Severe Tertiary Hyperparathyroidism with Brown Tumor and Multisystem Complications Mimicking Plasma Cell Dyscrasia in a Middle-Aged Man with Childhood-Onset FSGS

Abstract

Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a well-recognized complication of end-stage kidney disease (ESKD), encompassing abnormalities in calcium, phosphorus, parathyroid hormone (PTH), vitamin D metabolism, and bone turnover. In advanced cases, secondary or tertiary hyperparathyroidism may lead to severe skeletal disease, including osteitis fibrosa cystica and brown tumors, which can mimic hematologic malignancies. We present the case of a 47-year-old man with childhood-onset focal segmental glomerulosclerosis (FSGS), two prior kidney transplants, and long-standing dialysis dependence who presented with bone pain, pancytopenia, neurologic symptoms, and imaging abnormalities initially concerning for multiple myeloma. Comprehensive evaluation revealed a single unifying diagnosis: severe tertiary hyperparathyroidism (parathyroid hormone 1,467 pg/mL) with advanced renal osteodystrophy and brown tumor-like skeletal changes, without evidence of plasma cell dyscrasia or marrow infiltration. This case highlights the diagnostic pitfalls posed by extreme manifestations of CKD-MBD and underscores the importance of prioritizing cohesive pathophysiologic reasoning in complex ESKD patients.

Introduction

Patients with end-stage kidney disease (ESKD) can develop a wide spectrum of metabolic, hematologic, skeletal, and cardiovascular complications ¹ that collectively mimic primary hematologic malignancies.^2-5 In advanced stages, chronic kidney disease-mineral and bone disorder (CKD-MBD) may result in severe skeletal manifestations driven by secondary or tertiary hyperparathyroidism, including osteitis fibrosa cystica and brown tumors.^6-8 Concurrently, ESKD may contribute to pancytopenia, ⁹ cardiovascular disease, and systemic inflammation, further complicating the clinical picture.

Guided by Occam’s razor, the principle that a single unifying diagnosis should be sought to explain disparate clinical findings, we present the case of a 47-year-old man with childhood-onset focal segmental glomerulosclerosis (FSGS), two prior kidney transplants, and long-standing dialysis dependence. He presented with bone pain, pancytopenia, a history of hypercalcemia, neurologic symptoms, and imaging abnormalities initially suggestive of multiple myeloma. However, extensive evaluation revealed a single unifying etiology: severe tertiary hyperparathyroidism (parathyroid hormone 1,467 pg/mL) with advanced renal osteodystrophy and brown tumor-like changes, without evidence of plasma cell dyscrasia or marrow infiltration. This case underscores the importance of recognizing extreme manifestations of CKD-MBD in patients with long-standing ESKD and avoiding misattribution of CKD-related pathology to malignant disease.

Case Presentation

A 47-year-old man with a history of focal segmental glomerulosclerosis diagnosed at age 8, complicated by progression to end-stage kidney disease (ESKD) and dialysis dependence since age 12, presented with worsening musculoskeletal and neurologic symptoms. His renal history was notable for two prior kidney transplants, both of which ultimately failed, and he was currently receiving chronic hemodialysis via an arteriovenous fistula. Additional comorbidities included tertiary hyperparathyroidism, hyperlipidemia, premature multivessel coronary artery disease, and chronic heart failure.

The patient reported several years of progressive diffuse bone pain and chronic abdominal pain, along with a history of hypercalcemia. He presented acutely with severe cervical and thoracic back pain radiating to both arms, associated with numbness, tingling, and weakness that were worse on the left. His pain improved with forward flexion. On physical examination, he had marked spinal deformity with levoscoliosis, bilateral positive Spurling maneuvers, decreased strength and sensation in both upper extremities (worse on the left), bibasilar lung crackles, and significant bilateral lower-extremity edema.

Three months prior to presentation, he underwent coronary angiography for exertional symptoms and was found to have approximately 80% stenosis in three coronary vessels, requiring percutaneous coronary intervention with placement of three stents. Transthoracic echocardiography demonstrated chronic heart failure with improved ejection fraction (HFimpEF), with a left ventricular ejection fraction of 55-60%.

Laboratory evaluation demonstrated pancytopenia with borderline macrocytic anemia (hemoglobin 10.7 g/dL, mean corpuscular volume 99.7 fL), thrombocytopenia (platelets approximately 100 × 10⁹/L), and mild neutropenia (absolute neutrophil count 1.3 × 10⁹/L). Reticulocyte count was low at 0.9%, consistent with hypoproliferative anemia. Biochemical evaluation revealed severe tertiary hyperparathyroidism (parathyroid hormone 1,467 pg/mL), elevated alkaline phosphatase (295 U/L), hyperphosphatemia (phosphorus 5.1 mg/dL), and hypocalcemia while on cinacalcet therapy (corrected calcium of approximately 7.3 mg/dL). The patient was receiving phosphate binder therapy with sevelamer. Brain natriuretic peptide was markedly elevated (115,000 pg/mL), consistent with chronic volume overload in the setting of ESKD and ischemic cardiomyopathy.

Computed tomography (CT) of the cervical (Figure 1) and thoracic (Figure 2) spine demonstrated diffuse osteodystrophic changes with heterogeneous hypodense lesions involving multiple vertebral bodies. In the thoracic spine, there was severe vertebral body deformity with loss of normal trabecular architecture diffusely and loss of height at one level, concerning for advanced renal osteodystrophy with possible pathologic compression fracture. These imaging findings raised initial concern for a plasma cell dyscrasia.

Figure 1.

Cervical spine CT (sagittal bone window). Diffuse osseous demineralization with heterogeneous hypodense lesions involving the C3 and C4 vertebral bodies and irregular endplates, without associated soft tissue mass, consistent with renal osteodystrophy in the setting of tertiary hyperparathyroidism

Figure 2.

Thoracic spine CT (sagittal bone window). Sagittal CT demonstrates diffuse osteopenia, coarse trabecular architecture, and severe multilevel vertebral body deformities with focal loss of vertebral height, suggestive of advanced renal osteodystrophy with possible pathologic compression fracture

Given the combination of pancytopenia, bone pain, and concerning imaging findings, multiple myeloma with possible light-chain amyloidosis affecting the heart and kidneys was initially considered.

Diagnostic Workup

Serum protein electrophoresis demonstrated normal total protein (6.5 g/dL) and albumin (3.6 g/dL) levels without an M-spike. Fractionated globulins (alpha-1 0.3 g/dL, alpha-2 0.6 g/dL, beta-1 0.3 g/dL, beta-2 0.3 g/dL, gamma 1.4 g/dL) were consistent with a polyclonal pattern. Serum immunofixation showed no monoclonal proteins. Serum free light chains were elevated (kappa 204 mg/L, lambda 173 mg/L) with a preserved kappa-to-lambda ratio (∼1.18), indicating polyclonal elevation rather than clonal plasma cell proliferation. Beta-2 microglobulin was markedly elevated at 25.2 mg/L, attributed to impaired renal clearance.

Nutritional evaluation revealed normal vitamin B12 (600 pg/mL) and folate (7.1 ng/mL) levels. Iron studies showed low serum iron (42 µg/dL), normal total iron-binding capacity (261 µg/dL), and low transferrin saturation (19%), consistent with anemia of chronic kidney disease.

Bone marrow biopsy was performed to evaluate the etiology of pancytopenia. Peripheral blood demonstrated pancytopenia with macrocytic anemia, severe thrombocytopenia, mild anisocytosis, and scattered immature myeloid cells without blasts. Bone marrow aspiration and clot sections revealed hypocellular marrow (20-30% cellularity) with trilineage hematopoiesis and appropriate maturation, no significant dysplasia, no monoclonal proliferation, markedly reduced small megakaryocytes, mildly reduced iron stores (1+/4+), and no significant myelofibrosis. There was no evidence of leukemia, lymphoma, metastatic disease, or plasma cell neoplasm.

These findings excluded multiple myeloma and other hematologic malignancies. The patient’s cytopenias were attributed to ESKD-associated marrow hypoplasia and chronic disease, while the skeletal abnormalities were attributed to severe tertiary hyperparathyroidism with renal osteodystrophy and brown tumor-like remodeling.

Discussion

This case illustrates how extreme manifestations of chronic kidney disease-mineral and bone disorder can closely mimic plasma cell dyscrasias. Brown tumors arise from excessive osteoclastic activity driven by markedly elevated parathyroid hormone levels and may appear as well-circumscribed hypodense or lytic-appearing lesions on imaging studies.^2,6,8,10 These lesions may persist or even progress despite renal transplantation, particularly in the setting of uncontrolled or tertiary hyperparathyroidism. ¹¹ When accompanied by bone pain and pancytopenia, these findings can strongly resemble multiple myeloma.^2-5

Pancytopenia in ESKD is multifactorial and may result from uremia-related marrow suppression, chronic inflammation, anemia of chronic disease, reduced erythropoietin production despite exogenous supplementation, and medication effects. ⁹ Although secondary or tertiary hyperparathyroidism can cause marrow fibrosis, ¹⁰ this patient’s biopsy demonstrated hypocellularity without significant fibrosis, underscoring that severe cytopenias may occur even in the absence of overt myelofibrosis.

From a diagnostic reasoning perspective, this case demonstrates the interplay between Hickam’s dictum, recognizing that patients may have multiple coexisting diseases, and Occam’s razor, which favors a single unifying diagnosis. While the patient’s imaging and laboratory abnormalities reasonably prompted concern for plasma cell dyscrasia, comprehensive evaluation supported a single explanatory process: long-standing ESKD with severe tertiary hyperparathyroidism and advanced renal osteodystrophy.

The patient’s premature multivessel coronary artery disease further illustrates the systemic consequences of childhood-onset kidney disease. Decades of nephrotic-range proteinuria with resultant dyslipidemia, chronic inflammation, and disturbances in mineral metabolism likely contributed to accelerated atherosclerosis ¹ and heart failure by mid-adulthood.

Conclusion

In patients with long-standing ESKD, severe tertiary hyperparathyroidism may produce profound skeletal, hematologic, and systemic manifestations that closely resemble plasma cell dyscrasias. This case emphasizes the importance of recognizing advanced CKD-MBD as a unifying diagnosis and underscores the need for careful contextual interpretation of multisystem findings in patients with long-standing ESKD.