Mixed heterologous mesenchymal sarcomas (mixed mesodermal sarcomas) of the uterus

Mixed heterologous mesenchymal sarcomas (mixed mesodermal sarcomas) of the uterus Addition of 7 cases

DAVID L. EDWARDS, M.D. LEHMANN. STERLING, M.D.* RICHARD H. KELLER, M.D.* JAMES F. NOLAN, M.D. Los Angeles, California

6 of the total group of 10 patients with intra- and parauterine tumors having been seen during 1959 and 1960.

A R E v 1 E w of the clinical experience with mixed heterologous mesenchymal sarcomas (mixed mesodermal sarcomas) of the uterus, treated at the Los Angeles Tumor Institute and the California Hospital between the years 1950 and 1961, includes 7 proved intrauterine cases. Three additional cases were encountered in which the exact site of origin was not established, but the main masses of tumor were in parauterine locations involving principally the salpinx and broad ligament, with direct extension of the tumor to involve the outer portions of the uterus. These 3 cases undoubtedly are derived from the same type of tissue (presumably Mullerian) as the more prevalent intrauterine types which make up the principal subject of this paper. For this reason they will be mentioned in conjunction with the 7 tumors of established intrauterine origin. In 194-l, Lebowich and Ehrlich 1 " stated that the rare occurrence of this unusually malignant tumor made it the obligation of all physicians to report their experience. This review was stimulated by the recent increase in incidence noted at the Los Angeles Tumor Institute and the California Hospital, with

Classification

It is not the object of this re{Xlrt to enter into the current dispute regarding pathologic classification of these tumors. 8 • 14 • 18 · 't'. ~~ In reviewing the current literature and pathologic discussions of the previously reported 234 cases, it became apparent that the classification of this group of neoplasms has not met universal acceptance. We have found the classification championed by Ober's, '" useful and comprehensive and haw employed it as a frame of reference in this study. Ober 1 u uses the term "mesenchymal sarcoma of the uterus" to include the tumors featuring malignant mesenchymal tissue (leiomyosarcomas omitted). He thus includes under mesenchymal sarcomas not only the mixed mesodermal sarcomas (which fom1 the subject of this report) but also endometrial stromal sarcomas, carcinosarcomas, rhabdomyosarcomas, and other related tumors. He divides the mesenchymal sarcomas into pure and mixed types depending upon, respectively, the absence or presence of more than one malignant cell type. Each of the above two groups is further subdivided into homologous or heterologous

From the Los Angeles Tumor Institute and the California Hospital. *Present address: Salt Lake County General Hospital. Salt Lake City, Utah.

1002

Volume 85 Number 8

categories with respect to whether the sarcomatous component consists of clements entirely indigenous to the uterus, (i.e., endometrial stroma) or foreign to the uterus (e.g., striated muscle, cartilage, etc.) . Schematically, his classification of mesenchymal sarcomas is presented in Table I, with synonyms and examples of each category in parentheses. This paper, then, is concerned principally with mixed heterologous mesenchymal sarcomas (mixed mesodermal sarcomas), and the other groups will be mentioned only in passing. In adapting to this classification, the most serious histopathologic difficulty encountered was the identification of the presence of heterologous sarcomatous elements. In order to qualify as being of cartilaginous derivation, definite lacunae containing chondroblasts or chondrocytes set in a characteristic hyaline cartilaginous matrix were required. Cross striations were not always a sine qua non for labeling a sa:r;comatous cell a rhabdomyoblast since their demonstration with utmost certainty was often a matter of extreme difficulty. Occasionally the identification of tissue as being of striated muscle origin rested on the presence of numerous pleomorphic cells with abundant eosinophilic cytoplasm having a "strap" or "tadpole" shape. In an effort to assure some conformity of classification in this regard, microscopic sections from several representative problem cases were sent to Dr. William B. Ober of the Knickerbocker Hospital in New York City, who was, in essence, in agreement with our histologic interpretation and classification.20

Mixed heterologous mesenchymal sarcomas

l 003

Table I. Classification of mesenchymal sarcomas of the uterus Pure homologous (endometrial stromal sarcoma and endolymphatic stromal myosis) Pure heterologous (rhabdomyosarcoma, osteosarcoma, and chondrosarcoma) Mixed homologous (carcinosarcoma) Mixed heterologous (mixed mesodermal sarcoma)

Similarly, microsections and pathologic protocols of all other available uterine sarcomas from the two institutions during the same time period were reviewed. In the study group of 7 patients (mixed heterologous intrauterine sarcomas), 3 underw·ent total hysterectomy and presented predominantly intracavitary tumor masses between 3.5 and 11 em. in diameter. These were friable, mottled yellow to gray-red or pink, often glistening to granular, with areas of yellow necrosis and red hemorrhage (Fig. 1) . The diagnoses in the other 4 patients with intrauterine malignancies rested on the examination of uterine curettings of similar tumor tissue. The 3 subjects with parauterine mixed heterologous sarcoma presented extra-

Pathology

The pathologic evaluation of this series consisted of a review of the gross and microscopic protocols and hematoxylin and eosinstained microsections of all mesenchymal sarcomas from the Los Angeles Tumor Institute and the California Hospital during the time period in question. Where available, sections of these tumors stained with phosphotungstic acid and hematoxylin were also examined.

Fig. 1. Patient M. B. Gross photograph of an opened uterus containing intrauterine mixed heterologous mesenchymal sarcoma.

1004

Aptil 15, 1963 Am. J. Obst. & Gyn.,c.

Edwards et al.

Fig. 2. Patient M. B. Photomicrograph of a mixed heterologous mesenchymal uterine sarcoma showing malignant cartilage and epithelium. (Hematoxylin and eosin. x125.)

uterine masses from 9 to 37 em. in size, which were similar grossly to their intrauterine counterparts. All but I of these patients showed tumor at the resected margin or tumor beyond the surgical field at the time of the initial operation. Microscopically, all of the mixed heterologous tumors combined intimate admixtures of malignant glandular epithelium ( carcinoma) with malignant stromal tissue (sarcoma) (Figs. 5 and 6), which was differentiated to fom1 recognizable tissue foreign to the uterus, rhabdomyosarcoma in 5 instances (Figs. 3 and 8), and chondrosarcoma in 3 instances (Figs. 2, 4, and 7) . In a11 of the tumors the stromal elements predominated. All showed microscopic vein and lymphatic invasion. Histologic sections were aYailahle of metastatic lesions in 4 of the 7 cases at some stage of the disease. Two of these metastatic foci contained only the sarcomatous elements, 1 showed only carcinomatous tissues, and the last had a mixture of hoth epithelial and stromal components. Incidence

Fig. 3. Patient E. B. Photomicrograph of a mixed heterologous mesenchymal uterine sarcoma showing striated muscle cells. (Phosphotungstic acid and hematoxylin. x850. \

The incidence of various malignancies of the uterus seen during the past 12 year period is summarized in Table II. The proportions of the different tumor types in the uterine mesenchymal sarcoma group are not at great variance with those found by Ober. 18 An index of the disproportionately high incidence of the mesenchymal sarcomas as a whole in this series is seen in the fact that they total almost two thirds of the number of leiomyosarcomas of the myometrium. During the 12 year period, 4 75 patients with carcinoma of the uterine corpus were treated at the Los Angeles Tumor Institute and the California Hospital. This is an incidence of 6 per cent of all malignancies found in women. The incidence of mixed heterologous mesenchymal sarcomas during the same period was L47 per cent that of adenocarcinoma of the uterine corpus. Accordingly, this represents 0.088 per cent of all malignancies in women. Symmonds and Dockerty27 reported an incidence of 0. 7 per cent

Volume 85 Number 8

of mixed mesodermal sarcomas when compared to endometrial carcinomas. Of interest is the fact that the incidence of mixed heterologous mesenchymal sarcoma alone at these institutes is approximately equal to the incidence of all such sarcomas reported by 8 other authors.4, 9, H, 11, 21, z4, zs, 2s Comparison of the incidence of this tumor presents a difficult problem. For example, Sternberg, Clark, and Smith26 reported that 0.8 per cent of 26,114 gynecologic admissions presented with the tumor in question. The difficulty arose from the fact that an extremely high percentage of the patients seen by the members of the Los Angeles Tumor Institute have been referred because of a suspicion of malignancy. Therefore, the high incidence noted here is not ~f significance when applied to a cross section of the female population. An attempt has been made to bring the total number of reported cases of mixed mesodermal sarcoma up to date. This has proved to be a difficult task since the classification of these tumors has been so variable. Many authors do not specify the exact histologic findings or the criteria by which they accept or exclude cases under the heading of mixed mesodermal sarcoma. In some series a few of the cases show no definite heterologous components and would appear to be carcinosarcomas (mixed homologous mesenchymal sarcomas) .26 The series of Marcella and Cromer15 includes one extrauterine case in the tabulation. In view of the lack of uniformity of classification in previous reports, any tabulation of the total number of cases in the literature to date must be viewed as a rough approximation. If one accepts, with the above reservations, the tabulations of Glass and Goldsmith 5 of 94 cases, of Hardy and Moragnes6 of 22 additional cases, and the addition of 118 cases by Marcella and Cromer/ 5 the total in 1959 stood at 234. Since then 61 instances of mixed heterologous mesenchymal sarcoma~ have been added to the literature (as listed in Table III) to bring the approximate total to 295, including the 7 intrauterine cases presented in this paper.

Mixed heterologous mesenchymal sarcomas 1005

Fig. 4. Patient A. M. Photomicrograph of mixed heterologous mesenchymal uterine sarcoma showing malignant cartilage and epithelium. ( Hematoxylin and eosin. x125.)

Fig. 5. Patient J. U. Photomicrograph of a mixed heterologous mesenchymal uterine sarcoma showing malignant glands and stroma with some cells resembling rhabdomyoblasts ( 7 year survival). (Hematoxylin and eosin. x125.)

1006 Edwards et al.

. \m.

Table II. Incidence of patients with malignancies of the uterine corpus at the Los Angeles Tumor Institute and the California Hospital ( 1950 through 1961 ) Carcinoma of the uterine corpus Leiomyosarcoma of the uterus Mesenchymal sarcoma of the uterus Pure homologous (endometrial stromal sarcoma) Pure heterologous (rhabdomyosarcoma) Mixed homologous (carcinosarcoma) Mixed heterologous (mixed mesodermal sarcoma) Mesenchymal sarcoma of the paraut(·rine tissues Mixrd sarcoma

4 75

:w

13 ~

3 1

7 3

Table III. Uterine mixed mesodermal sarcomas reported in the literature Author

Hardy and Moragnes 6 Corscaden and Singh" Marcella and Cromert5 Laurainc and Monroe 11 Ober and Tove!lts Carter and McDona!dl Radman and Korman~ 1 Krupp ct aJ.to Our series

---------·-

Cases

Year

116 (rrview) 4 118 (review) 1 II 6

1952 1958 1959 1959

:.!

30

7 295

1959 \960 1960 1961 1962

Clinical data

The clinical histories and physical findings of the cases reported showed no significant variance from those previously reported. 2 • 5 • 18 26 7 • • " All 7 of the patients were Caucasian. The average age of the 7 with intrauterine mixed heterologous mesenchymal sarcoma was 62 years, the range being from 48 to 77 years. All the women were in the postmenopausal period. The most prominent presenting complaint was painless vaginal bleeding, which varied from spotting to what was recalled by the patient as usual for menstrual flow; 6 of the patients presented with this complaint. In 6 subjects the interval from the onset of bleeding until medical care was sought was less than 6 weeks. Only 3 of the 7 patients had borne 1 or more children. Five individuals had had at least one misrarriagc. and 2 were nulligravid.

J.

. \p1 ;; r·,. 1~ttl Obst. & Gy!u'<:.

Two patients (E. B. and A. M.) receive<.! prior irradiation for carcinoma of the et'rvix in sufficient quantity to control the lesions for 6 and 10 years, respectively. with no evidence of recurrence. It is of interest that in some reports/• ' 3 • 27 a moderately high number had undergone prior irradiation to the pelvis, often antedating the development of the mesenchymal sarcomas by many years. Krupp and co-workers, 10 on the other hand, had no subjects with histories of prior pelvic irradiation in a total series of 51 cases. Geiger, in a discussion of Krupp's paper,'" tabulates a list of case reports in which 17 of 56 patients (32.9 per cent\ underwent previous pdvic irradiation. The incidence of 2 out of 7 cases (28.7 per cent! in the currPnt rt>port is in kPeping- with tht· tigun: gin:n by Geiger 1" and would support the view that prior irradiation may he important in the pathogenesis of some of these tumors. Therapy

Therapy for this group of patients was highly individualized with all modes of treatment available being utilized in one instance or another. Table IV presents a detailed account of modes and results of treatment received by the patients with mixed hett'rologous tumor and a summary of the trt>atment and f'nd n·sults of the other gToups of mesenchymal sarcomas for comparison. The tabulation shows that, when possible, a total abdominal hysterectomy and salpingo-oophorectomy coupled with node dissection was employed. In addition, 2 mev. external xirradiation, cobalt6 " gamma irradiation externally. radium implantation, isotope perfusion, and chemotherapy, were utilized. Among the total of 10 intra- and para uterine mixed heterologous tumors, the chemotherapt:utic agents used include nitrogen mustard on 3 occasions, and cyclophosphamide and 5-fluorouracil each on 1 occasion. These therapeutic agents have been used in Yaried combinations with substantially no alteration in the patient's rapidly fatal course. Radiation as a mode of therapy has proved disappointing. 14 • ~ 7 The experience in this sf'rif's parallels that in previous reports with

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Mixed heterologous mesenchymal sarcomas l 007

regression of the size of the tumor being minimal or absent except in 1 patient (L. K.) who survived 12 years after intracavitary radium followed by hysterectomy. This experience includes all modes of radiation: high voltage x-rays, cobalt60 , radium, and isotopes. Although no conclusions can be drawn from this small series, the chemical agents have been disappointing, with no marked regression of the tumor size noted, and limited palliation achieved. Emphasis by McElin and Davis 13 is on early surgical intervention of radical nature if any reasonable result is to be obtained. Results

Fig. 6. Patient L. K. Photomicrograph of a mixed heterologous mesenchymal uterine sarcoma, showing malignant stroma and glands ( 12 year survival). (Hematoxylin and eosin. X125.)

Fig. 7. Patient L. K. Photomicrograph of a mixed heterologous mesenchymal uterine sarcoma showing malignant chondroid tissue. (Same case as Figs. 6 and 8). (Hematoxylin and eosin. X250.)

Metastases from these tumors occur early, are frequently distant, and may develop by direct extension, lymphogenous, and hematogenous spread. Eight of the total of 10 mixed heterologous tumors demonstrated local recurrences following operation. Widespread metastases were present in most of the patients during their terminal courses, with

Fig. 8. Patient L. K. Photomicrograph of a mixed heterologous mesenchymal uterine sarcoma showing malignant muscle cell with cross striations. (Hematoxylin and eosin. Xl250.)

1008 Edwards et al.

April l:i, l96:l

Am .

prominent involvement of the liver either clinically or at autopsy. Unusual sites of metastases encountered in these subjects include a metastasis to a parotid in one case

.f. Obst. & Gyncc.

(E. M.), and an expansile lesion to the tenth dorsal vertebra ( M. B.) . The prognosis is extremely poor (Table IV) with death ensuing in a short time.

Table IV. Modalities and results of therapy of uterine and parauterine mesenchymal sarcomas Patient

Year I II Age I diagnosed

Pure homologous A.L. 46 1955

Prior treatment

None

1961

None

Pure heterologous M.B. 1951 71

None

E.W.

76

v.c.

56

1955

None

M.J.

71

1956

None

Mixed homologous E.G. 1961 61

None

Hysterectomy and bilateral salpingo-oophorectomy Hysterectomy and bilateral salpingo-oophorectomy Hysterectomy and bilateral salpingo-oophorectomy

E. B.

67

1950

u.

54

1954

Radiation treatment for carcinoma of the cervix 6 years None

A. S.

57

1956

None

J.M.

71

1959

None

A.M.

48

1960

M.B.

77

1960

Radiation treatment for carcinoma of the cervix 10 years None

Mixed heterologous, parauterine E. M. 46 1959 None

T.W.

39

1960

None

E. C.

54

1960

None

·-----~·-~·-----·--·"--·-

E.:o;ternal radiation

Hysterectomy and bilateral salpingo-oophorectomy Hysterectomy and bilateral salpingo-oophorectomy

Mixed heterologous, intrauterine L.K. None 1950 60

J.

0 peration

None None

None None 2 mev., 4,590 rads, 46 days

Hysterectomy and bilateral salpingo-oophorectomy

2 mev., 4,420 rads, 43

Hysterectomy and bilateral salpingo-oophorectomy (elsewhere) Hysterectomy and bilateral salpingo-oophorectomy

None

Subtotal hysterectomy, 2 months Exploratory laparotomy and biopsy Exploratory laparotomy and biopsy Exploratory laparotomy and biopsy Hysterectomy and bilateral salpingo-oophorectomy

days

None 2 mev., 4,029 rads, 41 days

Couo, 3,040 rads, 27 days Co Go, 1,500 rads, 21 days 2 mev., 6,032 rads, 54 days

Hysterectomy and bilateral sal pingo-oophorectomy

Pelvis, 250 kv., 1,500 rads, 14 days Spine, 2 me\' .. 800 rads, 7 days

Hysterectomy and bilateral salpingo-oophorectomy (elsewhere)

3 abdominal ports: Co6o, 3,980 rads, days Co6o, 2,016 rads, days Co6o, 3,003 rads, days 2 me\'., 4,080 rads, days

Hysterectomy and bilateral salpingo-oophorectomy (elsewhere) Exploratory laparotomy and biopsy (elsewhere) ··-----.-"~-··~~--·

20 16 20 41

2 mev .. 't.200 rads, 42 days

····-.-······-·-~·-···~

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Mixed heterologous mesenchymal sarcomas 1009

diagnosis, and will be discussed in detail below. The average duration of life following diagnosis in this group, excluding the 2 long-term survivors, is 4.8 months, the

Five of the 7 patients with intrauterine mixed heterologous sarcoma died of the disease. Two of the 7 (28.6 per cent) remain alive at present, 7 years and 12 years after

Isotopes

Intrauterine radium

Chemotherapy

Clinical status

None

None

None

Living and well, 7 years

None

None

None

Living and well, 6 months

None

None

None

Dead, 10 months

None

None

None

Dead, 12 months

None

None

HN,

Dead, 11 months

Yes

None

None

Dead, 5 months

1,500 mg. hr.

None

None

Living and well, 12 years

None

None

None

Dead, 4 months

2,250 mg. hr.

Aul98, 100 p.c hypogastric perfusion

HN,

Living and well, 7 years

None

paz, intravenously, 3.02

HN,, 10 mg. hypogastric perfusion None

Dead, 2 months

None

Dead, 5 months

p.c

2,175 mg. hr.

Au 198, 180 p.c hypogastric perfusion None

None

None

Cyclophosphamide

Dead, 8 months

None

None

HN,

Dead, 12 months

None

None

None

Dead, 8 months

None

None

5-fluorouracil

Dead, 3 months

2,250 mg. hr.

Dead, 5 months

1010

Edwards et al.

range being from 2 to 8 months. All 3 of the subjects with parautcrine mixed heterologous sarcoma died within 1 year of the diagnosis. Thus, the figure of 90 per cent mortality within the first 2 years following diagnosis receives some support."· 10 • 27 In passing, the end results of treatment in the other groups of mesenchymal sarcomas (Table IV) are in keeping with those reported by Ober/ 8 and they bear out the impression that the pure homologous tumors behave much more favorably than the other mesenchymal sarcomas. Both of the patients with pure homologous tumors survived 6 months to 7 years after treatment, as opposed to death of 3 who had pure heterologous tumors and 1 with mixed homologous sarcoma within 1 year of diagnosis. The 2 surviving patients with mixed heterologous mesenchymal sarcoma are presented in detail. Case I. J. U., a 54-year-old white woman originally seen in 1954 following a subtotal hysterectomy performed prior to referral remains alive in 1961 with no evidence of recurrent disease. Two months following the subtotal hysterectomy a mass was noted to have developed in the left parametrial area. She was referred to the Los Angeles Tumor Institute, and an exploratory laparotomy revealed recurrence of the tumor in the left parametrium (Fig. 5). Perfusion of the area by means of colloidal gold (Au 198 ) in the left hypogastric artery was performed. This was followed by 2,250 mg. hours of radium administered as 75 mg. in 30 hours. An additional 4,209 r tumor dose was given by 2 mev. external x-irradiation followed by a course of nitrogen mustard. This is felt to represent vigorous therapy. Case 2. L. K., a 60-ycar-old white woman, was seen in 1950 with a 6 weeks' history of postmenopausal bleeding. Uterine curettage disclosed the presence of mixed heterologous mesenchymal sarcoma with an admixture of malignant glands and stroma in which rare malignant stromal cells contained definite cross striations (Figs. 6, 7, and 8) . She received a total of 1,500 mg. hr. of intrauterine radium. Four weeks later she underwent hysterectomy and salpingo-oophorectomy at the Cedars of Lebanon Hospital, Los Angeles. with residual tumor present in the hysterectomy specimen. She remains alive and without evi-

:\m,

April I'!, 196:1 & Gyncc.

J. Ob'L

dence of disease in 1962, 12 years original treatment.

;dt•~r

the

These cases are reported in this detail to add to the previously reported group of 12 patients surviving for 5 or more years. 1 • ~. 1 "· 13 18 27 • • This increases the collection of longterm survivors to 14. Analysis of the therapeutic agents used in these 14 subjects fails to offer any suggestion to aid in selecting a definitive approach to the problem of management. McElin and Davis 13 stress the use of the most vigorous approach available. With the limited information reported for analysis, the suggestion of these authors appears the most logical approach. With added case reports and additional cures, a more definitive course of management may eventually be developed. Summary

1. Seven cases of mixed heterologous mesenchymal sarcomas (mixed mesodermal sarcomas) of the uterus are presented covering the years 1950 through 1961, inclusively. 2. Sixty-one cases are added from the literature bringing the reported total to approximately 295. 3. Two of the 7 patients with intrauterine mixed heterologous mesenchymal sarcomas received irradiation to the cervix for carcinoma 6 and 10 years prior to the development of the mesenchymal sarcomas. 4. The factor of early diagnosis plays no significant role in the prognosis of the series here reviewed. Six of the 7 subjects had a definite diagnosis within 6 weeks following onset of symptoms. Five of the 7 patients died within 1 year. 5. Two long-term survivals ( 7 and 12 years) are presented in some detail. The reported number now totals 14. 6. Four patients received chemotherapy with no significant regression of the tumor and only limited palliation. One patient received chemotherapy in conjunction with all other modalities of therapy and remains alive and well. We wish to thank Dr. William B. Ober, of the Knickerbocker Hospital, New York, New York,

Volume 85 Number 8

for his assistance in reviewing selected microsec· tions and for his helpful suggestions with reference to classification of these tumors. We also wish to thank the following physicians for mak· ing available for review material pertaining to the respective patients: Dr. C. F. Baisinger, of San Bernardino, California (E. M.); Dr. Charles J. Wrobel, of the Viewpark Community Hos-

Mixed heterologous mesenchymal sarcomas 1011

pita!, Los Angeles, California ( T. W.); Dr. Gil· bert D. Curtis, of Behrens Memorial Hospital, Glendale, California (E. C.); and Dr. Nathan B. Friedman, of the Cedars of Lebanon Hospital, Los Angeles, California ( L. K.). The photomicrographs were taken by Mr. I. Lloyd Matlovsky, of the Los Angeles County General Hospital.

REFERENCES

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14. McFarland, K. T.: AM. J. 0BST. & GYNEC. 59: 1304, 1950. 15. Marcella, L. C., and Cromer, J. K.: AM. J. 0BsT. & GYNEC. 77: 275, 1959. 16. Nolan, J. F., and Harrison, L. A.: Obst. & Gynec. 17: 601, 1961. 17. Novak, E., and Anderson, D. F · AM. J. 0BsT. & GYNEC. 34: 740, 1937. 18. Ober, W. B., and Tovell, H. M. M.: AM. J. 0BST. & GYNEC. 77: 246, 1959. 19. Ober, W. B.: Ann. New York Acad. Sc. 75: 568, 1959. 20. Ober, W. B.: Personal communication. 21. Radman, H. M., and Korman, W.: AM. J. 0BST. & GYNEC. 80: 1115, 1960. 22. Randall, C. L.: AM. J. OBsT. & GvNEC. 45: 445, 1943. 23. Rubin, A.: AM. J. 0BST. & GYNEC. 77: 269, 1959. 24. Searight, F.: South M. J. 34: 326, 1941. 25. Smith, F. R.: New York J. Med. 41: 681, 1941. 26. Sternberg, W. H., Clark, W. H., and Smith, R. C.: Cancer 7: 704, 1954. 27. Symmonds, R. E., and Dockerty, M. D.: Surg. Gynec. & Obst. 100: 232, 1955. 28. Thornton, W. N., Jr., and Carter, J. P.: AM. J. 0BST. & GYNEC. 62: 294, 1951. 1407 South Hope St. Los Angeles, California