Nuclear protrusions in cells from cytologic specimens. Mechanisms of formation.

OBJECTIVE

To explore the mechanisms of formation of nuclear protrusions (NPs) encountered in cytologic specimens and specifically the possibility of their being the result of an aberrant division of the cell and to determine how widespread the NP phenomenon is in cells from various tissues.

STUDY DESIGN

Six hundred fifty-four cervical smears out of 5,000 with abundant cervical columnar epithelium examined were found to have many cells with NPs (group A). These cells were studied: (A) by light microscopy to define the structure and stages of formation of NPs, (B) by transmission electron microscopy (TEM), (C) by tubulin immunostaining for detection of mitotic spindle-associated microtubular structures, (D) by fluorescence in situ hybridization (FISH) utilizing X chromosome probes to monitor chromosomal movement into NPs, and (E) by direct fluorescence microscopy to examine autofluorescence patterns in cells with NPs. Also, tissue sections of 240 cervical cone biopsies, many including intraepithelial neoplasia (group B), were examined for NPs, and sections containing NPs were subjected to TEM. Last, 390 nongynecologic cytologic specimens from various lesions and organs obtained by fine needle aspiration or brushing methods were examined for the presence of NPs.

RESULTS

NPs were found in a variety of tissues, epithelial and nonepithelial. Their formation in the cases examined appeared to be related to cell division, as indicated by: the light microscopic findings; the TEM findings (centriole at their tip, indication of spindle formation, nucleolar movement into the NP and suggestion of chromosomal movement as well); positive tubulin immunostaining of centrosome-centriole in NPs and also of the underlying region of the nuclear pole, indicating the presence of microtubules consistent with mitotic spindle; and movement of one X chromosome into NPs, as shown by FISH.

CONCLUSION

NPs are formed in cells from a variety of tissues, epithelial and nonepithelial. In many cases they appear to result from aberrant cell division--namely, unipolar mitosis--occurring before prophase events are completed. Another possible mechanism of NP formation not involving cell division is through alteration or remodeling of the cytoskeleton of the cell; that was shown experimentally to produce nuclear volume and shape changes, including formation of protrusions.