The evaluation of bone marrow status is a key process in the initial workup of patients
diagnosed with lymphoma as it is the most common site of extranodal involvement in
lymphoid malignancies and plays an important role in staging and predicting prognosis
in patients with lymphomas. We studied 121 cases of non-Hodgkin lymphoma (NHL) and
Hodgkin lymphoma over a period of 3 years to gauge the incidence and pattern of marrow
involvement. The highest incidence of bone marrow involvement at our center was seen
in lymphoplasmacytic lymphoma followed by small lymphocytic lymphoma/chronic lymphocytic
leukemia (SLL/CLL), mantle cell lymphoma, and marginal zone lymphoma astounding the
fact that low grade lymphomas have a higher incidence of marrow involvement. The least
common incidence of marrow involvement was seen in diffuse large B cell lymphomas
(DLBCLs).
An interesting observation during the reevaluation of these cases was presence of
benign lymphoid aggregates (BLA) in bone marrow biopsy (BMB) specimens, which when
present, their distinction from NHL, particularly B cell lymphomas, can represent
a diagnostic challenge.
We encountered five cases with BLA including one SLL/CLL, one follicular lymphoma,
and three cases of DLBCL. Awareness about their morphological and immunohistochemical
characteristics is extremely important to avoid overstaging and overtreatment in lymphoma
cases. However, BLA have not been studied or described extensively in literature and
hence it is a potential pitfall.
BLA in bone marrow have been reported to be frequently associated with certain conditions
including aging, autoimmune diseases, inflammatory conditions, and infectious disorders.[1] They have also been reported to be commonly identified in patients with myeloproliferative
neoplasms, especially primary myelofibrosis. Moreover, an increased incidence of BLA
in patients with lymphoma who have been treated with rituximab has been reported.
These aggregates are often found in postchemotherapy bone marrow specimens and can
mimic residual lymphoma.[1]
BLA require diligent distinction from lymphoma involvement in bone marrow biopsies.
Criteria have been suggested in a limited number of studies to aid in this distinction.
Morphological and immunohistochemical differences between BLA and malignant lymphoid
aggregates in bone marrow biopsies are presented in [Table 1].[2]
[3]
Table 1
Morphological and immunohistochemical differences between benign and malignant lymphoid
aggregates in bone marrow biopsies
|
S. No.
|
Morphological characteristics
|
Benign lymphoid aggregates in BMB
|
Malignant lymphoid aggregates in BMB
|
|
Abbreviations: BMB, bone marrow biopsy; IHC, immunohistochemistry.
|
|
1.
|
Location
|
Interstitial, nonparatrabecular
|
Usually paratrabecular
|
|
2.
|
Size
|
Small size (< 600 µm)
|
Larger aggregates
|
|
3.
|
Borders
|
Distinct borders
|
Infiltrative edges
|
|
4.
|
Cytological atypia
|
No
|
Yes
|
|
5.
|
B and T cell number and pattern (on IHC)
|
Predominance of T cells or a mixture of B and T cells or a core of T cells surrounded
by B cells
|
Predominance of B cells or a core of B cells surrounded by T cells (except for germinal
center formation)
|
According to Johnston et al,[1] the identification of more than two of the listed five characteristics is strongly
suggestive of malignancy and was statistically associated with malignant diagnoses
in their study. Moreover, the loss of benign aggregates in deeper sections is considered
a prominent indicator of a benign process.[4]
To conclude, BMB is required for staging and evaluation of lymphomas and is performed
even when the likelihood of involvement is low, as it may portend an inferior clinical
outcome and impact therapy selection. The presence of BLA should therefore be considered
whenever examining the bone marrow biopsies. A good knowledge of morphology and immunohistochemistry
along with the clinical details, flow cytometry findings, and peripheral blood picture
are of utmost importance to guide the pathologist in this regard.
