Mohs micrographic surgery (MMS) is a surgical technique used to treat locally invasive malignant cutaneous tumors. It offers higher cure rates than other treatments and minimizes the removal of healthy peritumoral tissue.1

The original technique described by Dr. Mohs was the fixed-tissue technique, in which zinc chloride paste was applied to a lesion to achieve in situ fixation of the tumor tissue. The paste was removed after several hours and the tumor excised without anesthesia and with hardly any bleeding. The excised specimen was frozen and then horizontally sectioned for examination under a microscope.2 This procedure was repeated on successive days until all the margins of the final specimen were free of tumor. Dr. Mohs later described the fresh-tissue technique, in which successive layers of the tumor were removed under local anesthesia, without prior application of zinc chloride. This technique allowed surgeons to remove several layers of tumor and even repair the surgical defect on the same day and it became the method of choice for practically all MMS surgeons.3,4

The use of paraffin sections instead of frozen sections emerged for several reasons, including the difficulty of examining frozen sections for certain tumors, such as lentigo maligna (LM) and dermatofibrosarcoma protuberans (DFSP), the possibility of using immunostains in other cases, or simply lack of access to a cryostat. This modified procedure is known as slow Mohs. It has several variations, which are more common in Europe, that go under the names of 3D-histology, the perimeter technique, the Mohs-Tübingen technique, and the quadrant method. In all cases, however, including frozen-section MMS, 100% of tumor margins are examined through tangential sectioning rather than the standard vertical sectioning used in conventional surgery.5

Dr. Mohs’ technique was adopted first in the United States and then in Europe. An increasing number of Spanish hospitals from both the private and public health sectors have introduced MMS in recent decades, and their experience has been reported in both national and international journals.6–11 In 2012, the Spanish Academy of Dermatology and Venereology Foundation (FAEDV), in conjunction with the working group on Surgical Dermatology, Laser, and Cutaneous Oncology of the AEDV, decided to set up the Spanish Mohs Surgery Registry (REGESMOHS) in order to be able to describe the outcomes of MMS in Spain. The first cases were registered in July 2003. Previous studies have described the hospitals that perform MMS in Spain, together with the characteristics of the patients and tumors included in REGESMOHS.12,13

In this article we analyze the cases of MMS registered in REGESMOHS to date, with a focus on perioperative aspects (e.g., use of anticoagulants and antiplatelet agents), surgical technique, number of stages required to achieve tumor-free margins, surgical defect size and reconstruction, intraoperative complications, reconstruction of surgical defects, and use of resources.

REGESMOHS is a prospective cohort study involving 18 public and private hospitals throughout Spain that perform at least 1 MMS operation a week. All patients who undergo evaluation prior to MMS are successively included in the registry. The only patients not included are minors and those declared to be legally incapacitated.

The study was approved by the research ethics committee of Navarra, the Spanish Agency for Medicines and Medical Devices (AEMPS), and all the participating hospitals. It was conducted in compliance with the principles of the Declaration of Helsinki and current laws. All patients gave their written consent to participate in the study.

The different outcome variables are collected during patient visits. Data on demographics, associated conditions such as immunosuppression and diabetes mellitus, clinical and histopathologic features of the tumor, and previous treatments are collected at the first visit. At the second visit, a record is made of type of surgery, anesthesia, hospitalization, use of anticoagulants and antiplatelet agents during surgery, surgical defect size, other treatments, surgery duration, and intraoperative complications and morbidity. Short-term outcomes and complications are evaluated at the third visit. Finally, patients are evaluated for surgical outcomes, recurrences, and appearance of new tumors at subsequent follow-up visits, which are held at least once a year. The development of subsequent tumors in a given patient is described in the registry but only the first tumor is subject to follow-up.

Data are entered by the participating hospitals into an online system provided by the Research Unit of the FAEDV (OpenClinica Open Source software, version 3.1) following a standard protocol. The information entered is monitored continuously online. Additional site checks are made once a year to assess adherence to the protocol and check the information entered against the source documents. Stata statistical software (version 14.1) is used for data analysis.

We have described the current use of MMS in Spain based on information entered into REGESMOHS between July 2013 and January 2016. The data correspond to 1796 patients who underwent at least 1 MMS operation at one of the 18 participating hospitals. Our results provide insights into the use and technical complexity of MMS in Spain, as well as use of resources and short-term outcomes.

The strengths of the study lie in its prospective design and the analysis of data that are strongly representative of the state of MMS in Spain, as the participating hospitals account for a large proportion of all hospitals that perform this procedure in Spain.12

One limitation is related to the progressive inclusion of patients and recording of data, as some hospitals appear to have fewer patients than recorded in the initial report, indicating that they have either not operated on some patients or not entered the data into the online system. Minor changes to outcomes due to random variations can probably be expected in future publications.

The incidence of nonmelanoma skin cancer has increased exponentially in recent decades, and annual increases of between 3% and 8% have been reported in Europe, the USA, Canada, and Australia since 1960.14–16 MMS is the current gold standard for the treatment of high-risk BCC and SCC and it has also shown superior results to other techniques for other cutaneous cancers. A priori, however, the technique may not seem very cost-effective due to the infrastructure requirements, the need for trained personnel, and the time it takes. Data on these aspects of MMS can vary from country to country and accurate assessment is important for benchmarking purposes.

The use of MMS has been reported in several important studies, including prospective studies of a large Australian registry of patients treated with MMS between 1993 and 200217–19 and a series of prospective studies and randomized clinical trials comparing MMS and conventional surgery in the Netherlands.20–22

Our results for tumor location and patient sex are similar to those described in the initial report of REGESMOHS13 and other series. The only difference between our study and others that have included tumors other than BCC and SCC is the higher proportion of LM and DFSP cases. In our study, for example, these tumors accounted for 2.81% and 1.97% of cases, respectively, contrasting with rates of 0% and 0.5% in a recent study from the United Kingdom.22

Patients who had undergone solid organ transplantation represented the largest group of patients with immunosuppression in REGESMOHS (n=38). Transplant patients have a higher incidence of nonmelanoma skin cancer, and SCC in particular, and may be candidates for MMS.23,24

The proportion of patients who received antiplatelet or anticoagulant treatment (18%) is lower than that reported in other dermatologic surgery studies (29% for MMS patients25 and 35% for dermatologic surgery patients in general).26 The perioperative use of these treatments, however, was similar to that reported elsewhere.27,28

In our series, 33.1% of tumors were recurrent or persistent; this rate is identical to that reported for the Australian study of BCCs treated with MMS17 and very similar to the rate of 29.3% described by Hoorens et al.29 in the most recent study from the Netherlands. Like in our study, the most common previous treatment in these studies was surgery. It is noteworthy that, with the exception of cryotherapy, nonsurgical treatment was uncommon (< 3% for each treatment).

A mean of 1.6 stages (median, 1; range, 1-12) was required to achieve tumor-free margins. This figure is slightly lower than that of 1.7 (median, 2; range, 1-9) 17reported in Australia for BCC17 and identical to that of 1.6 (median, 1; range, 1-7) reported for SCC.19 In Europe, Flohil et al.20 reported a clearance rate of 43.5% with 1 stage (vs. 56.5% with ≥ 2 stages). In a series of 737 BCCs treated with MMS, Smeets et al.21 reported clearance rates of 25% and 46% for 1 and 2 stages, respectively. The corresponding rates for the UK series were 58% for 1 stage, 34% for 2 stages, 6% for 3 stages, 1% for 4 stages, and 0.5% for 5 or more stages.22

The surgical defect was repaired by a dermatologist in a very high proportion of patients in REGESMOHS (98.4% in total). On the whole, this rate is higher than previously reported rates. In a series of 12344 MMS operations performed in the United States (Brown University, Rhode Island) between 2005 and 2012, 17% of surgical defects in women and 8% of those in men were reconstructed by a plastic surgeon.30 In the Dutch series described by Hoorens et al.29 most of the surgical defects were repaired by dermatologists (84%), followed by head and neck surgeons (8.5%), plastic surgeons (6.2%), and other specialists, such as oculoplastic surgeons (1%-3%).

Flap closure, used in 47.2% of cases in our series, was the most common repair method used, coinciding with previous reports.31,32 Several decades ago, skin grafts used to be considered the most useful closure method in MMS, as they permitted earlier detection of possible recurrence. Now, however, flaps are more common than either grafting or healing by secondary intention due to the increased confidence in outcomes, improved surgical skills, smaller postsurgical defects, and the younger age of patients.

All the intraoperative complications reported in our series involved high blood pressure and/or intraoperative bleeding. Just 1 patient required hospitalization due to intraoperative- and postoperative bleeding, which is considered a major surgery-related complication.33,34

The median duration of surgery, 75minutes, indicates that, overall, MMS operations do not take much longer than conventional surgery of facial skin tumors that require reconstructive surgery with flap closure or grafts.

The characteristics of the patients and tumors treated by MMS in Spain are similar to those reported in similar studies from other geographic areas. The findings for short-term outcomes were also similar. The main differences in our series were the higher percentage of DFSP and LM cases treated and the higher proportion of surgical defects repaired by a dermatologist. Major intraoperative complications were very rare and median duration of surgery was only slightly higher than that reported for conventional surgery. Our data are useful for evaluating whether findings from other settings can be applied to Spain for hospitals planning to introduce MMS or for those already using MMS wishing to use benchmarking to identify areas for improvement. Our results may also be useful for effectiveness studies and should interest dermatologists and other health care specialists and managers.

REGESMOHS is funded by FAEDV with the collaboration of Roche Farma. Roche Farma had no involvement in the preparation of this manuscript.

The authors declare that they have no conflicts of interest regarding the content of this article.