Ossifying Adult Xanthogranuloma Open Access

A xanthogranuloma is a relatively common benign histiocytic condition of children and adults. Although ossification has been observed within many cutaneous lesions, its presence in xanthogranulomas is a feature that has not yet, to our knowledge, been reported. We describe a case of xanthogranuloma with marked osseous metaplasia on the trunk of a 41-year-old woman.

A previously healthy 41-year-old woman presented with a hard, yellowish, dome-shaped 2 × 3-cm cutaneous lesion on the left side of her trunk of many years' duration. The lesion was locally excised with free margins for histologic examination after a clinical diagnosis of xanthogranuloma. No evidence of recurrence or metastases has been observed 1 year and 2 months after resection.

The entire biopsy specimen measured 3.5 × 2.5 × 1.5 cm and was routinely fixed, processed, and stained with hematoxylin-eosin. Microscopically, the tumor was well circumscribed within the dermis (Figure 1) and was characterized by a diffuse proliferation of foamy histiocytes admixed with abundant Touton giant cells and a sparse chronic inflammatory infiltrate (Figure 2). The epidermis overlying the lesion was hyperplastic. The central part of the lesion showed trabeculae composed of mineralized osteoids with central lacunae housing osteocytes and surrounded by osteoblasts (Figure 1). Immunohistochemically, the tumor cells showed strong positivity for vimentin, KP1 (CD68), and LN3 (HLA-DR) (Figure 2, inset) and focal immunoreactivity for leukocyte common antigen (CD45) and CD4. Factor XIIIa, Mac-387 (L1 antigen), CD8, and CD34 were all negative. The pathologic diagnosis was “xanthogranuloma with metaplastic bone formation.”

A xanthogranuloma is a benign, self-limited, cutaneous fibrohistiocytic lesion that usually occurs on the head, neck, or trunk. Xanthogranulomas mainly affect infants in the first 6 months of life, with no sex predilection; however, in approximately 15% of these types of cases, lesions can be found as a solitary tumor in adolescents and adults, as in the present case. Previous reports have described special clinical variants of xanthogranuloma, including giant forms with exophytic or endophytic growth, atypical forms with extensive facial or generalized eruptions,1 and rare cases with visceral organ involvement.2 Moreover, cases of xanthogranuloma with peculiar histologic features such as the absence of foam and giant cells,3 increased mitotic activity,3 and the presence of “monster” or scalloped cells4 as well as deep-seated xanthogranulomas with subcutaneous and intramuscular involvement5 have also been reported. To our knowledge, this is the first report of metaplastic bone formation within a xanthogranuloma.

The presence of bone within the skin is an uncommon microscopic finding that may occur in various circumstances. First, it may be a primary event without a demonstrable preceding cutaneous lesion (eg, osteoma cutis, Albright hereditary osteodystrophy). Alternatively, the cutaneous ossification may be secondary to local conditions such as trauma or scarring (eg, acne scars, injection sites, hematomas, surgical scars), inflammatory processes (eg, morphea, systemic scleroderma, dermatomyositis, chronic venous stasis), or, most commonly, benign or malignant cutaneous tumors. The majority of these neoplasms tend to be epithelial or melanocytic and include pilomatricomas,6 basal cell carcinomas,7 common acquired melanocytic nevi8 and their specific variants (eg, Spitz nevi, blue nevi), and malignant melanomas.9 The melanocytic nevus is one of these tumors that most commonly shows metaplastic ossification; next most common are basal cell carcinomas and pilomatricomas (calcifying epithelioma of Malherbe).10 Ossification has also very occasionally been described in cutaneous fibrohistiocytic lesions such as dermatofibromas,11 malignant fibrous histiocytomas, plexiform fibrohistiocytic tumors,12 and atypical fibroxanthomas.13 

The etiopathogenesis of secondary ossification in skin lesions is not completely understood. The prevailing theory is that bone formation is a metaplastic process. Metaplasia is defined as “a reversible change in which one adult cell type (epithelial or mesenchymal) is replaced by another adult cell type.”14 In our case, no areas of mature cartilage were observed near the focus of ossification; thus, the cutaneous bone may have been directly formed from osteogenic stromal elements without a cartilaginous precursor (membranous or mesenchymal ossification). This type of ossification has also been proposed in most ossified tumors, such as the nevus of Nanta, in which, following trauma or folliculitis, there is subsequent osseous metaplasia of the inflammatory scar. In the present case, foci of dystrophic calcification, secondary to necrotic or hemorrhagic areas induced by trauma, may have contributed to the bone-forming process.

Finally, a focus of secondary ossification may be misdiagnosed as an osteoma cutis if elements of the underlying lesion are obscured.7 This error is especially serious if the underlying lesion is a malignant tumor such as a melanoma or basal cell carcinoma; hence, pathologists should be aware of this possibility.

The differential diagnosis includes those benign mesenchymal tumors in which Touton giant cells can be present in their composition, especially with the histiocytic variant of dermatofibroma (“histiocytoma”). Unlike the tumor cells in xanthogranulomas, the tumor cells in dermatofibromas are characteristically distributed in a fibrous background and show irregular outlines with infiltration of the adjacent dermis. Moreover, dermatofibromas often induce a marked overlying epidermal hyperplasia in the center of the lesion and show hyalinized collagen bundles surrounded by tumor cells in the periphery. Immunohistochemically, CD68 is readily observed not only in xanthogranulomas but also in the xanthomatous histiocytes of dermatofibromas. Unlike the tumor cells in dermatofibromas, the tumor cells in most xanthogranulomas are typically immunoreactive for HLA-DR, CD45, and CD4, as in our case. However, dermatofibromas are typically factor XIIIa positive,15 which is unlike the findings in our case.

In summary, we describe for the first time, to our knowledge, a rare variant of a xanthogranuloma characterized by a massive metaplastic bone formation in a 41-year-old woman.