PAGET'S DISEASE. 
John V. Shoemaker, A. M., M. D., 
Professor of Skin and Venereal Diseases in 
the Medico-Chirurgical College 
of Philadelphia. 
REPRINTED FROM THE 
Journal of Cutaneous and Genito-Urinary Diseases 
for May, 1895. [Reprinted from the Journal of Cutaneous and Genito-Urinary Diseases for May, 1895.] 
PAGET'S DISEASE. 
Professor of Skin and Venereal Diseases in the Medico-Chirurgical College of Philadelphia. 
JOHN V. SHOEMAKER, A. M., M. D., 
EM., female, fifty-two years of age, single. About two years 
and a half ago the patient was troubled with an itching which 
• affected all parts of the body. She remembers that she was 
sometimes obliged to scratch the right nipple, and thinks that she may 
have torn the skin with her nail. At all events, from that time the 
nipple began to be sore. Since its inception the disease has gradually 
spread. The skin has been raw almost from the beginning. The af- 
fected surface is tender, but it has never given rise to severe darting 
or lancinating pain. There is no glandular involvement in the corre- 
sponding axilla. The general health is unimpaired and she has lost 
little if any flesh. Perhaps she may have lost a little strength, but the 
decline is not marked. Her appearance is that of a well-nourished 
woman. With the exception of possible irritation by scratching, there 
has been no injury to the breast or nipple, but she has been told that 
when a week-old babe she suffered from inflammation of the breast, 
which suppurated. 
Present Appearance.-The nipple is so depressed as to be scarcely 
distinguishable, is of a vivid red color, and surrounded by a zone of the 
same hue. The surface is covered with a sanguinolent fluid mixed 
with a little pus. The inflammatory areola is about the size of a silver 
dollar. Its base is somewhat hard and its border is sharply defined. 
(See illustration.) 
This case is an excellent example of an affection which is of partic- 
ular interest from a diagnostic and setiological point of view. Paget's 
disease requires to be differentiated on the one hand from chronic ecze- 
ma, and on the other is thought to be related to certain other affections 
of the skin and mucous membrane. Prior to the paper of Sir James 
Paget, in 1874, the disease which has 'since been known by his name 
had generally been confounded with eczema and sometimes with 
psoriasis. Its points of distinction from the former malady will here- 
after be indicated. 
Copyright, 1895, by D. Appleton and Company. 2 
Okiginal Communications. 
Paget's disease is one of the rarer affections of the nipple. It usu- 
ally begins as a slight fissure or as an exfoliation of small horny scales. 
After the crusts have detached themselves a reddened surface is per- 
ceived. The advent of the disease is ordinarily accompanied by itch- 
ing, which, as a rule, disappears in the subsequent course. The process 
gradually invades the entire nipple and extends to the areola. The 
affected surface is of a bright red color, smooth or somewhat rough- 
ened by the presence of fine granulations. It is covered by a moder- 
Paget's Disease. 
ately free secretion which often dries into yellowish or brownish crusts. 
Beneath the ulcer a certain amount of induration can usually be de- 
tected. The raw surface readily bleeds. The term eczematiform stage 
has been applied to the period thus briefly described. The progress of 
the affection is very slow. In course of time the nipple becomes re- 
tracted and gradually disappears. The spot formerly occupied by the 
nipple may become depressed or ulcerated. Finally, the disease in- 
volves the mammary gland, which becomes swollen and undergoes 
malignant degeneration. Paget's disease attacks the right more often 
than the left nipple. Its duration varies in different cases. On an 
average the affection becomes epitheliomatous in from two to six years. 
Though most frequent upon the nipple, it may occur in other localities. 
Dr. Radcliffe Crocker has described a case in which the scrotum and 3 
Paget's Disease. 
penis were affected, and the diseased area, after having proved rebel- 
lious to more conservative methods, was at length excised. Sections 
demonstrated that the process had attained the epitheliomatous stage. 
A similar case has been reported from the clinic of Professor Pick, of 
Prague. A patient had been under treatment for eczema of the glans 
penis, with a tendency to the proliferation of epithelium and the for- 
mation of tubercles. After an operation for phimosis the eczema im- 
proved, but it subsequently returned and new growths the size of 
peas formed upon the glans and frenulum. The tumors were removed 
and the microscopical examination revealed a typical picture of carci- 
nomatous growth, together with a small-celled infiltration expressive 
of eczema. These occurrences in males are, however, altogether excep- 
tional. 
Paget's disease may be distinguished from chronic eczema by a num- 
ber of considerations. The course of an eczema may, indeed, be very 
tardy, but it usually exhibits periods of temporary or comparative sub- 
sidence alternating with acute exacerbation. Eczema of the nipple is 
often if not generally associated with manifestations of the same dis- 
ease upon other portions of the body. The lesions may not be coexist- 
ent, but a history of other eczematous outbreaks can usually be ob- 
tained. The margins of an eczematous patch are not abrupt, but 
shade gradually into the surrounding unaffected integument. There 
is infiltration in eczema, and it may be deep, but it is not always pres- 
ent to the same degree; at times much of the thickening and hardness 
is removed by absorption. Itching is a prominent subjective symptom 
of eczema. The nipple may be the seat of eczema at almost any age 
of life, but this localization is particularly apt to occur in nursing 
women. Eczema is not prone to undergo malignant change. 
All the features just indicated as characteristic of eczema are in 
contrast with the manifestations of Paget's disease. The latter is of 
slow evolution, and considerable periods of time may elapse during 
which little or no progress can be detected, but a decided retrogression 
of the lesion do not take place. The condition may not become 
aggravated, but neither will it improve. It is a solitary lesion, and 
will not simultaneously involve different regions of the body. The 
periphery of Paget's disease is sharply cut. There is no gradual fading 
from morbid to healthy tissue. The infiltration beneath the lesion is 
not always as thick as that of eczema, but it is persistent, and has a 
peculiar feel which has been likened to that of parchment. Itching is 
not a distinctive symptom of Paget's disease. It may be present in 
the beginning of a case, and may, in fact, be very distressing, but it 
generally subsides in the further evolution of the malady. Paget's 4 
Original Communications. 
disease rarely occurs before the fortieth year. It will not, as a rule, 
develop until or after the menopause. Retraction of the nipple is 
common in Paget's disease, but rare in eczema. The vivid and uniform 
color of the lesion is characteristic of the former affection. The sur- 
face, in that malady, is also apt to exhibit a somewhat papillomatous 
appearance which is not observed in eczema. Finally, if followed to 
its termination, Paget's disease is transformed into mammary cancer. 
The case which forms the basis of the present paper corresponds 
point to point with the foregoing portraiture of Paget's disease. The 
patient is fifty-two years of age, and it is the right nipple which is 
attacked. The outbreak of the disorder was preceded by itching, and 
it is possible that a tear of the nipple by the finger-nail afforded an 
avenue of entrance to the specific germ of the disease. On the con- 
trary, it is possible that the disease had been in existence for some time 
before it attracted the attention of the patient. Though the surface 
early became raw, the extension has been slow, and at the end of thirty 
months only the nipple and its areola are involved. The nipple is 
greatly retracted and the surrounding zone of disease corresponds 
exactly to the areola. In other words, the margin is sharply defined. 
A hardness, sufficiently distinct but of not much depth, underlies the 
ulcer. The color is uniform and intensely red. Bleeding is readily 
produced. The disease is still in the eczematiform stage. There is no 
swelling of the breast. Its tubules are not thickened. The axillary 
glands are not enlarged. 
While to naked-eye inspection Paget's disease seems to resemble 
eczema more closely than any other affection, the investigations of the 
past few years have suggested a closer relationship to several der- 
matoses which are apparently quite distinct. In 1889, M. Darier, of 
Paris, announced that, by a microscopical examination of scales taken 
from a case of Paget's disease, he had detected the presence of psoro- 
sperms, or coccidia, one of the classes into which the protozoa-the 
lowest forms of animal life-are divided. The organisms are generally 
found in the lower strata of the epiderm, the ducts of the cutaneous 
and mammary glands, and the sheaths of the hair follicles. Coccidia 
are unicellular organisms, roundish or elongated in form, composed of 
granular protoplasm, and contain one or more well-developed nuclei. 
They inhabit epithelial cells, in the interior of which they form pri- 
mary cysts. The cysts become filled with spores, burst and discharge 
the spores, which form the origin of new coccidia. The wall of the 
cyst has a double contour, from which the protoplasm is in places re- 
tracted, but is attached to the enveloping membrane in raylike pro- 
longations. It is difficult to bring out these bodies by staining, but Paget's Disease. 
5 
they may usually be detected by a power of four hundred to five hun- 
dred diameters. Several nucleated bodies may exist within one cyst 
wall. 
If we are able to accept this demonstration as conclusive, not 
only must Paget's disease be included in the category of animal 
parasitic affections, but it must be regarded as closely related to other 
maladies in which the same organism occurs, presumably as an ex- 
citing cause. 
Molluscum epitheliale, or molluscum contagiosum, is a rare disorder, 
which principally attacks children, and which, to the ordinary methods 
of observation, bears no likeness to Paget's disease of the nipple. In 
molluscum, numerous lesions, in different stages of development, are 
usually present upon the body. The face is the site of election, but 
other regions may be invaded. The lesions of molluscum epitheliale 
are rounded or pedunculated in form, and vary in size from a pinhead 
to a pea. Their color may be normal, pinkish, waxy, or glistening, 
the last giving rise to an appearance which has been aptly compared 
to pearl shirt buttons. The contents of the tumors are white and semi- 
fluid. They develop slowly, and are unattended, as a rule, by sub- 
jective symptoms. Molluscum contagiosum is so named because it not 
infrequently attacks simultaneously several members of the same 
family. Attempts at experimental inoculation have succeeded in at 
least three instances. 
The picture of molluscum epitheliale, consequently, is altogether 
different from that of Paget's disease, and purely clinical observation 
would never compare the two maladies. Yet in sections of the tumor 
of molluscum Darier and Neisser have found bodies which they look 
upon as coccidia. The latter author regards the molluscum corpuscle 
as a completely cornified epithelial cell occupied by the parasite, thinks 
that the disease is a form of epithelioma, and that it is better named 
epithelioma contagiosum. 
In treating of the clinical history of Paget's disease it was stated 
that, in its ultimate progress, it is transformed into or originates can- 
cer of the breast or other surface upon which it may be seated. Not- 
withstanding the decided difference in its gross appearance, molluscum 
epitheliale, as regards its minute pathological anatomy, has been con- 
sidered of epitheliomatons nature. In both disorders bodies believed 
by high authority to be coccidia have been found. These statements 
are, to say the least, suggestive, and it is to be hoped that the same 
line of investigation will be pursued until the identity of the organisms 
present in the two diseases shall be conclusively demonstrated or defini- 
tively disproved. 6 
Original Communications. 
Research has, moreover, proceeded a step further in the same direc- 
tion. The histo-pathology of carcinoma has been closely studied. 
The gross features of the disease are familiar to the practical surgeon. 
The details of its structure are well known to the microscopist. Once 
the carcinomatous process is started, we are able to follow each step of 
its evolution. We are still in doubt, however, as to the nature of its 
exciting cause. Cancer undoubtedly presents an analogy to the type 
of an infection. Efforts have been made, accordingly, by a number of 
observers, to discover a micro-organism which should be looked upon 
as its exciting cause. Many of these attempts have proved signal 
failures, but the studies of Darier, Albarran, and others have lent new 
interest to the subject. For the same psorosperms, or coccidia, which 
have been briefly described in this paper as being probably related 
setiologically to Paget's disease and to moliuscum epitheliale have 
been observed in carcinoma. As early as 1885 they were found by 
Albarran in a case of cancer of the jaw, and were identified by Malas- 
sez and Balbiani, expert authorities upon the lowest forms of animal 
and vegetable life. This discovery remained unpublished, but the 
psorosperms subsequently found by Darier were recognized by Ma- 
lassez as identical with those previously obtained by Albarran. Since 
that time they have been met with by other observers in cases of car- 
cinoma. Cornil has detected psorosperms in a section of cancer of the 
womb. Thoma, of Dorpat, found the same organisms in a mammary 
cancer which had not been preceded by Paget's disease. Wickham, 
who has also studied the subject, encountered coccidia in an epitheli- 
oma of the nose, and in two cases of epithelioma of the bladder the 
same bodies were seen by Albarran. 
The list of diseases in which psorosperms or coccidia are present 
is not yet, however, complete. Darier and Thibault have described a 
rare affection to which, on account of containing these organisms, 
they have given the name of vegetating follicular psorospermosis. 
This disease invades a considerable extent of surface. Its lesions 
begin as small papules, normal or nearly normal in color, which 
enlarge, acquire a hemispherical or flattened form, and become cov- 
ered with a firmly adherent grayish or blackish crust. The crust 
hardens, and is lodged in an infundibuliform depression, which corre- 
sponds to the dilated orifice of a hair follicle. A further development 
converts the lesions into prominent papillomatous growths. Adjacent 
growths may coalesce and cover a considerable surface with a sprouting 
mass, covered with cornified or thick and fatty concretions. From 
the craterlike depression sebaceous matter, either pure or mixed with 
pus, may sometimes be expressed. This malady is characterized by a Paget's Disease. 
7 
strong and peculiar odor. According to the writers to whom we owe 
the portraiture of vegetating follicular psorospermosis, it was formerly 
confounded with what is termed by French writers acne Iceratosa, or 
acne cornee, in which the sebaceous secretion undergoes cornification, 
with the follicular keratosis or ichthyosis of J. C. White, and with 
generalized molluscum epitheliale. The last-mentioned resemblance is 
of particular significance. 
One more affection remains which is probably related to those 
which have been already sketched. This was first described in a com- 
munication made to the Tenth International Congress by Albarran, 
who gave it the name of vesical psorospermosis. This disease is 
marked by proliferation of the epithelium of the bladder. The con- 
nective tissue of the organ likewise becomes involved, and the mucous 
membrane is thrown up in the form of papillary excrescences. The 
epithelial cylinders contained psorosperms in the two principal forms 
of roundish cells and spore-filled cysts. 
The study of the relation of microscopic and unicellular animal 
parasites to several affections which, although having points of contact 
or resemblance, possess also marked divergences, has led to the pro- 
posed formation of a group to be known as psorospermoses. The 
psorospermoses include Paget's disease, molluscum epitheliale, vege- 
tating follicular psorospermosis, vesical psorospermosis, and perhaps 
certain forms of superficial epithelioma. The whole question, how- 
ever, is to be regarded as still sub judice, especially as relates to carci- 
noma. It is only fair to add that the bodies figured by Darier are not 
universally accepted as coccidia but are by some authors thought to be 
simply degenerated or cornified epithelial cells.