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Endometrial ossification
Endometrial
ossification
KENNETH
J.
LANGDON
PARSONS,
GILBERT Boston,
H.
GANEM,
M.D. M.D.
FRIEDELL,
M.D
Massachusetts
tage. The last of these abortions, accompanied by fever, chills, and malaise after 8 weeks’ gestation, was 1 year before admission to this hospital. The uterus was curetted and the patient was given antibiotics. She dated the onset of inter-
T H E endometrium is an unusual site for heterotopic bone formation. To our knowledge only 25 cases of endometrial ossification have been reported to this time. In the 3 cases reported by Brocq and associates1 continued estrogen stimulation was cited as the most important factor in the pathogenesis. Reporting a single case, Flamand? also noted histologic evidence of prolonged estrogenic stimulation of the endometrium but suggested that an “embryonic potential factor” was more significant in the etiology. In many of the other cases,3-5 histories of repeated spontaneous abortions were obtained. The case discussed below is similar in this respect. The
patient
menstrual vaginal bleeding from this time. A few days prior to admission to the Massachusetts
Memorial
Hospitals
an
endometrial
biopsy was done by one of us (L. P.) in the course of studying the patient in his office. Microscopic examination vcaled marked acute
with and
squamous numerous
and
metaplasia spicules
of the chronic
specimen rccndometritis
of the endometrium
of bone,
some
containing
marrow (Figs. 1 and 2). Numerous neutrophils and plasma cells and a few macrophages were seen. Scattered foci of necrosis wcrr also notc,d in the endometrial stroma. The few glands present were straight or slightly coiled and outlined by columnar or cuboidal epithelium. Thcrc, were only rarr foci of calcification in the endotnetrium outside of the boric fragments. No &dcnce of recent pregnancy was SWII. After the pathologic findings wcrft rcportrd the patient was questioned about fsvidenccs of abnormal calcium metabolism but in this regard her history was negative. She had had no rcxnal or hladdrr calculi and no symptoms of peptic ulceration; she denied exccssivc, milk or vitamin D intakr. She had fracturtxd the coccyx in a fall srveral years brforca but had had nc, othf,t broken bones. She had had pulmonary tuberc.lllosis as a child, but chest films had brrn IYpeatedly negative during the past several years. There was no history of thyroid disease. Physical examination revealed a well-developed, well-nourished white woman whose vital signs and blood pressure wcrc normal. The significant findings were limited to pelvic examination. On himanual examination, the uterus
was a 32-year-old
white houscwife, gravida ix, para iii, who had had 5 abortions. She complained of irregularity of menstrual periods for 5 years and of a slight brownish red intermenstrual vaginal discharge for about 1 year. The latter was occasionally post coital. Menarchc was at age 11, and until 1954 the periods were regular with a 30 day interval between them and flow lasting 6 days. In 1954 she had a left salpingectomy for a ruptured tubal pregnancy. Subsequently the interval between the periods became irregular. Menses occurred every 3 to 5 weeks and flow varied in amount over an 8 day period. Her last full-term pregnancy was in 1952. Since that time she had had 5 spontaneous abortions, 4 of which wrre completed by curetFrom the Departments of Obstetrics and Gynecology and Pathology, Massachusetts Memorial Hospitals and Boston University School of Medicine.
1592
Volume .vumher
83 12
Endometrial
ossification
1593
was firm, slightly enlarged, and somewhat irregular. There was some induration in the left adnexal region; the right side was normal. Laboratory studies revealed a hemoglobin value of 11.8 Gm. and a hematocrit determination of 39 per cent. The white blood cell and differential counts were within normal limits, as were the prothrombin time, blood urea nitrogen level, and fasting blood sugar level. The serum calcium was 4.9 mEq. per liter, serum phosphorus 3.4 rug. per cent, and alkaline phosphatase 1.9 Bodansky units. Urinalysis, including a SulkoMitch test, was negative. A chest roentgenogram and an electrocardiogram were both negative. .A review of histologic material obtained from other hospitals revealed no endometrial ossification in material from the 4 previous curettagcs. Dilatation and curettage, followed by a total ahdominal hysterectomy, was performed on May 19, 1960. Gross examination of the opened hysterectomy specimen revealed a few long, thin spicuIes of bone on the hemorrhagic endometrial surface. Microscopically, in the curettings the cndometrium resembled that seen in the biopsy specimen. In addition, however, the glands in several areas showed definite secretory activity with pronounced subnuclear and supranuclcar vacuolization in the lining epithelial cells. Neither decidua nor trophoblast were found. There was slight adenomyosis and slight to moderate chronic
Fig. 1. Endometrial beneath fragments photomicrograph.
glands are seen at the right of bone in this low-power (Hematoxylin and eosin. x110.)
c,cGcitis with cpidermization. The postoperative course was uneventful and the patient was dischargrd on the tenth postoperative
day.
Comment
A common denominator between this case and many of the 25 previously reported is the history of repeated spontaneous abortions. Houlne and his associates” suggest that an important factor in these cases was the presence of fetal bone which served as a donor of calcium and other materials necessary for ossification. Although this might possibly be true, particularly in cases of abortion in the second trimester after ossification of the fetal skeleton has reached appreciable proportions, nevertheIess both calcification and ectopic bone formation can occur in the absence of pre-existing bone at various sites where there is prolonged chronic inflammation and tissue destruction. Both of
Fig. 2. Squamous metaplasia of endometrial is seen here in addition to the fragments at the upper and lower left. (Hematoxylin eosin. Xl 25.)
glands of bone and
1594
Ganem,
Parsons,
and
June Ii, 1%” AIU. J. Oh. & Gynce.
Friedell
these conditions are present in the endometrium of patients with repeated spontaneous abortions, and in our opinion they are more significant in the pathogenesis of endometrial ossification than the presence of fetal bone. Evidence of estrogenic stimulation of the endometrium was reported to be present in all except 4 of the 25 cases of Houlne and co-workers.” In the present case neither the
histologic nor the clinical findings suggested hyperestrinism. Similarly, there was neither clinical nor laboratory evidence of a disturbance in calcium metabolism, although these abnormalities were sought before hysterectomy. Serum calcium and phosphorus determinations were not mentioned in the other case reports cited, and it cannot bc stated whether or not they represented instances of disturbed calcium metabolism.
REFERENCES
1. 2. 3.
Brocq. M. M. P., Feyel, P., and Sluczewski, A., GynCc. et obst. 147: 613, 1948. Flamand, C.: Acta chir. belg. 49: 839, 1950. Bustos, F. M., and Brachetto-Brian, P.: Bol. y. trab., Acad. argent. cir. 31: 620, 1947.
4.
Adamson, OBST.
5.
N.
&
Ho&e, Gordeeff, 28: 467,
E., and 57: P., Kerneis, A.: Compt. 1958. GYNEC.
Sommers, S. C.: AM. J. 187, 1954. J. P., Michon, G., and rend. Sor. franG. gynkc.
ossification
KENNETH
J.
LANGDON
PARSONS,
GILBERT Boston,
H.
GANEM,
M.D. M.D.
FRIEDELL,
M.D
Massachusetts
tage. The last of these abortions, accompanied by fever, chills, and malaise after 8 weeks’ gestation, was 1 year before admission to this hospital. The uterus was curetted and the patient was given antibiotics. She dated the onset of inter-
T H E endometrium is an unusual site for heterotopic bone formation. To our knowledge only 25 cases of endometrial ossification have been reported to this time. In the 3 cases reported by Brocq and associates1 continued estrogen stimulation was cited as the most important factor in the pathogenesis. Reporting a single case, Flamand? also noted histologic evidence of prolonged estrogenic stimulation of the endometrium but suggested that an “embryonic potential factor” was more significant in the etiology. In many of the other cases,3-5 histories of repeated spontaneous abortions were obtained. The case discussed below is similar in this respect. The
patient
menstrual vaginal bleeding from this time. A few days prior to admission to the Massachusetts
Memorial
Hospitals
an
endometrial
biopsy was done by one of us (L. P.) in the course of studying the patient in his office. Microscopic examination vcaled marked acute
with and
squamous numerous
and
metaplasia spicules
of the chronic
specimen rccndometritis
of the endometrium
of bone,
some
containing
marrow (Figs. 1 and 2). Numerous neutrophils and plasma cells and a few macrophages were seen. Scattered foci of necrosis wcrr also notc,d in the endometrial stroma. The few glands present were straight or slightly coiled and outlined by columnar or cuboidal epithelium. Thcrc, were only rarr foci of calcification in the endotnetrium outside of the boric fragments. No &dcnce of recent pregnancy was SWII. After the pathologic findings wcrft rcportrd the patient was questioned about fsvidenccs of abnormal calcium metabolism but in this regard her history was negative. She had had no rcxnal or hladdrr calculi and no symptoms of peptic ulceration; she denied exccssivc, milk or vitamin D intakr. She had fracturtxd the coccyx in a fall srveral years brforca but had had nc, othf,t broken bones. She had had pulmonary tuberc.lllosis as a child, but chest films had brrn IYpeatedly negative during the past several years. There was no history of thyroid disease. Physical examination revealed a well-developed, well-nourished white woman whose vital signs and blood pressure wcrc normal. The significant findings were limited to pelvic examination. On himanual examination, the uterus
was a 32-year-old
white houscwife, gravida ix, para iii, who had had 5 abortions. She complained of irregularity of menstrual periods for 5 years and of a slight brownish red intermenstrual vaginal discharge for about 1 year. The latter was occasionally post coital. Menarchc was at age 11, and until 1954 the periods were regular with a 30 day interval between them and flow lasting 6 days. In 1954 she had a left salpingectomy for a ruptured tubal pregnancy. Subsequently the interval between the periods became irregular. Menses occurred every 3 to 5 weeks and flow varied in amount over an 8 day period. Her last full-term pregnancy was in 1952. Since that time she had had 5 spontaneous abortions, 4 of which wrre completed by curetFrom the Departments of Obstetrics and Gynecology and Pathology, Massachusetts Memorial Hospitals and Boston University School of Medicine.
1592
Volume .vumher
83 12
Endometrial
ossification
1593
was firm, slightly enlarged, and somewhat irregular. There was some induration in the left adnexal region; the right side was normal. Laboratory studies revealed a hemoglobin value of 11.8 Gm. and a hematocrit determination of 39 per cent. The white blood cell and differential counts were within normal limits, as were the prothrombin time, blood urea nitrogen level, and fasting blood sugar level. The serum calcium was 4.9 mEq. per liter, serum phosphorus 3.4 rug. per cent, and alkaline phosphatase 1.9 Bodansky units. Urinalysis, including a SulkoMitch test, was negative. A chest roentgenogram and an electrocardiogram were both negative. .A review of histologic material obtained from other hospitals revealed no endometrial ossification in material from the 4 previous curettagcs. Dilatation and curettage, followed by a total ahdominal hysterectomy, was performed on May 19, 1960. Gross examination of the opened hysterectomy specimen revealed a few long, thin spicuIes of bone on the hemorrhagic endometrial surface. Microscopically, in the curettings the cndometrium resembled that seen in the biopsy specimen. In addition, however, the glands in several areas showed definite secretory activity with pronounced subnuclear and supranuclcar vacuolization in the lining epithelial cells. Neither decidua nor trophoblast were found. There was slight adenomyosis and slight to moderate chronic
Fig. 1. Endometrial beneath fragments photomicrograph.
glands are seen at the right of bone in this low-power (Hematoxylin and eosin. x110.)
c,cGcitis with cpidermization. The postoperative course was uneventful and the patient was dischargrd on the tenth postoperative
day.
Comment
A common denominator between this case and many of the 25 previously reported is the history of repeated spontaneous abortions. Houlne and his associates” suggest that an important factor in these cases was the presence of fetal bone which served as a donor of calcium and other materials necessary for ossification. Although this might possibly be true, particularly in cases of abortion in the second trimester after ossification of the fetal skeleton has reached appreciable proportions, nevertheIess both calcification and ectopic bone formation can occur in the absence of pre-existing bone at various sites where there is prolonged chronic inflammation and tissue destruction. Both of
Fig. 2. Squamous metaplasia of endometrial is seen here in addition to the fragments at the upper and lower left. (Hematoxylin eosin. Xl 25.)
glands of bone and
1594
Ganem,
Parsons,
and
June Ii, 1%” AIU. J. Oh. & Gynce.
Friedell
these conditions are present in the endometrium of patients with repeated spontaneous abortions, and in our opinion they are more significant in the pathogenesis of endometrial ossification than the presence of fetal bone. Evidence of estrogenic stimulation of the endometrium was reported to be present in all except 4 of the 25 cases of Houlne and co-workers.” In the present case neither the
histologic nor the clinical findings suggested hyperestrinism. Similarly, there was neither clinical nor laboratory evidence of a disturbance in calcium metabolism, although these abnormalities were sought before hysterectomy. Serum calcium and phosphorus determinations were not mentioned in the other case reports cited, and it cannot bc stated whether or not they represented instances of disturbed calcium metabolism.
REFERENCES
1. 2. 3.
Brocq. M. M. P., Feyel, P., and Sluczewski, A., GynCc. et obst. 147: 613, 1948. Flamand, C.: Acta chir. belg. 49: 839, 1950. Bustos, F. M., and Brachetto-Brian, P.: Bol. y. trab., Acad. argent. cir. 31: 620, 1947.
4.
Adamson, OBST.
5.
N.
&
Ho&e, Gordeeff, 28: 467,
E., and 57: P., Kerneis, A.: Compt. 1958. GYNEC.
Sommers, S. C.: AM. J. 187, 1954. J. P., Michon, G., and rend. Sor. franG. gynkc.