A Case of Secondary Anetoderma Following Dermatofibroma

To the Editor: A 34-year-old Japanese woman presented to our outpatient clinic with a brown patch on her right popliteal fossa, present for approximately 2 years. The initial physical examination revealed a 13 × 11-mm brown nodule with clear borders (Fig. 1A). Dermoscopic examination showed a central white patch and a peripheral delicate pigment network (Fig. 1B). The lesion was initially considered to be a dermatofibroma, and follow-up was recommended due to the patient's pregnancy.FIGURE 1.: Clinical, dermoscopic, and histopathological findings. A, Lesion in the right popliteal fossa at the first visit. A brown patch is visible in the right knee fossa. B, Dermoscopic findings at the first visit. A central white patch and a peripheral delicate pigment network are observed. C, Ten months after the first visit. The patch has slightly enlarged and appears depressed, resembling a hernia when pressed with a finger. D, Dermoscopic findings 10 months later. In addition to the central white patch and peripheral delicate pigment network, a brown subcutaneous nodule is visible through the skin in the central area of the lesion. E, The epidermis is slightly thickened, with a well-defined mass located just beneath it, extending from the shallow to deep dermis. The border between the mass and the epidermis is clear (H&E). F, Fibroblast-like spindle-shaped cells proliferate along with collagen fibers within the lesion. No findings suggestive of malignancy are observed (H&E). G, Multinucleated giant cells are observed in the peripheral area of the lesion (H&E). H and I, Some multinucleated giant cells at the mass margins have phagocytotic images of elastic fibers. J, The elastic fibers in the perilesional dermis are reduced or absent compared with the normal dermis at the margins (Elastica–Masson staining). K, Immunostaining for CD34. L, Immunostaining for Factor-XⅢa.Approximately 10 months after the initial visit, the patient returned for excision of the nodule. The lesion had enlarged to 19 × 13 mm and exhibited a hernia-like depression on digital pressure (Fig. 1C). Dermoscopic examination revealed, in addition to the previously observed central white patch and peripheral delicate pigment network, a brown cutaneous nodule visible through the skin in the central area of the lesion (Fig. 1D). The lesion was excised under local anesthesia. Histopathological examination revealed a slightly thickened epidermis with a well-defined mass directly beneath it, extending from the superficial to deep layers of the dermis. The border between the mass and the epidermis was relatively clear (Fig. 1E). Within the mass, there was an irregular proliferation of collagen fibers and spindle-shaped fibroblast-like cells (Fig. 1F). Multinucleated giant cells were present in the tissue surrounding the mass, some containing hemosiderin deposits (Fig. 1G) and exhibiting elastophagocytosis (Figs. 1H, I). Notably, clumped elastic fibers were identified at the base of the mass, while elastic fibers in the surrounding dermis were reduced or absent (Fig. 1J). Immunohistochemical analysis showed that the mass was CD34-negative and factor XIIIa-positive (Figs. 1K, L). No findings suggestive of malignancy, such as nuclear atypia or mitosis, were observed. Based on these histopathological findings, we diagnosed the lesion as anetoderma secondary to dermatofibroma. There has been no recurrence after excision. Anetoderma was first described in 1892 by Jadassohn as erythematous macules that progressed into the characteristic atrophic-appearing, wrinkled patches of skin.1 It is characterized by well-circumscribed areas of atrophic macules or patches, with a predilection for the trunk and proximal extremities in women up to their forties. The lesions may be depressed or slightly pouch-like, with a distinct inward herniation on palpation that is limited by a surrounding rim of healthy skin. The color of the lesions can vary from flesh-colored to white, blue, or brownish-gray, and their size can range from a few millimeters to centimeters.2 Anetoderma is classified into 2 groups: primary anetoderma, which arises without a preceding condition, and secondary anetoderma, which develops at sites previously affected by an inflammatory dermatosis.2 Secondary anetoderma occurs after various skin diseases, including syphilis, leprosy, sarcoidosis, tuberculosis, granuloma annulare, Stevens–Johnson syndrome, HIV infection, folliculitis, Lyme disease, keratitis, lupus erythematosus, amyloidosis, B-cell lymphoma, mycosis fungoides, prurigo nodularis, pilomatricoma, juvenile xanthogranuloma, lymphocytoma, and so on.2 The pathogenesis of secondary anetoderma varies depending on the preceding lesion. Antiphospholipid antibodies are implicated in systemic lupus erythematosus and HIV infection, while elastase is involved in prurigo nodularis and pilomatricoma.2 Phagocytosis of elastic fibers by giant cells is associated with degradation of elastic fibers and lipoid necrosis. Some reports suggest that anoxic cell events, such as compression or microthrombi, result in elastic fiber breakdown.3 In our case, multinucleated giant cells exhibiting elastophagocytosis were observed in the tissue surrounding the mass, but not in its center. Clumped elastic fibers were present at the base of the mass, suggesting ongoing phagocytosis of elastic fibers. Notably, in addition to elastophagocytosis, hemosiderin deposition was conspicuous in the giant cells. This finding implies that the lesion was subjected to compression, potentially leading to hemorrhage and the subsequent development of anetoderma. In our case, the anetoderma may have been caused by dermatofibroma. To the best of our knowledge, there have been no previous reports of anetoderma secondary to dermatofibroma. The exact mechanism by which dermatofibroma caused anetoderma in this case remains unclear. However, it is likely that some correlation exists between pregnancy-related changes in elastic tissue and the appearance of anetoderma.4 Actually, there has been a case report of primary cutaneous follicle center lymphoma that exacerbated during pregnancy, with most lesions regressing and leaving areas of anetoderma after delivery.5 The mechanism by which pregnancy causes anetoderma remains unclear. However, increases in matrix metalloproteinases, potentially induced by elevated levels of estrogen and progesterone, have been implicated in processes such as vasodilation, placentation, and uterine expansion during normal pregnancy.6 While the expression of matrix metalloproteinases in the skin during pregnancy is unknown, if upregulated, they may contribute to the pathogenesis of anetoderma in pregnancy. Atrophic dermatofibroma was initially considered in the differential diagnosis. This variant, accounting for approximately 2% of all dermatofibromas, often occurs on the upper back of middle-aged women.7 Histologically, atrophic dermatofibroma shows more than 50% atrophy of the dermis immediately beneath the mass, with elevation of the underlying subcutaneous fat.8 Clinically, it presents as flat or depressed atrophic erythema, becoming more pronounced on digital pressure. The pathogenesis is believed to involve elastophagocytosis by the tumor cells of the dermatofibroma. In our case, while the clinical picture initially suggested atrophic dermatofibroma, histopathological examination revealed unchanged dermal thickness in the lesion area, with a decrease in elastic and collagen fibers in the surrounding dermis. These features led to the diagnosis of anetoderma. This case highlights a previously unreported association between dermatofibroma and secondary anetoderma, expanding our understanding of both conditions. Further research is warranted to elucidate the exact mechanisms underlying this association and to explore the potential role of pregnancy in the pathogenesis of secondary anetoderma.