A CASE OF PAGET’S DISEASE 
OF THE NIPPLE. 
BY 
George Thomas Jackson, M. D., 
NEW YORK, 
Professor of Dermatology in the Woman’s Medical 
College of the New York Infirmary ; and in 
the Medical Department of the 
University of Vermont. 
REPRINTED FROM THE 
Journal of Cutaneous and Genito-Urinary Diseases 
for November, 1896. [Reprinted from the Journal of Cutaneous and Genito-Urinary Diseases 
for November, 1896.] 
A CASE OF PAGET'S DISEASE OF THE NIPPLE.* 
By GEORGE THOMAS JACKSON, M. D., New York, 
Professor of Dermatology in the Woman’s Medical College of the New York Infirmary ; and 
in the Medical Department of the University of Vermont. 
THE unreliability of statistics is well shown by a glance at the 
statistical returns of the American Dermatological Association. 
In the combined returns from 1877 to 1893 no mention of 
Paget’s disease is made either under the commonly used title I have 
chosen for this paper, or under any other name suggested for it. These 
statistics cover 204,866 cases. Doubtless some cases are hidden from 
sight, or, better, buried forever under the title of epithelioma or carci- 
noma. In 1894, among 24,321 cases we find one case of the disease 
reported from Hew York. So far as I know there are no statistics 
so complete as ours are, yet how shall we regard the disease as to fre- 
quency of occurrence? Our statistics would say once in 229,187 cases, 
but not one of us would accept that as true. At any rate it is a rare 
disease. It so happened that in the autumn of 1895 I saw two cases 
of Paget’s disease, one in my service at the Woman’s Medical Col- 
lege of the Hew York Infirmary, and one in the practice of Dr. 13. 
Farquhar Curtis, of Hew York, who kindly sent the patient to me 
for confirmation of his diagnosis and opinion as to the advisability of 
operation. 
I would briefly report my own case. I would say that it was seen 
by Dr. George II. Fox and by Dr. B. Farquhar Curtis. The latter 
operated upon it, and by both of these gentlemen the diagnosis was 
confirmed. 
Matilda K., aged fifty-two years, born in Germany; married. 
The family history is unimportant. The patient gives a history of hav- 
ing had rheumatic fever when she was sixteen and when she was 
* Read at the Twentieth Annual Meeting of the American Dermatological Association, 
September 8, 1896. 
Copyright, 1896, by D Appleton and Company. 2 
Original Communications. 
twenty years of age. She was married when she was forty years old, 
and had two children. The youngest child was born ten years before 
the trouble with the breast. ' She suckled both her children, the last 
one for eighteen months. She never had any disease of the breast 
during lactation. She has always menstruated regularly, and does so 
still. She enjoyed good health up to December, 1894, when she had 
a slight stroke of apoplexy followed by paralysis, that in course of 
time lessened. The patient came to the dispensary in the fall of 1894 
for an intiammation about the right nipple. 1 did not see her then. 
Apparently it was taken for a simple intiammation and treated with 
simple remedies. These seem to have relieved her for a time. 
I saw her for the first time in May, 1895. At that time she pre- 
sented herself on account of a return of the inflammation of the nipple. 
She said that the first thing she noticed was that there was itching 
about the nipple, and that the areola became red and looked angry. 
When I saw her in May the appearances were those of a chronic 
eczema, some crusting, and an eroded surface. There was then no 
pain complained of. On account of the markedly circumscribed char- 
acter of the patch, its limitation to the nipple and areola, and the 
slight amount of induration of the lesion, together with some hardness 
of the breast, I made a tentative diagnosis of Paget’s disease, and 
directed that she be kept under observation and the lesion treated as 
an eczema. 
About the middle of September, 1895, she came again to my 
clinic. Since last seeing her a marked change had taken place. The 
nipple had become very much depressed. The whole areola was very 
much indurated. The site of the nipple and areola was occupied by 
an eroded, red, irregular-shaped patch. It was perfectly dry and 
looked raw. Outside of this there was a narrow line of apparently 
normal skin, and outside of all, extending nearly around the whole 
diseased patch, there a light brown, infiltrated, slightly elevated 
ridge. There were no dilated blood-vessels. The patient complained 
of a good deal of itching and of sharp, sticking pains in the breast. 
The breast felt hard, and the axillary glands of both sides w7ere en- 
larged. There now being no doubt of the nature of the trouble, am- 
putation was advised. 
On October 16, 1895, Professor B. Farquhar Curtis amputated 
the diseased breast in the Hew York Infirmary, and removed the en- 
larged glands from the right axilla. The patient made a good recov- 
ery, and was discharged from the Infirmary on October 30, 1895. A Case of Paget's Disease of the Nipple. 
3 
I saw the patient again on June 17, 1896. The scar from the 
operation was perfect. There was no sign of a return of the disease. 
There were no enlarged glands in the right axilla. The patient stated 
that she had been entirely free from pain since the operation. She 
had a second attack of paralysis in December, 1895. In the left 
breast there was a hard, circumscribed, nodular mass. She said that 
she had had this lump in the breast for years, and that it gave her no 
pain. 
We have here an instance of the development of what seemed to 
be a simple eczema into a well-marked case of Paget’s disease within 
about ten or eleven months. The clinical diagnosis was confirmed 
by the microscope. The pathological examination was made for me 
by my friend Dr. John Slade Ely, Professor of Histology and 
Pathological Anatomy in the Woman’s Medical College of the Hew 
York Infirmary, and Assistant in Pathology in the Medical Depart- 
ment of Columbia University. His report upon the findings in the 
case is as follows: 
Professor John Slade Ehfs Report. 
The specimen is a breast which has been removed by operation and 
comprises the entire mammary gland, a considerable piece of the skin 
covering it, and surrounding fat and pectoral muscle. 
The skin appears normal except where it covers the nipple and its 
areola, where it is somewhat coarsely seamed and appears to be thick- 
ened. Surrounding the areola there is a circumvallate depression, 
in places as much as two millimetres and a half in depth, which sepa- 
rates the thickened tissue of the areola from the normal surround- 
ing skin. Just within this depression there is a zone of hypersemia 
about two millimetres in breadth. Though coarsely seamed, as above 
mentioned, the skin covering the nipple and areola is in general 
smooth, showing neither ulceration nor crust formation. The nipple 
is not sunken or noticeably retracted, though it projects very little 
above the level of the surrounding skin. 
Median section through the nipple, its areola, and the entire breast 
shows the skin covering the nipple and areola to be distinctly thick- 
ened and the site of the mammary gland to be occupied by a large, 
dense tumor. This tumor measures 8.1 X 7.6 X 4.7 centimetres. 
It is quite sharply circumscribed, though not distinctly encapsulated, 
and, except where it is connected with the nipple by the lactiferous 
canals and their supporting connective tissue, it is completely sur- 4 
Original Comm un ioatiuns. 
rounded by fat. The substance composing the tumor is extremely 
dense, resembling in appearance the tissue of dense fibroma. It shows 
no distinct lobulation, but is somewhat mottled in places, as the re- 
sult, apparently, of the presence of small, more or less circular areas 
of somewhat less dense tissue of a slightly yellowish color. A few 
small cysts are evident, the largest not more than three millimetres 
in diameter, and containing clear or only slightly cloudy liquid ma- 
terial. The blood supply of the tumor appears to be meager. 
The fat tissue surrounding the tumor appears normal, as does also 
the portion of pectoral muscle attached to the specimen. 
Microscopic examination confirms the impressions obtained from 
gross inspection of the specimen. 
The skin covering the nipple and areola is much thickened. This 
is chiefly the result of a very considerable development of connec- 
tive tissue in the corium and of an inflammatory infiltration of its 
papillary layer, though the epidermis is also thicker than normal. 
These changes are evident everywhere in the skin covering the nipple 
and areola, but are more intense in that of the areola, and the details 
of the changes about to be described are those which have been ob- 
served in that region more particularly. 
The corium here is upward of four millimetres in thickness. Its 
deeper layer consists of bundles of dense connective tissue surround- 
ing masses of unstriped muscle. It is poorly supplied with blood- 
vessels, but where these are visible they are often surrounded by col- 
lections of cells, for the most part of the small spheroidal type and 
mononuclear. This cellular infiltration about the blood-vessels in- 
creases toward the more superficial layers of the corium, becoming 
very intense in the papillary portion, where it is not limited to the 
immediate proximity of the blood-vessels, but is quite general through- 
out the tissue. The cells here are also in great part of the small 
spheroidal variety and mononuclear, but there are also many larger 
spheroidal, polyhedral, and spindle cells. These cells all lie in a re- 
ticulum of fibrous connective tissue which is finer in the more super- 
ficial parts, coarser below. The cells and fibrous reticulum of the 
papillary layer are often not in close juxtaposition, but are separated 
by clear spaces such as are observed in tissues which have been the 
seat of oedema. This change is very marked. In the papillary layer, 
also, are many thin-walled blood-vessels, whose endothelium is swollen 
and whose lumina contain variable numbers of polynuclear leucocytes. 
The majority of these blood-vessels would appear to have been con- A Case of Paget's Disease of the Nipple. 
5 
siderably congested. A few polynuclear leucocytes are also observed 
in the tissue outside the blood-vessels. 
The changes in the epidermis are even more pronounced than 
those in the corium. All the layers of the epidermis are thickened. 
In the rete Malpighii the cells of the deepest layer appear to have 
undergone a more rapid multiplication than normal, being very closely 
packed together and rather small. More superficially the cells are 
seen to be passing through the various transitions characteristic of the 
rete mucosum, but in the majority more or less abnormity is dis- 
cernible. This appears to be due in most instances to swelling of 
the cell bodies, which are more spheroidal than normal and consist 
of rather coarsely granular protoplasm. Many of the cells also inclose 
clear, more or less globular spaces, now apparently empty. These 
spaces often occupy the greater part of the cell body, leaving only 
the nucleus intact, but usually a small amount of finely granular 
protoplasm surrounds the space, or is visible at one side of the cell 
surrounding the nucleus. At times these spaces appear to surround 
the nucleus in a ring, giving it a vacuolated appearance, and under 
these circumstances there is usually visible a distinct zone of proto- 
plasm about the vacuoli. The outlines of these peculiar cells are, 
as a rule, very distinct, though they can not be said to have a definite 
wall. In many instances the cells immediately adjacent to these 
swollen cells appear to have been compressed by their enlarged neigh- 
bors, at times presenting in section a distinctly crescentic appear- 
ance, the vacuolated cell occupying the concavity. The nuclei of the 
cells are for the most part well preserved, though occasionally some- 
what distorted in the vacuolated cells; their chromatin stains well 
with the ordinary nuclear dyes. 
In addition to the changes in shape and appearance of the cells 
of the rete Malpighii, there is also noticeable an increase in the inter- 
cellular spaces, which are distinctly broader than usual. This is par- 
ticularly evident in the region of the spine cells, where the channels 
separating the adjacent cells are very wide. These intercellular spaces 
now appear to be empty. 
The changes above described are everywhere evident, but are so 
intense in places as to completely destroy fhe regular stratification of 
the rete Malpighii and to give it the appearance of a confused mass 
of swollen epithelial cells loosely and indiscriminately thrown to- 
gether. 
The stratum granulosum of the epidermis is much thickened where Original Communications. 
the changes in the rete are pronounced, and the cells composing it 
are very granular and are larger than usual. The stratum lucidum 
is also much increased in thickness in places, apparently as the result 
of excessive swelling of its component cells, which are often almost 
spherical in shape. These swollen cells of the stratum lucidum show 
little besides the cell outline and a small faint nucleus, the entire cell 
body having been occupied by some substance which has disappeared 
in the process of preparation of the specimen, the space formerly occu- 
pied by it showing now only as a hollow cavity. The same separa- 
tion of the cells noticed in the rete Malpighii is also observable here. 
The stratum corneum is also greatly thickened. In its deeper' 
layers the cells are much swollen, presenting a similar appearance 
to those of the stratum lucidum, and throughout its entire thickness 
the intercellular spaces are markedly increased, forming irregular 
cavities, often of considerable size, now destitute of contents. 
The changes in the skin above described are sharply limited by the 
circumvallate depression surrounding the areola, the skin beyond this 
point showing no pathological change other than a moderate infil- 
tration of the perivascular spaces of the corium by small spheroidal 
cells, even this slight change quickly disappearing as the distance from 
the areola is increased. 
The lactiferous canals in the nipple and just beneath it are irregu- 
larly dilated, and are everywhere filled with desquamated, swollen, 
and degenerated epithelium and polynuclear leucocytes. In many 
of the epithelial cells distinct vacuoles are visible similar to those ob- 
served in the cells of the rete Malpighii, though this change is never 
so intense as in the skin. The connective tissue surrounding the lac- 
tiferous canals is moderately infiltrated with small spheroidal cells. 
Ho marked congestion of the blood-vessels about these canals is ob- 
served. 
The tumor, occupying the mammary gland, is composed for the 
most part of extremely dense, white fibrous tissue disposed in bundles 
of various sizes, often distinctly wavy and quite lawless in arrange- 
ment, many of which show evidence of hyaline degeneration. This 
connective tissue occupies the spaces between the lobules of the gland, 
separating them widely from one another, and penetrates the in- 
dividual lobules. Immediately about the acini of the lobules it is less 
dense and appears younger, connective-tissue cells being relatively 
more abundant. The network of fibers is here also very much more 
open than in the interlobular regions, disclosing many open spaces A Case of Paget's Disease of the Nipple. 
between the fibrils and presenting the apppearance often met with in 
cedematous tissues. The acini inclosed by this tissue are often widely 
separated by it, and show more or less abnormity of size and shape. 
Some degeneration of their lining epithelium is also noticeable, but 
this is far less striking than in the epithelium of the lactiferous ducts. 
Though in some instances the acini of the lobules branch somewhat 
irregularly, the impression conveyed is rather that of inflammatory 
hyperplasia than of adenoma. 
In places in the dense fibrous tissue of the tumor there are col- 
lections of small spheroidal cells, mononuclear, and resembling very 
young connective-tissue cells. These are interpreted as marking the 
site of active development of the connective tissue at the time of 
removal of the mass. 
Near the center of the tumor there are a number of small cystsr 
lined with cuboidal or irregular epithelium, and containing loose 
granular material and desquamated cells. A few of these cysts are 
regular in outline, but the majority of them are irregular, showing 
what appear to be papillary ingrowths of connective tissue into their 
lumina. These ingrowths consist of connective tissue of the same 
characters as that found about the acini of the lobules, and are covered 
with epithelium similar to that lining the rest of the cyst wall. The 
picture in these cases is very suggestive of that presented by the papil- 
lary ingrowths observed in the early stages of intracanalicular fibroma 
of the breast and in papillary cyst-adenomata of the ovary. 
Though numerous specimens have been stained for bacteria and 
for parasites of the sporozoa type, none have been found. 
The changes above described are substantially those which have 
existed in all the cases of Paget’s disease which have been subjected 
to careful pathological study. 
Consideration of the significance of these changes leads to the con- 
clusion that the lesion in the skin is essentially of an inflammatory 
nature. And they furthermore suggest that the inflammation which 
gave rise to them was of slow progress, was primarily and pre-emi- 
nently a change of the corium, and was of such a nature as to cause 
a very considerable connective-tissue development, and, by interfer- 
ence with the nutrition of the skin, to lead to an intensely cedematous 
condition of the epidermis and of the papillary layer of the corium. 
The tumor of the mammary gland may be regarded as fibroma 
durum or as the result of long-continued interstitial mastitis, the lines 
separating these two conditions being at the present time exceedingly 8 
Original Communications. 
vague. For my part, I would prefer to consider the present growth 
as fibroma of the so-called “ pericanalicular ” variety, basing this 
opinion chiefly on the lawlessness of the fibers composing it. It is 
certainly neither adenoma nor carcinoma. 
That the two conditions here met with should be associated ap- 
pears most natural when we remember the close similarity in the 
lesions (both consisting chiefly of connective-tissue development) 
and the intimate topographical and genetic relationship of the skin 
of the nipple and areola with the glandular element of the breast. 
The determination of the precise chronological sequence of the two 
conditions, however, presents some difficulty. In a large majority 
of the cases of Paget’s disease thus far studied, the attention of the 
patient has been attracted first to the lesion of the skin, and the mam- 
mary tumor has remained undetected until it has attained to a very 
considerable size or has been noticed by the physician in his examina- 
tion. This has led to a widespread belief, expressed also by Paget 
in his first description of the condition, that the change in the skin 
antedates the lesion of the gland and is in some remote way its cause. 
In the present case I am loath to regard the lesion in the skin as pri- 
mary, basing this opinion on the large size of the tumor, on the ex- 
treme density of the tissue composing it suggesting its long duration, 
on the nature and relatively slight intensity of the skin lesion, on 
the frequency of occurrence of fibrous growths in the breast independ- 
ently of any pre-existing skin lesion, and on the absence of any evi- 
dent aetiological factor in connection with the skin lesion other than 
the large fibrous tumor closely underlying it. 
In the description of the changes in the epidermis and in the 
lactiferous ducts mention has been made of certain spheroidal, clear 
spaces or vacuoles commonly met with in the epithelial cells. These 
have been described by Darier, Wickham, and others as psorospermse, 
and have been regarded by them as the primary seti©logical factor 
in the induction of the disease. A careful study of these “ bodies ” 
in the present case has produced a strong belief that they are in reality 
not psorospermae but spaces in the cells, and they have accordingly 
been described as such, spaces which have formed as the result of an 
accumulation of clear liquid within the cell bodies, such as is seen 
in extreme dropsy of cells or in hydropic degeneration, as it is char- 
acterized by Ziegler. This change is relatively frequent in the in- 
flamed skin covering superficial tumors—I have met with it in much 
greater intensity than in the present case in the epidermis covering A Case of Payees Disease of the Nipple. 
9 
a melano-sarcoma of the lieel—and 1 have seen nothing in the pres- 
ent case which is not abundantly explained on the supposition that 
the condition is here one of extreme inflammatory oedema of the cells. 
And in this connection it may be stated that I have seen appearances 
apparently identical with all those pictured by Wickham in his elabo- 
rate study and interpreted by him as indicative of the presence of 
psorospermas. And, finally, the sharp limitation of the supposed 
psorospermse to the epithelium seems to be inconsistent with any con- 
ception of them as parasites responsible for the genesis of a distant 
neoplasm in which they are not found. 
In conclusion, then, I find it much more consistent to consider the 
lesion of the skin as a secondary inflammatory process resulting in 
some way from the large underlying tumor of the mammary gland, 
and to admit that in the present state of our knowledge the precise 
exciting cause of the tumor and the exact manner in which its pres- 
ence induces the inflammation of the skin must be regarded as un- 
certain. 
After seeing my patient in June of this year (1896) I wrote to 
Dr. Ely, telling him that I found a tumor in the other breast. Reply- 
ing to my letter, he said: “ Its contents is an extremely interesting 
corroboration clinically of the findings of the report, both as to the 
nature of the tumor and as to the priority in time of the tumor to the 
skin lesion. Such fibrous growths as the tumor in the present case 
are very apt indeed to affect both breasts, while adenoma, carcinoma, 
etc., very rarely affect both. I think that you may be sure that the 
mass in the other breast is not carcinoma, but fibroma or interstitial 
mastitis.” 
It would a waste of time for me to dilate upon the symptoms 
of Paget’s disease of the nipple before such an audience. Dr. Ely has 
begun a critical study of its pathology which he hopes to publish in a 
short time. In writing this paper I had two objects in view—namely, 
to put on record another case of this rare disease, as it seems to me to be 
the duty of every one to report every case of a rare disease, and to elicit 
from you a discussion upon its treatment, as it is to such bodies as we 
are that the profession looks for guidance in the treatment of rare 
diseases. 
In looking over Wickham’s admirable treatise upon Paget’s dis- 
ease * you will find a record of some eighteen cases. Paget reported 
* Maladie de la peau dite maladie de Paget, Paris, 1890. Original Communications. 
fifteen cases not abstracted by Wickliam. Besides these, Elliot re- 
ported one case; * Jamieson reported in his Treatise on Skin Diseases 
two cases; t Audry, one case; Fleming, one case; # Anderson, one 
case; || Lewis, one case;A and Duhring, three cases. I do not offer 
this as a complete list of the cases reported, but they are unselected 
and enough for my present purpose. With the case now reported we 
have forty-five cases. Of these it is said that in twenty-four cases car- 
cinoma developed in the breast which was the site of Paget’s disease; 
in four of them the breast is said to have felt hard; and in one of 
them, my case, a fibroma was found as the cause of the hardness of the 
breast. That is, in twenty-nine out of the forty-five cases there was 
some disease of the gland in connection with the disease of the nipple. 
Only one of the forty-five cases is reported as cured by treatment ad- 
dressed to the skin. The history of the vast majority of them is that 
they grew steadily worse under treatment, no matter whether mild 
or most energetic with powerful caustics or the curette. On the other 
hand, in the cases operated on most did well, though in three of them 
a general carcinosis developed, and in one death resulted from a sec- 
ondary deposit in the brain. 
We learn from this that the tendency of the disease is to the de- 
velopment of carcinoma. Moreover, we find that it is eminently re- 
fractory to treatment addressed to the skin lesion. It is possible, as the 
histories show, to produce an amelioration. It is doubtful if a lasting 
cure can be obtained after the disease has plainly declared itself. We 
also find that we have reason to expect good results from amputation 
of the breast. 
When we consider the malignant tendency of the disease and its 
obstinacy to treatment, it seems to me that it is our duty in all cases 
to advise amputation of the breast just as soon as we are sure of our 
diagnosis. Of course, as long as there is any possibility of the trouble 
being a chronic eczema or a dermatitis of simple character, operative 
interference is not to be thought of. Usually it will not take one 
who is at all expert in dermatology very long to assure himself, 
•one way or the other, of the nature of the case. As most of the women 
* Journal of Genito-Urinary and Skin Diseases, 1892, vol. x, p. 2*72. 
f Anna], de dermat. et syph., 1896, t. vii, p. 644. 
X British Medical Journal, 1891, vol. i, p. 846. 
# Glasgow Medical Journal, 1892, vol. xxxvii, p. 188. 
|| Glasgow Medical Journal, 1892, vol. xxxviii, p. 132. 
A Medical Record, 1887, vol. xxxi, p. 641. A Case of Pagers Disease of the Nipple. 
11 
are past the childbearing age, and the breast is useless so far as any 
function of the organ is concerned, and as the mortality of breast 
amputations is very slight (Dr. B. Farquhar Curtis informs me that it 
is from one to four per cent), we can advise operation as a prevent- 
ive of future trouble with good grace. Of course, when there are 
signs of involvement of the breast, no one would hesitate to insist 
upon amputation of the gland. It is true that in my case my pa- 
thologist reports that the tumor of the breast was not malignant. 
But the clinical signs of carcinoma were present, and it would have 
been impossible, probably, to determine the nature of the tumor with- 
out amputation. I feel that I was justified in advising amputation 
even in this case, and in the absence of malignancy of the tumor, as 
the patient, by the comparatively trivial operation, was promptly 
cured of an otherwise practicably incurable disease, and at once freed 
from all pain and annoyance.