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Infected Endometriotic Cysts: Clinical Characterization and Pathogenesis
FERTILITY AND STERILITY Copyright c 1981 The American Fertility Society
Vol. 36, No.1, July 1981 Printed in U.SA.
INFECTED ENDOMETRIOTIC CYSTS: CLINICAL CHARACTERIZATION AND PATHOGENESIS
CECILIA L. SCHMIDT, M.D. RITA I. DEMOPOULOS, M.D. GERSON WEISS, M.D.* Department of Obstetrics and Gynecology, and Department of Pathology, New York University Medical Center, New York, New York
Although endometriotic cysts are common, the occurrence of infection in these lesions has not been reported. Of 510 consecutive endometriotic cysts diagnosed at New York University Medical Center between 1965 and 1979, eleven had pathologically confirmed evidence of infection. These patients were nulliparous and had a mean age of 34. 7 years at time of diagnosis and without long histories of endometriosis or pelvic infection. Nine of the eleven patients presented with lower abdominal pain and fever. White blood cell count and/or erythrocyte sedimentation rate were indicative of infection. All were anemic. Six patients underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy, and five patients were treated with conservative surgery. The morbidity of both groups was similar. The latter had a poor prognosis for fertility. Infected endometriotic cysts demonstrate a strong association with concomitant tubal infection and a weaker association with antecedent hysterosalpingography. Fertil Steril 36:27, 1981
than 4 cm in diameter!' 2 and the presence of frank pus within the cysts on gross examination or microabscess formation within the cyst wall. A microabscess was defined as a collection of polymorphonuclear leukocytes associated with tissue necrosis. 3 We conducted a retrospective analysis of the hospital charts of these 11 patients to obtain information on the clinical data, preoperative evaluation, operative findings, treatment, and postoperative course. Additional patient information was obtained from the attending physicians or clinic charts.
The entity of infected endometriotic cysts has not been recognized in the gynecologic literature. A retrospective analysis of 11 cases of pathologically-confirmed infected endometriotic cysts occurring over a 15-year period was undertaken, with attention to clinical characterization and possible pathogenesis. MATERIALS AND METHODS
Pathology reports at Bellevue and University Hospitals between January 1, 1965, and December 31, 1979, were reviewed for all cases of endometriotic cysts. The original tissue slides were further examined by a single pathologist for concomitant infection. The pathologic criteria for infected endometrioma included both endometrial glands and stroma within an ovarian cyst more
RESULTS
Of 510 cases of endometriotic cysts diagnosed over the 15-year interval, only 11 fulfilled the criteria for infected endometrioma. An additional 48 of the 510 patients showed pathologic salpingitis but had no infection within the cyst. An illustrative slide shows both endometrial components and microabscess formation in juxtaposition (Fig.
Received November 12, 1980; revised and accepted February 20, 1981. *Reprint requests: Gerson Weiss, M.D., Department of Obstetrics and Gynecology, New York University Medical Center, 550 First Avenue, New York, New York 10016.
1).
27
28
SCHMIDT ET AL.
FIG. 1. The wall of this infected endometriotic cyst is lined .,y a fibrinopurulent exudate (right) with subjacent mixed inflammatory cells, including plasma cells. A focal collection of endometrial glands with stroma (left) is noted in the wall (hematoxylin and eosin, original magnification x 48).
The mean age at time of diagnosis was 34.7 years, and the ages ranged from 28 to 44 years. All 11 patients. were nulliparous. Furthermore, seven were nulligravid. Of the four women who had previously conceived, three had undergone voluntary abortions and one had had a spontaneous abortion and later an ectopic pregnancy, necessitating a salpingectomy. The most common presenting symptoms were lower abdominal pain and fever (Table 1). The involuntary infertility occurring in six patients with a mean age of 33.7 years was long-standing, ranging from 6 to 17 years, with an average duration of 9.6 years. Five patients had had salpingitis in the past. Eighty percent had had only a single episode of infection, ranging from 3 to 12 years before the present surgical procedure. Two had been treated with oral antibiotics, and the infections in the other two had resolved spontaneously. The remaining woman had experienced chronic salpingo-oophoritis and had received a variety of oral and intravenous antibiotics. No surgical procedure had been performed during these episodes for documentation of inflammation. As seen in Table 2, endometriosis had previously been discovered in only two of the six patients who had undergone abdominal surgery. Both cases had occurred approximately 3 years before the infected endometriomas, had been unilateral endometriomas, and had been treated by oophorocystectomy. Three of the eleven patients had undergone hysterosalpingography within 1 month of the onset of symptoms. In fact, two of the three devel~
July 1981
oped symptoms within 1 week of the procedure. One hysterosalpingogram (HSG) had been read as "normal" with bilateral tubal spillage of dye. Another HSG showed dilated tubes with unilateral spillage. The third HSG showed bilateral distal occlusion. A pelvic mass displacing the uterine cavity had been noted in only two of the three HSGs but was later found by laparotomy in all three patients. Temperature on admission ranged from 99° to 103° F. In eight of the eleven patients, the temperature was greater than 100.4° F. On admission, nine patients had lower quadrant tenderness to palpation, and seven of them exhibited adnexal tenderness (Table 3) . Pelvic masses ranged in size from 4 to 20 em on examination. In the seven patients whose adnexal mass could not be separated from the uterus preoperatively, the infected endometriomas were greater than 10 em. All patients were anemic, and their hematocrit values ranged from 29.5% to 39%, with a mean of 34.5%. White blood cell counts (WBCs) at admission ranged from 7.1 to 18.8 x 109 cells per liter of blood, with a mean of 13.0. Of the seven patients who had simultaneously drawn WBCs and erythrocyte sedimentation rate (ESR) determinations, one or both were elevated. 4 Six patients were treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy, and five patients underwent conservative procedures, that is, excision of endometriotic tissue and resection of severely involved pelvic viscera with preservation of the uterus and at least one tube and ovary. 5 Tissue damage secondary to endometriosis and infection led to the following concomitant procedures: two appendectomies, an ileal resection with end-to-end reanastomosis, and a partial omental resection. Of the six patients undergoing total abdominal hysterectomy, three had endometriosis, one had myometritis, and one had uterine serosal endometriosis. TABLE 1. Presenting Symptoms Symptom
Lower abdominal pain Fever Infertility Dysmenorrhea Irregular cycles Diarrhea Dyspareunia Syncope Nausea and vomiting Tenesmus
No. of patients
9 9 6 4 4 3 3 1 1 1
Vol. 36, No.1
INFECTED ENDOMETRIOTIC CYSTS
29
TABLE 2. Previous Intraabdominal Surgery Patient
No. years before IE·
Type of surgery
Final diagnosis
V.A.
3
Right oophorocystectomy
Right Et
A.R.
3
Left oophorocystectomy
LeftE
C.K.
6
Cyst of right round ligament
M.D.
10
Partial resection of right round ligament Right salpingectomy
2.5
M.A.
20
J.H.
Laparoscopy
Ruptured right tubal pregnancy Pelvic adhesions
Appendectomy
Acute appendicitis
Ovaries at present surgical procedure
Left IE Right E Right IE Left corpus luteum cyst Left IE Normal right ovary Left IE Right E Right IE Left IE Right IE LeftE
*IE, infected endometrioma. tE, endometrioma.
As seen in Table 4, all nine histologically reviewed cases showed infected fallopian tubes as described intraoperatively in eight instances. In one of the two remaining patients in whom histology was not obtained, the fallopian tubes were conserved and felt to be normal. In the other case, one fallopian tube showed gross evidence of salpingitis and the other tube could not be found in the specimen. Therefore, ten patients exhibited some form of salpingitis if the gross diagnosis is accepted where pathologic review is unavailable. In the two cases where an appendectomy was performed, full-thickness appendicitis was not found. In the patient where the appendix was densely adherent to the infected right endometrioma and fallopian tube, and acute and chronic periappendicitis with endometriosis was found. The other showed appendicitis limited to the mucosa. The resected ileum revealed acute and chronic inflammation with ulceration, necrosis, and perforation. Cultures were obtained intraoperatively in eight patients but did not reveal predominance of anyone organism. Of note is that six of the eight TABLE 3. Findings of Physical Examination at Admission Finding
Lower quadrant tenderness Adnexal tenderness Adnexal mass Distinct from uterus Not distinct from uterus Rebound tenderness Guarding Cervical tenderness Upper quadrant tenderness Enlarged uterus Suprapubic tenderness Purulent cervical discharge Nodular uterosacral ligaments
No. of patients
9 7 9 2 7 5 4 3 2 2 1 1 1
cases occurred before 1973, when retrieval of anaerobic organisms was more limited. Most of the patients became afebrile by postoperative day 3, and all were without fever by the seventh postoperative day. All 11 patients were treated postoperatively with antibiotics. Of the five patients who were treated conservatively, only one patient has conceived, approximately 29 months postoperatively. The other four patients have remained infertile. In one of the five patients recurrent pelvic masses developed approximately eight weeks after discharge and resolved while the patient was being given antibiotics and danazol (Danocrine). The remaining four women did not receive hormonal treatment. The other patients have had no further complaints.
DISCUSSION
Infected endometriomas were discovered in 11 nulliparas in their later reproductive years who presented with an acute pelvic abscess without a long history of either pelvic inflammatory disease or endometriosis. Over half had long-standing infertility. Noteworthy was the presence of salpingitis in ten of the eleven patients, pathologically proven in nine. Salpingitis appears to be the most logical portal of infection. In only one case, where ileal necrosis and ulceration were found, could bowel contamination be postulated. In the one patient in whom salpingitis was reportedly absent and where no pathologic examination of the fallopian tubes was done, the source of infection remains an enigma. The hysterosalpingogram was found to be temporally related to the onset of symptoms.
July 1981
SCHMIDT ET AL.
30
TABLE 4. Comparison of Operative Diagnosis of Fallopian Tubes and Pathologic Diagnosis Patient
M.A. A.P. J.H. E. S. V. I. A.R. V.A.
K.A.
C. K.
M.D. G.D.
Operative diagnosis
Normal fallopian tubes Normal fallopian tubes Bilateral salpingitis Bilateral salpingitis Bilateral salpingitis Bilateral hydrosalpinx Unilateral salpingitis with normal contralateral tube Unilateral TOA with normal contralateral tube Unilateral TOA with normal contralateral tube Unilateral TOA with absent contralateral tube Unilateral TOA with contralateral salpingitis
Pathologic diagnosis
Not sampled Acute salpingitis Chronic follicular salpingitis Acute and chronic salpingitis Subacute salpingitis and acute mesothelial in. fiammation Acute and chronic salpingitis Acute and chronic salpingitis (only abnormal tube sampled) Acute and chronic salpingitis Acute and chronic salpingitis (only abnormal tube sampled) Acute and chronic salpingitis Tube not found in specimen (only abnormal tube sampled)
In summary, these patients appear to suffer from the cumulative effects of salpingo-oophoritis and endometriosis. Their prognosis for fertility seems bleak. The question of the rarity of infected endometriotic cysts needs to be addressed. Possible explanations include the following: (1) the thickened capsule of the endometrioma may hinder bacterial entrance from an infected tube; (2) difficulty in fulfilling the pathologic criteria for infected endometriomas may lead to underreporting of this entity. These hypotheses will require study for substantiation. REFERENCES 1. Sampson JA: The life history of ovarian hematomas (hemorrhagic cysts) of endometrial (MUllerian) type. Am J Obstet Gynecol 4:451, 1922 2. Sampson JA: Perforating hemorrhagic (chocolate) cysts of the ovary. Arch Surg 3:245,1921 3. Blaustein A: Inflammatory diseases of the ovary. In Pathology of the Female Genital Tract, Edited by A Blaustein. New York, Springer-Verlag, 1977, pp 387-392 4. Black WT: Abscess of the ovary. Am J Obstet Gynecol 31:487,1936 5. Hammond CB, Haney AF: Conservative treatment of endometriosis: 1978. Fertil Steril 30:497, 1978
Vol. 36, No.1, July 1981 Printed in U.SA.
INFECTED ENDOMETRIOTIC CYSTS: CLINICAL CHARACTERIZATION AND PATHOGENESIS
CECILIA L. SCHMIDT, M.D. RITA I. DEMOPOULOS, M.D. GERSON WEISS, M.D.* Department of Obstetrics and Gynecology, and Department of Pathology, New York University Medical Center, New York, New York
Although endometriotic cysts are common, the occurrence of infection in these lesions has not been reported. Of 510 consecutive endometriotic cysts diagnosed at New York University Medical Center between 1965 and 1979, eleven had pathologically confirmed evidence of infection. These patients were nulliparous and had a mean age of 34. 7 years at time of diagnosis and without long histories of endometriosis or pelvic infection. Nine of the eleven patients presented with lower abdominal pain and fever. White blood cell count and/or erythrocyte sedimentation rate were indicative of infection. All were anemic. Six patients underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy, and five patients were treated with conservative surgery. The morbidity of both groups was similar. The latter had a poor prognosis for fertility. Infected endometriotic cysts demonstrate a strong association with concomitant tubal infection and a weaker association with antecedent hysterosalpingography. Fertil Steril 36:27, 1981
than 4 cm in diameter!' 2 and the presence of frank pus within the cysts on gross examination or microabscess formation within the cyst wall. A microabscess was defined as a collection of polymorphonuclear leukocytes associated with tissue necrosis. 3 We conducted a retrospective analysis of the hospital charts of these 11 patients to obtain information on the clinical data, preoperative evaluation, operative findings, treatment, and postoperative course. Additional patient information was obtained from the attending physicians or clinic charts.
The entity of infected endometriotic cysts has not been recognized in the gynecologic literature. A retrospective analysis of 11 cases of pathologically-confirmed infected endometriotic cysts occurring over a 15-year period was undertaken, with attention to clinical characterization and possible pathogenesis. MATERIALS AND METHODS
Pathology reports at Bellevue and University Hospitals between January 1, 1965, and December 31, 1979, were reviewed for all cases of endometriotic cysts. The original tissue slides were further examined by a single pathologist for concomitant infection. The pathologic criteria for infected endometrioma included both endometrial glands and stroma within an ovarian cyst more
RESULTS
Of 510 cases of endometriotic cysts diagnosed over the 15-year interval, only 11 fulfilled the criteria for infected endometrioma. An additional 48 of the 510 patients showed pathologic salpingitis but had no infection within the cyst. An illustrative slide shows both endometrial components and microabscess formation in juxtaposition (Fig.
Received November 12, 1980; revised and accepted February 20, 1981. *Reprint requests: Gerson Weiss, M.D., Department of Obstetrics and Gynecology, New York University Medical Center, 550 First Avenue, New York, New York 10016.
1).
27
28
SCHMIDT ET AL.
FIG. 1. The wall of this infected endometriotic cyst is lined .,y a fibrinopurulent exudate (right) with subjacent mixed inflammatory cells, including plasma cells. A focal collection of endometrial glands with stroma (left) is noted in the wall (hematoxylin and eosin, original magnification x 48).
The mean age at time of diagnosis was 34.7 years, and the ages ranged from 28 to 44 years. All 11 patients. were nulliparous. Furthermore, seven were nulligravid. Of the four women who had previously conceived, three had undergone voluntary abortions and one had had a spontaneous abortion and later an ectopic pregnancy, necessitating a salpingectomy. The most common presenting symptoms were lower abdominal pain and fever (Table 1). The involuntary infertility occurring in six patients with a mean age of 33.7 years was long-standing, ranging from 6 to 17 years, with an average duration of 9.6 years. Five patients had had salpingitis in the past. Eighty percent had had only a single episode of infection, ranging from 3 to 12 years before the present surgical procedure. Two had been treated with oral antibiotics, and the infections in the other two had resolved spontaneously. The remaining woman had experienced chronic salpingo-oophoritis and had received a variety of oral and intravenous antibiotics. No surgical procedure had been performed during these episodes for documentation of inflammation. As seen in Table 2, endometriosis had previously been discovered in only two of the six patients who had undergone abdominal surgery. Both cases had occurred approximately 3 years before the infected endometriomas, had been unilateral endometriomas, and had been treated by oophorocystectomy. Three of the eleven patients had undergone hysterosalpingography within 1 month of the onset of symptoms. In fact, two of the three devel~
July 1981
oped symptoms within 1 week of the procedure. One hysterosalpingogram (HSG) had been read as "normal" with bilateral tubal spillage of dye. Another HSG showed dilated tubes with unilateral spillage. The third HSG showed bilateral distal occlusion. A pelvic mass displacing the uterine cavity had been noted in only two of the three HSGs but was later found by laparotomy in all three patients. Temperature on admission ranged from 99° to 103° F. In eight of the eleven patients, the temperature was greater than 100.4° F. On admission, nine patients had lower quadrant tenderness to palpation, and seven of them exhibited adnexal tenderness (Table 3) . Pelvic masses ranged in size from 4 to 20 em on examination. In the seven patients whose adnexal mass could not be separated from the uterus preoperatively, the infected endometriomas were greater than 10 em. All patients were anemic, and their hematocrit values ranged from 29.5% to 39%, with a mean of 34.5%. White blood cell counts (WBCs) at admission ranged from 7.1 to 18.8 x 109 cells per liter of blood, with a mean of 13.0. Of the seven patients who had simultaneously drawn WBCs and erythrocyte sedimentation rate (ESR) determinations, one or both were elevated. 4 Six patients were treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy, and five patients underwent conservative procedures, that is, excision of endometriotic tissue and resection of severely involved pelvic viscera with preservation of the uterus and at least one tube and ovary. 5 Tissue damage secondary to endometriosis and infection led to the following concomitant procedures: two appendectomies, an ileal resection with end-to-end reanastomosis, and a partial omental resection. Of the six patients undergoing total abdominal hysterectomy, three had endometriosis, one had myometritis, and one had uterine serosal endometriosis. TABLE 1. Presenting Symptoms Symptom
Lower abdominal pain Fever Infertility Dysmenorrhea Irregular cycles Diarrhea Dyspareunia Syncope Nausea and vomiting Tenesmus
No. of patients
9 9 6 4 4 3 3 1 1 1
Vol. 36, No.1
INFECTED ENDOMETRIOTIC CYSTS
29
TABLE 2. Previous Intraabdominal Surgery Patient
No. years before IE·
Type of surgery
Final diagnosis
V.A.
3
Right oophorocystectomy
Right Et
A.R.
3
Left oophorocystectomy
LeftE
C.K.
6
Cyst of right round ligament
M.D.
10
Partial resection of right round ligament Right salpingectomy
2.5
M.A.
20
J.H.
Laparoscopy
Ruptured right tubal pregnancy Pelvic adhesions
Appendectomy
Acute appendicitis
Ovaries at present surgical procedure
Left IE Right E Right IE Left corpus luteum cyst Left IE Normal right ovary Left IE Right E Right IE Left IE Right IE LeftE
*IE, infected endometrioma. tE, endometrioma.
As seen in Table 4, all nine histologically reviewed cases showed infected fallopian tubes as described intraoperatively in eight instances. In one of the two remaining patients in whom histology was not obtained, the fallopian tubes were conserved and felt to be normal. In the other case, one fallopian tube showed gross evidence of salpingitis and the other tube could not be found in the specimen. Therefore, ten patients exhibited some form of salpingitis if the gross diagnosis is accepted where pathologic review is unavailable. In the two cases where an appendectomy was performed, full-thickness appendicitis was not found. In the patient where the appendix was densely adherent to the infected right endometrioma and fallopian tube, and acute and chronic periappendicitis with endometriosis was found. The other showed appendicitis limited to the mucosa. The resected ileum revealed acute and chronic inflammation with ulceration, necrosis, and perforation. Cultures were obtained intraoperatively in eight patients but did not reveal predominance of anyone organism. Of note is that six of the eight TABLE 3. Findings of Physical Examination at Admission Finding
Lower quadrant tenderness Adnexal tenderness Adnexal mass Distinct from uterus Not distinct from uterus Rebound tenderness Guarding Cervical tenderness Upper quadrant tenderness Enlarged uterus Suprapubic tenderness Purulent cervical discharge Nodular uterosacral ligaments
No. of patients
9 7 9 2 7 5 4 3 2 2 1 1 1
cases occurred before 1973, when retrieval of anaerobic organisms was more limited. Most of the patients became afebrile by postoperative day 3, and all were without fever by the seventh postoperative day. All 11 patients were treated postoperatively with antibiotics. Of the five patients who were treated conservatively, only one patient has conceived, approximately 29 months postoperatively. The other four patients have remained infertile. In one of the five patients recurrent pelvic masses developed approximately eight weeks after discharge and resolved while the patient was being given antibiotics and danazol (Danocrine). The remaining four women did not receive hormonal treatment. The other patients have had no further complaints.
DISCUSSION
Infected endometriomas were discovered in 11 nulliparas in their later reproductive years who presented with an acute pelvic abscess without a long history of either pelvic inflammatory disease or endometriosis. Over half had long-standing infertility. Noteworthy was the presence of salpingitis in ten of the eleven patients, pathologically proven in nine. Salpingitis appears to be the most logical portal of infection. In only one case, where ileal necrosis and ulceration were found, could bowel contamination be postulated. In the one patient in whom salpingitis was reportedly absent and where no pathologic examination of the fallopian tubes was done, the source of infection remains an enigma. The hysterosalpingogram was found to be temporally related to the onset of symptoms.
July 1981
SCHMIDT ET AL.
30
TABLE 4. Comparison of Operative Diagnosis of Fallopian Tubes and Pathologic Diagnosis Patient
M.A. A.P. J.H. E. S. V. I. A.R. V.A.
K.A.
C. K.
M.D. G.D.
Operative diagnosis
Normal fallopian tubes Normal fallopian tubes Bilateral salpingitis Bilateral salpingitis Bilateral salpingitis Bilateral hydrosalpinx Unilateral salpingitis with normal contralateral tube Unilateral TOA with normal contralateral tube Unilateral TOA with normal contralateral tube Unilateral TOA with absent contralateral tube Unilateral TOA with contralateral salpingitis
Pathologic diagnosis
Not sampled Acute salpingitis Chronic follicular salpingitis Acute and chronic salpingitis Subacute salpingitis and acute mesothelial in. fiammation Acute and chronic salpingitis Acute and chronic salpingitis (only abnormal tube sampled) Acute and chronic salpingitis Acute and chronic salpingitis (only abnormal tube sampled) Acute and chronic salpingitis Tube not found in specimen (only abnormal tube sampled)
In summary, these patients appear to suffer from the cumulative effects of salpingo-oophoritis and endometriosis. Their prognosis for fertility seems bleak. The question of the rarity of infected endometriotic cysts needs to be addressed. Possible explanations include the following: (1) the thickened capsule of the endometrioma may hinder bacterial entrance from an infected tube; (2) difficulty in fulfilling the pathologic criteria for infected endometriomas may lead to underreporting of this entity. These hypotheses will require study for substantiation. REFERENCES 1. Sampson JA: The life history of ovarian hematomas (hemorrhagic cysts) of endometrial (MUllerian) type. Am J Obstet Gynecol 4:451, 1922 2. Sampson JA: Perforating hemorrhagic (chocolate) cysts of the ovary. Arch Surg 3:245,1921 3. Blaustein A: Inflammatory diseases of the ovary. In Pathology of the Female Genital Tract, Edited by A Blaustein. New York, Springer-Verlag, 1977, pp 387-392 4. Black WT: Abscess of the ovary. Am J Obstet Gynecol 31:487,1936 5. Hammond CB, Haney AF: Conservative treatment of endometriosis: 1978. Fertil Steril 30:497, 1978