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Mohs micrographic surgery for cutaneous malignancies is a tissue-sparing procedure that offers cure rates superior to that of other treatment options. Mohs surgery has evolved as the most reliable and cost-effective treatment modality for skin cancer, offering maximal preservation of normal tissue and therefore the lowest functional and cosmetic morbidity. It is a method of surgical excision with high intrinsic value that is cost-effective in comparison with traditional surgical excision. In this article, the main steps of this surgical procedure are outlined along with the tissue-processing concepts, the indications, limitations, and cost-effectiveness of Mohs micrographic surgery (MMS).
Mohs micrographic surgery for cutaneous malignancies is a tissue-sparing procedure that offers cure rates superior to that of other treatment options. Mohs surgery has evolved as the most reliable and cost-effective treatment modality for skin cancer, offering maximal preservation of normal tissue and therefore the lowest functional and cosmetic morbidity.
In this article, the main steps of this surgical procedure are outlined along with the tissue-processing concepts, the indications, limitations, and cost-effectiveness of Mohs micrographic surgery (MMS).
History
The concept of sequential tumor removal was originated by Frederic E. Mohs while in medical school in the early 1930s.
The procedure, appropriately named chemosurgery by its inventor because of the chemical interaction between zinc chloride and human tissue, began with the overnight application of 20% zinc chloride paste to the tumor.
In 1953, he began to use a “fresh-tissue technique” to excise smaller tumors involving the eyelids and omitted the zinc chloride step. The advantages of the fresh-frozen tissue technique were delineated at the next meeting of the American College of Chemosurgery in 1970 when Tromovitch and Stegman presented a series of 75 additional skin cancers treated with this method.
In 1986, reflecting the acceptance of the fresh tissue technique, the American College of Chemosurgery changed its name to the American College of Mohs Micrographic Surgery and Cutaneous Oncology to more accurately represent the clinical practice of this tumor-removal method.
In recent years the name has been changed to the American College of Mohs Surgeons for simplicity.
Overview
The MMS method of tissue processing identifies close to 100% of both the peripheral and the deep margin as opposed to a standard excision, which typically has 3-5% of the margin examined histologically (Figure 1).
The most important concept to grasp throughout this article is this: Mohs surgery is a specialized way of processing tissue to examine 100% of the excised margin. The concepts of the surgeon as the pathologist, and the technique of horizontal (en face) tissue processing, define Mohs surgery. The Mohs surgeon histologically interprets horizontal (en face) sections of fresh frozen tissue. There is no pathologist involved. Because the Mohs surgeon serves as the pathologist, she has the distinct advantage of understanding a tumor's histologic behavior and obtaining instant feedback during tumor extirpation. Mohs surgeons are challenged daily not only to recognize and correctly map tumor present at the margins of excision, but to identify and communicate histologic characteristics that may change the patient's management. It is important to identify whether a tumor is an aggressive subtype, if there is evidence of perineural or intravascular invasion, if the tumor is poorly differentiated, and if the tumor invades structures deep to the skin. These parameters define our recommendations for adjuvant therapy to our colleagues in otolaryngology, plastic surgery, oncology, and radiation oncology.
Figure 1Overview of the Mohs micrographic surgery technique vs the limitation of a conventional excision margins. In this example the limitation of the bread-loaf method becomes clear. No extension to the peripheral margins is detected and the excision is technically clear on margins; however, this is not an accurate margin assessment. Extension of the tumor to the surgical margin between sections D and E is missed because it is not sampled. (Printed with permission from Elsevier. Adapted with permission from Grekin RC. Mohs micrographic surgery. In: Robinson JK, Arndt KA, LeBoit PE, Wintroub BU (eds): Atlas of cutaneous surgery. Philadelphia, PA, WB Saunders, 1996.)
This tissue-processing method allows for complete circumferential peripheral and deep margin assessment using frozen section histopathology. The Mohs surgeon examines the tissue microscopically and indicates any residual cancer on a map (Figure 3A, B ). This way further excision is performed only where residual tumor is located and to the indicated depth (Figure 4). The excised tissue is frozen and again sectioned horizontally and then read along with the graphical mapping to ensure correct orientation.
Figure 2Typical Mohs histology laboratory with a cryostat on the left and a tissue staining hood on the right.
Figure 3(Top) The cartoon shows preparation and excision of the obvious tumor. (A) Left nasal ala with obvious tumor preoperatively. (B) Debunking with a curetting order to delineate tumor extension. (C) Stage 1 of MMS; note the 1-2 mm margin around the curetted boarder and the 30- to 45-degree angle of the scalpel. (D) Stage 1 MMS layer completed with scoring of the epidermis at the medial and lateral margin, which corresponds to the division of the specimen for processing. (Printed with permission from Elsevier. Adapted with permission from Grekin RC. Mohs micrographic surgery. In: Robinson JK, Arndt KA, LeBoit PE, Wintroub BU (eds): Atlas of cutaneous surgery. Philadelphia, PA, WB Saunders, 1996). (Bottom) This shows mapping and division of the specimen. (A) A scalpel of used to divide the specimen paying careful attention to maintaining the orientation. (B) The divided specimen on the map showing the correct orientation. (C) Map orienting the tissue specimen and denoting dye-markings of the deep margins. (Printed with permission from Elsevier. Adapted with permission from Grekin RC. Mohs micrographic surgery. In: Robinson JK, Arndt KA, LeBoit PE, Wintroub BU (eds): Atlas of cutaneous surgery. Philadelphia, PA, WB Saunders, 1996.)
Figure 4The cartoon depicts stage 2 and 3 of MMS. (A) Residual tumor is seen and drawn on the map noted by the colored in areas. (B) Stage 2 with a 2-mm margin around all positive areas. (C) Stage 2 tissue specimens and drawn map. (D) Stage 2 map denotes the positive tumor with the colored in areas. (E) Stage 3 tissue specimens and drawn map. (F) Postoperative defect after stage 3 of MMS. (Printed with permission from Elsevier. Adapted with permission from Grekin RC. Mohs micrographic surgery. In: Robinson JK, Arndt KA, LeBoit PE, Wintroub BU (eds): Atlas of cutaneous surgery. Philadelphia, PA, WB Saunders, 1996).
The area to be excised is anesthetized with a local anesthetic (usually lidocaine, 0.5%-1% solution) combined with epinephrine (1:200,000 or 1:100,000).
Figure 5Left forehead basal cell which the surgeon has outlined with a surgical marking pen.
The tumor is often debulked with a curette to better define the extent of the gross tumor margins. This debulking step allows the surgeon to “feel” for the depth, extent, and nature of the tumor (Figure 6).
When treating morpheaform basal cell carcinoma or other nonfriable tumors, curettage is often ineffective at debulking the tumor and does not accurately delineate the tumor extent.
Some Mohs surgeons prefer to sharply debulk these tumors with a scalpel to process the debulked specimen for tumor identification and categorization using vertical frozen sections.
Figure 6Curretting and debulking the tumor which allows the surgeon to “feel” for the extent of the tumor.
The excision is begun at a 45-degree angle to the skin, which allows the histotechnician to flatten the specimen more easily than if it was taken at a 90-degree angle. The excision continues around the entire tumor surface at a 45-degree angle and under the base of the tumor parallel to the surface so the tissue removed is shaped somewhat like a shallow bowl. To maintain precise orientation, the specimen and the adjacent tissue are “scored” with identifying marks (Figure 8). This can be done using suture, staples, or superficial scalpel incisions (“hatches”).
Figure 7Stage 1 of MMS, the surgeon excised the tumor with a narrow margin (1-2 mm from the curetted wound) with a scalpel angle of 45 degrees from the skin.
Figure 8To maintain precise orientation, the specimen and the adjacent tissue are “scored” with identifying marks; these “score” marks can be seen on the epidermis when the tumor is removed in order for the surgeon to have precise orientation when they return for further stages.
A 2-dimensional map of the wound is drawn for reference to the tissue orientation (Figure 9). The tissue is then subdivided into sections small enough to fit on a glass slide.
While maintaining orientation with respect to the area of excision, each stage is numbered with Roman numerals (I, II, III) and each section of the tissue is numbered with Arabic numbers
Dermatological surgery: Mohs micrographic surgery for treatment of basal cell carcinoma of the face-results of a retrospective study and review of the literature.
The cut edges are inked different colors for orientation during histologic examination (Figure 10). The map is likewise marked with either the inks or the symbols referenced with a legend to indicate color. The map shows the asymmetric identifying marks on the tissue, the different tissue subsections, and the exact color of the inked tissue. Commonly used inks are merbromin (red), ferrous ferrocyanide (blue), and India Ink (black); however, yellow, green, and purple are also used (Figure 10, Figure 11).
Usually, inking 2 adjacent sides of each section with different colors is sufficient to permit adequate 2-dimensional orientation, but additional colors are occasionally needed.
Figure 9A 2-dimensional map of the wound is drawn for reference to the tissue orientation.
The fresh, inked tissues are taken to the cryostat to be embedded and processed. The cut side of the tissue specimen is often mounted on a slide to ensure optimal flattening of the margin to be examined (Figure 12, Figure 13A ) and then embedded in mounting media to be frozen in the cryostat (Figure 12B).
There are various ways that histotechnicians embed the tissue for processing; these intricacies are beyond the scope of this article. In the cryostat, the tissue is frozen and cut into horizontal, en face sections.
Horizontal 8- to 10-μm sections are taken that allow visualization of the underside and periphery of the excised tissue (Figure 14, Figure 15). Histologic preparation for microscopic examination in MMS requires skill and practice. Several variations in technique exist.
Figure 12The cut side of the tissue specimen is often mounted on a slide to ensure optimal flattening of the margin to be examined. Remember, the histology technician is attempting to cut the peripheral and deep margins, so epidermal edges must be embedded carefully.
The prepared sections are fixed and stained, usually with hematoxylin and eosin or toludine blue (Figure 16) and presented to the Mohs surgeon for histologic examination. Any residual tumor found on the slides is indicated in red on the map. The surgeon can then return to the patient's defect with its “hatches” or “scores” at the edges and, with the aid of the Mohs map, pinpoint the exact location of the residual tumor for further excision.
Figure 16The prepared sections are fixed and stained.
Residual tumor is removed in successively numbered stages (Roman numerals) by modifying steps 1 through 6 until the surgical margins are free of malignancy (Figure 17A, B ). In this manner, uninvolved tissue is preserved as the tumor is sequentially removed. The precise map of each stage accurately records and documents the entire surgery and is retained as part of the patient's record.
After the Mohs technique is finished, the surgeon is left with a beveled defect with superficial nicks (Figure 18). This can be either repaired by the Mohs surgeon or referred to a colleague for reconstruction. Figure 19 demonstrates the slides that correlate with the Mohs map. It is easy to see that the tissue's orientation and mapping are key in MMS.
Figure 17(A) Mohs Map of MMS stage 1, which shows positive tumor. (B) The surgeon is taking the second stage of MMS with a 1- to 2-mm margin around the first stage.
Figure 19This shows the Mohs map and tissue slides and how they correlate to one another. The shape and size of the Mohs map illustrations are very similar to the actual size and shape of the Mohs layers taken.
Although frozen section analysis is the primary modality for tissue processing in Mohs surgery, permanent, paraffin-embedded sections with or without immunohistochemistry can be useful in specific circumstances. The term has been coined “slow” Mohs for those procedures in which the Mohs surgeon takes a layer and processes it en face with permanent sections instead of frozen. The “slow” part of this procedure is that it takes 48 hours to process slides instead of 30 minutes and the patients are sent home after each layer instead of awaiting further surgery. Slides processed with paraffin-embedded, permanent sections are of higher quality, making especially subtle and difficult tumor types easier to identify. For instance, when treating primary cutaneous adenocarcinoma, the Mohs surgeon may choose to achieve clear margins with frozen sections and then submit the tissue blocks or take an additional layer for permanent section processing. These permanent sections also allow for the addition of immunohistochemical stains during the processing period. Using immunohistochemical stains is much more reproducible on permanent sections than on frozen sections. Although there are multiple protocols for immunohistochemical staining on fresh tissue in the Mohs laboratory, they are time-consuming and highly dependent on the experience of laboratory personnel and the Mohs surgeon. This “slow” Mohs allows the surgeon to examine the peripheral and deep margins of subtle tumors with more confidence.
Mohs micrographic surgery for melanoma
Probably the most controversial use of frozen section Mohs surgery is in the treatment of melanoma and melanoma in situ (MIS).
; however, most Mohs surgeons use “slow” Mohs to clear melanocytic lesions. Compared with other treatment modalities for clinically ill-defined MIS, Mohs surgery provides the advantages of complete margin assessment, tissue conservation, and high cure rates.
With an experienced surgeon and Mohs laboratory, Mohs surgery with frozen or permanent sections offers significantly lower recurrence rates of 0% to 3.6% over a minimum follow-up period of 18 months.
Mohs surgery should be considered the treatment of choice for clinically ill-defined MIS, particularly in sun-exposed areas, and lentigo maligna of the head and neck. Clearance of the deep margin and reconstruction can once again be coordinated between the Mohs surgeon and otolaryngology, plastics, or other surgical colleagues if needed.
Indications
Many variables are considered in the evaluation of a patient for MMS. MMS is indicated for locally aggressive tumors that are difficult to eradicate by routine methods (Table 1). Table 2 lists the common indications for MMS. Tumors overlying embryonic fusion planes have a higher recurrence rate if treated by conventional methods rather than by MMS.
Fibrosis from previous excisions or radiation can complicate skin cancer growth patterns and buds of malignant tissue may proliferate asymmetrically throughout the scar tissue, making these ideal candidates for MMS. Surgical borders that were undermined during previous excision provide a lateral plane for tumor advancement.
MMS provides 3-dimensional mapping of the recurrent tumor as long as the tumor remains contiguous, and malignant extension can be followed microscopically with this technique.
Table 1Tumors treated with Mohs micrographic surgery
Another indication for MMS is tumors with perineural invasion. Perineural invasion by a malignancy provides a path of minimal resistance for distant tumor extension. Squamous cell carcinoma (SCC) are frequently associated with perineural invasion.
However, because of the inherent difficulty in identifying small foci of SCC with perineural invasion and the morbidity and mortality associated with perineural tumor recurrence in SCC, adjuvant radiation therapy after reconstruction is often a consideration.
Skin cancers can be treated by multiple modalities, including radiation, electrodesiccation, and curettage, chemotherapy creams, such as 5-fluouracil, immune modulators, such as imiquimod, cryotherapy, surgical excision, photodynamic therapy, and MMS. The goal of any skin cancer treatment is to provide the highest cure rate with minimal morbidity and good functional and cosmetic results in a cost-effective manner. Zitelli's calculation of costs documents that MMS is similar in cost to office-based traditional surgical excision and less expensive than ambulatory surgical facility-based surgical excision.
With these smaller wounds, more economical and simpler reconstructions may be possible. Moreover, important anatomic structures may be preserved. Previously, published studies have demonstrated the presence of larger surgical defects after conventional surgical excision when compared with Mohs micrographic surgery.
Bumstead and Ceilley found that 180% more tissue was removed in conventional surgery than MMS in primary skin cancers and 347% more tissue than MMS in recurrent tumors.
Studies have shown that MMS frequently preserves important anatomic structures and subsequent reconstructions are often less complicated or less extensive than the reconstructions envisioned before MMS.
Collaborations with otolaryngology, radiation oncology, and plastic surgery
It is in the collaboration with one's colleagues that specialists begin to understand each other's roles in tumor elimination, reconstructive surgery, and best patient outcomes. Much can be gained through collaborative efforts. Whether through partnering in tumor extirpation, reconstruction, or adjuvant therapy, patients are often best served when specialists work together.
The Mohs surgeons' unique expertise is that of finding, identifying, and eliminating tumor. However, we often use the talents of our colleagues to assist not only with tissue reconstruction, but with deep margin control.
Otolaryngologists and Mohs surgeons can work easily together on large and complicated cases. Mohs surgeons can clear the soft tissue margins while the otolaryngologists remove any remaining bony involvement and parotid involvement and dive into the deep tissue margins of vital facial structures that are not accessible to the Mohs surgeon under normal circumstances. An example of this is illustrated in Figure 20A-D . The Mohs surgeon outlines the tumor and a small margin of normal tissue is taken and processed for peripheral margin clearing (Figure 21). Although fresh bone can be chiseled and mapped as carefully as fixed bone, it is time-consuming and the protocol for frozen sections is labor-intensive. Additionally, the excision of bone is often traumatic for a conscious patient. When the involvement of bone is suspected, employing the aid of head and neck surgeons, orthopedic, and/or neurosurgeons is always good medicine.
Head and neck surgeons are also used when the Mohs surgeon identifies perineural involvement tracking through a foramen. Perineural invasion is a bad prognostic sign and, when present, radiation oncologists are often consulted to discuss the utility of adjuvant radiation even when the Mohs margins are “clear.”
Figure 20(A) A large melanoma on the left cheek. (B) The Mohs surgeon has drawn a 2- to 5-mm margin around this large tumor for slow Moh excision. (C) The margin is being excised and will be processed for peripheral tumor extension. (D) The lesion after the peripheral Mohs surgery layer has been taken. The deeper component of this tumor will be excised in the operating room by head and neck surgeons.
MMS is often underutilized by other specialists because of either ignorance of the Mohs procedure and its benefits, or a fear of competition. What needs to be understood is that Mohs surgeons are cutaneous oncologists and their forte is processing horizontal tissue sections, defining tumor margins, identifying tumor characteristics, and clearing the tumor. With Mohs surgeons as an integral part of the surgical team, optimal patient care with state-of-the-art techniques can be achieved.
Dermatological surgery: Mohs micrographic surgery for treatment of basal cell carcinoma of the face-results of a retrospective study and review of the literature.
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