Multiple adult-onset xanthogranuloma, an uncommon diagnosis.

Dear Editor,

A 77-year-old Caucasian male patient was referred to our Service for presenting brownish and erythematous-violet papules (4 to 8 mm), located bilaterally in arms, armpits, lower abdominal quadrants and thighs (Figure 1). There was no involvement of the face, dorsal surface of the joints or mucous membranes. The lesions, which were always asymptomatic, had evolved progressively for ten months.

Figure 1

Adult multiple xanthogranuloma. A. Detail of papule-nodular, brown and erythematous-violaceous lesions, asymptomatic, in the right arm. B. Detail of lesions on the right thigh

At the general objective examination, there were no significant alterations, namely ophthalmologic, cardiopulmonary and neurological. No systemic semiology or relevant family history coexisted. Among the patient's personal antecedents were major depression and anxiety disorder. Diagnoses of histiocytosis, particularly generalized eruptive histiocytoma, multiple adult xanthogranuloma (XGA), Erdheim-Chester disease and cutaneous metastases, were considered.

The histopathological study of a lesion showed infiltration of the dermis and, in particular, of the hypodermis by histiocytes with foamy cytoplasm, accompanied by Touton cells, occasional lymphocytes and rare eosinophils ( Figure 2). Infiltrate cells were CD68 positive and protein S100 and CD1a negative ( Figure 3).

Figure 2

Histopathology - hematoxylin-eosin, original magnification 400x. Infiltration of the entire thickness of the dermis by histiocytes with foamy cytoplasm, accompanied by multinucleated Touton giant cells

Figure 3

Immunohistochemistry - original magnification 100x. A: CD68 positive. B: S100 protein negative. C: CD1a negative

No alterations were observed in the complementary evaluation, which included: hemogram with leukogram; blood biochemistry; electrophoretic proteinogram and serum immunofixation; urinalysis, diuresis monitoring and pituitary hormone study; skeletal radiography; electrocardiogram; respiratory function tests; cranioenchephalic and thoraco-abdominopelvic tomodensitometry studies.

The diagnosis of multiple XGA was retained. In view of the asymptomatic character of the lesions and the patient's psychiatric history, we opted for therapeutic abstention with periodic observation.

Histiocytoses correspond to a set of proliferative diseases of the mononuclear phagocytic system and are grouped into Langerhans cell histiocytosis, malignant histiocytosis and non-Langerhans cell histiocytosis.[1]

Xanthogranuloma (XG) is the most common non-Langerhans cell histiocytosis,[1] but 71% of cases occur in children under one year of age.[2] In adults, it is rare, usually occurring in the third and fourth decades of life.[2] XG usually corresponds to an orange or erythematous-brown papule-nodule,[3] varying the tonality with the age of the lesions. [1] Contrary to what is observed in our patient and in juvenile XG (JXG), XGA usually occurs as a single lesion in 2/3 of cases located on the face, but may be seen in the trunk or limbs.[2,4] Multiple XGA, defined as more than five XG lesions, appears to be more common among men. [4]

JXG and XGA lesions present identical histopathology[2] and immunohistochemistry.[5] In older lesions, xanthomized cells and, characteristically, Touton cells are observed. [4] Immunohistochemistry confirms the presence of CD68 positive histiocytes; S100 protein and CD1a are negative, with variability of expression of factor XIIIa immunoreactivity.[3]

From the histopathological and immunohistochemical point of view, the findings observed in our patient could be classified as Erdheim-Chester disease. However, this can be excluded in the present case by the absence of extracutaneous changes, especially skeletal. It should be emphasized that, in generalized eruptive histiocytoma, non-Langerhans cell histiocytosis which should also be distinguished from XGA, no Touton cells are observed. These can, however, occur in disseminated xanthoma, which may form part of the lesion spectrum of XG, but is characterized by the periflexural lesional distribution. In multicentric reticulocyte histiocytosis, lesions are usually acral, accompanied by arthropathy, characterized by large multinucleated cells with voluminous ground-glass cytoplasm, findings that contrast with those observed in our patient.[3]

The etiopathogenesis of XGA is unknown. It was suggested the association with trauma, infections and neoplasias. [3] The association between JXG and hematological neoplasms is classic.[2,5] Cases of XGA, particularly multiple XGA, associated with thrombocytosis, chronic lymphocytic leukemia and monoclonal gammopathy have also been described,[3] not found in the patient described.

XGA lesions may appear before, concurrently or after the development of hematological pathology, and XG may be considered a cutaneous marker of hematological pathology. In other cases, the described evolution was benign.[3] The presence of concomitant extracutaneous lesions was reported in JXG, but not in XGA. [2,4] However, cases of solitary extractive XGA have been reported, with no coexisting skin lesions. [2] As noted in the present case, spontaneous regression is less likely in XGA than in JXG.[4]

The treatment of XGA is justified by numerous, uncomfortable or unsightly lesions. Surgical excision,[2,5] CO2[5] laser and the systemic retinoids, with emphasis on isotretinoin,[2,5] are described.

In conclusion, XGA is a rare and poorly understood form of non-Langerhans cell histiocytosis, with extensive differential diagnosis and the possibility of important systemic associations. Thus, patients should undergo a thorough evaluation, with histopathological and immunohistochemical study, making possible, on the one hand, the diagnosis and, on the other hand, the exclusion of the presence of associations. Regardless of the therapeutic option, the evolution of this pathology being not understood and its benign nature being uncertain, surveillance is recommended.