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Clinical Significance of Struma Ovarii
OLINIOAL SIGNIFICANOE OF STRUMA OV ARIl S. B.
GUSBERG,
M.D.,
AXD
D. K.
DANFORTH,
M.D., ~EW
YORK,
N.
Y.
(From the Sloane Hospital for Women and the Department of Obstetrics and Gynecology, Columbia Uni'l:ersity)
HERE have been eight cases of struma ovarii recorded in the pathologic files of the Sloane Hospital for Women in the past 20 years. This represents 2.7 per cent of 297 ovarian teratomata of all types which were examined during the same period. In addition to these, several thyroid rests have been observed; the diagnosis of ovarian struma, however, has been confined to those tumors whi<.>h contain significant quantities of thyroid tissue. Of the eight eases reported here, seven presented the usual array of clinical symptoms and signs which ordinarily accompany benign ovarian tumors: intermittent ahdominal pain, painless pelvic or abdominal masses, and, in one instance, acute abdominal pain due to torsion of the pedicle. In these cases, the presence of thyroid tissue is of pathologic interest only. The cystic tumors were generally multilocular, and three of the seven contained epidermoid clements charaderistic of the ordinary dermoid cyst. Microscopically, none of these cases showed evidence of hyperplastic changes in the thyroid tissue. The eighth case, however, presented a symptom complex of an unusual nature, the diagnostic and therapeutic implications of which arc deemed significant. This case is therefore presented in detail.
T
Oase Report Mrs. J. J., aged 53, para viii, gravida viii, presented herself at the Presbyterian Hospital in September, 1943, with the chief complaint of goiter of 35 years' duration. She was admitted to the surgieal wards for study shortly thereafter, and in October, readmitted for thyroidectomy. IIistory: On admission, there were three groups of significant symptoms: (a) A history of goiter-like swelling in the neck for 3;) years. This had been noted after her first pregnaney, and had enlarged thereafter with each pregnancy, and also to a notable degree for the five years prior to admission. (b) The patient had noted mild exertional dyspnea for approximately two years, and some difficulty in swallowing for several months prior to admission. She had had a relatively uneventful menopause 14 months before entry to the hospital, but since that time had experienced mild palpitation, insomnia, increased perspiration and some nervousness. Mild tremor of the fingers and increasing fatigability had been noted recentlv. (c) A progressively enlarging abdominal swelling had been present for 1% years. 537
5a8
AMERICAN ,JOURNAL OF OBS'r:f;~TRICS AXD GYNECOLOGY
Physical Bxamination confirmed the presence of thyroid and abdominal masses. The thyroid was enlarged to .. football" size. It felt irregularly cystic and lobular. The abdominal mass was irregular, cystic and moderately mobile; it filled the lower abdomen and rose almost to the costal margin on the left. There were no eye signs of thyrotoxicosis. 'l'here was a slight tremor, and mild cardiae hyperactivity. Moderate tachycardia was constant. The blood pressure on admission was 150/70. Laboratory Data: Rasal metabolic rates were obtained ranging from +30 per cent on 9/21/43 to--61 per cent on 10/21/43. These were followed by readings of -,56 pCI' eent on 11/1/43 andi 55 per cent on 11/8/43. Blood eholesterol was 161 mg.!;7o on 10/21/43 and blood iodine 15.1 gamma/% on 10/22/4B. This latter observation was made three weeks after cessation of a pl'{)vions ('oim,(' of iodine therapy and is considered sign ifi{'an t.
};'ig. l.·-·-The goiter X 150.
Course: On her first admission, the patient was given a course of iodine therapy which consisted of 1 c.e. of LngoJ '8 solution daily for 12 days. This had no perceptible effeet on her general status. On readmission, another course of Lugol '8 solution had a slight ameliorating effect on her pulse and 8ymptoms,but none on the basal metabl'J1ic rate. Since the abdominal tumor was regarded as an ovarian cyst, it was deemed advisable to deal with the thyroid problem first. Therefore, on 11/10/43 a partial thyroidectomy was performed. At operation, the thyroid was represented by a huge irregularly cystic nodular mass which measured approximately 26 cm. in its greatest diameter and weighed 920 Gm. on removal. Microscopic examination revealed acini which varied markedly in size; many were disten:ded by colloid and lined by flattened cuboidal cells; a few smaller acini were lined by higher cuboidal cells. In some of the more solid portions of the gland, focal
GUSBERG
A~D
DANFORTH:
STRUMA OVARII
collections of lymphocytes were seen. There were occasional areas of degeneration and old hemorrhage throughout. It was the opinion of Dr. V. Kneeland Frantz of the Department of Surgical Pathology of the Presbyterian Hospital, who examined these sections, that the bulk of the tissue was involuted; furthermore, she was not able to correlate the histologic picture with the clinical evidence of toxicity. The patient made a relatively uneventful recovery from the thyroidectomy. A moderate to mild tachycardia persisted, but its si6'1lificance was difficult to evaluate because of some anemia. The patient was improved subjectively. Her basal metabolic rate on 11/22/43 was +10 per cent. Throughout her hospital stay, she was kept on iodine therapy. The patient was discharged home Jor interval eonvalescence; she felt fairly well in the interim and was admitted to the Sloane Hospital in January, 1944, for removal of her abdominal tumor. Upon admission, there was mild tachycardia and nervousness; the blood pressure was 170/102. No other significant symptoms or signs of thyrotoxicosis were elicited.
Fig. 2.-The struma ovaril XliiO.
At laparotomy on 1/11/44, a large tumor'was found arising' from the left adnexal region and filling most of the abdominal cavity. The uterus appeared normal; the bowel was adherent to the tumor mass in several areas but the peritoneum was otherwise clear. A supravaginal hysterectomy and bilateral salpingo-oophorectomy were performed. Pathologic examination revealed the endometrium to be mildly hyperplastic, and the right ovary to be the site of a small serous cystadenoma. The left ovary had been replaced by a huge multilocular tumor mass measuring 23 by 12.5 by 8.5 cm. Approximately three liters of fluid had already been removed from one locule at operation. Some locuies were lined by a smooth grayish-tan membrane and contained clear yellow
540
A:\
fiuid. About one-third of the total volume of the tumol' was o('(,llpied b;v a honeycombed glall(l-like tissue wh ieh rfSPHl bled th~Toi(1 tissue grossly. On mi('roscopie examination, 11 varia1>l!' pattern was ('Iwounteredo Stratified squamous epithelium lilled sOllie of the spa('ps, whilt' numerous locules w('['(' lined by a single laYP1' of low ('olumnaJ' epit!Jplimll. The thyroid pOl'1ions of this (',Yst.ie teratoma also nn'ied. Tlwf'(' were sOllle small Heini dOSl'I~' al'J'angl'd with ('llhoidal epitheliulll lining' them, There 'were also some hu'gej' ;l('ini with low papillary infolding' and low ('o\umnar epithdillltl. It was llw imjlrPNsioll of Dr. F),(lllt:r; that tlH' ovarian struma showed mOl'(' pviden('(' of h,vIH'I'plasicl fUlIl Ipss of involution than 1Iw goitel'. The possihilit.\, t hat tIl(> t hyrotoxi('osis in this ('ase was diredh- related to 11](' ov:u'i;lIl struma was sLurg('stpd Tilt, probability that tht: ,;tj'UIIlH playC'(1 ~onl<' roll> ill thi~ ell'a'onill(' OWl'activity seems inCSe
Fit.!;. 3.-'T'hl::'
~trurna
()varii Xaou.
The patient made an uneventful n'{'overy frolll the operation, and has been well and without obserwd tac'hy('al'dia or thyrotoxiC' symptoms since, The hasal metaholiC' rate was 1)ot<>d at ,14 ]H'r ('('nt on 1/29/44 before discharg(' frolll t lIP hospital, and I ]H'J' ('('nt on 2/~1 /44. Discussion 'I'he case whieh Wl' have pl'esl'nted is notahlp in that a huge struma ('olli, a large struma ovarii, and ('vident thYJ'otoxic'osis W('l'C C'ocxistent. It is unfortunate that the possibility oj' IlHll'ian stl'111UH was not ('onsidered and the preliminary work-up ('HITied ont with thjs in mind. Despite the incomplet e data, Sl'veral points of interest haY(~ been derived from the case and from the review of the literature whi('h it has occasioned. The actual role of the ovarian tumor ill the production of the
GU8BEHG AXD DAXFOHTII:
8TRF)fA OVARII
541
hyperthyroidism is problematical, and no amo\lnt of stndy of the datu ean produce any ('onclusiw evidence. However, the comparative mieroseopie findings, the prohable meehanieal ('ontrihlltioll or the huge g'oiter to the elcvated hasal metabolie rate, and tht' persistent tachyeardia following thyroidec·tomy might all he eonsidel'ed as presumptive evidenee that the ovarian tumor eontrihnted to the thYl'010xieosis. That struma ovarii is eapahle of ])1"odw'ing or at least eontrihuting 10 thyrotoxieosis, is established. It is this ahility whieh distinguishes the ovarian struma among' all ovarian neoplasms, and removes it from the category of the simple pathologie c·nriosity. It should he emphasized that eases of fnuetioning ovarian struma may ('usily ('seape diagnosis, either through failure to appreeiatl' mild hyp('rth~'roid symptoms, or thl'ough (·hanel' avoidanee of thyroid tissue in the seetioning of large ovarian teratomata. In ]940, Emge estimated the rec'orded eases or struma ovarii at 150, of whieh 5 to 6 per e(mt were said to have produced thyrotoxieosis. 1 Sinec this time, some :31 ovarian strumuta have hecn reported ;2.!J of these, eight are said to have lW(,lI aceom panied by thy1'otoxieosis. Tn at least five eases, ('oi11('ident rlllarg(~ment of the thyroid was present. In three patients thyrotoxic symptoms were relieved by oophoreetomy alon('; in two of these, prior Nuhtotal thyroidectomy had failed to arrest the hyperthyroidism. It i,; of illtert'st t hat in most ~)f the eases in whieh such data are availahle, the oYUrian seehons have failed to show the presumed mieros{'opie stigmata of hyperthyroidism, despite aIl1elioration of symptoms by removal of the tUlllor. It would appeal' reasonable to ('onsider the ovarian struma a,; a JUB(,tioning part of the total thyroid tissue of the hody, whieh may react to iodine laek, to the thyrotropic hormone, or to other stimuli in a manner similar to that of the thyroid gland itself. If this hypothesis is tenahle, one might then ('onsider the removal of an ovarian struma as tantamount 10 subtotal ablation of the thyroid gland. 'l'he signal importunee of this disease pietul"c is manifested in the ease which presents distinet evidenee of thyrotoxieosis, plus enlargement of the thyroid gland, plus an ovaria11 tumor. If the thyroid does not by its very size demand removal, as it did in the ease herevyith presented. the, possibility of a fUl1etioning ovarian st rumH should he eonsidered, and the primary snrgieal eonsideratiol1 weighed. Two eases of apparently needless t.hyroidec·tomy in sl1<'h a situation are I"l'eorded in the reeent literature.
Summary
The ineidenee of struma ovarii among 297 ovarian teratomata of all types removed at the Sloane Hospital for 'Women during the past 20 years is 2.7 per ecnt. A ease is presented in which thyrotoxicosis, a large struma ovarii, and a huge goiter were coexistent. The reeent literature npon struma ovarii is briefly reviewed. 'l'he elinieal and therapeutic implieatiollS of this eondition arc eOllsidered.
542
AMERICi\~ JOURNAL OF OBSTETRICS A;-.II) GY~E:COL(}OY
References 1. 2. 3. 4.
5. 6. 7. 8. 9.
Bmge, L. A.: AM .•J. OSST. & GYXEC. 40: 7:~~, W40. Kleine, H. 0.: Zeutralbl. f. Gyn1ik. 63: 104D, 1()3fJ. Castano, C. A.: HoI. Soc. de ohst. y ginec. de Buenos Aires 19: 3]6, 1940. Murray, N. A., Dockerty, M. B., and Pemherton, J . de .T.: AM . .T. OSST. & GyX~;c. 44: ]34, 1!J42. Brown, A. I.., and Shoor, lIT.: Am. J. SUl'g. 55: In, 1!l42. Hundley, J. ~f.: AM. J. Os ST. & (fYXEC. 40: i 4D, 1D40. (Di~Cll~sion of Dr. Emge'A Paper. ) Wharton, L. H.: Gyneeology, With a Sertion 011 FemaJe l:ro!ogy, Philadelphia, 1943, W. B. Saunders Co., page 607. Sailer, S.: Am .•r. Clin. Path. 13: 27], I!H:1. Coh n, 8., a nd Kushner, J. D.: AM. J. OBST. & GVXEC. 47: 421, 1944.
GUSBERG,
M.D.,
AXD
D. K.
DANFORTH,
M.D., ~EW
YORK,
N.
Y.
(From the Sloane Hospital for Women and the Department of Obstetrics and Gynecology, Columbia Uni'l:ersity)
HERE have been eight cases of struma ovarii recorded in the pathologic files of the Sloane Hospital for Women in the past 20 years. This represents 2.7 per cent of 297 ovarian teratomata of all types which were examined during the same period. In addition to these, several thyroid rests have been observed; the diagnosis of ovarian struma, however, has been confined to those tumors whi<.>h contain significant quantities of thyroid tissue. Of the eight eases reported here, seven presented the usual array of clinical symptoms and signs which ordinarily accompany benign ovarian tumors: intermittent ahdominal pain, painless pelvic or abdominal masses, and, in one instance, acute abdominal pain due to torsion of the pedicle. In these cases, the presence of thyroid tissue is of pathologic interest only. The cystic tumors were generally multilocular, and three of the seven contained epidermoid clements charaderistic of the ordinary dermoid cyst. Microscopically, none of these cases showed evidence of hyperplastic changes in the thyroid tissue. The eighth case, however, presented a symptom complex of an unusual nature, the diagnostic and therapeutic implications of which arc deemed significant. This case is therefore presented in detail.
T
Oase Report Mrs. J. J., aged 53, para viii, gravida viii, presented herself at the Presbyterian Hospital in September, 1943, with the chief complaint of goiter of 35 years' duration. She was admitted to the surgieal wards for study shortly thereafter, and in October, readmitted for thyroidectomy. IIistory: On admission, there were three groups of significant symptoms: (a) A history of goiter-like swelling in the neck for 3;) years. This had been noted after her first pregnaney, and had enlarged thereafter with each pregnancy, and also to a notable degree for the five years prior to admission. (b) The patient had noted mild exertional dyspnea for approximately two years, and some difficulty in swallowing for several months prior to admission. She had had a relatively uneventful menopause 14 months before entry to the hospital, but since that time had experienced mild palpitation, insomnia, increased perspiration and some nervousness. Mild tremor of the fingers and increasing fatigability had been noted recentlv. (c) A progressively enlarging abdominal swelling had been present for 1% years. 537
5a8
AMERICAN ,JOURNAL OF OBS'r:f;~TRICS AXD GYNECOLOGY
Physical Bxamination confirmed the presence of thyroid and abdominal masses. The thyroid was enlarged to .. football" size. It felt irregularly cystic and lobular. The abdominal mass was irregular, cystic and moderately mobile; it filled the lower abdomen and rose almost to the costal margin on the left. There were no eye signs of thyrotoxicosis. 'l'here was a slight tremor, and mild cardiae hyperactivity. Moderate tachycardia was constant. The blood pressure on admission was 150/70. Laboratory Data: Rasal metabolic rates were obtained ranging from +30 per cent on 9/21/43 to--61 per cent on 10/21/43. These were followed by readings of -,56 pCI' eent on 11/1/43 andi 55 per cent on 11/8/43. Blood eholesterol was 161 mg.!;7o on 10/21/43 and blood iodine 15.1 gamma/% on 10/22/4B. This latter observation was made three weeks after cessation of a pl'{)vions ('oim,(' of iodine therapy and is considered sign ifi{'an t.
};'ig. l.·-·-The goiter X 150.
Course: On her first admission, the patient was given a course of iodine therapy which consisted of 1 c.e. of LngoJ '8 solution daily for 12 days. This had no perceptible effeet on her general status. On readmission, another course of Lugol '8 solution had a slight ameliorating effect on her pulse and 8ymptoms,but none on the basal metabl'J1ic rate. Since the abdominal tumor was regarded as an ovarian cyst, it was deemed advisable to deal with the thyroid problem first. Therefore, on 11/10/43 a partial thyroidectomy was performed. At operation, the thyroid was represented by a huge irregularly cystic nodular mass which measured approximately 26 cm. in its greatest diameter and weighed 920 Gm. on removal. Microscopic examination revealed acini which varied markedly in size; many were disten:ded by colloid and lined by flattened cuboidal cells; a few smaller acini were lined by higher cuboidal cells. In some of the more solid portions of the gland, focal
GUSBERG
A~D
DANFORTH:
STRUMA OVARII
collections of lymphocytes were seen. There were occasional areas of degeneration and old hemorrhage throughout. It was the opinion of Dr. V. Kneeland Frantz of the Department of Surgical Pathology of the Presbyterian Hospital, who examined these sections, that the bulk of the tissue was involuted; furthermore, she was not able to correlate the histologic picture with the clinical evidence of toxicity. The patient made a relatively uneventful recovery from the thyroidectomy. A moderate to mild tachycardia persisted, but its si6'1lificance was difficult to evaluate because of some anemia. The patient was improved subjectively. Her basal metabolic rate on 11/22/43 was +10 per cent. Throughout her hospital stay, she was kept on iodine therapy. The patient was discharged home Jor interval eonvalescence; she felt fairly well in the interim and was admitted to the Sloane Hospital in January, 1944, for removal of her abdominal tumor. Upon admission, there was mild tachycardia and nervousness; the blood pressure was 170/102. No other significant symptoms or signs of thyrotoxicosis were elicited.
Fig. 2.-The struma ovaril XliiO.
At laparotomy on 1/11/44, a large tumor'was found arising' from the left adnexal region and filling most of the abdominal cavity. The uterus appeared normal; the bowel was adherent to the tumor mass in several areas but the peritoneum was otherwise clear. A supravaginal hysterectomy and bilateral salpingo-oophorectomy were performed. Pathologic examination revealed the endometrium to be mildly hyperplastic, and the right ovary to be the site of a small serous cystadenoma. The left ovary had been replaced by a huge multilocular tumor mass measuring 23 by 12.5 by 8.5 cm. Approximately three liters of fluid had already been removed from one locule at operation. Some locuies were lined by a smooth grayish-tan membrane and contained clear yellow
540
A:\
fiuid. About one-third of the total volume of the tumol' was o('(,llpied b;v a honeycombed glall(l-like tissue wh ieh rfSPHl bled th~Toi(1 tissue grossly. On mi('roscopie examination, 11 varia1>l!' pattern was ('Iwounteredo Stratified squamous epithelium lilled sOllie of the spa('ps, whilt' numerous locules w('['(' lined by a single laYP1' of low ('olumnaJ' epit!Jplimll. The thyroid pOl'1ions of this (',Yst.ie teratoma also nn'ied. Tlwf'(' were sOllle small Heini dOSl'I~' al'J'angl'd with ('llhoidal epitheliulll lining' them, There 'were also some hu'gej' ;l('ini with low papillary infolding' and low ('o\umnar epithdillltl. It was llw imjlrPNsioll of Dr. F),(lllt:r; that tlH' ovarian struma showed mOl'(' pviden('(' of h,vIH'I'plasicl fUlIl Ipss of involution than 1Iw goitel'. The possihilit.\, t hat tIl(> t hyrotoxi('osis in this ('ase was diredh- related to 11](' ov:u'i;lIl struma was sLurg('stpd Tilt, probability that tht: ,;tj'UIIlH playC'(1 ~onl<' roll> ill thi~ ell'a'onill(' OWl'activity seems inCSe
Fit.!;. 3.-'T'hl::'
~trurna
()varii Xaou.
The patient made an uneventful n'{'overy frolll the operation, and has been well and without obserwd tac'hy('al'dia or thyrotoxiC' symptoms since, The hasal metaholiC' rate was 1)ot<>d at ,14 ]H'r ('('nt on 1/29/44 before discharg(' frolll t lIP hospital, and I ]H'J' ('('nt on 2/~1 /44. Discussion 'I'he case whieh Wl' have pl'esl'nted is notahlp in that a huge struma ('olli, a large struma ovarii, and ('vident thYJ'otoxic'osis W('l'C C'ocxistent. It is unfortunate that the possibility oj' IlHll'ian stl'111UH was not ('onsidered and the preliminary work-up ('HITied ont with thjs in mind. Despite the incomplet e data, Sl'veral points of interest haY(~ been derived from the case and from the review of the literature whi('h it has occasioned. The actual role of the ovarian tumor ill the production of the
GU8BEHG AXD DAXFOHTII:
8TRF)fA OVARII
541
hyperthyroidism is problematical, and no amo\lnt of stndy of the datu ean produce any ('onclusiw evidence. However, the comparative mieroseopie findings, the prohable meehanieal ('ontrihlltioll or the huge g'oiter to the elcvated hasal metabolie rate, and tht' persistent tachyeardia following thyroidec·tomy might all he eonsidel'ed as presumptive evidenee that the ovarian tumor eontrihnted to the thYl'010xieosis. That struma ovarii is eapahle of ])1"odw'ing or at least eontrihuting 10 thyrotoxieosis, is established. It is this ahility whieh distinguishes the ovarian struma among' all ovarian neoplasms, and removes it from the category of the simple pathologie c·nriosity. It should he emphasized that eases of fnuetioning ovarian struma may ('usily ('seape diagnosis, either through failure to appreeiatl' mild hyp('rth~'roid symptoms, or thl'ough (·hanel' avoidanee of thyroid tissue in the seetioning of large ovarian teratomata. In ]940, Emge estimated the rec'orded eases or struma ovarii at 150, of whieh 5 to 6 per e(mt were said to have produced thyrotoxieosis. 1 Sinec this time, some :31 ovarian strumuta have hecn reported ;2.!J of these, eight are said to have lW(,lI aceom panied by thy1'otoxieosis. Tn at least five eases, ('oi11('ident rlllarg(~ment of the thyroid was present. In three patients thyrotoxic symptoms were relieved by oophoreetomy alon('; in two of these, prior Nuhtotal thyroidectomy had failed to arrest the hyperthyroidism. It i,; of illtert'st t hat in most ~)f the eases in whieh such data are availahle, the oYUrian seehons have failed to show the presumed mieros{'opie stigmata of hyperthyroidism, despite aIl1elioration of symptoms by removal of the tUlllor. It would appeal' reasonable to ('onsider the ovarian struma a,; a JUB(,tioning part of the total thyroid tissue of the hody, whieh may react to iodine laek, to the thyrotropic hormone, or to other stimuli in a manner similar to that of the thyroid gland itself. If this hypothesis is tenahle, one might then ('onsider the removal of an ovarian struma as tantamount 10 subtotal ablation of the thyroid gland. 'l'he signal importunee of this disease pietul"c is manifested in the ease which presents distinet evidenee of thyrotoxieosis, plus enlargement of the thyroid gland, plus an ovaria11 tumor. If the thyroid does not by its very size demand removal, as it did in the ease herevyith presented. the, possibility of a fUl1etioning ovarian st rumH should he eonsidered, and the primary snrgieal eonsideratiol1 weighed. Two eases of apparently needless t.hyroidec·tomy in sl1<'h a situation are I"l'eorded in the reeent literature.
Summary
The ineidenee of struma ovarii among 297 ovarian teratomata of all types removed at the Sloane Hospital for 'Women during the past 20 years is 2.7 per ecnt. A ease is presented in which thyrotoxicosis, a large struma ovarii, and a huge goiter were coexistent. The reeent literature npon struma ovarii is briefly reviewed. 'l'he elinieal and therapeutic implieatiollS of this eondition arc eOllsidered.
542
AMERICi\~ JOURNAL OF OBSTETRICS A;-.II) GY~E:COL(}OY
References 1. 2. 3. 4.
5. 6. 7. 8. 9.
Bmge, L. A.: AM .•J. OSST. & GYXEC. 40: 7:~~, W40. Kleine, H. 0.: Zeutralbl. f. Gyn1ik. 63: 104D, 1()3fJ. Castano, C. A.: HoI. Soc. de ohst. y ginec. de Buenos Aires 19: 3]6, 1940. Murray, N. A., Dockerty, M. B., and Pemherton, J . de .T.: AM . .T. OSST. & GyX~;c. 44: ]34, 1!J42. Brown, A. I.., and Shoor, lIT.: Am. J. SUl'g. 55: In, 1!l42. Hundley, J. ~f.: AM. J. Os ST. & (fYXEC. 40: i 4D, 1D40. (Di~Cll~sion of Dr. Emge'A Paper. ) Wharton, L. H.: Gyneeology, With a Sertion 011 FemaJe l:ro!ogy, Philadelphia, 1943, W. B. Saunders Co., page 607. Sailer, S.: Am .•r. Clin. Path. 13: 27], I!H:1. Coh n, 8., a nd Kushner, J. D.: AM. J. OBST. & GVXEC. 47: 421, 1944.