American Journal of Dermatopathology:
Letter to the Editor
Consultant Dermatopathologist, Cutaneous Pathology, Nedlands, WA.
To the Editor:
In this journal, Wooff et al1 recently reported 2 cases of cutaneous squamous cell carcinoma with osteoclast-like giant cells. They discussed the differential diagnosis of this condition and concluded that the giant cells were an unusual reaction to the tumors, rather than representing neoplastic cells. Three similar cases were also reported in correspondence to this journal by Emanuel2 earlier in 2009.
At Cutaneous Pathology, during a recent archival review of 183 cases diagnosed as atypical fibroxanthoma (AFX), 4 lesions were identified with osteoclast-like giant cells. Two cases were confirmed as AFX on the clinical and histological appearances allied with a panel of immunostains that included multiple melanocytic and epithelial markers. The clinical features of the other 2 cases are shown in the Table 1. Both lesions exhibited atypical spindle-shaped cells invading the dermis without pigmentation, junctional activity, or obvious keratinization. In case 1, there was also a small complement of epithelioid cells. Scattered diffusely throughout each neoplasm were multinucleated giant cells of osteoclast-like appearance, which were CD68 positive (Figs. 1, 2).
Occasional multinucleated neoplastic cells were also present in case 1. These were distinguishable from the osteoclast-like giant cells by nuclei that showed highly irregular contours with hyperchromasia, pleomorphism, and cytoplasmic cytokeratin positivity (Fig. 3).
Although both neoplasms had been previously categorized as AFX, reexamination of the immunostains revealed focal weak MNF116 and AE1/3 positivity in the atypical neoplastic cells in both cases. The osteoclast-like giant cells were negative. Case 2 was subsequently stained with 34betaE12, which showed more generalized and stronger neoplastic cell staining than had been seen on the previous epithelial stains, with negative staining of the osteoclast-like giant cells. The appearances in each case were reinterpreted as representing poorly differentiated (sarcomatoid) squamous cell carcinoma with osteoclast-like giant cells.
Osteoclast-like giant cells seem to be a rare feature of AFX, seen in only 2 of 183 cases in this series (1.0%). Because of the difficulty of excluding a poorly differentiated squamous cell carcinoma, it is possible that some of the cases previously reported in the literature as AFX with osteoclast-like giant cells may be erroneous.
In summary, I agree with Wooff et al1 and Emanuel2 that rare squamous cell carcinomas in the skin may demonstrate included osteoclast-like giant cells that are most likely to be macrophage derived. Their presence may invoke confusion with AFX, especially if cytokeratin stains are weak or patchy. Consequently, I recommend the use of a range of cytokeratin stains to distinguish poorly differentiated squamous cell carcinomas from AFX and suggest including 34betaE12 in this panel. The utility of 34betaE12 has been previously highlighted in the literature after a poorly differentiated recurrent squamous cell carcinoma was misdiagnosed as AFX until a high-molecular weight cytokeratin was applied.3
Finally, as to whether the osteoclast-like giant cells are neoplastic or reactive, I suspect that both forms may occur. In most instances, the cells are likely macrophage derived (they are CD68 positive, negative with epithelial markers, and not cytologically atypical), whereas in other cases, they are multinucleated neoplastic cells. This would account for the atypia and positive epithelial markers reported in some previous cases.
T. W. Beer, MBChB, FRCPath, FRCPA
Consultant Dermatopathologist Cutaneous Pathology Nedlands, WA
1. Wooff J, Werner D, Murphy J, et al. Osteoclast-like giant cell reaction associated with cutaneous squamous cell carcinoma: a report of 2 cases and review of the literature. Am J Dermatopathol
2. Emanuel P. Osteoclast-type giant cells accompanying cutaneous squamous cell carcinoma. Am J Dermatopathol
3. Gray Y, Robidoux HJ, Farrell DS, et al. Squamous cell carcinoma detected by high-molecular weight cytokeratin immunostaining mimicking atypical fibroxanthoma. Arch Pathol Lab Med