Mohs micrographic surgery is a specialized surgical technique in which meticulous microscopic mapping of residual tumor guides the surgeon in complete extirpation of the cutaneous malignancy. In doing this, the technique seeks to ensure complete tumor eradication while maximizing normal tissue conservation. This approach appears to be superior to conventional surgical excision in the management of the most common cutaneous neoplasms, namely basal cell carcinoma (BCC)[1,2] and squamous cell carcinoma (SCC).
The increased cure rates for nonmelanoma skin cancer observed with Mohs surgery are largely attributable to the complete microscopic margin examination that occurs with its horizontal sectioning of the specimens. This is not the case with standard surgical excisions, as the majority of surgical pathologists continue to employ either cross-sectioning or bread-loaf sectioning to process tissue specimens. With these methods, less than 1% of the excised margin of the tumor is actually visualized. As a result, the potential for unrecognized margin involvement is much higher with step sectioning of tissue than with the Mohs technique. This difference translates into higher rates of tumor recurrence for standard excision
The field of Mohs micrographic surgery has evolved considerably since its conceptualization in 1936 by Dr. Frederic Mohs. The idea originated from Dr. Mohs' and others' work with the in vivo application of chemical cauterants to tumors of the skin for nonselective destruction. His observation of the unique in vivo fixative properties of one particular escharotic agent, zinc chloride paste, led him to the idea of microscopically controlled excision of tumors.
In Mohs' original technique, which was known as chemosurgery, zinc chloride paste was applied to the skin cancer and allowed to sit overnight. The patient returned the following day for surgical extirpation of the tumor followed by microscopic examination of horizontal sections of the specimen for margin clearance. The major limitations of the procedure were significant pain associated with application of the zinc chloride, prominent tissue inflammation secondary to the cauterant precluding reconstruction of defect, and the time-intensive nature of the 2-day procedure. The development of the fresh-tissue technique in 1974 by Stegman and Tromovitch allowed the procedure to be completed in 1 day and eliminated the pain and inflammation associated with use of zinc chloride. Since this innovation, Mohs surgery has become the gold standard for managing nonmelanoma skin cancers.
Mohs micrographic surgery begins with clinical identification by the physician of tumor margins through visual examination, palpation, and gentle curettage. After the surgical site is anesthetized with a local anesthetic, an incision is made with a scalpel just outside the clinically identifiable margins of the tumor. The distance between the clinical border of the neoplasm and the incision is variable, and depends on the type of malignancy, its size, and how well demarcated it is. In contrast to a traditional cutaneous excision, the incision is typically made at an angle of 30° to 45° with the skin such that the resulting excised specimen has a beveled edge to facilitate processing. At the time of incision, score marks are placed in both the specimen and the defect site for tissue orientation.
The tissue specimen is then transported to the histopathology laboratory, where the specimen is divided into smaller pieces based on the score marks and inked to preserve tissue orientation. A map correlating the surgical defect to the inked specimens is generated. In our laboratory, tissue specimens are pressed onto a glass slide and then freeze-mounted on a tissue chuck. This tissue flattening permits the tangential sectioning of the tissue, which makes Mohs surgery possible. The chucks are then placed in the cryostat for sectioning of the tissue. This yields 6- to 8-μm sections of the entire peripheral margins of the specimen including the base of the lesion. The slides are then stained with hematoxylin and eosin or, more rarely, toluidine blue. The generation of interpretable, highquality frozen section slides is a technically demanding task, which is highly dependent on the skill and experience of the histotechnician.
Next, the Mohs surgeon examines the slides for any evidence of tumor. If residual tumor is identified on the slides, the location is marked on the tissue map. This map is then returned to the patient's bedside for identification of the corresponding region of tumor involvement in the defect site. This area is subsequently removed for further tissue processing and examination, as described above. The process is repeated until the peripheral and deep margins are histologically free of tumor.
The final step in this process involves evaluation of the wound for second-intention healing vs reconstruction of the defect. Many factors enter into the appropriate determination at this juncture. These include the biologic nature of the malignancy removed, preservation of form and function of surrounding tissues, optimization of cosmesis, and patient comorbidities.
Use in Specific Tumor Types
Basal Cell and Squamous Cell Carcinomas
BCC and SCC are the two most commonly occurring cancers in the United States. Together, they comprise over 95% of all nonmelanoma skin cancers, accounting for over 1 million reported cases in 2004. Both tumors occur with increased frequency in fairskinned populations; however, BCCs outnumber SCCs by approximately 4:1. Exposure to ultraviolet radiation has repeatedly been identified as the single most significant factor in the etiology of both neoplasms. As a result, sunexposed areas of the skin are the most common locations of each tumor, with over 80% occurring on the face, scalp, neck, or dorsal hands. BCCs typically present as pearly pink papules with a rolled border and variable central ulceration (Figure 1). SCCs usually arise as a firm, erythematous hyperkeratotic papule or plaque (Figure 2).
Mohs micrographic surgery remains the gold standard for the surgical management of basal cell and squamous cell carcinomas. A review of over 10,000 cases of primary BCC treated with either standard surgical excision and traditional margin assessment or Mohs surgery revealed a long-term (> 5 year) recurrence rate of 10.1% for surgical excision vs 1.0% for Mohs surgery. For the management of recurrent BCC, the long-term recurrence rate for Mohs surgery was 5.6%, as compared to 9.8% for radiation therapy and 17.4% for surgical excision.
Equally superior results have been documented for the treatment of SCC with Mohs micrographic surgery (Figures 3 and 4). In a review of cases of SCC in the literature, Rowe et al reported recurrence rates of 3.1% for Mohs surgery vs 10.9% for surgical excision. For recurrent tumors, Mohs surgery yielded a recurrence rate of 10.0%, whereas surgical excision led to recurrences in 23.3% of cases.
Melanoma and Melanoma In Situ
Cutaneous melanoma is a neoplasm derived from melanocytes of the epidermis with the potential for both aggressive local growth and systemic spread. Melanoma in situ refers to a subtype of melanoma in which the neoplastic melanocytes are confined to the epidermis and associated adnexal structures without evidence of disease invading the adjacent dermis. The tumor typically presents as a brown to black patch, papule, or plaque with significant color variegation and border irregularity (Figure 5). The projected lifetime incidence of melanoma in the United States has increased to between 1% and 2%. Patient prognosis and staging are based on depth of tumor invasion (Breslow depth), tumor ulceration, nodal involvement, and the presence of local, in-transit, and systemic metastases.
Current guidelines for the surgical management of primary cutaneous melanoma are based on standard surgical excision, with increasing surgical margins depending on the depth of tumor invasion. Despite these recommendations, the potential therapeutic advantage of Mohs micrographic surgery to detect subclinical extensions of neoplastic cells missed by routine breadloaf sectioning and tissue conservation has prompted several clinicians to investigate the utility of this modality in the treatment of melanoma.
The first case series of melanoma patients treated with chemosurgery was reported by Frederic Mohs himself in 1950. His initial findings revealed local recurrence and survival rates comparable to those of traditional excisional surgery. Since that time, several other case series have documented similar or improved recurrence and survival rates with the use of Mohs micrographic surgery.[ 11-13] In the most recent and largest of these, Bricca et al reported a cohort of 625 consecutive patients with melanoma or melanoma in situ of the head and neck region who were treated with Mohs micrographic surgery. After a mean follow-up of 58 months, their results demonstrated local recurrence rates, metastasis rates, and disease-specific survival rates that were comparable to or better than those of historical controls for every Breslow stratification. In addition to increased tumor clearance, they found that this technique also provided tissue conservation in the majority of cases, as 6-mm margins were sufficient to clear 83% of melanomas.
• Controversies in Use for Melanoma—Despite recent encouraging results, several arguments remain against the use of Mohs micrographic surgery in the treatment of melanoma.
The first of these points concerns difficulties inherent to the histopathologic diagnosis of melanoma, and in particular melanoma in situ, on frozen tissue sections as compared to traditional paraffin-embedded sections. Differentiating the neoplastic cells of melanoma in situ from the background melanocytic hyperplasia of chronically actinic-damaged skin on paraffin sections can be challenging for the dermatopathologist. This task becomes more difficult when frozen sections are utilized, and has led some authors to propose that frozen sections are unreliable in the detection of margins of melanoma in situ.
However, in a review of 221 specimens, Zitelli et al found frozen sections to have a sensitivity of 100% and specificity of 90% in the diagnosis of melanoma as compared with routine paraffin sections. This improvement in diagnosis is the result of advances in immunohistochemical staining, as melanocytes, whether present individually or in small clusters, are now more readily identified on frozen sections. Of these immunostains, melanoma antigen recognized by T cells (MART-1) has proven to be the most sensitive except in the case of desmoplastic melanoma, in which the use of S-100 is indicated.[16,17]
A second theoretical argument against the use of Mohs micrographic surgery for melanoma is the belief that by taking wide margins around the tumor, the primary tumor as well as small local micrometastases are being excised, resulting in improved local recurrence and long-term survival rates vs narrow but complete excision of the primary tumor alone. This theory has not been substantiated by the data on excision of melanoma, which through the years has resulted in a reduction of the recommended surgical margins for melanoma.[ 8,9] It is also contradicted by studies displaying improved local recurrence, metastasis, and survival rates for Mohs micrographic surgery in the treatment of melanoma as compared to historical controls treated with conventional surgical resection.[11-13]
1. Rowe DE, Carroll RJ, Day CL: Long-term recurrence rates in previously untreated basal cell carcinoma: Implications for patient follow-up. J Dermatol Surg Oncol 15:315-328, 1989.
2. Rowe DE, Carroll RJ, Day CL: Mohs surgery is the treatment of choice for recurrent (previously treated) basal cell carcinoma. J Dermatol Surg Oncol 15:424-431, 1989.
3. Rowe DE, Carroll RJ, Day CL: Prognostic factors for local recurrence, metastasis, and survival rates in squamous cell carcinoma of the skin, ear, and lip. Implications for treatment modality selection. J Am Acad Dermatol 26:976- 990, 1992.
4. Abide JA, Nahai F, Bennett RG: The meaning of surgical margins. Plast Reconstr Surg 73:492-497, 1984.
5. Brodland DG, Amonette R, Hanke CW, et al: The history and evolution of Mohs micrographic surgery. Dermatol Surg 26:303-307, 2000.
6. Tromovitch TA, Stegman SJ: Microscopically controlled excision of skin tumors. Arch Dermatol 110:231-232, 1974.
7. Jemal A, Murray T, Ward E, et al: Cancer statistics, 2005. Ca Cancer J Clin 55:10-30, 2005.
8. Balch CM, Buzaid AC, Soong SJ, et al: Final version of the American Joint Committee on Cancer Staging System for cutaneous melanoma. J Clin Oncol 19:3635-3648, 2001.
9. Sober AJ, Chuang TY, Duvic M, et al: Guidelines of care for primary cutaneous melanoma. J Am Acad Dermatol 45:578-586, 2001.
10. Mohs FE: Chemosurgical treatment of melanoma: A microscopically controlled method of excision. Arch Dermatol Syph 62:269-272, 1950.
11. Bienert TN, Trotter MJ, Arlette JP: Treatment of cutaneous melanoma of the face by Mohs micrographic surgery. J Cutan Med Surg 7:25- 30, 2003.
12. Zitelli JA, Mohs FE, Larson P, et al: Mohs micrographic surgery for melanoma. Dermatol Clin 7:833-843, 1989.
13. Bricca GM, Brodland DG, Ren D, et al: Cutaneous head and neck melanoma treated with Mohs micrographic surgery. J Am Acad Dermatol 52:92-100, 2005.
14. Barlow RJ, White CR, Swanson NA: Mohs’ micrographic surgery using frozen sections alone may be unsuitable for detecting single atypical melanocytes at the margins of melanoma in situ. Br J Dermatol 146:290-294, 2002.
15. Zitelli, JA, Moy RL, Abell EA: The reliability of frozen sections for the evaluation surgical margins of melanoma. J Am Acad Dermatol 24:102-106, 1991.
16. Bricca GM, Brodland DG, Zitelli JA: Immunostaining melanoma frozen sections: The 1 hour protocol. Derm Surg 30:403-408, 2004.
17. Kelley LC, Starkus L: Immunohistochemical staining of lentigo maligna during Mohs micrographic surgery using MART-1. J Am Acad Dermatol 46:78-84, 2002.
18. Toker C: Trabecular carcinoma of the skin. Arch Dermatol 105:107-110, 1972.
19. Miller RW, Rabkin CS: Merkel cell carcinoma and melanoma: Etiological similarities and differences. Cancer Epidemiol Biomarkers Prev 8:153-158, 1999.
20. Yiengpruksawan A, Coit DG, Thaler HT, et al: Merkel cell carcinoma. Prognosis and management. Arch Surg 126:1514-1519, 1991.
21. Shaw JH, Rumball E: Merkel cell tumour: Clinical behaviour and treatment. Br J Surg 78:138-142, 1991.
22. O’Connor WJ, Roenigk RK, Brodland DG: Merkel cell carcinoma: Comparison of Mohs micrographic surgery and wide excision in 86 patients. Dermatol Surg 23:929-933, 1997.
23. Boyer JD, Zitelli JA, Brodland DG, et al: Local control of primary Merkel cell carcinoma: Review of 45 cases treated with Mohs micrographic surgery with and without adjuvant radiation. J Am Acad Dermatol 47:885-892, 2002.
24. Gloster HM, Harris KR, Roenigk RK: A comparison between Mohs micrographic surgery and wide surgical excision for the treatment of dermatofibrosarcoma protuberans. J Am Acad Dermatol 35:82-87, 1996.
25. Snow SN, Gordon EM, Larson PO, et al: Dermatofibrosarcoma protuberans: A report on 29 patients treated by Mohs micrographic surgery with long-term follow-up and review of the literature. Cancer 101:28-38, 2004.
26. Wacker J, Khan-Durani B, Hartschuh W: Modified Mohs micrographic surgery in the therapy of dermatofibrosarcoma protuberans: Analysis of 22 patients. Ann Surg Oncol 11:438- 444, 2004.
27. Huether MJ, Zitelli JA, Brodland DG: Mohs micrographic surgery for the treatment of spindle cell tumors of the skin. J Am Acad Dermatol 44:656-659, 2001.
28. Chanda JJ: Extramammary Paget’s disease: Prognosis and relationship to internal malignancy. J Am Acad Dermatol 13:1009-1014, 1985.
29. O’Connor WJ, Lim KK, Zalla MJ, et al: Comparison of Mohs micrographic surgery and wide excision for extramammary Paget’s disease. Dermatol Surg 29:723-727, 2003.
30. Coldiron BM, Goldsmith BA, Robinson JK: Surgical treatment of extramammary Paget’s disease: A report of six cases and a reexamination of Mohs micrographic surgery compared with conventional surgical excision. Cancer 67:933-938, 1991.
31. Marchesa P, Fazio VW, Oliart S, et al: Long-term outcome of patients with perianal Paget’s disease. Ann Surg Oncol 4:475-480, 1997.
32. Zollo JD, Zeitouni NC: The Roswell Park Cancer Institute experience with extramammary Paget’s disease. Br J Dermatol 142:59-65, 2000.
33. McCarter MD, Quan SH, Busam K, et al: Long-term outcome of perianal Paget’s disease. Dis Colon Rectum 46:612-616, 2003.
34. Sarmiento JM, Wolff BG, Burgart LJ, et al: Paget’s disease of the perianal region: An aggressive disease? Dis Colon Rectum 40:1187- 1194, 1997.
35. Hendi A, Brodland DG, Zitelli JA: Extramammary Paget’s disease: Surgical treatment with Mohs micrographic surgery. J Am Acad Dermatol 51:767-773, 2004.
36. Eliezri YD, Silvers DN, Horan DB: Role of preoperative topical 5-flourouracil in preparation for Mohs micrographic surgery of extramammary Paget’s disease. J Am Acad Dermatol 17:497-505, 1987.
37. Smith KJ, Tuur S, Corvette D, et al: Cytokeratin 7 staining in mammary and extramammary Paget’s disease. Mod Pathol 10:1069-1074, 1997.
38. Harris DW, Kist DA, Bloom K, et al: Rapid staining with carcinoembryonic antigen aids limited excision of extramammary Paget’s disease treated by Mohs surgery. J Dermatol Surg Oncol 20:260-264, 1994.
39. Goldstein DJ, Barr RJ, Cruz DJ: Microcystic adnexal carcinoma: A distinct clinicopathologic entity. Cancer 50:566-572, 1982.
40. Birkby CS, Argenyl ZB, Whitaker DC: Microcystic adnexal carcinoma with mandibular invasion and bone marrow replacement. J Dermatol Surg Oncol 15:308-312, 1989.
41. Park JY, Parry EL: Microcystic adnexal carcinoma: First reported case in a black patient. Dermatol Surg 24:905-907, 1998.
42. Chiller K, Passaro D, Scheuller M, et al: Microcystic adnexal carcinoma: Forty-eight cases, their treatment and their outcome. Arch Dermatol 136:1355-1359, 2000.
43. Friedman PM, Friedman RH, Jiang B, et al: Microcystic adnexal carcinoma: Collabora- tive series review and update. J Am Acad Dermatol 41:225-231, 1999.
44. Lebovitch I, Huilgol, Selva D: Microcystic adnexal carcinoma: Treatment with Mohs micrographic surgery. J Am Acad Dermatol 52:295- 300, 2005.
45. Wick MR, Cooper PH, Swanson PE, et al: Microcystic adnexal carcinoma: An immunohistochemical comparison with other cutaneous appendage tumors. Arch Dermatol 126:189-194, 1990.