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Surgical approach to multifocal carcinoma in situ of the vulva
Surgical approach to multifocal carcinoma in situ of the vulva PHILIP \vILLIAM
,J. DI
SAIA,
M.D.
M.
RICH,
M.D.
Thirty-nine patients with multifocal carcinoma in situ of the vulva were managed with en bloc removal of the involved skin and a split-thickness skin grafl to the surgical defect. The characteristic presentations of this clinical entity are reported and options for therapy are discussed. Thirty-nine percent of the patients developed a recurrence, but none of the recurrences was within the donated skin graft. No reports of dyspareunia or seriously altered sexual function were noted. The details of the surgical approach are outlined and modifications of the original procedure are described. (AM. J. OBSTET. GYNECOL. 140:136, 1981.)
HISTORICALLY, Bowen’ described two cases of indolent and recurring red, scaly. oozing lesions on the buttock and thigh, occurring in two men. Histologic review of these lesions revealed cellular atypism of a neoplastic nature. These two patients continued to have recurrences over a follow-up period of 12 to 18 years and no invasion occurred. Since that report there has been continuous confusion regarding this and similar lesions. In 1913, Knight2 reviewed the literature and reported 26 cases of carcinoma in situ of the vulva. In 19.53, De Lima and associates” collected 41 cases and remarked as to the rarity of this lesion. In 19%. Woodruff and Hildebrandt’ reported 13 cases of vulvar intraepithelial neoplasia and suggested the term “carcinoma in siLu.” Vulvar intraepithelial neoplasia has been considered ;t problem of postmenopausal women but recent experience suggests a much younger age group at risk-a patient in her 20s is not unusual.” In addition, there appears to be a detinite increase in the incidence of these vul\,ar lesions. Some of the increase is undoubtedly due to more accurate diagnosis: however, the flood of cases has raised the question of an etiologic agent (cal-cinogen or virus). Very few of these lesions are associated with occult
From thr Department of 06stetric.r Unirwr3ity of California. Iruinr.
and Gynecolo~.
Prrcentpd by wwitation at the Forty-seventh Annual Meeting of the Pacific Coast Obstetrical and Gynecological So&y, Monterey. California, October 6-1 I, 1980. Reprint requests: Dr. Philip J. Di Saia, Department of Ob.rtetnrs and Gynecoology, I01 City Dr., South, Orunge, California 92668. 136
invasive disease; therefore. local therapy has been the mainstay in localized disease. Topical chemotherapy has gained favor in some circles but local excision has the distinct advantage of allowing for complete histologic assessment; lesions with microinvasive foci can thus be found. However, for those patients who have more involvement of the vulva with multiple and frequently confluent lesions. the physician may find that local excisions are impractical. In 1968, Rutledge and Sinclair” reported a procedure for this latter group of patients which has come to be known as “the skinning vulvectomy with skin graft.” This report deals with 39 patients treated by a modification of the Rutledge procedure. Nlaterial The skin excision and gratt method was used in 39 patients between 1971 and 1979. All patients harbored multifocal disease with at least 3 quadrants of the vulva involved. In most cases, the patients exhibited 20 or more lesions and/or large conHuent areas over the vulvar skin. All patients were treated bp the authors. Clinical features Age. The age range was 25 to 56. Nineteen of the 39 patients were aged 35 or younger. Although there is an obvious selection process, with younger patients being referred to the authors for this procedure, the concentration of patients in the third and fourth decades is striking. Race. Only one of the 39 patients was non-Caucasian and that patient was black. The literature is noncommittal on this subject but we suspect that there is a 000%9378/811100136+10$01.00/0~
1981
l‘hr
C. V. klosby
Co.
Volume Number
140 2
predominance of these lesions in fair-skinned women. Symptoms. Pruritus was the predominant symptom in this series; however, it occurred in just under 50% of patients. In eight patients there was a history of the individual’s noting some vulvar irritation or “a lump.” Fully a third of the cases were diagnosed by the physician during a routine pelvic examination. The diagnosis was then substantiated by multiple biopsies of the vulva, often colposcopically directed. The disease appears to be asymptomatic in nearly 50% of patients. Diagnosis. The value of careful inspection of the vulva during routine gynecologic examinations cannot be overstated. Colposcopy has proved quite effective in detecting multifocal lesions because the magnification allows identification of smaller lesions. In the absence of colposcopy, lesions may be accentuated by application of 2% acetic acid to the vulvar skin and inspection with a bright light. Nuclear staining with 1% toluidine blue can be useful, though false negative and false positive rates are high. Vulvar biopsies were accomplished with a Keyes dermatologic punch (4 to 6 mm size) with the patient under local anesthesia. This instrument allows for removal of an adequate tissue sample and orientation for future sectioning. After obtaining the biopsy specimen, we use the Keyes punch to cut out a replica in an absorbable gelatin sponge. This is positioned in the skin defect and kept in place with a small dressing for at least 24 hours. Associated lesions. Thirty-eight percent of the patients had a previous documented history of either cervical or vaginal intraepithelial neoplasia, which points out the multifocal nature of the process. Several of the other patients gave a history of an “abnormal Papanicolaou smear” but no tissue diagnosis was available. Nature of lesions. The lesions presented as papules or macules, coalescent or discrete and multifocal. Lesions on the cutaneous surface of the vulva usually gave the appearance of lichenified or hyperkeratotic plaques, i.e., white epithelium. Lesions on the mucous membranes were usually macular and pink or red in appearance with coarse punctation noted colposcopitally. Six of the patients had what appeared to be hyperpigmented lesions, which ranged in color from mahogany to dark brown, and colposcopically appeared as raised epithelium with a dirty white color. These latter lesions stood out sharply when observed with a good light and all the lesions in those patients (including recurrences) had the pigmented quality. Twenty-five of the patients had detailed drawings of these lesions recorded and a composite is shown in Fig. 1. The highest occurrence of lesions was in the area of the perineal body, with the periclitoral area next and the labia minora third.
Surgical
approach
to multifocal
vulvar
carcinoma
137
Fig. 1. Composite of distribution of lesions in 25 patients suggesting the posterior vulvar and periclitoral areas as having the highest frequency of involvement. Selection of patients for procedure. The major reason for considering skinning vulvectomy and graft iS the importance to the patient of a more normal postoperative functional and cosmetic effect than is possible with a simple vulvectomy or extensive local excisions. These considerations are usually important in the treatment of the younger patient but every patient should be advised of her options. The use of a skin graft, when compared to vulvectomy alone, requires a much longer anesthetic, a second surgical site, 6 to 7 days of bed rest, and roughly a 100% increase in hospital days; this must be considered in the decision process, especially in older women with severe medical problems. All patients must be carefully examined for possible sites of early invasion and extensive biopsies of these areas must be obtained preoperatively to avoid unnecessary preparation of a patient who may not be a candidate for this procedure. Operative technique. The perineum was prepped as was the donor site, which in most cases was the medial aspect of the right thigh. The buttocks area can be and occasionally was utilized as the donor site but there are certain disadvantages to this site. First, the patient will be required to lie in bed for 7 days on this painful operative site and, second, a skin donation from this site requires that the patient be turned while under anesthesia before the vulvectomy itself can begin.
138
Di Saia and Rich
Fig. 2. Line of skin include all recognized mm.
excision lesions
carefully determined so as to with a visible clear margin of 5
An air-driven dermatome is utilized to take the graft at a thickness of i’/i,ooo of an inch. Draping is performed so as to leave the medial aspect of the right thigh exposed for cutting the skin graft. A small amount of mineral oil is applied to the skin as a lubricant after the prep solution is removed with a salinesoaked gauze. A tongue blade is used to apply traction on the skin in front of the moving dermatome. With moderate pressure applied to the area being cut, the dermatome is moved slowly up the thigh, and the desired segment of skin is removed. One can see the skin rolling up on itself as it is fed out the back of the dermatome. When enough skin has been cut, tension is applied to the segment removed and the segment is cut free from the preserved skin by means of a scalpel. The donor site is covered with gauze impregnated with scarlet red dye. It is our feeling that this dye promotes re-epithelialization of the area. An occlusive pressure dressing is applied over the graft site. The area of vulvar skin which is to be removed is outlined with a marking pencil (Fig. 2). These patients have been studied colposcopically prior to the operative procedure and the limits of disease have been carefully determined. The incision is made over the pencil marks. Care should be taken to have the scalpel perpendicular to the surface of the skin when the incision is made; this will prevent cutting the hair follicles on a bias and the resultant postoperative burrowing of hair shafts at the margin of the graft. There is a relatively avascular plane between the
Fig. 3. The epidermis and dermis only are subcutaneous tissue serving as a graft bed.
removed, with the
dermis and the subcutaneous tissue sometimes referred to as the superficial fascia. Development of this plane is considerably facilitated by means of blunt dissection. Utilization of the handle of the scalpel is especially effective. Bleeders are controlled with electrocautery. When the proper surgical plane has been found, a white sheen is noted on the undersurface of the dermis. Sharp and blunt dissection should be utilized alternately throughout the procedure. Traction and countertraction are essential to the proper dissection. The thickness of the skin which is to be removed consists essentially of the epidermis and the dermis only (Fig. 3). All of the subcutaneous tissue should be preserved as a graft bed (Fig. 4.) Preservation of all of the subcutaneous tissue not only promotes graft take but also optimizes the cosmetic and functional results by preserving the soft and pliable nature of the vulva. The clitoris is preserved even when lesions are apparent on the glans. Lesions on the surface of the glans can be shaved with a scalpel blade and re-epithelialization will occur with no loss of sensation. The skin of the prepuce can be removed, if necessary, with the shaft and glans of the clitoris left intact. The posterior dissection is usually left for last because it is the most difficult area in which to establish a good plane of dissection and bleeding is often encountered. The specimen is removed by choosing a line of incision on the mucous membrane of the vestibule. In most instances, the lesions stop at the hymenal ring, which is frequently the inner margin of dissection. Hemostasis
Volume Number
140 2
Surgical
graft bed is primarily adipose tissue and fascia; hemostasis is necessary prior to application of the
approach
to multifocal
vulvar
carcinoma
139
skin graft.
Fig. 5. The skin graft is sutured in place and the graft itself is “pie crusted” to allow serum to diffuse out from beneath the graft.
is established primarily with electrocautery and the driest possible field is selected as a graft bed. Suturing of the graft in place is begun peripherally by means of the standard technique where the needle is passed first into the graft and then through the preserved tissue. A running suture of 4-O polyglycolic acid or PGA-type suture is utilized. These thin grafts are very flexible and can be stretched to accommodate almost any defect. The graft is kept moist during the procedure with the use of saline loaded in a 20 ml syringe with an l&gauge, blunt-nose needle. This will later be utilized to irrigate the graft bed prior to application of the dressing and prevent the accumulation of clot between the graft and the subcutaneous tissue. Excess skin can be trimmed as one proceeds with the suturing. Care should be taken to apply the skin graft to the bed with the proper tension (Fig. 5). Excess tension will allow undue accumulation of serum between the skin graft and the subcutaneous tissue. Insufficient tension will allow wrinkling and redundancy which will not permit optimum skin take. Excess skin graft must be removed in order to achieve this proper tension. The graft is “pie crusted’ to allow escape of serum and prevent undue accumulation beneath the skin graft. During the first 3 to 5 days following the procedure, the skin is nurtured by diffusion of nutrients across a serum clot which develops between the subcutaneous tissue and skin graft. “Pie crusting” allows the distance between the subcutaneous tissue and the skin graft to be kept to a minimum in order to facilitate this process of diffusion.
A foam rubber dressing is next fashioned to the shape of the graft. This l-inch foam rubber serves as the most superficial layer of the pressure dressing applied to this area. Stay sutures are later tied over this piece of foam rubber, thus securing the dressing in place and immobilizing the graft. Placement of the stay sutures, first in the vagina and then on the peripheral skin, is accomplished next. The sutures are tagged with old-fashioned umbilical cord clamps which are color coded in pairs. This permits the final tying of the stay sutures in the proper order. Large portions of skin and vaginal mucous membrane should be taken in the placement of the stay sutures to minimize the probability that one or more sutures will be pulled out in the first 6 postoperative days. A catheter is placed in the bladder since the dressing which is to be applied will not permit voiding. A piece of nonadherent gauze is applied over the skin graft and the area is packed with moist cotton balls. These cotton balls have been soaked in an antibiotic solution which prevents anaerobes from proliferating in the dressing and producing an offensive odor. The moist cotton balls are easily molded into a pressure dressing above the nonadherent gauze. The l-inch piece of foam rubber previously fashioned is then placed over the moistened cotton balls and the stay sutures are tied. Color coding allows the vaginal suture to be identified with its matching peripheral skin suture. It is sometimes necessary to place a few additional sutures in order to fix the foam rubber dressing superior& and iyferiorly Again, generous por-
Fig.
4. The
optimum
140
Di Saia and Rich
Fig. 6. A 2%year-old tions
of skin
and
foam
rubber
are
patient
with
nec~essarv
multiple
to assure
lesions
of the labia
eration
h\ not providin:
CC’IIICI ot the graft;
stability.
posterior Rssults This
method
(#therapy
of’ patient
(Figs.
6 and !)5’%
is usually
period
areas
is complete
to resume the
skin
patients
acceptance
7). A rate
erative
coitus graft
has been and
of skin
obtained
and
quite lack
graf’t in the
satisfactory
of complicatiws take
within has returned
has complained
by
Most
of‘dyspareunia
and. in general, sexual response comparable to that in predisease taken to avoid creating vaginal
None af‘ter
in
of‘ the
6 months,
has been reported as periods. Care must be introital stenosis at op-
7 ;I large enough opening can create 3 tight ring
this and
of’ the
patients
have
developed
of’tidlou~-up
fl-om
I:! to 90 months.
a period
produce
ot the
recurrent
lesions
all ha\.e
been
on the preserved
of.recurrence
I-al areas
are able
sensation
over
areas
denuded
patients
complete 6 months.
85% postop-
of the
4 weeks. and
between
immediate
re-epithelialization in 8 weeks
in
perineum
fourchette
A third
terms and
and posterior-
above, tin
as well our
disease
f~-ee)
skin.
been
tiw
re>u/t.
‘I‘llis
clitoral
recurrences
an impro\ which
been
all of the recurrent possible rc’currcnces
and
presac-
technique
has resulted
and
common
As mentioned
and
ed cosmetic have
None
graf’t
most
perianal hood.
clitoris
understandablv
excision (as have are prepared for
the
skin
The
of the Rutledge
of the glans
recurrence
in the
periclitoral
modilication
presewation
dyspareunia.
has been
have as the
in the at the
calls
its prepuce and
in some
marlaged lesions).
and,
(if
functional with
perilocal
Patients in general.
Volume Number
140 2
Surgical
approach
to multifocal
vulvar
carcinoma
141
Fig. 7. Same patient as in Fig. 6, 12 months after grafting. In many patients the color of the graft remains lighter than the surrounding skin but texture and sensation are undistinguishable from those of o:ginal healthy skin. have been very understanding. One patient developed a keloid in a portion of the donor site but fortunately this appears to be slowly receding. Ten patients had some form of urinary tract infection from the indwelling Foley catheter used with the perineal dressing. In none of the 39 cases was invasive disease discovered in the operative specimen.
Comment Considerable interest in a nonsurgical approach to intraepithelial neoplasia of the vulva was initiated by Klein and associates’ and others8 following their reports of the use of 5-fluorouracil (5-FU) in a variety of cutaneous cancers. Woodruff and colleagues” ran lengthy clinical trials with the use of topical 5-FU cream and initially reported encouraging results. In 1978, Krupp and Bohm”’ reported on a review of 35 cases with an overall success rate of 63%. Buscema and associates” recently reported only three responses in 11
patients treated with topical chemotherapy. Success is obtained primarily in very well-motivated patients since therapy must be continued daily for 6 weeks and all patients experience intense pruritus accompanied by edema and weeping, which often require symptomatic therapy such as topical anesthetics. sitz baths, and analgesics. Very few reports detail the percentage of patients who abandon therapy (because of unacceptable side effects) after less than an adequate trial. Our experience with a limited trial suggests that 75% of patients will discontinue application of the drug after the first 7 to 10 days (far short of the necessary 42-day course). In addition, very few reports have long-term follow-up so that the recurrence rate following 5-FU therapy is unknown and more important the possible long-term effects of the drug itself on vulvar skin needs to be studied. For these reasons, our practice has been to utilize 5-FU cream only in patients who refuse operation and/or have very localized disease; we encour-
142
Di Saia and Rich
age tt~c skinning with
tfit’f’use
those
vutvectomy disease.
patients
1, ith
tot. ;I successfi~t ttw
dit‘fuse
Iargc
skin
general. of
area
graf’t
\ve
disease
completion
cat thei-at’!: great
with
In
have
are
poor
e-week
a
rccfuiring
in patients
elsewhei-e
in
fhund
suspicion
ot‘an
rhar
candictates
cot~rse
vttfvar
of top-
treatment
. etectrocautery.
utiti/ed
trrlsi\e
lor
ttiseasc
;it~.s’~
these sllc-I1
xvith
f~n~iie)
with
approach
or
tof)ical
the
total
rarefy
for
csin
a
responded
(dinitrochtoro‘Trials
01’ a
reporLed
iiot
\lost
authorities
01 the iiosis. bte
tissue
tliseax
optimum
b) the
is cfesirow f’uiictionat
fxiliciit sitler
ac‘ceptancx skin
cisiori,
significanl
had
in fjatients
or t)artiat tcast
toss who
none
of’ sexual ~1s
recfGre
targe
ot‘ our to
thr
paGents ttcvelot)inriir
icat
ex-
have
demonstrated 01 similar
II\
tori
hci-twa\
irris
\\;I\
ot)-
tcsiotis treated
;ii~rl
ivtiictr
of’ttic. with
ix’\ cxfcd cairi-
that such sitllations aiiecdote that t~odof~h~lti~~
tcd
II:I\C Lx11
itI-
f’rom
01 this
srutl?
0~11’
a
t hetic
ot
grouf~
resistance ‘I‘his
grotlt)
of
esf)eciatty “high-risk” recw-rent.
in the
main
and
tasting
the
has been
\ er)
others
skin
grat
t, sug-
within
ttw
skin
taken
rcsislance
in the categor\
or multiorgan
and
t hcsc
fx!cholog-
etrl.ation
mood
disease.
was that
c-onsitfer-abtc
~rottblesonw
removed
deser\w
“higli-risk” f)acould include
observation had
has
and
in thr
implied
a personal
that risk
our
of’ IWW lesions site.
assistance
knowledge greatest
tiave
III
not surprisiiig.
to iiiti.~ief~irliefi~il 101. this f)i-obtciti
wir h diffuse,
fx&nts
\~iitvectonl).
10’4
con~istt~nl
that is similar an eriofogic agent
inherent
In conclusion.
to coiIlocal
t)crinc;it
iiw
fxitieiits.
li~tir
a biops>
observation
an cctopic
patients
pa0111
rcrentty
suspect
serious consideration, tient groufx. This
in this
function.
\Ve spoken
absence an
f’rom
th?
of’ our
the
gesting
;III
M’ith
to
suggestect
1101
ot
In
\xc’I.~’
of no
is
to hc c~cmctytoma:,
prior
sitLL.
4nother
ha\,c
detaifett
clitoris).
has encouraged
grafts
f~i.~ctisf~ositioii
procedure
the
otten
been
recur-
of preserving state.
in
to the
ancf which
suggestive
assumed ttin
Lxma
diag-
~~outct
\+cre
iis<’
fx”iriits.
is apptica-
or widet)
traditionally
lvho
of
accurate
IO f,atieiits.
uas
remowl
report
has diffuse
of ttle Rutledge
has
most
in this
history
in the
patirllrs
the ~oiiitnon
tigfit,jeans,
.-\ previous
vLit\x
for
to ;I strong
otxrabtc 0111
substanw~
antf
from
teatts
routine
to
escef)L
due-e ti.ansfi)rmatioii neoptasia. Iii short,
of \ ut\ar
Surgical
and/or
(fxx~sc~~vation
ticiits
;\t
who
and
treatment
the
vufvectom~
c.o~inetic.
modification rrf)or’
alto~vs
patient
\vhwc
considered
txxc~~
the stqical.
utilized
~IL-LK~~LIIT
IO ttw
011h
that
is basically
in\ otvcd l’hc
ring
agree
in situ
other
tainetf f~odof~ti~
;lLlttl~m.
carcinoma
or
.I‘tiis
carcinogen
as
\\.as noted
iciidergarments
associ-
and
that
cream.
xvei-c
have
regression
torso
S-FL:
vLit\-a
surgery
Kaaf‘
DIV(:B
with
OIL
bitt
refxxt.
the tocccr
sut~f~teinentecf
similar
lesions
case
60 lesionson
to im~nLlnoth~r.af,~
laser
in this
as
a single
rcportett
fxltietlr
vritvar
arid
tract.
as etsewherr.
ctuestionccf
txacrice
(:i~yos~ii~gt.~~
genital
unidentified
as \vett
deodorants
tfisc~omlort.
been
skin
carcf‘ulty
creates
the
arca rcf>tac
f row of
the
skin
.lt
cd in an at’s-
inaiiiicr.
tcsion~
REFERENCES
I. Bowen, J. ‘I-.: Precancerous dermatosis-A study ot two cases of chronic atypical epithelial proliferation, J, Cutan. Dis. 30:241, 1912. 2. Knight, R. V.: Bowen’s disease of the VLIIW. ASI. .J, OBSTET. GYNIXOL. 46:513. 1943. 3. DeLima, 0. A., DeCuarnieri, N. (;.. and DeLima, M. I,. l‘.: Molestia de Bowen da vulva, Rev. Gynecol. Obstet. 47:95, 1953. -1. \Voodruff. J. I).. and Hildebrandt, E:. E:.: Carcinoma iI1 situ of the vuha, Obstet. Gynecol. 12:414, 195X. 5. Hilliard, G. D., Massey, F. M., and Wl‘oole, R. V., .Jr,: \‘ulvar neoplasia in the young. AM. J. OBSTET. GYNECOL.. 135: 1x5, 1979. 6. Rutledge, F., and Sinclair, M.: Treatment of intraepithelial carcinoma of the vulva by skin excision and graft, AM. J. OBSTET. GYNECOL. 102:806, 1968. 7. Klein, E., Helm, F., Milgrom, H.. et al.: Tumors of. the
Discussion DR. WILLIAM day’s f>resentation re&rts bv Brwwn~
E. LUCAS, San bv Dr. and
Diego, Calif’ornia. ToDi Saia underscores the recent associates’ anti Friedrich and
X.
9.
10.
Il.
12.
skin. keratoacanthoma: Local ettecrs 11t i-Huoroul-acil. Skin 1: 153. 1962. Litwin, M. S., Krementx, E. T.. Mansell, P. M’., et al.: Topical chemotherapy of tentigo maligna with 5-Huorou&i1 creme, Cancel’ 35:721, 1975. .’ Woodruff. I. D.. lulian. (1.. Purav, T.. et al.: The contemporary cha&ngeOof. carcinoma in situ of the vulva, AM. J. Ossrw. (;YNECol.. 115:677, 1973. Krupp. P. J., and Bohm, J. \V.: .i-Fluorouracil topical treatment 0K in situ vulvar tanccr, Obstet. Gynecol. 51:702. 197x. Buscema, J., Woodrutt. J. D.. t’armlq, ‘I‘. H.. and Genadry. R.: Carcinoma in situ of the vulva. Obstet. Gynecol. 55:225, 1980. Raaf, J. H.. Krown, S. E., Pinsky, (:. &I., et at.: ~I‘reatment of Bowen’s disease with topical dinitrochloroben/.ene and 5-Huorouracil,~Cancer 37:1633, 1976.
colleagues’ documenting a dramatic apparent increase in the incidence of’ carcinoma in situ of the vulva during the last decade, an experience which we ha\e shared at rhe University of‘ (:afif’ornia. San Diego.
Surgical
\vhere 58 patients with this diagnosis have been treated since 1973. A number of important questions have been raised and none answered as yet. Friedrich and colleagues recently reviewed the possible role of viral infections ot the \,ulva. No clear association can be made at the present time. The relationship of intraepithelial wha cancer to invasive cancer is also unclear. Are we to expect a significant increase in the incidence of invasive vulvar cancer one or two decades from now? This is an important question when one considers that 19 of this series of Z19 patients of Drs. Di Saia and Rich were under age 35 (49%). In San Diego, 30 of our 58 patients (52%‘) were under age 40 when initially treated. bYe agree with the authors that the primary approach should be surgical for the reason that this is the only sure way that the histologic width and depth of the lesion can be defined. Although they have not encountered early invasion among their 39 patients, three of our 5X patients were found to have superficial invasion in the surgical specimen, and Friedrich and associates reported that three of’ his series of 53 patients had superlicial invasion. M’e share Dr. Di Saia’s lack of enthusiasm for topical j-FL. This not only is usually unsuc‘cessful in treating multifi)cal disease but also requires a stoic patient to complete the required course of treatment. We abandoned its use several years ago after a limited trial. We also have some reservations about the use of the carbon dioxide laser for the reasons cited above, principally the lack of histologic control. Careful follow-up of laser-treated patients for at least 5 years will be necessary to establish the effectiveness and safety of this method. The authors have provided us with data documenting their good results with the use of skinning tomy and grafting in 39 patients. At UCSD we have used this approach, with minor technical differences, in 17 of 58 patients, with equally gratifying results. Long-term cosmetic and functional results and patient acceptance have in general been good. The chief disadvantage is the longer period of hospitalization and convalescence required. For this reason we favor wide local excision where possible. in order to take advantage of the ease with which relatively large areas of excision can be closed by mobilizing lateral flaps of skin at the level of Scarpa’s fascia. The depth of excision is exactly the same as described by the authors for skinning vulvectomy. Only epidermis and dermis are removed in a relatively avascular plane. The glans and hood of the clitoris are preserved when possible. Since the cosmetic and functional results with this approach have often been as good as those obtained with grafting, we are now using skin grafts less often than we did 2 or 3 years ago. 1 wonder if the authors may not utilize skin grafts less often as time goes on. ‘I‘he recurrence rate of 39?? reported in this paper is disturbing. Our recurrence rate to date has been less
v&c-
approach
to multifocal
vulvar
carcinoma
143
than 9% (five of 5X), but follow-up has been short in many cases. The need tar meticulous patient education and follow-up is underlined. Contrary to the authors’ experience we have seen one instance of recurrence in a skin-grafted area, approximately 2 years after the original procedure for very extensive multifocal carcinoma in situ. In conclusion, 1 wonder it‘ Dr. Di Saia might care to expand OII his thoughts presented here regarding the rising incidence of carcinoma in situ of the vulva and particularly its relationship to the subsequent development of invasive disease. REFERENCES
1. Buxema, J., Woodruf’t. J. D. Parmley, T. H., and Genadry, R.: Carcinoma in situ of the vulva, Obstet. Gynecol. 55:223. 1980. 2. Friedrich, E. G., Wilkinson, E. J., and Shifer, Y.: Carcinoma in situ of the vulva: A continuing challenge, AM. J. OBSTET.GYNECOL.
136:830,
1980.
DR. ED HILL, San Francisco, California. The problem alluded to by Dr. Di Saia is not indigenous to Southern California. We have noticed the same phenomenon in the Bay area. One of’the problems that we have noted is that these patients frequently come in after treatment for condyloma. I point out that not all that looks like a wart actually is a wart and that some carcinomas in situ bear a superficial resemblance to condylomas. The question is when should a biopsy of lesions which have the appearance of venereal warts be obtained. The tendency of this particular disease to concentrate in the area of the perineum and perineal body as well as the perianal region has also been noted. One of the problems that we have faced is the excision of the perianal lesions and whether or not to perform a temporary, diverting colostomy while the skin graft in the perianal area heals. Also we have had problems of anal strictures in those patients who have had skin grafts in a circumferential manner in the perianal region. One of our patients actually had perianal involvement that extended all the way in the natal cleft back to the area overlying the sacrum. How would you handle this particular problem? DR. IVAN LANGLEY,Portland, Oregon. This is a disease that has been “chased” by many people, including myself, for more than 30 years, each reporting a recurrence rate of about 30%. which is similar to that of Dr. Di Saia. Most of LIS haye not used the colposcopy as a method of observation but have removed only those lesions that were visible by the use of a hand lens; I believe this is a more common method of follow-up. The most common complication reported by the authors was urinary tract infection. I would recommend that they add suprapubic cystotomy to the procedure. This addition would reduce complications and offer the patient less discomfort.
One of‘ the most important things is distinguishing whether or not the lesion is invasive. Allow me to present the following method of’orienting the biopsy specimens. The sitnple cassette that is normally used in the pathology laboratory and the cellulose pads come f’rom the packaging of’cover slips. B! tneans of’s hand lens, the biopsy specimens can be ortented cot-rcctly in theit air-fixed state. The cellulose and tissue biopsy specitnens are processed through the Technicon and are sectioned as one, which results in guaranteed proper sectioning oC the tissue. There is one question that arises. lvhich Dr. L.uc-as alluded to. and that 1 would like to have Dr. Di Saia discuss. In all retrospective studies that I know of concerning carcinoma of’the vulva, one halfof‘the in\asivc lesions occur in patients with diffuse disease and one half’ develop in isolated ulcer l&m. However. with one third recurrent or persistent. there have been no reports of invasion in the treated patient regardless of t‘ollow-up tittte. This is certainly not true of’ the cervix nor is it true of‘ any orher malignancy. This fact leads one to believe rhat there must be something characteristic of’ this disease that is ditterent from others. DR. DAVID FIGGE, Seattle. Washington. One, of course, hesitates to take issue with Dr. Di Saia and his very excellent presentation. I do feel, however, sotnewhat uncomfortable with his suggestion to us that the colposcope is an effective tool to define rhe surgical margins for the resected skin that is to be supplanted by a skin graft. We have also walked down this same pathway and also harbor a good deal of enthusiasm for the colposcope. We have, ho!vever. reluctantly come to the conclusion that the colposcopc, as Dr. Langley suggests. offers very little advantage over the simple hand lens. Indeed, the margins of’ resection, as determined by colposcopy, in our experience bear very little resemblance to the margins of’ the disease in the skirt at hand. Only by exceeding the margins that could be visually determined by at least a 2 cm tnargin can we avoid the problem of’ recurrent carcinoma in situ. I would ask DI-. Di Saia if’ his patterns of‘ recurrence hear any correlation to the presence of disease at the resected margins in his surgical specimens. DR. HAROLD LYONS, Merced. California. It is not often thar otw gets a chance to suggest something ne\\ to this Society. ‘I‘wo years ago, I \\as invited to Las C~IICCS. New Mexico, by a group of’wterinarians to see a new product which they were using on cattle. L!nf’ortunately. .i(/; of’ all the cattle in the Big Sky Country developed carcinoma in situ of the eyelid and of’the eye itself. They have developed. at Alamogordo. what they call a lo\v-current field which heats tissue between the two poles of’ an instrument to approximately 110” (this can be varied), and they have discovered that by raising the temperature of’tissue to 1 IO” for SO seconds these lesions disappeared. All lesions of‘ the eye disappeared after treatment. It is necessary only to place a topical anesthetic on the eyeball to treat these animals.
They have hundreds and hundreds of pictures show ing complete resolution of the lesions. Large numbers of’ these instrumenls have been manutactured, \\,hich are used repeated]\- in the cattle industrv to cut down the incidence of death tram carcinoma of the eJ,e. It \vould be interesting to apply this kind of approach to vulvar lesions, because nothing would be destroyed in the process and evervthing could be observed as healing occurred. DR. DI SAIA (Closing), .I‘he problem of superhc.ial invasion is, of course. something that we have been concerned about for a Iong time. We pertitrm a great man) biopsies in cases where we feel there may be invasion. Fortunately, as has been pointed out by many of the discussants, the association of‘this disease with invasion is low. This disease does not appear to progress to invasive disease either quickly or in a high percentage of’ patients. All of us, however, have had patients with early tnalignancy in a “sea” ot‘ carcinoma in situ. so I know that there is an association. but I have no idea how we WOLI~~ approach the frequency or prevalence of the invasive cotnponent. Wide local excision is, I think. the mainsta\ of treatment, as Dr. Lucas tnentioned. ‘I-he development of’ peripheral skin Haps Mith suturing to the mucous membrane is something that we did try and maybe we should re-try. I have f‘ound that c.osttteTic and f’unctional results f’rom that type of procedure are not as good as with the skin graft. Recurrence lvithitt the graft is a real probletn. I have heard many reports of‘recurrences in the graf’t, !et ebery time that I have investigated said recurrences, and I always ask that a picture be sent, I have noticed that the recurrence is on the edge 01’ the preserved skin and sometimes extends over onto the graft. I haw yet to see anyone with a recurrence in the tniddle of. the skin graf’t, and the theory that topical skin has a resistance is something that I am ver!; interested in and would like to f’ollow through. The rtsing incidence of this disease and its etiology are, of course. beyond me. We did send a questionnaire to all of’ our patients, and about 27 of’ thctn responded. M’e were trying to determine what kinds of’ hygiene, deodorant sprays, and other things may be common among them. In the last 3 to 1 ).eat 5. I have questioned each patient exwtsivcly and can find no consistent topical etiologic agent. The only thing I find consistently is that everyone wears pantyhose and tight jeans and I do not know how IO interpret that tinditig. The herpes\irus has, of’ course, been suggested, and 10 of’ our 39 patients had a history consistent with herpes. Dr. Hill has brought out a very valid point. There is art anecdote in our specialty that podophyllin creates a situation that can be confused with carcinoma in situ or dysplasia of the vulva. I do not think that is true. I think that what happens is that all too many times we innocently treat carcinoma in situ with podophyllin thinking that we are treating condylomas. In this series of :39 patients, five were treated repeatedly with podophyilin
Surgical approach to multifocal vulvar carcinoma
for condylomas, but when the lesions did not go away biopsy was tinally done, they, of course, really had in situ disease. Grafting is difficult in patients with perianal disease. The bulky dressing really helps. All of these patients are given paregoric and Lomotil from Day 1 and we starve them. They do not have a bowel movement for 7 to 8 clays. We take the dressing off and then give them enemas. They tolerate this relatively wel1. I think in this way we have avoided using colostomies in patients who have to have grafting around the anus. Grafting all the way to the sacrum is again difficult, but the long-term result seems to be good and we do not hesitate to graft right around to the sacrum. Dr. Langley pointed out something, as did Dr. Figge, that is quite true. You do not have to use the colposcope. I repeatedly teach that the application of 3% acetic acid and a good light are all you need. It happens that I have a colposcope around all the time and I sort of like to look through it, so I use it. However, I really think that these lesions can be identified without a hand lens if you have a good light and you apply 3% acetic acid. I always take time in the operating room to apply 3% acetic acid so the students can see the dramatic way in which the lesions flare up with this simple procedure. The patterns of recurrence in the cases that we have had have not been correlated with positive margins.
145
That is probably something we should do. As I stated earlier, a lot of our recurrences were disease in the perianal area that we did noi recognize. They were often on skin tags (anal skin tags), and since then we have been more careful. We still prefer to do a local excision around the anus rather than grafting. I think, unless you have confluency, that you should not graft-just do a local excision. As you know, the anal skin is very loose, and you can take a lot of it out. We leave it open, and it heals well. Dr. Lyons’ comment is most interesting. I would wonder about our human use committee if I presented such an experiment to them, but I think it is something that is very interesting and should be looked into. There is something else, of an investigative nature, that is coming on the horizon that may be helpful. This is the use of 13-cis-retinoic acid, a derivative of vitamin A, which, in tissue culture and in animals, seems to have the ability to take neoplastic cells and mature them back to normal cells. It has been used in a few cases of skin cancer, and there is presently an investigation under way with the use of this material topically on dysplasia and carcinoma in situ of the cervix. If this works out well, we may have a way of treating this disease very easily. I might say that the application of 13-cis-retinoic acid is absolutely painless.
,J. DI
SAIA,
M.D.
M.
RICH,
M.D.
Thirty-nine patients with multifocal carcinoma in situ of the vulva were managed with en bloc removal of the involved skin and a split-thickness skin grafl to the surgical defect. The characteristic presentations of this clinical entity are reported and options for therapy are discussed. Thirty-nine percent of the patients developed a recurrence, but none of the recurrences was within the donated skin graft. No reports of dyspareunia or seriously altered sexual function were noted. The details of the surgical approach are outlined and modifications of the original procedure are described. (AM. J. OBSTET. GYNECOL. 140:136, 1981.)
HISTORICALLY, Bowen’ described two cases of indolent and recurring red, scaly. oozing lesions on the buttock and thigh, occurring in two men. Histologic review of these lesions revealed cellular atypism of a neoplastic nature. These two patients continued to have recurrences over a follow-up period of 12 to 18 years and no invasion occurred. Since that report there has been continuous confusion regarding this and similar lesions. In 1913, Knight2 reviewed the literature and reported 26 cases of carcinoma in situ of the vulva. In 19.53, De Lima and associates” collected 41 cases and remarked as to the rarity of this lesion. In 19%. Woodruff and Hildebrandt’ reported 13 cases of vulvar intraepithelial neoplasia and suggested the term “carcinoma in siLu.” Vulvar intraepithelial neoplasia has been considered ;t problem of postmenopausal women but recent experience suggests a much younger age group at risk-a patient in her 20s is not unusual.” In addition, there appears to be a detinite increase in the incidence of these vul\,ar lesions. Some of the increase is undoubtedly due to more accurate diagnosis: however, the flood of cases has raised the question of an etiologic agent (cal-cinogen or virus). Very few of these lesions are associated with occult
From thr Department of 06stetric.r Unirwr3ity of California. Iruinr.
and Gynecolo~.
Prrcentpd by wwitation at the Forty-seventh Annual Meeting of the Pacific Coast Obstetrical and Gynecological So&y, Monterey. California, October 6-1 I, 1980. Reprint requests: Dr. Philip J. Di Saia, Department of Ob.rtetnrs and Gynecoology, I01 City Dr., South, Orunge, California 92668. 136
invasive disease; therefore. local therapy has been the mainstay in localized disease. Topical chemotherapy has gained favor in some circles but local excision has the distinct advantage of allowing for complete histologic assessment; lesions with microinvasive foci can thus be found. However, for those patients who have more involvement of the vulva with multiple and frequently confluent lesions. the physician may find that local excisions are impractical. In 1968, Rutledge and Sinclair” reported a procedure for this latter group of patients which has come to be known as “the skinning vulvectomy with skin graft.” This report deals with 39 patients treated by a modification of the Rutledge procedure. Nlaterial The skin excision and gratt method was used in 39 patients between 1971 and 1979. All patients harbored multifocal disease with at least 3 quadrants of the vulva involved. In most cases, the patients exhibited 20 or more lesions and/or large conHuent areas over the vulvar skin. All patients were treated bp the authors. Clinical features Age. The age range was 25 to 56. Nineteen of the 39 patients were aged 35 or younger. Although there is an obvious selection process, with younger patients being referred to the authors for this procedure, the concentration of patients in the third and fourth decades is striking. Race. Only one of the 39 patients was non-Caucasian and that patient was black. The literature is noncommittal on this subject but we suspect that there is a 000%9378/811100136+10$01.00/0~
1981
l‘hr
C. V. klosby
Co.
Volume Number
140 2
predominance of these lesions in fair-skinned women. Symptoms. Pruritus was the predominant symptom in this series; however, it occurred in just under 50% of patients. In eight patients there was a history of the individual’s noting some vulvar irritation or “a lump.” Fully a third of the cases were diagnosed by the physician during a routine pelvic examination. The diagnosis was then substantiated by multiple biopsies of the vulva, often colposcopically directed. The disease appears to be asymptomatic in nearly 50% of patients. Diagnosis. The value of careful inspection of the vulva during routine gynecologic examinations cannot be overstated. Colposcopy has proved quite effective in detecting multifocal lesions because the magnification allows identification of smaller lesions. In the absence of colposcopy, lesions may be accentuated by application of 2% acetic acid to the vulvar skin and inspection with a bright light. Nuclear staining with 1% toluidine blue can be useful, though false negative and false positive rates are high. Vulvar biopsies were accomplished with a Keyes dermatologic punch (4 to 6 mm size) with the patient under local anesthesia. This instrument allows for removal of an adequate tissue sample and orientation for future sectioning. After obtaining the biopsy specimen, we use the Keyes punch to cut out a replica in an absorbable gelatin sponge. This is positioned in the skin defect and kept in place with a small dressing for at least 24 hours. Associated lesions. Thirty-eight percent of the patients had a previous documented history of either cervical or vaginal intraepithelial neoplasia, which points out the multifocal nature of the process. Several of the other patients gave a history of an “abnormal Papanicolaou smear” but no tissue diagnosis was available. Nature of lesions. The lesions presented as papules or macules, coalescent or discrete and multifocal. Lesions on the cutaneous surface of the vulva usually gave the appearance of lichenified or hyperkeratotic plaques, i.e., white epithelium. Lesions on the mucous membranes were usually macular and pink or red in appearance with coarse punctation noted colposcopitally. Six of the patients had what appeared to be hyperpigmented lesions, which ranged in color from mahogany to dark brown, and colposcopically appeared as raised epithelium with a dirty white color. These latter lesions stood out sharply when observed with a good light and all the lesions in those patients (including recurrences) had the pigmented quality. Twenty-five of the patients had detailed drawings of these lesions recorded and a composite is shown in Fig. 1. The highest occurrence of lesions was in the area of the perineal body, with the periclitoral area next and the labia minora third.
Surgical
approach
to multifocal
vulvar
carcinoma
137
Fig. 1. Composite of distribution of lesions in 25 patients suggesting the posterior vulvar and periclitoral areas as having the highest frequency of involvement. Selection of patients for procedure. The major reason for considering skinning vulvectomy and graft iS the importance to the patient of a more normal postoperative functional and cosmetic effect than is possible with a simple vulvectomy or extensive local excisions. These considerations are usually important in the treatment of the younger patient but every patient should be advised of her options. The use of a skin graft, when compared to vulvectomy alone, requires a much longer anesthetic, a second surgical site, 6 to 7 days of bed rest, and roughly a 100% increase in hospital days; this must be considered in the decision process, especially in older women with severe medical problems. All patients must be carefully examined for possible sites of early invasion and extensive biopsies of these areas must be obtained preoperatively to avoid unnecessary preparation of a patient who may not be a candidate for this procedure. Operative technique. The perineum was prepped as was the donor site, which in most cases was the medial aspect of the right thigh. The buttocks area can be and occasionally was utilized as the donor site but there are certain disadvantages to this site. First, the patient will be required to lie in bed for 7 days on this painful operative site and, second, a skin donation from this site requires that the patient be turned while under anesthesia before the vulvectomy itself can begin.
138
Di Saia and Rich
Fig. 2. Line of skin include all recognized mm.
excision lesions
carefully determined so as to with a visible clear margin of 5
An air-driven dermatome is utilized to take the graft at a thickness of i’/i,ooo of an inch. Draping is performed so as to leave the medial aspect of the right thigh exposed for cutting the skin graft. A small amount of mineral oil is applied to the skin as a lubricant after the prep solution is removed with a salinesoaked gauze. A tongue blade is used to apply traction on the skin in front of the moving dermatome. With moderate pressure applied to the area being cut, the dermatome is moved slowly up the thigh, and the desired segment of skin is removed. One can see the skin rolling up on itself as it is fed out the back of the dermatome. When enough skin has been cut, tension is applied to the segment removed and the segment is cut free from the preserved skin by means of a scalpel. The donor site is covered with gauze impregnated with scarlet red dye. It is our feeling that this dye promotes re-epithelialization of the area. An occlusive pressure dressing is applied over the graft site. The area of vulvar skin which is to be removed is outlined with a marking pencil (Fig. 2). These patients have been studied colposcopically prior to the operative procedure and the limits of disease have been carefully determined. The incision is made over the pencil marks. Care should be taken to have the scalpel perpendicular to the surface of the skin when the incision is made; this will prevent cutting the hair follicles on a bias and the resultant postoperative burrowing of hair shafts at the margin of the graft. There is a relatively avascular plane between the
Fig. 3. The epidermis and dermis only are subcutaneous tissue serving as a graft bed.
removed, with the
dermis and the subcutaneous tissue sometimes referred to as the superficial fascia. Development of this plane is considerably facilitated by means of blunt dissection. Utilization of the handle of the scalpel is especially effective. Bleeders are controlled with electrocautery. When the proper surgical plane has been found, a white sheen is noted on the undersurface of the dermis. Sharp and blunt dissection should be utilized alternately throughout the procedure. Traction and countertraction are essential to the proper dissection. The thickness of the skin which is to be removed consists essentially of the epidermis and the dermis only (Fig. 3). All of the subcutaneous tissue should be preserved as a graft bed (Fig. 4.) Preservation of all of the subcutaneous tissue not only promotes graft take but also optimizes the cosmetic and functional results by preserving the soft and pliable nature of the vulva. The clitoris is preserved even when lesions are apparent on the glans. Lesions on the surface of the glans can be shaved with a scalpel blade and re-epithelialization will occur with no loss of sensation. The skin of the prepuce can be removed, if necessary, with the shaft and glans of the clitoris left intact. The posterior dissection is usually left for last because it is the most difficult area in which to establish a good plane of dissection and bleeding is often encountered. The specimen is removed by choosing a line of incision on the mucous membrane of the vestibule. In most instances, the lesions stop at the hymenal ring, which is frequently the inner margin of dissection. Hemostasis
Volume Number
140 2
Surgical
graft bed is primarily adipose tissue and fascia; hemostasis is necessary prior to application of the
approach
to multifocal
vulvar
carcinoma
139
skin graft.
Fig. 5. The skin graft is sutured in place and the graft itself is “pie crusted” to allow serum to diffuse out from beneath the graft.
is established primarily with electrocautery and the driest possible field is selected as a graft bed. Suturing of the graft in place is begun peripherally by means of the standard technique where the needle is passed first into the graft and then through the preserved tissue. A running suture of 4-O polyglycolic acid or PGA-type suture is utilized. These thin grafts are very flexible and can be stretched to accommodate almost any defect. The graft is kept moist during the procedure with the use of saline loaded in a 20 ml syringe with an l&gauge, blunt-nose needle. This will later be utilized to irrigate the graft bed prior to application of the dressing and prevent the accumulation of clot between the graft and the subcutaneous tissue. Excess skin can be trimmed as one proceeds with the suturing. Care should be taken to apply the skin graft to the bed with the proper tension (Fig. 5). Excess tension will allow undue accumulation of serum between the skin graft and the subcutaneous tissue. Insufficient tension will allow wrinkling and redundancy which will not permit optimum skin take. Excess skin graft must be removed in order to achieve this proper tension. The graft is “pie crusted’ to allow escape of serum and prevent undue accumulation beneath the skin graft. During the first 3 to 5 days following the procedure, the skin is nurtured by diffusion of nutrients across a serum clot which develops between the subcutaneous tissue and skin graft. “Pie crusting” allows the distance between the subcutaneous tissue and the skin graft to be kept to a minimum in order to facilitate this process of diffusion.
A foam rubber dressing is next fashioned to the shape of the graft. This l-inch foam rubber serves as the most superficial layer of the pressure dressing applied to this area. Stay sutures are later tied over this piece of foam rubber, thus securing the dressing in place and immobilizing the graft. Placement of the stay sutures, first in the vagina and then on the peripheral skin, is accomplished next. The sutures are tagged with old-fashioned umbilical cord clamps which are color coded in pairs. This permits the final tying of the stay sutures in the proper order. Large portions of skin and vaginal mucous membrane should be taken in the placement of the stay sutures to minimize the probability that one or more sutures will be pulled out in the first 6 postoperative days. A catheter is placed in the bladder since the dressing which is to be applied will not permit voiding. A piece of nonadherent gauze is applied over the skin graft and the area is packed with moist cotton balls. These cotton balls have been soaked in an antibiotic solution which prevents anaerobes from proliferating in the dressing and producing an offensive odor. The moist cotton balls are easily molded into a pressure dressing above the nonadherent gauze. The l-inch piece of foam rubber previously fashioned is then placed over the moistened cotton balls and the stay sutures are tied. Color coding allows the vaginal suture to be identified with its matching peripheral skin suture. It is sometimes necessary to place a few additional sutures in order to fix the foam rubber dressing superior& and iyferiorly Again, generous por-
Fig.
4. The
optimum
140
Di Saia and Rich
Fig. 6. A 2%year-old tions
of skin
and
foam
rubber
are
patient
with
nec~essarv
multiple
to assure
lesions
of the labia
eration
h\ not providin:
CC’IIICI ot the graft;
stability.
posterior Rssults This
method
(#therapy
of’ patient
(Figs.
6 and !)5’%
is usually
period
areas
is complete
to resume the
skin
patients
acceptance
7). A rate
erative
coitus graft
has been and
of skin
obtained
and
quite lack
graf’t in the
satisfactory
of complicatiws take
within has returned
has complained
by
Most
of‘dyspareunia
and. in general, sexual response comparable to that in predisease taken to avoid creating vaginal
None af‘ter
in
of‘ the
6 months,
has been reported as periods. Care must be introital stenosis at op-
7 ;I large enough opening can create 3 tight ring
this and
of’ the
patients
have
developed
of’tidlou~-up
fl-om
I:! to 90 months.
a period
produce
ot the
recurrent
lesions
all ha\.e
been
on the preserved
of.recurrence
I-al areas
are able
sensation
over
areas
denuded
patients
complete 6 months.
85% postop-
of the
4 weeks. and
between
immediate
re-epithelialization in 8 weeks
in
perineum
fourchette
A third
terms and
and posterior-
above, tin
as well our
disease
f~-ee)
skin.
been
tiw
re>u/t.
‘I‘llis
clitoral
recurrences
an impro\ which
been
all of the recurrent possible rc’currcnces
and
presac-
technique
has resulted
and
common
As mentioned
and
ed cosmetic have
None
graf’t
most
perianal hood.
clitoris
understandablv
excision (as have are prepared for
the
skin
The
of the Rutledge
of the glans
recurrence
in the
periclitoral
modilication
presewation
dyspareunia.
has been
have as the
in the at the
calls
its prepuce and
in some
marlaged lesions).
and,
(if
functional with
perilocal
Patients in general.
Volume Number
140 2
Surgical
approach
to multifocal
vulvar
carcinoma
141
Fig. 7. Same patient as in Fig. 6, 12 months after grafting. In many patients the color of the graft remains lighter than the surrounding skin but texture and sensation are undistinguishable from those of o:ginal healthy skin. have been very understanding. One patient developed a keloid in a portion of the donor site but fortunately this appears to be slowly receding. Ten patients had some form of urinary tract infection from the indwelling Foley catheter used with the perineal dressing. In none of the 39 cases was invasive disease discovered in the operative specimen.
Comment Considerable interest in a nonsurgical approach to intraepithelial neoplasia of the vulva was initiated by Klein and associates’ and others8 following their reports of the use of 5-fluorouracil (5-FU) in a variety of cutaneous cancers. Woodruff and colleagues” ran lengthy clinical trials with the use of topical 5-FU cream and initially reported encouraging results. In 1978, Krupp and Bohm”’ reported on a review of 35 cases with an overall success rate of 63%. Buscema and associates” recently reported only three responses in 11
patients treated with topical chemotherapy. Success is obtained primarily in very well-motivated patients since therapy must be continued daily for 6 weeks and all patients experience intense pruritus accompanied by edema and weeping, which often require symptomatic therapy such as topical anesthetics. sitz baths, and analgesics. Very few reports detail the percentage of patients who abandon therapy (because of unacceptable side effects) after less than an adequate trial. Our experience with a limited trial suggests that 75% of patients will discontinue application of the drug after the first 7 to 10 days (far short of the necessary 42-day course). In addition, very few reports have long-term follow-up so that the recurrence rate following 5-FU therapy is unknown and more important the possible long-term effects of the drug itself on vulvar skin needs to be studied. For these reasons, our practice has been to utilize 5-FU cream only in patients who refuse operation and/or have very localized disease; we encour-
142
Di Saia and Rich
age tt~c skinning with
tfit’f’use
those
vutvectomy disease.
patients
1, ith
tot. ;I successfi~t ttw
dit‘fuse
Iargc
skin
general. of
area
graf’t
\ve
disease
completion
cat thei-at’!: great
with
In
have
are
poor
e-week
a
rccfuiring
in patients
elsewhei-e
in
fhund
suspicion
ot‘an
rhar
candictates
cot~rse
vttfvar
of top-
treatment
. etectrocautery.
utiti/ed
trrlsi\e
lor
ttiseasc
;it~.s’~
these sllc-I1
xvith
f~n~iie)
with
approach
or
tof)ical
the
total
rarefy
for
csin
a
responded
(dinitrochtoro‘Trials
01’ a
reporLed
iiot
\lost
authorities
01 the iiosis. bte
tissue
tliseax
optimum
b) the
is cfesirow f’uiictionat
fxiliciit sitler
ac‘ceptancx skin
cisiori,
significanl
had
in fjatients
or t)artiat tcast
toss who
none
of’ sexual ~1s
recfGre
targe
ot‘ our to
thr
paGents ttcvelot)inriir
icat
ex-
have
demonstrated 01 similar
II\
tori
hci-twa\
irris
\\;I\
ot)-
tcsiotis treated
;ii~rl
ivtiictr
of’ttic. with
ix’\ cxfcd cairi-
that such sitllations aiiecdote that t~odof~h~lti~~
tcd
II:I\C Lx11
itI-
f’rom
01 this
srutl?
0~11’
a
t hetic
ot
grouf~
resistance ‘I‘his
grotlt)
of
esf)eciatty “high-risk” recw-rent.
in the
main
and
tasting
the
has been
\ er)
others
skin
grat
t, sug-
within
ttw
skin
taken
rcsislance
in the categor\
or multiorgan
and
t hcsc
fx!cholog-
etrl.ation
mood
disease.
was that
c-onsitfer-abtc
~rottblesonw
removed
deser\w
“higli-risk” f)acould include
observation had
has
and
in thr
implied
a personal
that risk
our
of’ IWW lesions site.
assistance
knowledge greatest
tiave
III
not surprisiiig.
to iiiti.~ief~irliefi~il 101. this f)i-obtciti
wir h diffuse,
fx&nts
\~iitvectonl).
10’4
con~istt~nl
that is similar an eriofogic agent
inherent
In conclusion.
to coiIlocal
t)crinc;it
iiw
fxitieiits.
li~tir
a biops>
observation
an cctopic
patients
pa0111
rcrentty
suspect
serious consideration, tient groufx. This
in this
function.
\Ve spoken
absence an
f’rom
th?
of’ our
the
gesting
;III
M’ith
to
suggestect
1101
ot
In
\xc’I.~’
of no
is
to hc c~cmctytoma:,
prior
sitLL.
4nother
ha\,c
detaifett
clitoris).
has encouraged
grafts
f~i.~ctisf~ositioii
procedure
the
otten
been
recur-
of preserving state.
in
to the
ancf which
suggestive
assumed ttin
Lxma
diag-
~~outct
\+cre
iis<’
fx”iriits.
is apptica-
or widet)
traditionally
lvho
of
accurate
IO f,atieiits.
uas
remowl
report
has diffuse
of ttle Rutledge
has
most
in this
history
in the
patirllrs
the ~oiiitnon
tigfit,jeans,
.-\ previous
vLit\x
for
to ;I strong
otxrabtc 0111
substanw~
antf
from
teatts
routine
to
escef)L
due-e ti.ansfi)rmatioii neoptasia. Iii short,
of \ ut\ar
Surgical
and/or
(fxx~sc~~vation
ticiits
;\t
who
and
treatment
the
vufvectom~
c.o~inetic.
modification rrf)or’
alto~vs
patient
\vhwc
considered
txxc~~
the stqical.
utilized
~IL-LK~~LIIT
IO ttw
011h
that
is basically
in\ otvcd l’hc
ring
agree
in situ
other
tainetf f~odof~ti~
;lLlttl~m.
carcinoma
or
.I‘tiis
carcinogen
as
\\.as noted
iciidergarments
associ-
and
that
cream.
xvei-c
have
regression
torso
S-FL:
vLit\-a
surgery
Kaaf‘
DIV(:B
with
OIL
bitt
refxxt.
the tocccr
sut~f~teinentecf
similar
lesions
case
60 lesionson
to im~nLlnoth~r.af,~
laser
in this
as
a single
rcportett
fxltietlr
vritvar
arid
tract.
as etsewherr.
ctuestionccf
txacrice
(:i~yos~ii~gt.~~
genital
unidentified
as \vett
deodorants
tfisc~omlort.
been
skin
carcf‘ulty
creates
the
arca rcf>tac
f row of
the
skin
.lt
cd in an at’s-
inaiiiicr.
tcsion~
REFERENCES
I. Bowen, J. ‘I-.: Precancerous dermatosis-A study ot two cases of chronic atypical epithelial proliferation, J, Cutan. Dis. 30:241, 1912. 2. Knight, R. V.: Bowen’s disease of the VLIIW. ASI. .J, OBSTET. GYNIXOL. 46:513. 1943. 3. DeLima, 0. A., DeCuarnieri, N. (;.. and DeLima, M. I,. l‘.: Molestia de Bowen da vulva, Rev. Gynecol. Obstet. 47:95, 1953. -1. \Voodruff. J. I).. and Hildebrandt, E:. E:.: Carcinoma iI1 situ of the vuha, Obstet. Gynecol. 12:414, 195X. 5. Hilliard, G. D., Massey, F. M., and Wl‘oole, R. V., .Jr,: \‘ulvar neoplasia in the young. AM. J. OBSTET. GYNECOL.. 135: 1x5, 1979. 6. Rutledge, F., and Sinclair, M.: Treatment of intraepithelial carcinoma of the vulva by skin excision and graft, AM. J. OBSTET. GYNECOL. 102:806, 1968. 7. Klein, E., Helm, F., Milgrom, H.. et al.: Tumors of. the
Discussion DR. WILLIAM day’s f>resentation re&rts bv Brwwn~
E. LUCAS, San bv Dr. and
Diego, Calif’ornia. ToDi Saia underscores the recent associates’ anti Friedrich and
X.
9.
10.
Il.
12.
skin. keratoacanthoma: Local ettecrs 11t i-Huoroul-acil. Skin 1: 153. 1962. Litwin, M. S., Krementx, E. T.. Mansell, P. M’., et al.: Topical chemotherapy of tentigo maligna with 5-Huorou&i1 creme, Cancel’ 35:721, 1975. .’ Woodruff. I. D.. lulian. (1.. Purav, T.. et al.: The contemporary cha&ngeOof. carcinoma in situ of the vulva, AM. J. Ossrw. (;YNECol.. 115:677, 1973. Krupp. P. J., and Bohm, J. \V.: .i-Fluorouracil topical treatment 0K in situ vulvar tanccr, Obstet. Gynecol. 51:702. 197x. Buscema, J., Woodrutt. J. D.. t’armlq, ‘I‘. H.. and Genadry. R.: Carcinoma in situ of the vulva. Obstet. Gynecol. 55:225, 1980. Raaf, J. H.. Krown, S. E., Pinsky, (:. &I., et at.: ~I‘reatment of Bowen’s disease with topical dinitrochloroben/.ene and 5-Huorouracil,~Cancer 37:1633, 1976.
colleagues’ documenting a dramatic apparent increase in the incidence of’ carcinoma in situ of the vulva during the last decade, an experience which we ha\e shared at rhe University of‘ (:afif’ornia. San Diego.
Surgical
\vhere 58 patients with this diagnosis have been treated since 1973. A number of important questions have been raised and none answered as yet. Friedrich and colleagues recently reviewed the possible role of viral infections ot the \,ulva. No clear association can be made at the present time. The relationship of intraepithelial wha cancer to invasive cancer is also unclear. Are we to expect a significant increase in the incidence of invasive vulvar cancer one or two decades from now? This is an important question when one considers that 19 of this series of Z19 patients of Drs. Di Saia and Rich were under age 35 (49%). In San Diego, 30 of our 58 patients (52%‘) were under age 40 when initially treated. bYe agree with the authors that the primary approach should be surgical for the reason that this is the only sure way that the histologic width and depth of the lesion can be defined. Although they have not encountered early invasion among their 39 patients, three of our 5X patients were found to have superficial invasion in the surgical specimen, and Friedrich and associates reported that three of’ his series of 53 patients had superlicial invasion. M’e share Dr. Di Saia’s lack of enthusiasm for topical j-FL. This not only is usually unsuc‘cessful in treating multifi)cal disease but also requires a stoic patient to complete the required course of treatment. We abandoned its use several years ago after a limited trial. We also have some reservations about the use of the carbon dioxide laser for the reasons cited above, principally the lack of histologic control. Careful follow-up of laser-treated patients for at least 5 years will be necessary to establish the effectiveness and safety of this method. The authors have provided us with data documenting their good results with the use of skinning tomy and grafting in 39 patients. At UCSD we have used this approach, with minor technical differences, in 17 of 58 patients, with equally gratifying results. Long-term cosmetic and functional results and patient acceptance have in general been good. The chief disadvantage is the longer period of hospitalization and convalescence required. For this reason we favor wide local excision where possible. in order to take advantage of the ease with which relatively large areas of excision can be closed by mobilizing lateral flaps of skin at the level of Scarpa’s fascia. The depth of excision is exactly the same as described by the authors for skinning vulvectomy. Only epidermis and dermis are removed in a relatively avascular plane. The glans and hood of the clitoris are preserved when possible. Since the cosmetic and functional results with this approach have often been as good as those obtained with grafting, we are now using skin grafts less often than we did 2 or 3 years ago. 1 wonder if the authors may not utilize skin grafts less often as time goes on. ‘I‘he recurrence rate of 39?? reported in this paper is disturbing. Our recurrence rate to date has been less
v&c-
approach
to multifocal
vulvar
carcinoma
143
than 9% (five of 5X), but follow-up has been short in many cases. The need tar meticulous patient education and follow-up is underlined. Contrary to the authors’ experience we have seen one instance of recurrence in a skin-grafted area, approximately 2 years after the original procedure for very extensive multifocal carcinoma in situ. In conclusion, 1 wonder it‘ Dr. Di Saia might care to expand OII his thoughts presented here regarding the rising incidence of carcinoma in situ of the vulva and particularly its relationship to the subsequent development of invasive disease. REFERENCES
1. Buxema, J., Woodruf’t. J. D. Parmley, T. H., and Genadry, R.: Carcinoma in situ of the vulva, Obstet. Gynecol. 55:223. 1980. 2. Friedrich, E. G., Wilkinson, E. J., and Shifer, Y.: Carcinoma in situ of the vulva: A continuing challenge, AM. J. OBSTET.GYNECOL.
136:830,
1980.
DR. ED HILL, San Francisco, California. The problem alluded to by Dr. Di Saia is not indigenous to Southern California. We have noticed the same phenomenon in the Bay area. One of’the problems that we have noted is that these patients frequently come in after treatment for condyloma. I point out that not all that looks like a wart actually is a wart and that some carcinomas in situ bear a superficial resemblance to condylomas. The question is when should a biopsy of lesions which have the appearance of venereal warts be obtained. The tendency of this particular disease to concentrate in the area of the perineum and perineal body as well as the perianal region has also been noted. One of the problems that we have faced is the excision of the perianal lesions and whether or not to perform a temporary, diverting colostomy while the skin graft in the perianal area heals. Also we have had problems of anal strictures in those patients who have had skin grafts in a circumferential manner in the perianal region. One of our patients actually had perianal involvement that extended all the way in the natal cleft back to the area overlying the sacrum. How would you handle this particular problem? DR. IVAN LANGLEY,Portland, Oregon. This is a disease that has been “chased” by many people, including myself, for more than 30 years, each reporting a recurrence rate of about 30%. which is similar to that of Dr. Di Saia. Most of LIS haye not used the colposcopy as a method of observation but have removed only those lesions that were visible by the use of a hand lens; I believe this is a more common method of follow-up. The most common complication reported by the authors was urinary tract infection. I would recommend that they add suprapubic cystotomy to the procedure. This addition would reduce complications and offer the patient less discomfort.
One of‘ the most important things is distinguishing whether or not the lesion is invasive. Allow me to present the following method of’orienting the biopsy specimens. The sitnple cassette that is normally used in the pathology laboratory and the cellulose pads come f’rom the packaging of’cover slips. B! tneans of’s hand lens, the biopsy specimens can be ortented cot-rcctly in theit air-fixed state. The cellulose and tissue biopsy specitnens are processed through the Technicon and are sectioned as one, which results in guaranteed proper sectioning oC the tissue. There is one question that arises. lvhich Dr. L.uc-as alluded to. and that 1 would like to have Dr. Di Saia discuss. In all retrospective studies that I know of concerning carcinoma of’the vulva, one halfof‘the in\asivc lesions occur in patients with diffuse disease and one half’ develop in isolated ulcer l&m. However. with one third recurrent or persistent. there have been no reports of invasion in the treated patient regardless of t‘ollow-up tittte. This is certainly not true of’ the cervix nor is it true of‘ any orher malignancy. This fact leads one to believe rhat there must be something characteristic of’ this disease that is ditterent from others. DR. DAVID FIGGE, Seattle. Washington. One, of course, hesitates to take issue with Dr. Di Saia and his very excellent presentation. I do feel, however, sotnewhat uncomfortable with his suggestion to us that the colposcope is an effective tool to define rhe surgical margins for the resected skin that is to be supplanted by a skin graft. We have also walked down this same pathway and also harbor a good deal of enthusiasm for the colposcope. We have, ho!vever. reluctantly come to the conclusion that the colposcopc, as Dr. Langley suggests. offers very little advantage over the simple hand lens. Indeed, the margins of’ resection, as determined by colposcopy, in our experience bear very little resemblance to the margins of’ the disease in the skirt at hand. Only by exceeding the margins that could be visually determined by at least a 2 cm tnargin can we avoid the problem of’ recurrent carcinoma in situ. I would ask DI-. Di Saia if’ his patterns of‘ recurrence hear any correlation to the presence of disease at the resected margins in his surgical specimens. DR. HAROLD LYONS, Merced. California. It is not often thar otw gets a chance to suggest something ne\\ to this Society. ‘I‘wo years ago, I \\as invited to Las C~IICCS. New Mexico, by a group of’wterinarians to see a new product which they were using on cattle. L!nf’ortunately. .i(/; of’ all the cattle in the Big Sky Country developed carcinoma in situ of the eyelid and of’the eye itself. They have developed. at Alamogordo. what they call a lo\v-current field which heats tissue between the two poles of’ an instrument to approximately 110” (this can be varied), and they have discovered that by raising the temperature of’tissue to 1 IO” for SO seconds these lesions disappeared. All lesions of‘ the eye disappeared after treatment. It is necessary only to place a topical anesthetic on the eyeball to treat these animals.
They have hundreds and hundreds of pictures show ing complete resolution of the lesions. Large numbers of’ these instrumenls have been manutactured, \\,hich are used repeated]\- in the cattle industrv to cut down the incidence of death tram carcinoma of the eJ,e. It \vould be interesting to apply this kind of approach to vulvar lesions, because nothing would be destroyed in the process and evervthing could be observed as healing occurred. DR. DI SAIA (Closing), .I‘he problem of superhc.ial invasion is, of course. something that we have been concerned about for a Iong time. We pertitrm a great man) biopsies in cases where we feel there may be invasion. Fortunately, as has been pointed out by many of the discussants, the association of‘this disease with invasion is low. This disease does not appear to progress to invasive disease either quickly or in a high percentage of’ patients. All of us, however, have had patients with early tnalignancy in a “sea” ot‘ carcinoma in situ. so I know that there is an association. but I have no idea how we WOLI~~ approach the frequency or prevalence of the invasive cotnponent. Wide local excision is, I think. the mainsta\ of treatment, as Dr. Lucas tnentioned. ‘I-he development of’ peripheral skin Haps Mith suturing to the mucous membrane is something that we did try and maybe we should re-try. I have f‘ound that c.osttteTic and f’unctional results f’rom that type of procedure are not as good as with the skin graft. Recurrence lvithitt the graft is a real probletn. I have heard many reports of‘recurrences in the graf’t, !et ebery time that I have investigated said recurrences, and I always ask that a picture be sent, I have noticed that the recurrence is on the edge 01’ the preserved skin and sometimes extends over onto the graft. I haw yet to see anyone with a recurrence in the tniddle of. the skin graf’t, and the theory that topical skin has a resistance is something that I am ver!; interested in and would like to f’ollow through. The rtsing incidence of this disease and its etiology are, of course. beyond me. We did send a questionnaire to all of’ our patients, and about 27 of’ thctn responded. M’e were trying to determine what kinds of’ hygiene, deodorant sprays, and other things may be common among them. In the last 3 to 1 ).eat 5. I have questioned each patient exwtsivcly and can find no consistent topical etiologic agent. The only thing I find consistently is that everyone wears pantyhose and tight jeans and I do not know how IO interpret that tinditig. The herpes\irus has, of’ course, been suggested, and 10 of’ our 39 patients had a history consistent with herpes. Dr. Hill has brought out a very valid point. There is art anecdote in our specialty that podophyllin creates a situation that can be confused with carcinoma in situ or dysplasia of the vulva. I do not think that is true. I think that what happens is that all too many times we innocently treat carcinoma in situ with podophyllin thinking that we are treating condylomas. In this series of :39 patients, five were treated repeatedly with podophyilin
Surgical approach to multifocal vulvar carcinoma
for condylomas, but when the lesions did not go away biopsy was tinally done, they, of course, really had in situ disease. Grafting is difficult in patients with perianal disease. The bulky dressing really helps. All of these patients are given paregoric and Lomotil from Day 1 and we starve them. They do not have a bowel movement for 7 to 8 clays. We take the dressing off and then give them enemas. They tolerate this relatively wel1. I think in this way we have avoided using colostomies in patients who have to have grafting around the anus. Grafting all the way to the sacrum is again difficult, but the long-term result seems to be good and we do not hesitate to graft right around to the sacrum. Dr. Langley pointed out something, as did Dr. Figge, that is quite true. You do not have to use the colposcope. I repeatedly teach that the application of 3% acetic acid and a good light are all you need. It happens that I have a colposcope around all the time and I sort of like to look through it, so I use it. However, I really think that these lesions can be identified without a hand lens if you have a good light and you apply 3% acetic acid. I always take time in the operating room to apply 3% acetic acid so the students can see the dramatic way in which the lesions flare up with this simple procedure. The patterns of recurrence in the cases that we have had have not been correlated with positive margins.
145
That is probably something we should do. As I stated earlier, a lot of our recurrences were disease in the perianal area that we did noi recognize. They were often on skin tags (anal skin tags), and since then we have been more careful. We still prefer to do a local excision around the anus rather than grafting. I think, unless you have confluency, that you should not graft-just do a local excision. As you know, the anal skin is very loose, and you can take a lot of it out. We leave it open, and it heals well. Dr. Lyons’ comment is most interesting. I would wonder about our human use committee if I presented such an experiment to them, but I think it is something that is very interesting and should be looked into. There is something else, of an investigative nature, that is coming on the horizon that may be helpful. This is the use of 13-cis-retinoic acid, a derivative of vitamin A, which, in tissue culture and in animals, seems to have the ability to take neoplastic cells and mature them back to normal cells. It has been used in a few cases of skin cancer, and there is presently an investigation under way with the use of this material topically on dysplasia and carcinoma in situ of the cervix. If this works out well, we may have a way of treating this disease very easily. I might say that the application of 13-cis-retinoic acid is absolutely painless.