Giant Cell Atypical Fibroxanthoma: Does it Really Exist?

Zelger, Bettina G. M.D.; Soyer, H. Peter M.D.; Zelger, Bernhard M.D.

American Journal of Dermatopathology:
Letters To The Editor
Author Information

University of Innsbruck; Innsbruck, Austria (Zelger)

Department of Dermatology; University of Graz; Graz, Austria (Soyer)

Department of Pathology and Dermatology; University of Innsbruck; Innsbruck, Austria (Zelger)

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To the Editor:

We read with great interest the recent article, "Atypical Fibroxanthoma With Osteoclast-like Multinucleated Giant Cells," by Khan and Cockerell (1) describing a "rare variant of atypical fibroxanthoma (AFX)." Several points deserve comment.

First, as briefly mentioned by the authors, this is not the first description of a "giant cell variant of AFX." Similar cases have previously been described by Wilson et al. (2), Val-Bernal et al. (3), and, most recently-shortly before the current paper-by Tomaszewski and Lupton (4). Coupled with our experience of four similar cases (Table 1), this seems to indicate that this lesion is more common than generally believed.

Second, from the photomicrographs provided in all these articles, we strongly doubt the correctness of this diagnosis. Khan and Cockerell (1) show in their Fig. 1 a scanning magnification of a regular, symmetric lesion rich in giant cells evenly distributed throughout the whole lesion. No epidermal erosion, no tumoral necrosis, no variable crowding of tumor cells or nuclei, and no irregular distribution of the inflammatory infiltrate can be seen in their Figs. 2 to 6. Similarly, no single photomicrograph of the other five previously described cases (2-4) documents such features.

Yet, what does one see in all these cases? Considering the location of the lesions, i.e., the face and in one case, the forearm (4), as well as the age of the patients, all older than 65 years, where at least some epidermal atrophy is usually seen, all these lesions have fairly prominent acanthosis. Moreover, delicate sclerosis, regularly distributed peripheral lymphohistiocytic tissue response, and some focal storiform areas can be seen. Higher magnifications frequently even better outline many of these features, e.g., Figs. 2 and 6 by Khan and Cockerell (1), Figs. 3 and 4 by Wilson et al. (2), Fig. 1 by Val-Bernal et al. (3), and Figs. 3 and 4 by Tomaszewski and Lupton. Identical features could be seen in all our four cases (Fig. 1). Thus, from our point of view, we are dealing with a pseudosarcomatous variant of fibrous histiocytoma.

This entity was first described by Fukamizu et al. in 1983 (5) and confirmed several years later by Leyva and Santa Cruz (6) as well as Kutchemeshgi et al. (7). Interestingly, nearly all the lesions so far described occurred on the head or upper extremities. As these are also the predilection sites of AFX, this might easily explain their confusion with giant cell AFX. The comparatively high number of mitoses is notable, yet not discordant with such lesions. Numerous mitoses can be seen in a variety of benign lesions such as pyogenic granuloma, pseudolymphoma, nodular fasciitis, or dermatofibroma. This is particularly the case in early, i.e., evolving, phases of dermatofibromas which frequently develop rather rapidly within days to weeks after various injuries. Interestingly, such lesions are then often positive for factor XIIIa, E9, an antimetallothionein marker indicating high proliferating or metabolic activity, and proliferating cell nuclear antigen, a classic proliferation marker (Table 1). Although in our experience proliferating cell nuclear antigen is not helpful for differentiation between pseudosarcomatous dermatofibroma and AFX, both other markers may be. Apart from some peripheral and intratumoral stromal response, AFX is usually negative for factor XIIIa as it is with E9 (8). Moreover, the benign character of these lesions is also indicated by their diploid nature with flow cytometry, which has also been shown for "giant" (3) as well as other variants of AFX (9).

Third and finally, this series of articles (1-4), although trying to expand the horizon of AFX, indeed rather questions the concept as a whole: When most reputed (dermato-)pathologists such as Clay Cockerell, George Lupton, and Fernando Val-Bernal, diagnose AFX, where others such as Danny Santa Cruz, Ron Barr, or our group consider a dermatofibroma or histiocytoma, at least as a possibility, this documents the unspecificity of the AFX pattern. Indeed, this is nothing new as AFX is known as a diagnosis of exclusion after ruling out malignant melanoma, spindle cell squamous cell carcinoma and basal cell carcinoma, leiomyosarcoma, myofibrosarcoma, etc. by respective immunohistochemical and ultrastructural studies. We are at present preparing a large series of more than 80 lesions from our two centers originally diagnosed as AFX. When we looked at all these cases together we recognized that in one center (Graz) some adult xanthogranulomas and in the other (Innsbruck) some leiomyosarcomas and their close relatives, myofibrosarcomas, had been erroneously diagnosed as AFX. Moreover, the four cases of pseudosarcomatous dermatofibroma described above could be elaborated. Thus, AFX behaves similar to its deeply located counterpart malignant fibrous histiocytoma, which according to Fletcher (10) represents a potpourri of histogenetically different, dedifferentiated tumors including sarcomas, carcinomas, melanomas, and lymphomas.

We hope Drs. Khan and Cockerell as well as all the colleagues from the other papers (2-4) will not feel offended by our differing point of view and comments. We think their articles as well as the possibility to evaluate their concept and idea of AFX markedly increase the understanding of this enigmatic entity which maybe one day will disappear from the textbooks because of a more sophisticated and experienced approach to these lesions.

Bettina G. Zelger, M.D.

University of Innsbruck; Innsbruck, Austria

H. Peter Soyer, M.D.

Department of Dermatology; University of Graz; Graz, Austria

Bernhard Zelger, M.D.

Department of Pathology and Dermatology; University of Innsbruck; Innsbruck, Austria

Acknowledgement: The authors are grateful to Dr. Peter Puffer, Private Laboratory for Forensic Pathology and Pathology, Innsbruck, Austria, who contributed case 4 to this series. We thank Prof. J. Kay and Dr. M. Stark, University of Wales, Cardiff, United Kingdom for kindly providing us with the antimetallothionein marker E9.

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1. Khan ZM, Cockerell CJ. Atypical fibroxanthoma with osteoclast-like multinucleated giant cells. Am J Dermatopathol 1997;19:174-9.
2. Wilson PR, Strutton GM, Stewart MR. Atypical fibroxanthoma: two unusual variants. J Cutan Pathol 1989;16:93-8.
3. Val-Bernal JF, Corral J, Fernandez F, Gomez-Bellvert C. Atypical fibroxanthoma with osteoclast-like giant cells. Acta Derm Venereol 1994;74:467-70.
4. Tomaszewski MM, Lupton GP. Atypical fibroxanthoma. An unusual variant with osteoclast-like giant cells. Am J Surg Pathol 1997;21:213-8.
5. Fukamizu H, Oku T, Inoue K, Matsumoto K, Okayama H, Tagami H. Atypical ("pseudosarcomatous") cutaneous histiocytoma. J Cutan Pathol 1983;10:327-33.
6. Leyva WH, Santa Cruz DJ. Atypical cutaneous fibrous histiocytoma. Am J Dermatopathol 1986;8:467-71.
7. Kutchemeshgi M, Barr RJ, Henderson CD. Dermatofibroma with osteoclast-like giant cells. Am J Dermatopathol 1992;14:397-401.
8. Zelger B, Zelger BG, Ensinger Ch, Obrist P, Mikuz G. Metallothionein expression parallels the biologic behaviour of malignant fibrohistiocytic tumors. Int J Surg Pathol 1995;2(suppl):27.
9. Worrell JT, Ansari MQ, Ansari SJ, Cockerell CJ. Atypical fibroxanthoma: DNA ploidy analysis of 14 cases with possible histogenetic implications. J Cutan Pathol 1993;20:211-5.
10. Fletcher CDM. Pleomorphic malignant fibrous histiocytoma: fact or fiction? A critical reappraisal based on 159 tumors diagnosed as pleomorphic sarcoma. Am J Surg Pathol 1992;16:213-28.

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