Introduction
Plasma cell neoplasm is a systemic malignancy characterized by the uncontrolled proliferation of monoclonal plasma cells in the bone marrow, resulting in the production of nonfunctional immunoglobulins or immunoglobulin light chains, known as M-protein. Diagnosing this condition is challenging due to nonspecific symptoms, such as bone pain, fatigue, and aches at multiple sites [ 1 ]. Typically diagnosed in individuals aged 65–75 years with a male predominance [ 2 ], plasma cell neoplasms may be overlooked in younger female patients, where symptoms might be mistaken for aging or other conditions. Indications for testing include incidental findings of elevated total protein, unexplained anemia or cytopenias, hypercalcemia, renal impairment, lytic bone lesions, or unexplained osteopenia in patients with bone pain or fractures [ 3 ].
Breast cancer, the most common cancer among women globally, has seen reduced mortality rates due to advances in screening and treatment. However, its association with secondary malignancies, such as plasma cell neoplasms, is rare [ 4 ]. We present a case of a 44-year-old woman with invasive ductal carcinoma of the right breast, treated with chemotherapy, modified radical mastectomy, and radiotherapy. One-year post-treatment, she developed back pain, anemia, acute kidney injury, and bone lesions, initially suggestive of metastatic tumor deposits. Further evaluation revealed a plasma cell neoplasm, highlighting the diagnostic challenges of distinguishing between metastatic disease and primary bone disorders.
Case Report
A 44-year-old woman presented with a right breast nodule and was evaluated at our hospital. Examination revealed a retroareolar nodule with a peau d’orange appearance and enlarged right axillary lymph nodes. Biopsy confirmed grade 3 invasive ductal carcinoma, with immunohistochemistry indicating ER-negative, PR-low positive, and HER2/neu-positive status. A bone scan showed no lytic or metastatic lesions. The final diagnosis was carcinoma of the right breast, staged as cT4bN2M0. The patient received neoadjuvant chemotherapy with four cycles of Adriamycin and Cyclophosphamide, followed by four cycles of Paclitaxel. She then underwent right modified radical mastectomy and adjuvant radiotherapy over five weeks, followed by hormonal therapy with Tamoxifen.
One year later, the patient presented with lower back pain, vomiting, and constipation, managed with supportive care. Routine investigations revealed severe normocytic normochromic anemia, treated with blood transfusion and hematinics. One month later, she was readmitted for persistent anemia. Abdominal ultrasound showed bilateral bulky kidneys with increased cortical echogenicity, prompting kidney function, liver function, and electrolyte tests. These revealed acute kidney injury and hypokalemia. High-resolution CT of the chest and MRI of the lumbar spine identified multiple lytic lesions in the axial and appendicular skeleton, initially suggestive of metastatic bone disease.
Given the elevated total protein, globulins, and altered albumin-to-globulin ratio, serum protein electrophoresis (SPE) was performed using the Sebia Minicap system. The electrophoretogram ( Figure 1 ) revealed a distinct M band in the gamma region and reduced albumin levels.
This finding prompted further evaluation for plasma cell neoplasm, including serum free light chain estimation, bone marrow aspiration and biopsy, and serum calcium measurement. Results are shown in Table 2 .
Bone Marrow Biopsy was showing increased plasma cells clusters focal admixed with myeloid cells in the available intertrabecular spaces. Bone marrow aspiration was showing particulate and hypercellular marrow with reduced trilineage hematopoiesis and replaced by sheets of plasma cells. Imprint smears were showing variable cellularity with myeloid cells and increased plasma cells.
The patient was diagnosed with IgG kappa-type multiple myeloma. Palliative radiotherapy to the pelvis provided moderate symptom relief, followed by chemotherapy with the Lenalidomide, Bortezomib, and Dexamethasone (RVD) regimen.
Discussion
Bone lesions in breast cancer patients are commonly attributed to skeletal metastases, which may present with intractable bone pain, hypercalcemia, pathological fractures, nerve compression, spinal cord compression, or bone marrow suppression [ 5 ]. In this case, the patient’s back pain and bone lesions were initially suggestive of metastatic disease. However, the presence of acute kidney injury, elevated serum total protein, and globulins was atypical.
Elevated globulins are associated with acute infections, chronic inflammatory conditions, and plasma cell neoplasms [ 6 ]. As the patient had no signs of infection, SPE was performed, revealing a distinct M band (5.6 g/dL), suggestive of a plasma cell neoplasm. Further tests confirmed an altered kappa:lambda ratio (>100 mg/L kappa chains) and bone marrow with 80% plasma cells, confirming the diagnosis.
Studies, such as Mitchell et al., have reported a 4% increased detection rate of monoclonal gammopathies in patients with elevated globulins, with gamma globulins >4 g/dL associated with a 76% incidence of monoclonal gammopathies [ 7 ]. The hallmark features of multiple myeloma, encapsulated by the CRAB acronym (hypercalcemia, renal impairment, anemia, and bone lesions), were all present in this patient. Anemia occurs in ~70% of newly diagnosed myeloma cases, renal impairment in 20–40%, and lytic bone lesions in up to 80% [ 8 ].
Distinguishing between metastatic disease and plasma cell neoplasms is critical, as symptoms like hypercalcemia and anemia overlap. The elevated globulins, altered albumin-to-globulin ratio, and M band on SPE were pivotal in identifying plasma cell neoplasm in this case. Literature reports rare coexistence of breast cancer and plasma cell neoplasms, with Levi et al. noting five cases of multiple myeloma among 443 second neoplasms in breast cancer patients [ 9 ]. A French study reported a slightly increased incidence of multiple myeloma (SIRR, 1.5; 95% CI, 1.3–1.7) among breast cancer survivors, though leukaemia and myelodysplastic syndrome were more common [ 10 ]. Clayer and Duncan identified multiple myeloma in two of four breast cancer patients with new bone lesions [ 11 ]. A case report by Timon et al had a similar finding of development of multiple myeloma in a treated breast cancer patient suggesting that clinicians should consider multiple myeloma as a cause of lytic bone lesions without extra skeletal metastases [ 12 ].
Although haematological malignancies like leukaemia and lymphoma are more frequently reported in breast cancer survivors, plasma cell neoplasms mimicking bone metastases are rare [ 13 , 14 ]. The etiology of this association remains unclear, but treatment-related factors, such as chemotherapy, or genetic predispositions may contribute. Further research is needed to explore these mechanisms and the role of cumulative therapies in secondary malignancies.
Conclusion
Bone lesions in breast cancer patients are typically attributed to skeletal metastases. However, rare primary bone disorders, such as multiple myeloma, should be considered, particularly when accompanied by elevated total protein, globulins, and myeloma-defining events like CRAB symptoms. This case highlights the importance of a high index of suspicion and targeted investigations, such as serum protein electrophoresis, to differentiate plasma cell neoplasms from metastatic disease in breast cancer patients with bone lesions.
Declaration of Conflict of Interest
The authors declare no conflicts of interest that could influence the research or its findings. No financial or personal relationships with individuals or organizations that could bias this work exist.
Ethical Approval
This case report complies with the ethical principles for medical research involving human subjects as outlined in the Declaration of Helsinki. The patient provided informed consent for the use of her de-identified medical data for research and publication purposes.
Credit Author Statement
The corresponding author confirms that all listed authors have reviewed and agreed upon the descriptions of their contributions. The roles of the authors are as follows: Author 1 (Corresponding Author): Conceptualization, data collection, patient management, manuscript drafting, and final approval.
Author 2: Data analysis, laboratory investigations, and critical revision of the manuscript.
Author 3: Treatment planning, clinical follow-up, interpretation of diagnostic tests, and manuscript review.
Authors contributed to multiple roles as needed to ensure the accuracy and integrity of the case report.
Data Availability Statement
The data supporting the findings of this case report are included within the article, specifically in Tables 1 and 2 and Figure 1 . Additional de-identified patient data are available from the corresponding author upon reasonable request, subject to ethical and institutional approval.
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