Nuclear morphologic and morphometric analyses of nodular poorly differentiated lymphocytic lymphoma: Assessment of small cleaved nuclei

Abstract

Comparative analytic measurements of nuclear parameters in normal and neoplastic lymphocytes are limited. In the present morphometric study lymphocyte nuclear features in 21 cases of nodular poorly differentiated lymphocytic lymphoma (NPDLL) were assessed with respect to the theoretical aspects of some non-Hodgkin's lymphoma (NHL) classifications. The mean nuclear area of the lymphocytes in NPDLL is generally within the range of the areas of unstimulated (mature) lymphocytes of mantle and follicular regions of lymph nodes with reactive hyperplasia. On this basis, the neoplastic lymphocytes in NPDLL do not reflect, at least cytologically, the antigen-activated, transforming lymphocytes of normal follicular centers. All measured nuclear parameters of small, unstimulated lymphocytes of neoplastic follicles suggest that major proportions of this component are also part of the neoplastic cohort. Sectional nuclear profiles in NPDLL are much more irregular in shape and have a higher percentage of invaginations than normal lymphocytes. However, only 4 to 5 per cent of nuclear profiles in NPDLL are of sufficient depth to be termed clefted. Serial section reconstruction of both normal and neoplastic lymphocytes indicates the degree to which the numbers of invaginated or clefted nuclei are underestimated in the examination of histologic sections. For example, the 4 to 5 per cent of nuclear profiles with clefts in histologic sections of NPDLL actually represent about 25 to 30 per cent of the lymphocyte population. On the basis of computer modeling of stylized nuclei with simple invaginations of varying depths and serial section reconstruction of normal and neoplastic nuclei, it is likely that all lymphocyte nuclei have some form of nuclear membrane invagination and that in poorly differentiated lymphomas these invaginations may be single and multiple discrete indentations or linear, branching grooves. Assessment of the ratio of nuclear invagination depth to nuclear diameter in normal and neoplastic lymphocytes indicates that transforming normal lymphocytes in follicular centers do not undergo a phase of increased nuclear clefting and that this ratio is somewhat greater in lymphocytes in NPDLL than in follicular center lymphocytes. However, the latter effect is not due to increased depth of nuclear invaginations in NPDLL, but rather results from the fact that mean nuclear diameter in this subtype of NHL is considerably smaller than that of normal lymphocytes.(ABSTRACT TRUNCATED AT 400 WORDS)