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Mohs surgery, also known as chemosurgery, developed in 1938 by a general surgeon, Dr. Frederic E. Mohs, is microscopically controlled surgery used to treat common types of skin cancer. During the surgery, after each removal of tissue, while the patient waits, the pathologist examines the tissue specimen for cancer cells, and that examination informs the surgeon where to remove tissue next. The surgeon performing the procedure is also the pathologist reading the specimen slides. Mohs surgery is one of the many methods of obtaining complete margin control during removal of a skin cancer (CCPDMA – complete circumferential peripheral and deep margin assessment.) using frozen section histology. CCPDMA or Mohs surgery allows for the removal of a skin cancer with very narrow surgical margin and a high cure rate.
The cure rate with Mohs surgery cited by most studies is between 97% and 99.8% for primary basal cell carcinoma, the most common type of skin cancer. Mohs procedure is also used for squamous cell carcinoma, but with a lower cure rate. Two isolated studies reported cure rate for primary basal cell carcinoma as low as 95% and 96% (see the discussion below titled "Why is the Cure Rate so Varied?). Recurrent basal cell cancer has a lower cure rate with Mohs surgery, more in the range of 94%. It has been used in the removal of melanoma-in-situ (cure rate 77% to 98% depending on surgeon), and certain types of melanoma (cure rate 52%). Another study of melanoma-in-situ revealed Mohs cure rate of 95% for frozen section Mohs, and 98 to 99% for fixed tissue Mohs method.
Other indications for Mohs surgery include dermatofibrosarcoma protuberans, keratoacanthoma, spindle cell tumors, sebaceous carcinomas, microcystic adnexal carcinoma, merkel cell carcinoma, Paget's disease of the breast, atypical fibroxanthoma, leiomyosarcoma, and angiosarcoma. Because the Mohs procedure is micrographically controlled, it provides precise removal of the cancerous tissue, while healthy tissue is spared. Mohs surgery is relatively expensive when compared to other surgical modalities. However, in anatomically important areas (eyelid, nose, lips), tissue sparing and low recurrence rate makes it a procedure of choice by many physicians.
Originally, Dr. Mohs used an escharotic agent made of zinc chloride and bloodroot (the root of the plant Sanguinaria canadensis, which contains the alkaloid sanguinarine). The original ingredients were 40.0 gm Stibnite, 10.0 gm Sanguinaria canadensis, and 34.5 ml of saturated zinc chloride solution. This paste is very similar to "Hoxsey's paste" (see Hoxsey Therapy). Harry Hoxsey, a lay cancer specialist was developing a herbal tonic and paste designed to treat internal and external cancers. Hoxsey recommended applying paste to the affected area and within days to weeks, the area would necrose (cell death), separate from surrounding tissue and fall out. Dr. Mohs applied a very similar paste after experimenting with a number of compounds to the wound of his skin cancer patients. They were to leave the paste on the wound overnight, and the following day, the skin cancer and surrounding skin would be anesthetized, and ready to be removed. The specimen was then excised, and the tissue examined under the microscope. If cancer remained, more paste was applied, and the patient would return the following day. Later, local anesthetic and frozen section histopathology applied to fresh tissue allowed the procedure to be performed the same day, with less tissue destruction, and similar cure rate. The term "chemosurgery" remains today, and is used synonymously with Mohs micrographic surgery.
The Mohs procedure is essentially a pathology sectioning method that allows for the complete examination of the surgical margin. It is different from the standard bread loafing technique of sectioning, where random samples of the surgical margin are examined.
Mohs surgery is performed in four steps:
The procedure is usually performed in a physician's office under local anesthetic. A small scalpel is utilized to cut around the visible tumor. A very small surgical margin is utilized, usually with 1 to 1.5 mm of "free margin" or uninvolved skin. The amount of free margin removed is much less than the usual 4 to 6 mm required for the standard excision of skin cancers. After each surgical removal of tissue, the specimen is processed, cut on the cryostat and placed on slides, stained with H&E and then read by the Mohs surgeon/pathologist who examines the sections for cancerous cells. If cancer is found, its location is marked on the map (drawing of the tissue) and the surgeon removes the indicated cancerous tissue from the patient. This procedure is repeated until no further cancer is found. For best results a reconstructive plastic surgeon may be necessary.
The method is well described in current references. The mapping combined with the "smashing the pie pan" method of processing is the essence of CCPDMA surgery. If one imagines an aluminum pie pan as the blood covered surgical margin, and the top of the pie is the crust covered surface of the skin – the goal is to flatten the aluminum pie pan into one flat sheet, mark it, stain it, and examine it under the microscope. Another author uses the example of peeling the skin off an orange. Imagine an orange cut in half as the CCPDMA layer. The peel is the surgical margin. One can remove this peel and flatten it out on a glass slide to examine the roots of the invasive cancer. The mapping is simply how one stains and labels the sections for a microscopic examination. The sections can be processed in one piece (using relaxing incisions at multiple points, or hemisectioned like a "Pac-Man" figure), cut in halves, cut in quarters, or cut in multiple pieces. Single piece processing is acceptable for small cancers, and multiple piece sectioning facilitates processing and prevent artifacts. Single piece sectioning prevents errors introduced by soft, hard-to-handle tissue; or from accidental dropping or mislabeling of specimen. Multiple sectioning prevents compression artifacts, separation of tissue, and other logistical problems with handling large thin sheets of frozen skin.
Some physicians believe that frozen section histology is the same as Mohs micrographic surgery, but it is not. Mohs surgery is performed using fresh tissue while frozen section histology may or may not be CCPDMA. Non-CCPDMA histology usually utilizes a random tissue sampling technique called "bread loafing". Bread loafing is a statistical sampling method which examines less than 5% of the total surgical margin (imagine pulling 5 slices of bread out of a whole loaf of sliced bread and examining only those 5 slices to visualize the whole loaf). In CCPDMA processing, the entire surgical margin is examined (imagine one who examined the entire outside crust of the same loaf of bread). In statistical terms, the more slices of bread one examines, the lower the "false negative" rate will become. False negatives occur when a pathologist reads cancer excision as "free of residual carcinoma", even though cancer might be present in the wound and missed because of the random sampling. In reality, most pathology labs examine only 3 to 8 sections of the "loaf" in their margin determination. The alternatives to Mohs surgery are CCPDMA based surgical excision and non-CCPDMA surgical excision. Dr. Mohs and CCPDMA pathologists have perfected methods of examining the entire surgical margin.
Mohs surgery often leaves an open wound, which a plastic surgeon is ideally suited to close.
Each surgeon has his or her own convention. A typical convention is as follows
Epidermis l l l l l l l l l l BLUE - - - - - - - - - RED --------------------------------- YELLOW O O O O O O O GREEN X X X X X X X Missing Epidermis V V V V V V V V V V
Sometimes, for confirmation purposes, a second opinion will be asked of a pathologist to review pathology slides from Mohs cases. Traditional histology of skin tissue uses vertical sectioning – with the subcutaneous tissue at the bottom and the epidermis at the top. Mohs surgery uses tangential or horizontal sectioning, which can confuse the pathologists trained in the traditional method.
First, one has to determine the method of chromacoding or color-coding. The orientation of the Mohs map must be able to distinguish between medial, lateral, superior, and inferior.
Next, one has to determine if the surgeon followed the convention of mounting only 2 sections per case; as preferred by some authors; or did he/she perform serial sectioning through the block as preferred by other authors. If serial sectioning is performed, the distance between sections should be confirmed. Some surgeons utilize 100 micrometres between each section, and some utilize 200 micrometres between the first two sections, and 100 micrometres between subsequent sections (10 crank of tissue set at 6 to 10 micrometre is roughly equal to 100 micrometres if one allows for physical compression due to the blade).
Next, one determines if the entire epidermal border is present. Ideally 100% of the epithelial border should be present. Convention requires at least 95% of the epidermis to be present. However, some surgeons will make an exception for some missing epithelium at the apices of an elliptical excision around the specimen. Ideally, oval sections should be performed. However, for practical purposes on some lesions, a surgeon might cut the Mohs section to approximate the final closure defect. The apexes are often 1 cm or more from the tumor, so clear margins at the apices can be ignored. This is not the ideal by convention, but is appropriate on a case by case basis.
Next, one determines if the surgical margin is clear. With serial sectioning, one has to recreate the surgical specimen in a 3 dimensional way. The first section that touches the blade begins the 3 dimensional reconstruction. By using the 3-D reconstruction of the specimen, one can say that all the epithelial margin is present as one progresses from deep to superficial. If only 2 sections are present, ideally, both the sections should be clear. If the deeper section is positive, one has to ascertain the distance between the sections. Convention often calls for a clear margin of at least 200 micrometres. For ambiguous structures that resemble both adnexal structure and carcinoma, following the serial sections will allow for one to identify the structure as benign or malignant. With the 2 slides method, this might be impossible to perform, as no 3-D reconstruction is possible with only 2 sections.
Carcinoma appearance under Mohs micrographic sectioning can be difficult. Tangential cut of squamous cell can mimic squamous cell carcinoma (but without the atypia). Sections through the buds of hair follicles can resemble isolated islands of basal cell cancers, often even with retraction artifact. Serial section analysis is best for Mohs surgery.
The trend in skin surgery over the last 10 years has been to continue anticoagulants while performing skin surgery. Most cutaneous bleeding can be controlled with electrocautery, especially bipolar forceps. The benefit gained by ease of hemostasis is weighed against the risk of stopping anticoagulants; and it is generally preferred to continue anticoagulants.
The team consists of the Mohs surgeon, histotechnician, and assisting nurses. The Mohs surgeon identifies the cancer and its margin, often with the aid of dermatoscopy. He or she removes the cancer under local anesthetic and prepares it for histology processing. This is accomplished by cutting the specimen (if required), staining the specimen for orientation, and sending it to the lab.
The histotechnician prepares the tissue for Mohs processing by flattening the surgical margin on a flat surface first. Then the flat surgical surface is mounted on a cryostat to be sectioned and prepared for glass slides to be read by the pathologist.
In Mohs surgery, the surgeon acts as the pathologist. He or she examines the slide for residual tumors, and marks the location of the tumor on the pathology report.
The Mohs surgeon sometimes functions as the reconstructive surgeon. Some Mohs surgeons perform their own surgical repair, but with more challenging cases will enlist the help of a plastic surgeon.
These are topics for discussion, but errors introduced in the technique can introduce false negative errors. There are numerous reasons why the cure rate is not 100%. Some of Dr. Mohs data revealed a cure rate as low as 96%, but these were often very large tumors, previously treated by other modalities. Some authors claim that their 5 year cure rate for primary basal cell cancer exceeded 99% while other noted more conservative cure rate of 97%. The quoted cure rate for Mohs surgery on previously treated basal cell cancer is about 94%. Reasons for variations in the cure rate include,
Irrespective of the problems associated with Mohs surgery, a true cure rate approaching 100% can occur with primary basal cell carcinoma (previously untreated) if proper respect of the physician's limitation, the procedure's limitation, and his laboratory staff's limitation is paid. A conservative approach such as serial sectioning, good staining technique, and conservative Mohs margin (example: tumor at least 200 micrometre from the surgical margin) can assure the lowest recurrence rate.
Mohs surgery is not the answer for all skin cancers. Under select circumstances, radiation, topical chemotherapy, cryosurgery, electrodesiccation and curettage, and standard excision are better than Mohs surgery. Studies comparing the effectiveness of Mohs surgery to other modalities often fail to specify surgical margin, method of processing (bread loafing with 3 or 4 sections, bread loafing with 0.1 mm spacing, margin controlled, frozen section vs. standard histology); leaving little argument one way or another. Once a pathologist understands the simplistic nature of Mohs surgery, and its margin control ability – little need is called for clinical trial comparing Mohs surgery to surgical excision.
In reality, Mohs micrographic surgery is nothing more than frozen section histology using a unique peripheral margin control tissue processing technique. There is nothing magical about its cure rate or why years of training is required. When compared to many other described peripheral margin control tissue processing technique – the end result is the same – allowing for the complete examination of 100% of the surgical margin. The method is unique only in that it is a simple way to handle soft, hard to cut tissue. Once learned, any pathologists currently doing frozen section histology would realize how simple the technique is. It is better than doing serial bread loafing at 0.1 mm interval for improved false negative error rate simply in requiring less time, less tissue handling, and fewer glass slides mounted. Once mounted as tangential or horizontal sections, the pathologist simply has to relearn how to visualize skin structure on a tangential to horizontal view. In absent of a Mohs trained pathologist, peripheral sectioning followed by horizontal sectioning of the remaining center is equivalent to the Mohs method.
The clinical quotes for cure rate of Mohs surgery is from 97% to 99.8% after 5 years for newly diagnosed basal cell cancer, decreasing to 94% or less for recurrent basal cell cancer. Radiation oncologists quote cure rate from 90 to 95% for BCC's less than 1 or 2 cm, and 85 to 90% for BCC's larger than 1 or 2 cm. Surgical excision cure rate varies from 99% for wide margin (4 to 6 mm) and small tumor, to as low as 70% for narrow margins applied to large tumors. Here the weakness of the procedure is the histopathological processing, and not the surgeon himself. The fault of the surgeon is lack of understanding pathology laboratory methods, and failing to follow the standard of care for adequate surgical margin. Usually the cure rate using standard bread loafing is very low for narrow surgical margin and a large tumor, and very high for large margins on small tumors. It is the pathology lab that makes the difference, especially when frozen section is utilized in the operating theater. A randomized study assigning patients with recurrent facial basal cell cancer to either Mohs surgery or standard excision revealed no statistical difference in the treatment of primary basal cell carcinoma. It found a higher cure rate with Mohs surgery in the treatment of recurrent basal cell carcinoma (5 year recurrence rate of 2.4% for Mohs vs 12.1% for standard).
Cosmetic appearance for Mohs surgery is very good, if combined with good reconstructive surgical skills. Some Mohs surgeon utilize a plastic or reconstructive surgeon for the closure, and some Mohs surgeons perform the reconstruction by themselves. In certain area, the tip of the nose, and the nasal ala, Mohs surgery can result in significant deformity, and might require multiple staged reconstruction to rebuild the nose cosmetically. Radiation offers a very good non-traumatic option in these difficult to reconstruct areas.
In choosing a Mohs surgeon or reconstructive surgeon, it is mandatory that a patient request to see pictorial representation of his/her previous work. Then one can proceed to make a decision whether the Mohs surgeon should also be the reconstructive surgeon.
Few individuals argue about the cure rate for Mohs, especially pathologists familiar with the procedure. However, in recent years, a few authors suggested that Mohs surgery is no better than standard excision. The author in one study did not conclude the adequacy of the study as it is limited in size and short duration of the study (30 months). Extensive studies performed by Dr. Mohs involving thousands of patients with both fixed tissue and fresh tissue cases have been reported in the literature. Other surgeons repeated the studies with also thousands of cases, with nearly the same results.
Clinical 5 year cure rates with Mohs surgery:
Experienced Mohs surgeons have reported cure rates for melanoma-in-situ from 95% to 98% (depending on if it is small MIS, or lentigo maligna variant), much higher than previously reported by Dr. Mikhail of 77%.
These are only a small number of cases reported by Dr. Mohs, and numerous other articles by other authors have shown tremendous cure rates for primary basal cell carcinoma. However, with studies by Smeet, et al. showing a Mohs cure rate of about 95%, and another study in Sweden showing Mohs cure rate of about 94%; we really have to question if methodology practiced by Mohs surgeons around the world is of the same standard. Some surgeon also question if the standard 2 sections performed by some Mohs surgeons is adequate to control for false negative Mohs reports, as many surgeons prefer serial sectioning of multiple Mohs histology layers.
An example where clinical guidelines are issued by insurance companies; these guidelines are not indication that Mohs is the best method for the cancers described. These guidelines are subjective (why is younger than 40 years old a criterion?), and might not have any clear objective basis. Clinical guidelines currently adapted by Medicare insurance of the United States:
Medicare will cover reimbursement for Mohs micrographic surgery for accepted diagnoses and indications as listed below.
Mohs surgery can be applied to any relatively non-aggressive locally invasive tumor with a contiguous growth pattern (i.e. no skipped growth, or metastasis). Today, most Mohs procedures are performed by dermatologists. However, pathologists, plastic surgeons, and otolaryngologists have been trained and are utilizing Mohs surgery in their practice as well. Hopefully, as more physicians are trained in the method, Mohs surgery can be applied to other organs systems beside the skin. The limitation of this application to other tumors (i.e. prostate cancer, cervical cancer, laryngeal cancer) is that the tumor must be in the earliest stages and no metastasis has occurred. The second problem with Mohs surgery is the prolonged procedural time, which might require prolonged general anesthesia.
Currently, the American College of Mohs Surgery has limited training to physicians who have done a dermatology residency. The American Society for Mohs Surgery continues to encourage the training of physicians of all specialties to learn and apply the method invented by Dr. Frederick Mohs. The argument against physicians of other specialties than dermatology gaining Mohs training is that they are not adequately trained in dermatopathology. The argument for training other physicians beside dermatologists is that most Mohs surgeons do not make the initial diagnosis of the skin cancer – thus misdiagnosis can be avoided. The pathology of Mohs sections are then limited to a few easily identifiable cancers; and the pathology of normal skin is simple enough to gain in a short preceptorship.
Dr. Mohs, a general surgeon, encouraged physicians of all surgical specialties to learn and apply his technique to the treatment of skin cancer; it is understood that he never intended to limit his method to be utilized by dermatologists alone. In countries where dermatology is not well developed, the Mohs procedure can easily be learned by any surgeon or pathologist after a short preceptorship – the same way Dr. Mohs taught many current Mohs surgeons.
Quotation from Dr. Mohs first book:
"The book should be useful to physicians who may be called on to treat or advise regarding treatment of skin cancers and other conditions that are described. This includes dermatologists, surgeons, plastic surgeons, otolaryngologists, gynecologists, urologists, proctologists, pathologists, internists, and general practitioners."
The American College of Mohs Surgery is the organization that sets standards of care for fellowship trained Mohs surgeons who perform Mohs surgery as a primary function of their practice. Completion of a current ACMS fellowship require 1 to 2 years of training in the Mohs procedure including reconstructive and plastic surgery – in addition to 4 years of residency.
The American Society of Mohs Surgery is an organization of dermatologists who perform dermatology and Mohs surgery in their practice. ASMS Mohs surgeons are certified by a written and practical exam, and are required to submit to yearly peer review of their cases.
The American Board of Medical Subspecialities is in the process of reviewing Mohs micrographic surgery as a separate subspecialty. Mohs surgery has not been recognized as a separate subspeciality and there is no certifying board for Mohs Surgery at this time.
The American Osteopathic College of Dermatology is the only organization that recognized Mohs surgery as a separate subspecialty. The organization offers board certification exam through the auspice of the American Osteopathic Association.
The American Society for Dermatologic Surgery founded in 1970 is the largest organization of board certified dermasurgeons with over 5000 members who perform dermatologic surgeries including Mohs micrographic surgery.
The Association of Academic Dermatologic Surgeons has board certified dermasurgeon professors who have faculty appointments at major teaching hospitals and universities and are engaged in training medical students and residents in the practice of dermatologic surgery and Mohs micrographic surgery.