P. Caveriviere

Monoclonal antibodies in the diagnosis of Hodgkin's disease. The search for a rational panel.

A novel, comprehensive panel of monoclonal antibodies was tested in a large series of routinely processed lymph node biopsy specimens from patients with Hodgkins disease (69 cases), with the object of developing either definitive or adjunctive diagnostic criteria. B- and T-cell lymphomas and reactive states that could mimic Hodgkins disease were also assessed with the same monoclonal antibody panel. In addition to the popularly used anti-Leu-M1 (CD15), the panel included the recently produced Ber-H2 (CD30) antibody, which detects a formalin-resistant epitope of the Ki-1 antigen. The other monoclonal antibodies were directed against epithelial membrane antigen (Dako-EMA) and leukocyte common antigen (Dako-LC) (CD45), as well as B-cell (LN-1 and LN-2) and T-cell (MT1) associated antigens. The results showed clear phenotypic separation of nodular lymphocyte predominant subtype of Hodgkins disease from other subtypes. The lymphocytic and histocytic cells of nodular lymphocyte predominant Hodgkins disease were reactive for LN-1 (all cases) and anti-EMA (most cases) but negative for anti-Leu-M1 and Ber-H2. Within the other subtypes—i.e. nodular sclerosis and mixed cellularity—nearly all Reed-Steinberg cells and Hodgkins cells were positive for both anti-Leu-M1 and Ber-H2. Ber-H2 monoclonal antibody was observed to react more frequently with Reed-Sternberg cells and Hodgkins cells in Bouins- or formalin-fixed tissues. Pleomorphic T-cell lymphomas, which could mimic Hodgkins disease on morphology, created the same problem on phenotypic analysis. However, MT1 identified a significant proportion of T-cell lymphomas with Reed-Sternberg-like cells, having proven negative for Reed-Sternberg cells and Hodgkins cells in Hodgkins disease. Thus, a combination of anti-Leu-M1, Ber-H2, anti-EMA, LN-1, and MT1 monoclonal antibodies appears at present to be the most useful panel for the diagnosis and the differential diagnosis of Hodgkins disease.

Diagnostic features of primary malignant lymphomas of the thyroid with monoclonal antibodies

Primary malignant lymphomas (ML) of the thyroid are rare and their conclusive morphologic diagnosis is not always possible. The authors report diagnostic features of 11 cases of ML and one case of plasmacytoma of thyroid compared with chronic lymphocytic thyroiditis and undifferentiated carcinomas of thyroid in an immunohistochemical study using monoclonal antibodies (MoAb). The lymphoid nature of tumors could be identified in all cases with three MoAb on paraffin sections. In ML, tumor cells expressed leucocyte common antigen (Dako‐LC+) with negativity for epithelial membrane antigen (Dako‐EMA—) and cytokeratin (KL1—). Newer MoAb identifying B‐cell (LN‐1, LN‐2, MB2) and T‐cell‐associated antigens (MT1, UCHL1) not denatured by fixation, revealed B‐cell nature of tumor cells in all cases of ML. Among anti‐B MoAb, LN‐1 and MB2 were most consistent in their reactivity. In cryostat sections of three ML cases, the tumor cells expressed one or more B‐cell‐associated antigens. Plasmacytoma was negative for Dako‐LC and KL1 but positive for Dako‐EMA and monotypic cytoplasmic Ig.

Immunohistochemical profile of cutaneous B-cell lymphoma on cryostat and paraffin sections

Thirty cases of primary (23 cases) and secondary (seven cases) cutaneous B-cell lymphoma (CBCL) were studied by immunohistochemistry using a selected monoclonal antibody (MoAb) panel on both cryostat and paraffin sections. On cryostat sections all CBCL so tested were positive for surface membrane immunoglobulins (IgMk most often) and B-cell antigens (CD22+, CD37+ ) with a variable T-cell-reactive component identified by MoAbs against T-cell antigens (CD2, CD3, CD4, CD5, CD8). CD4-positive stromal T-cells were usually more numerous than CDS-positive cells. A strong (50–75% of total cells) stromal T-cell (CD2+, CD3+ ) reaction was found in centroblastic-centrocytic lymphoma. Small numbers of CD1+ Langerhans cells were found in most cases, but they were present in large numbers in follicular lymphoma. On paraffin sections, a combination of MoAbs against B-associated antigens (LN-1, MB2) identified B-cell lineage in virtually all cases of CBCL. CBCL was negative for MoAbs against T-associated antigens (MT1, UCHL1) with rare exceptions (two cases). However, MT1 and UCHL1 combined identified the T-cell nature of all cases of nonepidermotropic, nonmycosis T-cell lymphoma, which were initially predictive of B-lineage by histologic pattern.

Immunohistochemical detection of post-therapy residual testicular lymphoblasts in childhood acute lymphoblastic leukemia (ALL)

The aim of this study was to evaluate the diagnostic value of immunohistochemistry with monoclonal antibodies (MoAbs) in detecting residual blast cells in testicular biopsies from children with acute lymphoblastic leukemia (ALL). In a prospective study of 26 patients, testicular biopsies were performed after completion of therapy, and the average follow-up after biopsies was 29 months. After immunostaining, seven patients with negative biopsies on routine histology showed scattered, strongly calla-positive cells as well as cells reacting with anti-B (CD22) MoAb. Among these seven patients with residual blast cells, four had relapsed either in testes (n = 1), bone marrow and testes (n = 1), or in the bone marrow (n = 2). In contrast, among the 15 patients without residual blast cells, all but 1 remained in complete remission. In four other cases no definite conclusion was possible after immunohistochemical study. Four testicular biopsies from patients with occult infiltration were used as positive controls. Negative controls consisted of testicular biopsies from children with testicular ectopia and postmortem testicular tissue specimens. Results suggest that the risk of relapse is significantly higher in patients with positive immunohistochemical findings indicating persistent residual blast cells. However, the predictive value of these findings requires confirmation on a larger number of cases to have therapeutic implications.