Classical Hodgkin's Disease (a category which includes nodular sclerosis, mixed
cellularity, and lymphocyte-rich types)
Identifiable diagnostic Reed-Sternberg cells (RSC) found within the characteristic cellular environment of
HD, should be regarded as evidence of positive bone marrow involvement. Bone marrow involvement is found in
10% of the cases of untreated Hodgkin's disease (HD) (Bartl et al., 1982). However, the incidence raises in
parallel to the clinical stage. The criteria for the diagnosis of bone marrow involvement in a patient with
a previously established diagnosis of HD are less stringent than those required for the initial diagnosis of
HD (Rappaport et al, 1971). In this context, mononuclear Reed-Sternberg cells (abnormal cells with huge
nucleoli) in a cellular setting appropriate for the HD subtype are considered sufficient to establish the
diagnosis of bone marrow involvement. Marrow fibrosis is frequent and often prominent. Fibrosis should be
considered particularly suspicious in a patient with a diagnosis of HD. In cases in which only abnormal
mononuclear cells without huge nucleoli (nondiagnostic variants of RSC) or fibrosis are found in the marrow
biopsy, serial sections should be obtained. If abnormal mononuclear or diagnostic RSC are still not found,
immunohistochemistry should be used to confirm the diagnostic suspiciousness. The malignant cells in
classical Hodgkin's disease express CD30, CD15 (variably), and are usually negative with CD45, CD3, and
CD43. CD20 can be expressed in a proportion of Reed-Sternberg cells in 20 to 40% of the classic HD cases.
Other markers which can be used to highlight the presence of RSC include BLA.36 and fascin. The reactive
lymphocytes which are often very numerous in foci of HD involvement are predominantly CD4 positive T-cells.
It may be difficult to distinguish HD from anaplastic large cell lymphoma on occasion. In these cases, the
positivity of ALCL cells for CD45, CD3 (in the most common T-cell type), and ALK-1 allows its separation
from Hodgkin's disease. A word of caution. In cases in which the primary diagnosis of HD was not firmly
established do not rely on the presence of CD30 reactivity alone. CD30 can be expressed by a variable
proportion of B cell lymphomas (e.g. immunoblastic lymphoma, including transplant and AIDS related cases,
mediastinal sclerosing B cell), peripheral T cell lymphomas, and non-hematologic malignancies including germ
cell tumors, melanomas, and angiosarcomas.
Lymphocyte Predominance (LP) Hodgkin Disease
Bone marrow involvement is rare in this HD subtype (88% of patients present with clinical stage I or II
disease). In bone marrow sections, LP-HD can be distinguished from classical HD on the basis of the
reactivity for CD45 and CD20 of the diagnostic L&H (popcorn) cells. In most cases of nodular LP (LP
paragranuloma), the reactive lymphocytes are mostly B-cells. However, CD57 positive T-cells are also
detected. The latter are characteristically seen to surround the L&H cells, a phenomenon known as
"rosetting". Sheets of CD20 positive L&H cells are seen in rare cases of LP HD in transformation to large
B-cell lymphoma. The differential diagnosis includes TCRBCL in the bone marrow.
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