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Estrogen excretion in a case of theca-granulosa cell tumor
Communications
most layer. Poidevin’s animal experiments suggested that decidual incorporation was a major factor in scar weakness; this, of course, does not necessarily implicate decidual inclusion as a basis for delayed postpartum hemorrhage but does indicate weakness in subsequent pregnancies. As cited by Pedowitz and Schwartz,6 the two most important factors for evaluating potential scar strength, namely, surgical technique and healing power of the patient, cannot be ascertained from all available data. An afebrile postoperative course does not guarantee a “good” scar and a febrile course does not mean there is a “poor” scar. Although no evidence is offered, it may be that patients who have a self-limiting bleeding episode late after cesarean section may be those who exhibit scar weakness in subsequent pregnancies. Finally, the finding of endocervical glandular tissue and fibrovascular tissue in the wound area is worthy of mention. The cervix is composed mostly of fibrous tissue? and is less well vascularized than the uterus itself. For these reasons, healing of a wound surgically imposed in cervical tissue rather than uterine tissue could be expected to have poorer healing properties than if the wound were properly placed in the lower uterine segment. In the patient reported, the labor was considered to be of the hypertonic type, as in Heys’ case, and to be significantly prolonged, as in the 2 patients reported by Hansford and Weed.8 The latter authors also found that the tissue slough occurred from cervical tissue. Perhaps both hypertonic and prolonged labors lead to exaggeration of the lower uterine segment in that it is thinned out and “drawn up” more than is usually expected. Then, in an effort to get “as low as possible,” the cervix, rather than the lower segment, is incised at the time of cesarean section, providing a less-favorable healing site. REFERENCES
1. Treanor, T. A.: AM. J. OBSTET. GYNECOL. 83: 37, 1962. 2. MacVicar, J., and Graham, R. M.: Br. Med. J. 2: 29, 1973. 3. Ross, I. C.: Aust. N. Z. J. Obstet. Gynaecol. 5: 215, 1965. 4. Heys, R. F.: J. Obstet. Gynaecol. Br. Commonw. 70: 647, 1963. 5. Poidevin, L. 0. S.: J. Obstet. Gynaecol. Br. Commonw. 68: 1025, 1961. 6. Pedowitz, P., and Schwartz, R. M.: AM. J. OBSTET. GYNECOL. 74: 1071, 1957.
7. Danforth, 8.
53: 541, Hansford, Gynecol.
D. N.: AM. 1947. D. P., and 1: 317, 1953.
J.
in brief
OBSTET.
Weed,
J.
GYNECOL.
C.:
Estrogen excretion in a case theta-granulosa cell tumor CHRISTOPHER M.B.B.S.,
859
Obstet.
of
S. TARGETT, F.R.C.S.(EDIN.),
M.R.C.O.G. Mercy Maternity Hospital and Department Obstetrics and Gynaecology, University of Melbourne, Melbowne, Australia
of
I N A REVIEW 0 F theta-granulosa cell tumors, Fathallal found that 29 of 91 occurred in ovaries which showed no clinical enlargement. Laparotomy and, hence, definitive diagnosis were delayed in many patients because it was not appreciated that a clinically normal ovary could harbor such a tumor. Because these tumors are rarely diagnosed prior to laparotomy, only 8 cases have been reported where hormone assays were performed both before and after operationl+ (Table I). S. ,4., age 58, para 2, complained of sore breasts and vaginal bleeding of 6 weeks’ duration. The menopause had occurred 8 years earlier. There was no history of estrogen therapy. Examination revealed firm, tender breasts and normal pelvic findings except that the vaginal
epithelium
appeared to be stimulated by estrogens.
Under anesthesia, the right ovary was palpable, but its size was considered to be within normal limits. Curettings were reported as being derived from a polypoid proliferative endometrium of minimal activity. Total urinary estrogens measured 17.1 pug per 24 hours, and urinary pregnanediol measured 0.6 mg. per 24 hours. Abdominal hysterectomy and bilateral salpingo-oophorectomy were performed. On the third postoperative day, the patient stated that her breasts were no longer sore. Her convalescence was uneventful. The right ovary measured 4 by 3 by 2.5 cm., and several light yellow masses, 0.5 to 1.5 cm., were visible within its substance (Fig. 1). A section of these well-demarcated Areis (Fig. 2) showed cells typical of a theta-granulosa cell tumor with theta elements predominating. Rosette Reprint requests: Dr. Christopher ment of Obstetrics and Gynaecology, pital, Clarendon St., East Melbourne,
S. Targett, DepartMercy Maternity Hos3002, Australia.
860
Communications
Fig. 1. Section contact
Table
Author Beischer
showing right slide x4.)
from
I. Estrogen
excretion
and
and Browns
in
year ( 1972)
Brown and associates” Fathallar (1967) Procope” ( 1969) and case
colleagues”
ovary
patients
to be composed
with
Patient’s (years)
I
Woodruff Present
July 15, 1974
in brief
I
(1959)
(1963)
mainly
theta-granulosa age
44 21 33 77 75 62 53 68 58
formation was noted in a few areas. The chromatin pattern, although mainly vesicular, showed irregular clumping in some nuclei, and a number of mitotic figures were noted. Occasional cells contained fat droplets. The contralateral ovary measured 3 by 1.8 by 1.3 cm. and, on section, showed marked cortical stromal hyperplasia. Six weeks after operation, the urinary estrogen and pregnanediol values were 1.4 pg per 24 hours and 0.3 mg. per 24 hours, respectively. The assessment of estrogcnic activity in the postmenopausal patient involves an evaluation of symptoms, endomctrial histology, vraginal cytology, and, finally, measurcmcnt of urinary estrogen excretion. Unfortunately, there is often poor correlation between these indices, and, if
of cords
cell
Estrogens
113 64 13 25 17.8 4.6 19.6 21 17.1
(Direct
Endometrium
6 10
Cystic
7
is considered
rnent
may
hyperplasia
Cystic hyperplasia Hyperplasia Atrophic Cystic hyperplasia Proliferative Proliferative
4.5 6.8 7 1.4
each
srparately,
conflicting
asscss-
he made. it has been is not a
estrogcnir and vaginal thr
cells.
Gynecol.
hr.)
1 Postoperative
Thus, bleeding
Obstet.
tumors
(pg/24
PreoQerative
of tumor
Am. J.
prrsence
postmenopausal total urinary
activity. cytology of an
found reliable and do
that postmmopausal sign of abnormal endometrial histology not necessarily reflect
estrogen-secreting
tumor.
In
women, the norrrlal range of estrogen values is wide (2 to I6 I-cg
per 34 hours with a mean value of i pg pet 34 hour?). Urinary estrogen levels correlate closely with endometrial histology, but, even so, some
overlap
endometrial
occurs stimulation.
with
each
classification
of
Communications
Fig. 2. Photomicrograph cation x100.) -
of tumor
showing
theta
An ovarian tumor is a distinct possibility when more than 5 years have elapsed since the menopause, the urinary excretion of estrogens is greater than 20.0 p.g per 24 hours, the mean karyopyknotic and eosinophilic indexes exceed 20, and an estrogen effect is observed in the rndometrium.l Table I shows that the preoperative estrogen excretion in the present case (17.1 pg) is the lowest reported for a postmenopausal patient showing evidence of estrogenic activity with a theta-granulosa cell tumor. Ovarian cortical stromal hyperplasia may represent a response to prolonged low-grade estrogen stimulation or, conversely, may provide an alternative site for estrogen production when ovarian follicular activity ceases at the menopause. In support of the latter, it has been found that the removal of ovaries which show cortical stromal hyperplasia produces a significant decrease in estrogen excretion. Several studies have confirmed that cortical stromal hyperplasia in the contralateral ovary is often seen in association with a thcca ccl1 tumor. The coexistence is too frequent to IX fortuitous, and it may be postulated that the atromal hyperplasia in the same or contralateral ovary is responsible for the estrogenic activity attributed to some theta cell tumors. Its absence might then explain the well-documented
cells with
rosette
formation.
(Original
in brief
861
magnifi-
fact that not all of these tumors are hormonally active. Hysterectomy and oophorectomy are not advocated for all patients with postmenopausal bleeding. However, conservative management is contraindicated when abnormal estrogenic activity is present even when there is no clinical ovarian enlargement. Urinary estrogen assays in patients with postmenopausal bleeding when laparotomy is not planned should hasten definitive diagnosis and might show that small theta-granulosa cell tumors are more common than previously realized.
I wish to Johnston for Colin Lafferty
express my thanks to Miss M. L. the photomicrographs and to Drs. and Alan Bodey for helpful advice.
REFERENCES
1. Fathalla, M. F.: J. Obstet. Gynaecol. Br. Commonw. 74: 279, 1967. 2. Brown, J. B., Kellar, R., and Mathew, G. D.: J. Obstet. Gynaecol. Br. Emp. 67: 177, 1959. 3. Woodruff, J. D., Williams, T. J., and Goldberg, B.: AM. J. OBSTET. GYNECOL. 87: 679, 1963. 4. Procope, B. J.: Acta Endocrinol. 60: 1, 1969. (Suppl. 135.) 5. Beischer, N. A., and Brown, J. B.: Obstet. Gynecol. Survey 27: 205, 1972.
most layer. Poidevin’s animal experiments suggested that decidual incorporation was a major factor in scar weakness; this, of course, does not necessarily implicate decidual inclusion as a basis for delayed postpartum hemorrhage but does indicate weakness in subsequent pregnancies. As cited by Pedowitz and Schwartz,6 the two most important factors for evaluating potential scar strength, namely, surgical technique and healing power of the patient, cannot be ascertained from all available data. An afebrile postoperative course does not guarantee a “good” scar and a febrile course does not mean there is a “poor” scar. Although no evidence is offered, it may be that patients who have a self-limiting bleeding episode late after cesarean section may be those who exhibit scar weakness in subsequent pregnancies. Finally, the finding of endocervical glandular tissue and fibrovascular tissue in the wound area is worthy of mention. The cervix is composed mostly of fibrous tissue? and is less well vascularized than the uterus itself. For these reasons, healing of a wound surgically imposed in cervical tissue rather than uterine tissue could be expected to have poorer healing properties than if the wound were properly placed in the lower uterine segment. In the patient reported, the labor was considered to be of the hypertonic type, as in Heys’ case, and to be significantly prolonged, as in the 2 patients reported by Hansford and Weed.8 The latter authors also found that the tissue slough occurred from cervical tissue. Perhaps both hypertonic and prolonged labors lead to exaggeration of the lower uterine segment in that it is thinned out and “drawn up” more than is usually expected. Then, in an effort to get “as low as possible,” the cervix, rather than the lower segment, is incised at the time of cesarean section, providing a less-favorable healing site. REFERENCES
1. Treanor, T. A.: AM. J. OBSTET. GYNECOL. 83: 37, 1962. 2. MacVicar, J., and Graham, R. M.: Br. Med. J. 2: 29, 1973. 3. Ross, I. C.: Aust. N. Z. J. Obstet. Gynaecol. 5: 215, 1965. 4. Heys, R. F.: J. Obstet. Gynaecol. Br. Commonw. 70: 647, 1963. 5. Poidevin, L. 0. S.: J. Obstet. Gynaecol. Br. Commonw. 68: 1025, 1961. 6. Pedowitz, P., and Schwartz, R. M.: AM. J. OBSTET. GYNECOL. 74: 1071, 1957.
7. Danforth, 8.
53: 541, Hansford, Gynecol.
D. N.: AM. 1947. D. P., and 1: 317, 1953.
J.
in brief
OBSTET.
Weed,
J.
GYNECOL.
C.:
Estrogen excretion in a case theta-granulosa cell tumor CHRISTOPHER M.B.B.S.,
859
Obstet.
of
S. TARGETT, F.R.C.S.(EDIN.),
M.R.C.O.G. Mercy Maternity Hospital and Department Obstetrics and Gynaecology, University of Melbourne, Melbowne, Australia
of
I N A REVIEW 0 F theta-granulosa cell tumors, Fathallal found that 29 of 91 occurred in ovaries which showed no clinical enlargement. Laparotomy and, hence, definitive diagnosis were delayed in many patients because it was not appreciated that a clinically normal ovary could harbor such a tumor. Because these tumors are rarely diagnosed prior to laparotomy, only 8 cases have been reported where hormone assays were performed both before and after operationl+ (Table I). S. ,4., age 58, para 2, complained of sore breasts and vaginal bleeding of 6 weeks’ duration. The menopause had occurred 8 years earlier. There was no history of estrogen therapy. Examination revealed firm, tender breasts and normal pelvic findings except that the vaginal
epithelium
appeared to be stimulated by estrogens.
Under anesthesia, the right ovary was palpable, but its size was considered to be within normal limits. Curettings were reported as being derived from a polypoid proliferative endometrium of minimal activity. Total urinary estrogens measured 17.1 pug per 24 hours, and urinary pregnanediol measured 0.6 mg. per 24 hours. Abdominal hysterectomy and bilateral salpingo-oophorectomy were performed. On the third postoperative day, the patient stated that her breasts were no longer sore. Her convalescence was uneventful. The right ovary measured 4 by 3 by 2.5 cm., and several light yellow masses, 0.5 to 1.5 cm., were visible within its substance (Fig. 1). A section of these well-demarcated Areis (Fig. 2) showed cells typical of a theta-granulosa cell tumor with theta elements predominating. Rosette Reprint requests: Dr. Christopher ment of Obstetrics and Gynaecology, pital, Clarendon St., East Melbourne,
S. Targett, DepartMercy Maternity Hos3002, Australia.
860
Communications
Fig. 1. Section contact
Table
Author Beischer
showing right slide x4.)
from
I. Estrogen
excretion
and
and Browns
in
year ( 1972)
Brown and associates” Fathallar (1967) Procope” ( 1969) and case
colleagues”
ovary
patients
to be composed
with
Patient’s (years)
I
Woodruff Present
July 15, 1974
in brief
I
(1959)
(1963)
mainly
theta-granulosa age
44 21 33 77 75 62 53 68 58
formation was noted in a few areas. The chromatin pattern, although mainly vesicular, showed irregular clumping in some nuclei, and a number of mitotic figures were noted. Occasional cells contained fat droplets. The contralateral ovary measured 3 by 1.8 by 1.3 cm. and, on section, showed marked cortical stromal hyperplasia. Six weeks after operation, the urinary estrogen and pregnanediol values were 1.4 pg per 24 hours and 0.3 mg. per 24 hours, respectively. The assessment of estrogcnic activity in the postmenopausal patient involves an evaluation of symptoms, endomctrial histology, vraginal cytology, and, finally, measurcmcnt of urinary estrogen excretion. Unfortunately, there is often poor correlation between these indices, and, if
of cords
cell
Estrogens
113 64 13 25 17.8 4.6 19.6 21 17.1
(Direct
Endometrium
6 10
Cystic
7
is considered
rnent
may
hyperplasia
Cystic hyperplasia Hyperplasia Atrophic Cystic hyperplasia Proliferative Proliferative
4.5 6.8 7 1.4
each
srparately,
conflicting
asscss-
he made. it has been is not a
estrogcnir and vaginal thr
cells.
Gynecol.
hr.)
1 Postoperative
Thus, bleeding
Obstet.
tumors
(pg/24
PreoQerative
of tumor
Am. J.
prrsence
postmenopausal total urinary
activity. cytology of an
found reliable and do
that postmmopausal sign of abnormal endometrial histology not necessarily reflect
estrogen-secreting
tumor.
In
women, the norrrlal range of estrogen values is wide (2 to I6 I-cg
per 34 hours with a mean value of i pg pet 34 hour?). Urinary estrogen levels correlate closely with endometrial histology, but, even so, some
overlap
endometrial
occurs stimulation.
with
each
classification
of
Communications
Fig. 2. Photomicrograph cation x100.) -
of tumor
showing
theta
An ovarian tumor is a distinct possibility when more than 5 years have elapsed since the menopause, the urinary excretion of estrogens is greater than 20.0 p.g per 24 hours, the mean karyopyknotic and eosinophilic indexes exceed 20, and an estrogen effect is observed in the rndometrium.l Table I shows that the preoperative estrogen excretion in the present case (17.1 pg) is the lowest reported for a postmenopausal patient showing evidence of estrogenic activity with a theta-granulosa cell tumor. Ovarian cortical stromal hyperplasia may represent a response to prolonged low-grade estrogen stimulation or, conversely, may provide an alternative site for estrogen production when ovarian follicular activity ceases at the menopause. In support of the latter, it has been found that the removal of ovaries which show cortical stromal hyperplasia produces a significant decrease in estrogen excretion. Several studies have confirmed that cortical stromal hyperplasia in the contralateral ovary is often seen in association with a thcca ccl1 tumor. The coexistence is too frequent to IX fortuitous, and it may be postulated that the atromal hyperplasia in the same or contralateral ovary is responsible for the estrogenic activity attributed to some theta cell tumors. Its absence might then explain the well-documented
cells with
rosette
formation.
(Original
in brief
861
magnifi-
fact that not all of these tumors are hormonally active. Hysterectomy and oophorectomy are not advocated for all patients with postmenopausal bleeding. However, conservative management is contraindicated when abnormal estrogenic activity is present even when there is no clinical ovarian enlargement. Urinary estrogen assays in patients with postmenopausal bleeding when laparotomy is not planned should hasten definitive diagnosis and might show that small theta-granulosa cell tumors are more common than previously realized.
I wish to Johnston for Colin Lafferty
express my thanks to Miss M. L. the photomicrographs and to Drs. and Alan Bodey for helpful advice.
REFERENCES
1. Fathalla, M. F.: J. Obstet. Gynaecol. Br. Commonw. 74: 279, 1967. 2. Brown, J. B., Kellar, R., and Mathew, G. D.: J. Obstet. Gynaecol. Br. Emp. 67: 177, 1959. 3. Woodruff, J. D., Williams, T. J., and Goldberg, B.: AM. J. OBSTET. GYNECOL. 87: 679, 1963. 4. Procope, B. J.: Acta Endocrinol. 60: 1, 1969. (Suppl. 135.) 5. Beischer, N. A., and Brown, J. B.: Obstet. Gynecol. Survey 27: 205, 1972.