Bone marrow involvement in follicular lymphoma: Comparison of histology and flow cytometry as staging procedures

Abstract

Bone marrow (BM) examination is a routine staging procedure in follicular lymphoma (FL). Commonly, both BM histology as well as flow cytometry (FCM) of BM aspirates are performed. In order to compare the diagnostic value of these two techniques, we retrospectively evaluated trephine BM biopsies and listmode data of patients with a confirmed diagnosis of FL, obtained in parallel during a 5-year period. One hundred and thirty nine specimens from 91 patients with FL were eligible for analysis. After joint review, nine cases (6.5%) were reclassified, either in histology (six cases) or FCM (three cases). Seventy nine specimens (57%) showed no infiltration with both methods. Sixty specimens (43%) were scored positive for BM involvement by any of the two techniques. Concordant positive results were obtained in 41 cases (68% of positive BM). False negative results were obtained by FCM in 14 cases (23% of positive BM) and by histology in five cases (8%). Discrepant results between BM histology and FCM are frequent in patients with FL, most likely due to the predominantly paratrabecular infiltration and fibrosis typical for FL. Due to the lower false negative rate, trephine BM biopsy remains crucial for the detection of BM involvement in FL.

Assessment of bone marrow involvement in non‐Hodgkin’s lymphomas: comparison between histology and flow cytometry

“…Considering specific NHL subtypes, in our study FL is the histologic subtype with most discordant cases, largely represented by BMB+/FC− cases. These findings are in a good agreement with previous study (Table 5), and particularly with two recent reports focused specifically on BM involvement in FL (22, 23). Altogether, the data confirm that in FL, histology has a higher sensitivity than FC in detecting BM involvement; this is probably because of the common paratrabecular pattern in FL in which neoplastic cells are frequently tightly bound to bone trabeculae, and to the accompanying reticulin fibrosis.…”

“…A support of this hypothesis is the consideration that the quantitative assessment of infiltrate detected by the two techniques in FL cases showed a striking difference, with a significantly lower extent of infiltration evidenced by FC with respect to morphology, as also reported by Schmidt et al. (23), whereas in other subtypes (SLL, MCL, NMZL and SMZL), we found a quite complete overlap. Another significant finding, despite the relatively low number of cases, was the high rate of discordant results detected in LPL.…”

Diagnosis and Classification of Malignant Lymphoma and Related Entities in the Bone Marrow Trephine Biopsy

“…True neoplastic follicles are rare, occurring in less than 5% of cases, and can be distinguished from reactive lymphoid follicles by their bcl-2 positivity [36] . Due to the characteristic distribution of the neoplastic infiltrates, immunohistochemistry is of minor importance in cases with an established diagnosis of FL, but occasionally can detect small linear accumulations of neoplastic B cells lining the bony trabecules [10,37] . The neoplastic infiltrates in FL usually contain a high number of reactive T cells, which should not distract from a diagnosis if the typical morphological features are present.…”

“…Furthermore, assessment of marrow involvement by histology is not impeded by fibrosis, which is a frequent finding in lymphomatous infiltrates and may lead to false-negative results in BM aspirates due to sampling error [8][9][10] . For these reasons, the performance of a unilateral (or bilateral) BM trephine of adequate size with a minimal length of 2 cm, preferably examined by step sectioning, is regarded mandatory in patients with malignant lymphoma both for the initial determination of BM involvement and response evaluation [11,12] .…”

Consideration of exposure to pharmacological agents helps to avoid diagnostic pitfalls in bone marrow histopathology

“…Such biopsies should have at least a length of 1 cm containing minimally 10 representative bone marrow spaces and must be obtained from a bone area that has not been aspirated to avoid aspiration artifacts; usually the trephine needle should be drilled deeper into the iliac crest after aspiration. For lymphoma staging, biopsies of at least 2 cm or performance of bilateral biopsies has been recommended, since the trephine length clearly correlates with detectability of involvement [5][6][7]. One important detail to address is adequate fi xation and decalcifi cation [1,2,4]; these guarantee a good working immunohistological and molecular work-up [3,8], which is mandatory for specifi c questions like exact blast counting in MDS, proof of light chain restriction in plasma cell neoplasms or immunophenotyping and translocation analysis in lymphoma diagnostics.…”