A Patient's Journey: Diagnosing Kidney Lesions and Widespread Bone Disease

Table of Contents

• Background: Why This Case Matters
• The Patient's Diagnostic Journey
• Detailed Imaging Findings
• Laboratory Test Results
• Differential Diagnosis: What Could It Be?
• Final Diagnosis and Explanation
• What This Means for Patients
• Limitations of the Diagnostic Process
• Key Takeaways for Patients
• Source Information

Background: Why This Case Matters

This detailed case study illustrates the challenges patients and doctors face when diagnosing complex inflammatory conditions that can mimic more common diseases. The patient's seven-year journey through multiple hospitals and specialists shows how rare disorders can be mistaken for more common conditions like cancer or autoimmune diseases.

For patients with unexplained symptoms involving multiple organ systems, this case highlights the importance of persistent investigation and the value of specialized medical centers. The eventual diagnosis of Erdheim-Chester disease (a rare histiocytic disorder) demonstrates how new medical knowledge continues to evolve, helping doctors recognize patterns in complex cases.

The Patient's Diagnostic Journey

A 45-year-old woman was referred to Massachusetts General Hospital's rheumatology clinic for evaluation of possible IgG4-related disease after presenting with retroperitoneal fibrosis (scar tissue in the area behind the abdominal cavity). Her medical journey began seven years earlier when she underwent a bone marrow biopsy for mild persistent polycythemia (increased red blood cells) and leukocytosis (elevated white blood cells).

Five years before the current evaluation (two years before presentation), she developed polycythemia and left flank pain. Testing revealed a faint IgG kappa monoclonal band on immunoelectrophoresis, though other blood levels were normal. Ultrasound showed a 24-mm complicated cyst in her left kidney's upper pole with mural thickening and internal echoes, plus an 18-mm parapelvic cyst in the middle left kidney.

Seventeen months before presentation, abdominal CT scan showed the enhancing 24-mm mass in her left kidney that appeared suspicious for renal cell carcinoma. She underwent laparoscopic partial nephrectomy, but surprisingly, no tumor was found—only mild glomerulosclerosis, interstitial fibrosis, and arteriosclerosis.

Follow-up imaging over subsequent months revealed new kidney lesions, including a 19-mm exophytic enhancing lesion in her right kidney's lower pole that resembled the previously removed left kidney mass. A CT-guided biopsy of this lesion obtained only retroperitoneal tissue, which showed atypical fibrous tissue with inflammation but no cancer cells.

Detailed Imaging Findings

The patient underwent extensive imaging studies that revealed the progressive nature of her condition:

• Initial kidney findings: 24-mm complex cyst in left kidney upper pole, 18-mm parapelvic cyst in left kidney middle portion, 4-mm nonobstructive kidney stone
• Follow-up findings: New 19-mm hypoechoic lesion in right kidney lower pole appearing exophytic and enhancing
• Bone involvement: Whole-body PET-CT showed FDG uptake in both humeri, left radius, and both acetabula
• MRI results: Multiple enhancing marrow-replacing lesions in left humerus, left ilium, and both acetabula
• Progression: Later MRI showed additional 3-cm lesions in distal femurs, proximal tibias, and proximal fibulas

Radiographs confirmed lytic bone lesions (areas of bone damage) in the greater tuberosity of her left shoulder that corresponded to the abnormalities seen on PET-CT and MRI. Despite these extensive findings, there was no evidence of cortical bone destruction or metastatic disease.

Laboratory Test Results

The patient's laboratory findings provided important clues throughout her diagnostic journey:

• Hemoglobin: 14.6 g/dL (7 months before presentation), 15.6 g/dL (current presentation), 14.3 g/dL (5 months after)
• White blood cell count: 8600/μL (7 months before), 8700/μL (current), 9950/μL (5 months after)
• IgG levels: 1693 mg/dL (7 months before), 1969 mg/dL (current), 1593 mg/dL (5 months after) - all elevated above normal range
• IgG4 levels: 267 mg/dL (7 months before), 296.5 mg/dL (current), 275.4 mg/dL (5 months after) - consistently elevated
• Inflammatory markers: C-reactive protein 6 mg/L (7 months before), 4.8 mg/L (current), 4.3 mg/L (5 months after) - all normal
• Erythrocyte sedimentation rate: 23 mm/hr (7 months before), 29 mm/hr (current), 30 mm/hr (5 months after) - mildly elevated

Other notable findings included polyclonal hypergammaglobulinemia (elevated antibodies of various types), normal complement levels, negative autoimmune antibodies, and elevated free light chains with normal kappa:lambda ratio (1.78-1.82, slightly above normal range of 0.26-1.65).

Differential Diagnosis: What Could It Be?

The medical team considered multiple possible explanations for the patient's condition, systematically ruling out various categories of disease:

Ruled out conditions:

• Liver disease (normal liver function tests)
• Iatrogenic causes (no immunoglobulin therapy)
• Immunodeficiency disorders (no history of frequent infections)
• Infections (negative HIV, hepatitis, tuberculosis tests)
• Non-hematologic cancer (no cancer found on four biopsies)

Less likely conditions:

• Autoimmune diseases like Sjögren's syndrome (no sicca symptoms or autoantibodies)
• Autoinflammatory bone disorders like SAPHO syndrome (no sternum/clavicle involvement)
• IgG4-related disease (atypical presentation with extensive bone involvement)
• Castleman's disease (normal CRP, bone lesions present)
• Lymphoma (no lymphadenopathy or cortical bone destruction)

The team noted that the normal C-reactive protein level despite polyclonal hypergammaglobulinemia was particularly unusual, as inflammatory processes typically elevate CRP. This suggested a different driving mechanism behind her condition.

Final Diagnosis and Explanation

The final diagnosis was Erdheim-Chester disease, a rare non-Langerhans cell histiocytosis. This condition involves the accumulation of specific immune cells (histiocytes) in various tissues throughout the body.

Key features supporting this diagnosis included:

• Symmetrical long bone involvement (humeri, femurs, tibias)
• Retroperitoneal fibrosis without typical organ involvement
• Polyclonal hypergammaglobulinemia with normal CRP
• Lack of response to rituximab (a B-cell depletion therapy)
• Histiocytic infiltrates on multiple biopsies
• Progressive course with new bone lesions developing over time

The diagnosis was confirmed through biopsy of a left tibial lesion, which showed polytypic light-chain expression (indicating non-cancerous plasma cells), more than 30 IgG4+ plasma cells per high-power field, and an IgG4:IgG ratio greater than 40%. These findings, while suggestive of IgG4-related disease, occurred in the context of more widespread histiocytic infiltration characteristic of Erdheim-Chester disease.

What This Means for Patients

This case has several important implications for patients with complex medical conditions:

First, it demonstrates that rare diseases can mimic more common conditions, requiring persistence in diagnosis. The patient initially presented with findings suggestive of renal cell carcinoma, then IgG4-related disease, before arriving at the correct diagnosis of Erdheim-Chester disease.

Second, it highlights the importance of seeking care at specialized centers when dealing with complex multi-system diseases. The coordinated approach between rheumatology, radiology, pathology, and other specialties was essential in making the correct diagnosis.

Third, the case shows that normal inflammatory markers (like CRP) don't always rule out significant disease processes. Some conditions operate through different biological pathways that don't trigger conventional inflammatory responses.

Finally, this case illustrates that treatment response (or lack thereof) can provide important diagnostic clues. The patient's failure to respond to rituximab helped rule out typical IgG4-related disease and pointed toward alternative diagnoses.

Limitations of the Diagnostic Process

This diagnostic journey had several limitations that patients should understand:

• Multiple biopsies required: The patient underwent four separate biopsies over seven years before achieving a definitive diagnosis
• Imaging limitations: Early imaging suggested renal cancer that wasn't confirmed by pathology
• Treatment trial limitations: The patient couldn't complete the rituximab course due to an infusion reaction, limiting what could be learned from treatment response
• Rarity of condition: Erdheim-Chester disease affects approximately 1 in 500,000 people, making experience with the condition limited
• Overlap with other conditions: The histological findings overlapped with IgG4-related disease, creating diagnostic confusion

These limitations highlight why complex diagnoses often require time, multiple procedures, and consultation with various specialists before reaching certainty.

Key Takeaways for Patients

For patients facing complex diagnostic journeys, this case offers several important lessons:

1. Persist in seeking answers: Complex conditions may require multiple evaluations over time
2. Seek specialized care: Academic medical centers often have experience with rare conditions
3. Understand test limitations: Imaging can suggest conditions that biopsies don't confirm
4. Track your symptoms: Detailed symptom records help doctors identify patterns
5. Learn about your family history: The patient's family history of renal cancer was potentially relevant
6. Ask about second opinions: Multiple perspectives can be valuable in complex cases
7. Understand treatment goals: Sometimes treatments are tried diagnostically to see how diseases respond

Most importantly, this case shows that medical diagnosis is often a process rather than a single event, especially for rare multi-system diseases that don't fit typical patterns.

Source Information

Original Article Title: Case 30-2024: A 45-Year-Old Woman with Kidney Lesions and Lytic Bone Disease

Authors: Luke Y.C. Chen, M.D., M.M.Ed., Ambrose J. Huang, M.D., John H. Stone, M.D., M.P.H., and Judith A. Ferry, M.D.

Publication: The New England Journal of Medicine, September 26, 2024

DOI: 10.1056/NEJMcpc2402486

This patient-friendly article is based on peer-reviewed research from the Case Records of the Massachusetts General Hospital series. The original article presents detailed clinical, radiological, and pathological findings from an actual patient case discussed by experts at Harvard Medical School.