- Email: [email protected]
Granulosa cell tumors of the ovary with precocious puberty
GRANULOSA
CELL TUMORS OF THE PRECOCIOUS PUBERTY
OVARY
JOHN PARKS, M.D., WASHINGTON, D. C. (From the Department of Obstetrics and Gynecology, Untiers-ity
WITH
of Wkwnsti)
N THE 45 cases of malignancy of the ovary proved by microscopic examination at the Wisconsin General Hospital during the past eight years, five have been granulosa cell tumors. The age incidence in these c&ses has varied from five to sixty-four years. No case of bilateral involvement of the ovaries has been encountered. Every case, except that of a five-year-old girl, was treated by surgical removal of the tumor followed by x-ray therapy. There has been no known recurrence of the tumor in any of the cases. A summary of the 5 cases is given in Table I.
I
The particular purpose cell tumors on preadolescent patient.
of
this paper is to girls and to report
out.line a case
the influence occurring in
of granulosa a five-year-old
CASE REPORT [email protected]. M., aged 5 years, 3 months, was admitted to the Wisconsin General Hospital on Jan. 13, 1936. She was born two weeks prematurely by forceps delivery of a 27-year-old mother, who at the time of the child’s birth had had high blood pressure and albuminuria for one month. Birth weight was 5 pounds, 4 ounces. She developed normally until June, 1935, at which time her breasts began to enlarge and pubic hair began to appear. In September, 1935, following a dray of mild abdominal pain, she began to have a slight bloody vaginal discharge. Except for four or five intervals of ten to nineteen days of amenorrhea following each injection of “ follutein” given by her family physician, her menstrual flow remained constant. Her breasts continued to enlarge. Her facial expression became more mature. During the six months prior to her admission to the hospital, she gained about eight pounds in weight. Physical Ezamzination.--Patient was a well-developed, well-proportioned child about the size of an 8 year old. Height 44 inches. Weight was 51 pounds. Optic fundi were narmal. Blood pressure was 116/74. Breasts and nipples were well developed. There was an abundant growth of pubic hair. There was no axillary hair. Her hips were wide. The abdomen was slightly protuberant. An ovoid tumor about 8 by 5 cm. was palpable in the right lower quadrant of the abdomen. Labcnwtwy F&d.iags.---Urinalysis, blood counts, blood sugar, and nonprotein nitrogen were normal. X-ray plate of the cranial bones was normal. Bone age, of a chid of at least 10 years. as determined by the carpal bones, was that Asohheim-Zondek test w&a negative. No blood or urine studies for estrin were performed. Intelligence quotient was 125. Impressio%--Granulosa cell tumor of the right ovary. !f’reatm&.-Bight salpingo-oophorectomy was performed on Jan. 31, 1936. The left ovary was normal. The uterus was slightly larger and softer than normal. F&.oEo~y.--Bight ovarian tumor measured 8 by 5 by 4 cm. It had a grayish, granular, somewhat solid, fibrous cut surface with a thick capsule. Microscopically this was a cellular tumor with granulosa cells diffusely scattered throughout the fibrous stroma. There was a tendency to form cords and nests of cells. Small and moderate sized cysts were seen to be lined by several layers of cells. Postoperative Propess.-Beginning on the second postoperative day, a profuse menstrual flow lasted for forty-eight hours. After the eighth postoperative day there was no discharge from the vagina. By the twenty-iourtk day t&e brea&s 674
C.
F.
A.
E.
T. L.
L. w.
L
--
_-
--
PATIENT _D. M.
64
52
43
35
for
!
CASE@ OF GRANULOSA
CELL
TUMOR
OF THE
OVARY TREATf&ENT salpingo-oophorecI
I
HOSPITAL
PROGRESS Regression of puberty precox. Well after 15 months Well after three years
GENERAL
Curettage, left oophorectomy, uterine suspension, x-ray therapy
Right tomy
THE WISCONSIN
Curettage, r i g h t sal- Well after one year pingo-oophorectomy, supravaginal hysterectomy, “, x-ray - therapy -” Curettage, colporrhaphy, Well after three years left oophorectomy. Fixation of uterus. X-ray theranv A” I 1 Transfusion, excision of Discharged in good ruptured left ovarian health 20 days after tumor, x-ray therapy operation. No followup examination
I
!
FROM
1 GROSS PATHOLOGY i IIISTOLOGY I Right ovarian tumor 8 Mixed type by 5 by 4 cm. Thick capsule -Irregular menses for 6 Left ovarian tumor 16 Solid masses gramMenorrhagia. by 12 by 7 em. Well losa cells. Hyperyears. plasia of endomeFour months’ continuencapsulated trium ous bleeding Amenorrhea 1 ye a r. Right ovarian tumor 22 Solid masses of granMenorrhagia for 1 year. by 17 by 12 cm. Well ulosa cells. Endometrial hyperplasia Continuous flow for 5 encapsulated vears I I Brownish discharge 1 Left ovarian tumor 6 by Solid cellular tumor. year. Continuous bleed5 by 5 cm. Endometrial hypering 3 weeks plasia I I Menopause at 45. Reg- Large thin walled left Uniform masses of ular menses resumed at I ovarian t u m or filling - granulosa cells. Low grade malignancy 64 for 6 months. Conthe abdomen tinuous flow for 1I
I. SUMMARY OF FIVE X-Z AGE -SYMPTOMS (>ontinuous 5 bleeding 5 months
TABLE
676
AMRRICAN
JOURNAL
OF
OBSTIZTRICS
AND
GYNECOLOGY
were definitely smaller in size. A second Binet test on the twenty-fifth postoperative day showed her intelligence quotient to be 125. Re-examination on June 11, l9.W. showed that there had been a definite regression of secondary sex characteristics. The pubic hair had practically disappeared and the breasts were much smaller in discharge. size. The patient was seen again on May 4, 19.77. She had had no vaginal Her breasts were normal. The nipples were not prominent. No pubic hair was present. Her body configuration was that of the childhood type. The abdominal
Fig. 1. secondary sex characteristics Fig. l.- Precocious ulosa cell tumor of the right ovary. Fig. 2.-Precocious breast development resulting 5-year-old patient.
Fig.
2.
in a 5-par-old from
a grantiosa
girl
With C&
a p&n-
tumor
iI3 a
PARKS
:
d was well healed. The small , forward, and movable.
woull
QRANULOSA
CELL
6’77
TUMORS
uterus on bimanual examination The fornices were clear.
was
found
to
be
DISCUSSION A summary of the literature cases of granulosa cell tumors
mz
3.-Skeletal
growth
up to February, 1936 of the ovary causing
compared
with
that
of
revealed symptoms
a normal
only in
eight repo rted children UKnler
5-year-old
patien
Lt. aoms
ten y ears of age. Kleine has reported the youngest case with symptoms beginr at thi :ee years and five months. Practically all cases have shown the same sympt signs exhibited by t.he patient described above. The usual sympt, oms and 1jhysical of are : menstrual bleeding, marked acceleration of skeletal growth, hypertrophy and the development of pubic and axillary hair. Mental age is not the b Irea&,
678
AMERICAN
JOURNAL
OB
ORSTETRICS
.4ISD
GPNECOLOGS
Arnold Gesell, after thorough mental studies of influenced by puberty precox. cases of precocious pubescence, concluded that sexual precocity had no marked Mentality of two of the eight reported cases of effect on mental maturation. granulosa cell ‘tumors in children was definit~cly low. The usual abdominal finding is an unilateral tumor of the ovary. Exczh of right reported cases ha11 a palpable trlThe excess of rstrin produced by thcxrt mar. Aschheim-Zondek test may he positiw.
Fig.
4.-Recession
of
secondary a granulosa
sex characteristics fifteen months cell tumor of the right ovary.
after
removal
of
tumors is considered by Novak t,o be one of t,he strongest evidences of the direct rale played by the female sex hormone in the normal production of sex charaaters. Differential diagnosis is usually not difficult. Teratoma of the pineal body is a very rare c8uae of female sex precocity. Suprarenal adenomas and hypernephromas causs, in children, remarkable somatic growth and precocious development of the In bassophi& adenom~ of sex organs, but rarely cause premature menstruation.
PARKS
Mg.
Fig.
:
5.-Granulosa
I?.-Granulosa
GRANULOSA
cell
cell
tumor.
tumor.
CELL
low
High
679
TUMORS
power
power
X100.
X300.
th e pituitary, the patients are usually quite fat, changes in the eye gro: 01 Ids are fr equent, and birsutism is usually not a marked feature. Complete surgical removal of a granulosa tumor from a child brings a .bou t a ra .ther rapid regression of all precocious sexual characteristics. GALLINGEE
MUNICIPAL
HOSPITAL
CELL TUMORS OF THE PRECOCIOUS PUBERTY
OVARY
JOHN PARKS, M.D., WASHINGTON, D. C. (From the Department of Obstetrics and Gynecology, Untiers-ity
WITH
of Wkwnsti)
N THE 45 cases of malignancy of the ovary proved by microscopic examination at the Wisconsin General Hospital during the past eight years, five have been granulosa cell tumors. The age incidence in these c&ses has varied from five to sixty-four years. No case of bilateral involvement of the ovaries has been encountered. Every case, except that of a five-year-old girl, was treated by surgical removal of the tumor followed by x-ray therapy. There has been no known recurrence of the tumor in any of the cases. A summary of the 5 cases is given in Table I.
I
The particular purpose cell tumors on preadolescent patient.
of
this paper is to girls and to report
out.line a case
the influence occurring in
of granulosa a five-year-old
CASE REPORT [email protected]. M., aged 5 years, 3 months, was admitted to the Wisconsin General Hospital on Jan. 13, 1936. She was born two weeks prematurely by forceps delivery of a 27-year-old mother, who at the time of the child’s birth had had high blood pressure and albuminuria for one month. Birth weight was 5 pounds, 4 ounces. She developed normally until June, 1935, at which time her breasts began to enlarge and pubic hair began to appear. In September, 1935, following a dray of mild abdominal pain, she began to have a slight bloody vaginal discharge. Except for four or five intervals of ten to nineteen days of amenorrhea following each injection of “ follutein” given by her family physician, her menstrual flow remained constant. Her breasts continued to enlarge. Her facial expression became more mature. During the six months prior to her admission to the hospital, she gained about eight pounds in weight. Physical Ezamzination.--Patient was a well-developed, well-proportioned child about the size of an 8 year old. Height 44 inches. Weight was 51 pounds. Optic fundi were narmal. Blood pressure was 116/74. Breasts and nipples were well developed. There was an abundant growth of pubic hair. There was no axillary hair. Her hips were wide. The abdomen was slightly protuberant. An ovoid tumor about 8 by 5 cm. was palpable in the right lower quadrant of the abdomen. Labcnwtwy F&d.iags.---Urinalysis, blood counts, blood sugar, and nonprotein nitrogen were normal. X-ray plate of the cranial bones was normal. Bone age, of a chid of at least 10 years. as determined by the carpal bones, was that Asohheim-Zondek test w&a negative. No blood or urine studies for estrin were performed. Intelligence quotient was 125. Impressio%--Granulosa cell tumor of the right ovary. !f’reatm&.-Bight salpingo-oophorectomy was performed on Jan. 31, 1936. The left ovary was normal. The uterus was slightly larger and softer than normal. F&.oEo~y.--Bight ovarian tumor measured 8 by 5 by 4 cm. It had a grayish, granular, somewhat solid, fibrous cut surface with a thick capsule. Microscopically this was a cellular tumor with granulosa cells diffusely scattered throughout the fibrous stroma. There was a tendency to form cords and nests of cells. Small and moderate sized cysts were seen to be lined by several layers of cells. Postoperative Propess.-Beginning on the second postoperative day, a profuse menstrual flow lasted for forty-eight hours. After the eighth postoperative day there was no discharge from the vagina. By the twenty-iourtk day t&e brea&s 674
C.
F.
A.
E.
T. L.
L. w.
L
--
_-
--
PATIENT _D. M.
64
52
43
35
for
!
CASE@ OF GRANULOSA
CELL
TUMOR
OF THE
OVARY TREATf&ENT salpingo-oophorecI
I
HOSPITAL
PROGRESS Regression of puberty precox. Well after 15 months Well after three years
GENERAL
Curettage, left oophorectomy, uterine suspension, x-ray therapy
Right tomy
THE WISCONSIN
Curettage, r i g h t sal- Well after one year pingo-oophorectomy, supravaginal hysterectomy, “, x-ray - therapy -” Curettage, colporrhaphy, Well after three years left oophorectomy. Fixation of uterus. X-ray theranv A” I 1 Transfusion, excision of Discharged in good ruptured left ovarian health 20 days after tumor, x-ray therapy operation. No followup examination
I
!
FROM
1 GROSS PATHOLOGY i IIISTOLOGY I Right ovarian tumor 8 Mixed type by 5 by 4 cm. Thick capsule -Irregular menses for 6 Left ovarian tumor 16 Solid masses gramMenorrhagia. by 12 by 7 em. Well losa cells. Hyperyears. plasia of endomeFour months’ continuencapsulated trium ous bleeding Amenorrhea 1 ye a r. Right ovarian tumor 22 Solid masses of granMenorrhagia for 1 year. by 17 by 12 cm. Well ulosa cells. Endometrial hyperplasia Continuous flow for 5 encapsulated vears I I Brownish discharge 1 Left ovarian tumor 6 by Solid cellular tumor. year. Continuous bleed5 by 5 cm. Endometrial hypering 3 weeks plasia I I Menopause at 45. Reg- Large thin walled left Uniform masses of ular menses resumed at I ovarian t u m or filling - granulosa cells. Low grade malignancy 64 for 6 months. Conthe abdomen tinuous flow for 1I
I. SUMMARY OF FIVE X-Z AGE -SYMPTOMS (>ontinuous 5 bleeding 5 months
TABLE
676
AMRRICAN
JOURNAL
OF
OBSTIZTRICS
AND
GYNECOLOGY
were definitely smaller in size. A second Binet test on the twenty-fifth postoperative day showed her intelligence quotient to be 125. Re-examination on June 11, l9.W. showed that there had been a definite regression of secondary sex characteristics. The pubic hair had practically disappeared and the breasts were much smaller in discharge. size. The patient was seen again on May 4, 19.77. She had had no vaginal Her breasts were normal. The nipples were not prominent. No pubic hair was present. Her body configuration was that of the childhood type. The abdominal
Fig. 1. secondary sex characteristics Fig. l.- Precocious ulosa cell tumor of the right ovary. Fig. 2.-Precocious breast development resulting 5-year-old patient.
Fig.
2.
in a 5-par-old from
a grantiosa
girl
With C&
a p&n-
tumor
iI3 a
PARKS
:
d was well healed. The small , forward, and movable.
woull
QRANULOSA
CELL
6’77
TUMORS
uterus on bimanual examination The fornices were clear.
was
found
to
be
DISCUSSION A summary of the literature cases of granulosa cell tumors
mz
3.-Skeletal
growth
up to February, 1936 of the ovary causing
compared
with
that
of
revealed symptoms
a normal
only in
eight repo rted children UKnler
5-year-old
patien
Lt. aoms
ten y ears of age. Kleine has reported the youngest case with symptoms beginr at thi :ee years and five months. Practically all cases have shown the same sympt signs exhibited by t.he patient described above. The usual sympt, oms and 1jhysical of are : menstrual bleeding, marked acceleration of skeletal growth, hypertrophy and the development of pubic and axillary hair. Mental age is not the b Irea&,
678
AMERICAN
JOURNAL
OB
ORSTETRICS
.4ISD
GPNECOLOGS
Arnold Gesell, after thorough mental studies of influenced by puberty precox. cases of precocious pubescence, concluded that sexual precocity had no marked Mentality of two of the eight reported cases of effect on mental maturation. granulosa cell ‘tumors in children was definit~cly low. The usual abdominal finding is an unilateral tumor of the ovary. Exczh of right reported cases ha11 a palpable trlThe excess of rstrin produced by thcxrt mar. Aschheim-Zondek test may he positiw.
Fig.
4.-Recession
of
secondary a granulosa
sex characteristics fifteen months cell tumor of the right ovary.
after
removal
of
tumors is considered by Novak t,o be one of t,he strongest evidences of the direct rale played by the female sex hormone in the normal production of sex charaaters. Differential diagnosis is usually not difficult. Teratoma of the pineal body is a very rare c8uae of female sex precocity. Suprarenal adenomas and hypernephromas causs, in children, remarkable somatic growth and precocious development of the In bassophi& adenom~ of sex organs, but rarely cause premature menstruation.
PARKS
Mg.
Fig.
:
5.-Granulosa
I?.-Granulosa
GRANULOSA
cell
cell
tumor.
tumor.
CELL
low
High
679
TUMORS
power
power
X100.
X300.
th e pituitary, the patients are usually quite fat, changes in the eye gro: 01 Ids are fr equent, and birsutism is usually not a marked feature. Complete surgical removal of a granulosa tumor from a child brings a .bou t a ra .ther rapid regression of all precocious sexual characteristics. GALLINGEE
MUNICIPAL
HOSPITAL