have frequent necrosis, and have vascular or perineural invasion. Staining for LN-2 (CD74) has been reported to be stronger in MFH than in AFX [45]. The relationship between UV radiation and lesion development has not been found with MFH as it has for AFX, which suggests that MFH and AFX have different mechanisms of molecular pathogenesis [30, 31]. MFH has been reported to be more aggressive than AFX, often with more-frequent recurrences and a greater propensity to metastasize, and therefore has a poorer prognosis than AFX.

Summary: Treatment

¥Treatment of choice is complete surgical removal.

¥Recently, Mohs micrographic surgery has been found to be superior to wide local excision.

¥Recurrence rate has been reported to be 5%.

¥Long-term follow-up is important to detect recurrence and/or metastasis.

21.5Treatment

The treatment modality of choice for AFX is complete surgical removal. This is usually achieved using WLE, or total microscopic margin control is achieved using MMS (Fig. 21.4) [6, 33, 46, 47]. Historically, AFX has been treated with WLE because it was thought that complete, conservative, local excision was adequate treatment [4, 14, 48, 49]. A recommendation of 6-mm margins, similar to treatment recommendations for squamous cell carcinoma, was advocated [50]. However, no large studies have deÞned what constitutes adequate margins.

Many studies in recent decades have reported MMS to be superior to WLE for treatment of AFX, and therefore MMS is now the recommended treatment for AFX [6, 33Ð35, 46, 51Ð53]. The advantages of MMS are that it allows for both tissue conservation, which is especially important on the head and neck, and achievement of total microscopic margin control.

Two studies have compared WLE and MMS for the treatment of AFX. Davis et al. [33] reported their experience with 44 patients with AFX, of which 19 were treated with MMS and 25 were treated with WLE. There were no recurrences in patients treated with MMS after a mean follow-up of 29.6 months. In the 25 patients treated with WLE, there were 4 recurrences (16%) with a mean time to recurrence of 16 months [33, 53]. In a more recent study by Ang et al. [6] of patients with AFX, 59 of 88 tumors (67%) were treated with MMS, 23 (26.1%) were treated with WLE, and 6 (6.8%) were treated with other modalities (5 with electrodesiccation and curettage and 1 with shave excision). After a median follow-up of 4.5 years, there were no recurrences in those treated with MMS; there were 2 recurrences (8.7%) in patients treated with WLE after a median follow-up of 8.7 years.

Several other groups have reported their experience with the use of MMS for treatment of AFX [34, 35, 51, 54]. Of 13 cases of AFX treated with MMS reported by Seavolt et al. [35], follow-up data were available for 6 patients, and there were no recurrences after 2 years. Limmer et al. [51] reported treatment of AFX with MMS in six patients, and no recurrences were noted. In contrast to all previous studies reporting no recurrences after treatment with MMS, Huether et al. [34] reported 2 recurrences in 29 patients (6.9%) after a mean follow-up of 3.3 years.

The few data reported regarding the surgical margins necessary for tumor clearance have been conßicting. Limmer et al. [51] reported an average of 9-mm surgical margins for clearance of tumor. In contrast, Ang et al. [6] reported that the median margin needed for tumor clearance with MMS was 0.4 cm (range, 0Ð3.2 cm), but the margin was greater than 2.0 cm in two patients (3.4%). Therefore, if AFX is treated with WLE, a 2-cm margin would be necessary for clearance of 96.6% of tumors.

Because of the potential of AFX to metastasize to regional lymph nodes, sentinel lymph node biopsy has been suggested [7, 55]. However, there are essentially no data in the literature deÞning the role of sentinel lymph node biopsy after a diagnosis of AFX.

Adjuvant radiation therapy has been used both for locally recurrent AFX and for affected lymph nodes in metastatic disease [17, 50, 55]. The use of radiation therapy and/or adjuvant chemotherapy after surgical treatment of primary AFX, however, has not been reported.

The recurrence rate for AFX after removal has been reported to be 5% [19]. This rate is much different than the recurrence rates of 2Ð21% reported in the 1960s and 1970s [8, 48, 56, 57]. The true recurrence rate of AFX today is much lower than that reported in the past, most likely because more patients are being treated with MMS or because wider excision margins are being used with WLE. Because of the potential for recurrence, regular follow-up is necessary. Long-term follow-up including examination and palpation of the surgical site, palpation of regional lymph nodes, and possible evaluation for distant metastatic disease is also very important. This should be performed regularly for at least the Þrst 2 years after diagnosis, because this is when most recurrences and metastases have been reported to occur [6, 17].

Summary: Conclusion

¥AFX has the potential for regional and/or distant metastasis.

¥Complete surgical removal of the primary tumor, ideally with MMS, is recommended.

¥Long-term follow-up is important to detect recurrence and/or metastasis.

21.6Conclusion

It is important to recognize the potential for regional and/or distant metastasis with a diagnosis of AFX. Therefore, complete surgical removal of the primary tumor, ideally with MMS, is recommended. MMS allows for total microscopic margin control and at the same time allows for tissue conservation. This is especially important for tumors on the head and neck, where AFX is most likely to occur. Long-term followup is essential for monitoring for the development of recurrence or metastasis.

References

1.Helwig EB. Atypical Þbroxanthoma: proceedings of the 18th annual tumor seminar San Antonio Society of Pathologists, 1961. Tex State J Med. 1963;59:664Ð7.

2.Connors R, Ackerman A. Histologic pseudomalignancies of the skin. Arch Dermatol. 1976;112:1767Ð80.

3. Gleason BC, Calder KB, Cibull TL, et al. Utility of p63 in the differential diagnosis of atypical Þbroxanthoma and spindle cell squamous cell carcinoma. J Cutan Pathol. 2009;36:543Ð7.

4. Starink TH, Hausman R, Van Delden L, Neering H. Atypical Þbroxanthoma of the skin. Presentation of 5 cases and a review of the literature. Br J Dermatol. 1977;97:167Ð77.

5. Beer TW, Drury P, Heenan PJ. Atypical Þbroxanthoma: a histological and immunohistochemical review of 171 cases. Am J Dermatopathol. 2010;32(6):533Ð40.

6. Ang GC, Roenigk RK, Otley CC, Kim Phillips P, Weaver AL. More than 2 decades of treating atypical Þbroxanthoma at Mayo Clinic: what have we learned from 91 patients? Dermatol Surg. 2009;35:765Ð72.

7. Cooper JZ, Newman SR, Scott GA, Brown MD. Metastasizing atypical Þbroxanthoma (cutaneous malignant histiocytoma): report of Þve cases. Dermatol Surg. 2005; 31:221Ð5.

8.Dahl I. Atypical Þbroxanthoma of the skin: a clinicopathological study of 57 cases. Acta Pathol Microbiol Scand A. 1976;84:183Ð97.

9. Grosso M, Lentini M, Carrozza G, Catalano A. Metastatic atypical Þbroxanthoma of skin. Pathol Res Pract. 1987; 182:443Ð7.

10.Guiffrida TJ, Kligora CJ, Goldstein GD. Localized cutaneous metastases from an atypical Þbroxanthoma. Dermatol Surg. 2004;30:1561Ð4.

11.Helwig EB, May D. Atypical Þbroxanthoma of the skin with metastasis. Cancer. 1986;57:368Ð76.

12. Jacobs DS, Edwards WD, Ye RC. Metastatic atypical Þbroxanthoma of skin. Cancer. 1975;35:368Ð76.

13. Kargi E, Gungor E, Verdi M, et al. Atypical Þbroxanthoma and metastasis to the lung. Plast Reconstr Surg. 2003;111: 1760Ð2.

14. Kemp JD, Stenn KS, Arons M, Fischer J. Metastasizing atypical Þbroxanthoma: coexistence with chronic lymphocytic leukemia. Arch Dermatol. 1978;114:1533Ð5.

15. Lum DJ, King AR. Peritoneal metastases from an atypical Þbroxanthoma. Am J Surg Pathol. 2006;30:1041Ð6.

16. Muenster MR, Hoang MP. Left facial mass in an elderly man: metastasizing atypical Þbroxanthoma of the skin. Arch Pathol Lab Med. 2006;130:735Ð6.

17. New D, Bahrami S, Malone J, Callen JP. Atypical Þbroxanthoma with regional lymph node metastasis: report of a case and review of the literature. Arch Dermatol. 2010;146(12): 1399Ð404.

18.Sankar NM, Pang KS, Thiruchelvam T, Meldrum-Hanna WG. Metastasis from atypical Þbroxanthoma of skin. Med J Aust. 1998;168:418Ð9.

19.Weedon D. Tumors and tumor-like proliferations of Þbrous and related tissues. 2nd ed. London: Churchill Livingston; 2002.

20.Bourne RG. Paradoxical Þbrosarcoma of the skin (pseudosarcoma): a review of 13 cases. Med J Aust. 1963;1:504Ð10.

21.Finlay-Jones LR, Nicoll P, ten Seldam RE. Pseudosarcoma of the skin. Pathology. 1971;3:215Ð22.

22.Gordon HW. Pseudosarcomatous reticulohistiocytoma. Arch Dermatol. 1964;90:319Ð25.

23.Alguacil-Garcia A, Unni KK, Goellner JR, Winkelmann RK. Atypical Þbroxanthoma of the skin: an ultrastructural study of two cases. Cancer. 1977;40:1471Ð80.

24. Barr RJ, Wuerker RB, Graham JH. Ultrastructure of atypical Þbroxanthoma. Cancer. 1977;40:736Ð43.

25. Longacre TA, Smoller BR, Rouse RV. Atypical Þbroxanthoma. Multiple immunohistologic proÞles. Am J Surg Pathol. 1993;17:1199Ð209.

26. Hall PA, McKee PH, Menage HD, Dover R, Lane DP. High levels of p53 protein in UV-irradiated normal human skin. Oncogene. 1993;8:203Ð7.

27. Moan J, Peak MJ. Effects of UV radiation of cells. J Photochem Photobiol B. 1989;4:21Ð34.

28.Larson KL, Strauss BS. Inßuence of template strandedness on in vitro replications of mutagen-damaged DNA. Biochemistry. 1987;26:2471Ð9.

29.Vogelstein B, Kinzler KW. Carcinogens leave Þngerprints. Nature. 1992;355:209Ð10.

30. Dei Tos AP, Maestro R, Doglioni C, et al. Ultravioletinduced p53 mutations in atypical Þbroxanthoma. Am J Pathol. 1994;145:11Ð7.

31. Sakamoto A, Oda Y, Itakura E, et al. Immunoexpression of ultraviolet photoproducts and p53 mutation analysis in atypical Þbroxanthoma and superÞcial malignant Þbrous histiocytoma. Mod Pathol. 2001;14:581Ð8.

32.Luzar B, Calonje E. Morphological and immunohistochemical characteristics of atypical Þbroxanthoma with a special emphasis on potential diagnostic pitfalls: a review. J Cutan Pathol. 2010;37:301Ð9.

33.Davis JL, Randle HW, Zalla MJ, Roenigk RK, Brodland DG. A comparison of Mohs micrographic surgery and wide excision for the treatment of atypical Þbroxanthoma. Dermatol Surg. 1997;23:105Ð10.

34.Huether MJ, Zitelli JA, Brodland DG. Mohs micrographic surgery for the treatment of spindle cell tumors of the skin. J Am Acad Dermatol. 2001;44:656Ð9.

35.Seavolt M, McCall M. Atypical Þbroxanthoma: review of the literature and summary of 13 patients treated with Mohs micrographic surgery. Dermatol Surg. 2006;32:435Ð41.

36. Evans HL, Smith JL. Spindle cell squamous carcinomas and sarcoma-like tumors of the skin: a comparative study of 38 cases. Cancer. 1980;45:2687Ð97.

37.Fretzin DF, Helwig EB. Atypical Þbroxanthoma of the skin. A clinicopathologic study of 140 cases. Cancer. 1973;31: 1541Ð52.

38.Leong AS, Milios J. Atypical Þbroxanthoma of the skin: a clinicopathological and immunohistochemical study and a discussion of its histogenesis. Histopathology. 1987;11: 463Ð75.

39.Weiss SW, Goldblum JR. Enzinger and WeissÕs Soft Tissue Tumors, 5th edition, Mosby, 2008.

40.Rizzardi C, Angiero F, Melato M. Atypical Þbroxanthoma

and malignant Þbrous histiocytoma of the skin. Anticancer Res. 2003;23:1847Ð51.

41. Dotto JE, Glusac EJ. p63 is a useful marker for cutaneous spindle cell squamous cell carcinoma. J Cutan Pathol. 2006;33:413Ð7.

42.Gray Y, Robidoux HJ, Farrell DS, Robinson-Bostom L. Squamous cell carcinoma detected by high-molecular- weight cytokeratin immunostaining mimicking atypical Þbroxanthoma. Arch Pathol Lab Med. 2001;125: 799Ð802.

43.Greene LA, Cooper K. Atypical Þbroxanthoma: an immunohistochemistry update. Adv Anat Pathol. 2008;15:374.

44. Jensen K, Wilkinson B, Wines N, Kossard S. Procollagen 1 expression in atypical Þbroxanthoma and other tumors. J Cutan Pathol. 2004;31:57Ð61.

45. Lazova R, Moynes R, May D, Scott G. LN-2 (CD74). A marker to distinguish atypical Þbroxanthoma from malignant Þbrous histiocytoma. Cancer. 1997;79:2115Ð24.

46.Brown MD, Swanson NA. Treatment of malignant Þbrous histiocytoma and atypical Þbrous xanthomas with micrographic surgery. J Dermatol Surg Oncol. 1989;15:1287Ð92.

47.Dzubow LM. Mohs surgery report: spindle cell Þbrohistiocytic tumors: classiÞcation and pathophysiology. J Dermatol Surg Oncol. 1988;14:490Ð5.

48.Kempson RL, McGavran MH. Atypical Þbroxanthomas of the skin. Cancer. 1964;17:1463Ð71.

49. Poleksic S, Kalwaic HJ, Bialas RF. Benign atypical Þbroxanthoma or a malignant tumor? A warning. Case reports. Plast Reconstr Surg. 1976;58:501Ð5.

50. Wylie J, Hampton N, Telfer MR, Clarke AM. Atypical Þbroxanthoma: case series of 16 patients. Br J Oral Maxillofac Surg. 2010;48:466Ð8.

51.Limmer BL, Clark DP. Cutaneous micrographic surgery for atypical Þbroxanthoma. Dermatol Surg. 1997;23:553Ð8.

52. Nouri K, Rivas MP. A primer of Mohs micrographic surgery: uncommon indications. Skin Med. 2004;3:259Ð65.

53. Zalla MJ, Randle HW, Brodland DG, Davis JL, Roenigk RK. Mohs surgery vs. wide excision for atypical Þbroxanthoma: follow up. Dermatol Surg. 1997;23:1223Ð4.

54.Anderson PJ, McPhaden AR, Ratcliffe RJ. Atypical Þbroxanthoma of the scalp. Head Neck. 2001;23:399Ð403.

55. Sahn RE, Lang PG. Sentinel lymph node biopsy for highrisk nonmelanoma skin cancers. Dermatol Surg. 2007;33: 786Ð93.

56.Kroe DJ, Pitcock JA. Atypical Þbroxanthoma of the skin: report of ten cases. Am J Clin Pathol. 1969;51:487Ð92.

57.Vargas-Cortes F, Winkelmann RK, Soule EH. Atypical Þbroxanthomas of the skin: further observations with 19 additional cases. Mayo Clin Proc. 1973;48:211Ð8.