Bone Marrow Involvement in Anaplastic Large Cell Lymphoma:Immunohistochemical Detection of Minimal Disease and Its Prognostic Significance

Abstract

Bone marrow involvement by anaplastic large cell anaplastic large cell (ALC) lymphoma can be difficult to detect on routine morphologic examination alone. In a series of 42 patients with ALC lymphoma, the authors analyzed: (1) the usefulness of a limited panel of monoclonal antibodies directed against CD30 (Ber-H2, HRS4) and epithelial marrow involvement on routinely processed biopsy specimens; and (2) the prognostic significance of bone marrow involvement as detected on both morphologic and immunohistochemical grounds. On conventional examination, 17% of the patients were found to have bone marrow involvement at diagnosis. However, after immunohistochemical analysis, occult malignant cells were detected in 23% of the patients with negative bone marrow biopsy on routine histology. The low percentage of positive cases on routine morphologic examination compared to immunohistochemical examination was related to: (1) the scarcity of neoplastic cells which were scattered among hematopoietic cells; (2) the difficulty of distinguishing malignant cells from immature hematopoietic elements; and (3) the absence of alteration of the reticulin network. The authors observed a significant association between marrow infiltration and the presence of hematologic abnormalities (mostly anemia or cytopenias) at diagnosis, both in children and adult patients. More importantly, a significant lower survival was seen in patients with bone marrow involvement compared to those without bone marrow involvement. Immunohistochemistry with anti-CD30 and anti-EMA antibodies should be performed systematically in bone marrow biopsies from patients with ALC lymphoma to reliably identify the presence of bone marrow involvement that appears to carry a poor prognosis.

Anaplastic Large Cell Lymphoma: The Shifting Sands of Diagnostic Hematopathology

“…Bone marrow involvement is relatively common in ALCL, but may be easily missed in routine trephine sections or aspirate smears (58). The neoplastic cells usually infiltrate as single cells, and are most readily identified with stains for CD30, EMA, or ALK.…”

Role of Immunohistochemistry in Staging Diffuse Large B-cell Lymphoma (DLBCL)

“…Fraga et al (1995) reported that in a case series (n542) of anaplastic large cell lymphoma, routine histology detected marrow involvement in 17% cases. Routine IHC analysis using CD30 detected occult disease in a further 23% cases (Fraga et al 1995). We found BM involvement on routine histology in 19.2%, with a more modest 11.1% rate of occult involvement.…”

“…Scattered malignant cells may be missed quite easily on routine histology (Fraga et al 1995) but be more easily discernible on IHC analysis. Such cases were classified positive when numbers of B cells were increased compared with controls.…”

Anaplastic large cell lymphoma: pathology, genetics, and clinical aspects

“…5,9,10,[12][13][14]19 In a report analyzing bone marrow involvement in ALCL, the incidence was 17% with histology only, whereas 40% of cases were found to be positive when immunohistochemistry was combined. 20 Circulating tumor cells or involvement of the gastrointestinal tract or central nervous system (CNS) are rarely detected at diagnosis. 5,9,10 CNS relapse occurs in a small subset of patients.…”