NUCLEAR PROTRUSIONS IN CELLS FROM CYTOLOGIC SPECIMENS - MECHANISMS OFFORMATION

OBJECTIVE: To explore the mechanisms of formation of nuclear protrusio ns (NPs) encountered in cytologic specimens and specifically the possi bility of their being the result of an aberrant division of the cell a nd to determine how widespread the NP phenomenon is in cells front var ious tissues. STUDY DESIGN: Sis hundred fifty-four cervical smears out of 5,000 with abundant cervical columnar epithelium examined were fou nd 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 defection of mitotic spindle-associated microtubula r structures, (D) by fluorescence in situ hybridization (FISH) utilizi ng X chromosome probes to monitor chromosomal movement into NPs, and ( E) by direct fluorescence microscopy to examine autofluorescence patte rns in cells with NPs. Also, tissue sections of 240 cervical cone biop sies, many including intraepithelial neoplasia (group B), were examine d for NPs, and sections containing NPs were subjected to TEM. Last, 39 0 nongynecologic cytologic specimens from various lesions and organs o btained by fine needle aspiration or brushing methods were examined fo r 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 mi croscopic findings; the TEM findings (centriole at their tip, indicati on 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 n uclear pole, indicating the presence of microtubules consistent with m itotic 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 prop hase 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 nu clear volume and shape changes, including formation of protrusions.