Xanthoma combining osteonecrosis in knee joint: a case report

Abstract

Xanthoma typically occurs in the subcutaneous tissues, with rare cases of xanthoma in the joints. However, the case of knee joint osteonecrosis combined with xanthoma is even more uncommon. In this article, we described a 50-year-old female patient who suffered xanthoma in the knee joint on the basis of osteonecrosis of the knee joint. The primary clinical symptoms were knee joint pain and limited mobility. The patient initially received conventional treatment for osteonecrosis. However, there was no significant improvement. Later, we found a synovial xanthoma in the patient’s knee. Finally, she underwent arthroscopic excision of the knee joint synovial xanthoma. Following the procedure, her VAS score decreased from 7 to 2, and knee joint mobility increased from 10–103° to 10–140°. Through our follow-up, the patient did not exhibit symptom recurrence. This case is valuable as it provides a feasible therapeutic approach for future clinical applications.

Background

Xanthoma (or yellow fibroma) is a benign proliferative lesion commonly found in patients with hyperlipidemia, primarily occurring in soft tissues such as skin, tendons, and fascia. Pathologically, xanthomas exhibit macrophage-like monocytes, multinucleated giant cells, and numerous foam cells [1]. Currently, reports of xanthomas in joints are rare.

Knee osteonecrosis usually affects the femoral condyles, but it may also affect the epiphysis, metaphysis, and diaphysis. It is not fully understood what causes osteonecrosis of the bone. Decompression sickness, glucocorticoids, alcohol abuse, and dyslipidemia have been associated with osteonecrosis [2]. Clinically, patients with osteonecrosis may present with joint pain and swelling [3].

Xanthoma occurrence in patients with osteonecrosis is even rarer. To our knowledge, there have been no previously reported cases of knee osteonecrosis combined with knee joint synovial xanthoma. Therefore, we present a case report detailing the diagnosis and treatment process of a patient with osteonecrosis of the knee joint complicated by xanthoma. A comprehensive discussion is provided, incorporating clinical, radiological, and histopathological perspectives.

Case presentation

The patient, a 50-year-old female, presented to our hospital in 2018 with recurrent bilateral knee joint pain and swelling, complained about standing and walking difficulty. A specialized examination indicated tenderness around both knee joints, a slightly elevated skin temperature, and a limited flexion-extension range of 10–120°. To establish a diagnosis, a bilateral knee MRI and CT were performed, indicating osteonecrotic changes in both knee joints (Fig. 1).

Fig. 1

MRI and CT of both knees. (a): the CT of both knees; (b): the MRI of left knee; (c): the MRI of right knee; R: right knee; L: left knee

A biopsy of the right knee bone tissue was conducted, which indicated osteonecrosis. The results of immunohistochemistry, which showed CKpan(-), Vim(+), CD79a(-), CD3(-), EMA(-), P53(-), and Ki-67(-) (Fig. 2).

Fig. 2

Bone tissue biopsy. The arrow points to fragmented bone tissue with necrosis and fibrosis

Despite the patient’s four-year history of oral steroid use from 2005 ~ 2008, the distant nature of the medication led us to exclude steroid-induced causes. We administered intra-articular blockade therapy (lidocaine hydrochloride injection 0.1 g + compound betamethasone injection 7 mg + sodium hyaluronate injection 25 mg, once), edema reduction therapy (Extract of Horse Chestnut Seeds Tablets 0.8 g twice daily), and hyperbaric oxygen therapy to improve microcirculation to alleviate the patient’s symptoms. The patient was a postmenopausal woman and had a lower than normal bone mineral density. In addition, consider that bone resorption is greater than bone formation in patients with osteonecrosis. Therefore, the patient was treated with inhibition of bone resorption, including oral alendronate sodium (70 mg once weekly for one year starting in 2018), calcium carbonate and Vitamin D3 tablets (500 mg twice daily starting in 2018), subcutaneous injections of elcitonin (10u twice weekly for three months starting in 2019), and intravenous injections of denosumab (60 mg semi-annually for two years starting in 2020). Following treatment, there has been an improvement in the patient’s symptoms.

In 2022, the patient’s symptoms in the left knee joint worsened, prompting another visit to our hospital. However, the right knee joint has not deteriorated since 2019.MRI of the left knee joint indicated osteonecrosis, synovial hyperplasia and benign hyperplastic lesion (Fig. 3). Combining the imaging findings, we suspected a benign tumor within the knee joint, thus arthroscopic intervention was recommended. However, the patient opted to continue the conservative treatment, including anti-osteoporosis measures, anti-inflammatory medications, and analgesic support.

Fig. 3

MRI of the left knee at different times (T1). (a): Captured in the year 2018; (b): preoperative, captured in the year 2022; (c): postoperative, captured in the year 2023. The arrow points to xanthoma

In 2023, the patient’s left knee joint symptoms continued to worsen, accompanied by significant swelling and movement disorders. Regarding the physical examination, a positive floating patella test and knee tenderness were observed. The VAS score was 7, and the range of motion in the knee joint was limited to 10–103°. Muscle strength in the left lower limb was graded as IV. After discussed with the patient, a left knee arthroscopy performed under general anesthesia on November 10, 2023. The surgery removed a significant amount of tissue (Fig. 4).

Fig. 4

The tissue in the knee joint. (a): arthroscopy intraoperative pictures; (b): Tissue removed from the joint

The postoperative tissue biopsy indicated chronic synovitis with synovial hyperplasia, foam cell reaction, and multinucleated giant cell reaction, suggesting xanthoma-like proliferation. Immunohistochemistry showed Ki-67(5%+), CD138(focal+), CD68(+), CD163(+), S-100(-), EMA(-), and CKpan(-) (Fig. 5). The final diagnosis was knee joint synovial xanthoma. Postoperatively, the left knee joint swelling and pain reduced (VAS score: 3), and flexion-extension range increased to 10–140°.

Fig. 5

Xanthoma biopsy. The sample was stained with H&E and observed under a microscope at a magnification of 10X. The rectangle indicates synovial tissue hyperplasia, foam cell reactions, and multinucleated giant cell reactions

The patient has a history of inflammatory pseudotumor in the orbital region and received oral prednisone 4 mg daily from 2005 to 2008. There is also a four-year history of hypertension, and currently, blood pressure is within normal range. In 2021, the patient was diagnosed as hyperlipidemia, and no medications were applied. In 2022, the patient underwent a left nephrecture at our hospital due to loss of left kidney function resulting from severe hydronephrosis.

Results and discussions

The occurrence of osteonecrosis combined with xanthoma in the knee joint is an extremely rare condition, with no reported cases in previous literature. This is the first case report featuring the combination of osteonecrosis and xanthoma in the knee joint.

Osteonecrosis typically occurs at the ends of bones and rarely in the epiphysis or diaphysis [4]. It commonly results from local blood circulation disorders such as thrombosis, trauma, excessive glucocorticoid use, and lipid metabolism abnormalities, among other factors. Clinically, patients may present with focal pain, swelling, and even restricted mobility of adjacent joints. Additionally, characteristic features of infectious diseases, such as recurrent fever and increased white blood cell count, may also be observed [5, 6]. Initially, we attributed the patient’s symptoms to osteonecrosis. However, after conventional treatments, we observed significant improvement in the symptoms of the right knee joint, while the left knee showed less notable improvement. Subsequent MRI images revealed an abnormal mass in the knee joint (Fig. 3). This led us to suspect whether this abnormal mass was the cause of the symptoms. Following consent from the patient, we performed arthroscopic surgery. Postoperatively, the patient experienced gradual relief of pain in the left knee joint, with the VAS score decreased, and the range of motion increased. The postoperative pathological results confirmed the presence of xanthoma.

There are currently two theories regarding the formation of xanthoma [7]. The first theory suggests that local trauma or bleeding leads to the flow of fat into surrounding tissues, which is subsequently engulfed by macrophages, resulting in the accumulation of fat within these cells and the eventual appearance of foam-like macrophages. The extracellular cholesterol crystallizes into clefts, which induce an inflammatory reaction with giant cells and fibrosis. The second theory suggests that lipotrophic factors present in the blood of patients with autoimmune conditions may induce xanthomatous transformations in undifferentiated mesenchymal cells through a sequence of inflammatory reactions, with the subsequent accumulation of phagocytic histiocytes. The patient was diagnosed with hyperlipidemia after lipid metabolism abnormalities were detected in 2021. In 2022, synovial xanthoma appeared in the knee joint. Following our discussion, it was concluded that the patient’s knee joint synovial xanthoma was likely attributable to the lipid metabolism abnormality. Previous research has found that high cholesterol increases osteoclast differentiation and bone resorption, potentially leading to the occurrence of osteoarthritis [8]. Additionally, some studies indicate a certain correlation between elevated triglycerides and knee joint pain [9]. In this regard, we monitored the patient’s bone metabolism and lipid metabolism indicators during this period. We found that the patient’s bone resorption was active while bone formation was decreased. Concurrently, we observed an elevation in the patient’s triglyceride levels (Fig. 6). This is consistent with previous research. However, we cannot definitively determine whether the patient’s lipid metabolism abnormality is due to bone metabolism abnormalities or dietary factors. This prompts further consideration, suggesting the need for more in-depth basic experiments in the future to explore the relationship between bone metabolism and lipid metabolism and to further clarify whether there is a potential connection between osteonecrosis and xanthoma.

Fig. 6

Bone metabolism and lipid metabolism. PINP: Procollagen I N-Terminal Propeptide

In this case, we consider that the symptoms in the patient’s left knee joint may be caused by the knee joint synovial xanthoma. The synovitis caused by xanthoma and the occupation within the joint lead to knee joint pain, limited functional activity, and increased inflammation in the patients [10, 11]. After arthroscopic surgery, a substantial portion of the xanthoma and synovial tissue were removed, reducing the inflammatory factors in the knee joint. The patient’s left knee symptom improved significantly. In addition, considering the correlation between xanthoma and hyperlipidemia, we recommended oral lipid-lowering medication. However, the patient declined medication. Finally, we advised the patient to maintain a low-fat diet in their daily life to improve their hyperlipidemia state and prevent the recurrence of xanthomas. After discharge, we conducted a two-month follow-up and did not observe an exacerbation of knee joint pain in the patient. The VAS score was 2, and knee joint flexion and extension reached 10–150°.

Through this case, when clinicians encounter similar patients, it is crucial to determine whether the patient’s symptoms are caused by osteonecrosis or xanthoma. Our report may provide a feasible treatment approach for patients with osteonecrosis combined with xanthoma in knee joint.

There are a few limits of the study. Current research on xanthoma is mainly focused on dermatology, and the reason for its occurrence between knee joints is still unknown. Furthermore, whether the patient’s hyperlipidemia is caused by dietary factors or abnormalities in bone metabolism has not been sufficiently studied. There is currently no study explaining whether changes in bone metabolism can lead to abnormalities in lipid metabolism. Therefore, future research may require more animal experiments or genetic studies to explore the relationship between osteonecrosis and xanthoma and whether there is a genetic connection.

Conclusions

In summary, osteonecrosis combined with xanthoma in the knee joint is an exceptionally rare condition. This case suggests that, for patients with osteonecrosis combined with xanthoma, arthroscopic removal of the xanthoma in the knee joint is a feasible approach. It can alleviate knee joint pain and improve joint mobility. Considering that both conditions may manifest similar symptoms in the knee joint, it is crucial to identify their primary pathogenic causes.