Multiple myeloma is the most common plasma cell neoplasm, with an estimated 24,000 cases occurring annually.1 Symptomatic multiple myeloma most commonly presents with one or more of the cardinal CRAB phenomena of hypercalcemia, renal dysfunction, anemia, or lytic bone lesions.2 Less commonly, patients may present with plasmacytomas (focal lesions of malignant plasma cells), which may involve bony or soft tissues.1
Plasma cell neoplasms occasionally involve the joints, including the elbows, typically as plasmacytomas. The elbow is an unusual but reported location of plasmacytomas.3,4 A case of multiple myeloma and amyloid light-chain (AL) amyloidosis has been reported, with manifestations including pseudomyopathy, bone marrow plasmacytosis, and bilateral trochanteric bursitis.5Bursitis is defined as inflammation of the synovial-fluid–containing sacs that lubricate joints. The olecranon bursa is commonly affected. Etiologies include infection, inflammatory disease, trauma, and malignancy. Furthermore, there is an association between bursitis and immunosuppression.6,7 The most common modes of therapy used to treat bursitis are nonsteroidal anti-inflammatory drugs, corticosteroid injections, and surgical management.
Trochanteric bursitis has been attributed to multiple myeloma in one previous case report, but we are not aware of any previous cases of olecranon bursitis caused by multiple myeloma. Here, we present the case of a 46-year-old man with heavily pretreated multiple myeloma and amyloidosis who developed left olecranon bursitis contemporaneously with disease relapse; flow cytometric analysis of the bursal fluid demonstrated an abnormal plasma cell population, establishing the etiology.
Case presentation and summary
A 46-year-old man with a longstanding history of multiple myeloma developed swelling of the left elbow that was initially painless in September 2016. He had been diagnosed with IgA kappa multiple myeloma and AL deposition in 2011. Over the course of his disease, he was treated with the following sequence of therapies: cyclophosphamide, bortezomib, and dexamethasone, followed by melphalan-conditioned autologous peripheral blood stem cell transplant; lenalidomide and dexamethasone; carfilzomib and dexamethasone; pomalidomide, bortezomib, and dexamethasone; and bortezomib, lenalidomide, dexamethasone, doxorubicin, cyclophosphamide, and etoposide, followed by second melphalan-conditioned autologous peripheral blood stem cell transplant. In addition to treatment with numerous novel and chemotherapeutic agents, his disease course was notable for amyloid deposition in the liver, bone marrow, and kidneys, which resulted in dialysis dependence.
After the second autologous transplant, he achieved a very good partial response and experienced about 9 months of remission, after which laboratory evaluation indicated recurrence of IgA kappa monoclonal protein and free kappa light-chains, which increased slowly over several months without focal symptoms, cytopenias, or decline in organ function (Figure 1).
Twelve months after his second transplant, he presented in September 2016 with 4 weeks of left elbow swelling, with the appearance suggesting a fluid collection over the left olecranon process (Figure 2). The fluid collection was not painful unless bumped or pushed. The maximum pain level was 1-2 on a scale of 0-10. His daughter drained the fluid collection on 2 occasions, but it reaccumulated over 2 to 3 days. He reported no fevers, chills, or sweats. He did not have any redness at the site. He did not report any systemic symptoms.
Physical examination of the left elbow demonstrated a ballotable fluid collection associated with the olecranon, with no associated warmth, tenderness, or erythema. Bursal fluid was sampled, yielding orange-colored serous fluid with bland characteristics (Figure 3). Microbiologic studies were negative (Table 1). We did not suspect a malignant cause initially.
The fluid collection persisted despite treatment with nonsteroidal anti-inflammatory drugs and serial drainage procedures approximately twice per week. It became more erythematous and uncomfortable. We repeated diagnostic sampling at 13 months post-transplant. Cytospin revealed scant plasma cells. A multiparametric 8-color flow cytometric analysis was performed on the bursal fluid. It demonstrated the presence of a small abnormal population of plasma cells (0.04%). The abnormal plasma cells showed expression of CD138 and bright CD38 with aberrant expression of CD56, dim CD45, and loss of CD19, CD81 and CD27. They did not express CD117 or CD20 (Figure 4).
Because of the patient’s discomfort and his history of multidrug-refractory multiple myeloma, we obtained computed tomography imaging of the axial and appendicular skeleton, which demonstrated diffuse small lytic lesions, none larger than 3 mm, including the left elbow joint. The patient began systemic treatment with ixazomib, pomalidomide, and dexamethasone and then received radiation therapy of 20 Gy in 4 fractions to the left olecranon area. The bursal fluid collection remained stable in size but required periodic, though less frequent, drainage procedures. Unfortunately, the patient only tolerated 2 cycles of systemic therapy before experiencing hypercalcemia, exacerbation of hepatic amyloidosis, and a decline in performance status. He died 17 months after the transplant.
Our patient experienced left olecranon bursitis simultaneously with relapse of multiple myeloma and AL amyloidosis. Evaluation for infectious causes was negative, and the bursal fluid did not have strongly inflammatory characteristics. Furthermore, a small plasma cell population was isolated from the fluid. Imaging did not reveal an underlying dominant lytic lesion. Although we do not have direct pathologic confirmation, the clinical scenario and flow cytometry findings support our interpretation that the patient’s bursitis was caused by or at least related to underlying multiple myeloma. While reactive plasma cells are also CD38 positive and CD138 positive, they maintain the expression of CD19 and CD45 without aberrant expression of CD56 or CD117 and do not show loss of expression of CD81 or CD27. In this situation, we suspect that either a plasmacytoma involving the soft tissue of the bursa or amyloid infiltration of the synovium may have occurred. Anti-myeloma therapies and radiation therapy did not result in control of the bursitis, though it should be noted that the patient’s highly refractory disease progressed despite treatment with a combination of later-generation immunomodulatory imide and proteasome inhibitor therapies.
Cases of malignant bursitis have been reported several times in the literature, though nearly all of the instances involved connective tissue or metastatic tumors. Tumor histologies include osteochondroma,8,9 malignant fibrous histiocytoma,10 synovial sarcoma,11 and metastatic breast cancer.12
Hematologic malignancies are more rare causes of bursitis; our literature search identified a report of 2 cases of non-Hodgkin lymphoma mimicking rheumatoid arthritis. The joints were the knee and elbow. Synovial fluid from one case was clear and yellow, with leukocytosis with a neutrophilic predominance (similar to our case). In both cases, pathology confirmed lymphomatous infiltration of the synovium.13 Notably, we identified a case of a previously healthy 35-year-old woman with bilateral trochanteric bursitis. Biopsy of tissue from the right trochanteric bursa demonstrated positive birefringence, diagnostic of AL amyloidosis. The patient also had a biclonal paraprotein accompanied by calvarial lytic lesions. She was treated with a corticosteroid pulse and bisphosphonates, followed by autologous hematopoietic stem cell transplant. 5 Our case shares features with the above case, including the relatively young age of the patient and the presence of AL amyloidosis.
Our patient wished to avoid a surgical biopsy procedure, and therefore we utilized flow cytometry of the bursal fluid to establish that the etiology of fluid collection was consistent with his concurrent relapse of multiple myeloma. We believe that we are reporting the second case of multiple myeloma-associated bursitis and the first case associated with multiple myeloma relapse; to our knowledge, it is the first to be diagnosed with the aid of flow cytometry.
Because of our patient’s reliance on hemodialysis beginning one year prior to his presentation with olecranon bursitis, we entertain “dialysis elbow” within the differential diagnosis. Dialysis elbow is a relatively uncommon complication of dialysis, in which patients develop olecranon bursitis on the same side as the hemodialysis access after a prolonged (months to years) duration of hemodialysis. Serositis and mechanical forces are the hypothesized etiologies14; infectious and rheumatologic causes were excluded from the reported cases. Nevertheless, we favor a malignant cause based upon the flow cytometry findings indicating involvement by immunophenotypically abnormal plasma cells.
Our patient was treated initially with serial drainage and nonsteroidals, which had little impact. After diagnosis of a plasma cell population in the fluid, we offered local treatment with radiation and systemic treatment of multiple myeloma, which offered better but suboptimal control. Possible treatments for olecranon bursitis include surgery, corticosteroid injections, anti-inflammatories, and serial drainage. Nonsurgical management may be more effective than surgical management, and corticosteroid injection carries significant risks. On the other hand, serial drainage does not confer additional infection risk in cases with aseptic etiology.15 We combined conservative measures as well as treatment of the underlying disease, but we believe that our patient did not derive significant benefit because of the refractory nature of his disease; he also expressed a preference to avoid surgical intervention.
Bursitis is a rare but thought-provoking potential manifestation of multiple myeloma and AL amyloidosis; we believe that our patient’s bursitis was related to plasma cell neoplasia based upon co-occurrence with disease relapse. His bursitis turned out to be an early indicator of impending systemic relapse. In this particular case, in which the patient wished to avoid surgical intervention, flow cytometry was of great value, and we believe that our case is the first report of malignant bursitis being diagnosed by flow cytometry. Our patient’s case shares similarities with other biopsy-confirmed cases of malignant bursitis, but we were able to avoid the need for surgical biopsy or bursal stripping.
The authors thank Jennifer Wilham MT (ASCP), Pat Byrd MT (ASCP), and Darlene Mann MT (ASCP) for their technical support.