Multiple generalized xanthogranuloma in adult: case report and treatment.

Xanthogranuloma is a benign, asymptomatic, and self-healing disorder of non-Langerhans cell histiocytosis, affecting mostly infants, children, and rarely adults. Diagnosis is easy in typical cases but become more complex in unusual forms. We report a case of a 28-year-old male patient who presented with multiple diffuse brown-to-yellowish papulonodular eruptions over extremities, ears, face, trunk, and extensors of joints with almost bilaterally symmetrical distribution for a period of one month. Histopathological examination of the skin biopsy specimen revealed features of xanthogranuloma. The patient was put on isotretinoin 20 mg once daily. Most of the lesions subsided or flattened within two months of isotretinoin therapy. This case is interesting because of the severity and atypical nature of the disease and also, the patient responded with isotretinoin therapy. But further study is required to observe the effectiveness of isotretinoin in xanthogranuloma.

Introduction

Xanthogranulomas are benign, usually asymptomatic, self-healing, red, yellow, or brown papules, nodules composed of histiocytic cells that predominantly occur in infancy and childhood. Papules, nodules occur in skin, eyes, and viscera. Adamson first reported juvenile xanthogranuloma (JXG) in 1905. But during 1912, McDonough reviewed the condition and renamed it as nevoxanthoendothelioma. In 1954, Helwig and Hackney re-termed it as JXG, reflecting its histopathological appearance.[1] An adult form of xanthogranuloma was first described by Gartmann and Tritsch in 1963.[2] It belongs to a heterogeneous group of non-Langerhans cell histiocytoses, which are characterized by benign dermal proliferations of histiocytic cells in the absence of any known stimuli.

Approximately 35% of cases of JXG occur at birth, with as many as 71% of cases occurring in first year. Usually, xanthogranuloma is termed as JXG though around 10% of cases manifest in adulthood. Up to 81% of cutaneous JXG cases manifest as a solitary lesion. This form is also more common in cases of adult onset. Extracutaneous JXG is rare (3.9%) and most commonly involves eye. Histopathological examination of JXG demonstrates a variety of findings. A time-dependant progression exists in development of characteristic histological features which correlates with age of lesions. Early biopsy specimen reveals a dense monomorphous histiocytic infiltrate in dermis. Older lesions contain foam cells, Touton giant cells and foreign body giant cells. A mixed cellular infiltrate of neutrophils, lymphocytes, eosinophils and rarely mast cells may be noted.[3]

Anticipatory care, with patient reassurance, is appropriate because of self-limiting benign nature of disease. Ocular and systemic lesions may respond to steroids or radiotherapy. But diffuse and multiple cutaneous lesions also need some treatment.

Case Report

A 28-year-old healthy male patient presented in our department with one-month history of diffuse numerous papulonodular eruptions at extremities, ears, face, and trunk. The majority of lesions were present over extensors of joints. The lesions developed suddenly at first over right leg with mild itching. No other constitutional symptom was present. Cutaneous examination revealed yellow-brown, relatively well-demarcated papulonodular lesions with variable sizes (1–5 mm in diameter). Lesions were shiny, soft to elastic in consistency consistency present almost all over the body and majority being over upper and lower extremities, ears, and chin [Figure 1a–c]. The surface of some lesions were scaly. There was no vesiculation, erosion, or crusting. The mucous membranes, palms and soles were unaffected and ophthalmologic examination was normal. No other systemic involvement was noted. No other family members were affected.

Figure 1a-c

Yellow-brown relatively well-demarcated shiny elastic papulonodular eruptions

The following differential diagnosis was made: lepromatous leprosy, tuberous xanthoma and xanthogranuloma. Laboratory investigations, including routine hematological examination, liver and renal function test, were within normal range. Serum levels of lipids were not raised. The Ziehl-Neelsen and Fite stains for acid fast bacilli were negative.

Histopathological examination revealed dense granulomatous dermal infiltrates consisting of foam cells, giant cells (mainly Touton type), histiocytes, lymphocytes, and a few eosinophils and neutrophils mainly at upper dermis. The epidermis was thinned out without any grenz zone and inflammatory cells extended toward lower dermis to subcutaneous tissue [Figure 2a–c. A pathological confirmation of xanthogranuloma was made. X-ray of chest and skull were normal. Ultrasonography of abdomen and pelvis showed no visceral involvement.

Figure 2a-c

Granulomatous dermal infiltrates of foam cells, giant cells (Touton type), histiocytes, lymphocytes, neutrophils. [H & E stain; original magnifications: 2b ×10; 2a and c ×40]

The prognosis of disease was discussed with patient. As there was a diffuse involvement with disfigurement, we planed to give some treatment to improve disease process rapidly. We started isotretinoin 20 mg once daily after food. Patient was reviewed after one month and noted about 50% reduction of size of lesion [Figure 3]. He continued treatment for another one month and noticed that most of the lesions had flattened with yellowish and hyperpigmented macules [Figure 4]. Repeat lipid profile and liver function test was done and no abnormalities were detected.

Figure 3

Post-treatment photograph after one month of treatment

Figure 4

Post-treatment photograph after two month of treatment

Discussion

Histopathologically, xanthogranuloma in adult is identical to that of JXG.[4] Serum lipid profiles are normal in patients with both juvenile and adult form of xanthogranuloma. The number of lesions in adult xanthogranuloma is lesser than in juvenile form. Of 31 patients, 27 (87%) with adult onset xanthogranuloma in Japanese literature had a solitary lesion.[5] Multiple adult xanthogranuloma is a rare entity and 16 cases were reported since 1963.[6] There seemed to be no definite sites of predilection for adult onset xanthogranuloma and lesions were usually asymptomatic.[3] Spontaneous resolution does not occur in adult form, whereas juvenile form usually involutes spontaneously within a year.[7] Earlier published report of nine cases of adult xanthogranuloma did not notice any spontaneous resolution.[4] Extracutaneous involvements of eye, lung, testis and pericardium have been reported in patients with JXG.[7] In contrast, no concomitant extracutaneous lesions have been found in adult form, although solitary extracutaneous xanthogranuloma without cutaneous lesions have been reported.[8]

Etiology of xanthogranuloma is unknown. The tumor represents accumulations of differentiated histiocytes. These cells express phenotype of dermal dendrocytes, although a recent study has suggested that cell of its origin could be plasmacytoid monocytes.[9] The appearance of giant cell and foamy lipid-laden histiocyte occur late and they are almost certainly secondary events, possibly in response to cytokine production by the lesion histiocyte. JXG has been noted in association with different diseases like neurofibromatosis, Niemann-Pick disease, urticaria pigmentosa, juvenile chronic myelogenous leukemia. However no association was found with the adult form. Ocular and systemic lesions may respond to steroids or radiotherapy, and severe systemic JXG have required single and mutagenic chemotherapeutic regimens. Commonly, no treatment is necessary for cutaneous xanthogranuloma, but severe cutaneous involvement of adult form like our case may require some treatment to hasten disease improvement.

The growth of a number of tumor cell lines seems to be inhibited by retinoids, but response may be variable. It affects transformed cell surfaces and leads to anchorage-independent growth, cell adhesiveness and density-dependant growth.[10] For these reasons, we started isotretinoin and noticed significant clinical improvement within two months. As spontaneous resolution does not occur in adult xanthogranuloma, we think that this type of early resolution may be due to isotretinoin. But further large study is required to see the effectiveness of isotretinoin in xanthogranuloma.