Immunophenotypic characteristics of cerebrospinal fluid cells in children with acute lymphoblastic leukemia at diagnosis

Abstract

The presence of meningeal involvement in children with acute lymphoblastic leukemia (ALL) may have important prognostic and therapeutic implications. Conventional methods of diagnosing central nervous system (CNS) leukemia rely on the interpretation of cerebrospinal fluid (CSF) cell morphology, which may produce ambiguous results in the presence of minimal leukemic involvement. A methodology has been developed for immunophenotyping small numbers of CSF cells while preserving cell morphology. CSF samples from 33 children with CDlO (common ALL antigen [CALLA]) positive ALL were examined at initial presentation using both conventional morphology and this combined immunohistopathologic technique. Six (18%) of the samples con-HE IMPROVED outcome for acute lymphoblastic leu-T kemia (ALL) in childhood has made it essential to be able to accurately diagnose disease present in pharmacologic sanctuaries at diagnosis and during the course of therapy. In the era before the routine use of therapies specifically targeting leukemia in the central nervous system (CNS), a high proportion of children with ALL relapsed in this site.'-3 In addition, children manifesting C N S leukemia at initial diagnosis are felt to have an increased risk of relapse requiring the intensification of both systemic and C N S the rap^.^.^ Despite the importance attributed to the presence of C N S leukemia, there is little consensus as to the precise cerebrospinal fluid (CSF) cytologic abnormalities considered diagnostic for C N S and the incidence of CNS leukemia a t diagnosis can vary considerably depending on which diagnostic criteria are used.'Several factors contribute to the difficulty in determining the presence of C N S leukemia, including the small numbers of cells present in routine CSF samples and difficulties in interpreting the significance of morphologic abnormalities of small numbers of CSF cells in cytocentrifuge preparation^.'.^*'^ The demonstration of leukemia-associated cell surface antigens and nuclear TdT can enhance information available from cell morphology in determining whether or not cells are of leukemic origin. The common ALL antigen (CALLA), designated CDlO, has proved to be a useful leukemiaassociated antigen and is present on the leukemic cells in over 80% of childhood ALL cases while present on only a few normal lymphocytes." Similarly, nuclear terminal deoxynucleotidyl transferase (TdT) is present in the leukemic cells in over 90% of ALL cases." Whereas immunophenotyping techniques exploiting these and other cell markers are routinely used in examining peripheral blood and bone marrow samples to provide information regarding cell lineage, these techniques are rarely used in examining CSF specimens because of technical limitations imposed by the small cell populations present in most CSF samples.' However, several recent reports have studied CSF cells for the presence of TdT13-15 or cell surface antigensI6 in patients with malignancy and found these studies to be a valuable adjunct to the examination of cell morphology fo...

Cerebrospinal Fluid Biomarkers in Childhood Leukemias

“…Thirty-six percent of CSF samples in that study were also examined for the simultaneous presence of nuclear terminal deoxynucleotidy1 transferase (TdT) and demonstrated higher numbers of positive cells for both TdT and CD10. The authors concluded that a large proportion of children with ALL and negative CSF cytology may have CNS disease consistent with the presence of occult leukemic involvement, which can be detected with CD10/TdT staining [ 22 ].…”

Minimal requirements for the diagnosis, classification, and evaluation of the treatment of childhood acute lymphoblastic leukemia (ALL) in the “BFM family” cooperative group

“…The finding that cytomorphologically suspicious cells are TdT-negative may exclude CNS leukemia; the finding of TdT positivity (in red blood cell-free samples!) is highly predictive of, but not decisive for, CNS involvement [60,63,64].…”

Polymerase chain reaction on cerebrospinal fluid cells in the detection of leptomeningeal involvement by B‐cell lymphoma and leukaemia: a novel strategy and its implications

“…SCNSL, particularly of the leptomeninges, has been reported with an overall frequency of 3 . 7-9% in different series for extracerebral NHL (Herman et al, 1979;Johnson et al, 1984) and in a range from 1% to 15% of acute lymphoblastic leukaemia (ALL) in children at diagnosis (Homans et al, 1990).…”

“…Transformed lymphocytes showing mitotic activity or atypical features may be seen in CSF samples in benign conditions and may contribute to false-positive results (Borowitz et al, 1980;Pearson et al, 1982). False negative cytologic results also remain a problem because of the small number of malignant cells which may be present in CSF samples, and in some instances multiple CSF examinations may be required to obtain a definitive diagnosis (Ersbøll et al, 1985;Homans et al, 1990). One objective method is to demonstrate monoclonality of a lymphoid population by surface markers using antibodies against immunoglobulin (Ig) heavy and light chains (Li et al, 1986).…”

“…One objective method is to demonstrate monoclonality of a lymphoid population by surface markers using antibodies against immunoglobulin (Ig) heavy and light chains (Li et al, 1986). The paucity of cells in most CSF specimens and the technical or interpretative difficulties are presumably reasons why surface markers have not, to our knowledge, been widely applied in cases of suspected CNS lymphoma (Pearson et al, 1982;Homans et al, 1990).…”