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.

Microinvasive carcinoma of the cervix.

The depth and pattern of invasion were compared in 115 cases of microinvasive carcinoma. The 71 invading 1 mm. or less were focal (96 per cent) rather...
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