Microinvasive carcinoma of the cervix ROBERT JAMES
M. A.
WALTER Mrmphis,
RUCH,
M.D.
PITCOCK, A.
M.D.
RUCH,
JR.,
M.D.
Tennessee
The depth and pattern of invasion were compared in 115 cases of microinvasive carcinoma. The 71 invading I mm. or less were focal (96 per cent) rather than confluent (4 per cent) and were cured by simple hysterectomy (one vaginal vault recurrence). The 44 invading 2 to 5 mm. showed a co@uent pattern in 39 per cent; a need,for treating pelvic lymphatics was demonstrated by one with a positive hypogastric lymph node and by two pelvic recurrences. An additional 26 cases assessed as beyond microinvasive (6 to 10 mm. in depth) included&e of 16 without radical treatment who died from cancer, while all treated radically survived, includingJive with lymphatic involvement.
zation specimen has been the most widely used criterion to indicate therapy. Boyes and associates3 emphasized the microscopic pattern of invasion as a more important criterion than depth. Discrete foci of invasion, regardless of stromal depth, were found to respond in the same way as carcinoma in situ, whereas convergent patterns of invasiveness showed an increased risk of lymphatic involvement. To further evaluate these criteria of invasive depth, invasive pattern, and lymphatic involvement, we have reviewed the experience at Baptist Memorial Hospital, Memphis, Tennessee, from 1953 through 1968.
PAPANICOLAU CERVICOVAGINAL smear screening has made the evaluation of squamous dysplasia a common procedure in gynecologic practice. The curability of carcinoma in situ by simple hysterectomy is well established. Similarly, the need for more radical therapy by irradiation or operation including treatment of pelvic lymph nodes in the presence of invasive carcinoma of the cervix is universally accepted. However, there remains a need for more precise criteria to determine when microscopically invasive carcinoma of the cervix should be treated in the same manner as carcinoma in situ and when the increase in complications which attend radical therapy is justified. Assessment of lymphatic involvement by microinvasive carcinoma has been handicapped by the small number of reported cases in which pelvic lymphadenectomy has been done (without any prior irradiation).’ Pelvic wall recurrences have been uncommon. Discussion of the presence or absence of microscopic involvement of lymphatics usually has been neglected. Microinvasive carcinoma most commonly refers to lesions invading 5.0 mm. or less and, when so defined, has generally been shown to respond in the same manner as carcinoma in situ to simple hysterectomy, with only occasional exceptions.2 Therefore, the depth of invasion determined from the coniFrom
Baptist
Rrcriued,for Revised Accepted
April April
Memorial
Hospital.
publication
January
Methods and material All cases of microinvasive and frankly invasive carcinoma of the cervix were included. Tissue sertions were reviewed and classified as to both depth and pattern of invasiveness without knowledge of the subsequent course of the patient. All cervical conizations were evaluated by serial tissue blocks of the entire specimen. Routine serial microscopic sectioning was not done, although most often more than one section from each block was studied. Measurement of depth was made from the base of the surface epithelium or border of an occupied gland at the apparent source of invasion. Invasion was categorized as 1.O mm. or less, 2.0 to 5.0 mm., and 6.0 to 10.0 mm. A conservative attitude was maintained throughout the pathologic review. On the average, there was a tendency to downgrade the evaluation of the lesion as interpreted by the original pathologists. Florid grandular involvement (Fig. 1) was relegated
13, 1975.
14, 1975. 28, 1975.
Reprint requests: Dr. Robert Memphis, Tennessee 38103.
M. Ruth,
20 S. Dud@,
87
88
Ruth,
Pitcock,
and
Ruth
Fig. 1. Extensive or florid involvement of endocervical pattern may be difficult to differentiate from invasive is tangential to rhe surface but behaves as carcinoma magnification x 14.)
Table
I. Carcinoma
Hospital,
of cervix,
Memphis,
Baptist
Tennessee,
1953
Memorial
carcinoma
to
microinvasive
1’368
No. l)f (‘as5
lesions.
Carcinoma in situ* Stagr I IA Microinvasivet Endorervical IB 6 to 10 mm. Depth undeterminable Stage II Stage III Stage IV
849 368 (56.7%‘) 120 115 5 248 26 222 185 (28.5%) 63 (9.7%) 33 (5.0%)
the
Total
649
Carcinoma
*Ratio 7.4:1. t Prior cinoma.
to
the
invasive of
carcinoma
carcinoma
to review,
in situ
there
category
original mained
of
reviewed.
staging, A
obtained lesions,
to microinvasive
were
in situ.
microinvasive (Table
treatment,
minimum
and
of
a five-year
for all but three of and most were followed
recurrences
after
a follow-up
of
the
microinvasive five
years
may
of
carcinomas course
of
for
provided
in Table
Seventy-one (82
or
trachelectomy,
the
16 years
of
in
situ
re-
vasive
carcinoma
was
involving
and
Two
the
1 .O
treated with with
and
in(o
are
1 .O mm.
OI
imasioll. invasiw
mm.
less.
or
a
lesions Of
1 .O (III.
margin
of
of microin-
coniLation
time. with
these.
hyster-ectom)
a diagnosis
cold-knife
at the returned
and
tumor
by simple
usually
cervix
b)
conization)
‘l‘reatmenc
minimally;
of
at
less).
of
patients
treatment until they
not
treated
(no
microinvasive
had
were
and
rejected
Both were lost advanced carcinoma
parametria.
One
oi
these
not return until Of the remaining
six years after the original diagnosis. 11 patients not treared conservative-
carcinoma
ly,
had
suggest
that
short.)
two
study, 649
there cases
patients
lymphadenectomy
were of
849
invasive
carcinoma developed
radical (nodes
primarily and
hysterectomy negative).
by irradiation operation. Onlv
and or
to did
patients with Stage I at least ten years. (Late
be too
this
cent)
cuff.
treated irradiation carcinoma
per
63; does pencwa-
and
subclassified
penetration
58
III,
of invasive
or
depths
patients
in
invasive
biopsies
cervix
with
mm.
I
IB.
II and
to 5.0
ot
Stage
included
Stage
diagnosis
mm.
all patients
stromal
the
cases
endocervical were
cervical
a biopsy
as Stage
follow-up
further follow-up
to
other
remaining
18.5;
of depth
(1.0
2.0
II,
evaluation only
1 15
lesion The
of
confined
to 253
invasive
IA. Stage
all included
with
deeply
Evaluation
after
vaginal
Results During
Lesions
an
were
follow-up
tion.
were
clinical
included:
accurate
and
addition
Stage
Microinvasion
I). clinical
of
33.
allow
less
of
a visible
cases
IV,
were
In
there
cases
without 120
irradiation
car-
115
Five
Stage
I).
carcinoma,
carcinomas
carcinoma:
Only
(Table
cancer
196 cases of microinvasive
carcinoma
group of 196 after reassessment
Clinical
cases
glands by malignant epithelium is noted. I’his carcinoma, particularly if the plane of section in situ. (Hematoxylin and eosin. Original
with
pelvic-
nine
were
a combination 01x microinvasive
recurred after treatmenl. a 2 cm. nodule in the vaginal
“I‘his patient vault five scars
of
Volume Number
12s I
Microinvasive
Fig. 2. A few discrete tongues of invasive carcinoma are (Hematoxylin and eosin. Original magnification x 100.)
Table
II.
Five-year
survival
of
115
patients
with
microinvasive
Alive without residual cancer
Treatment Invasion of I mm. or less: 71 cases Simple hysterectomy Simple trachelectomy (stump) Radical hysterectomy Irradiation (k operation) No primary treatment
Alive residual
present
in this
carcinoma
with cancer
carcinoma
case without
of the
cervix.
of cervix
89
confluence.
115
cases
Dead without residual calzcer
Dead with residual cancer
Lost to
follow-up
Total
46 6 1 9 0
1 0 0 0 1*
2 1 1 0 -0
0 0 0 0 -1*
51 7 2 9 - 2
Total Invasion of2 to 5 mm: 44 cases Simple hysterectomy Simple trachelectomy (stump) Radical hysterectomy Irradiation (2 operation)
62
2
4
1
71
23t 2 7$ 10
0 0 0 10
0 0 0 -0
0 0 0 0
Total
42
0
0
24 2 7 - 11 44
*Refused further treatment after conization. tone patient with 3 mm. invasion, alive without evidence years. $Invasion of 5 mm.-one positive iliac node (preoperative 5 Invasion of 3 mm.-pelvic wall recurrence. after
a
simple
minimally
hysterectomy.
invading
Of
71
microinvasive
patients
carcinoma,
three Two
(4 per cent) had a confluent pattern of these were treated by conservative
and
one
was
asymptomatic. lymphatic
given
irradiation.
None
of
the
71
All
have
was
found
with
showing
only
five
invasion. operation,
(2 to 5 mm.).
Of 44 patients
to 5 mm. “simple”
stromal invasion, hysterectomy or
26 were tacheletomy.
patients
who
with
presented carcinoma
penetrating
a
treated One confluent 3 mm.
years,
had
lymphatic
years
vault
recurrence
Seven
involvement
in the
vaginal
patients
and died
have
positive confluent
having
2
by either of these type
of
and
not
lymphatics.
Ten
recurrent Eleven
carcinoma. patients
depth
One of
of
intracavitary iliac lymph carcinoma
operation.
radical
One
preoperative
3 mm.
node. 5 mm.
at seven
a recurrence
this
at
cul-de-sac.
hysterectomy these The in the
later, had
and
and
with
was
irradiation,
years
with
had
vault
had
lymphadectomy.
remained to
at five
radium).
involvement.
Microinvasion
microinvasive
of
of recurrence
yet uterus stroma
patient
irradiation
she
with had
a
contained with involved
a
is alive with
pelvic
treated
or
with
no
without
confluent
carcinoma
invading
to a
involving
lymphatic
channels
was
90
Ruth, Pitcock, and Ruth
Fig. 3. A confluent carcinona.
Fig. 4. A poorly magnification
growth
(Hematoxylin
and
defined X 17.)
pattern eosin.
confluent
is present with a relatively Original magnification x 10.)
growth
pattern
treated by intracavitary irradiation followed by a total hysterectomy. Two years later, she developed an 8 cm. recurrence involving the right common and external iliac lymph nodes and later died from cancer. Of these 44 patients with 2 to 5 mm. stromal penetration, 27 (61 per cent) had discrete foci of invasion (Fig. 2). None had involved lymphatics. Confluent lesions (Figs. 3 to 5) were present in 17 patients (39 per cent), and six of these had lymphatic invasion (Fig. 6). Of the patients with confluent lesions, five were treated by simple hysterectomy or trachelectomy with the one vaginal vault recurrence. One of these “cured” patients had lymphatic involvement. Four
lymphadenectomies
were
performed,
and
there
was a positive node in one of these patients. The one patient with pelvic wall recurrence had a confluent pattern and lymphatic involvement. Although she had
is present.
well-defined
(Hematoxylin
nodule
and
of
eosin.
invasive
Original
irradiation and operation, both modalities of treatment were confined to the uterus. Invasion (6 to 10 mm.). Of 248 Stage IB cases, 26 could be assessed as stromal invasion limited to 6 to IO mm. in either a conization or hysterectomy specimen (Table III). Five of 16 (3 1 per cent) treated by simple hysterectomy or trachelectomy died from the disease, whereas all 10 treated by radical therapy (either radical hysterectomy with lymphadenectomy or irradiation therapy with or without subsequent operation) survived at least five years. Evaluation of these 26 as to type of lesion revealed only two with discrete foci. Both of these were free from cancer at 10 years. One of the 10 patients who had confluent lesions but no lymphatic involvement and who were treated by simple hysterectomy C)I trachelectomy died from persistent cancer. Of fi\c
Volume Number
Microinvasive carcinoma of cervix
125
91
1
Fig. 5. Higher power of Fig. 5. (Hematoxylin
Fig. 6. Dilated lymphatic are involved. Original
magnification
Small
and eosin. Original
nests of carcinoma
are noted.
magnification
(Hematoxylin
x250.)
and eosin.
x250.)
patients who were treated conservatively, but who had demonstrable lymphatic involvement, four died from persistent cancer. Those “cured” by radical treatment included nine with confluent lesions, five of whom had involved lymphatics. No positive nodes were found at lymphadenectomy in any of the patients who had lymphatic channels involved with cancer; however, the lymph nodes were not serially sectioned. Complications of treatment. Major complications of treatment in 115 cases with microinvasive carcinoma included two patients treated conservatively who had medical complications resulting in death; one had septic emboli secondary to postoperative throm-
bophlebitis, and the other had a postoperative coronary attack. Autopsies showed no residual carcinoma. The only other major complication was a rectovaginal fistula in a patient treated with intracavitary and external irradiation. This was successfully closed, and she is living and well 12 years later. None of the 26 patients with Stage IB disease invading 6 to 10 mm. had a major complication, 16 having been treated conservatively and 10 radically.
Comment The use of depth of invasiveness as a criterion to evaluate the prognosis of microinvasive carcinoma confirmed that lesions involving 1 mm. or less can be
92
Ruth,
Table
III.
Pitcock,
and
Ruth
Five-year
survival
of 26 patients
Alive without cancer
Treatment Simple
hysterectomy
Discrete foci Confluent Confluent with lymphatics Simple
trachelectomy
Discrete foci Confluent Confluent with lymphatics Radical
hysterectomy
(with
lymphadectomy)
Discrete foci Confluent Confluent with lymphatics Irradiation
( k operation)
Discrete foci Confluent Confluent with lymphatics *Depth undeterminable
with invasive
in remaining
carcinoma
penetrating
Alive with carwr
6 to 10 mm.*
Dead without cancer
Dead with cancer
8 1 6 1 3 0 3 0
0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0
3 0 2 2 0 0 2
7
0
0
0
0 3 4 3 1 1 1
0 0 0 0 0 0 0
0 0 0 0 0 0 0
0 0 0 0 0 0 0
1
222 cases of Stage IB
successfully treated by simple hysterectomy, although advanced disease occurred in two patients who refused treatment after conization, and both eventually died from the disease. One vaginal vault recurrence developed five years after a simple hysterectomy. Vaginal vault recurrences from either carcinoma in situ or microinvasive carcinoma usually represent an inadequate margin of removed vagina. Pretreatment colposcopic study or Schiller’s staining should reduce this small incidence. The remaining 57 patients treated conservatively were cured. Lymphatic involvement was not found in any of the 71 cases. When microinvasion exceeds 1 mm., radical therapy must be considered, as six of the 44 patients with microinvasion of 2 to 5 mm. had lymphatic involvement. One had a positive lymph node in addition to lymphatic involvement. Two others, treated conservatively, had recurrences, one of the vaginal vault seven years postoperatively and the other of the lateral pelvic wall after two years. When invasion reached 6 to 10 mm., the distinct need for radical therapy was proved
since 3 1 per cent of the patients treated conservatively died from cancer. Microscopic patterns of invasion provided the best prognostic correlation in this series. Of the 115 patients with microinvasion, 95 showed a pattern of discrete foci invasion. None of these demonstrated lymphatic, involvement, and all were cured. A pattern of discrete focus of invasion was found in only two of the 26 cases with invasion of 6 to 10 mm., and both patients were cured. By contrast, of the 20 patients with microinvasion who exhibited confluent patterns of invasion, six had lymphatic involvement, one with a positive node, and two had recurrences. A confluent pattern was present in 92 per cent of the 20 cases invading 6 to 10 mm. Complications secondary to radical therapy in 39 patients (29 microinvasive plus 10 invading 6 to 10 mm.) consisted of one rectovaginal fistula. This is in contrast to the 37 per cent complication rate in the series of 27 patients reported by Dilworth and Maxwell.4
REFERENCES 1.
4. Dilworth,
2.
Ruth, R. M.: South. Med. J. 65: 1123, 1970. Savage, E. W.: AM. J. OBSTET. GYNECOL. 113: 708, 1972. 3. Boyes, D. A., Worth, A. J., and Fidles, H. K.: J. Obstet. Gynaecol. Br. Commonw. 77: 769, 1970.
GYNECOL.
E. E., and Maxwell, 84:
83,
1962.
G. E.: AM. J.
OBSTET.