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Endometrial metaplasia associated with endometrial adenocarcmoma
Endometrial metaplasia associated with endometrial adenocarcinoma Willie A. Andersen, M.D., Peyton T. Taylor, Jr., M.D., Robert E. Fechner, M.D., and Jo Ann V. Pinkerton, M.D. Charlottesville, Virginia Endometrial metaplasia is a complex group of epithelial proliferations. The relationship of metaplasia, other than squamous metaplasia, to endometrial adenocarcinoma has not been clearly established. Between 1969 and 1979, 183 patients diagnosed as having Stage I endometrial adenocarcinoma (according to International Federation of Gynecology and Obstetrics) were treated at the University of Virginia Medical Center. Sixty of the patients were treated with hysterectomy without preoperative irradiation. A histopathologic review was performed without knowledge of the clinical outcome and subsequent clinopathologic correlations were analyzed. On review, 32/60 had carcinoma without metaplasia and 15/60 had both carcinoma and metaplasia. Thirteen of the 60 patients were judged not to have cancer: 12 had both hyperplasia and metaplasia and one had hyperplasia without metaplasia. None of the 12 patients reclassified as having metaplasia had a recurrence or died of endometrial carcinoma. Patients with both metaplasia and carcinoma were significantly younger than patients with only carcinoma and the associated carcinomas were more frequently well differentiated. (AM J 0BSTET GYNECOL 1987;157: 597-604.)
Key words: Endometrial carcinoma, endometrial metaplasia
The human endometrium has a very wide range of histologic expressions in normal, hyperplastic, and neo plastic conditions. In spite of extensive studies spanning several decades, there is still controversy over the his tologic criteria of endometrial adenocarcinoma. 1"3 In 1980 an additional complication was added by Hen drickson and Kempson4 when they described the range of benign proliferative changes of the endometrium which they collectively called "nonneoplastic endome trial metaplasias." Although the familiar "squamous" metaplasia was included in their work, the focus was on "new" metaplastic processes, which included eosin ophilic, mucinous, papillary, tubal, and clear cell types. Does the identification or segregation of these meta plastic changes have any importance or does it only add further confusion? This report reviews cases in which the diagnosis was Stage I adenocarcinoma of the en dometrium with treatment by hysterectomy and dis cusses the relationship of metaplasia to carcinoma in these patients.
Material and methods Between 1969 and 1979, 183 patients with Stage I adenocarcinoma of the endometrium (International From the Departments of Obstetrics and Gynecology and Pathology, University of Virginia Medical Center. Presented as Official Guest at the Forty-ninth Annual Meeting of The South Atlantic Association of Obstetricians and Gynecologists, Hot Springs, Virginia, January 25-28, 1987. Reprint requests: Peyton T. Taylor, Jr., M.D., Box 387, University of Virginia Medical Center, Charlottesville, VA 22908.
Federation of Gynecology and Obstetrics, FICO) were identified through the tumor registry of the University of Virginia Medical Center. During this time period, 123 patients with adenocarcinoma clinically confined to the uterus were treated with preoperative radiation followed by exploration and hysterectomy. For this rea son, there were only 60 cases where there was a hys terectomy specimen without the confounding changes of irradiation. All available histologic material from the endometrial biopsy or curettage and the hysterectomy specimen was reviewed without knowledge of the pre vious diagnosis, treatment, or clinical course of the pa tient. The clinical records were abstracted, coded, and analyzed by use of the Statistical Package of the Social Sciences system of the Vogelbach Computing Center of Northwestern University, Version 9.0, 1984. Statistical significance was determined by X2 analysis of contin gency tables. Statistical significance was set at the 5% probability level. All cases were staged as FICO Stage I. After hyster ectomy, 17 patients received postoperative radiation therapy after surgical-pathologic correlation. No pa tients were lost to follow-up. The criteria for diagnosis of the various forms of metaplasia were those of Hendrickson and Kempson.< Representative photomicrographs of metaplasia are il lustrated in Figs. 1 to 4. The designation of hyperplastic endometrium re quired abnormal amounts of proliferative endometrial tissue, architectural complexity, or cytologic atypia. The 597
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Fig. 1. Syncytial papillary metaplasia consisting of uniform benign cells lacking well-defined borders that form small sheets and well-defined papillary projections. Neutrophils are often intermixed with the epithelium. (Hematoxylin and eosin. Original magnification x 125.)
Fig. 2. Tubular (ciliated) metaplasia characterized by cells with a variegated appearance resembling epithelium of the normal salpinx. Many of these cells contain cilia (arrow). Endometrial stroma surrounds most glands. (Hematoxylin and eosin. Original magnification x 125.)
classical adjectives of "cystic glandular," "adenoma taus," and "atypical" were used. The designation of adenocarcinoma required archi tectural and cytologic abnormalities as defined by Hen drickson and Kempson. 5 Results The diagnosis and interrelationship of metaplasia and cancer are given for both the biopsy/curettage specimen (Table I) and the hysterectomy specimen (Table II).
After the above criteria were applied, the diagnosis on the curretings from 13 patients (21%) was changed from carcinoma to hyperplasia without carcinoma. Eight had hyperplasia with atypia, four had adeno matous hyperplasia without atypia, and one had cystic hyperplasia without atypia. Eleven of these patients also had metaplasia. Six of the eight with hyperplasia and atypia had metaplasia as did all four of those with ad enomatous hyperplasia and the one patient with cystic hyperplasia. None of these patients had carcinoma in the hysterectomy specimen and none had recurrence
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Fig. 3. Eosinophilic metaplasia, which includes a cuboidal cell with eosinophilic cytoplasm and a centrally located, normal nucleus. The cells are all the same size and surrounded by endometrial stroma. (Hematoxylin and eosin. Original magnification x 125.)
Fig. 4. Mucinous metaplasia that has small cells with basal nuclei and mucus-filled cytoplasm on the luminal side of the cell. Variable amounts of endometrial stroma are adjacent to the stroma. (He matoxylin and eosin. Original magnification x 125.)
or died of endometrial carcinoma. The median follow up for this group is 80 months with a range of 25 to 139 months. Forty-seven patients had endometrial carcinoma on curettage (Table 1). Thirty-two had carcinoma without metaplasia and 15 had both carcinoma and metaplasia. The most common pattern of carcinoma was endo metrioid (28 patients). This was followed by "mixed" carcinomas (10 patients), serous papillary carcinoma (four patients), adenosquamous carcinoma (two pa tients), clear cell carcinoma (two patients), and poorly
differentiated small cell malignancy (one patient). All 10 cases of "mixed" carcinoma had an endometrioid component; eight cases had a serous papillary com ponent and two cases had a mucinous component. The types of endometrial carcinoma associated with the presence or absence of metaplasia are shown in Table III. Although no statistically meaningful corre lation could be drawn, there was always some compo nent of "endometrioid" carcinoma associated with metaplasia. The different patterns of metaplasia varied between
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Table I. Review diagnoses of endometrial biopsy/curettage specimens (N = 60) Carcinoma on curettings
Metaplasia on curettings Yes
15
Yes No
ll
Total
26
Total
32 ~
34
47 13 60
His tologic type
Endometrioid Adenosquamous Clear cell Papillary serous "True mixed" Other Total
Table II. Review diagnoses of hysterectomy specimens (N = 60)
Cancer without metaplasia
Cancer with metaplasia
17 2 2 4 6 1 32
ll
0 0 0 4 0 15
Total
28 2 2 4 10 1 47
Metaplasia in uterus
Carcinoma in uterus
Yes
Yes No
11
Total
Table III. The relationship of metaplasia and histologic type of carcinoma diagnosed in endometrial biopsy/curettage specimens
15
27
Total
25 8 33
40 20 60
the curettage and the hysterectomy specimen (Ta bles IV and V), probably reflecting a greater amount of histologic material for study in the latter. Although metaplasia was commonly seen as a single type, multiple types were seen in 52% of the curettage samples and 42% of the hysterectomy samples. There was no single type or combination of types of metaplasia more likely to be associated with malignancy. Both eosinophilic and ciliated metaplasia were found more frequently than squamous metaplasia. When metaplasia and malignancy coexisted in a cu rettage specimen, the malignancy was more likely to be well differentiated (85% grade 1) than in those cases without metaplasia (68% grade 2 or above). These differences did not achieve statistical significance (p = 0.06). The presence or absence of metaplasia did not correlate with the depth of invasion of the carcinoma into the myometrium. Although a "pushing" margin was seen more often when cancer and metaplasia co existed and an "infiltrative" pattern was more typical of cancer alone, the correlation was not of statistical significance. Patients with only metaplasia were significantly younger (57 ± 2.1 years) than patients with metaplasia and cancer (60 ± 1.3 years) or patients with cancer only (65 ± 2.1 years) (p = 0.04). Table VI shows the associated nonneoplastic diag noses when only metaplasia was seen in the endometrial curretings. The finding of some "normal" endome trium was significantly correlated with the absence of carcinoma (p = 0.01). Neither a lymphocytic stromal infiltrate nor stromal
foam cells correlated with the finding of carcinoma in the curettings. A desmoplastic response in the curet tings was likely to be associated with cancer and was noted in only one of the 11 cases of "pure" metaplasia. The correlation of desmoplastic reaction and can cer did not, however, achieve statistical significance (p = 0.06). There were nine deaths caused by cancer in the study group of 60 women. Only two of these occurred in patients with both metaplasia and carcinoma. None of the patients with only metaplasia in the curettings had carcinoma of the uterus, and none of these women had a recurrence or died of endometrial carcinoma. The life-table survival for all women with cancer (with or without metaplasia) was 81% ± 5.8%. The correspond ing figure for those with cancer and metaplasia was 91% ± 6.2% while those with cancer and no metaplasia had a 70% ± 10.8% survival prediction. These differ ences do not achieve statistical significance (p = 0.09). Comment
The endometrial metaplasias were thoroughly de scribed by Hendrickson and Kempson 4 in 1980 but there have been only a few subsequent discussions. 6 -8 The cases reported by them were, however, specifically selected to exclude carcinoma. We believe this has led some to conclude that the diagnosis of metaplasia pre cludes the possibility of a coexisting carcinoma of the endometrium, especially a carcinoma which could in vade the myometrium. 1 • 9 The present series emphasizes that metaplasias coexist in endometria with either en dometrial hyperplasia or carcinoma. Our experience with FIGO Stage I carcinoma indi" cates that metaplasia often coexists with carcinoma: 32% (15/47) in uterine curettings and 38% (15/40) in the hysterectomy material. Metaplasia was seen al most as often as hyperplasia with cancer. Although the association of squamous metaplasia and well differentiated adenocarcinoma has been described for decades (for example, adenoacanthoma), the coexis
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Table IV. Types of metaplasia encountered in endometrial biopsy/curettage specimens* Metaplasia
Squamous Mucinous Papillary Eosinophilic Tubal (ciliated) Clear cell
Patients with metaplasia
Total (N = 26)
5 4
5 3
io
11 1 1
Patients with metaplasia and cancer (N = 15)
onl_y (N
= 11)
7
2
8 4 0
4 19 5 1
Patients with metaplasia only (N = 12)
Total (N = 27)
2
*Patients could have more than one type of metaplasia.
Table V. Types of metaplasia encountered in hysterectomy specimens* Metaplasia
Squamous Mucinous Papillary Eosinophilic Tubal (ciliated) Clear cell
Patients wiih metaplasia and cancer (N = 15)
5 1
8
1
1
8 10 0
15 17 1
3
2 2
2
0 7 7
*Patients could .have more than one type of metaplasia.
Table VI. Nonneoplastic diagnoses associated with metaplasia on curettage* Diagnosis
Total
Metaplasia with cancer (N = 15)
Metaplasia only (N = 11)
(N = 26)
1 4 6
1 4 2
2 8
4
2
6
2
3
Cystic hyperplasia Adenomatous hyperplasia Atypical adenomatous hyperplasia Proliferative endometrium Atrophic endometrium ProliferiHive and atrophic endometrium
l l
l
8
2
*Patients could have more than one diagnosis.
tence of a variety of non-squamous metaplasias and adenocarcinoma has not heretofore been stressed. In our series the most common metaplasia coexisting with cancer was eosinophilic, not squamous, metaplasia. Silverberg 1 views endometrial metaplasia as havirig only "dubious distinction," important only in that they not be mistaken for carcinoma. We believe that the separation of benign metaplastic changes from malig nancy continues to be a critical problem. Thirteen of 60 patients (22%) who were originally diagnosed and treated as having cancer were felt to have only meta plasia and hyperplasia by cuurrent ctiteria. including silch patients in a therapeutic trial could iead to erro neous conclusions regarding the therapeutic outcomes. Distinguishing metaplasias from carcinoma admit tedly tan be difficult. Pattern diagnosis alone is unre liable. Careful attention to the cytologic detail and awareness of the architecture of metaplasias permit
their recognition. Other histologic variables were in vestigated for their utility in differentiating metaplasia from carcinoma, but only the presence o.f normaL en dometrium admixed with metaplasia reached statistical significance. Observed trends, however, suggested that the presence of a demoplastic response and scant or absent normal endometrium in the curettings often suggested the coexistence of cancer with metaplasia. The clinical setting of metaplasia, with or without associated <:arcinoina, closely parallels that of endo metrial hyperplasia. Metaplasja and hyperplasia tend to occur in rehitively younger women with abnormal uterine bleeding. Chronic oligoovulation, exogenous estrogen usage, exogenous obesity, and intrauterine contraceptive device usage have ail been reported tci be associated with metaplasia,<·6- 8 but our data were not coded to correlate these features. In this series, when metaplasia or hyperplasia was
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associated with carcinoma, the malignancies were mostly well differentiated and were more oftep of the endometrioid variety. There were rio instances iri either the curettage material or in the hysterectomy specimens where metaplasia seemed to merge into or to be trans formed into carcinoma, in spite of careful histologic rev1ew. In our study, we had no case in which cancer was absent in the curettings but present in the hysterectomy specimen. Since completion of this review, however, we have had two patients in whom there was only non squamous metaplasia in the formal curettings but in whom metaplasia and carcinoma were found in the removed uterus. In both patients the carcinoma was well differentiated but invaded the myometrium, in one case more than 50% of the wall thickness. In conclusion, metaplastic proliferations are impor tant not only because of the need to be differentiated from adenocarcinoma but because they can be found in association with carcinoma. This association is far more rich and varied than just the familiar adenoacan thoma and both the pathologist and the clinician inust be aware of the potential coexistence. If metaplasia is diagnosed in the setting of perimenopausal or post menopausal bleeding by office endometrial biopsy or curettage, a more complete sampling (formal curettage) should be considered. Because of the coexistence of metaplasia and adenoca~cinoma found in this retro spective review, we feel that the endometrial metapla sias should be viewed with concern. REFERENCES 1. Silverberg SG, New aspects of endometrial carcinoma. Clin Obstet Gynaecol1984;11:189-208. 2. Kurman RJ, Norris HJ. ·Evaluation of criteria for dis tinguishing atypical endometrial hyperplasia from well differentiated carcinoma. Cancer 1982;49:2547-59. 3. Winkler B, Alvarez S, Richart RM, Crum CP. Pitfalls in the diagnosis of endometrial neoplasia. Obstet Gynecol 1984; 64:185-94. 4. Hendrickson MR, KempSon RL Non-neoplastic metapla sias~epithelial and mesenchymal musical chairs. In: Sur gical pathology of the uterine corpus. Philadelphia: WB Saunders, 1980. 5. Hendrickson MR, Kempson RL, Endometrial epithelial metaplasias: proliferations . frequently misdiagnosed as adenocarcinoma-,-report of 89 cases and proposed classi fication. Ani J Surg Bathol 1980;4:525-42. 6. Rorat E, Wallack RG. Papillary metaplasia of the endo metrium: clinical ahd histopathologic considerations. Ob stet Gynecoll984;64:90S-2S. 7. Crum CP, Richart RM, Fenoglio CM. Adenoacanthosis of the endometrium: a clinicopathologic study in premeno pausal women. Am] Stirg Pathdll981;5:15-20. 8. Blaustein A. Morular metaplasia misdiagnosed as adena acanthoma in young women with polycystic ovarian dis ease. Am J Surg Pathol 1982;6:223-8. 9. Norris HJ, Conner MP, Kurman RJ. Preinvasive lesions of the endometrium. Clin Obstet Gynecoll986;13:725-38.
Editors' note: This manuscript was revised after these discussions were presented.
September 1987 Am J Obstet Gynecol
Discussion DR. MICHAEL P. BoRN, Miami, Florida (Official Guest). Endometrial metaplasia has been defined as the replacement of the endometrial glandular epithelium by an epithelium that is normally found in another 1 miillerian~derived organ such as the fallopian tube. Dr. Taylor and his colleagues asked the question, "Do the identification and segregation of these metaplastic changes have any real importance or do they only add further confusion?" The question is answered in the article's conclusion where it is asserted that the meta plasias are important because they may b.e confused with carcinomas and because they frequently coexist with carcinomas. Others have acknowledged these points separately2· 4 but have not highlighted their com bined significance as have Dr. Taylor and his co authors. If these conclusions are warranted, they pro vide ample justification for clinicians and pathologists alike to be aware of the existence and significance of the endometrial metaplasias. The data for this paper were generated by the review of curettage and hysterectomy specimens for 60 pa tients treated for FIGO Stage I endometrial carcinoma at the University of Virginia Medical Center between 1969 and 1979. This review identified 13 patients who did not have carcinoma. Eleven of these 13 patients had metaplasia that presumably led to the misdiagnosis. In addition, a high frequency of coexistence of meta plasia and carcinoma was identified. The incidence of coexistence was 32% in the curettage specimens and 37.5% in the hysterectomy specimens. Certainly these data should disabuse us of any misconception that the presence of metaplasia precludes the presence of car cinoma. The authors made additional important observa tions. They noted that rrietaplasias and hyperplasias are found in similar clinical settings, particularly that of the younger patient with abnormal uterine bleeding. Al though not documented in this study, other inves tigators believe that rrietaplasias are. stimulated by unopposed estrogen, both endogenous and exoge" nous.'· 5 Another observation of clinical interest is that the endometrial carcinomas found with coexistent metaplasia are usually well differentiated and usually of the endometrioid cell type; these patients generally have an improved 5-year survival rate when compared with that for carcinomas without metaplasia. This study was obviously retrospective. I would like to ask Dr. Tay lor if he is collecting any prospective data and, if so, whether estrogen and progesterone receptors are being determined. The 13 cases that were initially misdiagnosed, or per haps overdiagnosed, represent 21% of the study group. This would seem a startling statistic until we recognize it as merely illustrative of the continuing difficulty pa thologists have in agreeing on a classification for the proliferative endometrial lesions. In a review of 100 consecutive cases of endometrial hyperplasia referred to the Sloane Hospital for Women, 69% of the diag noses were downgraded by the reviewers! Debate con
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tinues about the existence and significance of endo metrial carcinoma in situ as well as the diagnostic cri teria for well-differentiated endometrial carcinoma. 13-9 In this erwironment of academic uncertainty, clinicians must communicate freely with their pathologists to be sure that the biologic potential of the endometrium is understood and that subsequent management is ap propriate. Hendrickson and Kempson 3 made an important dis tinction between metaplasias that are found in other wise unremarkable, nonhyperplastic endometrium and metaplasias found in the midst of atypical hyperplasias, which they called "metaplastic hyperplasias." The first group should pose no problem of interpretation for the pathologist and should be considered neither ma lignant nor premalignant. On the other hand, the "metaplastic hyperplasias" may well present a very com plex histologic picture subject to overdiagnosis. These authors believe that these "metaplastic hyperplasias" represent a subset of atypical aden,omatous hyperpla sias and share the generally accepted increased risk of subsequent development of adenocarcinoma. Perhaps the pivotal point is not the presence of metaplasias but rather the "company they keep." The two cases that occurred after the review was completed raise some interesting issues. These patients are reported to have "only metaplasia" in the curettings but metaplasia and carcinoma in the hysterectomy spec imens. Of greater concern is that in both cases the myo metrium was invaded. I would like to pose several ques tions regarding these cases. If only metaplasia was di agnosed on the curettings, what were the indications for hysterectomy? Was there atypical hyperplasia in the curettings as well? Is there any theory as to why the carcinomas were missed at curettage? Finally, how can we clinicians avoid similar pitfalls? The authors' conclusions are that the metaplasias are important because they may be misdiagnosed as ade nocarcinoma and because they may be frequently as sociated with carcinoma. In closing, I would like to ask Dr. Taylor two final questions. First, does he accept the concept of the "metaplastic hyperplasias" and their cat egorization as a subset of the atypical hyperplasias, im bued with their asssociatedimplications? Second, would he agree that, although a potential source of confusion, the true significance of the metaplasias does not lie in their presence alone but rather is dictated by the back ground endometrium, whether it be atrophic, prolif erative, hyperplastic, or malignant? REFERENCES l. Hendrickson MR, Kempson RL. Surgical pathology of the uterine corpus. Philadelphia: WB Saunders, 1980. 2. Silverburg SG. New aspects of endometrial carcinoma. Clin Obstet Gynaecol1984;11:189-208. 3. Hendrickson MR, Kempson RL. Endometrial epithelial metaplasias: proliferations frequently misdiagnosed as ad enocarcinoma-report of 89 cases and proposed classifi cation. Am J Surg Pathol 1980;4:525-42. 4. Winkler B, Alvarez S, Richart RM, Crum CP. Pitfalls in the diagnosis of endometrial neoplasia. Obstet Gynecol 1984; 64:185-94.
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5. Rorat E, Wallach RC. Papillary metaplasia of the endo metrium: clinical and histopathologic considerations. Ob stet Gynecol 1984;64:90s-2s. 6. Kurman RJ, Norris HJ. Evaluation of criteria for dis tinguishing atypical endometrial hyperplasia from well differentiated carcinoma. Cancer 1982;49:254 7-59. 7. Norris HJ, Tavassoli FA, Kurman RJ. Endometrial hyper plasia and carcinoma. Am] Surg Pathol1983;7:839-47. 8. Kurman RJ, Norris HJ. Letter to the Editor. Am J Surg Patholl984;8:719-20. 9. Hendrickson MR, Ross JC, Kempson RL. Letter to the Editor. Am J Surg Pathol 1984;8:720. DISCUSSER No. 2. I have a great deal of respect for the quality of pathologic diagnosis at the University of Virginia and so I question whether these interpreta tions would occur with that quality. This is more likely to occur in our community hospitals. One of the con• cerns that oncologists have had is that there is a lack of respect on the part of many of us for the lethality of endometrial carcinoma. It is considered a malig nancy that is readily curable. From your data, then, looking back from 1980, would it be fair to say that we should deduct from the cure rate of endometrial car cinoma some 15% to 20% that would indicate that it is indeed a more lethal disease than we have regarded it? DR. TAYLOR (Closing). Misinterpretation of patho logic results is a serious problem. It is particularly a problem from the point of clinical trials. A large num ber of patients do not have very aggressive lesions how ever these proliferative changes are described, so for prospective trials it is very difficult to interpret the out come. That does automatically shift survival downward. If the series is weighted with 20% very favorable lesions, the survival rate for endometrial cancer is lowered and the results do not look good. Do I accept metaplastic hyperplasias as a concept and are they judged by the "company they keep"? I think all 13 of these patients had hyperplasia. Eleven of those had metaplasia and hyperplasia. I am sorry that I did not make it clear that this is part of the "company they keep." I think what makes it so confusing is the architectural complexity of hyperplasia superimposed on metaplasia. These are very complex lesions. The examples of metaplasia with chronic infections and with intrauterine contraceptive device usage indicate that they are just a histologic re sponse. So I would say yes, my interpretation is that they are judged by the "company they keep." Do I accept it as a concept? I think it is real, that hyperplasias do exist with metaplastic changes, but this concept is different from the hyperplasias seen with chronic in fections and in younger people. As far as the two pa tients that I mentioned after the conclusion of the study and the indications for hysterectomy, one of them ac tually caused us to initiate the study, to see how often we had confused metaplasia with carcinoma or how often we had misdiagnosed it. This was an asymptom atic woman who had an endometrial biopsy specimen with ciliated and eosinophilic metaplasia. A curettage produced the same results, and the hysterectomy spec imen showed a well-differentiated invasive adenocar cinoma. However, there was no real hyperplasia in the
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biopsy specimen or the curettings. The second patient had hyperplasia with a great deal of metaplastic change, and metaplasia was the dominating feature that caught our attention. The lesion was designated as hyperplasia and metaplasia, then an invasive lesion was found at hysterectomy. I do not really have a good theory as to why we missed these lesions. We have looked back at the material, of course, in great detail, and on review the diagnosis was confirmed. The pitfalls, I think, are intellectual ones in that we believe that metaplasias in this age group and in this clinical setting are harmless.
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One of the articles we referred to said that metaplasias are of absolutely no clinical significance unless they are a source of confusion for the unwary pathologist. I think that even wary pathologists can be confused by this area, which is not so simple. I think it may be simple to talk about but hard to recognize. To me that is the pitfall. As far as prospective data, no we do not have that information. We have just completed this review of all of our cases of endometrial cancer. We are trying to plot out the future and we have not finished sorting the past or organizing it.
Conservative surgical management of isthmic ectopic pregnancies Harriet 0. Smith, M.D., Andrew A. Toledo, M.D., and John D. Thompson, M.D. Atlanta, Georgia During the 12-month study interval ending March 30, 1986, there were 203 ectopic pregnancies at Grady Memorial Hospital, a ratio of one ectopic gestation per 34 deliveries. Twenty patients with isthmic ectopic pregnancies were selected for treatment by one of three operative modalities. Seven patients with ruptured isthmic ectopic pregnancies underwent segmental tubal resection without reanastomosis. All four patients who underwent segmental tubal resection with primary microsurgical reanastomosis had postoperative hysterosalpingograms demonstrating bilateral tubal patency. One pregnancy has occurred in this group. Nine patients underwent linear salpingostomy. In five of the six patients who had postoperative hysterosalpingography, patency of the involved fallopian tube was demonstrated. Four of these nine patients, including one patient with contralateral tubal occlusion, have conceived. We conclude that linear salpingostomy for isthmic ectopic pregnancies is as effective as segmental tubal resection with primary microsurgical reanastomosis in achieving tubal patency. (AM J OBSTET GYNECOL 1987;157:604-10.)
Key words: Isthmic ectopic pregnancies. linear salpingostomy, primary microsurgical reanastomosis Linear salpingostomy has recently become the sur gical treatment of choice in the management of am pullary or infundibular ectopic pregnancies, especially when .future fertility is desired. 1·5 However, the opti mum surgical approach to isthmic ectopic pregnancies remains controversial. Three conservative operations have been described: (1) segmental resection of the involved portion of fallopian tube and reanastomosis at a later operation, (2) segmental resection and pri mary microsurgical reanastomosis, and (3) linear sal pingostomy.1·9 From the Department of Gynecology and Obstetrics, Emory University School of Medicine. Presented by invitation at the Forty-ninth Annual Meeting of The South Atlantic Association of Obstetricians and Gynecologists, Hot Springs, Virginia, January 25-28, 1987. Reprint requests: Harriet 0. Smith, M.D., Department of Gynecology and Obstetrics, Emory University and Affiliated Hospitals, 69 But ler St., S.E., Atlanta, GA 30303.
604
Segmental resection with microsurgical reanasto mosis at a later operation is the most favored tech nique.5·8 Objections to primary reanastomosis include the technical difficulties in performing reanastomoses at an untimely hour, the variable skills of the surgeons involved in performing microsurgery, the additional operating time required, and the difficulty in assessing patency of the other fallopian tube during operation. However, excision of the isthmic ectopic pregnancy and primary reanastomosis without the aid of the operating microscope or loupes have been described by Stangel et al. 9 They have successfully performed this operation on seven patients, two of whom later had intrauterine pregnancies. 7• 9 Linear salpingostomy for isthmic ectopic pregnan cies is seldom described in the literature and is gener ally disfavored. 5·8 The narrow isthmic lumen may be particularly susceptible to ectopic implantation if lin
Key words: Endometrial carcinoma, endometrial metaplasia
The human endometrium has a very wide range of histologic expressions in normal, hyperplastic, and neo plastic conditions. In spite of extensive studies spanning several decades, there is still controversy over the his tologic criteria of endometrial adenocarcinoma. 1"3 In 1980 an additional complication was added by Hen drickson and Kempson4 when they described the range of benign proliferative changes of the endometrium which they collectively called "nonneoplastic endome trial metaplasias." Although the familiar "squamous" metaplasia was included in their work, the focus was on "new" metaplastic processes, which included eosin ophilic, mucinous, papillary, tubal, and clear cell types. Does the identification or segregation of these meta plastic changes have any importance or does it only add further confusion? This report reviews cases in which the diagnosis was Stage I adenocarcinoma of the en dometrium with treatment by hysterectomy and dis cusses the relationship of metaplasia to carcinoma in these patients.
Material and methods Between 1969 and 1979, 183 patients with Stage I adenocarcinoma of the endometrium (International From the Departments of Obstetrics and Gynecology and Pathology, University of Virginia Medical Center. Presented as Official Guest at the Forty-ninth Annual Meeting of The South Atlantic Association of Obstetricians and Gynecologists, Hot Springs, Virginia, January 25-28, 1987. Reprint requests: Peyton T. Taylor, Jr., M.D., Box 387, University of Virginia Medical Center, Charlottesville, VA 22908.
Federation of Gynecology and Obstetrics, FICO) were identified through the tumor registry of the University of Virginia Medical Center. During this time period, 123 patients with adenocarcinoma clinically confined to the uterus were treated with preoperative radiation followed by exploration and hysterectomy. For this rea son, there were only 60 cases where there was a hys terectomy specimen without the confounding changes of irradiation. All available histologic material from the endometrial biopsy or curettage and the hysterectomy specimen was reviewed without knowledge of the pre vious diagnosis, treatment, or clinical course of the pa tient. The clinical records were abstracted, coded, and analyzed by use of the Statistical Package of the Social Sciences system of the Vogelbach Computing Center of Northwestern University, Version 9.0, 1984. Statistical significance was determined by X2 analysis of contin gency tables. Statistical significance was set at the 5% probability level. All cases were staged as FICO Stage I. After hyster ectomy, 17 patients received postoperative radiation therapy after surgical-pathologic correlation. No pa tients were lost to follow-up. The criteria for diagnosis of the various forms of metaplasia were those of Hendrickson and Kempson.< Representative photomicrographs of metaplasia are il lustrated in Figs. 1 to 4. The designation of hyperplastic endometrium re quired abnormal amounts of proliferative endometrial tissue, architectural complexity, or cytologic atypia. The 597
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Fig. 1. Syncytial papillary metaplasia consisting of uniform benign cells lacking well-defined borders that form small sheets and well-defined papillary projections. Neutrophils are often intermixed with the epithelium. (Hematoxylin and eosin. Original magnification x 125.)
Fig. 2. Tubular (ciliated) metaplasia characterized by cells with a variegated appearance resembling epithelium of the normal salpinx. Many of these cells contain cilia (arrow). Endometrial stroma surrounds most glands. (Hematoxylin and eosin. Original magnification x 125.)
classical adjectives of "cystic glandular," "adenoma taus," and "atypical" were used. The designation of adenocarcinoma required archi tectural and cytologic abnormalities as defined by Hen drickson and Kempson. 5 Results The diagnosis and interrelationship of metaplasia and cancer are given for both the biopsy/curettage specimen (Table I) and the hysterectomy specimen (Table II).
After the above criteria were applied, the diagnosis on the curretings from 13 patients (21%) was changed from carcinoma to hyperplasia without carcinoma. Eight had hyperplasia with atypia, four had adeno matous hyperplasia without atypia, and one had cystic hyperplasia without atypia. Eleven of these patients also had metaplasia. Six of the eight with hyperplasia and atypia had metaplasia as did all four of those with ad enomatous hyperplasia and the one patient with cystic hyperplasia. None of these patients had carcinoma in the hysterectomy specimen and none had recurrence
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Fig. 3. Eosinophilic metaplasia, which includes a cuboidal cell with eosinophilic cytoplasm and a centrally located, normal nucleus. The cells are all the same size and surrounded by endometrial stroma. (Hematoxylin and eosin. Original magnification x 125.)
Fig. 4. Mucinous metaplasia that has small cells with basal nuclei and mucus-filled cytoplasm on the luminal side of the cell. Variable amounts of endometrial stroma are adjacent to the stroma. (He matoxylin and eosin. Original magnification x 125.)
or died of endometrial carcinoma. The median follow up for this group is 80 months with a range of 25 to 139 months. Forty-seven patients had endometrial carcinoma on curettage (Table 1). Thirty-two had carcinoma without metaplasia and 15 had both carcinoma and metaplasia. The most common pattern of carcinoma was endo metrioid (28 patients). This was followed by "mixed" carcinomas (10 patients), serous papillary carcinoma (four patients), adenosquamous carcinoma (two pa tients), clear cell carcinoma (two patients), and poorly
differentiated small cell malignancy (one patient). All 10 cases of "mixed" carcinoma had an endometrioid component; eight cases had a serous papillary com ponent and two cases had a mucinous component. The types of endometrial carcinoma associated with the presence or absence of metaplasia are shown in Table III. Although no statistically meaningful corre lation could be drawn, there was always some compo nent of "endometrioid" carcinoma associated with metaplasia. The different patterns of metaplasia varied between
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Table I. Review diagnoses of endometrial biopsy/curettage specimens (N = 60) Carcinoma on curettings
Metaplasia on curettings Yes
15
Yes No
ll
Total
26
Total
32 ~
34
47 13 60
His tologic type
Endometrioid Adenosquamous Clear cell Papillary serous "True mixed" Other Total
Table II. Review diagnoses of hysterectomy specimens (N = 60)
Cancer without metaplasia
Cancer with metaplasia
17 2 2 4 6 1 32
ll
0 0 0 4 0 15
Total
28 2 2 4 10 1 47
Metaplasia in uterus
Carcinoma in uterus
Yes
Yes No
11
Total
Table III. The relationship of metaplasia and histologic type of carcinoma diagnosed in endometrial biopsy/curettage specimens
15
27
Total
25 8 33
40 20 60
the curettage and the hysterectomy specimen (Ta bles IV and V), probably reflecting a greater amount of histologic material for study in the latter. Although metaplasia was commonly seen as a single type, multiple types were seen in 52% of the curettage samples and 42% of the hysterectomy samples. There was no single type or combination of types of metaplasia more likely to be associated with malignancy. Both eosinophilic and ciliated metaplasia were found more frequently than squamous metaplasia. When metaplasia and malignancy coexisted in a cu rettage specimen, the malignancy was more likely to be well differentiated (85% grade 1) than in those cases without metaplasia (68% grade 2 or above). These differences did not achieve statistical significance (p = 0.06). The presence or absence of metaplasia did not correlate with the depth of invasion of the carcinoma into the myometrium. Although a "pushing" margin was seen more often when cancer and metaplasia co existed and an "infiltrative" pattern was more typical of cancer alone, the correlation was not of statistical significance. Patients with only metaplasia were significantly younger (57 ± 2.1 years) than patients with metaplasia and cancer (60 ± 1.3 years) or patients with cancer only (65 ± 2.1 years) (p = 0.04). Table VI shows the associated nonneoplastic diag noses when only metaplasia was seen in the endometrial curretings. The finding of some "normal" endome trium was significantly correlated with the absence of carcinoma (p = 0.01). Neither a lymphocytic stromal infiltrate nor stromal
foam cells correlated with the finding of carcinoma in the curettings. A desmoplastic response in the curet tings was likely to be associated with cancer and was noted in only one of the 11 cases of "pure" metaplasia. The correlation of desmoplastic reaction and can cer did not, however, achieve statistical significance (p = 0.06). There were nine deaths caused by cancer in the study group of 60 women. Only two of these occurred in patients with both metaplasia and carcinoma. None of the patients with only metaplasia in the curettings had carcinoma of the uterus, and none of these women had a recurrence or died of endometrial carcinoma. The life-table survival for all women with cancer (with or without metaplasia) was 81% ± 5.8%. The correspond ing figure for those with cancer and metaplasia was 91% ± 6.2% while those with cancer and no metaplasia had a 70% ± 10.8% survival prediction. These differ ences do not achieve statistical significance (p = 0.09). Comment
The endometrial metaplasias were thoroughly de scribed by Hendrickson and Kempson 4 in 1980 but there have been only a few subsequent discussions. 6 -8 The cases reported by them were, however, specifically selected to exclude carcinoma. We believe this has led some to conclude that the diagnosis of metaplasia pre cludes the possibility of a coexisting carcinoma of the endometrium, especially a carcinoma which could in vade the myometrium. 1 • 9 The present series emphasizes that metaplasias coexist in endometria with either en dometrial hyperplasia or carcinoma. Our experience with FIGO Stage I carcinoma indi" cates that metaplasia often coexists with carcinoma: 32% (15/47) in uterine curettings and 38% (15/40) in the hysterectomy material. Metaplasia was seen al most as often as hyperplasia with cancer. Although the association of squamous metaplasia and well differentiated adenocarcinoma has been described for decades (for example, adenoacanthoma), the coexis
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Table IV. Types of metaplasia encountered in endometrial biopsy/curettage specimens* Metaplasia
Squamous Mucinous Papillary Eosinophilic Tubal (ciliated) Clear cell
Patients with metaplasia
Total (N = 26)
5 4
5 3
io
11 1 1
Patients with metaplasia and cancer (N = 15)
onl_y (N
= 11)
7
2
8 4 0
4 19 5 1
Patients with metaplasia only (N = 12)
Total (N = 27)
2
*Patients could have more than one type of metaplasia.
Table V. Types of metaplasia encountered in hysterectomy specimens* Metaplasia
Squamous Mucinous Papillary Eosinophilic Tubal (ciliated) Clear cell
Patients wiih metaplasia and cancer (N = 15)
5 1
8
1
1
8 10 0
15 17 1
3
2 2
2
0 7 7
*Patients could .have more than one type of metaplasia.
Table VI. Nonneoplastic diagnoses associated with metaplasia on curettage* Diagnosis
Total
Metaplasia with cancer (N = 15)
Metaplasia only (N = 11)
(N = 26)
1 4 6
1 4 2
2 8
4
2
6
2
3
Cystic hyperplasia Adenomatous hyperplasia Atypical adenomatous hyperplasia Proliferative endometrium Atrophic endometrium ProliferiHive and atrophic endometrium
l l
l
8
2
*Patients could have more than one diagnosis.
tence of a variety of non-squamous metaplasias and adenocarcinoma has not heretofore been stressed. In our series the most common metaplasia coexisting with cancer was eosinophilic, not squamous, metaplasia. Silverberg 1 views endometrial metaplasia as havirig only "dubious distinction," important only in that they not be mistaken for carcinoma. We believe that the separation of benign metaplastic changes from malig nancy continues to be a critical problem. Thirteen of 60 patients (22%) who were originally diagnosed and treated as having cancer were felt to have only meta plasia and hyperplasia by cuurrent ctiteria. including silch patients in a therapeutic trial could iead to erro neous conclusions regarding the therapeutic outcomes. Distinguishing metaplasias from carcinoma admit tedly tan be difficult. Pattern diagnosis alone is unre liable. Careful attention to the cytologic detail and awareness of the architecture of metaplasias permit
their recognition. Other histologic variables were in vestigated for their utility in differentiating metaplasia from carcinoma, but only the presence o.f normaL en dometrium admixed with metaplasia reached statistical significance. Observed trends, however, suggested that the presence of a demoplastic response and scant or absent normal endometrium in the curettings often suggested the coexistence of cancer with metaplasia. The clinical setting of metaplasia, with or without associated <:arcinoina, closely parallels that of endo metrial hyperplasia. Metaplasja and hyperplasia tend to occur in rehitively younger women with abnormal uterine bleeding. Chronic oligoovulation, exogenous estrogen usage, exogenous obesity, and intrauterine contraceptive device usage have ail been reported tci be associated with metaplasia,<·6- 8 but our data were not coded to correlate these features. In this series, when metaplasia or hyperplasia was
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associated with carcinoma, the malignancies were mostly well differentiated and were more oftep of the endometrioid variety. There were rio instances iri either the curettage material or in the hysterectomy specimens where metaplasia seemed to merge into or to be trans formed into carcinoma, in spite of careful histologic rev1ew. In our study, we had no case in which cancer was absent in the curettings but present in the hysterectomy specimen. Since completion of this review, however, we have had two patients in whom there was only non squamous metaplasia in the formal curettings but in whom metaplasia and carcinoma were found in the removed uterus. In both patients the carcinoma was well differentiated but invaded the myometrium, in one case more than 50% of the wall thickness. In conclusion, metaplastic proliferations are impor tant not only because of the need to be differentiated from adenocarcinoma but because they can be found in association with carcinoma. This association is far more rich and varied than just the familiar adenoacan thoma and both the pathologist and the clinician inust be aware of the potential coexistence. If metaplasia is diagnosed in the setting of perimenopausal or post menopausal bleeding by office endometrial biopsy or curettage, a more complete sampling (formal curettage) should be considered. Because of the coexistence of metaplasia and adenoca~cinoma found in this retro spective review, we feel that the endometrial metapla sias should be viewed with concern. REFERENCES 1. Silverberg SG, New aspects of endometrial carcinoma. Clin Obstet Gynaecol1984;11:189-208. 2. Kurman RJ, Norris HJ. ·Evaluation of criteria for dis tinguishing atypical endometrial hyperplasia from well differentiated carcinoma. Cancer 1982;49:2547-59. 3. Winkler B, Alvarez S, Richart RM, Crum CP. Pitfalls in the diagnosis of endometrial neoplasia. Obstet Gynecol 1984; 64:185-94. 4. Hendrickson MR, KempSon RL Non-neoplastic metapla sias~epithelial and mesenchymal musical chairs. In: Sur gical pathology of the uterine corpus. Philadelphia: WB Saunders, 1980. 5. Hendrickson MR, Kempson RL, Endometrial epithelial metaplasias: proliferations . frequently misdiagnosed as adenocarcinoma-,-report of 89 cases and proposed classi fication. Ani J Surg Bathol 1980;4:525-42. 6. Rorat E, Wallack RG. Papillary metaplasia of the endo metrium: clinical ahd histopathologic considerations. Ob stet Gynecoll984;64:90S-2S. 7. Crum CP, Richart RM, Fenoglio CM. Adenoacanthosis of the endometrium: a clinicopathologic study in premeno pausal women. Am] Stirg Pathdll981;5:15-20. 8. Blaustein A. Morular metaplasia misdiagnosed as adena acanthoma in young women with polycystic ovarian dis ease. Am J Surg Pathol 1982;6:223-8. 9. Norris HJ, Conner MP, Kurman RJ. Preinvasive lesions of the endometrium. Clin Obstet Gynecoll986;13:725-38.
Editors' note: This manuscript was revised after these discussions were presented.
September 1987 Am J Obstet Gynecol
Discussion DR. MICHAEL P. BoRN, Miami, Florida (Official Guest). Endometrial metaplasia has been defined as the replacement of the endometrial glandular epithelium by an epithelium that is normally found in another 1 miillerian~derived organ such as the fallopian tube. Dr. Taylor and his colleagues asked the question, "Do the identification and segregation of these metaplastic changes have any real importance or do they only add further confusion?" The question is answered in the article's conclusion where it is asserted that the meta plasias are important because they may b.e confused with carcinomas and because they frequently coexist with carcinomas. Others have acknowledged these points separately2· 4 but have not highlighted their com bined significance as have Dr. Taylor and his co authors. If these conclusions are warranted, they pro vide ample justification for clinicians and pathologists alike to be aware of the existence and significance of the endometrial metaplasias. The data for this paper were generated by the review of curettage and hysterectomy specimens for 60 pa tients treated for FIGO Stage I endometrial carcinoma at the University of Virginia Medical Center between 1969 and 1979. This review identified 13 patients who did not have carcinoma. Eleven of these 13 patients had metaplasia that presumably led to the misdiagnosis. In addition, a high frequency of coexistence of meta plasia and carcinoma was identified. The incidence of coexistence was 32% in the curettage specimens and 37.5% in the hysterectomy specimens. Certainly these data should disabuse us of any misconception that the presence of metaplasia precludes the presence of car cinoma. The authors made additional important observa tions. They noted that rrietaplasias and hyperplasias are found in similar clinical settings, particularly that of the younger patient with abnormal uterine bleeding. Al though not documented in this study, other inves tigators believe that rrietaplasias are. stimulated by unopposed estrogen, both endogenous and exoge" nous.'· 5 Another observation of clinical interest is that the endometrial carcinomas found with coexistent metaplasia are usually well differentiated and usually of the endometrioid cell type; these patients generally have an improved 5-year survival rate when compared with that for carcinomas without metaplasia. This study was obviously retrospective. I would like to ask Dr. Tay lor if he is collecting any prospective data and, if so, whether estrogen and progesterone receptors are being determined. The 13 cases that were initially misdiagnosed, or per haps overdiagnosed, represent 21% of the study group. This would seem a startling statistic until we recognize it as merely illustrative of the continuing difficulty pa thologists have in agreeing on a classification for the proliferative endometrial lesions. In a review of 100 consecutive cases of endometrial hyperplasia referred to the Sloane Hospital for Women, 69% of the diag noses were downgraded by the reviewers! Debate con
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tinues about the existence and significance of endo metrial carcinoma in situ as well as the diagnostic cri teria for well-differentiated endometrial carcinoma. 13-9 In this erwironment of academic uncertainty, clinicians must communicate freely with their pathologists to be sure that the biologic potential of the endometrium is understood and that subsequent management is ap propriate. Hendrickson and Kempson 3 made an important dis tinction between metaplasias that are found in other wise unremarkable, nonhyperplastic endometrium and metaplasias found in the midst of atypical hyperplasias, which they called "metaplastic hyperplasias." The first group should pose no problem of interpretation for the pathologist and should be considered neither ma lignant nor premalignant. On the other hand, the "metaplastic hyperplasias" may well present a very com plex histologic picture subject to overdiagnosis. These authors believe that these "metaplastic hyperplasias" represent a subset of atypical aden,omatous hyperpla sias and share the generally accepted increased risk of subsequent development of adenocarcinoma. Perhaps the pivotal point is not the presence of metaplasias but rather the "company they keep." The two cases that occurred after the review was completed raise some interesting issues. These patients are reported to have "only metaplasia" in the curettings but metaplasia and carcinoma in the hysterectomy spec imens. Of greater concern is that in both cases the myo metrium was invaded. I would like to pose several ques tions regarding these cases. If only metaplasia was di agnosed on the curettings, what were the indications for hysterectomy? Was there atypical hyperplasia in the curettings as well? Is there any theory as to why the carcinomas were missed at curettage? Finally, how can we clinicians avoid similar pitfalls? The authors' conclusions are that the metaplasias are important because they may be misdiagnosed as ade nocarcinoma and because they may be frequently as sociated with carcinoma. In closing, I would like to ask Dr. Taylor two final questions. First, does he accept the concept of the "metaplastic hyperplasias" and their cat egorization as a subset of the atypical hyperplasias, im bued with their asssociatedimplications? Second, would he agree that, although a potential source of confusion, the true significance of the metaplasias does not lie in their presence alone but rather is dictated by the back ground endometrium, whether it be atrophic, prolif erative, hyperplastic, or malignant? REFERENCES l. Hendrickson MR, Kempson RL. Surgical pathology of the uterine corpus. Philadelphia: WB Saunders, 1980. 2. Silverburg SG. New aspects of endometrial carcinoma. Clin Obstet Gynaecol1984;11:189-208. 3. Hendrickson MR, Kempson RL. Endometrial epithelial metaplasias: proliferations frequently misdiagnosed as ad enocarcinoma-report of 89 cases and proposed classifi cation. Am J Surg Pathol 1980;4:525-42. 4. Winkler B, Alvarez S, Richart RM, Crum CP. Pitfalls in the diagnosis of endometrial neoplasia. Obstet Gynecol 1984; 64:185-94.
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5. Rorat E, Wallach RC. Papillary metaplasia of the endo metrium: clinical and histopathologic considerations. Ob stet Gynecol 1984;64:90s-2s. 6. Kurman RJ, Norris HJ. Evaluation of criteria for dis tinguishing atypical endometrial hyperplasia from well differentiated carcinoma. Cancer 1982;49:254 7-59. 7. Norris HJ, Tavassoli FA, Kurman RJ. Endometrial hyper plasia and carcinoma. Am] Surg Pathol1983;7:839-47. 8. Kurman RJ, Norris HJ. Letter to the Editor. Am J Surg Patholl984;8:719-20. 9. Hendrickson MR, Ross JC, Kempson RL. Letter to the Editor. Am J Surg Pathol 1984;8:720. DISCUSSER No. 2. I have a great deal of respect for the quality of pathologic diagnosis at the University of Virginia and so I question whether these interpreta tions would occur with that quality. This is more likely to occur in our community hospitals. One of the con• cerns that oncologists have had is that there is a lack of respect on the part of many of us for the lethality of endometrial carcinoma. It is considered a malig nancy that is readily curable. From your data, then, looking back from 1980, would it be fair to say that we should deduct from the cure rate of endometrial car cinoma some 15% to 20% that would indicate that it is indeed a more lethal disease than we have regarded it? DR. TAYLOR (Closing). Misinterpretation of patho logic results is a serious problem. It is particularly a problem from the point of clinical trials. A large num ber of patients do not have very aggressive lesions how ever these proliferative changes are described, so for prospective trials it is very difficult to interpret the out come. That does automatically shift survival downward. If the series is weighted with 20% very favorable lesions, the survival rate for endometrial cancer is lowered and the results do not look good. Do I accept metaplastic hyperplasias as a concept and are they judged by the "company they keep"? I think all 13 of these patients had hyperplasia. Eleven of those had metaplasia and hyperplasia. I am sorry that I did not make it clear that this is part of the "company they keep." I think what makes it so confusing is the architectural complexity of hyperplasia superimposed on metaplasia. These are very complex lesions. The examples of metaplasia with chronic infections and with intrauterine contraceptive device usage indicate that they are just a histologic re sponse. So I would say yes, my interpretation is that they are judged by the "company they keep." Do I accept it as a concept? I think it is real, that hyperplasias do exist with metaplastic changes, but this concept is different from the hyperplasias seen with chronic in fections and in younger people. As far as the two pa tients that I mentioned after the conclusion of the study and the indications for hysterectomy, one of them ac tually caused us to initiate the study, to see how often we had confused metaplasia with carcinoma or how often we had misdiagnosed it. This was an asymptom atic woman who had an endometrial biopsy specimen with ciliated and eosinophilic metaplasia. A curettage produced the same results, and the hysterectomy spec imen showed a well-differentiated invasive adenocar cinoma. However, there was no real hyperplasia in the
Andersen et al.
biopsy specimen or the curettings. The second patient had hyperplasia with a great deal of metaplastic change, and metaplasia was the dominating feature that caught our attention. The lesion was designated as hyperplasia and metaplasia, then an invasive lesion was found at hysterectomy. I do not really have a good theory as to why we missed these lesions. We have looked back at the material, of course, in great detail, and on review the diagnosis was confirmed. The pitfalls, I think, are intellectual ones in that we believe that metaplasias in this age group and in this clinical setting are harmless.
September 1987 Am J Obstet Gynecol
One of the articles we referred to said that metaplasias are of absolutely no clinical significance unless they are a source of confusion for the unwary pathologist. I think that even wary pathologists can be confused by this area, which is not so simple. I think it may be simple to talk about but hard to recognize. To me that is the pitfall. As far as prospective data, no we do not have that information. We have just completed this review of all of our cases of endometrial cancer. We are trying to plot out the future and we have not finished sorting the past or organizing it.
Conservative surgical management of isthmic ectopic pregnancies Harriet 0. Smith, M.D., Andrew A. Toledo, M.D., and John D. Thompson, M.D. Atlanta, Georgia During the 12-month study interval ending March 30, 1986, there were 203 ectopic pregnancies at Grady Memorial Hospital, a ratio of one ectopic gestation per 34 deliveries. Twenty patients with isthmic ectopic pregnancies were selected for treatment by one of three operative modalities. Seven patients with ruptured isthmic ectopic pregnancies underwent segmental tubal resection without reanastomosis. All four patients who underwent segmental tubal resection with primary microsurgical reanastomosis had postoperative hysterosalpingograms demonstrating bilateral tubal patency. One pregnancy has occurred in this group. Nine patients underwent linear salpingostomy. In five of the six patients who had postoperative hysterosalpingography, patency of the involved fallopian tube was demonstrated. Four of these nine patients, including one patient with contralateral tubal occlusion, have conceived. We conclude that linear salpingostomy for isthmic ectopic pregnancies is as effective as segmental tubal resection with primary microsurgical reanastomosis in achieving tubal patency. (AM J OBSTET GYNECOL 1987;157:604-10.)
Key words: Isthmic ectopic pregnancies. linear salpingostomy, primary microsurgical reanastomosis Linear salpingostomy has recently become the sur gical treatment of choice in the management of am pullary or infundibular ectopic pregnancies, especially when .future fertility is desired. 1·5 However, the opti mum surgical approach to isthmic ectopic pregnancies remains controversial. Three conservative operations have been described: (1) segmental resection of the involved portion of fallopian tube and reanastomosis at a later operation, (2) segmental resection and pri mary microsurgical reanastomosis, and (3) linear sal pingostomy.1·9 From the Department of Gynecology and Obstetrics, Emory University School of Medicine. Presented by invitation at the Forty-ninth Annual Meeting of The South Atlantic Association of Obstetricians and Gynecologists, Hot Springs, Virginia, January 25-28, 1987. Reprint requests: Harriet 0. Smith, M.D., Department of Gynecology and Obstetrics, Emory University and Affiliated Hospitals, 69 But ler St., S.E., Atlanta, GA 30303.
604
Segmental resection with microsurgical reanasto mosis at a later operation is the most favored tech nique.5·8 Objections to primary reanastomosis include the technical difficulties in performing reanastomoses at an untimely hour, the variable skills of the surgeons involved in performing microsurgery, the additional operating time required, and the difficulty in assessing patency of the other fallopian tube during operation. However, excision of the isthmic ectopic pregnancy and primary reanastomosis without the aid of the operating microscope or loupes have been described by Stangel et al. 9 They have successfully performed this operation on seven patients, two of whom later had intrauterine pregnancies. 7• 9 Linear salpingostomy for isthmic ectopic pregnan cies is seldom described in the literature and is gener ally disfavored. 5·8 The narrow isthmic lumen may be particularly susceptible to ectopic implantation if lin