Early squamous cell carcinoma of the uterine cervix

GYNECOLOGIC

6, 5 l-59

ONCOLOGY

Early Squamous

(1978)

Cell Carcinoma

III. Frequency

of Lymph

K.J. First

Department of Obstetrics University of Munich,

In the literature,

the

reported

metastatic case, the trium.

This

involvement of pelvic involved lymph nodes fact

has

therapeutic

March

and School of Midwives, 2, West Germany

IO, 1977

of lymph cases cancer

lymph were

Node Metastases

and Gynecology 8000 Munich

frequency

Cervix

LOHE

Received

is up to 10%. A review of the reported our own definition of early cervical

of the Uterine

node

and our own (early stromal

nodes located

occurs on the

metastases

in early

studies reveals invasion and

in less pelvic

than wall

cervical

cancer

that, according microcarcinoma),

I% of the and never

cases. in the

to

In every parame-

implications.

The majority of authors favoring radical treatment of early cervical cancer usually defend their position with regard to therapy by pointing to the possibility that early cervical cancer may invade or spread to lymph nodes even if the tumor itself has not yet penetrated very deeply [ 1,2, 1 I, 12, 16, 19-21,29,32,33,43,45]. Lymph node metastases thus play an important part within the whole set of problems regarding early cervical cancer. In the present study, we shall make some inquiries into and considerations of the frequency of lymph node metastases occurring in early cervical cancer. 1. PUBLISHED

FREQUENCY

OF LYMPH

NODE

METASTASES

The literature on the subject reveals that most authors agree on the infrequent occurrence of lymph node metastases in early cervical cancer. Reported frequencies range from 0.1 to 10%: up to l%, Braitenberg and Schtiller [6], Kaufmann et al. [28], Fettig [14], Hillemanns [23], Hillemanns and Limburg [24], Ruth [421, Mosler et al. [37], Stark [46], and Friedberg et al. [ 171; up to 2%, Zinser et al. [54], Ober [41], Castano-Almendral and Kaiser [S], and Kaser [27]: up to 3%, Younge and Kevorkian [53], Bajardi [3], and Kolstadt [30]: up to 4%, Belliveau and Grayson [4]; up to 6%, Boutselis et al. [5]; and up to lo%, Levitt and Rubin [33]. 2. LYMPH

NODE METASTASES IN EARLY CERVICAL REPORTED IN THE LITERATURE

CANCER

Adding up published cases of lymph node metastases in early cervical cancer or microcarcinoma (Table l), we find a total of 34 cases. Single case reports with distant tumor metastases were quoted many times and by many authors, thus 51 0090-8258/78/0061-0051$01.00/0 Copyright @ 1978 by Academic Press, Inc. All rights of reproduction in any form reserved.

MC

Small invasive carcinoma MC

WalZ[SI](1%2)

Braitenberg and SchiiUer[6J(l%2) Zinserefal. [54](1963)

I

MC

Lock[34](1%1)

Lange[3llw6o~

o”emin”tefcas of invasive tumor I?arlyca”cer

Fangerand ww

[13]

Invasive carcinana

Type of tumor

Friedell and Graham [ 181 (1959)

Murphy

TABLE

1

8x9~3”~”

12x 10x5nm

(Macroscopic?) thanland

?

7

Macroscopic,about anin+

less

1

Pinkie-nail sized, 3.nun i”fdtrativeca”cer

?

Afewmillinxters i”Wationb”t tide-reaching cancer

Size of tlnnor

step serial sections

?

Serial Sections

?

step serial sections

step serial sections

?

?

Many sections

7

Histologic Wk”P

MC

Ix larger, K&“lanneta/. [81 (1965). 1x borderline

Undefinable

Larger

ES1

hyst. +

AND

md.op.

?

rad. op. + Ini

t Ini.

md. op. t

co”us,abd. ml. op. + Ini. conus, “ag. Kid. op.

? Abd.

?Abd.rad.op.+lni.

?AM.

Biopsy,abd. Ini.

Biopsy, abr. abd. rad. op. + Ini. Biopsy, abd. rad. op. + Ini.

Biopsy,vag. vag. cuff

Diagnosdc procedure and therapy

IN THE LITERATURE MICROCARCINOMA

case

FILED AND

CO”lptiSO” with our definition of ESI-MC

OF MICROCARCINOMA WITH LYMPH NODE METASTASES OUR OWN DEFINITION OF EARLY STROMAL INVASION

Schii!Jer[43](1958)

1

Number of Cases

CASES

Early invasive carcincma Solidcarcinoma

Decker[11](1956)

Lax [32] (1953)

THIRTY-FOUR

In. left

et

Rec. tumorpelvic wall(lni.?), no histology

Pxunetrial side

Lni. iliac

Pelviclni.

Pelvic Ini. metastases

Lni. obturat. periaort.

Conglamof Ini.at the iliac bifurcation Ln. iliac. dextr.

After I year, recurrenttumor, iliac In. metastasis L”. obturat. dextr.

L.ocaliza~io” of lymph node met.as~S

COMPARED

WITH

. .._- .-...- .-.

Died of recurrence

?

After2 years, unremarkable ?

After I year, ““W&G&

Clinical course

. ..-..

[44](1970)

[7](1970)

Ulm [2ll

Sidhuetrrl.

Brandleral.

Fro&sand (1971)

[MI(l%9)

[15](1%9)

Fousheeetal.

Kolstadt

I

[38](1%9)

Musseyerd.

MC

Stage IA

I4

Stage IA

Stage IA

Cancer ti th early invasion

cancer

Microinvasive cancer Microinvasive cancer

I

2

I

I

I

1

Christophersonand Parker [91 (I%9 Enterline [ 12](1%5)

under

5 mm

12mmradially,4mm deeply Upto3mmdeeply=9, uptoSmmdeeply=5

Depth

7

DepthWlde~5lMl, cervixcircumference Depth under5 mm

7 Foursections

stepserial section

step serial Sections

step serial sections ?

Larger, ulm [501 (1972)

Larger

Larger

Biopsy. conus abd. rad. op. + Ini. ?AW.rad.op.+lni.

Abr.,ra?,atxl.rad.op. + lni. ?Abd.rad.op.+Ini.

?Abd.md.op.+lni.

MC?

Larger

?Atd.md.op.+lni.

?Lap.,radiation therapy Conus. x-ray

Larger

Undefinable

ESI?

Metastasesin pelvic Ini.

Ln. obhmtt. sin.

Ln. iliac. comm. dextr. Lni. metastases

Pelvic Ini.

Ln. obturat.

Ln. iliac (histology?)

Pelvic Ini.

After I year unremarkable 7

diedof recurrence

After5 years, unremarkable

AfterSyem, unremarkable Afterllyears, unremarkable

After2.5yeaJx Unremarkable After9years. unremarkable

54

K. J. LOHE

creating the impression that lymph node metastases are not infrequent in early cervical cancer. Critical analysis of the 34 published cases of lymphatic metastases in early cervical cancer shows that the dimensions of 26 of these tumors [6, 7, 18, 21, 30-32, 38, 43, 44, 511 exceeded the limits of early stromal invasion [ES11 and microcarcinoma [MC] as given by us [55]. We regard them as so-called histologically proven carcinomas 1401, at least. Documentation of three other cases of lymph node metastases [ 11, 12, 341 is so poor that no classification can be made. The case reported by Zinser et al. [54] is based exclusively on clinical observations. A pelvic node metastasis was thought to have occurred more than 1 year after treatment but it was not v.erified histologically. Among the four remaining cases of lymph node metastases in early cervical cancer, there are two cases which might still be accepted as microcarcinoma (the second case reported by Walz [5 11 and Foushee et al. 1151) and two other cases which might be classified as early stromal invasion [9, 131. According to Kaufmann et al. [28], the second case published by Walz is at the upper limit of a microcarcinoma. Foushee et al. [15] only mention an infiltration depth of less than 5 mm in their case but fail to report the tumor length and width (cf. the cases of “microcarcinoma with lymph node metastases” published by Froewis and Ulm [21], all of which showed, as Ulm [50] later conceded, tumor lengths of more than 10 mm and therefore are no longer microcarcinomas according to our definition). Of the two cases of early stromal invasion, documentation of the one published by Christopherson and Parker 193is particularly poor. The fact that none of these four patients with lymph node metastases seems to have died of her disease is of particular significance. It is thus clear that, under critical assessment and in the light of our criteria, out of the 34 cases of “microcarcinoma with lymph node metastases” only four cases, at most, may actually be regarded as such. Since most of these cases are probably published in view of their infrequency, one can justly regard the occurrence of remote tumor spread in the case of the early cervical carcinoma defined here as a rarity. 3. PUBLISHED FREQUENCY OF LYMPH NODE METASTASES SURGICALLY TREATED EARLY CERVICAL CANCER LYMPHADENECTOMY

IN CASES WITH

OF

Examining the frequency of histologically proven lymph node metastases in the published cases of early cervical cancer (early stromal invasion and/or microcarcinema) in which surgical treatment included lymphadenectomy (Table 2), we find, after deduction of the three Stage IB cases with lymph node metastases [7, 30, 381, metastatic tumor invasion of the pelvic lymph nodes in 2 of the 605 patients (0.3%). Incidentally, follow-up examination of these two patients did not reveal any recurrence. Of these 605 patients with lymphadenectomy, there are 29 patients with early stromal invasion and 37 patients with microcarcinoma in our own series. None of these cases had shown metastatic lymph node involvement despite a very inten-

Total of all cases [No. (%)I

Held [221 (1961) Way [521 (1964) Coppleson and Reid [IO] (1967) Mussey et al. [381 (1969) Foushee et a/. [I51 (1969) Brand1 et al. [71 (1970) Artner and Holzner 121 (1971) Tscharf [48] (1972) Total [No. (%)I

Mestwerdt and Wespi [361 (1973) Own results Total [No. (%)I

Boutselis et al. [Sl (1971) Own results Total [No. (%)I

-

I (0.6) -

1 (0.2) 2 (0.3)

29 I59 (100) 2 37 39 (100) 34 26 60 52 (+I) 29 68 (+I) 126 I2 407 (loo) 605 (100)

ES1 ES1 MC MC MC ES1 and/or MC ES1 and/or MC ES1 and/or MC ES1 and/or MC ES1 and/or MC ES1 and/or MC ES1 and/or MC ES1 and/or MC ES1 and/or MC

-

-

-

24

ES1

I (+I = IB)

(+I = IB)

(+I = IB)

-

-

After 5 years, unremarkable After I I years, unremarkable After I year, unremarkable -

-

-

After 2.5 years, unremarkable After 5 years, unremarkable -

24 4 49 IO I7 (+ I)

I

ES1 ES1 ES1 ES1 ES1

Clinical course of the patients with lymph node metastases

2

Number of cases with lymph node metastases

HAVING HAD A LYMPHADENECTOMY: OUR OWN SERIES

ES1

CANCER AND FROM

ESIiMC

PATIENTS WITH EARLY CERVICAL PATIENTS FROM THE LITERATURE

605

Number of lymphadenectomies

OF NODAL INVOLVEMENT IN THIS FIGURE INCLUDES

Christopherson and Parker [9] (1964) Ullery et al. [491 (1965) Margulis et al. I351 (1967) Thompson [471 (1968) Ng and Reagan [391 (1969) Kolstadt [303 (1969)

Reference War)

FREQUENCY

56

K. J. LOHE

sive histological examination of an average of I8 pelvic lymph nodes examined per case. A reliable method of microscopic searching for lymph node metastases is the following. The pelvic lymph nodes are removed, placed in different containers according to the anatomical region of origin, and fixed with a modified Bouin solution (Dubosq, Brazil) containing picric acid. After a 24-hr fixation, the lymph nodes are separated from the surrounding fat, numbered, and cut in about l-mmthick slices. After additional fixation in 70% alcohol, the single slices are embedded in paraffin and closely packed together one to another. From each paraffin block, four stepwise serial sections with an interval of 200 pm are prepared. If no metastasis is found, the entire block is cut in the same manner. The reliability of the described histological procedure was demonstrated by Huhn in 1964 [26]. By using the same method on 172 surgical specimens with cervical carcinoma, Huhn found pelvic lymph node metastases in 36% (including tumor cell emboli, which are small tumor cell foci not anchored to the lymph sinus wall) and glandular epithelial inclusions in 43% of all cases: Both figures are high and thus most unusual when compared to the published data up to that time. Although in 24 cases of microcarcinoma Huhn found no metastatic seeding in lymph nodes, he stressed the possibility, no matter how small, of such an event occurring in this form of neoplasia. Even the discovery of tumor metastases, as we know today, does not necessarily mean the death of the patient. In about 50% of women suffering from cervical cancer with histologically proven lymph node metastases, a S-year survival rate is obtained without further treatment [ 171. The localization of the lymph node metastases reported in the literature on early cervical cancer is very important from a therapeutic viewpoint. After a thorough study of each published case of metastatic invasion of the regional lymph nodes, we can say that in all these cases only lymph nodes of the pelvic wall were involved metastatically. The literature discloses not a single case in which early cervical cancer was accompanied by metastatic invasion of the parametrial lymph nodes. 4. CONCLUSIONS

Our own results and the data of the literature show that metastatic involvement of the regional lymph nodes in early cervical cancer as defined by us is the exception, indeed, and is observed in less than 1% of the patients. This fact is of paramount significance from a therapeutic point of view. If nodal dissection is indicated, extirpation of the pelvic wall lymph nodes will suffice and need not include removal of the parametrial tissues. In this way, the intraoperative preparation of the ureter can be avoided in each case and the high number of severe postoperative complications such as ureter fistula can be reduced to a minimum. ACKNOWLEDGMENT For help with the English language, I thank Dr. A. P. Anzil, Munich.

LYMPH

NODE

METASTASES

IN

EARLY

CERVICAL

57

CARCINOMA

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(1%9).

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(1964).

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58

K. J.

LOHE

27. Kaser, 0. Die formale und klinische Problematik des beginnenden Cervixcarcinoms, in Rundtischgesprach zum IV. Hauptthema, Arch. Gyniikol. 207, 353 (1969). 28. Kaufmann, C., Ober, K. G., and Huhn, F. 0. Das beginnende Karzinom der Cervix uteri (sog. Mikrokarzinom). Ein Erfahrungsbericht zur Prognose und Therapie an Hand von 130 Beobachtungen, Geburfsh. Frauenheilk. 25, I 12- 13 1 (1965). 29. Kirkland, J. A. The cytological and histological diagnosis of dysplasia, carcinoma in situand early invasive carcinoma of the cervix, Aust. N. 2. J. Obstet. Gynaecol. 6, 15-19 (1%6). 30. Kolstadt, P. Carcinoma of the cervix stage IA. Diagnosis and treatment, Amer. .I. Obstet. Gynecol. 104, 1015-1022 (1969). 3 I. Lange, P. Part II. Pelvic node metastasis in early cancer of the cervix, in Clinical and histological studies lymph

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in the

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47. Thompson, W. R. Microinvasive carcinoma of the uterine cervix, J. Arkansas Med. Sot. 65, 139-144 (1968). 48. Tscharf, H. Zur Behandlung der Friihstadien des Zervixkarzinoms, Arztl. pray. 24, 4608 (1972). 49. Ullery, J. C., Boutselis, J. G., and Botschner, A. C. Microinvasive carcinoma of the cervix, Obstet. Gynecol. 26, 866-875 (1965). 50. Ulm, R. Kollum-Ca: Lymphknoten mitentfernen, Med. Tribune Kongressber. 7, I (1972). 5 1. Walz, W. Symposium on cervical lesions: May one treat the “early invasive carcinoma (microcarcinema)” less radically than the more extensive invasive carcinoma?, Acta Cytol. 6, 176 (1%2). 52. Way, S. Microinvasive carcinoma of the cervix, Acta Cytol. 8, 14-15 (1964). 53. Younge, P. A., and Kevorkian, A. Y. Carcinoma in situ of the cervix. The problems of detection

LYMPH

NODE

METASTASES

IN

EARLY

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CARCINOMA

59

and evaluation in regard to therapy, in CZBA Foundation Study Group No. 3, Cancer of the Cervix. .Diagnosis of early forms, London, pp. 83-96 (1959). 54. Zinser, H. K., Meissner, H., and Biitzelen, H. P. Diagnostische und therapeutische Betrachtungen an 403 Friihfkillen, Geburtsh. Frauenheilk. 23, 321-342 (1963). 55. Lohe, K. J. Early squamous cell carcinoma of the uterine cervix. I. Definition and histology, Gynecol. Oncol. 6, lo-30 (1978).