Pulmonary Aspergillosis in a Patient with Hodgkin’s Lymphoma: ¹⁸F FDG PET-CT In Diagnosis and Assessment of Treatment Response

A 30-year-old lady with stage IV Hodgkin’s lymphoma, initially presenting with multiple pulmonary nodules, received adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) and ifosfamide, carboplatin and etoposide (ICE) chemotherapy regimens followed by stem cell transplantation. While on Nivolumab, an immune checkpoint inhibitor, she developed recurrent episodes of fever lasting one week. In Fig 1, Maximum intensity projection (A), axial CT (B) and fused reassessment ¹⁸F FDG PET CT (C) images showed metabolically active irregular peripherally enhancing lesions (indicated by solid arrow in B) with feeding vessels, air bronchogram and peripheral ground glass halo in both lungs, giving a ‘floret’ appearance; a few prominent metabolically active mediastinal lymph nodes were also seen. There was no evidence of other lymph nodal or extranodal disease. With the atypical F-18 FDG PET CT scan findings of ‘florets’ in the bilateral lung fields, pulmonary infection, likely fungal in aetiology, was suggested, with no evidence of lymphoma relapse. To our knowledge, this unusual ‘floret’-like appearance in the lungs is sparsely documented in the literature but may be considered a potential imaging correlate of fungal infection. Pioltelli et al. have reported the association between stem cell transplantation and invasive fungal infections in patients with lymphoproliferative disorders.^[1] Pulmonary aspergillosis has been noted in patients on nivolumab for non-small cell lung carcinoma.^[2-4]

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Fig 1: (A) Maximum intensity projection image of the ¹⁸F FDG PETCT study; (B and C) fused and axial CT images showed metabolically active irregular peripherally enhancing lesions (indicated by solid red arrow in B) with feeding vessels, air bronchogram and peripheral ground glass halo in both lungs; a few promininet metabolically active mediastinal lymph nodes were also seen. There was no evidence of other lymph nodal or extranodal disease. FDG: Fluorodeoxyglucose; PET/CT: Positron emission tomography/computed tomography

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In this patient, broncho-alveolar lavage (BAL) was performed; however, examinations for acid-fast bacilli and fungi yielded negative results. Quantification of galactomannan from broncho-alveolar lavage revealed an index of 0.67(Normal range: < 0.5 ODI-Optical density index). The results were indeterminate and >1.0 for invasive aspergillosis in BAL (0.5-0.9 ODI indeterminate range ODI is positive, suggesting invasive aspergillosis). ODI and BAL indices have shown good correlation between the test and diagnosis of invasive fungal infections.^[5]

The patient was treated with empirical anti-fungal therapy (voriconazole), based on ¹⁸F FDG PET CT findings, after a tumour board discussion, for a duration of six months, which is known to be an appropriate choice^[6] post which maximum intensity projection (A), axial CT (B) and fused reassessment ¹⁸F FDG PET-CT (C) images show resolution of previously seen irregular peripherally enhancing lesions in both lungs. No significant lymphadenopathy was noted on this study. ¹⁸F FDG PET-CT aids in the diagnosis and response assessment of patients with suspected fungal infections [Fig 2].^[7-9] Molecular diagnostics for invasive fungal infections include PCR (sensitivity of 90% and specificity of 95%) and metagenomic Next-Generation Sequencing (NGS) with variable sensitivity and specificity of 48.6% and 99.1%.^[10] Imaging is non-invasive and is increasingly employed to provide early, indirect evidence of fungal infection— especially when definitive diagnostic methods are delayed or inconclusive. The atypical ‘floret’ pattern observed in the lungs on ¹⁸F FDG PET-CT contributed not only to the diagnosis of a likely fungal infection but also helped rule out other sites of lymphomatous involvement. Additionally, it served as a useful tool for assessing response to antifungal therapy. The patient remains under follow-up and is currently doing well, with no evidence of lymphoma relapse or active fungal infection.

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Fig 2: (A) Maximum intensity projection; (B) Axial CT and (C) fused ¹⁸F-FDG PET CT images show resolution of previously seen irregular peripherally enhancing ground glass lesions in both lungs. No significant lymph nodal or extranodal disease was noted, representing disease remission. FDG: Fluorodeoxyglucose; PET/CT: Positron emission tomography

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