in identifying TCs during MMS. They noted that since not all follicular ORS produce CK 15, it may be negative. C-erb-15 was found to be a stain that correlated with aggressive behavior [62].

Summary: Conclusions

•Immunostaining is an adjunctive technique for MOHs micrographics surgery that is helpful in determining tumor extension when it is unclear with H & E stained frozen sections due to inflammation, fibrosis, or muscle and nerve invasion.

15.8Conclusions

MMS has been utilized for a variety of cutaneous tumors especially in cosmetically sensitive areas, and in particular, tumors with ill-defined extensions into the surroundingtissueandrecurrenttumors.Immunostaining has been a helpful adjunct in many cases on FS to determine the extent of the tumor, when this assessment would be difficult, if not impossible to accomplish with routine H & E. It results in smaller margins of resection and less recurrences, which is likely to reduce health care costs associated with managing recurrences. In a study conducted in 2001, 13 of 108 (12%) laboratories were utilizing immunostains on frozen sections [31]. However, with new protocols with faster processing times reported in the literature, increased cost-effec- tiveness, as well as enhanced familiarity with the technique, immunostaining will likely be more widely used by dermatologic surgeons in the future.

References

1. Drake LA et al. Guidelines of care for Mohs micrographic surgery. American Academy of Dermatology. J Am Acad Dermatol. 1995;33(2 Pt 1):271–8.

2. Cherpelis BS et al. Innovative 19-minute rapid cytokeratin immunostaining of nonmelanoma skin cancer in Mohs micrographic surgery. Dermatol Surg. 2009;35(7):1050–6.

3. Lane JE, Kent DE. Surgical margins in the treatment of nonmelanoma skin cancer and Mohs micrographic surgery. Curr Surg. 2005;62(5):518–26.

4.Robinson JK, Gottschalk R. Immunofluorescent and immunoperoxidase staining of antibodies to fibrous keratin.

Improved sensitivity for detecting epidermal cancer cells. Arch Dermatol. 1984;120(2):199–203.

5. Maize J, BW, Hurt M, LeBoit P, Metcalf, J, Smith T, Solomon A. Cutaneous Pathology. Philadelphia: Churchill Livingstone; 1998.

6. El Tal AK et al. Immunostaining in Mohs micrographic surgery: a review. Dermatol Surg. 2010;36(3):275–90.

7. Bricca GM, Brodland DG, Zitelli JA. Immunostaining melanoma frozen sections: the 1-hour protocol. Dermatol Surg. 2004;30(3):403–8.

8. Mondragon RM, Barrett TL. Current concepts: the use of immunoperoxidase techniques in Mohs micrographic surgery. J Am Acad Dermatol. 2000;43(1 Pt 1):66–71.

9. Zitelli JA, Brown C, Hanusa BH. Mohs micrographic surgery for the treatment of primary cutaneous melanoma. J Am Acad Dermatol. 1997;37(2 Pt 1):236–45.

10.Griego RD, Zitelli JA. Mohs micrographic surgery using HMB-45 for a recurrent acral melanoma. Dermatol Surg. 1998;24(9):1003–6.

11. Zitelli JA, Moy RL, Abell E. The reliability of frozen sections in the evaluation of surgical margins for melanoma. J Am Acad Dermatol. 1991;24(1):102–6.

12.Cohen LM et al. Successful treatment of lentigo maligna and lentigo maligna melanoma with Mohs’ micrographic surgery aided by rush permanent sections. Cancer. 1994;73(12): 2964–70.

13.Gross EA, Andersen WK, Rogers GS. Mohs micrographic

excision of lentigo maligna using Mel-5 for margin control. Arch Dermatol. 1999;135(1):15–7.

14. Zalla MJ et al. Mohs micrographic excision of melanoma using immunostains. Dermatol Surg. 2000;26(8):771–84.

15.Kelley LC, Starkus L. Immunohistochemical staining of lentigo maligna during Mohs micrographic surgery using MART-1. J Am Acad Dermatol. 2002;46(1):78–84.

16.Ohsie SJ et al. Immunohistochemical characteristics of melanoma. J Cutan Pathol. 2008;35(5):433–44.

17. Thosani MK, Marghoob A, Chen CS. Current progress of immunostains in Mohs micrographic surgery: a review. Dermatol Surg. 2008;34(12):1621–36.

18. El Shabrawi-Caelen L, Kerl H, Cerroni L. Melan-A: not a helpful marker in distinction between melanoma in situ on sun-damaged skin and pigmented actinic keratosis. Am J Dermatopathol. 2004;26(5):364–6.

19.Hendi A, Brodland DG, Zitelli JA. Melanocytes in long-standing sun-exposed skin: quantitative analysis using the MART-1 immunostain. Arch Dermatol. 2006;142(7):

871–6.

20. Maize Jr JC et al. Ducking stray “magic bullets”: a Melan-A alert. Am J Dermatopathol. 2003;25(2):162–5.

21.Geisse JK. Re: Questionable utility of Melan-A/Mart-1 immunoperoxidase staining while doing Mohs surgery for

melanoma. Dermatol Surg. 2005;31(4):495.

22. Cherpelis BS et al. Comparison of MART-1 frozen sections to permanent sections using a rapid 19-minute protocol. Dermatol Surg. 2009;35(2):207–13.

23. Kikuchi A, Shimizu H, Nishikawa T. Expression and ultrastructural localization of HMB-45 antigen. Br J Dermatol. 1996;135(3):400–5.

24. Menaker GM et al. Rapid HMB-45 staining in Mohs micrographic surgery for melanoma in situ and invasive melanoma. J Am Acad Dermatol. 2001;44(5):833–6.

25. Skelton HG et al. HMB45 negative spindle cell malignant melanoma. Am J Dermatopathol. 1997;19(6):580–4.

26. Bhardwaj SS, Tope WD, Lee PK. Mohs micrographic surgery for lentigo maligna and lentigo maligna melanoma using Mel-5 immunostaining: University of Minnesota experience. Dermatol Surg. 2006;32(5):690–6; discussion 696–7.

27. Albertini JG et al. Mohs micrographic surgery for melanoma: a case series, a comparative study of immunostains, an informative case report, and a unique mapping technique. Dermatol Surg. 2002;28(8):656–65.

28. King R et al. Microphthalmia transcription factor. A sensitive and specific melanocyte marker for melanoma diagnosis. Am J Pathol. 1999;155(3):731–8.

29. Stranahan D et al. Immunohistochemical stains in Mohs surgery: a review. Dermatol Surg. 2009;35(7):1023–34.

30. Glass LF et al. Rapid frozen section immunostaining of melanocytes by microphthalmia-associated transcription factor. Am J Dermatopathol. 2010;32(4):319–25.

31.Robinson JK. Current histologic preparation methods for Mohs micrographic surgery. Dermatol Surg. 2001;27(6):555–60.

32.Jimenez FJ et al. Immunohistochemical techniques in Mohs micrographic surgery: their potential use in the detection of neoplastic cells masked by inflammation. J Am Acad Dermatol. 1995;32(1):89–94.

33.Jacques C, de Aquino AM, Ramos-e-Silva M. Cytokeratins and dermatology. Skinmed. 2005;4(6):354–60; quiz 360–1.

34. Zachary CB et al. Rapid cytokeratin stains enhance the sensitivity of Mohs micrographic surgery for squamous cell carcinoma. J Dermatol Surg Oncol. 1994;20(8):530–5.

35. Smeets NW et al. Adjuvant cytokeratin staining in Mohs micrographic surgery for basal cell carcinoma. Dermatol Surg. 2003;29(4):375–7.

36. Albregts T et al. Squamous cell carcinoma in a patient with chronic lymphocytic leukemia. An intraoperative diagnostic challenge for the Mohs surgeon. Dermatol Surg. 1998;24(2): 269–72.

37. Latza U et al. Ber-EP4: new monoclonal antibody which distinguishes epithelia from mesothelial. J Clin Pathol. 1990;43(3):213–9.

38. Tellechea O et al. Monoclonal antibody Ber EP4 distinguishes basal-cell carcinoma from squamous-cell carcinoma of the skin. Am J Dermatopathol. 1993;15(5):452–5.

39. Kist D et al. Anti-human epithelial antigen (Ber-EP4) helps define basal cell carcinoma masked by inflammation. Dermatol Surg. 1997;23(11):1067–70.

40.Katz KH et al. Dense inflammation does not mask residual primary basal cell carcinoma during Mohs micrographic surgery. J Am Acad Dermatol. 2001;45(2):231–8.

41. Krunic AL et al. The use of antidesmoglein stains in Mohs micrographic surgery. A potential aid for the differentiation of basal cell carcinoma from horizontal sections of the hair follicle and folliculocentric basaloid proliferation. Dermatol Surg. 1997;23(6):463–8.

42.Abdelsayed RA et al. Immunohistochemical evaluation of basal cell carcinoma and trichepithelioma using Bcl-2, Ki67, PCNA and P53. J Cutan Pathol. 2000;27(4):169–75.

43. Gloster HM, Harris Jr KR, Roenigk RK. A comparison between Mohs micrographic surgery and wide surgical excision for the treatment of dermatofibrosarcoma protuberans. J Am Acad Dermatol. 1996;35(1):82–7.

44.Haycox CL et al. Immunohistochemical characterization of dermatofibrosarcoma protuberans with practical applications for diagnosis and treatment. J Am Acad Dermatol.

1997;37(3 Pt 1):438–44.

45. Roh MR, Bae B, Chung KY. Mohs’ micrographic surgery for dermatofibrosarcoma protuberans. Clin Exp Dermatol. 2010;35:849–52.

46.Garcia C et al. Dermatofibrosarcoma protuberans treated with Mohs surgery. A case with CD34 immunostaining variability. Dermatol Surg. 1996;22(2):177–9.

47.Jimenez FJ et al. Immunohistochemical margin control

applied to Mohs micrographic surgical excision of dermatofibrosarcoma protuberans. J Dermatol Surg Oncol. 1994;20(10): 687–9.

48. O’Connor WJ et al. Comparison of Mohs micrographic surgery and wide excision for extramammary Paget’s disease. Dermatol Surg. 2003;29(7):723–7.

49.Mohs FE, Blanchard L. Microscopically controlled surgery for extramammary Paget’s disease. Arch Dermatol. 1979; 115(6):706–8.

50.Hendi A, Brodland DG, Zitelli JA. Extramammary Paget’s disease: surgical treatment with Mohs micrographic surgery. J Am Acad Dermatol. 2004;51(5):767–73.

51.Coldiron BM, Goldsmith BA, Robinson JK. Surgical treat-

ment of extramammary Paget’s disease. Cancer. 1991;67(4): 933–8.

52. Smith KJ et al. Cytokeratin 7 staining in mammary and extramammary Paget’s disease. Mod Pathol. 1997;10(11): 1069–74.

53. Harris DW et al. Rapid staining with carcinoembryonic antigen aids limited excision of extramammary Paget’s disease treated by Mohs surgery. J Dermatol Surg Oncol. 1994; 20(4):260–4.

54. Chilukuri S, Peterson SR, Goldberg LH. Granular cell tumor of the heel treated with Mohs technique. Dermatol Surg. 2004;30(7):1046–9.

55. Gardner ES, Goldberg LH. Granular cell tumor treated with Mohs micrographic surgery: report of a case and review of the literature. Dermatol Surg. 2001;27(8):772–4.

56. Abraham T et al. Mohs surgical treatment of a granular cell tumor on the toe of a child. Pediatr Dermatol. 2007;24(3): 235–7.

57.Smith SB et al. Mohs micrographic surgery for granular cell tumorusingS-100immunostain.DermatolSurg.2002;28(11): 1076–8.

58.Marra DE, Schanbacher CF, Torres A. Mohs micrographic

surgery of primary cutaneous mucinous carcinoma using immunohistochemistry for margin control. Dermatol Surg. 2004;30(5):799–802.

59. Ortiz KJ et al. A case of primary mucinous carcinoma of the scalp treated with Mohs surgery. Dermatol Surg. 2002; 28(8):751–4;discussion 754.

60.Cecchi R, Rapicano V. Primary cutaneous mucinous carcinoma: report of two cases treated with Mohs’ micrographic

surgery. Australas J Dermatol. 2006;47(3):192–4.

61. Bellezza G, Sidoni A, Bucciarelli E. Primary mucinous carcinoma of the skin. Am J Dermatopathol. 2000;22(2): 166–70.

62.Allee JE et al. Multiply recurrent trichilemmal carcinoma with perineural invasion and cytokeratin 17 positivity. Dermatol Surg. 2003;29(8):886–9.