© The Author(s) 2011
Received: 24 February 2011
Accepted: 24 October 2011
Published: 11 November 2011
Xanthogranulomatous osteomyelitis is a rare type of inflammatory process which is characterized by composition of immune cell aggregation on histological studies. Delayed-type hypersensitivity reaction of cell-mediated immunity may be implicated in its pathogenesis. Gross and radiological examination can mimic malignancy, and differentiation should be confirmed by histopathological evaluation. We describe the case of a 14-year-old Afghan boy presenting with pain in right shoulder and left leg with prior history of trauma. Fever, limitation in right shoulder range of motion, and tenderness in right shoulder and left thigh were detected following examination. Mild leukocytosis, elevated alkaline phosphatase, and increased erythrocyte sedimentation rate with negative C-reactive protein (CRP) were revealed. X-ray imaging showed mixed density, periosteal reaction, and cortical disruption. Computed tomography (CT) scan revealed lesions involving medulla and cortex, periosteal reaction with soft tissue component, and bone marrow infiltration in right humerus and left fibula. On magnetic resonance imaging (MRI), signal abnormalities in medulla, metaphysis, and diaphysis of the left fibula associated with cortical irregularity and diffuse soft tissue hypersignal areas were demonstrated. Finally, xanthogranulomatous osteomyelitis was confirmed by histological sample. The clinical manifestations and radiographic and laboratory findings of this rare condition are discussed.
KeywordsXanthogranulomatous osteomyelitis Inflammatory Humerus Fibula
Xanthogranulomatous inflammation process, including xanthogranulomatous osteomyelitis (XO), is a chronic inflammatory disease characterized histologically by abundant foamy periodic acid-Schiff (PAS)-positive histiocytes in the initial stages, giant cells, fibrosis, and calcification together with polymorphonuclear leukocytes, activated plasma cells, and lymphocytes of polyclonal origin. It can involve any organ, but the most common sites are kidney and gallbladder [1, 2]. Other organs such as lung, brain, and bone are rarely affected. Bone involvement is accompanied by systemic and regional clinical presentations such as pain, fever, and leukocytosis. Delayed-type hypersensitivity reaction of cell-mediated immunity may be implicated in its pathogenesis. Grossly, it is a mass-like lesion extending to enclosing tissues which can mimic infiltrative cancer . There is a long list of differential diagnoses, with the main ones discussed being Langerhans cell histiocytoses, Erdheim–Chester disease (ECD), chronic recurrent multifocal osteomyelitis (CRMO), and metastatic renal cell carcinoma. Clinical background and histopathological examination differentiate between them for exact diagnosis.
In this report we describe an entity involving two bones independently, one in upper and the other in lower extremity, simultaneously.
A 14-year-old Afghan boy was admitted to our hospital, presenting with right shoulder and left thigh pain with prior history of moderate trauma. The pain had gradual onset, increasing over the last 8 weeks.
Physical examination during this visit revealed a febrile patient with oral temperature of 38°C and other vital signs normal. Range of motion of the left ankle was normal but was reduced in the right shoulder. Left ankle, left fibula, and right humerus were tender, and swelling existed in lateral side of the left ankle.
Serological tests showed mild leukocytosis (white blood cell, WBC = 12,000 cells/mL) accompanied with mild polymorphonuclear predominance (70%), elevated alkaline phosphatase (350 IU/L), increased erythrocyte sedimentation rate (119 mm/h), and negative CRP. Results of serum biochemical profile including liver and renal function tests were within normal values.
In the last few decades, Cozzutto reported the first two cases of XO, involving first rib and epiphysis of tibia, respectively . These pseudotumoral lesions are benign in nature, but should be differentiated from malignant disease. In its imaging and clinical manifestations, XO is very similar to carcinoma, but a characteristic histopathological finding can differentiate XO from carcinoma. A correlation between xanthogranulomatous disorders and trauma or infection is hypothetical. As reported in this review, our case had a history of trauma prior to any manifestation. Vankalakunti et al.  reported XO of ulna in a 50-year-old postmenopausal woman presenting with 2-year history of progressive swelling in the extensor side of her right forearm. The lesion was curetted out, and cancellous iliac crest graft interposed. Although no organism was found in the tissue culture in that case, Staphylococcus aureus was revealed in our patient’s culture.
Cennimo et al.  reported a xanthogranulomatous reaction in index finger and wrist of a man complaining of pain and swelling for 1 year, unresponsive to antibiotics. Xanthogranulomatous reaction and positive culture of Mycobacterium marinum were demonstrated in his bone biopsy. They performed radical synovectomy of the lesion, administering minocycline, clarithromycin, and ethambutol. A relationship between bacterial infection and xanthogranulomatous inflammation has been determined in several organs such as kidneys and the gastrointestinal (GI) system, but remains undetermined for bone [4, 7–11].
Initially, relying on radiological and gross examination, the list of rare differential diagnoses includes Langerhans cell histiocytoses, Erdheim–Chester disease (ECD), chronic recurrent multifocal osteomyelitis (CRMO), xanthoma, infiltrative storage disorder, malakoplakia, fibrohistiocytic tumor, and metastatic renal cell carcinoma [12–16].
ECD is a rare non-Langerhans cell histiocytosis of unknown etiology, being a multisystemic xanthogranulomatous infiltration with almost constant bone involvement. In our patient, whole-body bone scan failed to show any other site of inflammation, thus ECD was ruled out.
Langerhans cell histiocytosis is a group of idiopathic disorders characterized by proliferation of specialized, bone marrow–derived Langerhans cells and mature eosinophils. Unifocal Langerhans cell histiocytosis presents as a single osteolytic lesion, usually affecting long or flat bones. Multifocal Langerhans cell histiocytosis shows osteolytic lesions involving the calvaria, the sella turcica, the mandible, the vertebrae, and/or the long bones of the upper extremities. Although lesions typically appear granulomatous, with a reactive background of macrophages, eosinophils, multinucleated giant cells, and T cells, the key to diagnosis is identification of pathologic Langerhans cells. The Birbeck granule is their distinctive ultrastructural hallmark [17, 18]. In our case, no Birbeck granules were demonstrated, therefore Langerhans cell histiocytosis was ruled out.
CRMO is a rare condition in which a child’s bones become inflamed and painful. The symptoms are very similar to those of osteomyelitis: unifocal or multifocal, initially osteolytic, later hyperostotic and sclerotic lesions mainly in the metaphyses of the long bones and shoulder girdle, although any bone can be affected [19, 20]. This differential diagnosis was also ruled out histopathologically. Other differential diagnosis was ruled out with the help of biopsy. There is little experience of XO, and we should manage these patients in the light of xanthogranulomatous inflammation in other organs.
We present this case primarily due to its rarity and curability. While xanthogranulomatous osteomyelitis is benign, it can mimic malignant bone lesion in its imaging and clinical manifestations, and appropriate differentiation is crucial. Currently, histopathological examination of lesions is the most specific for diagnosis.
Conflicts of interest
This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution and reproduction in any medium, provided the original author(s) and source are credited.
- Franco V, Aragona F, Genova G et al (1990) Xanthogranulomatous cholecystitis. Histopathological study and classification. Pathol Res Pract 186:383–390PubMedView ArticleGoogle Scholar
- Antonakopoulos GN, Chapple CR, Newman J et al (1988) Xanthogranulomatous pyelonephritis. A reappraisal and immunohistochemical study. Arch Pathol Lab Med 112:275–281PubMedGoogle Scholar
- Maeda T, Shimada M, Matsumata T et al (1994) Xanthogranulomatous cholecystitis masquerading as gallbladder carcinoma. Am J Gastroenterol 89:628–630PubMedGoogle Scholar
- Cozzutto C (1984) Xanthogranulomatous osteomyelitis. Arch Pathol Lab Med 108:973–976PubMedGoogle Scholar
- Vankalakunti M, Saikia UN, Mathew M, Kang M (2007) Xanthogranulomatous osteomyelitis of ulna mimicking neoplasm. World J Surg Oncol 30(5):46View ArticleGoogle Scholar
- Cennimo DJ, Agag R, Fleegler E, Lardizabal A, Klein KM, Wenokor C, Swaminathan S (2009) Mycobacterium marinum hand infection in a “Sushi Chef”. Eplasty 14(9):e43Google Scholar
- Machiz S, Gordon J, Block N, Politano VA (1974) Salmonella typhosa urinary tract infection and xanthogranulomatous pyelonephritis: case report and review of literature. J Fla Med Assoc 61:703–705PubMedGoogle Scholar
- Gauperaa T, Stalsberg H (1977) Renal endometriosis: a case report. Scand J Urol Nephrol 11:189–191PubMedView ArticleGoogle Scholar
- Goodman M, Curry T, Russell T (1979) Xanthogranulomatous pyelonephritis (XGP): a local disease with systemic manifestations: report of 23 patients and review of literature. Medicine 58:171–181PubMedView ArticleGoogle Scholar
- Guarino M, Reale D, Micoli G, Tricomi P, Cristofori E (1993) Xanthogranulomatous gastritis: association with xanthogranulomatous cholecystitis. J Clin Pathol 46:88–90PubMed CentralPubMedView ArticleGoogle Scholar
- Nakashiro H, Haraoka S, Fujiwara K, Harada S, Hisatsugu T, Watanabe T (1995) Xanthogranulomatous cholecystis. Cell composition and a possible pathogenetic role of cell-mediated immunity. Pathol Res Pract 191:1078–1086PubMedView ArticleGoogle Scholar
- Kayser R, Mahlfeld K, Grasshoff H (1999) Vertebral Langerhans-cell histiocytosis in childhood—a differential diagnosis of spinal osteomyelitis. Klin Padiatr 211:399–402PubMedView ArticleGoogle Scholar
- Amezyane T, Abouzahir A, Bassou D, Zoubeir Y, Hammi S, Mahassin F, Ohayon V, Archane MI (2009) Pseudo-tumoral and ischemic encephalic Erdheim-Chester disease. Rev Neurol (Paris) 165(6–7):591–595View ArticleGoogle Scholar
- Hamada T, Ito H, Araki Y, Fujii K, Inoue M, Ishida O (1996) Benign fibrous histiocytoma of the femur: review of three cases. Skeletal Radiol 25:25–29PubMedView ArticleGoogle Scholar
- Kossard S, Chow E, Wilkinson B, Killingsworth M (2000) Lipid and giant cell poor necrobiotic xanthogranuloma. J Cutan Pathol 27:374–378PubMedView ArticleGoogle Scholar
- Girschick HJ, Huppertz HI, Haemsen D, Krauspe R, Muller-Hermelink HK, Papadppoulos T (1999) Chronic recurrent multifocal osteomyeli tis in children: diagnostic value of histopathology and microbial testing. Hum Pathol 30:59–65PubMedView ArticleGoogle Scholar
- Favara BE, Feller AC, Pauli M et al (1997) Contemporary classification of histiocytic disorders. The WHO Committee on Histiocytic/Reticulum Cell Proliferations. Reclassification Working Group of the Histiocyte Society. Med Pediatr Oncol 29(3):157–166PubMedView ArticleGoogle Scholar
- Weitzman S, Egeler RM (2008) Langerhans cell histiocytosis: update for the pediatrician. Curr Opin Pediatr 20(1):23–29PubMedView ArticleGoogle Scholar
- Datta P (2008) Chronic recurrent multifocal osteomuelitis (CRMO). JBR-BTR 91:92–93PubMedGoogle Scholar
- Chun CS (2004) Chronic recurrent multifocal osteomyelitis of the spine and mandible: case report and review of the literature. Pediatrics 113(4):e380–e384PubMedView ArticleGoogle Scholar