Chapter 244. Mohs Micrographic Surgery

Mohs micrographic surgery (MMS) is a surgical technique developed to excise skin cancer under complete microscopic control. The fresh frozen tissue technique is used, which permits immediate examination of the specimen, and the tissue is oriented in a way to permit evaluation of all surgical margins. This is distinct from the traditional bread loafing technique used to process tissue specimens. A special orientation is combined with a precise mapping technique, which leads to maximal conservation of normal tissue. The technique was developed by Dr. Frederick Mohs approximately 80 years ago using a fixed tissue technique that relied on zinc chloride paste. The original term, chemosurgery refers to the use of the tissue fixative which is no longer used. As a result, the term chemosurgery is considered archaic.1 MMS has been described by various names such as chemosurgery, microscopically controlled excision, and microscopically oriented histographic surgery. The latter is an attempt at creating an acronym to replace the eponymous term Mohs.

In the past several decades, the mapping component has been retained but the procedure has been refined using frozen tissue rather than fixed tissue, which has permitted more efficient patient care. The advantages of MMS over conventional excisional surgery include maximum cure rate and optimal preservation of healthy tissue. The latter serves to enhance cosmetic outcome and preserve function where applicable. MMS is now recognized as the standard of care for the treatment of various skin cancers in indicated circumstances. The most common cancers treated by this method are basal cell carcinoma (BCC, 73%) and squamous cell carcinoma (SCC, 23%).2 A defining characteristic of MMS is that the surgeon acts to interpret the histopathologic specimens. Specifically, the MMS procedure requires a single physician to act in two integrated but separate distinct capacities as surgeon and pathologist. MMS is a highly technical procedure that requires meticulous attention to detail and considerable training and experience to achieve the expected high cure rates.

Mohs surgery is performed under local anesthesia in the office setting or in an ambulatory center. In unusual cases, where multiple cancers or complex malignancies are to be removed, sedation may be used.3 Prior to surgery, it is essential to have the patient affirmatively identify the biopsy site as very often the biopsy site may fade due to postbiopsy healing. It has been shown that in 25% of patients, who had prior biopsy, no remnants of tumor were found during MMS. 4 This is consistent with the fact that the inflammatory process may contribute to elimination of residual cancer cells after biopsy. The fundamental elements of MMS are listed in Table 244-1. A complete medical history and list of medications should be documented before surgery is performed. Anticoagulants are not contraindicated and data have shown that they should not be discontinued prior to MMS. 5 Once the patient is properly positioned, it is important to mark the clinical tumor border with a surgical pen. Local anesthesia is then obtained by injection (Fig. 244-1). Marking the clinical borders of the tumor is necessary since the local anesthetic may cause blanching that can obscure the tumor borders. The most commonly used local anesthetic is 1% or 2% lidocaine with 1:100,000–200,000 epinephrine (Fig. 244-2). After the surgical site is gently curetted to determine the clinical extent of the cancer, a specimen is taken using the Mohs technique. (Fig. 244-3). This is considered the first Mohs stage. A thin layer of tissue is excised using a scalpel and incising the skin at a 45° angle. Nicks are made in the surrounding tissue to denote tissue orientation and mapping (Fig. 244-4). In some cases, double nicks can help in the orientation of the tissue.6 Mapping of the tissue is a crucial step in MMS. The topographic map allows the Mohs surgeon to relate the microscopic findings to the excised tissue and the anatomic reference points at the surgical site (Fig. 244-5) The Mohs map is typically created by drawing freehand, using a template or digitally using computerized software (Fig. 244-6). The tissue is brought to the adjacent laboratory (another key element of the Mohs technique is the presence of a contiguous lab under the supervision of the Mohs surgeon). Color coding of specimens is critical. The Mohs technician or the surgeon marks the borders of the tissue with different colors to allow orientation relative to the Mohs map. Usually two dyes are used such as red and black or black and yellow (Fig. 244-7). One of the dyes is represented on the map as a solid line and the other as a dotted line. The tissue is then processed by a technician who is specifically trained in the en face method of sectioning. The tissue is frozen and is cut horizontally on a microtome. In contrast to traditional paraffin sections, which are cut vertically (bread-loaf sections) the Mohs sections theoretically allows 100% of the tumor margins (depth and periphery) to be examined. Most Mohs surgeons use hematoxylin-eosin stain (83%) and a minority use toluidine blue as the preferred stain. The latter stain helps distinguish basal cell carcinoma from hair follicles by highlighting mucopolysaccharides in the stroma.7 In between the Mohs stages, the wound is dressed temporarily and the patient waits either in the procedure room or in a dedicated waiting room. Slide preparation takes 20–30 minutes on average. Examination of the slides by the surgeon is then performed in the laboratory. Residual cancer noted microscopically is marked on the Mohs map and the process of excision, mapping, and processing is repeated until all margins are free of tumor (Figs. 244-8, 244-9). High quality frozen sections are mandatory for the success of MMS8 Figs. 244-10 and 244-11 illustrate how the Mohs technique ensures complete tumor removal. Once MMS is complete, the wound is evaluated and reconstruction is either performed at that time by the Mohs surgeon or the wound is allowed to heal by second intention. In complex cases, collaboration with other reconstructive surgeons may be indicated. Reconstructive surgery has become an important and integral aspect of the care of the skin cancer patient. The original chemosurgery defects healed by second intention, but the current defects that result from the fresh tissue technique permit primary closures, adjacent tissue transfer, and grafts. As a result, parallel advances in reconstructive surgery have been significant in the evolution of MMS.

Cost-Effectiveness of Mohs Surgery

Currently, the major indications for MMS are based on the anatomic location of the tumor, tumor size, histology, and patient considerations. Mohs surgery is typically used on the head and neck and for difficult or biologically challenging tumors elsewhere.

Mohs Surgery for Basal Cell Carcinoma

BCC accounts for approximately 75%–80% of all cases of non-melanoma skin cancer. This tumor has a predilection for the head and neck as it is related to ultraviolet light exposure. Despite an extremely low metastatic rate (0.0028%), BCC can be locally aggressive and cause significant tissue destruction. Of special importance are high-risk BCCs: those in the midfacial location (the so-called H zone which includes the nose, periocular region, lips, ears), recurrent and incompletely excised tumors, BCC with aggressive histological characteristics (sclerosing, basosquamous, infiltrative, and micronodular), BCC with perineural involvement, and BCC in which tumor size exceeds 2 cm. MMS is also very helpful in treating BCC with indistinct clinical borders. The aggressive tumor subtypes tend to be large, have ill-defined borders, and tend to recur when treated with other modalities. MMS has been shown to result in superior cure rates for high-risk BCCs compared with other approaches. Rowe et al found in their meta-analysis a recurrence rate of 10.1% for primary BCCs treated with simple excision, whereas MMS–treated lesions had only a recurrence rate of 1%.10 Other studies have confirmed that MMS yields the highest cure rate in primary tumors (98.6%–99%) and in recurrent tumors11,12 In the case of recurrent cancers, the 5-year recurrence rate of recurrent BCCs was 17% with simple excision and only 4.5% with MMS.11,13 A recent study in Europe showed that MMS is preferred over surgical excision for the treatment of recurrent facial BCC on the basis of significantly fewer recurrences after MMS than after surgical excision. However, because there was no significant difference in recurrence of primary BCC between treatment groups, treatment with surgical excision is probably sufficient in most cases of routine primary BCC.14 BCCs located on the ear, nose, eyelids, and lips have higher recurrence rates when treated by simple excision. The reason is believed to be the tendency of the surgeon to conserve as much tissue as possible, thus risking incomplete excision. Some of the aggressive subtypes of BCC (morpheaform, infiltrative) tend to recur in those locations. These aggressive subtypes may spread along scars, perichondrium, periosteum, perineurium, and fascial planes. The advantage of MMS as a tissue sparing technique was demonstrated for higher-risk BCCs requiring multiple stages of MMS.15 Large BCCs (>2 cm) tend to be more aggressive, and have a higher recurrence rate than smaller cancers. They are usually present for longer duration, allowing the cancer to penetrate the surrounding tissue more extensively. MMS is especially advantageous in this situation. Incompletely excised tumors tend to recur as more aggressive tumors 12%–41% of the time. Recurrent tumors tend to be subtle at first, but when they clinically reappear they can be aggressive, demonstrating extension along deep tissue planes. MMS for recurrent cancer yields the highest cure rates (93%–96%) compared to 80%–83% for other modalities.14

Mohs Surgery for Squamous Cell Carcinoma

Squamous cell carcinoma (SCC) is the second most common skin cancer among whites.16 More than 200,000 new tumors are estimated to occur in the United States each year, and there is a significant increase in the incidence of SCC around the world.17 Most cases of primary cutaneous SCC are induced by UV radiation. SCC may also occur on nonexposed skin in the pelvic area including the penis where the cause is usually infection with carcinogenic subtypes of human papilloma virus. Although SCCs and BCCs are treated similarly, they are biologically distinct. SCC metastasizes at a much higher rate and accordingly has a higher mortality rate than BCC even though its metastatic rate remains very low on an absolute basis. Metastases are more common in the setting of chronic scar (37.9%), or certain anatomic locations.18 The indications for MMS are similar to BCC, but additionally involve identifying and reducing the risk for metastasis. MMS permits tracking SCC along nerves or when the histology is highly infiltrative, thus increasing the chance of complete extirpation. As with BCC, histologic pattern is important in determining the potential aggressiveness. Tumors that are poorly differentiated and/or have perineural involvement have a worse prognosis. Locations such as the ear, penis, lip, and digits, lesions greater than 2 cm, and those occurring in scars carry a higher risk of metastasis and local recurrence. The five-year cure rate for primary SCC of the skin with MMS is 97.4% to 96.9% versus 92% (95%–82%) with simple excision, and 90% for radiation therapy.19 The difference in cure rate increases with the location such as primary SCC of the lip (97.7% vs. 89.5%) and ear (94.7% vs. 81.3%). For recurrent SCC, the cure rate with MMS is 94.1% to 90% versus 76.7% for simple excision and 65%–50% with radiation therapy. (Tables 244-2 and 244-3). The importance of MMS in the treatment of SCC with perineural invasion has also been documented.20,21 MMS has also been proven to be effective for treating Bowen disease with a 5-year recurrence rate of approximately 6%.22 Immunosuppressed patients including organ transplant patients have a disproportionate number of SCCs and also carry a greater risk of more aggressive disease. Recent studies show that SCC is up to 65 times as likely to develop in transplant recipients as in age-matched controls.23 Increased incidence, younger age at onset, higher incidence of multiple tumors, and increased biologic aggressiveness of SCC in these patients is manifested by an increased risk of local recurrence, regional and distant metastasis, and mortality. MMS is an important treatment option in these high-risk patients to minimize recurrence and mortality risks.24

Mohs Surgery for Cutaneous Melanoma

The role of MMS for management of malignant melanoma is highly controversial. Melanoma in situ (MIS), which typically occurs on sun-damaged skin, can be difficult to interpret on frozen section. A review of MMS for melanoma in situ indicated that the recurrence rates for melanoma in situ post-MMS varied from 0%–3.6%.25 One author claims that MMS for melanoma in situ can maximize the cure rate.26 At some centers, a modified MMS is used in which a 2- to 3-mm margin is excised beyond the final frozen section margin and submitted for permanent paraffin-embedded sections. These sections are processed in the MMS en-face method so that 100% of the peripheral margins are visualized. In addition, a technique of rush permanent sections has been described.27 The introduction of immunohistochemistry (IHC) staining may make MMS more reliable as a treatment for MIS. In one study 100% correlation was found between frozen sections stained with MART-1 and paraffin-embedded sections.28 Many surgeons who do perform Mohs surgery for MIS have begun to use intraoperative IHC to identify melanocytes in frozen sections, and MART-1 is currently the preferred immunostain. S100 and HMB-45 have traditionally been used to identify melanocytes but have variable sensitivity and specificity. Although the processing time of MMS frozen sections is less than with paraffin sections, it is still more labor intensive than traditional hematoxylin and eosin-based frozen sections. The need for more accurate diagnosis of MIS in MMS has led to the development of rapid permanent paraffin-embedded sections (R13) and rapid IHC staining.29

Mohs Surgery for Dermatofibrosarcoma Protuberans

Dermatofibrosarcoma protuberans (DFSP) is a rare spindle cell cutaneous tumor with low-grade malignancy. It is a slow growing tumor and, for many years, wide local excision has been the treatment of choice. MMS has become the preferred treatment in most clinical circumstances with recurrence rates as low as 1.3%.30

Mohs Surgery for Other Cutaneous Malignancies

MMS has been used to treat a wide range of cutaneous malignancies. The consensus indications outlined by the American Academy of Dermatology31 include verrucous carcinoma, keratoacanthoma, dermatofibrosarcoma protuberans, atypical fibroxanthoma, malignant fibrous histiocytoma, leiomyosarcoma, adenocystic carcinoma of the skin, sebaceous carcinoma, extramammary Paget disease, erythroplasia of Queyrat, oral and central facial paranasal sinus neoplasms, microcystic adnexal carcinoma, apocrine carcinoma of the skin, certain aggressive locally recurrent benign tumors, and Merkel cell carcinoma. All cutaneous malignancies that exhibit a contiguous pattern of radial growth and can be interpreted on frozen section should theoretically be amenable to MMS.

However, less than 2% of the tumors treated with MMS are rare cutaneous malignancies. For this reason, it is important to remember that because a lesion can be treated by MMS does not mean that it should be treated in that way. If the Mohs surgeon does not have experience in reading rare tumors and cannot collaborate with a dermatopathologist, the lesion is best treated in another fashion or by a more experienced Mohs surgeon. The introduction of immunostains in MMS in the last decade has created the opportunity to explore its use in treating other cutaneous tumors.32

Microcystic adnexal carcinoma has been shown to have only 5% recurrence rate with MMS.33 Treatment of primary sebaceous carcinoma of the eyelid with MMS has yielded excellent results.34 MMS is more effective and superior to standard surgical excision in the treatment of extramammary Paget disease.35 The effectiveness of MMS in the treatment of dermal spindle cell tumors has also been suggested.36

Safety, Patient Satisfaction and Complications

MMS is performed in an office or ambulatory center setting rather than hospital operating rooms. A study performed in almost 4,000 patients that underwent MMS showed that MMS can safely be performed in the office or outpatient hospital setting.37 Patients treated with MMS have well-established long-term satisfaction.38