Diagnostic Cytology
Basal Cell Hyperplasia—Reserve Cell Hyperplasia
Reserve cell hyperplasia is defined as the appearance of one or
more layers of primitive, undifferentiated cells in a subcolumnar
position between an overlying endocervical lining epithelium
and an underlying basement membrane. The earliest form of
reserve cell hyperplasia is a single layer of subcolumnar cells9
(Fig. 8.22). Proliferation of the subcolumnar reserve cells may
involve only one or two layers of cells beneath columnar epithe-
lium or may attain a considerable thickness.
Much controversy surrounds the origin of these reserve cells.
Hypotheses about their origin include10:
1. Ingrowth of basal cells from the stratum
germinativum of adjacent normal stratified squamous
2. Origin from fetal squamous basal cells in the pre-
existing stratified squamous epithelium lining of the
urogenital sinus;
3. Origin from undifferentiated fetal rests;
4. Origin from endocervical columnar cells; and
5. Origin from cervical stromal cells.
Fluhmann arbitrarily states that the primitive subcolum-
nar cells are of epithelial origin and arise above the basement
Fig. 8.22 Reserve cell hyperplasia.
The earliest form of reserve cell
hyperplasia is the appearance of a single layer of primitive cells beneath the
endocervical columnar lining epithelium (H&E x HP).
membrane directly from the columnar cells by a process termed
Evidence to definitely exclude their origin from
stromal cells is lacking.
The epithelium lining the endocervical canal is derived
embryologically from the coelomic epithelium lateral to the
urogenital ridge and the subsequently developed mullerian
system. The stroma of the uterine cervix, derived from the primi-
tive mesoderm at the site of the urogenital ridge, may regain
certain of its embryologic potentialities to supply replacement
cells through a poorly defined basement membrane. The most
logical derivation, however, is from the same coelomic epithe-
lium as that from which the columnar cells are derived.
Contrary to what is often stated, these reserve cells are not
comparable to the basal cells of the original stratified squamous
epithelium, because these cells are already dedicated to the for-
mation of squamous cells, whatever the degree of final differ-
entiation (maturation) may be. These two types of reserve cells
also differ in keratin phenotype.
Reserve cell hyperplasia per se is not a significant reaction
biologically, but it is a frequently occurring nonspecific reaction
of the endocervical mucosa.12,13
Cells are usually arranged in the form of a sheet. Cell borders are
usually poorly defined, and thus the cell aggregates often have
the appearance of a syncytium, lacking the loss of polarity and
the disorganization usually observed in carcinoma in situ.
In cervical smears, it is not unusual to find a single layer of
columnar endocervical cells tightly attached to the margin of a
sheet of reserve cells. Pure reserve cells are infrequently identifi-
able in cervical smears. The presence of reserve cells in cervical
smears probably implies that the overlying columnar layer has
been dislodged. When present, these reserve cells are usually
arranged in larger syncytial aggregates called microbiopsies.
Cells are relatively small, irregular, and polygonal. The small
amount of cytoplasm, which is ill defined, is cyanophilic and
may be finely vacuolated. Nuclei are small, relatively uniform
in size and shape, and bean shaped, round, or oval and may
show longitudinal grooves. Nuclear chromatin is finely granu-
lar and is comparable to the nuclear chromatin of the normal
interphase nucleus of the columnar cell. Hyperchromasia is
uncommon, but in marked proliferation, nuclear chromatin
may be arranged in coarser chromatin masses.14 Nucleoli are
not identifiable.12,13
Key features of reserve cell hyperplasia
• Cells typically arranged in a 2-dimensional sheet;
• Cytoplasmic borders often indistinct;
• Group polarity and organization maintained;
• Columnar endocervical cells may be attached to the
• Cells are small, irregular to polygonal;
• Small amount of ill-defined cytoplasm which is cyano-
philic and vacuolated;
• Nuclei are small, bean-shaped, round to oval, with
grooves; and
• Nuclear chromatin is finely granular typically without
The cells arising in reserve cell hyperplasia are noteworthy,
because in some instances they are reminiscent of those seen in
carcinoma in situ. Proliferation of the subcolumnar reserve cells
may involve only one or two layers of cells beneath the columnar
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