Beginnings

Dr Frederic E. Mohs first conceived of the concepts underlying Mohs micrographic surgery (MMS) in the 1930’s while he was a Brittingham Research Assistant to Professor Michael F. Guyer, Chairman of the Department of Zoology at the University of Wisconsin. They were studying the potential curative effects of injecting various substances into different neoplasms. During one experiment, a 20% solution of zinc chloride was injected and inadvertently caused tissue necrosis. Microscopic analysis showed that the tissue retained its microscopic structure as if it had been excised and processed for routine pathologic examination. Dr Mohs realized that this in situ fixation effect could be coupled with surgical excision to remove neoplasms in a microscopically controlled serial manner. In addition, he conceived of the idea of using horizontal frozen sections to evaluate 100% of the specimen margins (deep and peripheral) rather than traditional vertical sections or random step sections, which examine only 0.01% of the total surface area of an excised tumor.

Fixed tissue technique

Mohs tested numerous in situ fixatives before choosing zinc chloride. Arsenic trioxide, phenol, and mercuric chloride were associated with systemic toxicity. Antimony trichloride was found to distort tissue structures. Sodium hydroxide and potassium hydroxide liquefied tissue and resulted in loss of tissue structures. Zinc chloride was chosen because (1) it preserved necessary microscopic features for analysis, (2) had good penetration into the tissues with precise control of fixation depth when the thickness of paste applied and the time interval between application and excision were varied, (3) lacked interference with subsequent second-intention healing, (4) lacked systemic toxicity, (5) was safe to handle, and (6) lacked odor. In addition, the fixation process stopped spontaneously after about 18 hours. This property resulted in the separation of fixed tissue from the underlying healthy tissue with its vasculature intact, allowing for rapid healing and epithelialization. Mohs and Guyer also demonstrated in murine models that exposure to zinc chloride was not associated with an increased risk of metastasis.

Next, Mohs with the aid of an 85-year-old owner of a local pharmacy developed a vehicle (paste) to topically deliver and release the zinc chloride. After some modifications, Mohs chose a mixture of zinc chloride, stibnite (a granular antimony ore), and Sanguinaria canadensis (bloodroot) powder. In an effort to limit untrained physicians from inappropriately using this material, Mohs patented the paste, sold the rights to the Wisconsin Alumni Research Foundation for $1 in 1944, and arranged for the Department of Pharmacy at the University of Wisconsin to supply it to physicians who were certified to use it properly.

Finally, Mohs made several other improvements that increased the effectiveness and efficiency of the procedure, such as orienting the excised tissue layer so as to produce complete horizontal sections, putting multiple sections on a single slide, and color coding the tissue edges for proper orientation.

Initially, Mohs wanted to name the technique microsurgery, but this term was already used to describe the dissection of small structures using a microscope. He then chose the name chemosurgery because the skin cancers that were being treated were first chemically fixed in situ before being excised.

Mohs treated his first human patient on June 23, 1936 in the dermatology clinic at the Wisconsin General Hospital. In 1941, he published his first clinical article in the Archives of Surgery in which he reported the treatment of 440 consecutive patients over a period of 4 years. Because Mohs was describing a surgical technique, the first series of articles were published in surgical journals. Despite this choice of surgical journals, few surgeons contacted Mohs about his technique. Because the most accessible and common tumors that he had treated were on the skin, he turned his attention to the dermatologic community. After his lecture at the 1946 meeting of the American Academy of Dermatology, publication of an article in Archives of Dermatology , and his lecture to the Dermatology Section of the California Medical Association in 1948, Mohs came to believe that dermatologists would accept the technique more readily than any other specialty. In fact, literally hundreds of dermatologists came to visit Mohs in Madison and learn his technique.

In addition to introducing chemosurgery to the medical community, he also popularized using second-intention wound healing extensively. Until then, tradition stated that first-intention surgical repairs were always superior to second-intention wound healing. Mohs found that in many instances, especially on concave surfaces, second-intention healing had comparable and sometimes even superior cosmetic outcomes when compared with first-intention surgical repairs.

Fixed tissue technique

Mohs tested numerous in situ fixatives before choosing zinc chloride. Arsenic trioxide, phenol, and mercuric chloride were associated with systemic toxicity. Antimony trichloride was found to distort tissue structures. Sodium hydroxide and potassium hydroxide liquefied tissue and resulted in loss of tissue structures. Zinc chloride was chosen because (1) it preserved necessary microscopic features for analysis, (2) had good penetration into the tissues with precise control of fixation depth when the thickness of paste applied and the time interval between application and excision were varied, (3) lacked interference with subsequent second-intention healing, (4) lacked systemic toxicity, (5) was safe to handle, and (6) lacked odor. In addition, the fixation process stopped spontaneously after about 18 hours. This property resulted in the separation of fixed tissue from the underlying healthy tissue with its vasculature intact, allowing for rapid healing and epithelialization. Mohs and Guyer also demonstrated in murine models that exposure to zinc chloride was not associated with an increased risk of metastasis.

Next, Mohs with the aid of an 85-year-old owner of a local pharmacy developed a vehicle (paste) to topically deliver and release the zinc chloride. After some modifications, Mohs chose a mixture of zinc chloride, stibnite (a granular antimony ore), and Sanguinaria canadensis (bloodroot) powder. In an effort to limit untrained physicians from inappropriately using this material, Mohs patented the paste, sold the rights to the Wisconsin Alumni Research Foundation for $1 in 1944, and arranged for the Department of Pharmacy at the University of Wisconsin to supply it to physicians who were certified to use it properly.

Finally, Mohs made several other improvements that increased the effectiveness and efficiency of the procedure, such as orienting the excised tissue layer so as to produce complete horizontal sections, putting multiple sections on a single slide, and color coding the tissue edges for proper orientation.

Initially, Mohs wanted to name the technique microsurgery, but this term was already used to describe the dissection of small structures using a microscope. He then chose the name chemosurgery because the skin cancers that were being treated were first chemically fixed in situ before being excised.

Mohs treated his first human patient on June 23, 1936 in the dermatology clinic at the Wisconsin General Hospital. In 1941, he published his first clinical article in the Archives of Surgery in which he reported the treatment of 440 consecutive patients over a period of 4 years. Because Mohs was describing a surgical technique, the first series of articles were published in surgical journals. Despite this choice of surgical journals, few surgeons contacted Mohs about his technique. Because the most accessible and common tumors that he had treated were on the skin, he turned his attention to the dermatologic community. After his lecture at the 1946 meeting of the American Academy of Dermatology, publication of an article in Archives of Dermatology , and his lecture to the Dermatology Section of the California Medical Association in 1948, Mohs came to believe that dermatologists would accept the technique more readily than any other specialty. In fact, literally hundreds of dermatologists came to visit Mohs in Madison and learn his technique.

In addition to introducing chemosurgery to the medical community, he also popularized using second-intention wound healing extensively. Until then, tradition stated that first-intention surgical repairs were always superior to second-intention wound healing. Mohs found that in many instances, especially on concave surfaces, second-intention healing had comparable and sometimes even superior cosmetic outcomes when compared with first-intention surgical repairs.

Fresh tissue technique

Although the fixed tissue technique had higher cure rates than conventional excision, there were limitations to the technique. Each layer took 1 day to complete because of the time required for the paste to fix the tissue before excision, and patients with large tumors requiring excision of multiple layers had to return daily, sometimes for many days. The paste was painful and caused local inflammation and often fever and lymphadenopathy. Although Mohs usually used second-intention healing, when some patients needed surgical reconstruction there would be delays because of postoperative sloughing of the final fixed tissue layer which could take 5 to 7 days to complete. Trying to solve these problems led to the development of the fresh tissue technique.

Mohs actually used the fresh tissue technique in some of his original cases when performing the fixed tissue technique. For example, if cartilage on the ear or nasal ala were being approached, the final layer was excised without prior fixation to avoid damage to the underlying cartilage.

In 1951, one of Mohs’ trainees, Dr R. R. Allington, showed him his technique for first debulking a cancer and then achieving hemostasis with dichloroacetic acid. Mohs was so impressed with the idea that he started using it himself. In 1953, he began to make movies of this technique. While filming the removal of a pigmented basal cell carcinoma from a lower eyelid, removal of small extensions of the carcinoma was delaying the filming. To speed up the process, Mohs removed the next 2 layers using local anesthesia without any fixation in what is now known as the fresh tissue technique. After that, he started using the technique for most eyelid cancers and some cancers in other locations. He first wrote about the technique in the book Skin Surgery in 1956. He also presented this technique and a series of 70 patients at the 1969 meeting of the American College of Chemosurgery and published the results in Bulletin of the American College of Chemosurgery .

The publication by Tromovitch and Stegman of a series of 102 patients in 1974 in Archives of Dermatology is generally recognized by many authorities as being the turning point at which the fresh tissue technique became widely accepted. The investigators initially named the technique microscopically controlled excision to differentiate it from the fixed tissue technique, which then was called Mohs’ chemosurgery, and they presented the first series of patients treated with the fresh tissue technique at the American College of Chemosurgery meeting in 1970. The fresh tissue technique had clear advantages over the fixed tissue technique. The fresh tissue technique eliminated the need for the zinc chloride paste, which could cause the patient considerable discomfort; a tumor requiring excision of multiple layers could usually be removed in a single day; reconstruction could be performed the same day without waiting for the eschar caused by the zinc chloride paste to separate from the underlying viable tissue; unnecessary and uncontrolled fixation beyond the final required surgical margin was avoided. This final aspect was important because it could, in some cases, prevent uncontrolled perforation of underlying structures such as the nose. Mohs later published a much larger series of 3466 patients undergoing fresh tissue technique in which he reported a 99.8% cure rate for nonmelanoma skin cancers.

Although the fresh tissue technique had become the predominant way of performing MMS, Mohs continued to use the fixed tissue technique for melanoma, large extensive neoplasms involving bone, osteomyelitis, penile carcinoma, and gangrene. He thought that because the incisions for layers was made only through fixed tissue containing nonviable melanocytes, the risk of disseminating the malignant melanocytes and possibly causing metastasis was lower than for the fresh tissue technique. For extensive neoplasms involving bone and osteomyelitis, he thought that the bone could more easily be removed with the fixed tissue technique. For penile carcinoma, hemostasis was less problematic with the fixed tissue technique. For removing gangrene and other necrotic processes, Mohs found that the fixed tissue technique caused fixation a few millimeters beyond the area of necrosis and produced healthy granulation tissue, which could lead to faster healing.