Correlation of FDG-PET-CT with Bone Marrow Aspiration and Biopsy at the Initial Staging in Follicular Lymphoma: Can We Omit Bone Marrow Biopsy in Some?

Introduction: The role of FDG PET-CT in follicular lymphoma is limited to accurate assessment of disease extent in early stage patients and selection of biopsy site in cases of suspected high- grade transformation. Despite the known FDG avidity of follicular lymphoma, FDG PET-CT has not yet been included as part of standard staging procedures in these patients. FDG PET-CT has shown significant correlation with bone marrow biopsy in Hodgkin and diffuse large B-cell lymphomas. In this retrospective analysis we have assessed the correlation of PET-CT with that of bone marrow biopsy, the reference standard for assessment of bone marrow infiltration in follicular lymphoma.

Methods: We retrospectively analyzed electronic medical records and database of patients with newly diagnosed follicular lymphoma registered at Tata Memorial Centre from July 2009 to Jun 2014, who underwent complete staging workup as per the current recommendations along with whole body ¹⁸FDG-PET/CT. The demographic features, performance status, stage, LDH, nodal sites, haemoglobin, follicular lymphoma international prognostic index (FLIPI), FDG PET-CT findings (bone marrow involvement, pattern of involvement- focal or diffuse, sites of marrow involvement, liver and spleen uptake, SUVmax of most FDG avid lesion) and bone marrow aspiration/biopsy (morphology, immunohistochemistry and immunophenotyping on aspirate, where available) findings were recorded. Focal uptake in marrow on baseline PET-CT was considered as marrow involvement if post therapy PET-CT showed resolution of these lesions. The sensitivity, specificity, negative and positive predictive value of PET-CT in detecting bone marrow infiltration was assessed taking bone marrow biopsy as gold standard. The factors responsible for discordant results were analyzed.

Results: A total of 54 patients (males-38, females-16) were included in analysis with median age of 50 years, (range 22-73 years). At diagnosis 83% (45 patients) had stage III or IV disease and 57% patients had high-risk FLIPI score. Approximately 88% patients had good performance status (ECOG-<2). Bone marrow showed infiltration in approximately 60% (32 patients) on biopsy and immunophenotyping. PET-CT showed bone marrow involvement in 18 patients (focal-12, diffuse -6). In 4 patients with focal PET-CT positivity, bone marrow was uninvolved. However, post therapy these lesions showed resolution, thus confirming the presence of disease pretherapy. The sensitivity, specificity, positive and negative predictive value of PET/CT with respect to biopsy was 43.7%, 81.2%, 77.8% and 50% respectively. However, if we include the above mentioned 4 cases as true positives, then specificity and positive predictive value improves to 100% each. In addition, PET-CT could accurately predict absence of bone marrow involvement in stage I and stage II disease (100% concordance). The median SUVmax of most FDG avid lesion was 13.1 (5.25-34.93). However the SUVmax did not correlate with grade of lymphoma as the node biopsy was not done based on PET-CT results.

Conclusion: This study shows that in patients with advanced stage follicular lymphoma bone marrow biopsy can be omitted if PET-CT shows focal or diffuse bone marrow uptake. Similarly, patients with early stage disease with no bone marrow uptake on PET-CT can be spared from bone marrow biopsy.