Extramedullary Relapse of Multiple Myeloma After Total Knee Arthroplasty: Implications for Orthopaedic Surgeons—A Case Report and Literature Review

Abstract

Multiple myeloma (MM) is a hematologic B-cell malignancy characterized by clonal plasma cell proliferation in the bone marrow. Extramedullary disease is a more aggressive form of MM, in which monoclonal cells proliferate outside the bone marrow, forming plasmacytomas. This case highlights a 56-year-old male presenting with an extramedullary recurrence of MM in the soft tissue surrounding the incision site of his total knee arthroplasty. Fortunately, following radiation and chemotherapy, his most recent evaluation demonstrated complete resolution of the nodules within the radiation field. As orthopaedic surgeons, this case serves as an important reminder to remain vigilant about prior malignancies that may complicate perioperative management.

Introduction

Multiple myeloma (MM) is a hematologic B-cell malignancy characterized by ≥ 10% clonal plasma cells in the bone marrow, often presenting with hypercalcemia, anemia, renal dysfunction, and lytic bone lesions [1,2]. Typically affecting individuals over 65, MM has a multifactorial etiology and frequently evolves from monoclonal gammopathy of undetermined significance at a rate of 1% to 2% annually [1]. Treatment focuses on prolonging survival and managing complications through immunomodulatory agents, proteasome inhibitors, monoclonal antibodies, and autologous hematopoietic stem cell transplantation [1]. Extramedullary disease (EMD), an aggressive MM subtype, occurs in 3% to 5% of newly diagnosed patients and 6% to 20% of relapsed/refractory cases, with a higher prevalence in younger males and potential links to novel agent therapies [[3], [4], [5], [6]].

We report a novel case of a 56-year-old man with a history of MM in remission who, 4 months after total knee arthroplasty (TKA), developed biopsy-proven peri-incisional plasma cell nodules, successfully treated with radiation therapy (800 cGy) and subsequent chemotherapy. TKA, a widely performed procedure with satisfaction rates of 80%-100%, is projected to reach 3 million annually by 2030 [7,8]. While infection, instability, and aseptic loosening remain leading causes of revision [9], this case highlights the need for heightened awareness of neoplastic recurrence in MM patients presenting with atypical postoperative findings, given the rising volume of TKAs and associated complications.

Case history

The patient is a 56-year-old male with a past medical history of obstructive sleep apnea, type 2 diabetes mellitus, hypertension, chronic low back pain, and normocytic anemia. He presented to the emergency department in September 2020 with complaints of progressively worsening right shoulder pain, which had been ongoing since March 2020.

On physical examination, the patient had a firm, immobile, mildly tender, and well-circumscribed mass measuring approximately 10 × 10 cm over the posterior aspect of the right shoulder, extending superiorly from the region of the scapular spine. Radiographic evaluation, including radiograph, computed tomography (CT), and magnetic resonance imaging of the right shoulder, revealed a destructive mass involving the acromion, scapular spine, and superior soft tissue. Dystrophic calcifications were present, with some inferior extension into the glenoid neck and associated supraclavicular lymphadenopathy (Figs. 1 and 2). To assess for systemic involvement, a positron emission tomography (PET) scan and bone survey were performed, which demonstrated widespread lytic lesions throughout the spine, ribs, and right humerus. Laboratory studies revealed a monoclonal protein spike (2.9 g/dL) in the gamma region on serum protein electrophoresis. The patient subsequently underwent an open biopsy of the right scapular mass. Histopathology revealed sheets of plasma cells with kappa light chain restriction, consistent with a plasmacytoma in the setting of underlying multiple myeloma. He was initiated on systemic chemotherapy and received a course of radiation therapy, ultimately achieving remission.

Figure 1.

CT views of the right shoulder demonstrating destructive lytic mass of the right scapula on initial presentation. Coronal (a) and axial (b) CT scan views of the right shoulder demonstrating a large soft tissue mass involving the acromion and scapular spine as well as the superior soft tissue with dystrophic calcifications. There is some extension inferiorly into the glenoid neck with evidence of supraclavicular lymphadenopathy. The mass measures roughly 12.8 × 9.1 × 7.8 cm.

Figure 2.

Radiographs of the right shoulder demonstrating destructive lytic mass of the right scapula on initial presentation. Anteroposterior (a) and scapular y (b) radiographs of the right shoulder demonstrating bony destructive changes of the acromion with areas of dystrophic calcification. There are mild osteoarthritic degenerative changes noted at the glenohumeral joint as well.

In December 2021, the patient underwent an elective right TKA for primary osteoarthritis. Preoperative evaluation by his orthopedic surgeon, primary care physician and hematology/oncology physician including laboratory analysis, electrocardiogram and preoperative radiographs were overall unremarkable. PET CT scan in February 2021 demonstrated a favorable response to chemotherapy with no new lesions. Approximately 4 months later, in April 2022, he began to notice the development of soft tissue nodules around the surgical incision site on his right knee. He denied similar nodules elsewhere on his body. The nodules were tender, particularly with kneeling, but were otherwise nonpainful. They were observed at this time and thought to be due to scar tissue by his arthroplasty surgeon. He again presented to clinic in October 2022 and was referred to orthopaedic oncology. Physical examination at that time revealed multiple firm, mobile subcutaneous nodules measuring 1-3 cm along the anterior aspect of the right knee. While some nodules extended distal to the previous surgical approach, they were generally centered around the surgical site. Radiographs of the right knee demonstrated no evidence of lytic lesions, periprosthetic fracture, or component loosening. (Fig. 3). PET scan performed prior to right total knee arthroplasty showed no increased uptake in the right knee region (Fig. 4).

Figure 3.

Anteroposterior radiograph of the right knee demonstrating right total knee arthroplasty 10 months postoperatively. Anteroposterior radiograph of the right knee demonstrating a right total knee arthroplasty in good mechanical alignment without evidence of component failure or loosening. No evidence of periprosthetic fracture. No evidence of lytic lesions.

Figure 4.

PET CT views prior to right total knee arthroplasty. Coronal (a) and axial (b) PET CT views demonstrating no increased activity at the right knee prior to right total knee arthroplasty.

An ultrasound-guided needle biopsy of the nodules was performed, and histologic analysis revealed plasma cell infiltration consistent with plasmacytoma in the setting of known plasma cell myeloma. A repeat PET scan at that time did not show increased metabolic activity in the right knee region, despite the presence of new plasmacytomas (Fig. 5). The patient subsequently underwent localized radiation therapy, which resulted in complete resolution of the nodules within the radiation field by his most recent follow-up in January 2023. He was also restarted on systemic chemotherapy. A few residual nodules remained just distal to the radiation field, along the medial proximal shin, but these were stable on follow-up. The patient continued receiving systemic chemotherapy for his remaining nodules but otherwise he has not had recurrence elsewhere; his prognosis remains favorable. Informed consent was obtained from the patient for publication of his clinical course in this report.

Figure 5.

PET CT views after diagnosis of extramedullary MM recurrence. Sagittal (a), coronal (b), and axial (c) PET CT views demonstrating no increased activity at the right knee where the patient experienced an extramedullary recurrence of his MM in the soft tissues surrounding his total knee arthroplasty incision.

Discussion

To our knowledge, this is the first reported case of EMD in MM manifesting as peri-incisional plasmacytomas following TKA, a procedure not previously associated with EMD relapse. Unlike prior reports of EMD in scar tissue from fracture fixation or tumor resection, this case highlights a novel clinical scenario involving elective joint replacement in a patient with MM in remission.

EMD in MM is an aggressive subtype characterized by the proliferation of monoclonal plasma cells outside the bone marrow, leading to plasmacytoma formation [2,[10], [11], [12]]. These lesions typically arise from hematogenous dissemination and may manifest at initial diagnosis or during relapse. The incidence of EMD in newly diagnosed MM ranges from 0.5% to 4.8%, rising to 3.4%-14% in cases of relapse [2]. At presentation, EMD most frequently involves the skin and soft tissues, whereas relapse often affects visceral organs, including the liver, kidneys, lymph nodes, central nervous system, breast, pleura, and pericardium [2,11]. Less commonly, extramedullary plasmacytomas (excluding solitary plasmacytomas (SPs)) occur in atypical sites such as skeletal muscles, periorbital tissues, the sternum, and the spine, typically as recurrences following initial remission [2,[10], [11], [12], [13], [14], [15]]. Paraskeletal plasmacytoma originates from skeletal tumors following bone disruption, while SP denotes a single clonal plasma cell mass (bone or extramedullary) with minimal bone marrow plasmacytosis and no additional symptoms. Plasma cell leukemia is defined by ≥ 20% and ≥2 × 10⁹/L circulating plasma cells. Historically, paraskeletal plasmacytoma’s inclusion as an EMD subtype remains debated, whereas SP and plasma cell leukemia are excluded [16,17].

Overall, the relapse of tumors within scar tissue is a seldom-observed phenomenon among cancer patients. Our patient was in remission preoperatively and had no signs uptake in the operative site on PET scan from Feb 2021. Of note, relapse/emergence is described via 1 of 2 pathways. The first involves direct seeding of malignant cells into the wound tissue during invasive procedures, such as tissue sampling or tumor resection. The second occurs through systemic dissemination, either via lymphatic channels or hematogenous spread, into the wound site [[18], [19], [20], [21], [22]]. Surgical trauma and wound healing may create a permissive microenvironment for circulating plasma cells to seed, potentially driven by inflammatory cytokines or angiogenesis at the surgical site. In our case, the absence of known disease at the surgical site preoperatively and negative PET imaging support hematogenous dissemination over direct seeding.

This case raises a valid observation in that orthopaedic surgeons more often than not will encounter a patient with a history of tumors in their careers, particularly those involving the musculoskeletal system. Understanding a patient's previous malignancies, even if in remission, becomes essential because it informs the surgeon about the nature of the original malignancy, its treatment, and the likelihood of recurrence, which can significantly impact surgical planning and postoperative outcomes.

Preoperatively, we often have to hold systemic therapies, and in our case, we held the patient’s Lenalidomide. Postoperatively, we often will have close follow-up at 2 weeks, 6 weeks, 3 months, 6 months, and 1 year, at a minimum, suggesting that this ought to encourage us to carefully inspect the skin, palpate for any masses, and maintain a strong suspicion of recurrence should our physical exam be abnormal or an in an oncologic patient having atypical pain after arthroplasty. Fortunately, our patient had gross, macroscopic findings along his scar which made identifying, biopsying, and confirming his recurrence of EMD rather expedient, allowing him to get the appropriate treatment in a timely manner.

Per our review, this serves as the first case of EMD recurring at the surgical site following arthroplasty. Most similarly, other authors identified a case report of plasmacytomas arising from the surgical scar of a 71-year old male undergoing internal fixation of a presumed osteoporotic-associated fracture with intramedullary nailing who was also in remission with no evidence of disease progression [18]. A biopsy of the soft tissue near a fractured bone revealed immature plasma cells with high mitotic activity and significant apoptosis. Several weeks postsurgery, the patient’s operated arm exhibited progressive swelling. The disease advanced, and the patient succumbed to progressive renal failure 10 months following recurrence.

Muchtar et al. describe 6 other MM patients with EMD relapse in scar tissue, including 2 cases from their series and 4 from prior reports. All cases involved immunoglobulin G or kappa light chain subtypes. An extramedullary plasmacytoma (EMP) was present at diagnosis in 2 cases. Lactate dehydrogenase levels, normal at diagnosis, were elevated at EMP progression in 5 cases where data were reported. Prior treatments included novel agents (eg, lenalidomide, bortezomib, thalidomide) and autologous hematopoietic stem cell transplantation in 5 cases. Invasive procedures preceding EMP varied (eg, fracture fixation, tumor debulking, tooth extraction), with EMP localizing to sites such as the arm, sacral region, and gingiva. Treatments for EMP, including radiotherapy and chemotherapy (eg, VDT-PACE, bendamustine), yielded poor responses, with 6 patients experiencing progressive disease and death within 3-10 months of recurrence. Overall survival from MM diagnosis ranged from approximately 10 months to 9 years, with 1 patient achieving complete remission and surviving over 24 months postrecurrence [18].

This case underscores the need for orthopaedic surgeons to be well-versed in recognizing common postoperative complications such as infection, aseptic loosening, and instability, while also maintaining a heightened suspicion for malignant recurrence in oncologic patients, including those with multiple myeloma (MM) in remission. Such vigilance is essential for enabling prompt diagnosis and intervention, which can significantly improve patient prognosis and quality of life. In our patient, the successful response to systemic chemotherapy and radiation therapy, with no disease progression at over 18 months, stands in stark contrast to prior reports where delayed diagnosis or visceral EMD was associated with poorer outcomes [18]. To enhance the quality of care, preoperative oncologic evaluations, including PET/CT scans or serum marker assessments, may be judiciously considered for patients with MM, including those in remission, to evaluate the risk of relapse prior to surgery, guided by individual clinical characteristics and risk profiles. Although PET/CT scans demonstrate high sensitivity for detecting plasmacytomas, in our patient, this imaging modality did not reveal evidence of active disease either preoperatively or postoperatively [23]. This may be attributed to the limited ability of PET/CT to detect very small lesions. In cases of high clinical suspicion, alternative approaches such as magnetic resonance imaging or tissue biopsy may be considered [24]. Postoperatively, the absence of PET-avid lesions could be confounded by increased physiologic metabolism secondary to recent surgical intervention, which may obscure the PET signal from subtle soft tissue lesions. Additionally, standardized postoperative surveillance protocols, including regular physical examinations and imaging for atypical symptoms, could facilitate earlier detection of complications like EMD. Equally critical is fostering multidisciplinary collaboration between orthopedic surgeons and oncologists to ensure comprehensive management of MM patients undergoing surgery, ultimately optimizing clinical outcomes.

Summary

MM is a hematologic B-cell malignancy characterized by clonal plasma cell proliferation in the bone marrow. Extramedullary MM is a more aggressive form of the disease where the plasma cells proliferate outside of the bone marrow and form plasmacytomas involving soft tissues or visceral organs. In patients with history of MM in remission, it requires a high index of suspicion to identify recurrence in cases of new soft tissue masses with unclear imaging findings. Physicians must be mindful when caring for patients with previous malignancies as it can complicate perioperative management. This case demonstrates that soft tissue manifestations postoperatively can be the only sign of recurrence of prior malignancy and need to be recognized early. Biopsy of the suspected lesion(s) can help clinicians definitively diagnose extramedullary plasmacytomas in these cases and proper treatment can be initiated.

Conflicts of interest

Drew D. Moore was a one-time product consultant for Stryker in 2025.

The other authors declare no potential conflicts of interest.

For full disclosure statements refer to https://doi.org/10.1016/j.artd.2025.101834.

Informed patient consent

The author(s) confirm that written informed consent has been obtained from the involved patient(s) or if appropriate from the parent, guardian, power of attorney of the involved patient(s); and, they have given approval for this information to be published in this case report (series).

CRediT authorship contribution statement

Donald C. Hefelfinger: Writing – review & editing, Writing – original draft, Project administration, Methodology, Investigation, Formal analysis. Mohamed-Ali Sareini: Writing – review & editing, Writing – original draft, Project administration, Methodology, Investigation, Formal analysis. Drew D. Moore: Writing – review & editing, Supervision, Project administration, Investigation, Conceptualization.