Electron Microscopic Analysis of Lymphocyte Nuclei in Non-Hodgkin's Lymphoma

Ultrastructural studies of normal and neoplastic lymphocytes are presented that qualitatively and quantitatively assess the central cell organelle currently used by surgical pathologists in the classification of non-Hodgkin's lymphoma, the nucleus. Events occurring during normal lymphocyte transformation can be used to appreciate essential mechanisms involved in producing the appearance of the nucleus as seen by microscopy. Quantitation of nuclear subcompartments by morphometric image analysis reveals that determination of nuclear size is primarily due to the ribonucleoprotein materials distributed between condensed chromatin masses, the interchromatinic (euchromatin or nuclear matrix) region. Furthermore, such investigations show that amounts and distribution of condensed chromatin in lymphocyte nuclei cannot be adequately assessed from routine histologic sections. Ultrastructural morphometric analysis of representative cases of the principal subtypes of NHL indicates that the atypical morphologic appearance of neoplastic lymphocytes results from a complex interplay between total amounts of condensed chromatin in nuclei and the size of individual aggregates of condensed chromatin, one or both of which may be abnormal in NHL. Abnormalities of interchromatinic materials are also likely involved in ordering the gross appearance of the nucleus. Understanding of both the dynamic capabilities of the nucleus, and the organization of and interplay between the various subcompartments of this organelle will be helpful in improving the classification of NHL by surgical pathologists.