- Email: [email protected]
The cytology of endometriosis
The cytology of endometriosis STUART Winnipeg,
C. Manitoba,
LAUCHLAN,
M.B.,CH.B.,
F.R.C.P.
(C)
Canada
criteria, each was recorded separately. Thus, the 49 examples of endometriosis accepted for further study were drawn from 45 patients. The blocks and slides used for original diagnosis were again employed. No recuts or serial sections were made, except in 2 instances. In one, serial sections were made at the time of initial examination in order to demonstrate an unrelated finding. In the second instance, serial sections were made of the abdominal wall lesion previously reported as showing endocervical-type epithelium. Examination of these revealed the additional feature of ciliated epithelium lining a number of the glands.
THE MORE RIGID definition of endometriosis demand the histologic demonstration of typical endometrial glandular and stromal tissue for substantiation of the diagnosis. The definition is strict in order to exclude the many forms of peritoneal inclusion found in the pelvis. It is relaxed on occasion to admit only the stromal component in the more rare condition of stromal endometriosis. Diagnoses based on the epithelium alone are considered, at best, dubious. The definitions, though rigid, are limited in the sense that endometrial epithelial and stromal tissue do not necessarily exhaust the cellular potentialities of endometriosis. In light of the recent demonstration by Lauchlanl of endocervical-type epithelium in an abdominal scar, a review was made of those cases of endometriosis recorded in the files of the Winnipeg General Hospital. In this survey, cases from 1962 to the present time were drawn out and restudied. Only those instances showing the characteristic epithelium and stroma of endometriosis were diagnosed for the purposes of this study. Many were rejected for lack of one or other histologic component, and the final series of 49 acceptable examples falls considerably short of the number believed, on clinical and other grounds, to represent instances of endometriosis. No case of adenomyosis was included in this survey and, on somewhat arbitrary grounds, no case involving the uterine serosa was included. No attempt was made to assign a “primary” site to the disease process, and where two or more locations were each the site of disease satisfying the diagnostic From the Department of Pathology, Winnipeg General Hospital.
Results Three types of epithelial cell-endometrial, endocervical, and ciliated-were specifically sought, and the results are charted in Table I. Endometrial epithelium, one of the two required criteria for diagnosis, was present in all instances. Endocervical epithelium was more rare. It was demonstrated in three cases-in an abdominal scar, in a hernial sac, and in an ovary. In all 3 instances in which endocervical epithelium was demonstrated, abundant or moderately abundant ciliated epithelial cells were also present. Ciliated epithelial cells were a remarkably common finding. Table I gives the frequency of their occurrence in rough terms. The true incidence is almost certainly higher than this, for there are a number of limiting factors in a series of this sort. The hemorrhagic destruction of epithelium, most common in the ovaries and oviducts, often leaves only a small strip of cells for satisfactory examination. Blood or secretion resting on the
The
533
534
F&l uary 15, 1966 Am. J. Obst. & Gynec.
Lauchlan
Table I
Site
Ovaries Oviducts Surgical scars Hernial sacs Umbilicus Appendix Vagina Colon
32 5 3 2 2
2 2 1
32 5 3 2 2 2 2
1 0 1 1
1
0 0 0
2 0 0
1
0
0
Table II.
Semiquantitative epithelium
ciliated Site
Ovaries Oviducts Surgical scars Hernial sacs Umbilicus
Three plus
10 0 2 0 1
24 5 3
assessment
of
ciliation. It seems likely that serial blocking of entire lesions followed by multiple sectioning would reveal a higher proportion of ciliated epithelium. An attempt was made in this study to present a semiquantitative evaluation of the prominence of ciliated cells in endometriosis. Wherever such cells were demonstrated, a rough estimate of their number was made as three plus (seen regularly and with ease), two plus (seen with moderate diligence), and one plus (seen only after prolonged search). Table II is a classification of these categories in each site. Comment
Two
One
plus 6 4,
plus 8
0 1 1
1 0 0
1
luminal borders of epithelium may obscure any cilia present, and so force a negative report which may not always be justified. Finally, the pitfall of mistaking cytoplasmic or secretory projections from the luminal surfaces of endometrial cells demands an ultracautious approach to the assessment of
Endometriosis, commonly regarded as the presence of endometrium-like tissue in inappropriate sites, is clearly not an uncomplicated cellular phenomenon. The presence of varying proportions of cells of endocervical type and of ciliated epithelium indicates rather a proliferation of cells of wider Milllerian potentiality whose ultimate differentiation, though preponderantly endometrial, is by no means invariable. This admixture of cell types in predominantly pure Miillerian lesions is not, of course, unique to endometriosis. Forty-five of 400 mutinous cysts examined by Cariker
Fig. 1. A strip of ciliated epithelium in an area of endometriosis showing the characteristically broad cell. The long axis of the nucleus tends to adopt a horizontal position.
Volume Number
94 4
and Dockerty* showed a mixture of serous and mutinous elements, and, conversely, mucinous areas in predominantly serous cysts are not uncommon. Ciliated epithelium is, of course, a frequent component of serous cysts. The current tendency, exemplified by Hertig and Gore,3 to consider endometriosis and the serous and pseudomucinous tumors as related entities appears to be a valid one. “Transitional” inclusion cysts and the various “formes fruste” which abound in the pelvis form a logical intermediate group between simple infolding of pelvic peritoneum and the more highly differentiated Mi.illerian derivatives. They are characterized by much cellular variability, and one small cyst may be lined by more than one cell type. The local factors exercising an inductive influence over the final differentiation are not known. The ciliated cell is not, of course, to be glibly equated with the epithelium lining the oviduct. Apart from the secretory cell population of the oviduct lining, it should be remembered that ciliated cells are not uncommonly found in the uterine endometrium itself. Here, however, they are less
Cytology
of endometriosis
535
frequently encountered and are lessconspicuous than those in extrauterine situations, a finding in keeping with that of Dougherty and Anderson4 who commented that it typified the propensity of Miillerian epithelium for undergoing degrees of metaplasia. Ciliated cells were generally, though certainly not always, both shorter and broader than the endometrial cells, and their plump nuclei tended to adopt a horizontal rather than a vertical position in the cell (Fig. 1). The cellular differences, coupled with the greater prominence of these cells in endometriosis compared with “normal” endometrium, justifies the suspicion that intrauterine ciliation may, in fact, represent a degree of endometrial dystrophy or Miillerian unripeness which may be of pathologic significance. Conclusion
The cytologic make-up of endometriosis is presented. The relationship of endometriosis to other lesionsof pelvic peritoneum and the possible relationship of such lesions to disorders of normal endometrial development is discussed.
REFERENCES
1. Lauchlan, Stuart C.: AM. J. OBST. & GYNEC. In press. 2. Cariker, Mildred, and Dockerty, Malcolm: Cancer 7: 302, 1954. 3. Hertig, Arthur T., and Gore, Hazel: Tumors of the ovary and fallopian tube, Armed Forces Institute of Pathology, 1961, p. 76.
4.
Dougherty, R.: AM.
Cary J. OBST.
M., and Anderson, Marie & GYNEC. 89: 23, 1964.
700 William Avenue Winnipeg 3, Manitoba,
Canada
C. Manitoba,
LAUCHLAN,
M.B.,CH.B.,
F.R.C.P.
(C)
Canada
criteria, each was recorded separately. Thus, the 49 examples of endometriosis accepted for further study were drawn from 45 patients. The blocks and slides used for original diagnosis were again employed. No recuts or serial sections were made, except in 2 instances. In one, serial sections were made at the time of initial examination in order to demonstrate an unrelated finding. In the second instance, serial sections were made of the abdominal wall lesion previously reported as showing endocervical-type epithelium. Examination of these revealed the additional feature of ciliated epithelium lining a number of the glands.
THE MORE RIGID definition of endometriosis demand the histologic demonstration of typical endometrial glandular and stromal tissue for substantiation of the diagnosis. The definition is strict in order to exclude the many forms of peritoneal inclusion found in the pelvis. It is relaxed on occasion to admit only the stromal component in the more rare condition of stromal endometriosis. Diagnoses based on the epithelium alone are considered, at best, dubious. The definitions, though rigid, are limited in the sense that endometrial epithelial and stromal tissue do not necessarily exhaust the cellular potentialities of endometriosis. In light of the recent demonstration by Lauchlanl of endocervical-type epithelium in an abdominal scar, a review was made of those cases of endometriosis recorded in the files of the Winnipeg General Hospital. In this survey, cases from 1962 to the present time were drawn out and restudied. Only those instances showing the characteristic epithelium and stroma of endometriosis were diagnosed for the purposes of this study. Many were rejected for lack of one or other histologic component, and the final series of 49 acceptable examples falls considerably short of the number believed, on clinical and other grounds, to represent instances of endometriosis. No case of adenomyosis was included in this survey and, on somewhat arbitrary grounds, no case involving the uterine serosa was included. No attempt was made to assign a “primary” site to the disease process, and where two or more locations were each the site of disease satisfying the diagnostic From the Department of Pathology, Winnipeg General Hospital.
Results Three types of epithelial cell-endometrial, endocervical, and ciliated-were specifically sought, and the results are charted in Table I. Endometrial epithelium, one of the two required criteria for diagnosis, was present in all instances. Endocervical epithelium was more rare. It was demonstrated in three cases-in an abdominal scar, in a hernial sac, and in an ovary. In all 3 instances in which endocervical epithelium was demonstrated, abundant or moderately abundant ciliated epithelial cells were also present. Ciliated epithelial cells were a remarkably common finding. Table I gives the frequency of their occurrence in rough terms. The true incidence is almost certainly higher than this, for there are a number of limiting factors in a series of this sort. The hemorrhagic destruction of epithelium, most common in the ovaries and oviducts, often leaves only a small strip of cells for satisfactory examination. Blood or secretion resting on the
The
533
534
F&l uary 15, 1966 Am. J. Obst. & Gynec.
Lauchlan
Table I
Site
Ovaries Oviducts Surgical scars Hernial sacs Umbilicus Appendix Vagina Colon
32 5 3 2 2
2 2 1
32 5 3 2 2 2 2
1 0 1 1
1
0 0 0
2 0 0
1
0
0
Table II.
Semiquantitative epithelium
ciliated Site
Ovaries Oviducts Surgical scars Hernial sacs Umbilicus
Three plus
10 0 2 0 1
24 5 3
assessment
of
ciliation. It seems likely that serial blocking of entire lesions followed by multiple sectioning would reveal a higher proportion of ciliated epithelium. An attempt was made in this study to present a semiquantitative evaluation of the prominence of ciliated cells in endometriosis. Wherever such cells were demonstrated, a rough estimate of their number was made as three plus (seen regularly and with ease), two plus (seen with moderate diligence), and one plus (seen only after prolonged search). Table II is a classification of these categories in each site. Comment
Two
One
plus 6 4,
plus 8
0 1 1
1 0 0
1
luminal borders of epithelium may obscure any cilia present, and so force a negative report which may not always be justified. Finally, the pitfall of mistaking cytoplasmic or secretory projections from the luminal surfaces of endometrial cells demands an ultracautious approach to the assessment of
Endometriosis, commonly regarded as the presence of endometrium-like tissue in inappropriate sites, is clearly not an uncomplicated cellular phenomenon. The presence of varying proportions of cells of endocervical type and of ciliated epithelium indicates rather a proliferation of cells of wider Milllerian potentiality whose ultimate differentiation, though preponderantly endometrial, is by no means invariable. This admixture of cell types in predominantly pure Miillerian lesions is not, of course, unique to endometriosis. Forty-five of 400 mutinous cysts examined by Cariker
Fig. 1. A strip of ciliated epithelium in an area of endometriosis showing the characteristically broad cell. The long axis of the nucleus tends to adopt a horizontal position.
Volume Number
94 4
and Dockerty* showed a mixture of serous and mutinous elements, and, conversely, mucinous areas in predominantly serous cysts are not uncommon. Ciliated epithelium is, of course, a frequent component of serous cysts. The current tendency, exemplified by Hertig and Gore,3 to consider endometriosis and the serous and pseudomucinous tumors as related entities appears to be a valid one. “Transitional” inclusion cysts and the various “formes fruste” which abound in the pelvis form a logical intermediate group between simple infolding of pelvic peritoneum and the more highly differentiated Mi.illerian derivatives. They are characterized by much cellular variability, and one small cyst may be lined by more than one cell type. The local factors exercising an inductive influence over the final differentiation are not known. The ciliated cell is not, of course, to be glibly equated with the epithelium lining the oviduct. Apart from the secretory cell population of the oviduct lining, it should be remembered that ciliated cells are not uncommonly found in the uterine endometrium itself. Here, however, they are less
Cytology
of endometriosis
535
frequently encountered and are lessconspicuous than those in extrauterine situations, a finding in keeping with that of Dougherty and Anderson4 who commented that it typified the propensity of Miillerian epithelium for undergoing degrees of metaplasia. Ciliated cells were generally, though certainly not always, both shorter and broader than the endometrial cells, and their plump nuclei tended to adopt a horizontal rather than a vertical position in the cell (Fig. 1). The cellular differences, coupled with the greater prominence of these cells in endometriosis compared with “normal” endometrium, justifies the suspicion that intrauterine ciliation may, in fact, represent a degree of endometrial dystrophy or Miillerian unripeness which may be of pathologic significance. Conclusion
The cytologic make-up of endometriosis is presented. The relationship of endometriosis to other lesionsof pelvic peritoneum and the possible relationship of such lesions to disorders of normal endometrial development is discussed.
REFERENCES
1. Lauchlan, Stuart C.: AM. J. OBST. & GYNEC. In press. 2. Cariker, Mildred, and Dockerty, Malcolm: Cancer 7: 302, 1954. 3. Hertig, Arthur T., and Gore, Hazel: Tumors of the ovary and fallopian tube, Armed Forces Institute of Pathology, 1961, p. 76.
4.
Dougherty, R.: AM.
Cary J. OBST.
M., and Anderson, Marie & GYNEC. 89: 23, 1964.
700 William Avenue Winnipeg 3, Manitoba,
Canada