Book - Contributions to Embryology Carnegie Institution No.56-16

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Chapter 16. Villous Nodules

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العربية | català | 中文 | 中國傳統的 | français | Deutsche | עִברִית | हिंदी | bahasa Indonesia | italiano | 日本語 | 한국어 | မြန်မာ | Pilipino | Polskie | português | ਪੰਜਾਬੀ ਦੇ | Română | русский | Español | Swahili | Svensk | ไทย | Türkçe | اردو | ייִדיש | Tiếng Việt    These external translations are automated and may not be accurate. (More? About Translations)

Mall FP. and Meyer AW. Studies on abortuses: a survey of pathologic ova in the Carnegie Embryological Collection. (1921) Contrib. Embryol., Carnegie Inst. Wash. Publ. 275, 12: 1-364.

In this historic 1921 pathology paper, figures and plates of abnormal embryos are not suitable for young students.

1921 Carnegie Collection - Abnormal: Preface | 1 Collection origin | 2 Care and utilization | 3 Classification | 4 Pathologic analysis | 5 Size | 6 Sex incidence | 7 Localized anomalies | 8 Hydatiform uterine | 9 Hydatiform tubal | Chapter 10 Alleged superfetation | 11 Ovarian Pregnancy | 12 Lysis and resorption | 13 Postmortem intrauterine | 14 Hofbauer cells | 15 Villi | 16 Villous nodules | 17 Syphilitic changes | 18 Aspects | Bibliography | Figures | Contribution No.56 | Contributions Series | Embryology History

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Pages where the terms "Historic Textbook" and "Historic Embryology" appear on this site, and sections within pages where this disclaimer appears, indicate that the content and scientific understanding are specific to the time of publication. This means that while some scientific descriptions are still accurate, the terminology and interpretation of the developmental mechanisms reflect the understanding at the time of original publication and those of the preceding periods, these terms and interpretations may not reflect our current scientific understanding.     (More? Embryology History | Historic Embryology Papers)
Fig. 284. Conceptus showing numerous trophoblastic nodules. (After Sommering.)

That the occurrence of numerous small nodules on the villi of young conceptuses must have attracted the attention and aroused the curiosity of early embryologists, one can not doubt. They often are so conspicuous, so spherical, and, when located on the tips of the villi, also so striking in appearance, that they could not be easily overlooked. Hence it does not surprise one that Miiller (1847), in his interesting monograph on moles, described them, and that Sommering (1799) had represented them, as figure 284, reproduced from the latter, shows. Miiller remarked that he did not always find them, and that they sometimes were absent in normal specimens. As will appear later, this is a very interesting and probably also a significant observation. Langhans (1877), in connection with a thoroughgoing microscopic examination of the placenta, spoke of these appendages as "insular nodules of maternal tissue," and also represented one. Langhans spoke of them as being 1 mm. in diameter, and said that their white color and turbid nature distinguished them from the more transparent swellings of the villi themselves. Their form was said to vary, and some were found to be located on the curved, enlarged processes of the villi, while others capped these processes. Microscopically, they were said to be composed of large, oval, round, polyhedral, spindleand star-shaped cells, usually a little flattened, which could easily be distinguished from the fetal cells by their size alone. Langhans stated that the cells composing these islands were decidual in origin, but that their nuclei were the size of the nuclei of the epithelium which separated them from the stroma of the villus. Langhans regarded them as decidual prolongations which penetrated the fetal placenta, and which hence might appear on the surface of the chorionic membrane itself.


As long as the exact origin of the placenta had not been decided at this time, it need not surprise one that Langhans should speak of these nodules as being composed of maternal tissue. Moreover, everyone who has examined conceptuses still implanted in or aborted with the decidua will admit that often it is impossible to draw a definite line of separation between the cells composing these nodules and the adjacent decidua. But it is not unlikely that exact differentiation between the two tissues is possible by the use of histochemical methods.


Kastschenko (1885) referred to the insular nodules of Langhans merely as cell nodules (Zellknoten), and stated that they are always composed of chorionic epithelium. It is not clear to me, however, whether Kastschenko did not, after all, confuse these nodules with syncytial buds. Besides, he stated that, although these cell nodules develop from the epithelium of the chorion, they later become serotina cells.


Heinz (1888) stated that the "insulae of maternal tissue" are especially common in placenta from the third to the sixth month, and that he never found them at term. He concluded that they are always composed of maternal tissue, that they are firm, and are located halfway between the serotina and the tips of the villi. In figures 3 to 5 accompanying his article, good representations of sections of villi with nodules partly embedded in the stroma of the villi are found. Heinz believed that they became separated from the rest of the maternal tissues by the growth of the villi, and thus became isolated and related to the latter. He thought that as the villi develop they begin to devour the maternal tissue with which the implanting conceptus is in contact, and that these nodules represented the only remnants of these maternal tissues. While Langhans thought that these nodules are formed merely by the invasion of the maternal by the fetal tissues, Heinz believed that they resulted from an invasion of the maternal tissues by villi, with accompanying destruction of the former. In support of his opinion, he referred to the well-known destructive power of the villi first revealed by Virchow, who called attention to the invasion of the maternal blood-vessels by fetal villi.


Minot (1889), contrary to Heinz, declared that the nodules within the villi are commoner in old placentae, a conclusion which prompts the inference that Minot may have regarded them and the so-called decidual islands of contemporary literature as identical.


Hofmaier (1890), in describing his Case V,a conceptus 20 by 5 mm., containing an embryo of 4 mm., stated that small nodules the size of the head of a pin were present everywhere on the villi. These nodules the author regarded as composed of decidual cells.


Kossman (1892) also spoke of insular nodules of maternal tissue and made fine drawings of sections cut 3 to 4 /z thick. He declared that it was plain that these nodules were composed of decidual tissue in which some of the villi became embedded, his idea being that portions of decidua became isolated from the rest and then were retracted by villi which lost their attachment to the decidua. Kossman stated that he never found nodules covered entirely by syncytium, as reported by Kastschenko, and doubted the occurrence of such. He further concluded that the cells composing these nodules do not simulate those composing the Langhans layer nearly as closely as Kastschenko had stated.


Crosti (1896) also spoke of these nodules and referred to them as appendici duraie, saying that they become hydropic in retained conceptuses.


In discussing conceptuses of the sixth week, Webster (1901) stated that he could distinguish three kinds of "Zellknoten." One was said to be composed of "undoubted decidual cells, along with a mass of cells which evidently belong to the proliferated Zellschicht at the end of an attached villus." These were said to be surrounded more or less by syncytium and might contain portions of it and also of the villi. Webster regarded this form of nodule as due to decidual elevations upon which the villi were implanted. A second form of Zellknoten was said to be composed solely of closely placed villi, along with several processes or strands of the syncytial layer. The third variety was said to be composed of villi surrounded by fibrin.


Pfannenstiel (1903) thought that the villous nodules are composed partly of decidua, but Rossi-Doria (1905) frankly stated that they are nothing but proliferations of the Langhans layer, especially common on the tips of the villi. RossiDoria nevertheless believed that the syncytium also may take part in their formation through proliferation by amitosis. This investigator, who made a careful examination of a conceptus 9 by 8 mm., stated that the trophoblastic nodules which form on the ends of the branches of the villi begin to appear after the second week of pregnancy. He concluded that they form not only on the free, but also on the fastening villi (Haftzotten), and doubted whether syncytium really can invade these nodules, as held by some investigators. J. Kollman (1907) also reported them in a conceptus 8 weeks old, and showed villi joining after passing through the nodules, forming what he called "villi adherentes."


If these nodules, found in such number on villi of many abortuses, and represented so well in the conceptus from Sommering, shown in figure 284, are decidual in origin, then it is clear that their substance is in fact preformed, and if they antedate the formation of the villi it would seem that they might appear very soon after the formation of the latter. If, on the other hand, they are products of the epithelium of the villi, then a short interval after the formation of the latter is necessary to enable such accumulations to form. No one has held that they are direct products of the ovular ectoderm, which secondarily become related to the villi, and, from what has been described in the earliest known implantation stages, it would seem that this is not the case. Although the ectoderm of the implanting ovum apparently is extremely active, probably especially so during the invasive stage of the implantation, these nodules apparently do not arise directly from it.


In the description of some of the cases, and also in publications, I have sometimes used the term trophoblastic nodule. The cells composing these nodules, however, undoubtedly arise from the Langhans layer, the syncytium usually being absent; and since the nodules really are not remnants of the early trophoblast, it would perhaps be better to relinquish this term altogether and to refer to them merely as villous nodules. However, I have been greatly puzzled to find a good name for these special masses of cells arising from the Langhans layer. The term insular nodule, introduced by Langhans, would be entirely acceptable did it not carry with it the possibility of confusion with decidual islands, for if they really were islands, confusion would be particularly likely, because Langhans thought that they were maternal in origin. The term cell-nodule (Zellknoten), introduced by Kastschenko, also is not without objection for the same reason. The designation "appendici durate" used by Crosti does not recommend itself either, because one scarcely can speak of most of them as appendages, for the simple reason that they are almost wholly embedded in the stroma of the villi. Then, too, they are so small that one scarcely feels justified in speaking of them as hard. In very young villi the designation trophoblastic or trophodermic nodules would seem quite appropriate, especially since they frequently contain syncytial masses among the Langhans cells; but later on, long after the trophoderm or trophoblast has ceased to exist as such, this designation seems far less appropriate.


Nor is the term villous nodules wholly unobjectionable, for they are not, as a rule, composed to any appreciable extent of villi, though a group of 6 or more villi not infrequently pass through or are united by them. But since it seemed the least objectionable term, I have adopted it.

That these nodules really have the origin attributed to them by Rossi-Doria seems undoubted, although it is not impossible that rarely they may contain some adhesions or inclusions of decidual cells. These would be entirely accidental, however, and would result from portions of the decidua adhering to or being surrounded by the proliferating Langhans cells, and thus becoming included in the nodules. If, as Rossi-Doria stated, and as I believe, they arise from the Langhans layer of the villi, then the fact that they frequently contain masses of syncytium within their interior or at their margins offers no difficulties to those who believe that the syncytium arises from this layer. Nor would it be difficult to explain the presence of included syncytial masses within the nodules upqn the assumption that the syncytial layer has an origin independent of the Langhans layer. But in any case, an origin from either of these layers would imply that they might be expected to be especially numerous in any condition in which unusual activity occurs in these layers. Hydatiform degeneration is such a condition, and that these nodules are especially numerous in many of the specimens of hydatiform degeneration can easily be demonstrated. Whenever the epithelial proliferation is very pronounced, however, it does not manifest itself in the formation of nodules, but in the production of irregular trabeculse, garlands and even trellis-works of cell-cords, such as represented in figure 9 (plate 1, Chap. IV). It also is conceivable that these spherules might form during the stage of spontaneous regression of Iryperactivity of the epithelium or in the earlier stages of hyperactivity; for a more or less spherical nodule manifestly could result only from proliferation in many instead of predominatingly in one or two directions only.

I have also found these nodules common upon the ends of the villi, as is shown so well to the left in figure 285 and still better in figure 116 (plate 10, Chap. VIII). But, as noticed by previous investigators, and as shown in figures 285 and 286, they are not limited to these locations. I have never found them stalked, but always sessile, and embedded in the stroma of the villi even, as shown in figure 287. Indeed, not infrequently the epithelial proliferation, instead of resulting in an elevation upon the surface of the villi, extends largely into the stroma, so that sections of nodules were completely surrounded by it. All manner of transition stages between extravillous and intravillous locations were seen, and more or less hemispherical accumulations also were found directly upon the chorionic membrane.

It is not at all uncommon to find these nodules located nearer the base of a villous tree, as shown in figures 288 and 289. This does not, however, imply that those so located were not apical once, for they may have formed on a short sidebranch which they completely surrounded. Not infrequently several villi, even up to half a dozen or more, may be united by and terminate in a single nodule, as shown in figure 291; or they may penetrate it, as represented by Kollman. Not infrequently considerable groups of nodules are found in a single small region, as illustrated by the teased preparation shown in figure 290. It is not uncommon to find half a dozen or more nodules in section in a single field of the microscope under low magnification of cross-sections of villi, and when they are so numerous as this the villi in these areas may look matted in consequence.


They never seem to attain any considerable size, seldom becoming larger than 1 to 2 mm. This would seem to imply that, whatever the cause of their formation, the process is self-limited. I have never seen a chorionic vesicle in which large areas were capped or united by these proliferations, as are the early villi by trophoderm, for example; but they are decidedly resistant and persist long after the villi have degenerated. Nor have I ever seen them detached, for they seem to retain their hold even after the villi become decidedly macerated, as illustrated in figure 292. I, too, have found them most common in relatively small chorionic vesicles, and never have seen one on mature, normal villi.


Since I used no special microchemical methods, I can add but little to what is recorded in the literature regarding their structure. I do not believe, however, that the syncytial inclusions are syncytial in origin, or that they are ordinarily degeneration products. They seem to arise directly from the cells composing the nodules. Hence, as stated elsewhere (Meyer, 1918), this conclusion, if correct, off ers further confirmatory evidence of the origin of the syncytium from the Langhans layer. It can easily be demonstrated that the villous syncytium is penetrated rapidly, as a rule, by proliferation of the underlying Langhans layer, and all stages in this process of protrusion of the cellular accumulations, through the underlying syncytium, can be found. Since marked proliferation of the Langhans layer can occur without hyperactivity on the part of the syncytium, it also is clear that the syncytium may for this reason alone fail to take part in the formation of these nodules. No matter how numerous the syncytial buds in cases of exquisite early hydatiform degeneration, for example, I have never seen appearances suggesting in the slightest the origin of these nodules from syncytium. It is difficult to form an opinion of their functional significance, but it does not seem improbable to me that they may result from an attempt on the part of the younger branches of the villi to gain contact with the decidua and so restore better nutritional conditions.


Description of Plates

Plate 24

Mall Meyer1921 plate24.jpg

Fig. 283. Cross section of intensely fibrous villi from No. 7656. (See Chapter XV.)

Fig. 284. Conceptus showing numerous trophoblastic nodules. (After Sommering.)

Fig. 285. Portion of chorionic vesicle showing an apical villous nodule to the right and others elsewhere. No. 1495a. X2.4.

Fig. 286. Chorionic vesicle showing numerous small villous nodules. No. 2197. XI. 6.

Fig. 287. A villous nodule completely surrounded by stroma, except at its free surface not shown in the figure. No. 556.

Fig. 288. A villous nodule near the base of a villous tree. No. 2365. X7.2.

Fig. 289. Villous nodules and lichen-like streamers on a villous tree. No. 2204. X7.2.

Fig. 290. A group of teased villi bearing numerous trophoblastic nodules. No. 2225. X4.8.

Fig. 291. Several villi ending in a single trophoblastic nodule. No. 308. X4.8.

Fig. 292. A macerated villous tree, one branch of which bears a nodule on its extremity. No. 2472. X7.2.


Plate 24: Fig. 283 | Fig. 284 | Fig. 285 | Fig. 286 | Fig. 287 | Fig. 288 | Fig. 289 | Fig. 290 | Fig. 291 | Fig. 292 | Chapter 16 Villous Nodules


Embryology - 6 Dec 2019    Facebook link Pinterest link Twitter link  Expand to Translate  
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العربية | català | 中文 | 中國傳統的 | français | Deutsche | עִברִית | हिंदी | bahasa Indonesia | italiano | 日本語 | 한국어 | မြန်မာ | Pilipino | Polskie | português | ਪੰਜਾਬੀ ਦੇ | Română | русский | Español | Swahili | Svensk | ไทย | Türkçe | اردو | ייִדיש | Tiếng Việt    These external translations are automated and may not be accurate. (More? About Translations)

Mall FP. and Meyer AW. Studies on abortuses: a survey of pathologic ova in the Carnegie Embryological Collection. (1921) Contrib. Embryol., Carnegie Inst. Wash. Publ. 275, 12: 1-364.

In this historic 1921 pathology paper, figures and plates of abnormal embryos are not suitable for young students.

1921 Carnegie Collection - Abnormal: Preface | 1 Collection origin | 2 Care and utilization | 3 Classification | 4 Pathologic analysis | 5 Size | 6 Sex incidence | 7 Localized anomalies | 8 Hydatiform uterine | 9 Hydatiform tubal | Chapter 10 Alleged superfetation | 11 Ovarian Pregnancy | 12 Lysis and resorption | 13 Postmortem intrauterine | 14 Hofbauer cells | 15 Villi | 16 Villous nodules | 17 Syphilitic changes | 18 Aspects | Bibliography | Figures | Contribution No.56 | Contributions Series | Embryology History

Historic Disclaimer - information about historic embryology pages 
Mark Hill.jpg
Pages where the terms "Historic Textbook" and "Historic Embryology" appear on this site, and sections within pages where this disclaimer appears, indicate that the content and scientific understanding are specific to the time of publication. This means that while some scientific descriptions are still accurate, the terminology and interpretation of the developmental mechanisms reflect the understanding at the time of original publication and those of the preceding periods, these terms and interpretations may not reflect our current scientific understanding.     (More? Embryology History | Historic Embryology Papers)