ABSTRACT: Mohs micrographic surgery is a surgical technique that seeks to ensure the clearance of cutaneous tumors while maximizing normal tissue conservation. This is accomplished through the sequential removal of thin layers of tissue in which the entire peripheral and deep margins are examined for residual tumor. This approach appears to be superior to conventional surgical excision in the treatment of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), the two most common cancers of the skin. Its efficacy in treating BCC and SCC has led clinicians to explore the role of Mohs micrographic surgery in the management of less common cutaneous neoplasms, such as melanoma, Merkel cell carcinoma, dermatofibrosarcoma protuberans, extramammary Paget’s disease, and microcystic adnexal carcinoma.
Mohs micrographic surgery is a specialized surgical technique in which meticulous microscopic mapping of residual tumor guides the surgeon in complete extirpation of the cutaneous malignancy. In doing this, the technique seeks to ensure complete tumor eradication while maximizing normal tissue conservation. This approach appears to be superior to conventional surgical excision in the management of the most common cutaneous neoplasms, namely basal cell carcinoma (BCC)[1,2] and squamous cell carcinoma (SCC).
The increased cure rates for nonmelanoma skin cancer observed with Mohs surgery are largely attributable to the complete microscopic margin examination that occurs with its horizontal sectioning of the specimens. This is not the case with standard surgical excisions, as the majority of surgical pathologists continue to employ either cross-sectioning or bread-loaf sectioning to process tissue specimens. With these methods, less than 1% of the excised margin of the tumor is actually visualized. As a result, the potential for unrecognized margin involvement is much higher with step sectioning of tissue than with the Mohs technique. This difference translates into higher rates of tumor recurrence for standard excision
The field of Mohs micrographic surgery has evolved considerably since its conceptualization in 1936 by Dr. Frederic Mohs. The idea originated from Dr. Mohs' and others' work with the in vivo application of chemical cauterants to tumors of the skin for nonselective destruction. His observation of the unique in vivo fixative properties of one particular escharotic agent, zinc chloride paste, led him to the idea of microscopically controlled excision of tumors.
In Mohs' original technique, which was known as chemosurgery, zinc chloride paste was applied to the skin cancer and allowed to sit overnight. The patient returned the following day for surgical extirpation of the tumor followed by microscopic examination of horizontal sections of the specimen for margin clearance. The major limitations of the procedure were significant pain associated with application of the zinc chloride, prominent tissue inflammation secondary to the cauterant precluding reconstruction of defect, and the time-intensive nature of the 2-day procedure. The development of the fresh-tissue technique in 1974 by Stegman and Tromovitch allowed the procedure to be completed in 1 day and eliminated the pain and inflammation associated with use of zinc chloride. Since this innovation, Mohs surgery has become the gold standard for managing nonmelanoma skin cancers.
Mohs micrographic surgery begins with clinical identification by the physician of tumor margins through visual examination, palpation, and gentle curettage. After the surgical site is anesthetized with a local anesthetic, an incision is made with a scalpel just outside the clinically identifiable margins of the tumor. The distance between the clinical border of the neoplasm and the incision is variable, and depends on the type of malignancy, its size, and how well demarcated it is. In contrast to a traditional cutaneous excision, the incision is typically made at an angle of 30° to 45° with the skin such that the resulting excised specimen has a beveled edge to facilitate processing. At the time of incision, score marks are placed in both the specimen and the defect site for tissue orientation.
The tissue specimen is then transported to the histopathology laboratory, where the specimen is divided into smaller pieces based on the score marks and inked to preserve tissue orientation. A map correlating the surgical defect to the inked specimens is generated. In our laboratory, tissue specimens are pressed onto a glass slide and then freeze-mounted on a tissue chuck. This tissue flattening permits the tangential sectioning of the tissue, which makes Mohs surgery possible. The chucks are then placed in the cryostat for sectioning of the tissue. This yields 6- to 8-μm sections of the entire peripheral margins of the specimen including the base of the lesion. The slides are then stained with hematoxylin and eosin or, more rarely, toluidine blue. The generation of interpretable, highquality frozen section slides is a technically demanding task, which is highly dependent on the skill and experience of the histotechnician.
Next, the Mohs surgeon examines the slides for any evidence of tumor. If residual tumor is identified on the slides, the location is marked on the tissue map. This map is then returned to the patient's bedside for identification of the corresponding region of tumor involvement in the defect site. This area is subsequently removed for further tissue processing and examination, as described above. The process is repeated until the peripheral and deep margins are histologically free of tumor.
The final step in this process involves evaluation of the wound for second-intention healing vs reconstruction of the defect. Many factors enter into the appropriate determination at this juncture. These include the biologic nature of the malignancy removed, preservation of form and function of surrounding tissues, optimization of cosmesis, and patient comorbidities.
Use in Specific Tumor Types
Basal Cell and Squamous Cell Carcinomas
BCC and SCC are the two most commonly occurring cancers in the United States. Together, they comprise over 95% of all nonmelanoma skin cancers, accounting for over 1 million reported cases in 2004. Both tumors occur with increased frequency in fairskinned populations; however, BCCs outnumber SCCs by approximately 4:1. Exposure to ultraviolet radiation has repeatedly been identified as the single most significant factor in the etiology of both neoplasms. As a result, sunexposed areas of the skin are the most common locations of each tumor, with over 80% occurring on the face, scalp, neck, or dorsal hands. BCCs typically present as pearly pink papules with a rolled border and variable central ulceration (Figure 1). SCCs usually arise as a firm, erythematous hyperkeratotic papule or plaque (Figure 2).
Mohs micrographic surgery remains the gold standard for the surgical management of basal cell and squamous cell carcinomas. A review of over 10,000 cases of primary BCC treated with either standard surgical excision and traditional margin assessment or Mohs surgery revealed a long-term (> 5 year) recurrence rate of 10.1% for surgical excision vs 1.0% for Mohs surgery. For the management of recurrent BCC, the long-term recurrence rate for Mohs surgery was 5.6%, as compared to 9.8% for radiation therapy and 17.4% for surgical excision.
Equally superior results have been documented for the treatment of SCC with Mohs micrographic surgery (Figures 3 and 4). In a review of cases of SCC in the literature, Rowe et al reported recurrence rates of 3.1% for Mohs surgery vs 10.9% for surgical excision. For recurrent tumors, Mohs surgery yielded a recurrence rate of 10.0%, whereas surgical excision led to recurrences in 23.3% of cases.
Melanoma and Melanoma In Situ
Cutaneous melanoma is a neoplasm derived from melanocytes of the epidermis with the potential for both aggressive local growth and systemic spread. Melanoma in situ refers to a subtype of melanoma in which the neoplastic melanocytes are confined to the epidermis and associated adnexal structures without evidence of disease invading the adjacent dermis. The tumor typically presents as a brown to black patch, papule, or plaque with significant color variegation and border irregularity (Figure 5). The projected lifetime incidence of melanoma in the United States has increased to between 1% and 2%. Patient prognosis and staging are based on depth of tumor invasion (Breslow depth), tumor ulceration, nodal involvement, and the presence of local, in-transit, and systemic metastases.
Current guidelines for the surgical management of primary cutaneous melanoma are based on standard surgical excision, with increasing surgical margins depending on the depth of tumor invasion. Despite these recommendations, the potential therapeutic advantage of Mohs micrographic surgery to detect subclinical extensions of neoplastic cells missed by routine breadloaf sectioning and tissue conservation has prompted several clinicians to investigate the utility of this modality in the treatment of melanoma.
The first case series of melanoma patients treated with chemosurgery was reported by Frederic Mohs himself in 1950. His initial findings revealed local recurrence and survival rates comparable to those of traditional excisional surgery. Since that time, several other case series have documented similar or improved recurrence and survival rates with the use of Mohs micrographic surgery.[ 11-13] In the most recent and largest of these, Bricca et al reported a cohort of 625 consecutive patients with melanoma or melanoma in situ of the head and neck region who were treated with Mohs micrographic surgery. After a mean follow-up of 58 months, their results demonstrated local recurrence rates, metastasis rates, and disease-specific survival rates that were comparable to or better than those of historical controls for every Breslow stratification. In addition to increased tumor clearance, they found that this technique also provided tissue conservation in the majority of cases, as 6-mm margins were sufficient to clear 83% of melanomas.
• Controversies in Use for Melanoma—Despite recent encouraging results, several arguments remain against the use of Mohs micrographic surgery in the treatment of melanoma.
The first of these points concerns difficulties inherent to the histopathologic diagnosis of melanoma, and in particular melanoma in situ, on frozen tissue sections as compared to traditional paraffin(Drug information on paraffin)-embedded sections. Differentiating the neoplastic cells of melanoma in situ from the background melanocytic hyperplasia of chronically actinic-damaged skin on paraffin sections can be challenging for the dermatopathologist. This task becomes more difficult when frozen sections are utilized, and has led some authors to propose that frozen sections are unreliable in the detection of margins of melanoma in situ.
However, in a review of 221 specimens, Zitelli et al found frozen sections to have a sensitivity of 100% and specificity of 90% in the diagnosis of melanoma as compared with routine paraffin sections. This improvement in diagnosis is the result of advances in immunohistochemical staining, as melanocytes, whether present individually or in small clusters, are now more readily identified on frozen sections. Of these immunostains, melanoma antigen recognized by T cells (MART-1) has proven to be the most sensitive except in the case of desmoplastic melanoma, in which the use of S-100 is indicated.[16,17]
A second theoretical argument against the use of Mohs micrographic surgery for melanoma is the belief that by taking wide margins around the tumor, the primary tumor as well as small local micrometastases are being excised, resulting in improved local recurrence and long-term survival rates vs narrow but complete excision of the primary tumor alone. This theory has not been substantiated by the data on excision of melanoma, which through the years has resulted in a reduction of the recommended surgical margins for melanoma.[ 8,9] It is also contradicted by studies displaying improved local recurrence, metastasis, and survival rates for Mohs micrographic surgery in the treatment of melanoma as compared to historical controls treated with conventional surgical resection.[11-13]