LYMPHOID FOLLICLES AND LYMPHOID HYPERPLASIA VS. LYMPHOMA
Lymphoid follicles may be observed, usually in adult subjects, especially after the age of fifty. The
follicles are usually well circumbscribed round or ovoid, nonparatrabecular structures. A germinal center
(GC) may be identified in a proportion of the cases. The germinal center may be highlighted by staining
dendritic reticulum cells with CD21 and CD23. On immunohistology, the follicles consist of a heterogeneous
population of CD20 positive B-cells and CD3 positive T-cells.
B-cell hyperplasia
Usually T cells outnumber B cells in normal and reactive marrows. In bone marrows in which follicular
hyperplasia with prominent GCs is detected, the number of CD20 positive cells may be higher. Marked degrees
of follicular hyperplasia can be seen in patients with chronic autoimmune conditions (e.g. lupus, rheumatoid
arthritis), myelodysplastic syndromes, aplastic anemia, chronic myeloproliferative disorders, toxic
myelopathy, and viral infections.
The differentiation of benign lymphoid infiltrates from nodular infiltrates of B-cell lymphoma is, however,
particularly difficult in bone marrow biopsy specimens taken from patients with a known diagnosis of
malignant lymphoma. Reactive lymphoid hyperplasia must be distinguished from marrow involvement by low
grade malignant lymphomas, principally follicular, small or mixed cell type, small lymphocytic, mantle cell,
and marginal zone types. In these cases a complete B-cell panel which includes CD20, CD5, CD23, CD43, and
CD10 can be particularly useful. In addition, BCL-2 stain can be useful in distinguishing GC hyperplasia
from follicular lymphoma small or mixed cell type involving the bone marrow. However, the effective value
of this approach is still controversial (Fakan et al, 1996). Cyclin D1 is useful to confirm or exclude
mantle cell lymphoma, a malignant lymphoma subtype in which the architectural and cytologic findings in
involved marrows can closely mimic other low grade subtypes.
In difficult cases, the determination of clonality by polymerase chain reaction (PCR) analysis of the
immunoglobulin heavy chain genes could be of help for the distinction of benign and malignant lymphoid
infiltrates. A recent study has shown that microdissection of small nodular lymphoid infiltrates from
paraffin-bone marrow sections increases the sensitivity of IgH gene rearrangement analysis. To avoid
detection of biologically irrelevant clonal populations, comparison of PCR products obtained from the bone
marrow and the primary lymphoma biopsy is advisable. Although this genetic approach seems of considerable
interest, in our experience, the poor quality of the DNA extracted from nitric acid decalcified bioptic
material prevents in most cases a successful PCR amplification.
Polymorphic hyperplasia
Reactive polymorphic lymphohistiocytic aggregates containing numerous plasma cells can be frequently seen in
marrow biopsies from patients with HIV infection. Occasionally these aggregates may mick peripheral T cell
lymphoma or Hodgkin's disease marrow involvement. In these cases immunohistology can be helpful by
demonstrating the presence of CD8 positive T-lymphocytes which usually represent the predominant lymphoid
component and relatively rare CD20 positive immunoblasts in these aggregates. EBER or LMP-1 expression can
be used to detect the presence of EBV, which can be associated with these lesions. Kappa and lambda
immunostains can be used to confirm polyclonality in the plasma cells.
T-cell hyperplasia
Characteristically seen in marrow from patient with systemic viral infection. In most of these cases, the
predominant T cell subset is represented by CD8 positive cytotoxic T cells. T cell hyperplasia may be
associated with diffuse hemophagocytosis and macrophage hyperplasia which can be confirmed by staining the
macrophages with CD68. A peculiar case of atypical T cell hyperplasia simulating peripheral T cell lymphoma
can be seen after dilantin treatment.
References
- Farhi DC: Germinal centers in the bone marrow. Hematol Pathol 1989; 3:133-6
- Kremer M, Cabras AD, Fend F, Schulz S, Schwarz K, Hoefler H, Werner M: PCR analysis of IgH-gene
rearrangements in small lymphoid infiltrates microdissected from sections of paraffin-embedded bone marrow
biopsy specimens.Hum Pathol. 2000; 31:847-53.
- Leers MP, Theunissen PH, Ramaekers FC, Schutte B, Nap M: Clonality assessment of lymphoproliferative
disorders by multiparameter flow cytometry of paraffin-embedded tissue: an additional diagnostic tool in
surgical pathology. Hum Pathol 2000; 31:422-7
- Singer et al: Bone marrow involvement in phenytoin induced 'pseudolymphoma'. Clin Oncol (R Coll
Radiol). 1993; 5:397-8.
- Thiele J, Zirbes TK, Kvasnicka HM, Fischer R: Focal lymphoid aggregates (nodules) in bone marrow
biopsies:differentiation between benign hyperplasia and malignant lymphoma-a practical guideline. J Clin
Pathol 1999;52:294-300
- Wasman J, Rosenthal NS, Farhi DC: Mantle cell lymphoma. Morphologic findings in bone marrow
involvement. Am J Clin Pathol 1996;106:196-200
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