Introduction
MM is a clonal plasma cell malignancy of the bone marrow characterized by the production of monoclonal immunoglobulins. It most commonly affects individuals in their 70s. 1 Patients typically present with symptoms of bone pain, anemia, renal dysfunction, and hypercalcemia. MM is diagnosed by the presence of ≥10% clonal plasma cells in the bone marrow or with a biopsy-proven plasmacytoma. 1 MM is usually limited to the bone marrow; however, some patients develop extramedullary disease (EMD). Extramedullary plasmacytomas (EMP) can be present since the initial diagnosis or appear along the course of the disease indicative of a more aggressive presentation. 1 The incidence of EMPs changes depending on the diagnostic criteria, imaging techniques, and disease phase. At the time of MM diagnosis, EMPs have an incidence of 1.75-4.5%, which increases in the relapsed phase to 3.4-10%. 2 Improvements in imaging modalities, mainly PET-CT and MRI, have contributed to higher detection rates making the incidence of EMD at diagnosis 6-10%. 3 A retrospective analysis of 226 MM patients presenting with plasmacytomas identified EMD in 176 cases. Among these, the most frequently affected sites were the skin and muscle (24%), followed by the pleura (12%), lymph nodes (10%), liver (9%), and central nervous system (6%). 3 In newly diagnosed MM skin was found to be the most commonly involved tissue however liver, kidneys, lymph nodes, CNS, breast, pleura, and pericardium were more common in relapsed/refractory MM. 3 Early radiologic detection of EMPs is critical in the management of MM; particularly ultrasound helps the identification of soft tissue EMPs, especially superficial sites such as skin, subcutaneous tissue, and muscle. 4 Multimodal ultrasonography characterizes the morphology and vascularity of the lesion allowing the differentiation of benign lesions from malignant. In addition, sonographic assessment allows for guided biopsy, facilitating early histopathological confirmation. 4
Case Report
History and Examination
A 59-year-old man previously known to have MM, diagnosed in April 2024, presented for an ultrasound for two palpable indurations in his left upper and lower back. He received four cycles of the VCD regimen (Bortezomib,Cyclophosphamide, and Dexamethasone) following diagnosis and achieved remission confirmed by both serum and urine immunofixation demonstrating absence of detectable M-protein, and it has lasted until October 2025. At that time, daratumumab (Darzalex) was initiated, but the disease progressed early in the course of treatment. Subsequently, therapy was switched to teclistamab, and he has completed three doses to date. Notably, the cutaneous lesions on his back developed during the period of remission. A renal evaluation was performed, revealing proteinuria that improved during remission but worsened with disease progression. Renal biopsy was deferred in accordance with the patient’s preference. The indurations were not tender, firm, nonmobile and growing in size. On inspection, two violaceous, oval shaped, protruding, well defined lesions were visualized.
Investigations and Management
Ultrasound Findings
Two protruding indurations are noted in the left upper and lower back corresponding to 1.2 x 1.5 cm and 2.7 x 5.2 cm oval well circumscribed heterogeneous hypoechoic solid subcutaneous masses. Both lesions exhibit internal arterial vascularity on Doppler evaluation ( Figure 1 ). Figure 1. (A) Grayscale ultrasound image of the left upper back lesion, demonstrating a 1.2 × 1.5 cm well-circumscribed heterogeneous hypoechoic subcutaneous mass. (B) Grayscale ultrasound image of the left lower back lesion, demonstrating a 2.7 × 5.2 cm well-circumscribed heterogeneous hypoechoic subcutaneous mass. (C) Color Doppler ultrasound image of the left upper back lesion showing internal arterial vascularity. (D) Color Doppler ultrasound image of the left lower back lesion showing internal arterial vascularity
Histopathological Findings
A tru-cut biopsy specimen weighing 16 grams was obtained from the soft tissue mass infiltrating the back muscle. Macroscopically, the specimen consisted of three core biopsies, each measuring approximately 1.4 cm in length, received in formalin and entirely submitted for microscopic evaluation.
Microscopic examination demonstrated a diffuse proliferation of plasma cells infiltrating and dissociating skeletal muscle fascicles, with areas of fibro-hyalinized connective tissue. Immunohistochemical staining revealed that the neoplastic plasma cells were extensively and diffusely positive for CD138 and restricted to lambda light chain expression, while negative for kappa light chain, CD3, and CD20. These findings are diagnostic of a plasma cell neoplasm with lambda light chain restriction.
Although PET/CT and whole-body MRI are considered the preferred imaging modalities for assessing the extent of extramedullary disease in multiple myeloma, these studies were not available in the present case. Consequently, it was not possible to determine with certainty whether the back lesions represented isolated extramedullary involvement or part of more widespread extramedullary disease. This should be considered a limitation of our report.
Outcome and Follow up
The histopathological diagnosis of extramedullary plasmacytoma involving the subcutaneous tissue and skeletal muscle was communicated to the hematology team and interpreted as evidence of extramedullary progression of the patient’s multiple myeloma. Systemic treatment with teclistamab was continued, as it had recently been initiated at the time of diagnosis of the soft tissue lesions. The patient tolerated treatment without major adverse events requiring discontinuation.
At the first clinical follow-up, approximately 8 weeks after the biopsy, the patient remained clinically stable. The cutaneous masses persisted but showed no significant increase in size on physical examination, and no new soft tissue lesions were identified. The patient reported no pain, ulceration, bleeding, or functional impairment related to the lesions. Renal function remained stable, although persistent proteinuria was noted and continued to be managed conservatively in accordance with the patient’s preference to defer renal biopsy.
The patient continues to undergo close follow-up with the hematology service, with serial clinical examinations and laboratory monitoring to assess treatment response and detect further disease progression. Because PET/CT and whole-body MRI were unavailable, radiologic assessment of the overall burden of extramedullary disease was limited. Ongoing surveillance has therefore relied on clinical evaluation, biochemical markers, and targeted imaging when clinically indicated ( Table 1 ). Table 1. Timeline of Clinical Events Date Clinical event April 2024 Diagnosed with multiple myeloma April–August 2024 Received four cycles of VCD; achieved complete remission (negative serum and urine immunofixation) During remission Two painless left back indurations first noticed and progressively enlarged October 2025 Biochemical/clinical relapse; daratumumab initiated Shortly thereafter Ultrasound demonstrated two vascular subcutaneous masses Following ultrasound Ultrasound-guided core biopsy confirmed lambda-restricted extramedullary plasmacytoma After early progression on daratumumab Switched to teclistamab (three doses administered)
Table 1.
Timeline of Clinical Events
| Date | Clinical event |
| April 2024 | Diagnosed with multiple myeloma |
| April–August 2024 | Received four cycles of VCD; achieved complete remission (negative serum and urine immunofixation) |
| During remission | Two painless left back indurations first noticed and progressively enlarged |
| October 2025 | Biochemical/clinical relapse; daratumumab initiated |
| Shortly thereafter | Ultrasound demonstrated two vascular subcutaneous masses |
| Following ultrasound | Ultrasound-guided core biopsy confirmed lambda-restricted extramedullary plasmacytoma |
| After early progression on daratumumab | Switched to teclistamab (three doses administered) |
Patient Perspective
The patient expressed appreciation for the timely evaluation of the newly developed soft-tissue masses and the prompt biopsy that established the diagnosis. He understood that the lesions represented progression of his multiple myeloma and agreed with continuation of systemic therapy. At the latest follow-up, he reported that the lesions were not painful and had not significantly affected his daily activities.
Discussion
Plasmacytomas are localized tumors composed of monoclonal plasma cells and are classified according to their site of origin. Extramedullary plasmacytoma (EMP) refers to a plasma cell neoplasm arising in soft tissues outside the bone and without an underlying osseous lesion. In contrast, extramedullary disease (EMD) is a broader term describing plasma cell infiltration occurring outside the bone marrow microenvironment in patients with multiple myeloma (MM). When EMD develops as a manifestation of established MM, it is referred to as extramedullary multiple myeloma (EMM). EMM most commonly results from hematogenous dissemination of malignant plasma cells that have acquired the ability to survive independently of the bone marrow niche. This should be distinguished from paraskeletal disease, in which a plasmacytoma extends directly from an adjacent bone lesion through cortical disruption into surrounding soft tissues. In the present case, the patient had established MM and biopsy-proven soft-tissue plasma cell infiltration; therefore, the lesions are considered manifestations of EMM presenting as secondary extramedullary plasmacytomas. 1 , 2
Plasmacytoma is a type of B-cell neoplasm composed of abnormal plasma cells that aggregate to form a tumor mass. Based on the site of origin, plasmacytomas are classified into two main types: solitary bone plasmacytoma (SBP), which arises from the bone marrow and typically presents as a single lesion in the spine, pelvis, skull, or other skeletal sites; and EMP, which originates from extraosseous or mucosal tissues and presents as soft tissue lesions. 5 In this discussion, the primary focus is on EMP. First described by Schridde in 1905, EMP is recognized as part of the spectrum of plasma cell malignancies. 6 EMPs are further categorized into primary EMP and secondary EMP, the latter representing an extramedullary manifestation of MM. 2 EMP is relatively rare, accounting for only about 2% of all plasma cell neoplasms. 7 , 8
EMPs can be a manifestation of advanced MM. In such cases, they are referred to as extramedullary multiple myeloma (EMM). These lesions result from hematogenous dissemination of malignant plasma cells and are located within soft tissue sites. It is crucial to differentiate between two distinct types of plasmacytomas associated with MM: EMM, as described above, where plasma cells infiltrate soft tissues via the bloodstream; and MM with paraskeletal disease, where plasmacytomas arise due to direct extension from bone marrow lesions, following cortical bone disruption. 9 The diagnosis of EMP requires a comprehensive approach, including clinical assessment, laboratory investigations, advanced imaging, and histopathological confirmation. Plasmacytoma is distinguished from MM by the presence of a single lesion (either in bone or soft tissue), normal bone marrow (typically with <5% plasma cells), a normal skeletal survey aside from the identified lesion, absent or minimal monoclonal protein (M-protein), and no evidence of end-organ damage (i.e., absence of CRAB features: hypercalcemia, Renal impairment, Anemia, or Bone lesions). 10
MM cells can disseminate hematogenously from the bone marrow and become independent of the marrow microenvironment, allowing infiltration of various soft tissue and organ systems. 11 Although EMP is a rare manifestation of MM, it poses a diagnostic challenge due to its non-specific imaging features, which can mimic other malignancies or inflammatory conditions. 12 There is limited literature describing the imaging characteristics of extraosseous plasmacytomas, making accurate diagnosis and staging dependent on a multimodality imaging approach. Each imaging modality contributes uniquely to characterizing lesion extent, guiding staging, and monitoring therapeutic response. Ultrasound is generally not the first-line imaging modality for detecting EMP, particularly in cases where lesions are deeply located within organs or not superficial. Instead, it is typically considered a complementary tool that must be correlated with more reliable or preferred imaging modalities such as PET/CT, as well as with histopathological findings. In fact, ultrasound plays a limited role in the detection and diagnosis of MM overall. Modalities such as CT, MRI, and FDG-PET are preferred and widely recommended for identifying extraosseous and especially soft tissue involvement in MM. 13 A retrospective analysis conducted in 2025 on patients with MM and extramedullary manifestations described EMM findings using two ultrasound modalities: B-mode and contrast-enhanced ultrasound (CEUS). On B-mode ultrasound, EMMs appeared hypoechoic with either smooth or irregular borders. In contrast, CEUS revealed that most EMMs exhibited arterial hyperenhancement or isoenhancement, while a smaller number showed parenchymal iso- or hypoenhancement. 14 Additionally, ultrasound has been used to report rare presentations of EMM in locations such as the breast and mesenteric lymph nodes. 15 , 16 Ultrasound can play an important role in detecting superficial or organ-based EMP. In our case, high-resolution ultrasound revealed focal areas of soft tissue induration, which were subsequently confirmed as plasmacytomas through histopathological correlation. These findings are consistent with previously reported ultrasound characteristics of EMPs, including hypoechoic or heterogeneous echotexture, well-defined or indistinct margins, and increased vascularity on Doppler imaging. The presence of extramedullary manifestations in MM is indicative of a poor prognosis and typically reflects an advanced stage of disease. A retrospective study evaluating the prognosis of 226 patients with relapsed MM found that those experiencing soft tissue-related extramedullary relapse had significantly worse overall survival compared to patients with bone-related extramedullary involvement (5 months vs. 12 months). 17 Furthermore, a systematic literature review published in 2022 analyzed the occurrence of EMD in MM. It reported an incidence rate of 0.5% to 4.8% in newly diagnosed multiple myeloma (NDMM) and 3.4% to 14% in relapsed or refractory multiple myeloma (RRMM). Across multiple studies, prognosis was consistently poorer in patients with EMD than in those without. Among soft tissue plasmacytomas, true EMD, defined as disease occurring at sites without direct connection to bone, was associated with worse outcomes than paraskeletal involvement. CNS infiltration, in particular, carried the worst prognosis. 3 EMPs can present at the initial diagnosis of MM, may serve as the first clinical indication leading to MM diagnosis due to a suspicious mass, or can appear later in the disease course, often signifying progression and an associated poor prognosis. 18 Failure to detect EMPs early may result in incorrect disease staging, potentially leading to suboptimal treatment decisions, as specific therapies are indicated based on accurate staging. Given that the presence of EMP in MM is considered an aggressive disease manifestation with a poor prognosis, treatment strategies tend to be more intensive. In cases where EMP occurs in isolation, without a confirmed diagnosis of MM, radiotherapy remains the first-line treatment due to the high radiosensitivity of these tumors. Patients who tend to achieve the best results with radiotherapy include those with head and neck EMPs, tumor size < 4 cm, age < 50 years, and absence of serum M-protein. 19
Following histopathological confirmation, the back lesions were managed as manifestations of systemic relapsed multiple myeloma rather than isolated extramedullary plasmacytomas. Consequently, treatment was directed toward systemic disease with teclistamab, and local radiotherapy was not administered. While radiotherapy is highly effective for solitary extramedullary plasmacytomas and may provide excellent local control or palliation of symptomatic lesions, patients with systemic or relapsed multiple myeloma generally require systemic anti-myeloma therapy to address the underlying disease burden. Therefore, the management strategy should be individualized according to the extent of disease, symptom burden, and overall treatment goals within a multidisciplinary setting.
The sonographic appearance of extramedullary plasmacytoma is not pathognomonic and should be interpreted in conjunction with the patient’s clinical history and laboratory findings. The differential diagnosis of a superficial hypoechoic vascular soft-tissue mass includes benign lesions such as lipoma, although lipomas are typically well-circumscribed, compressible, predominantly echogenic or isoechoic to subcutaneous fat, and demonstrate little or no internal vascularity on Doppler imaging. Malignant lesions such as soft-tissue sarcoma, lymphoma, and metastatic deposits may also present as hypoechoic vascular masses with overlapping ultrasound features. Inflammatory processes, including abscesses or focal inflammatory pseudotumors, may likewise appear as heterogeneous soft-tissue masses but are usually associated with pain, surrounding inflammatory changes, or systemic signs of infection. In patients with a known history of multiple myeloma, the presence of a new vascular soft-tissue mass should raise suspicion for extramedullary plasmacytoma; however, imaging findings alone are insufficient for diagnosis. Therefore, image-guided biopsy with histopathological and immunohistochemical evaluation remains the gold standard for establishing the diagnosis and excluding other neoplastic or inflammatory conditions. 18
One of the most noteworthy aspects of this case is the development of biopsy-proven extramedullary plasmacytoma during a period of apparent serological remission, as demonstrated by negative serum and urine immunofixation. This finding underscores the recognized biological heterogeneity of multiple myeloma, in which extramedullary disease may evolve independently of bone marrow disease and conventional serological markers. The acquisition of a plasma cell clone capable of surviving outside the bone marrow microenvironment has been associated with reduced dependence on marrow-derived growth signals, altered expression of adhesion molecules, and increased metastatic potential. Consequently, serological remission does not necessarily exclude ongoing or emerging extramedullary disease. This case highlights the importance of thorough clinical examination and prompt evaluation of new soft-tissue masses in patients with multiple myeloma, regardless of favorable laboratory findings. Suspicious lesions should undergo appropriate imaging and, when indicated, image-guided biopsy to avoid delayed diagnosis and ensure timely modification of therapy.
The occurrence of extramedullary plasmacytoma despite negative serum and urine immunofixation highlights an important clinical challenge in the management of multiple myeloma. Although immunofixation is a valuable tool for monitoring treatment response, it primarily reflects systemic monoclonal protein production and may fail to detect localized extramedullary progression. Extramedullary disease may arise from plasma cell clones that have acquired biological characteristics allowing proliferation independent of the bone marrow microenvironment, resulting in clinical progression despite apparent serological remission. Therefore, new or enlarging soft-tissue masses in patients with multiple myeloma should prompt further evaluation regardless of favorable laboratory findings. In the present case, PET/CT and repeat bone marrow biopsy were not performed following detection of the lesions. Consequently, it was not possible to determine the full extent of systemic or extramedullary disease or to assess concurrent bone marrow involvement. Comprehensive restaging with whole-body imaging and repeat bone marrow evaluation, when clinically appropriate, would have provided additional information regarding disease burden and may have further informed prognostic assessment and therapeutic decision-making. 19
Reports describing superficial soft-tissue plasmacytomas involving the back are limited in the literature. Most cases of extramedullary multiple myeloma involve the upper aerodigestive tract, skin, lymph nodes, liver, pleura, or other visceral organs, whereas involvement of the superficial posterior trunk is rarely documented. Furthermore, the imaging characteristics of these lesions, particularly on ultrasound, remain poorly described, with most published reports focusing on PET/CT or MRI findings 20 - 23 ( Table 2 ). Our case contributes to the existing literature by illustrating the sonographic appearance of superficial back plasmacytomas, including heterogeneous hypoechogenicity and internal arterial vascularity, together with histopathological confirmation. This case highlights that new superficial soft-tissue masses in patients with multiple myeloma, even in uncommon locations such as the back, should prompt consideration of extramedullary plasmacytoma and early image-guided biopsy to establish the diagnosis. Table 2. Selected Published Cases of Soft-Tissue Extramedullary Plasmacytoma in Multiple Myeloma and Comparison With the Present Case Study Patient Soft-tissue site Imaging Histopathology Distinguishing feature Ruiz Santiago et al. (2010) 20 52-year-old man Subcutaneous fascia of the calf MRI EMP confirmed by biopsy Demonstrated that superficial soft-tissue EMP can mimic other soft-tissue tumors; emphasized biopsy for diagnosis. Ames et al. (2017) 21 51-year-old man with MM Bilateral thigh musculature Ultrasound, MRI, PET/CT EMP confirmed by biopsy Included a literature review showing extremity soft-tissue lesions are exceptionally uncommon among reported EMPs. Martí et al. (2021) 22 54-year-old man with MM Thoracic wall, abdominal wall, and extremities PET/CT MM with multiple soft-tissue plasmacytomas Highlighted the value of PET/CT in identifying disseminated soft-tissue disease. Gaube et al. (2021) 23 79-year-old woman with MM Right arm soft tissue CT/MRI and pathology EMP confirmed by biopsy Demonstrated successful radiotherapy for isolated soft-tissue EMP. Present case 59-year-old man with MM Superficial left upper and lower back (subcutaneous tissues) Ultrasound with Doppler Lambda-restricted EMP confirmed by core biopsy Rare superficial back involvement with detailed ultrasound and Doppler findings correlated with histopathology, highlighting ultrasound as a useful first-line tool for evaluating superficial masses.
Table 2.
Selected Published Cases of Soft-Tissue Extramedullary Plasmacytoma in Multiple Myeloma and Comparison With the Present Case
| Study | Patient | Soft-tissue site | Imaging | Histopathology | Distinguishing feature |
| Ruiz Santiago et al. (2010) 20 | 52-year-old man | Subcutaneous fascia of the calf | MRI | EMP confirmed by biopsy | Demonstrated that superficial soft-tissue EMP can mimic other soft-tissue tumors; emphasized biopsy for diagnosis. |
| Ames et al. (2017) 21 | 51-year-old man with MM | Bilateral thigh musculature | Ultrasound, MRI, PET/CT | EMP confirmed by biopsy | Included a literature review showing extremity soft-tissue lesions are exceptionally uncommon among reported EMPs. |
| Martí et al. (2021) 22 | 54-year-old man with MM | Thoracic wall, abdominal wall, and extremities | PET/CT | MM with multiple soft-tissue plasmacytomas | Highlighted the value of PET/CT in identifying disseminated soft-tissue disease. |
| Gaube et al. (2021) 23 | 79-year-old woman with MM | Right arm soft tissue | CT/MRI and pathology | EMP confirmed by biopsy | Demonstrated successful radiotherapy for isolated soft-tissue EMP. |
| Present case | 59-year-old man with MM | Superficial left upper and lower back (subcutaneous tissues) | Ultrasound with Doppler | Lambda-restricted EMP confirmed by core biopsy | Rare superficial back involvement with detailed ultrasound and Doppler findings correlated with histopathology, highlighting ultrasound as a useful first-line tool for evaluating superficial masses. |
A limitation of the present case is the lack of long-term clinical follow-up after the diagnosis of extramedullary plasmacytoma and initiation of teclistamab therapy. Consequently, the patient’s long-term response to treatment, disease progression, and overall outcome could not be assessed. Future clinical, laboratory, and imaging follow-up, particularly with whole-body imaging modalities such as PET/CT or MRI when clinically indicated, would provide valuable insight into treatment response, disease evolution, and the prognostic implications of extramedullary disease in patients with multiple myeloma.
An additional limitation of the present report is the absence of representative histopathological photomicrographs (H&E and immunohistochemical staining). Despite repeated attempts to retrieve the original pathology images from the pathology department, these images were not available for inclusion because they could not be recovered from the archival records. Their absence limits the completeness of the visual documentation supporting the diagnosis. Nevertheless, the diagnosis of extramedullary plasmacytoma was established on the basis of detailed histopathological examination and immunohistochemical findings demonstrating diffuse CD138 expression with lambda light-chain restriction and negative staining for kappa, CD3, and CD20, as described in the Case Presentation. In addition, the lack of long-term clinical follow-up after initiation of teclistamab therapy precluded assessment of long-term treatment response, disease progression, and overall outcome. Future follow-up incorporating whole-body imaging, when available, would provide further insight into disease evolution and therapeutic response.
Another limitation of this report is the absence of several baseline hematologic disease characteristics, including the ISS/R-ISS stage, bone marrow plasma cell percentage, cytogenetic/FISH profile, and the baseline M-protein isotype and quantification. These data were unavailable because complete records from the patient’s initial diagnostic evaluation were not accessible. Their absence limits comprehensive characterization of the underlying multiple myeloma and restricts clinicopathologic correlation with the subsequent development of extramedullary disease.
Conclusion
In conclusion, our case shows that superficial EMPs can be readily detected on ultrasound when they involve accessible soft-tissue sites. Recognizing their characteristic sonographic features and correlating with histopathology is essential for prompt diagnosis, particularly in patients with known MM.
Author Contributions: Jawad Hmayed: Conceptualization, data curation, investigation and writing original draft.
Doha Fadel : Imaging and writing original draft.
Anthony Bayeh: Conceptualization, imaging and writing original draft.
Chris Jreij: Data curation, investigation and writing original draft.
Karam Karam: Data curation, investigation and writing original draft.
Lamita El Sett: Imaging, investigation and writing original draft.
Charbel Fares: Conceptualization, Imaging, data curation, investigation and writing original draft.
Funding: The authors received no financial support for the research, authorship, and/or publication of this article.
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
ORCID iDs
Doha Fadel https://orcid.org/0009-0000-4917-5272
Karam Karam https://orcid.org/0009-0001-1914-320X
Ethical Considerations
This article is exempt from ethical approval in our institution.
Consent to Participate
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the case.
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