Precursor T cell Lymphoblastic Leukemia/Lymphoma
Most cases of lymphoblastic lymphoma are of T-cell type and show a characteristic ALL-T cell like
immunophenotype (see section on ALL) which can be easily documented in marrow sections. Rare cases of
lymphoblastic lymphoma show a precursor B-cell phenotype. These cases also show a characteristic
immunophenotype (i.e. positivity with TdT, see previous section on ALL) and can be easily separated from BL
and Burkitt-like cases.
Peripheral T-cell and NK-cell Neoplasms
Although less common than with B-cell lymphomas, involvement of the bone marrow is also seen in cases of
PTCL. The pattern of involvement may be either diffuse or focal; paratrabecular localization is only rarely
seen. In areas of bone marrow involvement, a prominent vascularity and reticulin fibrosis is often
observed. Immunohistochemistry can be used to identify atypical T-cell often present within polymorphic
cell infiltrates rich in reactive cells. The latter may include eosinophils, plasma cells, neutrophils,
endothelial cells, and epithelioid histiocytes, which are often arranged in clusters. These may impart a
granulomatous appearance which can be better shown by staining the marrow sections with CD68 antibodies. In
some case of PTCL, the presence of a prominent component of reactive erythrophagocytic or hemophagocytic
histiocytes can resemble "malignant histiocytosis" involving the bone marrow.
The neoplastic cells in PTCL usually express CD3, CD5, and CD43. CD7 is not uncommonly lost. CD4 is
positive in most cases. CD8 expression is less common in PTCL (exceptions the intestinal T-cell lymphoma
associated with enteropathy, and a subset of large granular lymphocytic leukemia) and is more often seen in
marrow showing reactive T-lymphocytosis as seen in patients with viral infections (e.g. EBV) or in cases of
infection associated hemophagocytic syndrome. A cytotoxic phenotype which is seen in certain subsets of
PTCL (e.g. nasal-type NK/T-cell lymphoma) can also be documented by TIA-1, perforin, and CD56
In addition to the positivity of the malignant cells with CD30, ALK-1 is currently used to identify marrow
involvement due to anaplastic large cell lymphoma T cell type (ALCL-T). However, in our experience, ALK
staining can be negative in otherwise typical ALCL cases.
Bone marrow involvement by PTCL can occasionally be very subtle and difficult to recognize.
Immunohistochemistry may be required for a positive identification of the malignant cells. Such
inconspicuous involvement is frequently seen with anaplastic large cell lymphoma (ALCL). However, the
strong CD30 positivity and the presence of reactivity with ALK-1 antibody allows for a positive
identification of the lymphoma cells in these cases.
The paraffin reactive CD56 antibody can be used in marrow sections to demonstrate T-cell large granular
lymphocytic leukemia, aggressive NK leukemia, and the rare marrow involvement by nasal and nasal-type NK/T
Immunohistochemistry is also particularly useful in diagnosing marrow involvement in cases of hepatosplenic
(gamma/delta) T-cell lymphoma (HSTCL). In these case, a characteristic intravascular involvement of the
bone marrow sinusoids by the lymphoma cells is observed. However, in other cases, the involvement can be
very subtle (Nosari et al, 1999). In most HSTCL cases the malignant cells show the typical immunophenotype
of gamma-delta T cells (CD2+, CD3+, CD4-, CD8-, CD7+, gamma-delta T-cell receptor-positive, and alpha-beta
T-cell receptor-negative) with clonal T-cell receptor gene. In addition, the cells contain a cytolytic
granule-associated protein, TIA-1, indicating a cytotoxic T-cell differentiation.
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