Mohs Micrographic Surgery

• Complete resection of cutaneous malignancy
• Minimize defect (i.e., preserve tissue)
• Facilitate reconstruction

Indications defined by the American Academy of Dermatology include basal cell carcinomas (BCC) and squamous cell carcinomas (SCC), some early melanoma (lentigo malignant melanoma), and some rare cancers such as Merkel cell carcinoma (AAD.org).

• The decision to choose the Mohs technique versus intraoperative histopathologic examination is multifactorial, including patient preference, surgeon comfort, location of the lesion, availability of a Mohs surgeon, and availability of a pathologist to perform frozen section evaluation.
• The Mohs technique allows for assessment of circumferential skin and deep tumor margins in a horizontal plane.
• Excision of periocular BCC and SCC, and monitoring of surgical margins, might require more than the horizontal orientation afforded by the Mohs technique, necessitating additional histopathologic assessment for 3D orientation of tumor planes.
• For example, tumors that invade the orbit require additional histopathology to assess the degree of orbital invasion.
• Lid margin basal cell and squamous cell carcinoma may be assessed by the Mohs technique; alternatively, wedge excision might be preferred, with histopathologic assessment of the surgical margins on either side of the lesion and at the base of the specimen.
• Medial canthal tumors can ideally be studied by the Mohs technique.
• Deep invasion beyond the surface of the skin requires histopathologic evaluation beyond the Mohs technique; specifically, if the tumor extends into vital structures and surgical resection with local anesthetic is not possible, Mohs micrographic resection is an unacceptable treatment option (Nehal, Elsevier, 2014).

Lentigo maligna and malignant melanoma in-situ, which can be removed by the Mohs technique according to AAD guidelines, require permanent histopathology because frozen section processing ruptures melanocytes.

A retrospective review of Mohs surgery for sebaceous cell carcinoma of the eyelid found no 5-year difference in outcomes for Mohs patients (n=115) compared to wide excision (n=245) (JAAD 2019:80:1608).

Malignancies which are more difficult to eradicate locally, such as leiomyosarcoma, apocrine/eccrine carcinoma, Merkel cell carcinoma, mucinous carcinoma, and sebaceous carcinoma, have traditionally required wider surgical margins, beyond histopathologically confirmed tumor free margin, and the Mohs technique might be inappropriate for these tumors.

Contraindications to the Mohs technique include periocular malignant melanoma, which requires permanent sections to ensure complete resection, and orbital tumors.

Patient history:

• Past medical history
• Previous interventions in the distribution of the lesion (i.e., radiation, surgery, cryotherapy)
• Prior intervention can alter tissue architecture and blur the distinction between healthy and tumor-involved tissue
• No studies have directly assessed the optimal technique for resection of recurrent tumor after cryotherapy or radiation – wider resection might be necessary

Clinical examination:

• Assess size, location, mobility, and depth of lesion
• In cases of suspected deeper involvement, review orbital imaging
• Perform lacrimal irrigation in cases of suspected nasolacrimal involvement

Preoperative assessment:

• The decision to continue or discontinue anticoagulants must be based on considerations related to both the Mohs surgeon’s excision and the oculofacial surgeon’s reconstruction.
• Discontinuing antithrombotic agents to minimize bleeding and facilitate reconstruction carries a risk of thrombotic event.
• When a skin graft is being contemplated for reconstruction of the eyelid, indications for discontinuing anticoagulants can stem from the reconstruction, not necessarily the excision.
• The recent dermatology literature suggests a trend towards continuing warfarin and aspirin in Mohs surgery.
• In one recent survey, 87% of procedural dermatologists discontinue prophylactic aspirin, 37% discontinue medically necessary aspirin, 44% discontinue warfarin, 77% discontinue nonsteroidal anti-inflammatory drugs, and 77% discontinue vitamin E (Kirkorian AY, Dermatol Surg, 2007).
• In one study, severe postoperative bleeding occurred in 4 patients among 760 patients undergoing Mohs surgery while continuing anticoagulants (Shimizu I, J Am Acad Dermatol, 2008).

Duration of lesion: Basal cell carcinoma is believed to double in size over 6–12 months, so longer durations suggest larger, deeper lesions.

Preoperative antibiotics are generally not required; Mohs micrographic resection does not meet American Heart Association criteria for the use of prophylactic antibiotics

Resection with frozen section controls:

• “En face” technique
• Each surgical margin is inked
• Each margin is frozen for sectioning
• Serial sections are cut and stained with hematoxylin and eosin and micrographic analysis is performed
• Levin and coauthors assessed 200 lesions that were resected with this technique, and identified a 1% recurrence rate for BCC (Levin F, Arch Ophthalmol, 2009).

The “Slow Mohs” technique is generally employed for subtle tumors that might be overlooked or difficult to identify with conventional Mohs’ micrographic resection (i.e., lentigo maligna). Specimens are handled as expedited permanent sections:

• The specimen is oriented and borders are inked.
• Specimens are embedded in paraffin.
• Serial sections are cut and stained.
• Histologic analysis is performed according to the usual Mohs technique.
• The technique can be an alternative for malignant melanoma.
• Then, et al. reported 14 patients with periocular malignant melanoma that underwent slow Mohs resection; there were 2 cases of local recurrence over a median of 36 months’ follow-up (Then S-Y, Dermatol Surg, 2009).
• The authors chose slow Mohs, given the historic problems inherent to frozen sections in interpreting the borders of resection in melanoma; the freezing process can rupture melanocytes, making identification of clear margins difficult, and artifacts that result from freezing make assessment of the margins technically problematic

Cryotherapy/cryosurgery:

• Although the cure rate is lower, this is still a reasonable option with > 90% cure rate for basal cell carcinoma.
• It is rapid and cost-effective, but highly operator-dependent.
• One disadvantage is the inability to monitor and assess tumor margins (Tuppurainen K. Graefe’s Arch Clin Exp Ophthalmol. 1995).
• Generally preferred for premalignant disease (actinic keratosis, Bowen’s disease, squamous cell carcinoma in-situ, lentigo maligna) (Murchison AP, Clin Exp Ophthalmol 2011)
• Disadvantages include possible damage to adnexal structures and/or the eye and potential for cosmetic deformity.

Radiation therapy:

• Has a higher rate of recurrence than other modalities of treatment
• A significant disadvantage is that with recurrence, surgical treatment and delineation of margins becomes more difficult
• Generally reserved for poor surgical candidates or those who refuse surgery (Leshin B, Surv Ophthalmol, 1993).

Imiquimod:

• Anecdotal reports of benefit in BCC – not routinely used around the eye
• 5% cream administered 5x/day
• Associated with discomfort and conjunctivitis (Carneiro RC, Ophthal Plast Reconstr Surg, 2012).
• One study reported a 3-year clearance rate of 81.8% after the use of imiquimod in lesions > 10 mm, as compared to a 100% rate for lesions < 10 mm (de Macedo EM, BMC Ophthalmol, 2015).

Vismodegib:

• Hedgehog signaling pathway is selectively upregulated in BCC.
• Vismodegib is an antagonist of the hedgehog pathway – reserved for use in select cases with inoperable disease.
• Reports of effective use in 50% of patients with BCC (Gill HS, JAMA Ophthalmol, 2013)
• Side effects, including malaise, gastrointestinal issues, weight and hair loss, and decreased or altered sense of taste, limit utility.
• Reserved for poor surgical candidates and those with multiple or deep lesions
• Can also use vismodegib in neoadjuvant role, to reduce an anterior orbital lesion prior to resection, thus sparing the globe (Kahana A, JAMA Ophthalmol, 2013).

Other medical therapies being explored include epidermal growth factor inhibitors and tyrosine kinase inhibitors.

• Generally, performed under local anesthetic
• Visible distribution of the lesion is marked and infiltrated with anesthetic:
• Lesion is excised, and hemostasis is obtained with cautery
• The skin is incised at a 45-degree angle around the marked distribution of the lesion
• The lesion is removed in its entirety in a horizontal plane, either with a scalpel or a scissors
• Often, the specimen is divided into smaller sections, and the borders are marked with colored ink (generally, methylene blue); a map must be preserved to ensure proper orientation
• Immediate microscopy is performed:
• Sections are placed on a mount; the sections must be flattened to create an even horizontal plane
• Tissue is frozen in a cryostat
• 5–10-micron sections are generated by cutting the sections horizontally to include lateral and deep margins in one section, and mounted on slides
• Staining is performed (generally with hematoxylin and eosin), and margins are assessed microscopically.
• If residual tumor is detected, the spot of persistent tumor is marked on the map, and additional resection is performed and evaluated in the location of the lesion.
• Once the margins are found to be free of residual tumor, reconstruction is performed.

• Postoperative medications
• Acetaminophen for pain control
• Topical ophthalmic antibiotic ointment
• Describe other management considerations
• Serial follow-up to assess for recurrence
• Review final histopathology

• Hemorrhage is generally related to anticoagulants.
• Recurrence requires re-excision.
• Recurrence rates are quite low, with 3% recurrence noted for basal and squamous cell periocular Mohs procedures at median follow-up of 46 months (Br J Derm 2019:180:1176).
• 8% recurrence rate after excision of previously excised tumors (Malhotra R, Ophthalmology, 2004)
• Recurrence with medial canthal disease is particularly worrisome with a higher risk of orbital tumor progression.

• Developed in 1938
• Pioneered by Dr. Frederic Mohs at the University of Wisconsin
• Between 1992 and 2012, the use of Mohs surgery expanded by 332%.
• There are concerns about increased costs; the total cost of Mohs surgery exceeds $2 billion/year (Ravitskiy L, Dermatol Surg, 2012).

1. AAO, Basic and Clinical Sciences Course. Section 4: Ophthalmic Pathology and Intraocular Tumors; Section 7: Orbit, Eyelids, and Lacrimal System, 2013-2014.
2. Ad Hoc Task Force, Connolly SM, Baker DR, Coldiron BM, et al. AAD/ACMS/ASDSA/ASMS 2012 appropriate use criteria for Mohs micrographic surgery: a report of the American Academy of Dermatology, American College of Mohs Surgery, American Society for Dermatologic Surgery Association, and the American Society for Mohs Surgery. J Am Acad Dermatol. 67(4):531-50, 2012.
3. Alam M, Ibrahim O, Nodzenski M, et al. Adverse events associated with mohs micrographic surgery: multicenter prospective cohort study of 20,821 cases at 23 centers. JAMA Dermatol. 149(12):1378-85, 2013.
4. Bonifas JM, Pennypacker S, Chuang PT, et al. Activation of expression of hedgehog target gene in basal cell carcinomas. J Invest Dermatol. 116:739–42, 2001.
5. Carneiro RC, de Macedo EM, Matayoshi S. Imiquimod 5% cream for the treatment of periocular Basal cell carcinoma. Ophthal Plast Reconstr Surg. 26(2):100–2, 2012.
6. Christensen SR and Aasi SZ. In: Mohs Micrographic Surgery. Nouri K, ed. London: Springer, 2012.
7. de Macedo EM, Carneiro RC, de Lima PP, et al Imiquimod treatment efficacy in the treatment of periocular nodular basal cell carcinoma: a non-randomized trial. BMC Ophthalmol, epub ahead of print, 2015).
8. El-Sawy T, Sabichi AL, Myers JN, et al. Epidermal growth factor receptor inhibitors for treatment of orbital squamous cell carcinoma. Arch Ophthalmol. 130(12):1608-11, 2012.
9. Gill HS, Moscato EE, Chang AL, et al. Vismodegib for periocular and orbital basal cell carcinoma. JAMA Ophthalmol.;131(12):1591-4, 2013.
10. Gill HS, Moscato EE, and Seiff SR. Eyelid margin basal cell carcinoma managed with full-thickness en-face frozen section histopathology. Ophthal Plast Reconstr Surg, 30: 15-9, 2014.
11. Ivan D, Prieto VG, Esmaeli B, et al. Epidermal growth factor receptor (EGFR) expression in periocular and extraocular sebaceous carcinoma. J Cutan Pathol. 37:231–6, 2010.
12. Kahana A, Worden FP, Elner VM. Vismodegib as eye-sparing adjuvant treatment for orbital basal cell carcinoma. JAMA Ophthalmol. 131(10):1364-6, 2013.
13. Kirkorian AY, Moore BL, Siskind J, et al. Perioperative management of anticoagulant therapy during cutaneous surgery: 2005 survey of Mohs surgeons. Dermatol Surg. 33(10):1189-97, 2007.
14. Leshin B, Yeatts P, Anscher M, Montano G, et al. Management of periocular basal cell carcinoma: Mohs micrographic surgery versus radiotherapy. Surv Ophthalmol. 38(2):193–212, 1993.
15. Levin F, Khalil M, McCormick SA, et al. Excision of Periocular Basal Cell Carcinoma With Stereoscopic Microdissection of Surgical Margins for Frozen-Section Control, Arch Ophthalmol, 127: 1011-5, 2009.
16. Malhotra R, Huilgol SC, Huynh NT, et al. The Australian Mohs database, part II: periocular basal cell carcinoma outcome at 5-year follow-up. Ophthalmol, 1114: 631-6, 2004.
17. Maubec E, Petrow P, Scheer-Senyarich I, et al. Phase II study of cetuximab as a first-line single-drug agent in patients with unresectable squamous cell carcinoma of the skin. J Clin Oncol. 29(25):3419-26, 2011.
18. Murchison AP, Walrath JD, and Washington CV. Non-surgical treatments of primary, non-melanoma eyelid malignancies: a review. Clin Exp Ophthalmol, 39: 65-83, 2011.
19. Nehal KS, Tudisco M, and Busam KJ. Frozen sections and pathologic evaluations of sections from Mohs surgery. In: Dermatopathology, Busam KJ ed. Elsevier, 2014.
20. Otley CC.Continuation of medically necessary aspirin and warfarin during cutaneous surgery. Mayo Clin Proc, 78: 1392–1396, 2003.
21. Palamaras I, McKenna JD, Robson A, et al. Microcystic Adnexal Carcinoma: A Case Series Treated with Mohs Micrographic Surgery and Identification of Patients in Whom Paraffin Sections May Be Preferable. Dermatol Surg. 36(4):446-452, 2010.
22. Ravitskiy L, Brodland DG, and Zitelli JA. Cost analysis: Mohs micrographic surgery. Dermatol Surg, 38: 585-94, 2012.
23. Shimizu I, Jellinek NJ, Dufresne RG, et al. T. Multiple antithrombotic agents increase the risk of postoperative hemorrhage in dermatologic surgery. J Am Acad Dermatol, 58: 810–816, 2008.
24. Stern RS. Cost effectiveness of Mohs micrographic surgery. J Invest Dermatol, 133: 1129-31, 2013.
25. Then S-Y, Malhotra R, Barlow R, et al. Early Cure Rates with Narrow-Margin Slow-Mohs Surgery for Periocular Malignant Melanoma. Dermatologic Surgery. 35(1):17-23, 2009.
26. Tuppurainen K. Cryotherapy for eyelid and periocular basal cell carcinomas: 166 cases over an 8-year period. Graefe’s Arch Clin Exp Ophthalmol. 233:205–8, 1995.
27. Weesie F, Naus NC, Vasilic D, Hollestein LM, van den Bos RR, Wakkee M. Recurrence of periocular basal cell carcinoma and squamous cell carcinoma after Mohs micrographic surgery: a retrospective cohort study. Br J Dermatol. 2019 May;180(5):1176-1182. doi: 10.1111/bjd.17516. Epub 2019 Feb 10. PMID: 30536656; PMCID: PMC6849866.
28. While B, Salvi S, Currie Z, et al. Excision and delayed reconstruction with paraffin section histopathological analysis for periocular sebaceous carcinoma. Ophthal Plast Reconstr Surg, 30: 105-9, 2014.
29. Zhou C, Wu F, Chai P, Shi Y, Ye J, Shi X, Tan J, Ding Y, Luo Y, Esmaeli B, Jia R, Fan X. Mohs micrographic surgery for eyelid sebaceous carcinoma: A multicenter cohort of 360 patients. J Am Acad Dermatol. 2019 Jun;80(6):1608-1617.e1. doi: 10.1016/j.jaad.2018.12.053. Epub 2019 Jan 9. PMID: 30639290.