An 11 Years Delayed Diagnosis of Primary Pulmonary Diffuse Large B Cell Lymphoma

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An 11 Years Delayed Diagnosis of Primary Pulmonary Diffuse Large B Cell Lymphoma

Primary pulmonary diffuse large B-cell lymphoma (DLBCL), though rare, represents a significant diagnostic challenge due to its heterogeneous clinical presentation and imaging features. This case report details an unprecedented 11-year delay in diagnosing pulmonary DLBCL in a 72-year-old male patient, underscoring the importance of considering indolent lymphoma in persistent pulmonary consolidations despite atypical disease progression.

Clinical Presentation and Initial Course

In May 2007, the patient first presented with cough, expectoration, fever, and right lung abnormalities on computed tomography (CT), including patchy opacities and consolidations [Figure 1A]. Initial management with antibiotics resolved symptoms, but follow-up imaging revealed persistent abnormalities. The patient declined further invasive investigations, such as bronchoscopy, and opted for annual surveillance. Over the next 11 years, serial CT scans demonstrated stable imaging findings in the right lung, characterized by non-progressive opacities and consolidations [Figure 1B, 1C]. Despite the lack of clinical deterioration, these persistent radiographic changes hinted at an underlying chronic process.

Acute Exacerbation and Diagnostic Turning Point

Eleven years after initial presentation, the patient developed acute symptoms, including high fever, dyspnea, productive cough, and fatigue. Physical examination revealed lung dullness and moist rales, while laboratory tests showed neutrophilia. Sputum cultures identified Escherichia coli and Aspergillus species. Repeat CT demonstrated rapid progression of consolidations in the right lung [Figure 1D]. Empirical antibiotic and antifungal therapies failed to improve symptoms, prompting further investigation.

A positron emission tomography (PET)/CT scan revealed intense fludeoxyglucose (FDG) uptake in the right lung [Figure 1E], raising suspicion for malignancy. Transbronchoscopic lung biopsy of the right upper lobe confirmed the diagnosis of primary pulmonary DLBCL (non-germinal center subtype).

Pathological and Immunohistochemical Findings

Histopathological examination demonstrated lymphoid hematopoietic malignancy with diffuse infiltration of large atypical cells. Immunohistochemistry revealed a CD20(+), CD79a(+) B-cell lineage with high proliferative activity (Ki-67: 90%). Additional markers included Bcl-6(+), multiple myeloma oncogene 1 (MUM1)(+), and Bcl-2(+). Negative results for CD3, CD5, CD10, and Epstein-Barr virus-encoded RNA (EBER) excluded other lymphoma subtypes and viral associations [Figure 1G].

Treatment Response

The patient received two cycles of R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Subsequent CT imaging showed marked resolution of consolidations [Figure 1F], accompanied by symptomatic improvement. This rapid response highlighted the efficacy of immunochemotherapy in DLBCL, even after prolonged indolent progression.

Clinical Significance and Discussion

Primary Pulmonary DLBCL: Epidemiology and Diagnostic Challenges

Primary pulmonary lymphoma (PPL) constitutes 0.5%–1.0% of pulmonary malignancies, with DLBCL representing 5%–20% of PPL cases. DLBCL typically presents with aggressive clinical behavior, characterized by cough, dyspnea, and constitutional symptoms. Radiographic patterns vary widely, including nodular, interstitial, or consolidative lesions. Notably, mediastinal lymphadenopathy is uncommon, complicating differentiation from infectious or inflammatory lung diseases.

This case is exceptional due to the 11-year latency between initial radiographic abnormalities and definitive diagnosis. The patient’s stable imaging findings over a decade defied typical DLBCL progression patterns, which usually involve rapid deterioration. The absence of immunosuppression, immunodeficiency, or occupational risk factors further obscured the diagnosis.

Role of PET/CT and Biopsy in Indolent Lesions

PET/CT proved pivotal in redirecting the diagnostic approach. The FDG-avid right lung lesion prompted tissue sampling, which remains the gold standard for lymphoma diagnosis. The case reinforces the importance of considering malignancy in non-resolving consolidations unresponsive to antimicrobial therapy, particularly when supported by metabolic imaging.

Therapeutic Implications

Historically, DLBCL carries a variable prognosis, with 5-year survival rates ranging from 0% to 60%. The introduction of R-CHOP has substantially improved outcomes through synergistic targeting of CD20-positive B-cells (rituximab) and cytotoxic chemotherapy. This patient’s dramatic response aligns with studies demonstrating enhanced survival and reduced relapse rates with immunochemotherapy.

Lessons for Clinical Practice

  1. Persistent Radiographic Abnormalities: Pneumonia-like consolidations unresponsive to therapy warrant re-evaluation for malignancy, even after prolonged stability.
  2. Metabolic Imaging Guidance: PET/CT should be considered in atypical cases to identify biopsy targets.
  3. Histopathological Confirmation: Transbronchial biopsy remains critical for diagnosing indolent lymphomas masquerading as chronic infections.
  4. Timely Immunochemotherapy: Early initiation of R-CHOP may achieve significant remission, even in delayed diagnoses.

Conclusion

This case illustrates the diagnostic odyssey of a patient with primary pulmonary DLBCL, emphasizing the need for heightened clinical vigilance in non-resolving pulmonary lesions. The 11-year indolent phase followed by acute progression challenges conventional understanding of DLBCL biology, suggesting potential heterogeneity in disease behavior. Rapid response to R-CHOP underscores the importance of timely intervention once diagnosed. Clinicians must remain alert to the protean manifestations of pulmonary lymphomas to avoid diagnostic delays and optimize outcomes.

doi.org/10.1097/CM9.0000000000000378

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