A Case of Eruptive Xanthoma With the Lipidization of Keratinocytes

To the Editor: A 60-year-old man presented to the dermatology clinic with a 3-month history of multiple small nodules on his hands and trunk without any obvious symptoms. There has been a gradual increase in the number of lesions recently. His medical history and family history were unremarkable. The results of blood count, routine urine, and liver and kidney function tests were normal. The total cholesterol level was 8.9 mmol/L (normal range 2.80–5.20), and the triglyceride level was 21.3 mmol/L (0.35–1.70). Biopsy of a subcutaneous nodule on the left thumb was performed (Fig. 1A). Histopathology revealed foam cells that were diffusely distributed in the dermis and pagetoid in the epidermis, where there were intercellular bridges that surrounded the foam cells (Figs. 1B, C). Immunohistochemistry showed that both S100 and CD1a were negative in foam cells, while CD68 was diffusely positive in foam cells in the dermis but negative in those in the epidermis (Fig. 1D). The foam cells in the epidermis showed positive expression of cytokeratin AE1/AE3, but negative in dermis (Fig. 1D). Based on these findings, a diagnosis of eruptive xanthomas was made.FIGURE 1.: A, A subcutaneous nodule on the left thumb. Histopathology revealed foam cells in the dermis and in the epidermis (B, HE ×40; C, HE ×100). D, The foam cells in the dermis were strongly positive for CD68, but negative in the epidermis (×200). E, The foam cells in epidermis were positive for AE1/AE3, but negative in dermis (×200).Xanthomas are usually a cutaneous sign of a disorder of lipid metabolism and are usually seen in adults, although children with familial hypercholesterolemia may present with xanthomas. Skin biopsy may be required and reveals the characteristic lipid-filled macrophages in the dermis. In this case, the histopathology of the dermis was characterized by the infiltration of a large number of foam cells and a small number of foam cells in the epidermis in a pagetoid pattern. As expected, S100 and CD1a expressions were negative in the dermis, but CD68 expression was strongly positive. Interestingly, however, the foam cells in the epidermis did not express CD68. In other words, the foam cells in the dermis and the epidermis were not identical. We further performed immunohistochemical detection of AE1/AE3. The results showed that dermal foam cells were negative for AE1/AE3, while epidermal foam cells were positive for AE1/AE3. In addition, there were intercellular bridges around the foam cells in the epidermis. Therefore, it is suggested that the foam cells in the epidermis were derived from the lipidization of keratinocytes. To the best of our knowledge, the lipidization of keratinocytes in xanthomas has rarely been reported. It may be worthwhile to clarify the exact mechanism involved. Epidermotropism is a pathological finding that describes the spread of cells of diverse origins into the epidermis from an underlying dermal or subcutaneous nodule. Northcutt1 previously reported a case of epidermotropic xanthoma and found similar foam cells in the epidermis, but unlike in our case, immunohistochemistry showed that the foam cells in the epidermis were positive for CD68. The clinical manifestation was a small solitary papule on the left nasal tip. Some scholars believe that the patient may have had a special manifestation of nasal fibrous papulosis rather than a real xanthoma.2 Recently, another study has reported a rare case of multicentric reticulohistiocytosis presenting as epidermotropic papular xanthoma, but the foam cells in the epidermis were also CD68-positive, which is different from this case.3 In conclusion, clear cell proliferations of the skin are a diverse group of lesions characterized by cells with abundant clear cytoplasm. The epidermotropic change seen in xanthoma is a very unusual finding. Histologic diagnosis can be challenging. Key immunohistochemical staining patterns of the different entities are required for proper consideration. In this article, we report a case of xanthoma in which there were focally lipidized keratinocytes. Although the exact mechanism is still unclear, this unique pathological change is interesting. Whether it is an independent xanthoma subtype or just an accidental pathological phenomenon is worth verifying.