Mohs micrographic surgery is one of the most important procedures in dermatologic surgery, mainly because: (1) it can effectively treat common skin malignant tumors while ensuring minimal postoperative defects, which is clinically significant and has been recognized as the gold standard for the treatment of common skin malignant tumors; (2) the emergence of Mohs micrographic surgery has pushed many dermatologists to take up the scalpel again to treat skin tumors, and has greatly contributed to the development of surgical dermatologic surgery. (3) Mohs micrographic surgery is a unique procedure in dermatologic surgery, targeting skin tumors, and is therefore considered an important symbol of the existence of dermatologic surgery as a subdiscipline of dermatology. In conclusion, the birth and development of Mohs micrographic surgery is a milestone for dermatologic surgery, and as a dermatologist engaged in dermatologic surgery, one should fully understand and master Mohs micrographic surgery.
1.History of Mohs micrographic surgery
Mohs microscopic tracing surgery is named after the American physician Frederid Mohs. In the 1930s, Frederic E. Mohs, a medical student, was studying the effects of various chemical sclerosing agents on animal tissues with his teacher. He discovered that when zinc chloride was injected into animal tissues, the tissue was necrotic but the microstructure was intact. He then wondered: if zinc chloride was injected into tumors, would it be possible to not only destroy the tumor tissue for therapeutic purposes, but also to clearly observe the extent of the treatment? Through experiments, Frederic E. Mohs’ idea was confirmed. In order to reduce the side effects of zinc chloride injections, he then consulted a pharmacist and developed a 45% zinc chloride paste, and thus the concept of “chemosurgery” was born. The paste had many advantages over the solution injection, such as easy to control the depth of treatment, the ability to stop the tissue fixation after 18h of topical application, less systemic absorption, less taste, and less possibility to induce tumor metastasis. However, chemosurgery was not widely accepted at that time, and in most cases only patients with surgery intolerant tumors were recommended to Frederic E. Mohs, and chemosurgery was only a “last resort”. In 1956, Frederic E. Mohs published the first monograph on chemical surgery, which shook the dermatological community with its precise and complete clinical data, leading to the eventual widespread acceptance of chemical surgery.
Admirably, Frederic E. Mohs did not revel in his success, but clearly realized that the topical use of zinc chloride paste still had significant shortcomings, such as the procedure being too time-consuming. It usually takes 24 h of zinc chloride topical application to achieve optimal tumor fixation, and if tumor remnants are still found, it takes more than 24 h to repeat the previous steps. In addition, after the removal of the tumor tissue fixed with zinc chloride paste, the inflammatory reaction of the wound was very strong due to the chemical effect, which caused great difficulties in the repair of the surgical defect, and the second stage healing of the surgical defect was used as a last resort at that time. After repeated experiments, Frederic E. Mohs decided to abandon the chemical surgery he had been studying for more than 20 years and proposed the “fresh tissue technique”, i.e., butterfly excision of the tumor, directional labeling, frozen section detection, and then directional excision of the tumor. The “Fresh Tissue Technique”, which involves butterfly excision of the tumor, targeted labeling, frozen section detection, and targeted excision of the residual tumor. The fresh tissue technique does not require a long wait for “chemical action”, has no special effects on the surrounding tissues, and allows the application of a variety of shaped repair methods to repair the surgical defect. Thus, Mohs micrographic surgery in the true sense of the word today was born. With the large amount of clinical data reported, Mohs micrographic surgery became more and more widely accepted and today is the gold standard for the treatment of malignant skin tumors with single focal continuous invasive growth. In honor of Frederic E. Mohs and to promote Mohs micrographic surgery, the American College of Chemical Surgery was founded in 1967, renamed the Mohs College of Micrographic Surgery and Cutaneous Oncology (ACMMSCO) in 1986, and will be renamed the Mohs College again in 2009, and today the organization is the nation’s premier authority on training dermatologic surgeons. Today, the organization has become a specialized authority for the training of dermatologic surgeons in the United States.
Looking back on the development of Mohs Micrographic Surgery, one cannot help but admire the courage of Frederic E. Mohs to deny himself and to continue his research. It was the birth of Mohs micrographic surgery that greatly inspired dermatologists, who had long focused on drug therapy, to engage in the treatment of skin tumors, and along with the popularity of fresh tissue technology, led more and more dermatologists to study surgical defect-forming and repair techniques, and later dermatologists improved new flap techniques such as the bilobed flap that cannot be partially attributed to Frederic E. Mohs. In conclusion, Mohs’ microscopic tracing surgery has played a great role in promoting the development of dermatologic surgery.
2.The clinical significance of Mohs microscopic tracing surgery
Mohs micrographic surgery is highly respected mainly because of its clinical significance. For tumors on the body surface, patients are concerned about two issues: (1) whether the tumor can be cured; and (2) whether it will affect the appearance after surgery. From the perspective of the principle of Mohs micrographic surgery, it can solve both of these problems. First of all, Mohs micrographic surgery can ensure that the tumor is removed under direct vision, and although repeated resections are sometimes required, in most cases, the surgery can be completed within one day. The impact on the patient’s psychological well-being is also different. Second, Mohs micrographic surgery ensures minimal surgical defects and maximum preservation of normal skin tissue. As we all know, skin tumors often occur in exposed areas such as the head and face, and the size of the surgical defect is very meaningful to the shaped repair. The clinical significance of Mohs micrographic surgery has become more and more important as the standard of living has improved and people are paying more attention to the aesthetics of their appearance, even in the elderly population. From an epidemiological point of view, non-melanoma skin tumors, such as basal cell carcinoma, are the most prevalent tumors in humans. Although the incidence of these tumors is significantly lower in Asian races than in Caucasian Caucasians (European and American Caucasians), the absolute number of non-melanoma skin tumors occurring in Asian states is also striking because of the large absolute population size. In addition, the incidence of skin tumors in China seems to be on the rise with the aging population, changing life patterns, and environmental pollution. In conclusion, there is a huge clinical demand for Mohs microstroke surgery in China, and Chinese patients need the latest and best treatment for skin tumors. In a review of previous literature [2], the 5-year cure rate of primary basal cell carcinoma treated with conventional surgery is only 90-93%, while treatment with Mohs micrographic surgery can reach 98-99%. For recurrent basal cell carcinoma, the 5-year cure rate of conventional surgery is only 80.1%, while the cure rate of Mohs micrographic surgery can reach 94.4%. The above facts show that Mohs micrographic surgery is very valuable and should be the first choice of treatment for common skin malignancies not only in Europe and America but also in Asian countries like China. Chinese dermatologists have the obligation to provide the best treatment for their patients.
3.The basic principle of Mohs microscopic tracing surgery
The rationale of Mohs micrographic surgery explains 2 advantages of this procedure: (1) to ensure the clean cut of the tumor; (2) to minimize the primary defect of the surgery. Cutaneous malignant tumors usually do not grow uniformly and invasively outward and may form a “pseudopod” pattern in some directions. Therefore, it is easy to miss the residual tumor, especially the residual tumor in the “pseudo-foot” part, and finally misjudge the “clean tumor cut”. Therefore, it is easy to miss the residual tumor, especially the residual tumor in the “pseudo-foot” part, and finally misjudge the “clean tumor”. How can we fully detect the excised tumor specimens and accurately judge whether there is residual tumor? Generally, the excised tumor specimen is a hemisphere, and if the lateral wall and bottom surface can be thoroughly examined, comprehensive detection can be achieved. Since the tissue is elastic, if the lateral wall of the tumor specimen is pressed down so that it is in the same plane with the bottom surface, then the entire lateral wall and bottom surface can be detected by cutting across the plane, which is the basic principle of Mohs microscopic tracing surgery to ensure the clean tumor. Of course, in practice, the specimen can be divided into small pieces in order to facilitate downward pressure on the lateral wall, and the central part of the specimen can also be removed to play the role of tissue release. In order to facilitate sectioning, freezing technique can also be used to fix the shape of the specimen when performing frozen sectioning. The principle of “minimizing surgical primary defect” is based on directional staining, directional labeling and directional resection. In practice, according to the location and shape of the tumor, the tumor is traced on the corresponding anatomical part of a pattern map, and after cutting the tumor specimen, it is divided into several pieces according to the size of the tumor, and each piece is marked with a number and the location and code of each piece is marked on the pattern map. In other words, no matter how messy the specimens are placed, they can be traced back to the original position of the body according to the code. One of the lateral edges of the specimen is then stained with a special dye and marked on the pattern map. The dye does not elute during the section production process, so the position of the residual tumor is further pinpointed when the section is read based on whether the tumor residue is close to the stained edge or not, whereby the physician can accurately and finely excise the residual tumor while maximizing the preservation of normal skin. Since the lateral wall of the tumor specimen is pressed to the plane where the bottom surface is located, the residual tumor found close to the epidermal side when reading the frozen section indicates that the width of excision is not enough, and if the tumor is close to the subcutaneous area, the depth of excision is not enough. The continuous integrity of the tissue, especially the epidermis, must be ensured during the filming process, otherwise the significance of performing Mohs microscopic tracing procedure is lost. In addition, if dense aggregates of inflammatory cell infiltration are found in the section, it should be treated as residual tumor.
4. Pre-operative preparation and intra-operative and post-operative considerations
According to the principle of Mohs micrographic surgery mentioned above, Mohs micrographic surgery requires excision, detection, re-excision, re-detection, and so on, until the tumor is excised and finally formed to repair the surgical defect, so the patient repeatedly enters the operating room during Mohs micrographic surgery, and the waiting time is long. According to the characteristics of Mohs microscopic tracing surgery, some special preoperative preparations should be made from the perspective of surgical hardware environment, patient status and physician respectively.
4.1 Hardware environment: Conventional outpatient operating room conditions should be available, but since patients are mostly elderly, tools and plans for emergency resuscitation of cardiovascular and cerebrovascular diseases should be available, and electrocoagulants should preferably be selected for bipolar electrocoagulation, in addition there should be a patient rest area immediately adjacent to the operating room, and in some hospitals because the operating room is placed in a ward, hospital beds can be provided for patients to rest and wait.
4.2 Patient status: Patients will be psychologically stressed by surgery, and repeatedly going in and out of the operating room will aggravate it. A detailed explanation of the surgical plan should be given to the patient before surgery, and the patient’s blood pressure and blood glucose should be regulated, and the patient should be sedated before surgery if necessary. Patients are free to eat and drink between surgeries, and it is best to keep the external pressure dressing on to prevent bleeding. For elderly people with a history of cardiovascular disease, it is best to implement cardiac monitoring.
4.3 Physician workup: The patient’s health status and psychological status should be thoroughly assessed. Since the procedure involves mostly light-exposed areas, it is also important to have a true understanding of the patient’s expectations of the outcome of the incisional molding repair. The physician should give a detailed explanation of the surgical prognosis to the patient and family and emphasize the importance of postoperative follow-up. Special emphasis should be placed here on the treatment of recurrent tumors. Since the breadth and depth of subcutaneous involvement of recurrent tumors is often difficult to judge from the epidermal involvement, often the seemingly small recurrent skin lesions are very large after excision, and it is difficult for many patients to accept the reality at this time. Therefore, in the face of recurrent tumor cases, it is important to explain in advance the various situations that may occur and adjust the patient’s expectations to a reasonable level in all aspects.
4.4 Make good preparation of preoperative instruments: Mohs microscopic tracing surgery requires some special items, including: ① pattern diagrams for marking tumor location and resection orientation. Usually, it is necessary to prepare frontal, left side and right side diagrams of face, front and back side diagrams of left and right ear, pattern diagrams of head and occiput, front and back side diagrams of trunk extremities, pattern diagrams of foot plantar surface, pattern diagrams of perineum and scrotum area. ②Vessels for transporting specimens, either flat dishes or stainless steel lunch boxes. A piece of paper can be placed at the bottom of the vessel, with squares drawn on it as needed, and then marked with numbers accordingly so that the specimens can be numbered. (iii) Dye for marking the orientation of the specimen. The special feature of this dye is that it does not elute during the production process, and only a small number of foreign professional brands are now able to meet the demand. From a practical point of view, the step of marking the stain can be completely replaced by measures such as scratching, so the marking dye is not necessary.
There are some other precautions to be taken intraoperatively and postoperatively in Mohs microscopic tracing surgery: ① Proper use of antibiotics is required. Because of the long duration of Mohs micrographic surgery and the fact that the incision is not sutured between procedures and is only covered with a dressing, there are indications for the use of antibiotics to prevent infection. Usually only 3 days of antibiotics are required (including the day of surgery). ②If the surgery involves a more superficial area of the facial nerve branches or if the tumor is deeply involved, be sure to explain to the patient the possibility and consequences of damaging the nerve. ③Make sure to pay attention to the preservation and management of frozen sections of Mohs microscopic tracing surgery, which is an important legal document and academic information.
5.Mohs microscopic tracing procedure steps
5.1 Operation steps: ①Tumor location and shape are traced on the pattern map; ②Routine disinfection, marking the outer edge of the tumor and local anesthesia; ③Scribe the skin with a scalpel at 1 mm from the outer edge of the tumor as the initial operation area. In addition, a deep cut can be made across the tumor edge to mark the direction of the tumor edge; ④ excise part of the central tumor tissue, but it should not be too deep, and the function is to loosen the tissue; ⑤ excise the tumor along the third step of the scratch, and grasp the depth of excision according to the nature of the tumor; ⑥ stop the bleeding of the wound thoroughly, put pressure on the dressing, and use anti-adhesion dressing for the bottom layer of the dressing, and let the patient wait for the rest area. The tumor specimen should be divided into several pieces, each piece should contain epidermis, and then stain one side of the cut edge, and number each piece of specimen; ⑧ mark the specimen division, staining position and number on the pattern diagram; ⑨ send the marked specimen to frozen section; ⑩ when making frozen section, freeze and fix the shape after pressing down the side wall of the specimen, and then perform OCT embedding. The slices are cut from the bottom side, and each slice should have intact epidermis, dermis and subcutaneous tissue; the slices are also numbered according to the specimen number; after HE staining, the surgeon reads the slice and marks the position on the pattern map if residual tumor is found; the patient enters the operating room from new, is routinely disinfected, the extent of expansion is marked, and additional local anesthetic is administered. When excising the tissue, it is advisable to carry a little epidermis for subsequent excision in order to determine the direction, even if the residual tumor is only present in the dermis. According to the size of the new specimen, it is re-divided into several pieces and stained and labeled, and likewise marked again on the pattern diagram, and the specimen is sent for frozen section; the film is read, and if residual tumor is still found, the above steps are repeated until the tumor is judged to be cleanly cut; depending on the location, shape and size of the surgical primary defect, a shaped repair is performed.
5.2 Frozen section staining procedure: 10% formalin fixation (15min) → water wash (2 times) → hematoxylin (10min) → water wash (2 times) → hydrochloric acid alcohol (color separation, rapid) → water wash (2 times) → ammonia (anti-blue) → water wash (2 times) → eosin (8min) → water wash (2 times) → 80% alcohol (1min) → 95% alcohol (1min) → pure alcohol I (2min)→pure alcohol II (2min)→xylene I (5min)→xylene II (10min)→sealing (bright resin glue).
6.Indications for Mohs microscopic tracing surgery
Mohs microscopic tracing surgery is used to determine whether the tumor is clean or not by thoroughly examining the outer edge of the tumor specimen. Therefore, Mohs microscopic tracing surgery is suitable for single focal continuous growth of skin malignant tumors, such as basal cell carcinoma and squamous cell carcinoma. The reason why Mohs micrographic surgery is considered to be the best method for treating common skin malignancies is related to the fact that common skin tumors are different from other systemic tumor growth forms. For example, basal cell carcinoma of the nose, if not treated aggressively, may completely destroy the nose after several years and even invade the skull eventually leading to death, but metastases to other organs rarely occur in the most severe cases. The following skin tumors are routinely considered indications for Mohs micrographic surgery: basal cell carcinoma, squamous cell carcinoma, Bowen’s disease, bulging dermatofibrosarcoma, malignant fibrous histiocytic sarcoma, verrucous carcinoma, sebaceous gland carcinoma, extramamammary Paget’s disease, smooth muscle sarcoma, adenoid cystic carcinoma of the small sweat glands, Merkel cell carcinoma, and sweat adenocarcinoma. Malignant melanoma is relatively easy to metastasize distantly and is not a single focal continuous growth skin malignancy, but clinical studies have confirmed that Mohs micrographic surgery is more effective in treating malignant melanoma that has no evidence of metastasis yet. Therefore, Mohs micrographic surgery is also clinically relevant to reduce tumor load and remove focal tumors in most malignant tumor cases.
The aggressiveness of skin malignancies varies by tissue type. For example, the common tissue types of basal cell carcinoma are superficial, nodular, scleroderma-like, and micronodular. The latter two are recognized to be more aggressive. Undifferentiated, hypodifferentiated, spindle cell, and spine-loosening squamous cell carcinomas are also among the more aggressive tumors. It is recommended that Mohs microscopic tracing should always be used for more aggressive skin malignancies, because whether this tumor is excised or not has a more significant impact on the patient’s prognosis. Mohs micrographic surgery is also recommended for tumors larger than 2 cm in diameter, tumors with unclear clinical boundaries, tumors secondary to radiation therapy, tumors secondary to immunosuppression, and tumors in children that are more aggressive and more likely to recur.
Studies of skin tumors have found that anatomical site is associated with tumor recurrence rates. Areas such as periocular, perinasal, temporal, scalp, preauricular, mucous membrane, lips, extremities and genitalia are considered to be areas of high risk for tumor recurrence and metastasis and are recommended for complete treatment with Mohs micrographic surgery.
Another indication for Mohs micrographic surgery in a non-medical sense is the need for aesthetics. Many patients, especially women, are very concerned about the aesthetic effect of the surgery, and skin tumors often occur in light-exposed areas. As mentioned above, Mohs micrographic surgery can ensure minimal surgical defects and facilitate shaping and repair, so Mohs micrographic surgery should also be used to meet the need for postoperative aesthetic effect.
In summary, the indications for Mohs micrographic surgery are as follows (note: malignant skin tumors refer to single focal continuous invasive growth tumors) [3]: malignant skin tumors of the head and face, malignant skin tumors of the trunk and extremities >2 cm in diameter, malignant skin tumors at high risk of recurrence, tumors with unclear clinical boundaries, recurrent malignant skin tumors, secondary malignant skin tumors, tumors with The tumor has aggressive histological pattern, etc.
7.Exclusion criteria of Mohs microscopic tracing surgery
Mohs microscopic tracing surgery requires the cooperation of nurses and technicians, and more expensive equipment such as frozen section machine, so the economic cost of surgery is higher than general surgery. In addition, the operation time is longer because of the need for repeated testing of tumor specimens. Faced with the higher cost and time of surgery, the treatment should be chosen according to the actual situation of the patient. For example, if the patient is older, in poor health and the skin tumor is small and growing slowly, it is not necessary to choose Mohs micrographic surgery. For example, patients with mental retardation and mental disorders are not suitable for Mohs micrographic surgery because they cannot cooperate with the surgery for a long time.
8.Mohs micrographic surgery in China
Mohs micrographic surgery was not really introduced into China until the beginning of this century, but it has developed rapidly, and many hospitals have recognized the significance of Mohs micrographic surgery and carried out it one after another. The popularity of Mohs micrographic surgery in China still faces some problems, such as: (1) some hospitals are unable to integrate skin pathology and surgical techniques, so Mohs micrographic surgery cannot be performed; (2) Mohs micrographic surgery is not yet well known by Chinese physicians and patients, which leads to many cases of delayed treatment; (3) some people think that Mohs micrographic surgery is not suitable for the treatment of skin tumors. (3) Some people think that Mohs micrographic surgery is not needed in China because of the low incidence and low invasiveness of skin tumors; (4) Some people refuse to perform Mohs micrographic surgery because Mohs micrographic surgery is time-consuming and laborious and they have too many patients. As mentioned earlier China’s large population numbers and the reality of an increasingly aging society predict the increasing prevalence of skin tumors in China. As China’s economy develops, Chinese patients with skin tumors have the right and the ability to choose the best treatment options, and it is incumbent upon Chinese dermatologists to provide the best options for their patients, who should not choose treatment based on the number of patients and their workload. With regard to surgical techniques, the principle of moving from simple to complex and from few to many can be followed. For example, the training of Mohs microscopic tracing surgeons can start with the study of common tumor pathology and does not require all surgeons to be dermatopathologists. Some hospitals start Mohs micrographic surgery by collaborating with the hospital pathology department to perform frozen section production. In conclusion, it is the responsibility of Chinese dermatologic surgeons to promote the popularization of Mohs microscopic tracing surgery, and it is also the demand of Chinese skin tumor patients and the inevitable development of the discipline of dermatologic surgery.