eMedicine Specialties > Dermatology > Surgical

Mohs Micrographic Surgery

Author: Maureen Ann Mooney, MD, Partner, Cascade Eye and Skin Centers; Clinical Staff, Division of Dermatology, University of Washington
Coauthor(s): Edward Parry, MD, Fellowship Director, Clinical Professor, Department of Dermatology, Louisiana State University Medical School
Contributor Information and Disclosures

Updated: Feb 27, 2009

Introduction

Mohs micrographic surgery (MMS) is a surgical technique for the removal of certain cutaneous carcinomas that allows precise microscopic marginal control by using horizontal frozen sections. For example, MMS has become the treatment of choice for basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) at high risk for local recurrence.

The advantages of this technique as compared with those of other options for treating cutaneous neoplasms include the following:

• Superior cure rates
• Maximal tissue conservation
• Ability to trace perineural or infiltrating tumors histologically
• Low cost relative to that of radiation therapy, excision with frozen sections, or surgery in hospital operating rooms
• Negligible risk of complications from anesthesia, because of the almost exclusive use of local anesthesia in Mohs surgical procedures

For excellent patient education resources, visit eMedicine's Cancer and Tumors Center. Also, see eMedicine's patient education articles Skin Cancer and Skin Biopsy.

History

Frederic E. Mohs originated the technique of Mohs micrographic surgery while working as a cancer research assistant during medical school in the early 1930s. While testing the irritant effect of an intratumoral injection of 20% zinc chloride, he incidentally observed that the microscopic detail of the tissue was retained as if the tissue had been excised and immersed in a fixative solution. This observation was the genesis of the idea of excising cancer under microscopic control.

A zinc chloride paste was developed and used to fix cancer in situ. This paste enabled the tissue to be removed and examined microscopically. That is, the tissue was fixed while it was still on the patient by applying the paste to the tumor, which was then excised layer by layer, processed by using horizontally oriented sections, and microscopically examined. This method enabled 100% of the tumor margin to be examined. Thus, the fixed-tissue technique of Mohs chemosurgery evolved.

The technique offered remarkably high cure rates but also some drawbacks, including the following:

• The application of zinc chloride paste in situ was uncomfortable for the patient.
• Only one stage of Mohs surgery could usually be performed each day.
• Zinc chloride paste caused tissue necrosis; therefore, waiting for sloughing of any remaining fixed tissue postoperatively before reconstruction could be performed was necessary.

While making a film in 1953 to demonstrate the fixed-tissue technique for a BCC of the eyelid, Dr. Mohs performed the last few layers without fixative in order to expedite the process. The horizontal frozen sections he obtained worked so well that Dr. Mohs continued this fresh-tissue technique for all eyelid carcinomas. In 1969, he reported a 5-year cure rate of 100% using the fresh-tissue technique to excise eyelid carcinomas. Wide acceptance of the fresh-tissue technique increased substantially after the publication of Tromovitch and Stegman's series in 1974 and Mohs' series in 1976.

Additional advantages of the fresh-tissue technique compared with the fixed-tissue technique of Mohs surgery include the following:

• Avoidance of the pain caused by tissue fixation in situ
• Ability to perform multiple stages in one day
• Ability to repair the defect as soon as tumor-free margins are achieved

The term Mohs chemosurgery was originally used to denote the fixed-tissue technique; the term, Mohs chemosurgery: fresh-tissue modification, was used to denote the newer fresh-tissue technique. However, the use of chemo in the name was confusing to patients and physicians; as a result, the terms Mohs surgery and Mohs micrographic surgery came into existence. Currently, Mohs micrographic surgery is the official name for this surgical technique, whether fresh or fixed tissue is used, although the fresh-tissue technique is more commonly used than the fixed-tissue technique. The acronym MOHS, micrographically oriented histographic surgery, has also been proposed, but it has not achieved widespread recognition.

Changes in nomenclature have also occurred in the Mohs College as the terms have evolved. The first annual meeting of the American College of Chemosurgery occurred in 1967. In 1986, the American College of Chemosurgery changed its name to the American College of Mohs Micrographic Surgery because most surgeons were using the fresh-tissue technique rather than the fixed-tissue technique. In 1987, the name was again changed to the American College of Mohs Micrographic Surgery and Cutaneous Oncology (ACMMSCO) to more accurately reflect the clinical practices of its members.

As of October 2006, the ACMMSCO had approximately 800 members. To become a member of the ACMMSCO, a physician must complete a 1- or 2-year fellowship approved by the college.

Technique

The cornerstone of Mohs micrographic surgery is based on the observation that cutaneous neoplasms often grow contiguously with unpredictable, lengthy, rootlike extensions that can grow deeply or laterally from the clinically apparent lesion.

Traditional methods of tumor excision involve the removal of the clinically evident tumor along with an additional margin of normal-appearing tissue. The additional margin is removed because malignant extensions are microscopic; the malignant extensions cannot be clinically visualized or palpated. After the tumor is excised, conventional microscopic processing is used to check the margins of the specimen for residual tumor. Representative vertical sections may be obtained at 2- to 4-mm intervals throughout the specimen by using the bread-loaf method and in each of 4 quadrants by using the quadrant method.

When the tissue sample is microscopically seen to be tumor free, the entire margin from which the sample was obtained is also assumed to be tumor free. However, a tumor that is determined to have clear margins by using this method may have fingerlike extensions in the unexamined intervals, because less than 1% of the interface between the specimen and the patient is actually examined histologically. The failure of these methods to permit consistent identification of residual tumor explains the incidence of local recurrence despite the finding of margins that appear to be tumor-free.

When the horizontally oriented Mohs micrographic surgery technique is used to examine surgical margins, almost 100% of tumor margins are microscopically examined, as opposed to approximately 0.01% with traditional histologic methods.

Fresh-tissue technique

The process of performing the fresh-tissue technique of Mohs micrographic surgery varies according to individual practices among physicians, but the basic procedure as described below.

In step 2, after waiting several minutes for maximal anesthesia and vasoconstriction, some surgeons use a curette to debulk the tumor, which tends to be softer than the surrounding normal skin, to better delineate its extent. However, this method may be ineffective with morpheaform BCCs or other nonfriable tumors.

In step 3, to allow precise orientation of the specimen, some surgeons tattoo the tumor with a substance such as methylene blue, whereas others use hatch marks, sutures, staples, or superficial scalpel incisions at the periphery of the specimen.

In step 4, the tissue is then excised with the scalpel angled 45° to the skin to bevel the edge to facilitate histologic processing. The excision is continued circumferentially around the tumor at a 45° angle and under the skin parallel to the surface so that the deep margin is excised horizontally.

In step 5, hemostasis is achieved by using spot electrodesiccation, suture ligatures, Surgicel/Oxycel, pressure, or other methods.

In step 6, a 2-dimensional map of the patient's defect is drawn. This map incorporates the hatch marks, sutures, staples, or incisions used to orient the specimen.

In step 7, the tissue is divided along the tattooed or scored lines and inverted (dermis turned up). The edges of the specimen are then color-coded with tissue dyes.

In step 8, the technician mounts the tissue as it is presented, flattening the undersurface in an even horizontal plane. The technician then cuts 5- to 7-µm horizontal frozen sections of each tissue specimen by using a cryostat. By compressing each saucerized piece of tissue and sectioning the specimen horizontally from the deep margin upward, the entire undersurface and epidermal margin of the excised specimen is theoretically processed. Histologic preparation for microscopic examination in Mohs micrographic surgery requires skill and practice. Minor variations in technique may exist.

In step 9, the slides are stained (usually with hematoxylin-eosin or toluidine blue). The Mohs micrographic surgeon, who also serves as the pathologist, interprets the results.

In step 10, any residual neoplasm is marked on the map in red ink. The surgeon can then precisely remove additional tissue where residual tumor is identified. In this manner, uninvolved tissue is preserved because only the areas with residual tumor are sequentially removed.

In step 11, with the fresh-tissue technique, the resulting defect can be reconstructed immediately.

Coordinating the roles of the dermatologist, pathologist, cutaneous and/or oncologic surgeon, and reconstructive surgeon ensures the least amount of error when the histopathologic and clinical findings of each patient are correlated.

Fixed-tissue technique

The fixed- and fresh-tissue techniques are similar. However, the fixed-tissue technique differs because the tissue fixation is accomplished before excision; this process eliminates the need for anesthesia and creates a blood-free surgical field.

The fixed-tissue technique is used infrequently; however, some surgeons find it helpful in certain circumstances. For example, the blood-free field may be useful for penile carcinomas because of the associated vascularity of the tissue.

The fixed-tissue technique is as follows.

In step 1, the tumor is debulked with a curette, and dichloroacetic acid is applied to increase the penetration of the zinc chloride paste and facilitate hemostasis. The dichloroacetic acid is a keratolytic agent; therefore, heavily keratinized areas require the application of more of the agent, whereas ulcerated surfaces do not necessarily require application of the acid.

In step 2, a layer of zinc chloride paste is applied. This paste consists of a combination of stibnite, bloodroot powder (Sanguinaria canadensis), and a saturated solution of zinc chloride. The thickness of the layer depends on the depth of penetration desired.

In step 3, the fixative paste is covered with an occlusive dressing to protect the adjacent uninvolved skin; this paste remains in place for 6-24 hours. The penetration of this potent fixative depends on many factors, including the amount applied, the duration of application, the vascularity of tissue, and the type of tissue. The fixative is used sparingly if tissue conservation is critical, such as when the tumor is located on the nasal ala or pinna of the ear.

In step 4, after tissue fixation, the fixed-tissue technique is performed in a manner similar to the fresh-tissue technique. With the scalpel angled 45° to the skin (thus beveling the edge), an incision is made in the fixed tissue near the border of the unfixed tissue and continued in the fixed tissue parallel to the skin surface. After microscopic examination of the tissue sections, additional fixative is applied to any remaining areas of tumor involvement for another 6-24 hours.

In step 5, residual tumor is excised in the same manner, generally at a rate of one stage of excision per day.

In step 6, when a tumor-free defect is achieved, the remaining fixed tissue is allowed to slough; this process generally takes a few days.

In step 7, the defect can then be repaired or allowed to heal by means of secondary intention.

Special stains

In recent years, immunostaining has facilitated the successful removal of a number of cutaneous malignancies. Selective labeling of malignant cells can help to more clearly delineate tumors that may be masked by inflammation and is helpful when a tumor presents with subtle or nonspecific histologic features.

Examples of immunostaining techniques include antikeratin for BCC and SCC, anti-CD34 for dermatofibrosarcoma, MART-1 for malignant melanoma, and anticarcinoembryonic antigen for extramammary Paget disease (EMP). However, the disadvantages and limitations of incorporating immunohistochemistry into a Mohs surgery practice include the additional processing time and cost involved, as well as more time-consuming interpretations. However, progress continues to be made in an effort to make immunostains more cost effective.
 
For example, Kimyai-Asadi and colleagues reported a 20-minute rapid MART-1 immunostaining protocol that has significantly improved the efficiency in the workflow.¹ As research and development advance, the use of immunohistochemistry in Mohs surgery is expected to become a more widely used technique.

Indications: BCC and SCC

Mohs micrographic surgery has become the treatment of choice for BCCs and SCCs at high risk for local recurrence. Although most low-risk BCCs and SCCs can be successfully treated by using routine methods (eg, curettage and electrodesiccation, excisional surgery, cryosurgery), high-risk tumors are best treated with Mohs micrographic surgery. For example, a superficial type of BCC on the arm usually is easily treated with routine methods because of its nonaggressive histologic growth pattern and nonfacial location.

Basal cell carcinoma

All recurrent tumors or high-risk primary tumors with 1 or more of the following features are candidates for Mohs micrographic surgery:

• Aggressive histologic growth pattern
  • Sclerosing BCC (morpheaform BCC)
  • Infiltrating BCC
  • Metatypical BCC
  • Keratotic BCC
  • Contiguous tumors (BCC and SCC)
  • Multicentric BCC
  • Clinically ill-defined micronodular BCC
  • Perineural and perivascular growth patterns
  • Field-fire BCC
  • Deep tissue or bone involvement
• Location in anatomic sites at which conventional treatment modalities have a higher potential risk of recurrence
  • Periorbital and canthal regions
  • Central third of the face
  • Columella
  • Periauricular-tragal region
  • Postauricular sulcus region
  • Perioral region
  • Nasofacial sulcus and perinasal region
• Location at anatomic sites that require tissue conservation for optimal reconstruction
  • Nasal tip and alae
  • Lips, both cutaneous and vermilion
  • Eyelids
  • Auricular helix and canal
  • Hands and feet
  • Genitalia
  • Other
• Large size (>2 cm)
• History of incomplete removal
• Rapid growth or aggressive clinical behavior
• Tumors in patients with immunosuppression
• Tumors arising in patients with a history of previous radiation therapy
• Tumors in young patients, especially facial lesions in young women
• Patients with basal cell nevus syndrome
• Long-standing or neglected tumors

Recurrent tumors

Mohs micrographic surgery is an excellent therapy for any recurrent tumor. BCCs tend to grow along the path of least resistance. When a tumor is excised and the wound is closed, the entire area of undermining provides a plane for extension of any incompletely excised tumor. Fibrosis from previous excisions and radiation can restrict the growth of a recurrent BCC and cause it to grow in unpredictable patterns. As a result, recurrent tumors tend to have much higher recurrence rates after conventional excision than primary tumors. Although Mohs micrographic surgery can result in the successful removal of recurrent tumors in 96% of the cases, conventional treatments achieve success only approximately 50% of the time.

Incompletely excised tumors

Tumors with pathologically reported positive margins persist and recur in 33-43% of cases followed up for 2-5 years. Mohs micrographic surgery is an excellent way to treat these lesions, because it enables microscopic tumor extensions to be tracked precisely. Mohs micrographic surgery is indicated before recurrence occurs.

Aggressive histologic subtypes

Tumors with an aggressive histologic nature (eg, micronodular, infiltrative, sclerosing/morpheaform, or keratinizing BCCs) have a higher rate of recurrence than nodular or superficial BCCs. Tumor removal with conventional margins is shown to result in incomplete removal at a rate of 6.4% for nodular BCC and 3.6% for superficial BCC. In contrast, the clinically ill-defined micronodular, infiltrative, and morpheaform tumors have much higher rates of incomplete removal of 18.6%, 26%, and 33.3%, respectively.

The high rates of recurrence of these latter histologic subtypes with conventional excision reflect the degree of subclinical spread, which may not be adequately demonstrated on routine histopathologic examination. For example, morpheaform BCCs have subclinical extensions that average 7.2 mm beyond the clinically apparent tumor margins.

A field-fire BCC is a type of BCC with discontinuous multicentric foci that may be a result of previous irradiation to the area, exposure to other carcinogens, or recurrence of the primary tumor at multiple foci. This type of tumor is best treated with Mohs micrographic surgery, because the margins of field-fire BCCs are difficult to determine clinically.

Location

Cosmetically and functionally critical areas of the face that require tissue conservation at the time of surgery include the nasal ala, columella, junction of the ala with the nasolabial fold (ie, nasofacial sulcus), medial and lateral canthi, eyelids, preauricular and postauricular areas, philtrum, and vermilion borders of the lips. Other areas in which tissue conservation is important include the hands, feet, and anogenital areas.

Many of these anatomic areas also have unusually high recurrence rates for skin cancers that arise within them. Recurrence rates for primary BCC in these areas treated with conventional methods are as high as 43% on the lateral canthus, 33% on the superior orbital rim and brow, 24% on the ear, and 19% on the nose. In contrast, only 0.5% of primary BCCs located on the neck, trunk, and extremities treated with conventional methods recur within 5 years. Certain areas on the scalp also have high recurrence rates.

Size

The rates of success in treating BCC with conventional surgical methods decrease with increasing tumor size. After treatment with standard modalities, primary BCCs smaller than 6 mm recur in 3.2% of the cases, those 6-9 mm recur in 5.2-8% of the cases, and BCCs larger than 9 mm recur in 9% of the cases. Tumors larger than 0.6-1 cm on the face and those larger than 2 cm on the trunk and extremities are best treated with Mohs micrographic surgery for a maximal rate of cure.

Recurrence rates and treatment

Table 1. Recurrence Rates

Open table in new window

*Less than 5 years, no statistics for 5-year follow-up.

Table 2. Treatment of BCC

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Squamous cell carcinoma

SCC is the second most common skin cancer in whites and the second most common tumor treated with Mohs micrographic surgery. Cutaneous SCCs are responsible for 2000-5000 deaths annually in the United States. Most cutaneous SCCs are at low risk for recurrence or metastasis. Small, well-differentiated, primary SCCs on actinically damaged skin have a metastatic rate of 1% or less and are easily treated with standard modalities (eg, curettage and electrodesiccation, excisional surgery, cryosurgery). However, a subset of these tumors may be aggressive; these present more of a challenge to the surgeon because of their increased ability to metastasize.

The metastatic rate of SCC varies depending on the tumor's degree of histologic differentiation, size, depth of invasion, and location; on the presence of perineural or perivascular involvement; and on the underlying medical conditions, such as immunosuppression. Metastasis most commonly occurs after previous unsuccessful treatment. Therefore, appropriate initial therapy of SCCs is critical.

Mohs micrographic surgery is the treatment of choice for high-risk SCCs; it has a local recurrence rate of 3% compared with 13% for all non–Mohs micrographic surgery modalities. Recurrent tumors have a 25-45% metastatic rate, depending on anatomic site. The 5-year survival rate for metastatic SCC is only 25%. The recognition and successful treatment of high-risk tumors is important for patient survival. The criteria for high-risk SCCs are listed below. SCCs that meet these criteria are best treated with Mohs micrographic surgery.

Factors that indicate a high risk for local recurrence or metastasis include the following:

• Large size (>2 cm)
• Depth of invasion greater than 4 mm
• Recurrent tumors
• Histologic subtype
  • Undifferentiated
  • Poorly differentiated
  • Acantholytic (pseudoglandular)
• Anatomic site
  • Periorbital and canthal region
  • Central third of the face
  • Columella
  • Ear
  • Preauricular-tragal region
  • Postauricular sulcus
  • Lower extremities
  • Genitalia
  • Temple
  • Scalp
  • Lip (cutaneous and mucosal areas)
  • Other mucous membranes
  • Nail bed and matrix
• Perineural or perivascular invasion
• Rapid growth
• Long duration
• History of incomplete removal
• Tumors in patients with immunosuppression
• Ionizing irradiation–induced lesions
• Tumors arising in certain areas
  • Previously irradiated skin
  • Thermal and radiation scars
  • Chronic sinus tracts and ulcers
  • Chronic osteomyelitis
  • Lichen sclerosis et atrophicus
  • Discoid lupus erythematosus
• Certain genodermatoses

Size and depth

The size of the tumor and the depth of invasion are the 2 most important prognostic factors. Most metastasizing cutaneous SCCs are reported to be greater than 2 cm in diameter. Tumor invasion deeper than 4 mm, or Clark level IV and V tumors, have higher metastatic and recurrence rates than those with invasion of less than 4 mm. Rowe et al reported that SCCs with a depth less than 4 mm, or Clark level I-III, have a local recurrence rate of 5.3% and a metastatic rate of 6.7%. Lesions deeper than 4 mm, or Clark level IV or V tumors, have a local recurrence rate of 17.2% and a metastatic rate of 30.3%.

Recurrent tumors

Recurrent tumors have a metastatic rate of 25-45%, depending on anatomic site. Because metastases occur most commonly after previous unsuccessful treatment, Mohs micrographic surgery is the treatment of choice for recurrent tumors. With Mohs micrographic surgery, the local recurrence rate for these tumors is reported to be 10%, compared with 23% with standard excision.

Histologic subtype

Most SCCs are small, are well differentiated, and arise on actinically damaged skin. These SCCs are nonaggressive and have a metastatic rate of less than 1%. Poorly differentiated histologic features are seen in only 19.1% of all cutaneous SCCs but accounts for 51% of SCCs that metastasize. These tumors have more than double the recurrence rate and 3 times the metastatic rate of well and moderately differentiated SCCs. Adenoid (eg, pseudoglandular, acantholytic) SCCs also have an increased rate of metastases.

Anatomic site

Mohs surgery is indicated for SCCs that arise in locations at high risk for recurrence or metastases. In particular, the ear and mucous membranes are sites consistently reported to have a higher risk of metastases. Metastatic incidences of 11% and 13.7% are reported for SCCs on the ear and lips, respectively. SCCs of the penis, scrotum, and anus have higher metastatic rates than SCC of the lip. Other areas at high risk include the periorbital and canthal areas, central third of the face, columella, lower extremities, temple, scalp, and nail bed and matrix.

SCCs within a burn scar, those within a site of previous irradiation, and those induced by chronic osteomyelitis have an incidence of metastasis of 18%, 20%, and 31%, respectively.

Perineural or perivascular invasion

SCCs with perineural invasion are at greater risk for recurrence, lymph node metastases, and distant metastases. The more aggressive SCCs often show perineural invasion. Recurrent SCCs and the larger SCCs are examples of tumors that are more likely to involve perineural invasion. Perineural invasion is reported in 64% of tumors with a diameter of 2.5 cm or larger, but only in 11% of tumors with a diameter of 2.5 cm or less involve perineural invasion.

Tumors with perineural invasion have a local recurrence rate of 47.2% and a metastatic rate of 47.3%. With perineural invasion, the local recurrence rate after standard excision followed by radiation is almost 50%. Radiation therapy alone is reported to result in an 80% recurrence rate. The treatment of choice for SCC with perineural invasion appears to be Mohs micrographic surgery followed by radiation therapy. Three studies of this combined treatment involving a total of 32 patients demonstrated a recurrence rate of 6%. However, the cases in these series were followed up for less than 3 years. Studies with longer follow-up periods and larger numbers of patients are ongoing.

Rapid growth

SCCs that visibly enlarge between the time of diagnosis and treatment are especially aggressive. The metastatic rate of rapidly growing tumors on the ears and eyelids is 3 times that of slower growing SCCs.

Indications: Other and Unusual Tumors

Other tumors

Mohs micrographic surgery is applied to many different types of tumors in different clinical settings. While its use and application is clear and straightforward in most instances, its use for the treatment of certain tumors is controversial because of various factors (eg, multifocality, discontinuous growth patterns, in-transit metastasis, inherent disadvantages of frozen sections vs permanent sections). The following discussion focuses on the less controversial additional indications for Mohs micrographic surgery.

Verrucous carcinoma^2,3

Verrucous carcinoma is a distinctive clinicopathologic variant of SCC that most commonly affects the mouth (eg, oral florid papillomatosis), foot (eg, epithelioma cuniculatum), and penis (eg, giant condyloma of Buschke-Löwenstein). Although verrucous carcinoma rarely metastasizes, it penetrates deeply, invading contiguous structures. Although tumors treated with excision have a cure rate of 80%, the reported cure rate with Mohs surgery approaches 98%.

Keratoacanthomas^4,5,6,7,8,9

Keratoacanthomas (KAs) are cutaneous tumors that histologically resemble SCCs, but they have a tendency to spontaneously involute. Several reports of metastatic KAs exist. Whether these tumors were KAs or misdiagnosed SCCs or whether KAs actually are a variant of SCC is debatable. KAs are reported to have a recurrence rate of 8%. Similar to SCC, recurrent KAs are often histologically aggressive and can metastasize.

A KA can cause extensive local destruction, particularly if it arises on the eyelid or nose, before regression occurs. This extensive local destruction is especially problematic with some of the variants of KA, such as giant KA, KA centrifugum marginatum, and subungual KA. For example, giant KAs can become larger than 9 cm and have a predilection for the nose and dorsum of the hands. Predicting which KAs will progress to the giant variant by either clinical or histologic means is not possible.

Because of the unpredictability of spontaneous regression and their potentially destructive nature, recurrent KAs and KAs near vital structures (where tissue conservation is warranted) are ideally treated with Mohs micrographic surgery.

Extramammary Paget disease^{10,11,12,13,14,15,16,17}

EMP begins as an erythematous eczematoid, slowly spreading plaque that usually affects sites with a high density of apocrine glands (eg, vulvar, perineal, perianal regions). The penis, axillae, umbilicus, eyelids, and external auditory meatus are less common sites.

The histogenesis of EMP remains controversial. EMP is usually a primary tumor; however, it may be secondary to an adnexal or visceral carcinoma. Approximately 25% of cases have an underlying cutaneous adnexal carcinoma; this carcinoma is mostly of the apocrine type, but it is sometimes derived from eccrine, periurethral, perianal, or Bartholin glands. In addition, 10-15% of patients have an internal carcinoma that appears to be of etiologic significance. In these cases, the epidermal pagetoid cells are thought to represent epidermotropic metastases. The prognosis in cases associated with an underlying malignancy is poor, with a mortality rate of 50% or higher.

Local recurrence of EMP is common because of histologic extension beyond the clinically apparent extent of the tumor. The recurrence rate with standard excision is 31-61%, whereas Mohs micrographic surgery has fared somewhat better with recurrence rates of 23-33%. The high rate of recurrence despite visualization of the entire tumor margin is thought to be due to the multifocal growth pattern of this tumor. Some surgeons use topical fluorouracil before performing Mohs excision. The fluorouracil causes marked inflammation and erythema of the involved skin, which better delineates the margins of the tumor.

A rapid carcinoembryonic antigen stain is used to distinguish between artifactual vacuoles and pagetoid cells with routine hematoxylin and eosin staining.

Mohs micrographic surgery is advantageous for the treatment of EMP because of its lower recurrence rate and tissue-sparing capability in critical areas such as the anogenital region.

Microcystic adnexal carcinoma^{18,19,20,21,22,23}

Microcytic adnexal carcinoma (MAC), also referred to as sclerosing sweat duct carcinoma, is a more recently described, uncommon, malignant eccrine tumor that is known for its aggressive local invasion of tissue.

At histologic examination, the superficial component is made up of numerous keratinous cysts, small islands and strands of basaloid cells, and squamous epithelium with variable ductal differentiation. The deeper component has smaller nests and strands of cells in a dense, hyalinized stroma. When superficial biopsy is performed, the histologic features of a MAC can be mistaken for those of tumors such as a BCC, SCC, syringoma, or desmoplastic trichoepithelioma.

Clinically, MAC most often appears as a solitary flesh-colored indurated plaque on the face of middle-aged women. Because of its nondescript appearance and clinical and histologic resemblance to other benign and malignant neoplasms, MAC is incorrectly diagnosed in 30% of the cases.

MAC rarely metastasizes; however, it usually involves deep soft tissue and dermis and has a propensity for perineural invasion.

Because MAC grows contiguously, it is well suited for removal with Mohs micrographic surgery. Local recurrences after traditional excisional surgery approach 47%. However, the relative rarity of this tumor has rendered comparative trials regarding treatment difficult.

A report of a retrospective study involving 48 cases with a mean follow-up time of 3.2 years was recently published. The study showed that Mohs micrographic surgery is clearly advantageous compared with standard excision with respect to the number of procedures required for cure. Of 23 patients treated with standard excision at the onset, 7 (30%) required at least 1 other procedure compared to none (0%) of 22 treated with Mohs micrographic surgery. In addition, standard excision is more likely to lead to a larger defect than Mohs micrographic surgery. Mohs micrographic surgery should be strongly considered as a first-line modality for the treatment of MAC.

Dermatofibrosarcoma protuberans^{24,25,26,27,28,29,30,31,32,33,34,35,36,37,38}

Dermatofibrosarcoma protuberans (DFSP) is an uncommon, slow-growing, locally aggressive tumor with a marked tendency for local recurrence, but it rarely metastasizes. Although DFSP is traditionally thought to be of fibrohistiocytic lineage, the histogenesis is presently in dispute.

Wide surgical excision with a margin of at least 3 cm down to the fascia is the recommended treatment. Despite the wide surgical margins, multiple recurrences are frequently reported. Multiple recurrences after inadequate initial treatment may result in the dedifferentiation of the tumor into high-grade sarcomas, with a subsequent increased risk of metastasis.

One review of the world literature revealed a recurrence rate of 1.6% when Mohs micrographic surgery was used for the treatment of DFSP versus a 20% recurrence rate with wide excision. One study showed that if standard excisions are performed, margins of 1 cm around the primary tumor left microscopic residual tumor in 70.7% of cases. Margins of 2 cm left residual tumor in 39.7%; margins of 3 cm, 15.5%; and margins of 5 cm, 5.2%. Some tumors were not completely excised with 10-cm margins.

During Mohs micrographic surgery, delineating the true borders at the periphery of the specimen can occasionally be difficult because sparse malignant cells may resemble normal fibroblasts. The immunostain CD34 is selectively expressed by DFSP, and its use should improve the ability to differentiate the neoplastic cells from fibroblasts. CD34 is also used to detect those cells masked by inflammation.^39,40 At times, Mohs micrographic surgery may be followed by excision of a conservative additional margin for permanent section evaluation to ensure the removal of all involved tissue to the greatest extent possible.

Mohs micrographic surgery is well established for the treatment of primary and recurrent DFSPs and is suggested as the treatment of choice for DFSP.

Sebaceous carcinoma^41,42,43

Sebaceous carcinoma (SC) is an uncommon aggressive malignant tumor derived from the adnexal epithelium of the sebaceous glands. SCs can arise in ocular or extraocular sites, and they have such diverse clinical presentations and histologic growth patterns that the diagnosis often is delayed for months to years.

Both ocular and extraocular SCs have high rates of recurrence (33-34%) and distant metastases (30-32%). The high rate of recurrence of SC may result from misdiagnosis that results in undertreatment. SCs may have multicentric, noncontiguous foci and pagetoid or intraepithelial spread that results in incomplete excision of SCs with either traditional methods or the Mohs micrographic surgery technique.

Several early reports demonstrated success with Mohs micrographic surgery, and some advocate its use as the treatment of choice for SCs that do not involve the orbit, regional nodes, or distant organs. Mohs micrographic surgery offers the potential for maximal tissue conservation and the highest cure rate. However, in these situations, paraffin-embedded sections, oil red O staining of frozen sections, and other techniques are used to assist in determining tumor-free margins. Careful clinical and radiologic follow-up is recommended.

Atypical fibroxanthoma⁴⁴

Atypical fibroxanthoma is a low-grade malignancy that is thought to be a superficial variant of a malignant fibrous histiocytoma. This tumor is most often seen in actinically damaged skin on the head and neck of elderly patients, but sporadic cases are reported on the trunk and extremities.

Conventional surgery is considered the mainstay of therapy because recurrence rates are typically less than 10-16%. Atypical fibroxanthomas are successfully treated with Mohs micrographic surgery, and preliminary results show the potential for lower rates of recurrence in addition to maximal tissue conservation. To the author's knowledge, because of the low number of cases, no studies have been performed to adequately compare the effectiveness of Mohs micrographic surgery versus conventional excision.

Malignant melanoma^1,45,46

The issue of treating melanoma with Mohs micrographic surgery is controversial. In frozen sections of severely sun-damaged skin, even clinically uninvolved skin may have atypical keratinocytes, a loss of normal epidermal architecture, and atypical melanocytes that may simulate in situ melanoma and result in false-positive margins. Because of these observations, some advocate the use of paraffin-embedded sections or special stains. Several immunostains are available for melanoma that can be used on frozen sections. These include HMB-45, S-100, Mart-5, and Melan-A (A-103). However, those who use frozen sections alone cite impressive results with Mohs micrographic surgery and achieve survival and metastatic rates comparable to those of wide surgical excision. In addition, they achieve narrower excision margins without a higher risk of local recurrence due to incomplete excision.

The advantage of the Mohs technique is that 100% of the surgical margin of the specimen, including the periphery and undersurface, is examined. In contrast, only 0.01% of the margin is sampled when a standard surgical pathologic technique is used. The maximal amount of normal tissue is conserved with the Mohs method; this is of particular value in treating tumors on the face or in other critical areas.

Unusual tumors

Many other cutaneous neoplasms (see list below) are treated by using the Mohs micrographic surgery technique. Mohs micrographic surgery is used alone or as an integral part of an overall treatment approach for these unusual neoplasms. However, the small number of such cases precludes any conclusions about the utility of this technique.

• Adenoid cystic carcinoma of the skin⁴⁷
• Angioendothelioma
• Angiosarcoma⁴⁸
• Apocrine carcinoma of the skin
• Certain aggressive locally recurrent benign tumors
• Eccrine adenocarcinoma¹⁶
• Erosive adenomatosis of the nipple⁴⁹
• Erythroplasia of Queyrat
• Glandular carcinoma
• Granular cell tumor
• Hemangioendothelioma
• Hemangiosarcoma
• Leiomyosarcoma^50,51,52
• Liposarcoma
• Lymphoepitheliomalike carcinoma of the skin
• Malignant cylindroma
• Malignant fibrous histiocytoma^53,54
• Malignant schwannoma
• Neuroendocrine carcinoma of the skin (Merkel cell carcinoma)
• Oral and central facial paranasal sinus neoplasms
• Other tumors that are histologically contiguous with locally aggressive growth

Preoperative Evaluation

Preoperative planning

Preoperative planning for MMS is important to ensure that the surgery is as uneventful and safe as possible. The Mohs surgeon thoroughly investigates and evaluates the patient's history and previous treatment, as well as gross appearance and histopathologic features of the skin tumor. During the Mohs surgical consultation, the MMS technique is thoroughly explained to the patient; the surgeon discusses the advantages and disadvantages of MMS compared with other therapeutic options, as well as possible complications of the surgery. Wound care and reconstructive options are also discussed with the patient.

Interdisciplinary cooperation with other specialists may be necessary if the Mohs surgeon anticipates an extensive or high-risk defect that requires specialized repair or use of an additional therapeutic modality. If interdisciplinary cooperation is necessary, consultation with the appropriate specialist should be initiated prior to the day of the Mohs surgery, and care should be coordinated between the Mohs surgeon and the other specialists.

Inquiries are made regarding the patient's general health, prior operations or hospitalizations, medications, and allergies, as well as their social and occupational situation. The Mohs surgeon should specifically ask about any conditions that may cause a problem during or after surgery. The surgeon should be aware of an underlying diabetes mellitus, cardiovascular or pulmonary compromise, history of prolonged bleeding, or tendency for keloid and/or scar formation.

Certain medications may also need to be discontinued prior to surgery. Inquiries should be made about the patient's use of aspirin, warfarin sodium (Coumadin), heparin, dipyridamole (Persantine), vitamin E, clopidogrel bisulfate (Plavix), ticlopidine hydrochloride (Ticlid), niacin, fish oil tablets (omega-3 fatty acids), and nonsteroidal anti-inflammatory medications. These medications should be stopped or modified if possible after consultation with the prescribing physician. All other medications should be taken as prescribed, even on the morning of surgery.

Prophylactic medications

During the consultation, the Mohs surgeon also determines whether prophylactic antibiotics are necessary. The American Heart Association (AHA) recommends the use of prophylactic antibiotics for dental and/or oral and/or upper respiratory tract procedures, as well as some genitourinary and/or gastrointestinal procedures, in patients with high- or moderate-risk cardiac conditions to prevent the development of bacterial endocarditis.

Mohs surgery does not usually fall into any of the above categories; however, many authorities advocate the use of prophylactic antibiotics for Mohs surgery (or other lengthy surgical procedures) for patients with a history of prostheses (valves or joints), nonphysiologic heart murmurs or valvular disease, or mitral valve prolapse. Consideration is also given to those patients who are diabetic or immunosuppressed. In addition, if a graft or flap is used to close the wound and antibiotics are not given prophylactically, antibiotics are often given for a week after the procedure.

The most commonly used antibiotics for prophylaxis include dicloxacillin and cephalexin (2 g PO 1 h prior to surgery). For patients who are allergic to penicillin, this author uses either cefdinir (600 mg 1 h prior to surgery, unless the patient had an anaphylactic reaction to penicillin), azithromycin (500 mg PO 1 h prior to surgery) or clindamycin (600 mg PO 1 h prior to surgery).

Miscellaneous considerations

Many of the patients undergoing the MMS procedure are elderly and may have cardiovascular conditions that must be assessed. However, because the technique is usually performed by using local anesthesia, cardiovascular conditions are less of an issue. Procedures in patients with pacemakers and defibrillators may require special planning.

In addition to ascertaining the medical history of the patient, other miscellaneous considerations should be addressed. For example, patients should not drink alcohol 24 hours prior to the procedure or 48 hours after the procedure to reduce the risk of bleeding. Cigarette smokers should be advised to decrease smoking to the greatest degree possible for 1 week before and 1 week after surgery to decrease the risk of tissue necrosis.

All patients should eat a light breakfast prior to the Mohs procedure and bring along a snack because the procedure is lengthy and may deplete the patient's energy and alter the blood sugar level. Patients should also be instructed to wear casual, warm, layered clothing with buttons, rather than pullover clothing. Arrangements should be made to have the patient escorted home after the surgery; in most cases, the patient should not be allowed to leave the facility alone.

Disadvantages, Limitations, and Complications

Disadvantages

Disadvantages of MMS include the following:

• The procedure may become tedious, prolonged, and exhausting for the patient; especially if the case is difficult or complex.
• An inability to remove a large or difficult tumor in one day may preclude immediate reconstruction after complete excision.
• If the surgeon uses an unnecessarily large number of stages to clear small tumors on a routine basis, the cost of treatment may be high.
• MMS requires a specially trained dermatologist and ancillary personnel.
• Multiple injections of local anesthetic can cause discomfort for the patient.

As previously discussed, MMS is usually an outpatient procedure. On average, the Mohs procedure takes 3 hours to complete; however, some cases may take an entire day or longer. Additional time may be required when tumors are more extensive than usual. In these cases, the procedure may become prolonged, tedious, and exhausting for the patient. In addition, reconstruction by a different specialist may require delayed closure (that is, a separate surgical procedure, perhaps on another day, to repair the defect).

MMS is cost-effective because of its high cure rate and because it is usually performed with local anesthesia on an outpatient basis. The cost of MMS compares favorably with that of excision with frozen-section interpretation. The difference is that superior cure rates are obtained with MMS because of the complete review of the surgical margin with horizontally oriented tissue processing, and MMS requires only one specialized provider to serve as the surgical oncologist, pathologist, and reconstructive surgeon. However, if MMS is used in skin cancers that could adequately be treated with routine modalities (eg, curettage and desiccation), it no longer remains cost- effective.

Limited accessibility may be a problem in some communities because of the need for a dermatologist with specialized training and for ancillary support personnel trained in performing the procedure.

Limitations

MMS is indicated for the treatment of skin tumors that primarily spread by direct extension, that is, tumors that grow contiguously. MMS fails in tumors that have satellitosis, a multicentric origin, or skip areas. However, routine surgical excision also fails, often at the expense of excessive tissue sacrifice. Therefore, although MMS is most successful in treating certain cutaneous neoplasms, it also can be used alone or in a multidisciplinary approach to achieve the highest possible cure rate for a variety of difficult-to-treat tumors.

MMS may be limited by the extent of the tumor. MMS is indicated for special situations such as tumors that are deeply penetrating or have perineural invasion. If the tumor is so deeply invasive that it involves bone and/or vital structures, a multidisciplinary approach is indicated. For example, tumors that invade bone may need to be cleared peripherally by means of MMS. A specialist, such as an otolaryngologist and/or head and neck surgeon, may be consulted to treat the deep component of the tumor.

At times, the morbidity of a surgical approach for a tumor outweighs the benefit. At those times, other therapeutic options, such as radiation therapy, should be considered.

Other limitations of MMS may include the following:

• Noncontiguous tumors and/or disconnected foci in tumors may result in recurrence.
• Adjunctive therapy may be necessary to ensure cure.
• The extent of the tumor may be too great for the tumor to be amenable to surgery.

Complications

When a surgical procedure is performed, even under ideal conditions, a risk of complications always exists. Similar to other dermatologic surgical procedures, the most common complications include postoperative hematoma formation, seroma formation, wound dehiscence, flap necrosis, graft failure, infection, contact dermatitis to antibiotic ointments or dressing materials, excessive granulation formation, keloid and/or hypertrophic scar formation, hyperpigmentation and/or hypopigmentation, and recurrence of the tumor.

In general, complications from MMS are few and usually minor. Furthermore, the likelihood of tumor recurrence is much less with MMS than with other more routine therapeutic modalities.

Summary

MMS, by virtue of its unique horizontally oriented frozen sections, affords the highest cure rates and maximum tissue conservation in the management of specific primary and recurrent skin cancers. The Mohs micrographic surgeon acts as a dermatologist, dermatologic/oncologic surgeon, pathologist, and (when applicable) reconstructive surgeon. The Mohs micrographic surgeon adds a valuable skill in the treatment of advanced and complicated skin cancers; with interdisciplinary cooperation, this contribution is exceedingly beneficial to the patient.

Multimedia

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Media file 1: The conventional bread-loaf technique for checking tissue margins by using vertical sections. Less than 1% of the margin is evaluated, as compared with almost 100% of the margin with the Mohs micrographic technique. As illustrated here, residual tumor may not be found and may recur.

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Media file 2: Illustration of the Mohs micrographic surgical technique.

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Media file 3: Mohs microscopic surgery is generally indicated for the treatment of tumors in areas where a high risk of recurrence exists and cosmetic results are critical.

Keywords

MMS, Mohs' micrographic surgery, Mohs micrographic surgery, Mohs surgery, Mohs' surgery, Mohs chemosurgery, microscopically controlled excision, microscopically oriented histographic surgery, fresh-tissue technique, fixed-tissue technique, basal cell carcinoma, BCC, squamous cell carcinoma, SCC

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