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Amnion nodosum: A lesion of the placenta apparently associated with deficient secretion of fetal urine
AMNION NODOSUM: ASSOCIATED WITH BENJAMIN (From
the
1kpurtszenf.s
of
A LESION DEFICIENT H. Pathology,
OF THE PLACENTA APPARENTLY SECRETION OF FETAL URINE
LANDING, the
M.D.,
Boston School)
BOSTOS, f,yi,tt,c/-iz
MASS.
lTospifnl
cwtl
Hwtnrtl
Mrd.‘ctrl
M
AJOR congenital malformations of the urinary tract, resulting in deliciency of excretion of fetal urine into the amniotic sac, are known to be responsible for some cases of oligohydramnios,‘* z but in the majority of cases reported the placenta is either not described or stated to be normal. However, a small group of placentas has been described. the ma,jot*ity from cases of’ oligohydramnios, which showed a lesion previously called “amniotic nodules” (Amnionkniitchen) .3-R, I’)* I1 These placentas show man>- small nodules, which are most numerous in the placental portion of the amnion; therefore, the name “amnion nodosum” is suggested for this condition. Although this lesion of the amnion had been observed on two previous occasions in the Department of Pathology at the T!oston Lying-in Hospital. it, had been considered an incidental finding of unknown significance until i1 cdasr observed recently served to focus interest on it and to prompt this study. Materials The index files were reviewed with respect to lesions of the amnion, a,nd in all suggestive cases specimens were examined microscopically. In addition, the protocols for all infants examined at autopsy from 1931 to the present were reviewed, and all cases with congenital malformations (a total of 200 infants) were selected. The term congenital malformations was used to include abnormalities of development such as Meckel’s diverticulum, malrotation of the intestine, and polydactylia, which were never causes of death in this series, as well as the more serious anomalies, congenital heart disease, imperforate anus. tracheoesophageal fistula, diaphragmatic hernia, absent or polyc,ystic kidneys. anencephaly, myelomeningocele, harelip and cleft palate, and others. The placentas of 112 of these 200 infants had been examined both gt~sly and microscopically, but the microscopic sections did not include the amnion in 37 cases, so that 75 placentas of infants with congenital malformations confirmc~l at autopsy were available for study. In adclition, the placentas of 200 infant,s who did not die from congenital anomalies were studied as a control series. Results Amnion nodosum was found in 8 placentas, 3 from the group dexed under abnormalities of the amnion and 5 from the group of died with congenital malformations. No cases were found in the centas. The nat.ure of the fetus associatetl with each of these 8 listed in Table T. 1 %?I!1
of cases ininfants who control plaplacentas is
In only 2 of these 8 cases were the amniotic nodules noted grossly, but in both they appeared as multiple, firm, rounded, raised yellow spots 1 to 3 mm. in diameter on the amnion of bot,h the membranes and the fetal surface of the placenta. TABLE
I.
NATURE
OF THE
FETI:S
IN 8 CASES
OF AMXION ___--
Renal aeenesis syndrome9 Polycy&o kidneys Hypoplastic polycystic kidneys One kidney polycystic and one imperforate anus and vagina, cleft palate Stillborn with multiple anomalies Stillborn (no autonsv1
hypoplastic, diaphragmatic (no
autopsy)
NODOSUM CASES ” 1 1
anencephaly, hernia, 1 2 1
Microscopically (Figs. 1 and 2) these nodules are seen to be rounded-tooval masses, most commonly situated on the surface of the amnion, but occasionally embedded in the amniotic mesoderm, or even projecting through it into the cleft between the amnion and chorion. They consist of varying proportions of squamous cells of the amniotic fluid and a matrix of collagen, as shown by Mallory’s aniline blue and phosphotungstic acid hematoxylin stains. The amniotic epithelium either is absent in the region of the nodules or partially persists beneath them as small strips or inclusion cysts. The appearance of these structures suggests that they are the result of adhesion of masses of amniotic squamae to the surface of the amnion, with subsequent degeneration of the amniotic epithelium and invasion of the squamous-cell mass by connective tissue. Masses of amniotic squamae applied to the surface of the amnion These lesions show no relation have been observed in some of these sections. to squamous metaplasia or to polypoid hyperplasia of the amnion, two processes which seem to be related and which may tend to occur together, nor do they seem to result from degenerative changes in either of these lesions.
Comment Of the eleven previously described placentas which may be instances of this process,“-s, lo, I1 three are rather doubtful,“, F, * but the other eight appear to show the same lesion. Of these no mention is made of the condition of the fetus in five cases 3, 4, 5, lo, I1 one fetus” is described as having no major congenital malformations, and two fetuses 3* 7 had major anomalies of the urinary tract. Thus, it seems that the condition, amnion nodosum, is the result of oligohydramnios rather than the cause, and that it is not associated with oligohydramnios of any given cause. Major congenital malformations of the urinary tract are probably the most common cause of a significant degree of oligohydramnios, and apparently were the factors leading to the production of amnion nodosum in five of the eight cases reported here. However, if amnion nodosum is simply the result of processes set under way by failure of fetal urine secretion, it may occur in some cases of intrauterine death of normally formed fetuses, if abortion is delayed for a sufficiently long period after the death of the fetus. Whether this is the explanation of the occurrence of amnion nodosum in the three placentas of stillborn infants on whom postmortem examination was not performed, which are described earlier, cannot be stated, but two of these infants had multiple anomalies visible on external examination, so that the presence of major anomalies of the urinary tract cannot be ruled out entirely. Two possible mechanisms by which oligohydramnios leads to amnion nodosum can be suggested. One is that amniotic squamae from the abnormally
Fig. Fig. ejection Fig. connective
l.-Amnion nodosum. into amniotic mesodcrm 2.-Rorder of amniotic tissue (eosin-methylene
There is absence (eosin-methylene nodule showing blue stain,
2. of amniotic epithelium in involved blue stain, X40). nmss of amniotic squamae partially X 725 ).
au?as inv
1:&k!
LANDING
Am. .J. Obst. & ~;~.rrec. December.
1950
concentrated amniotic fluid adhere to the surface of the amnion and produce secondary degeneration of the amniotic epithelium ; the masses of adherent squamae are then invaded by the amniotic mesoderm. An alternative explanation is that fetal movements produce traumatic erosion of the amniotic epithelium, and the squamae adhere to the exposed mesoderm and become incorporatecl in it as it proliferates. It is not possible to decide between these two possible mechanisms on the ba,sisof the data available.
Summary Amnion nodosum is a process characterized by multiple, focal lesions of the amnion, consisting of masses of adherent amniotic squamae partially invaded by amniotic mesoderm. The nodules thus formed have previously been called Anbnionkniitchen (amniotic nodules). This report is based on a study of amnion nodosum occurring in the placentas of eight stillborn infants or infants with major congenital renal anomalies. The study suggests that amnion nodosum is the result of processes set under way by oligohydramnios, caused most commonly by deficiency of fetal urine excretion.
References 1. Bar&-am, Erik: Acta obst. et gynec. Scandinav.10: 134, 1930. 2. Bates,G. S.: AM. J. OBST. & GYNEC. 25: 41, 1933. 3. Bergendal!8.: Acta obst. et gynec. Scandinav.9: 41, 1930.
4. 5. 6. 7. 8. 9. IO. 11.
Burdzinskr, T.: Quoted by Bergendal, S.3 von Franque, 0.: Monatschr. f. Geburtsh. u. GynLk. 6: 36, 1897. Beitr. z. Geburtsh. u. Gynak. 8: 1, 1903. Holzapfel, K.: Nordenson, N. G.: Acta obst. et gynec. Scandinav. 12: 267, 1932. Pilgram, H.: Quoted by Bergendal, S.3 Potter, Edith L.: J. Pediat. 29: 68, 1946. Schulz, K.: Beitr. z. path. Anat. u. z. allg. Path. 82: 185, 1929. Sitzenfrey, A.: Beitr. z. Geburtsh. u. Gynak. 17: 1, 1911.
the
1kpurtszenf.s
of
A LESION DEFICIENT H. Pathology,
OF THE PLACENTA APPARENTLY SECRETION OF FETAL URINE
LANDING, the
M.D.,
Boston School)
BOSTOS, f,yi,tt,c/-iz
MASS.
lTospifnl
cwtl
Hwtnrtl
Mrd.‘ctrl
M
AJOR congenital malformations of the urinary tract, resulting in deliciency of excretion of fetal urine into the amniotic sac, are known to be responsible for some cases of oligohydramnios,‘* z but in the majority of cases reported the placenta is either not described or stated to be normal. However, a small group of placentas has been described. the ma,jot*ity from cases of’ oligohydramnios, which showed a lesion previously called “amniotic nodules” (Amnionkniitchen) .3-R, I’)* I1 These placentas show man>- small nodules, which are most numerous in the placental portion of the amnion; therefore, the name “amnion nodosum” is suggested for this condition. Although this lesion of the amnion had been observed on two previous occasions in the Department of Pathology at the T!oston Lying-in Hospital. it, had been considered an incidental finding of unknown significance until i1 cdasr observed recently served to focus interest on it and to prompt this study. Materials The index files were reviewed with respect to lesions of the amnion, a,nd in all suggestive cases specimens were examined microscopically. In addition, the protocols for all infants examined at autopsy from 1931 to the present were reviewed, and all cases with congenital malformations (a total of 200 infants) were selected. The term congenital malformations was used to include abnormalities of development such as Meckel’s diverticulum, malrotation of the intestine, and polydactylia, which were never causes of death in this series, as well as the more serious anomalies, congenital heart disease, imperforate anus. tracheoesophageal fistula, diaphragmatic hernia, absent or polyc,ystic kidneys. anencephaly, myelomeningocele, harelip and cleft palate, and others. The placentas of 112 of these 200 infants had been examined both gt~sly and microscopically, but the microscopic sections did not include the amnion in 37 cases, so that 75 placentas of infants with congenital malformations confirmc~l at autopsy were available for study. In adclition, the placentas of 200 infant,s who did not die from congenital anomalies were studied as a control series. Results Amnion nodosum was found in 8 placentas, 3 from the group dexed under abnormalities of the amnion and 5 from the group of died with congenital malformations. No cases were found in the centas. The nat.ure of the fetus associatetl with each of these 8 listed in Table T. 1 %?I!1
of cases ininfants who control plaplacentas is
In only 2 of these 8 cases were the amniotic nodules noted grossly, but in both they appeared as multiple, firm, rounded, raised yellow spots 1 to 3 mm. in diameter on the amnion of bot,h the membranes and the fetal surface of the placenta. TABLE
I.
NATURE
OF THE
FETI:S
IN 8 CASES
OF AMXION ___--
Renal aeenesis syndrome9 Polycy&o kidneys Hypoplastic polycystic kidneys One kidney polycystic and one imperforate anus and vagina, cleft palate Stillborn with multiple anomalies Stillborn (no autonsv1
hypoplastic, diaphragmatic (no
autopsy)
NODOSUM CASES ” 1 1
anencephaly, hernia, 1 2 1
Microscopically (Figs. 1 and 2) these nodules are seen to be rounded-tooval masses, most commonly situated on the surface of the amnion, but occasionally embedded in the amniotic mesoderm, or even projecting through it into the cleft between the amnion and chorion. They consist of varying proportions of squamous cells of the amniotic fluid and a matrix of collagen, as shown by Mallory’s aniline blue and phosphotungstic acid hematoxylin stains. The amniotic epithelium either is absent in the region of the nodules or partially persists beneath them as small strips or inclusion cysts. The appearance of these structures suggests that they are the result of adhesion of masses of amniotic squamae to the surface of the amnion, with subsequent degeneration of the amniotic epithelium and invasion of the squamous-cell mass by connective tissue. Masses of amniotic squamae applied to the surface of the amnion These lesions show no relation have been observed in some of these sections. to squamous metaplasia or to polypoid hyperplasia of the amnion, two processes which seem to be related and which may tend to occur together, nor do they seem to result from degenerative changes in either of these lesions.
Comment Of the eleven previously described placentas which may be instances of this process,“-s, lo, I1 three are rather doubtful,“, F, * but the other eight appear to show the same lesion. Of these no mention is made of the condition of the fetus in five cases 3, 4, 5, lo, I1 one fetus” is described as having no major congenital malformations, and two fetuses 3* 7 had major anomalies of the urinary tract. Thus, it seems that the condition, amnion nodosum, is the result of oligohydramnios rather than the cause, and that it is not associated with oligohydramnios of any given cause. Major congenital malformations of the urinary tract are probably the most common cause of a significant degree of oligohydramnios, and apparently were the factors leading to the production of amnion nodosum in five of the eight cases reported here. However, if amnion nodosum is simply the result of processes set under way by failure of fetal urine secretion, it may occur in some cases of intrauterine death of normally formed fetuses, if abortion is delayed for a sufficiently long period after the death of the fetus. Whether this is the explanation of the occurrence of amnion nodosum in the three placentas of stillborn infants on whom postmortem examination was not performed, which are described earlier, cannot be stated, but two of these infants had multiple anomalies visible on external examination, so that the presence of major anomalies of the urinary tract cannot be ruled out entirely. Two possible mechanisms by which oligohydramnios leads to amnion nodosum can be suggested. One is that amniotic squamae from the abnormally
Fig. Fig. ejection Fig. connective
l.-Amnion nodosum. into amniotic mesodcrm 2.-Rorder of amniotic tissue (eosin-methylene
There is absence (eosin-methylene nodule showing blue stain,
2. of amniotic epithelium in involved blue stain, X40). nmss of amniotic squamae partially X 725 ).
au?as inv
1:&k!
LANDING
Am. .J. Obst. & ~;~.rrec. December.
1950
concentrated amniotic fluid adhere to the surface of the amnion and produce secondary degeneration of the amniotic epithelium ; the masses of adherent squamae are then invaded by the amniotic mesoderm. An alternative explanation is that fetal movements produce traumatic erosion of the amniotic epithelium, and the squamae adhere to the exposed mesoderm and become incorporatecl in it as it proliferates. It is not possible to decide between these two possible mechanisms on the ba,sisof the data available.
Summary Amnion nodosum is a process characterized by multiple, focal lesions of the amnion, consisting of masses of adherent amniotic squamae partially invaded by amniotic mesoderm. The nodules thus formed have previously been called Anbnionkniitchen (amniotic nodules). This report is based on a study of amnion nodosum occurring in the placentas of eight stillborn infants or infants with major congenital renal anomalies. The study suggests that amnion nodosum is the result of processes set under way by oligohydramnios, caused most commonly by deficiency of fetal urine excretion.
References 1. Bar&-am, Erik: Acta obst. et gynec. Scandinav.10: 134, 1930. 2. Bates,G. S.: AM. J. OBST. & GYNEC. 25: 41, 1933. 3. Bergendal!8.: Acta obst. et gynec. Scandinav.9: 41, 1930.
4. 5. 6. 7. 8. 9. IO. 11.
Burdzinskr, T.: Quoted by Bergendal, S.3 von Franque, 0.: Monatschr. f. Geburtsh. u. GynLk. 6: 36, 1897. Beitr. z. Geburtsh. u. Gynak. 8: 1, 1903. Holzapfel, K.: Nordenson, N. G.: Acta obst. et gynec. Scandinav. 12: 267, 1932. Pilgram, H.: Quoted by Bergendal, S.3 Potter, Edith L.: J. Pediat. 29: 68, 1946. Schulz, K.: Beitr. z. path. Anat. u. z. allg. Path. 82: 185, 1929. Sitzenfrey, A.: Beitr. z. Geburtsh. u. Gynak. 17: 1, 1911.