reconstruction to be performed on the same day the cancer is removed further optimizing the patient's care, convenience and surgical outcome. Guideline Questions (1) What are the indications for MMS? (2) Are there any cases where the use of MMS is inappropriate?# Background

# Nonmelanoma skin cancer (NMSC)
Nonmelanoma skin cancer (NMSC) is the most commonly diagnosed cancer among Canadians. 1 The most prevalent form of NMSC is basal cell carcinoma (BCC), followed by squamous cell carcinoma (SCC). Together they account for approximately 95% of all cases of NMSC in Canada. 2 From 1988 to 2007, there were 66,192 BCCs, 19,959 invasive SCCs, and 12,494 SCCs in situ in Alberta. 3 Sunlight exposure is the most significant risk factor in the etiology of NMSC. Fair complexion, lighter hair and eye colour, and a positive personal or family history are also risk factors for developing BCC or SCC. 4,5 There are many approaches to the treatment of NMSC. Generally, the primary goal of treatment is complete tumour eradication with maximal preservation of function and cosmesis. Current guidelines for the management of BCC and SCC consider surgery (including standard excision, Mohs micrographic surgery, or curettage and electrodessication) as the most effective treatment option for most cases of NMSC.  Other treatment options include cryotherapy, radiation, photodynamic therapy, and topical therapy. This guideline focuses on the indications for Mohs micrographic surgery (MMS) in NMSC.

# Mohs micrographic surgery (MMS)
Mohs micrographic surgery (MMS) is a specialized technique, originally developed by Dr. Frederick E. Mohs, which has been refined to allow the precise microscopically controlled removal of skin tumors. The technique involves excising a skin tumor with a minimum margin, and processing the tissue in a very specific way using a fresh frozen preparation technique to create pathology slides. This ultimately allows the surgeon to examine the entire margin of the excised skin cancer. MMS is suitable for the surgical extraction of tumors that have a contiguous pattern of growth occurring on sensitive body sites such as the face, hands feet and genitals where the sparing of healthy surrounding tissue is considered essential. In certain cases, the skin cancer may be debulked or curetted prior to removing a layer of tissue. This debulking is not considered as taking a layer of skin.
The Mohs procedure begins with the precise marking of clinically tumor free margins immediately adjacent to the skin tumor (and any associated scar) to be removed. Typically utilizing local anesthesia, these margins are incised in a beveled fashion and a precise layer of tissue is removed surgically. This tissue layer is color inked in a manner devised to map its orientation relative to the patient's surgical wound. The beveled margins of the layer are then flattened to facilitate frozen section processing. The resultant tissue sections are subsequently stained so microscopic slides can be produced that demonstrate 100% of the tissue margins for examination.
The performance of Mohs technique includes the capability to provide reliable pathologic analysis of these slides. If tumor is noted to persist at the margin, its location is related back to the original tissue map and another layer is incised while again sparing tissue not involved by tumor. A correlating map of this layer is generated again being sure to include color inked margins to preserve it precise orientation. This process is repeated until all margins are clear of tumor microscopically. This insures that the Mohs technique attains some of the highest success rates in the treatment of non-melanoma skin cancer -up to 99%.
Finally, MMS involves the knowledge and skill to offer management of the resulting surgical wound including complex reconstructive surgical flap repair as necessary. The combination of this expertise allows 5.   Yes *Area H: "mask areas" of face (central face, eyelids, eyebrows, periorbital, nose, lips , chin, mandible, preauricular and postauricular skin/sulci, temple, ear), genitalia, hands, and feet. Area M: cheeks, forehead, scalp, neck, and pretibia. Area L: trunk and extremities (excluding pretibial, hands, feet, nail units, and ankles). Location independent of size may constitute high risk. *High-risk histologic subtypes: acantholytic (adenoid), adenosquamous (showing mucin production), desmoplastic, or metaplastic (carcinosarcomatous) subtypes.  Clark level defines depth of invasion, with level I being confined to the epidermis as a carcinoma in situ and with all other levels being invasive tumours that extend into the dermis. Clark level V tumours extend all the way through the dermis and have entered the subcutaneous fat layer.
(Recurrent disease: Level of Evidence: III 63 and IV 61  Results: 2

# Inclusion Criteria:
Randomized controlled trials, controlled clinical trials, or multicenter studies conducted on humans that were published between 1997 and 2018 in English. Study topic had to be on basal cell or squamous cell carcinoma where treatment included Moh's micrographic surgery. Studies needed to report on at least one of the following: treatment outcomes, tumour reoccurrence rates, or quality of life. Reference sections from all included articles were screened for additional literature.

# Exclusion Criteria:
Reasons for excluding abstracts (571 articles reviewed) -Single centre retrospective review with surgical outcomes only (ie. Factors predictive of more surgical stages) -Assessment of surgical rates -Access to care studies/cost analysis/ looking at differences between centres to assess access to care -Proposed deficit vs mohs deficit -Surgical outcomes slow mohs -Earlier version of article -Incidence epidemiological studies Predictors of satisfaction with Mohs (no comparisons to other treatments)

# Search for Existing Guidelines:
The National Guidelines Clearinghouse and individual guideline organizations were searched for practice guidelines relevant to this topic. A total of fifteen clinical practice guidelines with at least one recommendation directly related to MMS were identified from the following organizations or groups: American Academy of Dermatology, National Comprehensive Cancer Network, UptoDate, and American Society for Dermatologic Surgery, British Association of Dermatologists, London Cancer Alliance, Scottish Intercollegiate Guidelines Network, Cancer Council Australia, and the UK National Multidisciplinary Guidelines committee.

# Literature Search Outcomes:
In total 1098 primary articles were identified from the Medline/ Pubmed/ Embase/ Cochrane literature searches of which 571 articles were unique. 492 articles were excluded based on an abstract screen, and a further 35 were excluded after a full-text screen, leaving 44 articles. 7 articles were added after a review of the reference sections from the included articles.
In total, 51 primary articles were identified and included in the literature search (below). 22 articles were focused on both BCC and SCC (Appendix A Table 1), 18 focused exclusively on BCC (Appendix A Table 2), and 11 focused exclusively on SCC (Appendix A Table 3).
Additionally, 13 relevant guidelines were identified and reviewed by the guideline working group (Appendix A Table 4).  (77) Key Findings: 1) MMS is recommended as a first-line option for high-risk primary or recurrent basal cell carcinoma or squamous cell carcinoma 2) MMS may be considered as one of the options for squamous cell carcinoma, especially where tissue preservation or margin controls are challenging, or when the tumor is at a critical anatomical site 3) In squamous cell carcinoma in situ (Bowden's disease), MMS may be indicated for digital and penile tumour, or in recurrent or incompletely excised lesions. 4) MMS may be considered for melanoma in situ (lentigo maligna) and Merkel cell carcinoma, especially when the tumor is in a sensitive area and there are concerns of functional impairment from an excision that is too radical. 5) Although the size of the lesion should be analyzed together with its location and histological pattern, MMS could be a better treatment option for tumors larger than 2 cm which present higher chance of incomplete removal with conventional surgery. 6) MMS leads to a smaller recurrence rate than conventional surgery for dermatofibrosarcoma protuberans. 7) The majority of the recommendations on the use of MMS for skin cancers were based on evidence of limited quality and need to be interpreted with caution. More high-quality trials are required to elucidate the role of MMS on skin cancers. Cancer Care Ontario: Patient Indications for Mohs Micrographic Surgery, 2018 (13) Recommendations: 1. Surgery (with postoperative or intraoperative marginal assessment), or radiation for those who are ineligible for surgery, should remain the standard of care for patients with skin cancer given the lack of high-quality, comparative evidence. 2. MMS is recommended for those with histologically confirmed recurrent basal cell carcinoma (BCC) of the face, and is appropriate for primary BCCs of the face that are >1 cm, have aggressive histology, or are located on the H zone of the face (Figure 1-1). 3. MMS should be performed by physicians who have completed a degree in medicine or equivalent, including a Royal College of Physicians and Surgeons of Canada Specialist Certificate or equivalent, and have received advanced training in MMS. 4. Surgery (with postoperative or intraoperative marginal assessment), or radiation for those who are ineligible for surgery, should remain the standard of care for patients with skin cancer given the lack of high-quality, comparative evidence. 5. MMS is recommended for those with histologically confirmed recurrent basal cell carcinoma (BCC) of the face, and is appropriate for primary BCCs of the face that are >1 cm, have aggressive histology, or are located on the H zone of the face (Figure 2-1). 6. MMS should be performed by physicians who have completed a degree in medicine or equivalent, including a Royal College of Physicians and Surgeons of Canada (RCPSC) Specialist Certificate or equivalent, and have received advanced training in MMS. Guidelines of care for the management of cutaneous squamous cell carcinoma JAAD, 2018 (7) Recommendations: 1. Stratification of localized SCCs using the NCCN guideline framework is recommended for clinical practice. Clinicians should refer to the BWH tumor classification system to obtain the most accurate prognostication of patients with localized cSCC. 2. The recommended biopsy techniques for cSCC are punch biopsy, shave biopsy, and excisional biopsy. The biopsy technique used will depend on the characteristics of the suspected malignancy (morphology, location, etc) and the judgment of the physician. The biopsy size and depth should be adequate to provide the recommended clinical information and pathology report elements to permit accurate diagnosis and guide therapy.

# Guideline Developer
Recommendations 3. A treatment plan that considers recurrence rate, preservation of function, patient expectations, and potential adverse effects is recommended. C&E may be considered for low-risk, primary cSCC in none terminal hairebearing locations. For low-risk primary cSCC, standard excision with a 4-to 6-mm margin to a depth of the mid-subcutaneous adipose tissue with histologic margin assessment is recommended. Standard excision may be considered for select high-risk tumors. However, strong caution is advised when selecting a treatment modality for high-risk tumors without a complete margin assessment. MMS is recommended for high-risk cSCC.t biopsy may be considered if the initial biopsy specimen is inadequate for accurate diagnosis. 4. If surgical therapy is not feasible or preferred, radiation therapy (eg, superficial radiation therapy, brachytherapy, external electron beam therapy, and other traditional radiotherapy forms) can be considered when tumors are low risk, with the understanding that the cure rate may be lower. Cryosurgery may be considered for low-risk cSCC when more effective therapies are contraindicated or impractical. Topical therapies (imiquimod or 5-FU) and PDT are not recommended for the treatment of cSCC on the basis of available data. There is insufficient evidence available to make a recommendation on the use laser therapies or electronic surface brachytherapy in the treatment of cSCC. 5. Surgical resection, with or without adjuvant radiation therapy and possible systemic therapy are recommended for regional lymph node metastases. Combination chemoradiation therapy should be considered for inoperable disease. Epidermal growth factor inhibitors and cisplatin, as a single agent or in combination therapy, may be considered, as they have demonstrated efficacy for metastatic disease, albeit on the basis of limited data. Multidisciplinary consultation and management, particularly in immunosuppressed individuals, is recommended for patients with locoregional or distant metastases. In some cases, such consultation may be appropriate for patients with locally advanced disease without known metastases. Patients with advanced disease should be provided with or referred for best supportive and palliative care to optimize symptom management and maximize quality of life. 6. After diagnosis of a first SCC, screening for new keratinocyte cancers (BCC or cSCC) and for melanoma should be performed on at least an annual basis. Patients with a history of cSCC should be counseled on skin self-examination and sun protection. Topical and oral retinoids (eg, tretinoin, retinol, acitretin, and isotretinoin) should not be prescribed to reduce the incidence of keratinocyte cancers in those with a history of cSCC, unless they are SOTRs. In the situation of SOTRs, only acitretin may be beneficial. Dietary supplementation of selenium and b-carotene is not recommended to reduce the incidence of future keratinocyte cancers in those with a history of cSCC. There is insufficient evidence to make a recommendation on the use of oral nicotinamide, DFMO, or celecoxib in the chemoprevention of cSCC. Guidelines of care for the management of basal cell carcinoma JAAD, 2018 (6) Recommendations: 1. Stratification of localized BCC using the NCCN guideline framework is recommended for clinical practice. 2. The recommended biopsy techniques for BCC are punch biopsy, shave biopsy, and excisional biopsy. The biopsy technique used will depend on the characteristics of the suspected malignancy (morphology, location, etc) and the judgment of the physician. The biopsy size and depth should be adequate to provide the recommended clinical information and pathology report elements to permit accurate diagnosis and guide therapy. Repeat biopsy may be considered if initial biopsy specimen is inadequate for accurate diagnosis. 3. A treatment plan that considers recurrence rate, preservation of function, patient expectations, and potential adverse effects is recommended. C&E may be considered for low-risk tumors in none terminal hairebearing locations. For lowrisk primary BCC, surgical excision with 4-mm clinical margins and histologic margin assessment is recommended. Standard excision may be considered for select high-risk tumors. However, strong caution is advised when selecting a treatment modality without complete margin assessment for high-risk tumors. Mohs micrographic surgery is recommended for high-risk BCC. 4. Cryosurgery may be considered for low-risk BCC when more effective therapies are contraindicated or impractical. If surgical therapy is not feasible or preferred, topical therapy (eg, imiquimod or 5-FU), MAL-or ALA-PDT, and radiation therapy (eg, superficial radiation therapy, brachytherapy, external electron beam, and other traditional radiotherapy forms for BCC) can be considered when tumors are low risk, with the understanding that the cure rate may be lower. Adjustment of topical therapy dosing regimen on the basis of side effect tolerance is recommended. There is insufficient evidence to recommend the routine use of laser or electronic surface brachytherapy in the treatment of BCC. 5. Multidisciplinary consultation and smoothened inhibitors are recommended for patients with metastatic BCC. If treatment of metastatic BCC with smoothened inhibitors is not feasible, platinum-based chemotherapy or best supportive care is recommended. If surgery and radiation therapy are contraindicated or inappropriate for the treatment of locally advanced BCC, or if residual tumor persists following surgery and/or radiation therapy and further surgery and radiation therapy are contraindicated or inappropriate, systemic therapy with a smoothened inhibitor should be considered. Patients with advanced disease should be provided with or referred for best supportive and palliative care, to optimize symptom management and maximize quality of life.
BCC: Mohs micrographic surgery may be considered as a first-line option for high-risk primary BCC, incompletely excised high-risk BCC, and most recurrent BCCs amenable to surgery.
High-risk primary or recurrent SCC: Mohs micrographic surgery should always be considered for lesions with poorly defined borders, particularly if such lesions occur on cosmetically sensitive areas, such as face, hands, and feet. For reasons of cosmesis and function, SCCs on certain sites (eyebrows, eyelids, nose, hands, and feet) should also be treated as high risk, with preferential use of Mohs micrographic surgery to spare as much as possible of the surrounding healthy tissue. American Society for Dermatologic Surgery, 2015 (5) BCC: Mohs surgery is the treatment of choice for high-risk BCCs and recurrent BCCs because of its high cure rate and tissue-sparing benefit. Because the most effective treatment for any BCC is Mohs surgery, it also remains the best treatment option for tumors at high risk of recurrence after other treatment modalities.

# British Association of Dermatologists, 2014 (71)
SCC: Mohs micrographic surgery may be indicated for digital SCC in situ (around the nail in particular) and for some cases of genital (especially penile) SCC in situ for its tissue-sparing benefits. There may also be a role for Mohs in recurrent or incompletely excised lesions.
London Cancer Alliance, 2014 (72) BCC: poorly defined borders, high-risk site (i.e. H-zone), aggressive histology such as morphoeic or infiltrative or micronodular, perineural invasion, lymphovascular invasion, recurrent tumors (or incompletely excised), large tumors (>2cm), immune-compromised patient SCC: poorly defined borders, high-risk site (i.e. H-zone), perineural invasion, lymphovascular invasion, recurrent tumors (or incompletely excised), large tumors (>2cm), immune-compromised patient, persistent Bowen's disease at awkward site (i.e. genitals, eyelid, scalp, nails)

# Scottish Intercollegiate Guidelines Network (SIGN), 2014 (73)
Mohs micrographic surgery should be considered at the MDT meeting, for selected patients with high-risk tumours where tissue preservation or margin control is challenging, and on an individual case basis for patients with any tumour at a critical anatomical site. This guideline was originally developed in August 2019.

# Maintenance
A formal review of the guideline will be conducted in 2020. If critical new evidence is brought forward before that time, however, the guideline working group members will revise and update the document accordingly. 

# Abbreviations