REPORT OF A CASE OF ECTOPIC GES- 
TATION ASSOCIATED WITH TUBER- 
CULOSIS OF THE TUBES, PLACENTA, 
AND FETUS. 
BY 
ALFRED SCOTT WARTHIN, M.D., 
INSTRUCTOR IN PATHOLOGY, UNIVERSITY OF MICHIGAN, ANN ARBOR. 
FROM 
THE MEDICAL NEWS, 
September 10, 1896. [Reprinted from The Medical News, Sept. 19, 1896. | 
REPORT OF A CASE OF ECTOPIC GESTATION 
ASSOCIATED WITH TUBERCULOSIS 
OF THE TUBES, PLACENTA, 
AND FE TUS.1 
By ALFRED SCOTT WARTH1N, M.D., 
INSTRUCTOR IN PATHOLOGY, UNIVBRSITY OF MICHIGAN, 
ANN ARBOR. 
In so far as I have been able to discover, the case which 
I present in this report is unique in being the first case of 
extrauterine pregnancy associated with tuberculosis of the 
tubes, that has yet been observed. While the field of the 
etiology of ectopic gestation is thus enlarged by the ad- 
mission of a new factor, the case becomes more important 
because of the undoubted proof of the existence of tuber- 
culosis in the placenta and fetus. For this reason its re- 
lation to the question of the inheritance of tuberculosis 
gives the case the greatest scientific interest. This ques- 
tion, still open to discussion, receives here important evi- 
dence as to the possibility of the infection of the child from 
a diseased parent in its intrauterine life. 
The patient who forms the subject of this report was 
from the clinic of Dr. James N. Martin, Professor of 
Gynecology and Obstetrics in the University of Michigan, 
and to his kindness and courtesy I am indebted for the his- 
tory of the case and the results of the operation. The 
history is briefly as follows : 
Mrs. F. C., thirty-eight years of age, had been married for 
thirteen years. She had had no children and no abortions. 
Her periods had always been regular until August, 1895. 
At that time she menstruated in the second week, and 
then did not have a return until February, 1896. From 
1 Read before the Michigan State Medical Association, June, 
1896. 2 
August to October she felt well, but early in that month 
she had a sudden attack of sharp and sickening pains low 
down in her left side. The patient described these pains 
as darting in all directions, and “ feeling as if the navel 
was being pulled backward. ” There was a decided ten- 
dency to collapse, but the symptoms soon subsided. Two 
days after she had another, but less severe attack, and 
six days later she was again attacked with pains so severe 
that the use of morphin was necessary. After the attack 
the patient felt very weak and faint; a general peritonitis 
followed, and it was thought that there was an intestinal 
obstruction. From this attack she recovered slowly. Four 
weeks later she had sensations of throbbing, heat, and pain 
in the pelvis. This was followed by an abundant dark- 
brownish discharge from the vagina, containing soft, 
cheesy masses, looking like thick pus. Toward the end 
of each discharge an offensive odor was noticed. These 
discharges continued at intervals for about three weeks, 
being always preceded by sensations of throbbing, heat, 
and pain. At this time there was passed something re- 
sembling a small sack. From the beginning of the trouble 
the patient gradually declined and lost strength. She could 
not rest upon either side because of drawing sensations. 
Her periods returned in February and again in March. 
These lasted but one day, the usual duration having been 
from one and a half to three days. The amount was small 
and there was much pain. She had also at times a thick 
white discharge from the vagina, small in amount. 
She was admitted to the University Hospital on the 
26th of March, 1896. Her general condition at this time 
was fair, there was a slight anemia; she was weak but 
not emaciated. Her appetite was fair, but digestion was 
not normal. The bowels were regular. Her locomotion 
was not difficult. There were no symptoms on the part 
of heart or lungs. During the week preceding the opera- 3 
tion she had no temperature, and there was nothing in the 
general aspect of the case to suggest tuberculosis. 
The physical examination was made on the 27th. The 
examination of the heart and lungs was negative. On the 
left side and low down close to the walls of the pelvis, 
there were dulness and some thickening. The vault of the 
vagina was tense. The cervix and uterus rested back- 
ward, the uterus being immovable, and very sensitive. It 
measured two and a half inches. At the left of the ute- 
rus, extending obliquely outward and upward toward the 
wall of the pelvis, there was an oval mass, rather irregular 
in outline and very sensitive. This pushed the uterus to 
the right, and the cervix somewhat backward. No exam- 
ination of the blood was made. The urine examination 
was negative with the exception of the presence of a small 
amount of pus. Neither this nor the -vaginal discharge 
was stained for tubercle bacilli. 
With the exception of the cessation of the menses, the 
patient had had no symptoms or signs that would lead her 
to believe that she was pregnant, and she did not think that 
she was in that condition. The diagnosis of extrauterine 
pregnancy was, however, made by Dr. Martin, and the 
patient was prepared for operation. This took place on 
the 3d of April. 
A median incision was made. The parts were found 
to be very vascular, and there were many adhesions be- 
tween the uterus, appendages, and intestines. The right 
tube was found to be tortuous and enlarged, and the ovary 
cystic. These were removed and the stump cauterized. 
In the fimbriated extremity was a nodular hemorrhagic 
mass, about the size of a hazelnut. This was separated 
during the operation and preserved for future examina- 
tion. The left ovary was found in about its normal loca- 
tion. It was enlarged and cystic. Above it, and attached 
to it by many adhesions, extended the thickened and 
twisted tube which passed upward into a mass about the 4 
size of a cocoanut. This mass was covered by friable 
adhesions, and lay up well toward the intestines. The 
distal portion of the tube passed into the lower surface of 
this mass and was lost in the adhesions covering it. 
About an inch to the right of this the greatly thickened 
tube was again found and traced on to the uterus, the 
cyst, therefore, arose from the tube about an inch and a 
half from this organ. The mass was dissected out with 
the greatest difficulty. When the adhesions covering the 
upper surface were removed, the head of a fetus was seen 
protruding from a rent in this portion of the mass. In re- 
moving the cyst the distal portion of the tube, together 
with the ovary, was separated. These were also removed. 
The uterine portion of the tube was severed about one- 
half inch from the uterus, and the stump cauterized. The 
cyst was then opened in the presence of the class and the 
fetus demonstrated, but the tubercular nature of the tubal 
disease was not then suspected. After the demonstra- 
tion, the specimens were placed in four per cent, solution 
of formalin and brought to my laboratory. 
On the next morning I began my examination of these, 
with the following results : 
Right ovary and tube.—The right ovary was about the 
size of a small walnut; its surface was slightly nodular. 
Between it and the tube there was a mass of new tissue, 
about one-fourth of an inch thick, nodular, and hemor- 
rhagic. From this mass a piece attached to the fimbrite 
had been removed during the operation. The cut surface 
of the ovary showed the usual hyalin and cystic degene- 
ration of the Graafian scars. The gross appearance of 
the small hemorrhagic mass was so characteristic of the 
hemorrhagic tubercles of the peritoneum, that it was at 
once cut and stained. The suspicion was confirmed by 
the microscopical picture. The mass consisted almost 
entirely of epithelioid cells; in some portions there was a 
reticulum of rather coarse connective-tissue fibers. There 5 
were also large areas of caseous necrosis, and among the 
epithelioid cells at the periphery of the caseated areas there 
were occasional giant-cells with many nuclei. Many of 
these giant-cells showed beginning caseation. There 
were but few blood-vessels. Large areas showed exten- 
sive recent hemorrhages, while others gave evidence of 
old extravasation by the large amount of hemosiderin 
scattered throughout the tissue. Sections of this mass 
were stained for tubercle bacilli in the usual way, with 
carbolic fuchsin, and the presence of the bacilli in scanty 
numbers was demonstrated. 
On cutting into the distended right tube it was found to 
be filled with a soft, cheesy substance, which had not been 
entirely hardened by the formalin. Smears were made 
from this and stained for tubercle bacilli, with negative 
results. Thin transverse sections of the tube were then 
hardened in absolute alcohol, embedded in celloidin and 
cut. Some of these sections were stained with the Van 
Gieson’s stain, and others with hemalum. These sec- 
tions, on examination, were found to give a beautiful pic- 
ture of tubal tuberculosis. The wall of the tube was 
much thickened, the vessels were congested, and there 
were numerous areas of hemorrhage and small-celled in- 
filtration in the connective tissue, and between the layers 
of muscle. Small miliary tubercles were also numerous 
throughout the wall and under the outer coat. In many 
sections the lumen of the tube was entirely filled by a 
mass of tubercles in all stages of growth, the epithelium 
of the plications of the mucosa being entirely lost. The 
tubercles were chiefly epithelioid, with a limited small- 
celled infiltration around the periphery. In some sections 
giant-cells were numerous, in others only a few could be 
found. Extensive areas of caseation with occasional 
masses of calcification were found in some sections. In 
others the lumen was only partly obstructed, and 
numerous small miliary tubercles were scattered through 6 
the mucosa just beneath the epithelium, which was pre- 
served. These tubercles were epithelioid, with a moder- 
ate small-celled infiltration. Giant-cells were numerous, 
but caseation was not extensive. Masses of calcification 
were not uncommon. In many places the folds of the 
mucosa presented a perfectly normal structure, except for 
the presence of the tubercles, but in others there was a 
marked inflammatory process with destruction of the mu- 
cosa, and the presence of large areas of small-celled in- 
filtration. Some of these areas were freshly hemorrhagic, 
others were full of hemosiderin. Toward the uterine end 
of the tube the process became more miliary in type, and 
less marked. The sections of this tube stained for the 
bacilli gave negative results. 
Left (roary.—The left ovary was much larger than the 
right, about the size of a large walnut. The surface was 
uneven and covered with the stringy remains of many ad- 
hesions which had bound it to the cyst. Many small 
cysts projected on its surface, and on its upper margin a 
true corpus luteum presented. The cut surface showed 
numerous small cysts, hyalin scars, and a true corpus 
luteum, about three-quarters of an inch in diameter, and 
of a pale yellow. The convoluted inner margin sur- 
rounded a mass of coagulated mucin which was slightly 
hemorrhagic. The fimbriated extremity of the tube was 
occluded by a small hemorrhagic mass, and in the fim- 
briae were several small cysts and a few small, firm, 
yellowish nodules. The tube was much distended and 
twisted, but became about normal in size at the point 
where it passed into the cyst. On the surface of the tube 
and ovary there were several small, irregular, brownish 
masses attached loosely by thin bands of adhesions. Sec- 
tions of these nodules showed them to be hemorrhagic 
tubercles of the same character as the one from the right 
ovary, having the same resemblance to the hemorrhagic 
tubercles so often found on the peritoneum. 7 
Sections of the distal end of the tube, when examined 
microscopically, gave a picture similar to that of the right 
side. There was a miliary tuberculosis of the mucosa, 
Fig. i. 
a—Normal tissue of cord, b—Wall of umbilical vessel, c—Lu- 
men of vessel, d—Areas of caseation, f-—Small-celled infiltra- 
tion. g—Epithelioid cells, h—Masses of calcification. 
SECTION OF UMBILICAL CORD (ABOUT I75X).1 
but in some sections the appearance was that of a diffuse 
process affecting also the walls of the tube. There were 
1 Made from formalin-hardened and celloidin-imbedded portion 
of cord, stained with Van Gieson’s stain. Owing to the partial 
necrosis of the cord it was necessary to greatly overstain in order 
to bring out the nuclei, the tuberculous area, however, staining 
much more deeply than the tissue of the cord. 8 
large areas of caseation and calcification. Sections from 
this part of the tube, stained for the tubercle bacilli, gave 
negative results. The portion of the tube between the 
uterus and the cyst was also twisted and greatly distended, 
especially at the point where it passed into the cyst where 
its diameter reached an inch. It was filled with yellowish 
material of the consistence of firm cheese. The micro- 
scopical examinations of sections taken from this portion 
of the tube showed a chronic diffuse tuberculosis rather 
than a miliary process. The lumen was almost entirely 
filled in some places by a reticulated tubercular mass con- 
taining numerous giant-cells; and there were many areas 
of caseation and calcification. Only a few of the epithelial 
folds remained preserved. In many places the process 
extended into the muscular coat, and quite large tubercles 
were occasionally found there. 
Cyst.—The cyst consisted of an outer capsule inclosing 
the red, spongy, and irregular-shaped mass, which com- 
prised the placenta and the fetal membranes. The outer 
surface of the cyst was rough, somewhat irregular, and 
covered with the remains of stringy adhesions. On cut- 
ting through the wall numerous yellow areas were found, 
of varying size, from that of a pin-head to that of a 
small finger-nail. Some of these were firm, others were 
soft and cheesy. These masses extended throughout the 
placenta and fetal membranes. In the cavity of the cyst 
lay a male fetus, flattened and somewhat macerated, about 
seven inches in length. Its age was evidently between 
three and four months, the finger-nails and the glans penis 
being formed, but the prepuce and scrotum not yet devel- 
oped. The umbilical cord was about eight inches long, 
and arose from the lower part of the cyst, very near the 
large tubercular mass in the uterine portion of the tube. 
Fetus.—At about three-fourths of the length of the 
cord, from its origin toward the fetus, there were several 
well-marked nodules, one containing yellowish caseous 9 
material, the largest one quite firm, except in its center, 
which was soft and yellow. These were cut off for hard- 
ening and embedding. The fetus was also opened, and 
the liver, spleen, kidneys, and lungs, were removed and 
hardened. These organs were almost entirely necrosed, 
the liver consisting only of a reddish, cheesy mass, crumb- 
ling into bits. Some of the yellow areas in the cyst-wall 
and placenta were also prepared for examination. The 
microscopic examination of the sections taken from the 
cyst-wall showed it to be the greatly distended tube, as 
the thin layers of muscle could still be detected. The 
yellowish areas in the wall proved to be giant-ceiled epi- 
thelioid tubercles with calcification. The examination of 
the similar areas in the placenta showed them to be the 
same thing. Throughout the whole placental tissue typi- 
cal tubercles could be found. In one section, stained for 
tubercle bacilli, their presence was demonstrated. 
The tuberculous changes in the placenta could be sepa- 
rated into two groups according to their location, a villous 
and an intervillous form. In the first the earliest changes 
took place within the villus itself, the epithelioid cells 
arising from the connective-tissue cells of the villus, or 
possibly from the endothelial cells of the placental capilla- 
ries, though this could not be shown. Whatever the origin 
of the tubercle, it is certain that in its development the 
connective-tissue cells of the villi play the chief part in the 
production of the epithelioid cells. In those villi in which 
the process was in an early stage and confined to its inner 
portion the outer surface remained intact, but with the in- 
creased growth of the tubercle this was lost, and the 
epithelioid cells had broken through into the intervillous 
spaces. In its further growth the tubercular tissue com- 
pletely filled these spaces, and in many cases extended 
around normal villi which stood out sharply against it. 
The intervillous tubercles were far more abundant than 
those originating primarily in the villi. In these the first 10 
change observed was a proliferation of cells on the surface of 
the villus at a point where the outer layer of cells could no 
Fig. 2. 
TUBERCULOSIS OF PLACENTA (17OX).1 
a—Epithelioid cells. b—Giant-cells, c—Areas of caseation. 
d—Small-cell infiltration, e—Masses of calcification, f—Fibrin. 
villi (Most of these show mucous degeneration and 
calcification), h—Red blood-corpuscles. 
longer be seen. The connective tissue of the villus, how- 
ever, presented no change. It is probable that here the 
1 From portion of placenta hardened in formalin and alcohol ; 
cut in celloidin and stained with hematoxylin. 11 
epithelioid cells arose from a proliferation of the cells cov- 
ering the villi. The growth of the tubercle is then out- 
ward into the blood-spaces and consists of a proliferation 
of its own epithelioid cells. This growth, in many cases, 
was very extensive, filling in completely the spaces be- 
tween many villi and entirely surrounding them. In many 
cases prolongations of epithelioid cells could be seen ex- 
tending out into the masses of fibrin which filled many of 
the blood-spaces. The areas of caseation were in those 
parts of the new tissue farthest away from the circulating 
blood, and, as a rule, the giant-cells lay in the central 
portions of the mass, and not at the periphery. In some 
cases the tubercular growth seemed to extend inward into 
the tissue of the villi as well as out into the blood-spaces. 
The majority of the villi primarily affected, as well as those 
surrounded by tubercular tissue, showed more or less de- 
generation. In many of them the entire outer layer of 
cells was lost, the connective-tissue nuclei stained very 
faintly, and there was mucous or fatty change with large 
masses of calcification. These changes are all shown in 
the drawing in which the intervillous form is reproduced. 
As to the manner of infection of the placenta, it seems 
very probable that the bacilli set free from the diseased 
maternal structures of the tube came with the maternal 
blood into the intervillous spaces. Here they were depos- 
ited upon the surfaces of the villi of the fetal placenta and 
set up their characteristic changes. As to the primary 
tubercles in the villi the origin is not so clear. It may, 
however, be supposed that their production may be due to 
an entrance of bacilli into the circulation of the villi, and 
hence into the fetal vessels, at those points where the epi- 
thelioid cells have grown into the villus from its surface; 
and with the caseation and breaking down of the new tis- 
sue the bacilli have been set free into the capillaries of the 
villi, and so could pass into the circulation of the fetus. 
Since it is definitely shown that the placental tissue has no 12 
immunity against tuberculosis, there is no reason to believe 
that the spread of the process through it would differ in 
any way from that in any other part of the body. 
The sections from the nodules in the cord showed, near 
the necrosed wall of a large vessel, a loosely reticulated 
tissue of epithelioid cells and small-celled infiltration. No 
giant-cells were found, but the character of the tissue with 
areas of caseation marked it as undoubtedly tubercular. The 
microscopical examination of the internal organs was neg- 
ative. The liver consisted almost entirely of formless dead 
matter. Hundreds of sections of this were stained for the 
bacilli with negative results. It is greatly to be regretted 
that we did not recognize the existence of tuberculosis be- 
fore the specimens were put into the formalin, as the 
presence of bacilli in the internal organs might have been 
shown by injecting animals with portions of the organs, or 
by making cultures from them. Only in the lung was 
anything like a tubercle found. On cutting this organ, 
after hardening preparatory to imbedding, two whitish 
areas about the size of small pin-heads were seen. On 
section these proved to be two small areas of complete 
necrosis where the structure was lost, while the tissue 
about showed faintly staining nuclei without this loss of 
form. These were, therefore, very highly suggestive of 
miliary tubercles, but the fact could not be positively de- 
cided. One of my assistants thought that he discovered 
tubercle bacilli in a section of the kidney stained for these, 
but when 1 went to look at them they could not be found. 
Therefore, so tar as the fetus is concerned, the actual 
demonstration in its structures of tubercular changes must 
be confined to the membranes and cord, but it seems 
almost certain that the internal organs must have been 
similarly affected, though this could not be demonstrated 
beyond all doubt. 
The patient died of general peritonitis on the 13th of 
April, ten days after the operation. An autopsy was re- 13 
fused, so the existence of tuberculosis in the other organs 
could not be ascertained. As mentioned before, there 
were no signs or symptoms which would lead us to sus- 
pect any other localization of the disease, so that I think 
the case may be looked upon as a primary tuberculosis of 
the genital tract. From a sister of the patient it was 
learned that a year and a half ago the latter’s husband 
had been ill with fever, night-sweats, general weakness, 
and loss of flesh, and was on this account thought to have 
consumption, but he afterward entirely recovered. The 
family physician, in answer to my letter of inquiry, in- 
formed me that the husband is now perfectly well, with- 
out signs or symptoms of tuberculosis. Specimens of his 
urine, which were sent to me for examination for tubercle 
bacilli, have not arrived, so I have been unable to throw 
any definite light upon the etiology of the patient’s condi- 
tion, or to establish any relation between it and her hus- 
band’s symptoms of a year and a half ago. 
In conclusion, tuberculosis of the tubes, it seems to me 
from this case, must be considered as an etiological factor 
in the production of ectopic gestation. If the obstruction 
of the tube hindering the progress of the ovum toward the 
uterus is the chief factor, we have in the almost complete 
obliteration of the canal by the numerous miliary tubercles 
in the mucosa, a most favorable condition for its occur- 
rence. It is very probable that the salpingitis which is 
found to exist in almost every case of extrauterine preg- 
nancy, and which is usually looked upon as the causal 
factor, may, in more cases lhan is now suspected, be found 
to be tuberculous. 
Up to a very short time ago, tuberculosis of the female 
genital tract, though it had been known to exist for a long 
period of time, did not assume that importance which it is 
now beginning to hold. During the last three years it 
has been shown that far from being a rare disease, it 
occurs in a very large proportion of all the cases treated 14 
for inflammatory disease of this tract. Wiliiams, of Johns 
Hopkins, in a very exhaustive article in the ‘ ‘Johns Hopkins 
Hospital Reports for 1892,” reviews the subject up to that 
year. He makes the statement that in his own experience, 
about eight per cent, of all the cases in which the appen- 
dages are removed for inflammatory disease are tubercu- 
lar ; in other words, every twelfth case of adherent tubes 
and ovaries, or pus-tubes, is of tubercular origin. He 
further emphasizes the difficulty of making a microscopic 
diagnosis. Of his cases only twenty-five per cent, were 
suspected tuberculosis, seventy-five per cent, being un- 
suspected as far as this condition was concerned. Since the 
ultimate diagnosis is, therefore, a microscopical one, it is 
very probable that a wider experience in making these exam- 
inations will increase greatly the proportion in which it is 
found to occur. The importance, on this account, of a 
technical examination, as a matter of routine, in all of the 
cases of tubal inflammation, cannot be too strongly urged. 
Tuberculosis of the ovary is not so common as that of 
the tubes, but still occurs so frequently that it cannot be 
looked upon as a rare condition. It is most frequently 
met with on the surface of the organ, but Williams and 
numerous other observers have found it in the body of the 
ovary, even in the wralls of cystic tumors. With it there 
is usually found a tuberculosis of the tubes or uterus. In 
our own case the small nodules attached to the surface of 
the ovaryr are really tubercles of the peritoneum. It is here 
worthy of note that tuberculosis of the tubes must be 
looked upon as perhaps the most important factor of in- 
fection in tubercular peritonitis. It is due largely to the 
fact that laparotomy has lately been so extensively adopted 
as a cure for this condition that the occurrence of tuber- 
cular salpingitis has been discovered to be of so frequent 
occurrence, since in the majority of cases the conditions 
have been found to be coexistent. The small nodules 
that were found in this case may, I think, be looked upon 15 
as an early stage of tubercular peritonitis in which the in- 
fection undoubtedly arose from a diseased tube. The 
location of the tubercles upon the surface of the ovary and 
in the fimbriated extremity all point strongly to this mode 
of origin. It should be mentioned here, however, that 
some authorities believe the tubal disease to be always 
secondary to that of the peritoneum, the tube taking in the 
bacilli from the peritoneal cavity. 
Up to the date of Williams’ article in 1892, only one case 
of tuberculosis of the placenta had been reported, and from 
the description given of that case its nature is somewhat 
doubtful. But F. Lehmann, in 1893 (Deutch. med. Woch- 
enschr., 1893), found typical tubercles in the placenta of a 
woman dying from acute miliary tuberculosis in the seventh 
or eighth month of preganncy. Schmorl and Kockel, in 
1894 (Beitriige v. Seigler, xvi, 1894), also made a report 
upon this condition, so that this is the third instance in 
which placental tuberculosis has been reported. Schmorl, 
Birch-Hirschfeld, and Landouzy, had, however, demon- 
strated the presence of the tubercle bacilli in the blood of 
the placenta and of the fetal organs, and were able to 
make cultures and successful inoculations with material 
from these organs. Histological changes were not defi- 
nitely ascertained by these investigators. 
The presence of the tubercles in the umbilical cord 
makes the case important, because it is the first one re- 
ported in which that condition has been found. This 
gives added evidence to the still-mooted questions of the 
inheritance in the child of tuberculosis from the mother. 
I regret deeply that I could not satisfy myself as to the 
presence of tubercle bacilli in the internal organs of the 
fetus, as it seems almost certain that they must be present. 
The cases mentioned above, in which the presence of 
the bacilli was demonstrated in the fetus, were all cases 
of acute miliary tuberculosis, the mother dying in preg- 
nancy. It seems very improbable that infection of the 16 
fetus in this disease can play much part in the inheritance 
of tuberculosis because of the death of parent and child 
before birth occurs. It would be more important to prove 
the possibility of intection from a localized tuberculosis of 
the tubes or uterus in which condition the fetus might go 
to full term and delivery, and so come infected into the 
world. This case, I think, goes very far toward proving 
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