Hodgkin lymphoma (HL) is a B-cell neoplasm characterized by neoplastic cells—Reed-Sternberg cells and their variants—in a prominent inflammatory and fibrous background (1, 2, 3, 4, 5).

Different morphologic subtypes of HL are recognized by the World Health Organization (WHO) (Table 24.1; see Appendix A for WHO 2008 classification). Bone marrow involvement by HL occurs most often in mixed cellularity disease and least often in nodular lymphocyte predominant disease (6, 7, 8, 9, 10, 11, 12, 13, 14).

HL occurs de novo and as a transformation of posttransplantation lymphoproliferative disorder and other B-cell neoplasms, especially B-cell chronic lymphocytic leukemia’small lymphocytic lymphoma (15, 16, 17).

Clinically, bone marrow involvement by HL is associated with systemic symptoms, advanced clinical stage prior to bone marrow sampling, infradiaphragmatic involvement, mixed cellularity disease, anemia, leukocytes less than 6 × 10⁹‘L, age 35 years or more, and iliac and’or inguinal involvement (18, 19, 20, 21, 22, 23, 24).

As it has become easier to predict bone marrow involvement, the indications for marrow biopsy have decreased. Bone marrow sampling is no longer routinely performed for HL. A unilateral core biopsy is probably adequate in most cases requiring bone marrow sampling, although bilateral sampling may have a role in patients with a high risk of bone marrow disease. Marrow biopsies are greatly superior to aspirates in yielding a diagnosis of HL.

HL rarely presents initially or exclusively in the bone or bone marrow. This presentation occurs human immunodeficiency virus (HIV) most often in patients infected by HIV and only occasionally in non-HIV-infected patients (25, 26, 27). (see below).

The peripheral blood often shows anemia and eosinophilia (28, 29, 30, 31, 32, 33). Other reported findings include immune-mediated and cyclic cytopenias, thalassemia-like microcytic anemia, and large granular lymphocytosis.

Bone marrow aspirate smears may show granulocytic hyperplasia, eosinophilia, and’or reactive plasmacytosis, and rarely demonstrate the Reed-Sternberg (RS) cells diagnostic of HL (22,34, 35, 36). In general, the diagnosis is not made on the basis of bone marrow aspirate findings.

Bone marrow biopsy sections may show involvement by HL as well as hematopoietic changes and other findings (Figs. 24.1, 24.2, 24.3, 24.4, 24.5, 24.6and 24.7). The neoplastic infiltrate may be focal or diffuse and is composed of lymphocytes, eosinophils, plasma cells, and Reed-Sternberg cells and variants, embedded in fibrous stroma. Extensive fibrosis may dominate the morphologic findings and preclude adequate aspiration. Necrosis has also been reported. RS cells and variants are found in cellular areas of the infiltrate and not among hematopoietic cells. Careful examination of multiple sections may be required to identify RS cells and variants. If the diagnosis of HL has been previously established in a lymph node or other site, an RS variant is sufficient for the diagnosis of HL in the bone marrow; if not, a diagnostic RS cell should be sought (37).