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Clinical Anatomy 11:379–389 (1998)

Behavior of Radial Forearm Skin Flaps Transplanted

into the Oral Cavity
D. BADRAN,1 D.S. SOUTAR,2 A.G. ROBERTSON,3 O. REID,1 E.W. MILNE,1 S.W. MCDONALD,1*
AND R.J. SCOTHORNE1
1Laboratory of Human Anatomy, University of Glasgow, Glasgow, United Kingdom
2 Department of Plastic and Reconstructive Surgery, Canniesburn Hospital, Glasgow, United Kingdom
3Beatson Oncology Centre, Western Infirmary, Glasgow, United Kingdom

Radial forearm skin flaps transplanted into the oral cavity in patients undergoing treatment for
intra-oral tumors frequently acquire a gross appearance resembling that of buccal mucosa. This
article reports studies of biopsies of the flaps in 53 patients, of which 21 showed changes at
some stage in the follow-up period. The project aims to determine whether 1) the change in the
epithelium to a mucosal form is genuine or reactive, 2) a creeping replacement of epidermis
results from the surrounding buccal epithelium, 3) alterations in the epidermis could be
associated with changes in the dermis, 4) the change is caused by radiotherapy. Examination of
the biopsies by resin histology and transmission electron microscopy shows that the changes
may be reversible: it suggests that they are reactive in nature, and related to the degree of
dermal inflammation, rather than to the effect of radiotherapy. The dermis persists as such and
is not replaced by buccal lamina propria. Clin. Anat. 11:379–389, 1998. r 1998 Wiley-Liss, Inc.

Key words: skin flaps; epidermis; histological features; radiotherapy; inflamma-

tion; reactive changes; reconstructive surgery

INTRODUCTION mucous membrane consistency with time.’’ Biologi-

The Plastic and Reconstructive Surgery Unit at
Canniesburn Hospital is the regional center to which
most patients with oral tumors in the West of Scotland
are referred. Treatment usually involves excision of
the tumor and reconstruction using a free radial
forearm skin flap (Soutar et al., 1983) combined with
radiotherapy (Robertson et al., 1985, 1986), depending
on the tumor stage (UICC, 1987).
During follow-up, it is frequently found that the
flap changes in color and texture and, on naked-eye
inspection, resembles the buccal mucosa. The change
was common in patients who had received radiother-
apy. The reason for the changed appearance of the flap
is unclear. The question is of both biological and clin-
ical interest. If the intraoral skin flap were to assume
permanently the characteristics of the oral mucosa, i.e.,
of the recipient site, the change would be acceptable,
both functionally and cosmetically, to the patient and
to the surgeon. There are previous claims of such a
change: Lawson (1985), discussing the use of pectoralis
major myocutaneous flaps in oral cavity reconstruction,
states that ‘‘the epithelium changes from keratinizing
to non-keratinizing epithelium resulting in a pseudo
cally, however, such a change would be very surprising,
in view of the abundant experimental evidence that
the maintenance of the regional characteristics of an
adult epithelium is dependent, in part, on influences of
the subjacent connective tissue and, in part, on regional
variations in the competence of the epithelium to re-
spond to these influences (Billingham and Silvers, 1968;
Mackenzie and Hill, 1984; Hill and Mackenzie, 1984;
Sengel, 1986; Coulomb et al., 1989). Since the radial fore-
arm flap consists of epidermis and its associated dermis
and hypodermis, one would expect the graft to retain
some, at least, of the characteristics of the donor site.
This study aims to answer the following questions:
1) Is the alteration in the appearance of the epithe-
lium to a ‘‘mucosal’’ form a genuine or a reactive
change?
2) Is there a creeping replacement of the epidermis
by surrounding (host) buccal epithelium?
*Correspondence to: Dr. S.W. McDonald, Laboratory of Human
Anatomy, University of Glasgow, GLASGOW, G12 8QQ.
Received 30 June 1997; Revised 25 September 1997

r 1998 Wiley-Liss, Inc.

 Member at www.medicsindex.com
380 Badran et al.
3) Is the native dermis of the graft replaced by
buccal stroma, which might then reinstruct the
overlying epithelium to assume buccal character-
istics?
4) Is the change caused by radiotherapy?
MATERIALS AND METHODS
Patients
The patients in this study, which extended for 30
months, fell into 2 groups; Group 1: 40 patients already
being treated for intraoral tumors at the start of the
study, Group 2: 13 patients who presented for treat-
ment during the period of the study.
Group 1
Group 1 consisted of 25 males and 15 females,
selected because of the suitability of their flaps for
biopsy and their willingness to participate in the study.
At the time of surgery, their ages ranged from 29–81
years. Thirty-eight of the patients had had a squamous
cell carcinoma of the oral epithelium; in the other two
the diagnosis was adenocarcinoma and acinic cell
carcinoma. Twenty-five patients had received a course
of postoperative radiotherapy in the the form of 6,000
cGy in 30 fractions over 6 weeks. A further three had
received a similar course preoperatively and 12 pa-
tients were treated by surgery only.
At the start of the study, a biopsy of the flap was
collected from all patients and, in six individuals, a
sample of lining (i.e., non-keratinized) buccal mucosa
was also obtained. A second biopsy of the flap was
subsequently taken in six patients.
Group 2
Group 2 consisted of 9 males and 4 females aged
between 35 and 75 years. All were diagnosed as having
squamous cell carcinoma of the oral epithelium. In
addition to surgery, nine patients received radio-
therapy as described above. One had previously had
radiotherapy and, like the other three subjects who
had early tumors, received surgery only.
At transplantation, samples of skin were collected
from all flaps. They were immediately fixed in 3%
glutaraldehyde in Millonig’s buffer (pH 7.4) and pro-
cessed into resin. Sections 1 µm thick were stained
with Azur II, resorcin fuchsin or periodic acid-Schiff
and hematoxylin.
Biopsy
Biopsies were taken with the informed consent of
the patient and the approval of the Hospital Ethical
Committee.
Under local anesthesia, a fusiform biopsy was taken
from the graft. All samples were processed as de-
scribed above.
The degree of inflammation in the dermis was
assessed on the following scale:
Grade 0: occasional inflammatory cells,
Grade 1: scattered inflammatory cells,
Grade 2: small aggregates of inflammatory cells,
Grade 3: large aggregates of inflammatory cells,
Grade 4: diffuse inflammatory reaction,
Grade 5: connective tissue components masked by
inflammatory cells.
Transmission Electron Microscopy
Sections for electron microscopy were obtained on a
Reichert-Jung Ultracut E microtome using standard
techniques (Weakley, 1981) and examined on a Philips
EM301 transmission electron microscope.
In the analysis of the light and electron microscopi-
cal material only qualitative observations were used.
RESULTS
Gross Appearance
Group 1. The 40 patients in Group 1 had received
treatment up to 8 years before the start of the project.
When the study commenced, the flaps in 28 of these
patients looked like normal skin (Fig. 1), whereas in
the remaining 12 subjects they resembled adjacent
buccal mucosa in whole (Fig. 2) or in part (Fig. 3). In
the 15 patients treated by surgery only, 5 flaps
were changed in appearance, whereas in the 25 who
Figs. 1–4 show the transplanted radial forearm skin flaps of four
different patients.
Fig. 1. Non-irradiated radial forearm flap 1 year after surgery. The
flap has retained the appearance of forearm skin.
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Fig. 2. Non-irradiated flap (arrows) 7 years after surgery showing
a surface similar to buccal mucosa.
received surgery and radiotherapy, 7 flaps were
changed.
One patient’s flap developed the appearance of
buccal mucosa during the 30 months of the study; this
occurred 8 years after operation. During the study, 5
changed flaps (3 irradiated and 2 non-irradiated)
showed a partial return to the appearance of normal
skin. A further 3 flaps (1 irradiated and 2 non-
irradiated) acquired a silver-white color (Fig. 4).
In flaps showing partial change, some of the changed
areas were peripherally, others centrally, placed. This
observation argues against creeping replacement of
the graft epithelium by buccal epithelium, which
would have resulted in the changed areas lying at the
periphery of the graft. In flaps which had completely
Fig. 3. Non-irradiated flap (arrows) 3 years after surgery. This flap
had previously shown more extensive change towards the form of
buccal mucosa. Keratinized areas have become more extensive. Hairs
are present in the areas with the appearance of skin.
Behavior of Skin Flaps in Oral Cavity 381
Fig. 4. Flap (arrows) which had developed a silver-white surface
6 months after radiotherapy.
acquired the appearance of buccal mucosa, a fine scar
indicated the margins of the flap. Hairs were seen in
many of the flaps of patients treated by surgery only,
but they were absent following radiotherapy.
Group 2
Four of the 13 patients in Group 2 were treated by
surgery only; their flaps retained the appearance of
skin throughout the study. Of the 9 irradiated patients,
the flap of one soon recovered from the radiation and
had the appearance of normal skin. The flaps in the
other 8 developed, in whole or in part, a silver-white
surface and 2 of these had regained the appearance of
skin by the end of the study.
Table 1 correlates the number of patients in Groups
1 and 2, whose flaps did or did not show changes at any
time during the study, with treatment involving radio-
therapy. Changed flaps were more common following
radiotherapy but were also seen in patients treated by
surgery only. Chi-squared test showed no significant
difference between the two regimes of treatment
(Chi-squared ⫽ 0.80; df ⫽ 1).
Light Microscopy
Forearm skin. Biopsies of forearm skin were ob-
tained at the time of initial operation from all 13
patients in Group 2. The appearances were typical of
TABLE 1. Number of Changed and Unchanged Flaps
Following Treatment by Surgery Only and in Combination
with Radiotherapy
Surgery Only Surgery ⫹ Radiotherapy Total
Unchanged 13 19 32
Changed 6 15 21
Total 19 34 53
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382 Badran et al.

thin skin (Fig. 5); the epidermal/dermal interface was

plane; few mitotic figures were visible in the stratum
basale; the stratum spinosum was 3–5 cells thick and
there was no stainable glycogen; the stratum granulo-
sum was 2–3 cells thick and the stratum corneum
formed a thin layer and showed the typical basket
weave pattern. In the dermis, occasional inflammatory
cells, mainly lymphocytes, were seen (Grade 0). Hair
follicles, sweat glands, and their ducts were seen in all
samples but sebaceous glands were identified in only 3
samples. In the reticular dermis, fiber bundles were
irregular in orientation and closely packed whereas, in
the papillary dermis they were less densely arranged.
Buccal Mucosa
Nineteen biopsies of oral mucosa, of the lining
(non-keratinized) variety, were obtained from patients
in Groups 1 and 2 (Fig. 6). The epithelium was 3–4
times thicker than the epidermis, and the superficial
and middle layers were rich in glycogen. The most
superficial cells retained pyknotic nuclei (parakerato-
sis) but there was no true stratum corneum, nor was a

Fig. 6. Buccal mucosa. The epithelium is thicker than that of flap

skin. There is no stratum corneum.

stratum granulosum seen in any sample. In the lamina

propria, a few inflammatory cells, mainly lymphocytes
and neutrophils, were seen (Grade 0–1). The collagen
and elastic fibers were irregularly arranged and less
closely packed than in the dermis of forearm skin.
Some samples showed accessory salivary glands.
Intraoral Radial Forearm Flaps
In total, 77 biopsies were obtained from the flaps of
patients in Groups 1 and 2. On the basis of their gross
appearance, the flaps could easily be classified as
changed or unchanged. The histological appearance of
the following groups of flaps will be described sepa-
rately:

1) postoperative period before radiotherapy,

Figs. 5–10 are all photomicrographs of vertical resin sections,
stained with Azur II, ⫻125.
Fig. 5. Resin section of thin skin of radial forearm flap at time of
surgery. Sweat glands (S) and a hair follicle (F) are indicated.
2) unchanged; irradiated and non-irradiated,
3) changed; irradiated and non-irradiated,
4) partial reversion to appearance of skin, after
‘‘mucosal change’’; irradiated and non-irradiated.
Postoperative Period Before Radiotherapy
Biopsies were taken from four patients 18–20 days
after operation and before radiotherapy. Grossly, the
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Behavior of Skin Flaps in Oral Cavity 383

Unchanged Flaps
A total of 36 biopsies was obtained from the
unchanged flaps of patients in Groups 1 and 2 (Fig. 8).
Eighteen of the biopsies were from irradiated subjects,
18 from the 15 non-irradiated patients. There were no
obvious differences in epidermal structure between
the irradiated and non-irradiated groups. Most speci-
mens showed regression of the hypertrophic changes
seen in the postoperative group, but a few still showed
thickening of the stratum spinosum, with glycogen in
its superficial layers. In all biopsies, the stratum
granulosum was reduced to 3–5 cell layers, but there
was mild hyperkeratosis in the stratum corneum in
some samples.
In four specimens from irradiated patients, the
interface between the epidermis and dermis was
plane. In the dermis of some irradiated flaps, collagen
bundles were less closely packed than in healthy
forearm skin and elastic fibers were more numerous,
thicker and more tortuous and randomly orientated.
Fibroblasts showed characteristic enlargement in irra-
diated flaps. All flaps showed mild or no inflammatory
reaction in the dermis (Grade 0–2). In the reticular

Fig. 7. Postoperative biopsy of flap, 20 days after transplantation.

Compared to thin skin, the epithelium is thicker, particularly in the
stratum spinosum where intercellular spaces are prominent. The
epidermal-dermal interface is undulating.

flaps had the appearance of skin and absorbable

sutures lay at their margins. On histological examina-
tion, the epidermis was thickened by about 3 times (cf.
Figs. 5 & 7). The stratum basale showed little change,
with few mitoses. The stratum spinosum was hypertro-
phic, with more cell layers, enlarged cells and nuclei,
and widened intercellular spaces, with prominent
spines. The cytoplasm was more basophilic and, in the
more superficial spinous layers, was rich in glycogen.
The stratum granulosum varied between the biopsies:
in one, keratohyalin granules and ghosts of nuclei were
seen in the horny layer. The stratum corneum of the
fourth biopsy resembled that of thin skin.
The epidermal-dermal interface was undulating in
all samples, with deep rete ridges and high dermal
papillae. In all, the papillary dermis showed scattered
inflammatory cells (Grade 1), mainly lymphocytes and
a few plasma cells. The deeper part of the reticular
dermis showed dilated capillaries surrounded by a few
inflammatory cells. Hair follicles and sweat glands Fig. 8. Section of unchanged non-irradiated flap, 64 months after
were seen in all samples but none showed sebaceous transplantation. The histological appearance resembles thin skin. An
glands. arrector pili muscle (M) is visible.
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384 Badran et al.

dermis, inflammatory cells, when seen, were mostly

lymphocytes and were largely perivascular in position.
Blood and lymphatic capillaries were dilated in all
samples and endothelial cell swelling was seen in the
blood capillaries of the irradiated material. Hair fol-
licles were seen in biopsies from 7 of the 15 non-
irradiated patients but were not found following radio-
therapy. Sweat glands and/or ducts were seen in all
biopsies from non-irradiated flaps but in only 12
biopsies from the 18 irradiated subjects; because of
difficulty of access, the biopsies of some of the
irradiated flaps may not have been deep enough to
show sweat glands. Sebaceous glands were not seen in
any sample.

Changed Flaps
Twenty-one of the 53 patients in the study showed
changes in their flaps (Figs. 2 & 3); 6 had been treated
by surgery only and 15 had received postoperative
radiotherapy.
The epidermis was markedly thicker than in thin
skin and in many flaps it had deeper rete ridges and an
indistinct stratum corneum (Fig. 9). A few lympho-
cytes and neutrophils infiltrated the epithelium.
In the stratum basale, mitotic figures were more
numerous than in forearm epidermis and in the
unchanged flaps, numbering 2–4 per high power field.
The basal keratinocytes were widely separated.
The stratum spinosum was markedly increased in
thickness in all flaps. Occasional mitotic figures were
seen in the basal parts of this layer. In the deeper parts,
adjacent cells made contact at prominent spines pro-
jecting into wide intercellular spaces (spongiosis). The
cells of the more superficial layers of the stratum
spinosum were closely packed and the spaces between
them almost absent. These cells were enlarged and
had a higher glycogen content than those in the lower
layers. Vesicles were noted in the upper part of the
stratum spinosum in recently irradiated flaps.
The stratum granulosum was variable, absent in
some parts and thinner than in forearm skin in others.
Parakeratosis was a common feature of these flaps,
both irradiated and non-irradiated, and a few nucle-
ated cells sloughed from the surface. Some flaps
showed thin flakes of anucleate cornified cells. Vesicles
were noted in the stratum corneum of irradiated flaps.
The dermal-epidermal interface of some biopsies
was highly undulating, with high connective tissue
papillae. The basement membrane appeared intact in
sections stained by the PAS technique. In some
irradiated flaps, dermal elastic fibers were abundant,
thickened, tortuous, and randomly distributed.
Variable grades of inflammatory reaction occurred in
the dermis (Grades 2–5); in some flaps it was so severe
Fig. 9. Section of a flap, 26 months after transplantation, whose
gross appearance resembled buccal mucosa. The epithelium is mark-
edly thickened and the interface between it and the underlying
connective tissue is highly undulating. The connective tissue compo-
nents are masked by the presence of large numbers of inflammatory
cells (Grade 5). This flap had not been irradiated.
that it masked the dermal components. The inflamma-
tory cells were mainly plasma cells and lymphocytes;
many were in perivascular positions. In the deeper
dermis, occasional mast cells were seen. In three
samples (2 recently irradiated and 1 non-irradiated)
the reticular dermis contained large numbers of extrava-
sated erythrocytes. The deep part of the reticular
dermis of irradiated flaps was more cellular than in
non-irradiated ones. Giant fibroblasts were seen in the
irradiated samples. Blood and lymphatic capillaries
appeared dilated in all flaps. Hair follicles were ob-
served in two of the non-irradiated flaps but in none of
those subjected to radiotherapy. Sweat glands and/or
their ducts persisted in all non-irradiated flaps but in
only 9 of the 15 irradiated flaps.
Flaps Showing Partial Reversion
During the routine follow-up of the patients, a
number of flaps which had wholly or partially acquired
the appearance of oral mucosa subsequently reverted
to the appearance of skin. In some the areas resem-
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Behavior of Skin Flaps in Oral Cavity 385

bling oral mucosa were smaller, in others they ap-

peared silver-white.

1) Reduction in Size of the Changed Area

Biopsies were taken from four flaps which showed
partial reversion from a previous biopsy at the same
site. Three were from irradiated patients and one was
from a non-irradiated patient. Biopsy material came
from reverting areas of these flaps.
The histology resembled that described for the
changed flaps; there were, however, some differences:

1) Although still increased in thickness compared

with thin skin, the epithelium was thinner than
in the previous biopsies.
2) In the stratum basale, mitotic figures appeared
fewer than in the earlier biopsies.
3) In the earlier biopsies of two of these flaps, the
stratum granulosum had been absent but was
present in the later biopsies.
4) In some of the later biopsies the stratum cor-
neum had become well-defined.
5) Dermal inflammation was reduced in the biop-
sies of three of the four flaps. Two of the
irradiated specimens showed Grade 4 at the first
biopsy but Grade 3 at the second. The non-
irradiated flap had originally shown Grade 5 but Fig. 10. Flap showing partial recovery, 36 months after transplan-
the later biopsy showed Grade 4. tation, with a silver-white appearance on gross examination. The
histology resembles that of changed flaps but, compared to earlier
2) Silver-white Appearance biopsies, the epithelium is thinner and the dermal inflammatory
reaction reduced. The surface shows parakeratosis.
Thirteen biopsies were taken from the flaps which
had acquired a silver-white appearance (Fig. 4): 11
were from irradiated flaps and two were from non- uted to these features which resembled the
irradiated ones. The two non-irradiated and one of the lesions of psoriasis.
irradiated specimens were collected from Group 1 3) In the six individuals with previous biopsies,
patients. The other 10 irradiated specimens came from mitotic figures were less frequent in the stratum
Group 2 patients, two of whom had repeated biopsies. basale of the biopsies with the silver-white
An earlier biopsy, before the silver-white color devel- appearance.
oped, had been taken from some of these patients 4) In the six flaps previously biopsied, the later
allowing comparison of the flap histology before and biopsies of five showed reduction of dermal
after the development of the silver-white appearance. inflammatory reaction.
The histology of the flap when showing the silver-
white appearance (Fig. 10) was generally similar to Electron Microscopy
that described earlier for the changed flaps. Some This part of the study aimed to determine whether,
differences were observed, however: at the ultrastructural level, the flap epithelium re-
sembled that of skin or buccal mucosa. In addition to
1) The epithelium was thicker than in thin skin, samples of forearm skin collected at the time of
but for those flaps from which a previous sample surgery, the following biopsies were examined:
was available, it had become thinner since the
earlier biopsy. 1) healthy buccal mucosa: 2 patients
2) The stratum corneum remained parakeratotic, 2) unchanged flaps: 2 patients—1 irradiated; 1
but many parakeratotic cells were loosely at- non-irradiated
tached to the surface, either as single cells or in 3) changed flaps: 5 patients—4 irradiated; 1 non-
clusters. The silver-white appearance was attrib- irradiated
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386 Badran et al.

4) recovering flaps: 3 patients—2 irradiated; 1 non-
irradiated.
Unchanged Flaps
Biopsies of flaps which grossly resembled skin
retained the electron microscopical appearances of
thin skin (Fig. 11). In particular, the following were
observed: superficial electron-dense squames, cells
rich in keratohyalin granules forming a stratum granu-
losum, coarse electron-dense bundles of tonofilaments
in cells of the stratum spinosum.
Changed Flaps
Four of the five changed flaps showed ultrastruc-
tural appearances intermediate between those of skin
and buccal mucosa. The fifth specimen, which had
been irradiated, was similar to buccal mucosa.
Two of the changed flaps resembled buccal mucosa
in having nucleated surface cells. There were more

Fig. 11. T.E.M. of thin skin (a) and of an irradiated unchanged flap (b). Both show keratinized surface
cells (K), a stratum granulosum (G), and coarse tonofilament bundles in the stratum spinosum (S). Bar ⫽
2 µm.
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layers of cells in the epithelium than in skin. The
stratum granulosum was absent. In one specimen, that
which resembled buccal mucosa in every way, tonofila-
ments were inconspicuous (Fig. 12 a,b). In the other,
tonofilament bundles were somewhat coarser than in
buccal mucosa, particularly in the deeper cells (Fig. 12
c). Microvillous projections on the surfaces of the cells
were less obvious than in buccal mucosa.
The other three changed flaps, which included the
non-irradiated specimen, showed electron-dense super-
ficial squames. One showed numerous keratohyalin
granules. All showed cytoplasmic tonofilament bundles
intermediate in character between those of buccal
mucosa and skin. One specimen, with an epithelial
thickness and surface squames similar to skin, showed
tonofilament bundles which were somewhat coarser
than in the other changed flaps but still more delicate
than those seen in skin and in unchanged flaps. Again,
in all specimens, the microvillous surface projections
of the cells were less obvious than in buccal mucosa.
Flaps Showing Partial Recovery of Skin-like
Gross Appearance
The three biopsies taken from recovering flaps, like
most of the changed flaps, showed features intermedi-
ate between skin and buccal mucosa. All showed
electron-dense surface squames. Two showed kerato-
hyalin granules. Whereas all three showed tonofila-
ment bundles finer than those of skin, comparison
with earlier biopsies showed coarsening of the bundles.
In summary, the electron microscopical study de-
tected two structural alterations in changed flaps:
1) a qualitative reduction of keratohyalin granules,
2) cytoplasmic tonofilament bundles finer than
those in skin.
These features varied in degree between individual
changed flaps. No specific differences could be de-
tected between irradiated and non-irradiated speci-
mens. Unchanged flaps resembled thin skin. Some
changes towards the form of thin skin were visible in
the recovering flaps.
DISCUSSION
While sample sizes are small, the changes which
occur in skin flaps transplanted to the oral cavity fall
into two categories:
1. Changes in response to transplantation itself.
The epidermis in biopsies taken in the postopera-
tive period, before irradiation, showed hypertrophy,
and hyper- and parakeratosis, with increased cytoplas-
Behavior of Skin Flaps in Oral Cavity 387
mic basophilia and accumulation of glycogen in the
stratum spinosum. In biopsies taken later, from un-
changed flaps, and from those changed flaps which
had subsequently reverted to the appearance of nor-
mal skin, these epidermal changes had regressed. A
very similar sequence of changes was described in
orthotopic human skin autografts by Scothorne and
Scothorne (1953), and it seems likely that in each case
the changes represent the early and later responses to
the process of transplantation.
2. Changes involving other factors: radiation, infec-
tion.
Twenty-one of the 53 patients in this study showed
a gross change in the appearance of the flap from the
morphology of skin towards that of oral mucosa at
some stage in the period of observation. Although the
change frequently followed radiotherapy, it also oc-
curred in non-irradiated patients at any time after sur-
gery, and there was no significant difference in the in-
cidence of this changed appearance between irradiated
and non-irradiated patients. In three of these patients,
all of whom had received radiotherapy, the changed
appearance reverted to normal after various intervals
and some of the others showed partial reversion.
Histologically, biopsies of the changed flaps dif-
fered from normal thin skin in that the epithelium was
thicker and showed parakeratosis, increased glycogen
content, loss of keratohyalin granules, and finer tono-
filament bundles. Whereas the changed epithelium, in
several respects, resembled normal buccal epithelium,
the underlying connective tissue retained the struc-
ture of dermis and contained sweat glands, but showed
marked inflammatory changes in many specimens.
These features, together with enlarged intercellular
spaces in the epithelium and the reversible nature of
the changes, at least in some individuals, indicate a
reactive rather than a genuine change. The histologi-
cal features of the flap epithelium were similar in both
irradiated and non-irradiated patients although some
differences could be recognized in the dermis.
It is clear that, while radiotherapy may have a role in
initiating the change, other factors must also be
important. In a few patients, changes in the appear-
ance were associated with infection with Candida
albicans and in one patient the flap reverted to the
appearance of normal skin following treatment of the
infection. The relative roles of radiotherapy, infection,
and other forms of trauma in the etiology of the
observed changes in the flaps remain unclear. The
gross appearance of the flap, however, is related to the
number of inflammatory cells infiltrating the dermis.
Forearm skin and buccal mucosa showed Grade 0 and
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Fig. 12. T.E.M. of typical cells in buccal mucosa (a) and in as in buccal mucosa. The other changed flap (c) showed tonofilament
changed irradiated skin flaps (b & c). Both flaps had living superficial bundles which were coarser than in buccal mucosa but finer than in thin
cells. The fields illustrated were mid-way through their thickness. In skin or unchanged flaps (cf. Fig. 11). Bar ⫽ 2 µm.
one of the changed flaps (b) tonofilament bundles were inconspicuous
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Grade 0–1 inflammatory changes respectively. Postop-
erative flaps showed Grade 1 inflammation. In un-
changed flaps the degree of reaction varied from
Grade 0–2 while in the changed flaps it was Grades
2–5. Inflammatory changes diminished as flaps re-
gained the appearance of skin.
While the connective tissue deep to the epithelium
retained the general features of dermis, recent work has
indicated that adult and fetal fibroblasts differ in func-
tions such as their response to cytokines (Ellis et al.,
1997). It is possible that transplantation and/or radio-
therapy resulted in functional changes in the fibroblast
population and consequent alterations in the overlying
epidermis.
It is concluded that the change in the appearance of
the radial forearm skin flap, to that of buccal mucosa,
does not represent a true, permanent change in epithe-
lial type. It did not occur consistently at the periphery
of the graft: this argues against the possibility that it
was the result of creeping replacement by surrounding
buccal epithelium. In many cases it was reversible, and
its occurrence seemed to be directly related to the
degree of inflammation in the dermis. The presence of
inflammation is not surprising, considering the factors
which predispose to the development of oral cancer:
excessive smoking, drinking, and poor oral hygiene,
which continued in at least some of the patients after
treatment. Of particular interest and importance was
the fact that the dermis of the flap persisted as such
and was not replaced by lamina propria at the host site.
The dermis would therefore be expected to continue
giving its instructive signals to the overlying epithelium,
which maintained its essential epidermal characteris-
tics.
ACKNOWLEDGMENTS
The authors are grateful to Miss Margaret Hughes
for photography and to the staff of the Combined
Clinic.
Behavior of Skin Flaps in Oral Cavity 389
REFERENCES
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