Microbiology, inflammation, and Viral infections
Fig. 7.8 Squamous metaplasia (atypical reactive cells, ARC I).
(Papanicolaou x MP).
Degenerative, Regenerative (Repair), and Metaplastic
Changes in Inflammation
The epithelial cells of the lower genital tract (ectocervix, endocer-
vix, and transformation zone), under the influence of persistent
irritation (infectious and non-infectious) and repair, undergo
morphologic changes commonly referred to as metaplasia.
These essentially reflect a benign process of tissue repair. An
overestimation of reparative changes is a most common error
in interpretive cytology. Geirsson and co-workers8 referred to
these as atypical reparative changes (ARC). The majority of
these changes are believed to be derived from the columnar and
squamous epithelia, but reserve or pluripotential cells may be
involved in the genesis of the metaplasia. It must be appreciated
that there is a continuum of changes observed in the healing
phase. Cytomorphologic changes, for convenience, are grouped
under the term metaplasia. Some of these morphologic changes
can be indistinguishable from "early" intraepithelial dysplastic
alterations, observed within both the squamous and the glan-
dular epithelia. These cellular features are grouped as "atypi-
cal squamous or glandular cells of undetermined significance"
(ASC, AGC) (discussed elsewhere).
The earliest discernible changes are referred to as presquamous
metaplasia: columnar differentiation phase, or type I ARC of the
cervical columnar epithelium. Under the effect of chronic irritation
and repair processes, the surface cells of the columnar epithelium
continue to mature, and there is a proliferation of the basal or
reserve cells. These small, undifferentiated cells commonly occur
in small tissue fragments. They have high nucleus-to-cytoplasmic
(N/C) ratios and prominent nucleoli (Fig. 7.8). The nuclear chro-
matin is fine and uniformly distributed, and the nuclear mem-
brane is well delineated and thin. These may have an inflammatory
background. The cells of subluminal origin (progenitor cells) can
often be mistaken for undifferentiated neoplasia.
As the changes evolve, the subluminal cells differentiate from
the germinal layers upward. These changes reflect the immature
squamous metaplastic epithelium and have been referred to as
ARC II. The cells may appear to be columnar and have exces-
sive goblet cell proliferation and mucus production. Signet-
ring forms may be recognized. These cells can have numerous
macronucleoli, coarse chromatin, and modest but pale cyto-
plasm. If not carefully examined, the changes can be mistaken
for a neoplastic lesion of the endocervix (Fig. 7.9). Presence of
Fig. 7.9 Squamous metaplastic changes with columnar cell
hyperplasia (ARC II).
LBGS (Papanicolaou x MP).
Fig. 7.10 Metaplastic changes revealing keratinizing stratified
squamous metaplasia (ARC III).
LBGS (Papanicolaou x MP).
heavy acute inflammation generally helps in the correct inter-
pretation of these changes. In the LBGS, inflammation is less
obvious and these cells often occur as small tissue fragments
and may be reported as AGC.
As the changes progress from the subluminal, via the pre-
squamous, to the
keratinizing stratified squamous phase,
become oval or polygonal with sharp borders and dense cyto-
plasm. They lie in sheets and reveal no obvious cilia and mucus.
Intercellular bridges may be seen at times. These cells with their
metaplastic changes have been called ARC type III. The nuclear
changes may be reactive or degenerative with pyknosis. These
cells may be mistaken for squamous cell carcinoma (Fig. 7.10).
When stressed, as by a chronic irritation or an infective injury,
squamous epithelium responds in a number of ways. These
changes essentially represent alteration of functional differen-
tiation of the affected cells and are mostly cytoplasmic in nature.
Proper identification of these cytoplasmic features is necessary,