Systemic Juvenile Xanthogranuloma Involving the Bone Marrow, Multiple Bones, and the Skin That Developed During Treatment of Acute Lymphoblastic Leukemia in Remission State

Abstract

Juvenile xanthogranuloma (JXG) is a rare benign disorder classified as non-Langerhans cell histiocytosis, with unclear etiology and pathogenesis. JXG is generally characterized by solitary or multiple cutaneous nodules that resolve spontaneously over a few years. JXG rarely presents as extracutaneous lesions that progress to a symptomatic systemic disorder through multiple organ involvement. We encountered a systemic JXG case involving the bone marrow, multiple bones, and the skin during acute lymphoblastic leukemia (ALL) treatment. A 16-year-old boy undergoing ALL treatment experienced unexplained prolonged fever and scalp, hip joint, and right knee joint pain for 2 weeks during interim maintenance chemotherapy. Bone marrow pathologic findings revealed no evidence of leukemia relapse but showed diffuse infiltration of histiocytes with several Touton-type giant cells; the stains were positive for CD68 and negative for CD1a and S100 protein. Bone and skin biopsies confirmed the findings. Symptoms have resolved since maintenance chemotherapy, which included vincristine, dexamethasone, 6-mercaptopurine, and methotrexate. Bone marrow involvement of JXG is very rare, occurring only in patients less than 1 year of age; however, this case was reported in an adolescent during ALL treatment.

Multiple Xanthogranulomas in a Teenager

“…Clinical appearance and histology were consistent with the typical findings of JXG across all cases. Yellow to brown papules and nodules were the most frequently reported description of lesions [1,[3][4][5][6]. No cases revealed pink to brown plaques as seen in our patient.…”

“…Systemic JXG was present in a patient undergoing chemotherapy for leukemia at the onset of the lesions [4]. The remaining cases were limited to the skin and were associated with normal hematological studies.…”

“…Most common locations of the lesions were on the extremities, trunk, and face. Treatment course varied among the cases [1,[3][4][5][6]. Routine follow-up was elected for two patients, given the benign nature of the disease and tendency for self-resolution [1,5].…”

“…Self-resolution does occur, but with lesser frequency in older patients with multiple lesions [2]. Histologic examination reveals mixed infiltrate of mononuclear cells and multinucleated giant cells with the Touton-type giant cells appearing in 95% of cases [2,4]. Immunohistochemistry is positive for CD68 and often factor XIIIa [2].…”

“…Immunohistochemistry is positive for CD68 and often factor XIIIa [2]. JXG is differentiated from Langerhans cell histiocytosis with a negative S-100 protein and CD1a [4].…”