Numerous asymptomatic papulo-nodules and plaques in a young male.

A 16-year-old boy born of non-consanguineous marriage presented with numerous solid elevated lesions over his body. To start with, the lesions were asymptomatic flesh-colored papules over the face 1 year back and gradually, they progressed to attain the present status. Cutaneous examination revealed multiple brown-colored papules, discrete as well as confluent, yellow to brown-colored, well-circumscribed and smooth-surfaced nodules and plaques of varied sizes over face, more concentrated over the eyelids and chin, ears, neck, axillae, elbows, popliteal fossae, scrotum and oral mucosa [Figures 1–3]. Hairs, nails and teeth did not reveal any abnormality. There was no history of seizures, dysphagia, dyspnea, hoarseness of voice, blindness, increased urinary frequency, bone pain or any gastrointestinal complaints. Family history was non-contributory. Systemic examinations including ophthalmologic, oropharyngeal and otorhinolaryngological referral were done and nothing was found to be abnormal. Laboratory investigations including complete blood count, biochemistry panel, lipid profile, thyroid function tests, urinalysis, ECG, chest X-ray, and ultrasonographic studies of the abdomen were within normal limits. A skin biopsy was done from multiple sites. Histopathological examination in all the specimens showed diffuse proliferation of histiocytes, admixed with Touton giant cells, foam cells, scalloped macrophages, lymphocytes and eosinophils in the dermis [Figures 4–6]. Immunohistochemical staining for CD1a was found to be negative, whereas CD 68 and factor XIIIa were positive.

Figure 1

Multiple discrete and confluent brown-colored papules, nodules and plaques over the face and whitish papules on oral mucosa (a-c)

Figure 3

Multiple discrete and confluent papulo-nodules and plaques on the upper extremity and external genitalia (a-c)

Figure 4

Photomicrograph showing acanthosis and a dermal lesion composed of massive infiltration (H and E, ×10)

Figure 6

Photomicrograph showing foam cells (arrow a), Touton giant cells (arrow b), lymphocytes and eosinophils (H and E, ×40)

Well-circumscribed and smooth-surfaced papulo-nodules and plaques of varied sizes on the axilla and small papules over neck and ear (a-c)

Photomicrograph showing a dermal lesion composed of sheets of scalloped macrophages (arrow) and histiocytes (H and E, ×40)

Question

What is the diagnosis?

Answer

Xanthoma disseminatum

Discussion

Since its first description by Montgomery and Osterberg in 1938, nearly 100 cases have been reported in the world literature. Xanthoma disseminatum (XD) is a condition in which lipid deposition occurs secondary to a histiocytic proliferation.[1] Age at onset of XD can range from 8 months to 85 years with a definite gender predilection (male to female ratio of 2:1). Its pathogenesis remains unclear; the non-neoplastic but pathological non-X histiocytic cell proliferation reaction pattern of macrophage/monocyte origin is perhaps triggered by some superantigens.[2]

Depending upon its evolution and prognosis, it is grouped into three forms: (1) a self-healing form with spontaneous resolution; (2) a persistent form (commonest) in which lesions may never resolve; and (3) a very rare progressive form with organ dysfunction and central nervous system involvement.[3] The disorder can be differentiated from eruptive xanthomas, malignant histiocytosis, and Langerhans cell histiocytosis through age at onset serum lipoprotein profiles, histopathologic findings, and immunohistochemical results. An early lesion is basically a histiocytic proliferation and the mature lesion is composed of an admixture of histiocytes, foam cells, Touton giant cells, and plenty of inflammatory cells within the dermis. This histiocytic proliferation goes in favor of a histiocytic disorder, with Touton giant cells representing an accentuated xanthomatoid reaction, and immunohistochemistry staining positive for CD 68 and factor XIIIa support it being a disorder of histiocytes/macrophages, whereas negative staining for S-100, CD1a and Birbeck granules reliably excludes Langerhans cell histiocytosis.[4] In early lesions, scalloped macrophages dominate the histologic picture. In contrast, papular xanthoma and diffuse plane xanthoma show only a minority of nonfoamy cells. More developed lesions may still show scalloped cells, but xanthomatization occurs in most cases.[4,5] In our case, lesions both in early and late stages were present. A table showing the salient points of difference between papular xanthoma, progressive nodular histiocytosis, generalized eruptive histiocytoma and XD has been provided [Table 1].

Table 1

Points of difference between papular xanthoma, progressive nodular histiocytosis, generalized eruptive histiocytoma and xanthoma disseminatum

The treatment modalities have shown variable results. Eisendle et al. reported that oral prednisolone and azathioprine showed no improvement but a combination of lipid-lowering agents or azathioprine and cyclophosphamide was found to be useful.[6] Kang et al. reported the successful use of a combination of oral steroids, clofibrate, and chemotherapy.[7] Bone marrow transplantation has been used successfully in a case of life-threatening xanthogranuloma disseminatum in neurofibromatosis type-1 in a recent report by Savaşan et al.[8] In 2011, Khezri et al. reported a case series in which 2-chlorodeoxyadenosine therapy was found useful in maintaining remission and long-term control of cutaneous lesions, wherein among eight cases of XD, a positive response to treatment with 2-chlorodeoxyadenosine was seen in five cases.[9]