three months or less, 10% had been taught during their dermatology SpR training, and the remainder indicated other forms of training. 

A combination of skills and interests in skin surgery and histopathology are required for an MMS service. 

• Dr John Mckenna is consultant dermatologist and Mohs micrographic surgeon, University Hospitals Leicester

Competing interests: None declared

References

1. Mosterd K, Krekels G, Nieman F et al. Surgical excision versus Mohs’ micrographic surgery for primary and recurrent basal-cell carcinoma of the face: a prospective randomised controlled trial with 5-years’ follow-up. Lancet Oncol 2008; 9(12): 1149-56. 

2. Marsden J, Newton-Bishop J, Burrows L et al. Revised UK guidelines for the management of cutaneous melanoma 2010. Br J Dermatol 2010; 163: 238-56. 

3. Cliff S. Mohs micrographic surgery for BCC. MIMS Dermatology 2009; 5(2): 39-40.

4. Mann J, Al-Niaimi F, Cooper A et al. A national survey of Mohs micrographic surgery in the UK. Br J Dermatol 2016; 174: 225-7.