thie papillary neoplasms of the breast* similar way

THIE PAPILLARY NEOPLASMS OF THE BREAST*I. BENIGN INTRADUCTAL PAPILLOMA

C. D. HAAGENSEN, M.D., ARTHUR PURDY STOUT, M.D.,AND JIM S. PHILLIPS, M.D.

NEW YORK, N. Y.

FROM THE DEPARTMENT OF SURGERY, PRESBYTERIAN HOSPITAL, AND THE LABORATORY OF SURGICAL PATHOLOGY,

COLUMBIA UNIVERSITY, NEW YORK.

THE PAPILLARY NEOPLASMS of the mam-mary gland continue to present a difficultdiagnostic and therapeutic problem for sur-geons, although a century has gone by sincethe awakening of modem pathology. In1905 J. Collins Warren,20 in presenting anew classification for benign tumors of thebreast, made an ardent plea for closer co-operation between pathologist and surgeon.Then, as now, correlation of the clinical fea-tures of the papillary tumors of the breastwith their pathologic characteristics was thekey to the confusion which still surroundsthem.

There are two main types of papillaryneoplasms of the breast-the benign intra-ductal papillomas which are relatively fre-quent, and the malignant papillary carci-nomas, which are rare. Both give rise to aserous or bloody nipple discharge. Thesetwo lesions, so different in their prognosis,have often been confused. It is our purposeto point out the clinical and pathologic fea-tures which distinguish them. In the pres-ent paper we will discuss the benign intra-ductal papillomas, and present our data re-garding them from the Presbyterian Hospi-tal and the Laboratory of Surgical Pathol-ogy of the College of Physicians and Sur-geons. In a subsequent report we will dealwith malignant papillary carcinomas in asimilar way.

HISTORICALJ. Collins Warren, in the paper we have

referred to, was one of the first to recognize* Submitted for publication February, 1950.

the benign character of "papillary cyst-ade-noma," and to recommend that the surgicalattack on these lesions be limited to localexcision. Earlier observers had often re-garded these lesions as malignant, and hadused a variety of terms to describe them-adenocystoma papilliferum mammae, vil-lous papilloma, papillary fibroma, duct pa-pilloma, cystoadenoma intracanaliculare,proliferous cysts, carcinome villeux, or ductcancer. Warren reported nine cases of in-traductal papillary cystoadenoma from theMassachusetts General Hospital, six ofwhich were treated successfully by localexcision.

Greenough and Simmons in 19078 madeanother study of the Massachusetts GeneralHospital data and reported 20 cases of pa-pillary cysto-adenoma. In 17 patients thelesion was benign. Seven of these patientshad simple mastectomy, and the remainingten had local excision. In two of the tenthe disease recurred locally, presumablydue to incomplete excision. The follow-upof this group of patients was not complete,only one of them being followed for as longas four years. Nevertheless, Greenough andSimmons believed that they had sufficientevidence to conclude that papillary cysto-adenoma ordinarily requires only local ex-cision.

In three of their cases adenocarcinomawas found in the wall of the papillarytumor. One of these patients died of recur-rent carcinoma four years after mastectomy.Greenough and Simmons therefore con-

18

THE PAPILLARY NEOPLASMS OF THE BREAST

FIG. 1

9352

itu v.c .S DA p iLir1 1In i. - U. --*. si-, .............,#A.- -; ..... ...

FIG. 2 FIG. 3

FIG. 1.-Three examples of intraductal papillary tumors. A is the more solid form whichalmost filled the cystic cavity and had a broad sessile base. B and C are more delicate and fri-able tumors with a small attachment to one part of the wall of the widely dilated ducts fromwhich they spring. In each instance the bloody fluid filling the ducts has been evacuated.

FIG. 2.-A small intraductal papillary tumor within a dilated duct at a distance of 4 cm.from the apex of the nipple.

FIG. 3.-A benign intraductal papilloma of the breast forming a 13 cm. tumor.

cluded that these papillary tumors maysometimes undergo malignant transfor-mation.

In 1916 Dean Lewis,1 of Chicago, in a

discussion of bleeding nipple, emphasizedthat a discharge of serum or blood from

the nipple is usually indicative of be-

nign intraductal papilloma, and not ofcarcinoma. He advised operative searchfor, and excision of the papilloma, even

when no tumor can be palpated. Hepointed out that in these cases theregion in which the growth lies can be de-termined by the appearance of the dis-

19

Volume 138Number 1

HAAGENSEN, STOUT AND PHILLIPS

charge when pressure is made over it.Lewis believed that local excision sufficesfor intraductal papilloma, and that in theoccasional case in which malignant trans-formation occurs this change can be de-tected from the gross appearance of thelesion.

Miller and Lewis,14 in 1923, reviewedtheir experience with 40 patients with aserous or bloody discharge from the nippleand found that it was due to benign intra-ductal papilloma in 32 per cent and to car-

cinoma in 68 per cent. This predominanceof cases of carcinoma led Lewis to take amore grave view of nipple discharge thanhe had presented in his earlier paper. Heemphasized that a serous or bloody nippledischarge is evidence of a pathologic lesionwhich should be searched for and identified.

In 1917 Judd" reviewed the MayoClinic records of 100 patients with serous or

bloody nipple discharge and reported that57 per cent were proved to have carcinoma.All of the patients with carcinoma had a

palpable breast tumor, a fact which ledJudd to use the presence of a tumor as a

distinguishing feature between nipple dis-charge due to carcinoma and nipple dis-charge due to intraductal papilloma. Noneof Judd's intraductal papillomas formed a.

palpable tumor. He therefore advocatedmastectomy for all patients with nipple dis-charge and a palpable tumor, but conserv-

ative treatment for those in whom no tumorcould be detected.

Joseph C. Bloodgood was another con-

temporary student of breast neoplasms whodiscussed intraductal papilloma in a seriesof papers (Bloodgood, 1921, 1922, 1932).He regarded it as a relatively innocuouslesion. He did not think it pre-cancerous.

In his opinion a serous or bloody dischargewas ordinarily due to intraductal papilloma-not to carcinoma. In his series of cases ofcarcinoma of the breast a discharge fromthe nipple was noted in only one per centprior to the palpation of a breast tumor.

In 1927 Deryl Hart'0 reviewed the JohnsHopkins' data concerning "intracystic pa-pillomatous tumors of the breast, benignand malignant" and wrote one of the bestavailable papers on the subject. He studied95 cases with benign papillary lesions and24 malignant ones. Forty-eight per cent ofthe benign lesions had a nipple discharge,which in a relatively large number had beenpresent for many years. In 20 per cent notumor was palpable. Local excision suf-ficed for cure of these benign papillomas.

A nipple discharge occurred in only 12.5per cent of Hart's cases with malignant pap-illary lesions. The duration of symptomswas usually short. A tumor was present inevery malignant lesion, and in most cases

the clinical picture suggested malignantdisease. Hart emphasized the necessity ofcarrying out radical mastectomy for thesemalignant lesions.

In Hart's series there was only one casein which the clinical history suggested thata benign papillary lesion had transformedinto a malignant one.

Adair (1930)1 presented a very differentpoint of view. He reviewed 108 cases ofsanguinous discharge from the nipple andreported that in 47.2 per cent the symptomwas due to malignant and in 52.8 per centto benign lesions. Forty-nine out of 57benign lesions were classified as intraductalpapillomas or papillary cystoadenoma, and17 out of 49 carcinomas were classified as

papillary adenocarcinoma. Adair concludedthat a serosanguinous or bloody dischargesignified the presence of a carcinoma aboutas often as it did a benign lesion, and thatbenign papillary cystoadenomas eventuallydeveloped into papillary adenocarcinomas.

In their book, published in 1931, Chea-tle and Cutler5 presented elaborate histo-logic evidence in support of their belief thatbenign papillomas may evolve into carci-noma. They did not include any convincingclinical evidence in support of this belief.Nevertheless they advocated simple mastec-

20

Annals of SurgeryJanuary, 195i


tomy as the proper treatment for papilloma.Saphir and Parker in 194017 made an in-

teresting study of the papillary lesions inthe breast. They studied 58 intraductalpapillomas and divided them into threegroups. Forty-two were placed in Group Iand designated as the fibrous type, ninewere placed in Group II and called theglandular type, and seven were placed inGroup III and termed the transitional type.They regarded the first two groups as welldifferentiated tumors and benign, but feltthat the latter group, which was not glan-dular in structure, being made up of more

or less solid masses of cells without connec-

tive tissue stalks, was potentially malignant.In 1941 Gray and Wood7 again reviewed

the experience at the Mayo Clinic regard-ing discharge from the nipple. Eighty-eightpatients with a serous or bloody nipple dis-charge proved to have benign papilloma.Simple mastectomy was carried out in al-most all of these cases. In 87 other patientswith a serous or bloody nipple discharge a

diagnosis of malignant papilloma was made.The details of the clinical signs in these pa-

tients with presumed malignant lesions are

not given beyond the fact that 52, or 60 per

cent, had no palpable tumor. The diagnosisof carcinoma was based upon the micro-scopic findings. It is of interest to note thatthe Mayo Clinic pathologists classified thelesions in 44 of these 52 patients as GradeI adenocarcinoma. This fact, and the pho-tomicrograph that Gray and Ward includeof one of these tumors, leads us to believethey were only benign papillomas.

Estes and Phillips6 have recently (1949)studied a series of 87 cases of intraductalpapilloma seen in their clinic and concludethat simple mastectomy is the proper treat-ment, although none of their patientstreated by local excision subsequently de-veloped carcinoma.

It is this tendency to employ a compara-

tively radical method of treatment for whatis in our opinion a benign breast lesion

which has stimulated us to review our own

experience in the Presbyterian Hospital.The data for our study of intraductal

papillary cysto-adenoma are from the rec-

ords of the Presbyterian Hospital and theLaboratory of Surgical Pathology of theCollege of Physicians and Surgeons. It in-cludes all the cases diagnosed as papillomaof the female mammary gland for the years

1916 to 1941, inclusive. We reviewed 367hospital records, 14 of which had insufficientdata for tabulation, leaving 353 for furtherconsideration.

It seemed wise at the outset to dividethe benign papillary lesions of the breastinto two types-those which were of suffi-

TABLE I.-Intraductal Papilloma of the FemaleMammary Gland-Presbyterian Hospital

1916-1941 inclusive.

Total case records ................................... 367

Insufficient data for tabulation ........................ 14

Total benign papillary tumors ......................... 353

Microscopic papillomas ............................... 243

Gross intraductal papillomas .......................... 110

Gross intraductal papilloma with unreleated carcinoma(not papillary) . .................................... 2

Gross intraductal papilloma for analysis .... ............ iCS

cient size to be evident on gross inspection,and those which were discovered only inmicroscopical study.

The former type constitute a -definitedisease entity in which one or more papil-lomas grow within a relatively localized di-lated portion of a duct, or in several adja-cent ducts, and attain sufficient size to fillup the duct and become evident grossly(Figs. 1 and 2). The delicate filamentousprocesses of the lesion easily break off or

are damaged and the serum or blood whichescapes finds its way along the diseasedduct and discharges from its opening on thenipple surface. A serous or bloody dis-charge is almost always the symptom whichbrings the patient to the physician. In manyof these patients the papilloma is not largeenough to be palpable at all, while in othersit may be felt or rather suspected as a radiallinear thickening beneath or adjacent to

21

Volume 133Number 1


the areola. The overwhelming majority ofthese intraductal papillomas are situated inthe central area of the breast in the largerducts near their termination in the nipple.There were records of 108 such benign in-traductal papillomas in our data (Table I).

The microscopic papillomas do not inthemselves constitute a separate disease en-tity. These lesions are one of the manifes-tations of the protean lesion which we call,for want of a better name, cystic mastitis.They are small multiple papillary projec-tions, with or without fibrous cores, whichproject into the ducts and cysts of chroniccystic mastitis. These lesions are alwaysmultiple, often involve the ducts in manyareas of the breast, and do not have a pre-dilection for any special portion of it. Thesemicroscopic papillomas rarely, if ever, pro-duce nipple discharge. They are describedin the literature as papillary hyperplasia,diffuse papillomatosis, cystiferous prolifer-ation, etc. We had data concerning 243 ofthese microscopic papillary lesions. Sincewe shall not attempt to deal with cysticmastitis in the present paper, we will notdiscuss them further.

CLINICAL CHARACTERISTICS

Age. The ages of our patients with in-traductal papilloma had a wide range, theyoungest being 19 and the oldest 82. Theirmean age incidence was, however, some-what younger than that of patients withbreast carcinoma in our hospital (Fig. 14).

Nipple Discharge. A nipple dischargewas the most frequent symptom in our pa-tients with intraductal papilloma. A san-

guinous or serous discharge occurred in 78cases, or 72 per cent. This sign occurredpredominantly in the central lesions.Eighty-six per cent (Table II) of the cen-

tral tumors, as compared to only 29 per centof the peripheral tumors had this type ofnipple discharge. The discharge was

serous in 23 of the 78 cases, and bloody in55 cases. In most patients it was noted onlyintermittently, as evidenced by an occa-

sional stain on the brassiere or night gown.Long intervals would go by without anydischarge in some patients. In other pa-tients the discharge was more consistentand abundant, slight pressure on the breastbeing sufficient to produce a flow of severaldrops of serum or blood.

In a few patients there was a relation-ship between tumor formation and the dis-charge. A tumor would slowly develop overa period during which there would be nonipple discharge. A profuse dischargewould then occur and the tumor would dis-appear as the distended duct or cyst emp-tied. This cycle would be repeated over

and over again.

TABLE II.-The Site in the Breast and the Fre-quency of Nipple Discharge in 108 Cases of Intra-ductal Papilloma-Presbyterian Hospital-1916-1941

Percent Number Cases PercentSite in Number of Total No. with Nipple with Nipplethe Breast Cases of Cases Discharge Discharge

Central ...... 81 75% 70 86.4%Peripheral .... 27 25% 8 29.6%

All sites .... 108 100% 78 72.1%

In an effort to determine why some pap-illomas cause a discharge from the nippleand others do not, all of the microscopicsections were reviewed with this questionin mind. We found that the more solidglandular type of papillary disease in whicha discharge is less frequent was more com-

monly located in the periphery of thebreast. This type of papillary proliferationalso predominated in those centrally locatedlesions that did not show discharge fromthe nipple. The highly papillary growthswith multiple long dendritic processes

which could readily be broken by the slight-est trauma were found more commonly inthe central portion of the breast.

Tumor. A tumor was recorded as beingpresent in almost all of the cases of intra-ductal papilloma which we studied. Thisfact suggests that in years gone by oper-

ation was done in our hospital for patients

Annals of SurgeryJanuary, 1951


FIG. 4

FIG. 4.-Benign papilloma growing in a ductwithin the nipple and presenting as a granulatinglesion froimi its orifice on the nipple surface.

FIG. 5.-A benign intraductal papilloma of thebreast producing skin retraction.

F*IG. 3

with a nipple discharge only when a tumorwas palpated. Today, we not infrequentlydiagnose and excise intraductal papillomasthat are not palpable.

The 108 intraductal papillary cysto-ade-nomas in our group of cases ranged in sizefrom 0.3 cm. to 10.5 cm. Almost all were

small, usually measuring only three or fourmillimeters in diameter and extendingalong the duct in which they arose for one

or two centimeters. In a good many of thecases the operator found a small roundedcystic structure containing bloody fluid and

papilloma but failed to trace the duct ex-

tending from it to the base of the nipple.There was only one very large tumor in

our series. The patient (M.F., No. 693230)was a Negro housewife, 59 years old, whocame to the Presbyterian Hospital Novem-ber 15, 1939. One year previously she hadnoticed a tumor of her left breast. It hadgrown steadily. There had not been any

nipple discharge.Examination showed a 13 cm. firm

tumor in the upper central portion of theleft breast (Fig. 3). The tumor had a lobu-

23

Volume 133Number 1


lated and circumscribed character and wasfreely movable. Although there were di-lated veins in the skin over it, there was noedema or redness of the skin and no en-larged axillary or supraclavicular nodes. Atoperation a biopsy for frozen section wasmistakenly diagnosed as carcinoma. Radicalmastectomy was therefore done. The diag-nosis from paraffin sections was also carci-noma, but re-study of these sections re-cently has convinced us that our originaldiagnosis was an error and that the lesionwas only a benign intraductal papilloma.

In rare cases the papilloma is situatedwithin the portion of a duct traversing thenipple. In this locatioil it may be palpableas a thickening within the nipple, or it maypresent through the dilated orifice of theduct as a friable granulating lesion (Fig. 4).

Retraction Signs. Retraction signs werenot systematically sought for and recordedin all of the cases in our series and we arenot able to give any exact figures as to theirfrequency. We do know, however, that inoccasional cases retraction signs were pro-duced by benign papilloma. These retrac-tion signs included both flattening of thenipple (Case No. 504405), as well as

dimpling of the overlying skin and distor-tion of the contour of the breast. A goodexample of the latter type of retraction signwas seen in the case of Mrs. E. F. (No.263648). She was a 72-year-old housewifewho came to the hospital complaining of a

bloody discharge from the left nipple whichshe had noted for the previous four months.The discharge consisted of a drop of very

black blood noted every other day. Shewent to her local physician, who discovereda tumor in the breast and referred her tothe hospital.

Examination showed a firm, 3 cm. tumorlying beneath the edge of the areola of theleft breast in the radius of four o'clock. Themass was relatively fixed in the surroundingbreast tissue and there was marked dimp-ling of the overlying skin. When the arms

were raised, a deep notch became evidentin the contour of the breast at the site ofthe tumor, as shown in Fig. 5. The breastand the tumor within it were freely mov-able over the chest wall.

The surgeon mistakenly chose to do a

radical mastectomy without frozen section.Pathologic examination of the breastshowed that the tumor mass consisted ofan intraductal papilloma solidly filling up a

cystic structure. On microscopical exam-ination the lesion proved to be a benignintraductal papilloma. The patient diedlnine years later following operation for a

strangulated femoral hernia.Retraction signs are of course due to

fibrosis in and around a breast lesion, andsince it is not unusual to see a good deal offibrosis of the duct wall at the site of papil-loma, as well as in the adjacent breast tis-sue, we may expect to find clinically evi-dent retraction signs in occasional patientswith benign papilloma.

Pain. Pain was noted as a symptom inonly two of our 108 patients with intraduc-tal papilloma.

Signs of Inflammation. In one of our

patients the clinical picture suggested an

abscess. The patient (No. 386,472), a

woman of 41 years who had not been preg-nant for some years, developed swellingand tenderness of the left breast, accom-

panied by throbbing pain and the escape ofa few drops of blood from the nipple. Aweek later, when she came into the hospital,there was a 4 cm. indurated area in theouter middle sector of the breast. The skinover the outer half of the breast was red-dened and abnormally warm. Pressureupon the area of induration produced aflow of "dark reddish pus" from the nipple.Culture of this material showed hemolyticStaphylococcus aureus.

The lesion was excised and proved to bea small intraductal papilloma filling a dis-tended duct, accompanied by acute inflam-mation in the surrounding breast tissue.

24

Annals ot SurgeryJanuary, 1951

Volume 133 THE PAPILLARY NEOPLASMS OF THE BREASTNumb.? 1

ci ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~cS1 S. a n~~~~~~~~~~~~~~~~~~~~~~~* ,.X s4 .. e n @Xs ~~~i * . . Co:1 =i_25


Duration of Symptoms. One of the clin-ical features of intraductal papilloma thatweighs strongly in favor of the benignnature of the lesion is its long duration. Inour data the duration of symptoms was re-corded in 103 of the 108 cases (Fig. 15). In11 the symptoms had been present for tenyears or more, and in eight other patientssymptoms had been present for five yearsor more.

A typical case history of a papillarycystoadenoma of long duration was that ofS. K. (No. 493048) a housewife 38 years

old. Seventeen years previously, followingweaning her first child, she had developed a

discharge from the left nipple. It consistedof a few drops of brownish fluid which shenoted only at intervals of from one to threemonths. She learned that by squeezing thebreast she could express a small quantity ofthe discharge. This seemed to relieve herof a feeling of discomfort in the breastwhich she had from time to time. Duringtwo subsequent pregnancies, 12 and eightyears previously, the discharge had disap-peared and did not recur until after thebabies were weaned.

Two years previously she had noted a

small lump beneath the areola of the leftbreast. This seemed to decrease somewhatin size when she squeezed her breast toexpress the discharge. Examination showeda freely movable 2.5 cm. tumor beneath theareola. There were no retraction signs.

At operation September 9, 1936 a thin-walled cystic structure filled with brownfluid and containing a papilloma growingfrom a broad base was found. The lesionwas excised, together with a small amountof adjacent breast tissue. Twelve years laterOctober 19, 1948, there had been no recur-

rence of either tumor or discharge.In other patients of ours with a sero-

sanguinous nipple discharge who wentthrough pregnancy, the disclharge did notdisappear during pregnancy or lactation,but stained the milk with blood and led to

the abandonment of nursing. Some patientsnoted that their nipple discharge was in-creased with the onset of menstruation;others reported no change during the men-strual cycle.

Long intervals of freedom from the dis-charge were not uncommon, as in the caseof A. L. (No. 504404), a nursemaid of 62years. She had first noted a sero-sanguinousnipple discharge ten years previously. Aftera few weeks the discharge ceased andnever re-appeared. Five years previouslyshe had first discovered a tumor beneaththe nipple. This had not changed in size,but it had recently become tender.

Examination showed a firm 3 x 3 cm.mass beneath the areola of the right breast.The mass was attached to the skin of theoverlying areola, and to the nipple, whichwas somewhat flattened.

At operation December 16, 1936 thetumor was found to be a cyst containingbrownish fluid and partly filled by a papil-loma. The cyst was excised. The patienthad had no recurrence when last seen 11years later (December 6, 1947).

BILATERAL PAPILLOMA

Involvement of both breasts by papil-lary diseases sometimes occurs. We haveseen several cases in which the disease ap-peared first in one breast, and then, after an

interval of several years, in the other one.In one of our patients, E. H., a Negro wid-owed housewife of 49 years, (No. 511025),both breasts became involved almost con-

temporaneously. Twelve years before sheapplied for treatment she woke one morn-ing to find her nightgown stained with a

bloody discharge from the left nipple. Thedischarge appeared about twice a weekfrom then on. A year later, the same phe-nomenon occurred in the right breast. Astime went on, the discharge became more

copious from the right breast. It was in-creased during menstruation.

Examination showed a 1 x 0.5 cm. mov-able tumor at 12 o'clock, beneath the edge

26



of the right areola. Pressure over this tumorproduced a discharge of bloody fluid fromthe right nipple. There was no tumor in theleft breast and no discharge could be pro-duced by pressure upon it.

The surgeon in charge of the patient dida bilateral simple mastectomy on January16, 1939. Pathologic examination of theright breast showed that the subareolartumor was an 8 mm. friable, intraductalpapilloma, attached by a single stalk to thewall of a dilated duct. Other small papil-lomas were found widely scattered through-out the duct system.

Pathologic examination of the left breastshowed numerous small papillomas widelyscattered throughout the duct system ofthe breast. Microscopically, all of the pap-

illomas were benign.This type of extensive involvement of

both breasts by benign papillary disease isinfrequently seen. In our experience, mostof the papillary lesions which are wide-spread in the breast and which involve a

large area of its periphery prove to be pap-

illary carcinomas.

PATHOLOGY

Intraductal papillary tumors are simplyproliferations of duct epithelium which pro-

ject outward into a dilated lumen from one

or more focal points. The proliferatedepithelial cells are supported upon vascularstalks which may be thin and delicate or

broad and extensive (Figs. 6 and 7). Theproliferations may be obviously papillary or

so completely anastomosing as to seem toform glandlike spaces (Figs. 8 and 9). Thegross appearance of these tumors is variedand depends upon the relative quantitiesof their component elements, together withthe presence or absence of fresh or oldblood, necrosis and fibrosis. If they havesuffered from repeated trauma, cicatricescan form not only in the papillary projec-tions but also in the wall of the dilated duct.Such scars may include glandlike tubes

which can create a false impression of infil-trative growth (Fig. 10). Another exampleof this is shown in the intraductal papillarytumor involving the orifice of a nipple ductillustrated in Fig. 4. Here the original ductwall has almost disappeared, leaving theepithelial proliferations in a mass of scar

tissue suggesting the infiltrative growth ofcancer. The criteria which enable one todifferentiate between benign and malig-nant, not only in such a case as this butalso where the growth is wholly enclosedwithin an intact duct wall, are found in thecells themselves. In benign growths thecells will resemble the appearance of nor-

mal duct epithelium whether of the usualtype or the so-called apocrine cells of largesize with small nuclei and acidophilic gran-

ular cytoplasm. It must be rememberedthat normal duct cells vary considerably.Not only are they capable of enlargementwhen engaged in secretory activity but theycan act as phagocytes and undergo degen-erative changes with swelling and fatty in-filtration. In order to judge whether or notsuch abnormal appearing cells are cancer-

ous, one must be familiar with these variouschanges which can take place in non-can-

cerous cells. In doubtful cases the decisiongenerally rests upon the nucleus; if this hasthe appearance of anaplasia with hyper-chromatism, accentuation of the chromatinnetwork or large nucleoli, and particularlyif there are more than rare, widely sepa-

rated mitoses, the growth can safely be con-

sidered cancer. We include a photomicro-graph (Fig. 11) of a papillary carcinomawhich was partly intraductal in order toillustrate this point and to provide a com-

parison with the features of benign papil-lary tumor cells (Figs. 8, 9 and 10). In thesubsequent paper dealing with papillarycarcinoma this feature of differential diag-nosis will be elaborated. Here it may beemphasized that recognizable solitary nod-ules of papillary carcinoma almost never

show traces of benign intraductai prolifera-27

Volume 133Number 1


FIG. 10

Fic. I 1

FIG. 10.-Benign intraductal papillary tumor showing the effect of scar-ring. Glandlike proliferations seem to invade downward from the surfaceinto the capsule. None of tumor cells has the characteristics of malignancy.

FIG. 11.-Detail from a partly intraductal papillary carcinoma to empha-size the appearance of cancer cells in papillary formation.

Annals of SurgeryJanuarY, 1951

Volume 133 THE PAPILLARY NEOPNumber 1

tions, so that in doubtful cases if there aremicroscopic cells which one might betempted to consider cancerous within anotherwise benign papillary tumor, our ex-perience shows that the technic elsewheredescribed for the local excision of benignpapillomas will also cure such tumors.Either these cells are not cancer cells, or ifone chooses to regard them as such, thecondition is comparable to cancer in situ.Because we have no proof that this condi-tion in breast papillary tumors has ever ledto the development of true clinical cancerwe have classified tumors showing epith-elial proliferations of this sort with the restof the benign intraductal papillary tumors.

TREATMENT

The treatment of the 108 patients withbenign intraductal papilloma in our seriesvaried considerably depending upon thesurgeon in charge of the patient. The periodcovered by our study extended over 25years and almost all of the surgeons on thehospital staff were concerned. Some of oursurgeons persisted in believing that intra-ductal papilloma is a potentially malignantlesion and therefore were inclined to carryout radical therapy. Fortunately for thepurposes of our study, the majority of oursurgeons were convinced of the benignancyof this lesion and were content to do con-servative local excision. Table III showsthe type of treatment in our series of cases.Thirty-two of our patients had either radicalor simple mastectomy, while in 76 onlylocal excision of the lesion was performed.

The 32 cases in which radical or simplemastectomy was performed are of no realvalue to us from the viewpoint of determin-ing whether intraductal papilloma is benignor malignant, because in these cases thedisease may have been cured by the treat-ment even if it was malignant. It is never-theless worth-while to refer briefly to thisgroup of cases.

In the 12 patients in whom radical mas-

'LASMS OF THE BREAST

tectomy was carried out the reason for thisneedlessly radical therapy was in every in-stance a mistaken diagnosis of carcinoma.In three of these cases the surgeon was re-sponsible for the error. In two of thesecases he proceeded without a biopsy, whilein a third case he went ahead on the basisof an incorrect aspiration biopsy diagnosisof carcinoma made in another hospital. Inthe remaining nine cases the pathologistwas responsible because he made a mis-taken microscopic diagnosis of carcinoma.

In four of these cases this mistake wasmade with adequate paraffin sections avail-able for study, but in the remaining fivecases the pathologist based his opinion

TABLE III.-The Treatment of Intraductal Papil-loma According to the Site of the Lesion in the

Breast-Presbyterian Hosp tal-1916-1941Central Pet iplicral Total Percent

Type of Treatment Site Site All Sites of Total

Radical mastectomy. . 9 3 12 11%Simple mastectomy. 16 4 20 18.5%Local excision........ 56 20 76 70.5%,

Total treated...... 81 27 108 100%

solely upon frozen sections. During thepast ten years we have not made a mistakeof this kind because we have learned inquestionable cases not to rely upon frozensections in distinguishing benign from ma-lignant papillary tumors of the breast. Fro-zen sections are not adequate for this diffi-cult microscopical diagnosis. During thelast decade it has been our practice to ad-vise biopsy only in cases in which the sur-geon, when exploring a supposed papillomaof the breast for which he intends to do asimple local excision, finds features whichsuggest the possibility of the lesion beingmalignant. Following removal of a satisfac-tory piece of the lesion the wound is closed,and we wait for paraffin sections uponwhich to base our diagnosis. If the lesionproves to be benign, it is locally excised ata second operation. If it is malignant, rad-ical mastectomy is done. We believe that

29

HAAGENSEN, STOI

the disadvantage of having to delay andcarry out our definitive treatment at a sec-ond stage is more than compensated for bythe avoidance of the risk of subjecting thepatient to an unnecessary radical mastec-tomy for a benign papilloma.

In 20 patients simple mastectomy wasdone. The reasons for this choice were notalways apparent in the case records. Insome instances the surgeon's lack of con-fidence in his pathologist's ability to distin-guish benign papillary disease from carci-noma in the breast was the basic reason.This was the obvious explanation for the

UJT AND PHILLIPS Annals of SurgeryJT ANDPHILLIPS ~JanUary,1951dealing with an intraductal papilloma untilthe pathologist made the diagnosis for him.

In a limited number of cases surgeonswith a better knowledge of the diseasemade a correct clinical diagnosis of benignpapilloma, determined its site, and made acircumareolar incision which permittedthem to turn back a flap to the base of thenipple. The diseased duct was then iden-tified and dissected out, cut off at the baseof the nipple, and traced distally until thepapilloma within it was found. The dis-eased duct, or ducts, together with a wedge-shaped sector of the surrounding breast tis-

TABLE IV.-Follow-up of 76 Patients with Intraductal Papilloma Treated by Local ExsionPresbyterian Hospital 1916-1941

Total Cases Died of Cured Rec. of Papilloma Devel-Treated Intercurrent oped Total

Site in by Local Lost Dis. Before 5 Yr. 10 Yr. Under After Car- Cases Percentthe Breast Excision Track of 5 Yrs. + + 5 Yrs. 5 Yrs. cinoma Followed Follow-upCentral ...... 56 3 3 28 20 2 0 0 53 94.6%Peripheral ..... 20 1 0 12 7 0 1 0 19 95.%All sites...... 76 4 3 40 27 2 1 0 72 94.7%

five cases in which biopsy and frozen sec-tion were done and the pathologist made adiagnosis of benign papilloma, yet the sur-geon proceeded to remove the breast. Inone other case the surgeon was told by thepathologist that the frozen section showed a"precancerous" lesion; he of course did amastectomy. In four additional cases thesurgeon had not localized the papilloma byhis clinical examination and he failed tofind it at operation. He resolved this di-lemma by performing a simple mastectomy,and excused his drastic therapy on theground that it was a prophylactic measureagainst the development of carcinoma.

In the 76 patients in whom local exci-sion was the method of treatment the thor-oughness of the excision varied with theoperator's understanding of the pathologyof intraductal papilloma. In most of thecases the surgeon simply cut down uponthe tumor and excised it, and did not at-tempt to identify it and dissect out theduct or ducts in which the papilloma arose.Often he did not recognize that he was

sue, were then excised. This in our opinionis the ideal therapy.

FOLLOW-UP

Table IV shows the follow-up of 76 pa-tients in whom local excision of an intraduc-tal papilloma was performed. It was pos-sible to follow 72, or 94.7 per cent of the 76patients. Only four were lost after all meansof contact were exhausted.

Three of the 72 patients died of inter-current disease before five years hadelapsed, one month, two years and fourmonths, and one year and four months fol-lowing operation. Three other patients de-veloped recurrences, two under five years,and one more than five years after the orig-inal operation. In two other patients thatwere followed for five or more years, onedeveloped a new papilloma in the oppositebreast after nine years, and the other a newpapilloma in the opposite quadrant of thesame breast after eight years. No patient inthis series developed carcinoma.

30


Details of the histories of the three pa-tients that developed recurrence after localexcision and the two patients who devel-oped new papillomas elsewhere in theirmammary tissue follow:

Case 1.-Mrs. 0. R. (No. 267438) was a 38-year-old female, first seen in 1930, complainingof a bloody discharge from the left nipple of7 years duration. She had had a lump in herbreast for 6 weeks. On examination she had a4 by 5 cm. mass at the areolar margin that wasfreely movable. On July 16, 1930, the tumor was

excised locally. The surgeon failed to recognizethe nature of the lesion and cut directly downon the tumor and excised it without tracing theduct to the nipple or identifying its peripheral ex-

tension. With this kind of limited excision it isvery likely that part of the duct or ducts contain-ing papilloma were left behind. Microscopicallythe original lesion was a benign intraductal papil-loma.

Approximately 4 years later there was a re-

currence in the scar of the previous operation.January 16, 1934, the new tumor was biopsied, afrozen section diagnosis of carcinoma made, andradical mastectomy carried out. Fixed sections,however, proved the lesion to be identical withthe original benign intraductal papilloma. Thepatient was subsequently followed for 6 years andhad no further trouble.

Case 2.-Mrs. D. B. (No. 524840) was firstseen in August, 1937, when she was 34 years ofage. She complained of a bloody discharge fromthe left nipple, of 3 years duration, a lump in thisbreast of one vear's duration. Examination re-vealed a 2 by 3 cIn. shotty mass at the upper inneraerolar margin. On August 20, 1937, a partial mas-

tectomy was done. In this patient also the lesionwas cut down upon and shelled out bluntly with-out any attempt to trace the duct system eithercentrally or peripherally. Microscopically it was a

benign intraductal papilloma.In 1941 there was a 0.5 cm. recurrent tumor

in the scar of the previous operation. On Febru-ary 6, 1941, a second partial mastectomy was done.At this time a pyramidal sector of breast tissue,including the diseased duct system centrally andperipherally and down to the pectoral fascia, was

removed. In July, 1946, 5 years later, she was freeof disease in both breasts.

Case 3.-Mrs. V. H. (No. 447480) 48 yearsold, came to the Presbyterian Hospital in April,1935. She complained of a lump in the right breastof 3 weeks duration, without a history of nippledischarge. There was a 2 by 2.5 cm. mass in the

upper outer quadrant of the right breast. She wasoperated upon April 10, 1935. The tumor was cutdown upon and found to be a cyst filled with fri-able hemorrhagic tissue. It was then crudely ex-cised. No attempt was made to trace the extentof duct involvement by the papilloma. Recurrencein the scar was noticed approximately 7 years later,when examination showed a 4 cm. mass beneaththe scar of the previous operation. A second oper-ation was done on September 24, 1942. Biopsyshowed that the tumor was still a simple benignintraductal papilloma, and another local excisionwas done. She was last seen in April, 1948, fiveand one-half years later, without evidence of tumorin either breast.

Case 4.-Mrs. M. R. (No. 564041), 30 yearsold, came to the Presbyterian Hospital, October20, 1938. She had noticed a small crusted area onher left nipple for over a year. There was a sm-allamount of yellowish discharge from it from timeto time. Palpation of the breast failed to revealany tumor. Close inspection of the nipple showedthit the orifice of one of the nipple ducts wasdilated and that projecting from it was a soft, red-dish, papillary mass about 3 mm. in diameter. Thiswas assumed to be an intraductal papilloma of theterminal portion of the duct. At operation a sectorof the nipple, including the diseased duct, was ex-

cised. The excision was carried to the base of thenipple and a little way down into the breast. Mi-croscopic examination showed that the lesion wasindeed an intraductal papilloma. It projected fromthe orifice of the duct and extended down alongits branches to the base of the specimen. It wasnot certain from the study of the microscopic sec-tions that the papilloma had been excised in itsentirety.

The follow-up of this patient showed, how-ever, that the excision was adequate, for she hashad no further trouble with the left breast. Butnine years later (June 18, 1947) she entered an-other hospital for bleeding from the right nipple.A local excision of the subareolar area was doneand benign intraductal papilloma found.

This case is therefore an example ofthe development of a new papilloma in thecontralateral breast.

Case 5.-Mrs. H. H. (No. 584608), a house-wife of 38 years, came to the Presbyterian Hospi-tal on July 15, 1939, because of a tumor in herleft breast which she had noticed 14 months pre-viously. There had been no nipple discharge. Ex-amination showed a firm but circumscribed 3 cm.tumor just beyond the mesial edge of the leftareola. At operation on August 5, 1939, the tumor

31

Volume 133Number 1

HAAGENSEN, STOUT AND PIHILLIPS

was found to be cystic and filled with friable papil-lary tissue. It was excised, and microscopic exam-

ination confirmed the diagnosis of benign intra-ductal papilloma.

In 1947 the patient noted a new tumor in theleft breast. It lay in a different site than her orig-inal tumor, being at the lateral rather than themedial edge of the areola. It was 3 cm. in diame-ter. At operation on October 15, 1947, the lesionwas found to be a group of small cysts containingpapillary tissue. The dilated ducts containing papil-loma were traced to the base of the nipple and re-

sected, together with the cystic mass. The lesionwas, like the original tumor 8 years previously, a

benign intraductal papilloma. When the patientwas last seen in January, 1949, there had been no

further recurrence.

We assume that this case illustratesthe development of a new intraductal pap-

illoma in another sector of a breast pre-

viously involved by the same type of lesion.The follow-up in a considerable niimber

of patients in this series was a long one.

Table V lists 31 cases in which local exci-sion only was done and in which the totalobservation period, including the length oftime symptoms had been present beforetreatment, and the length of the follow-upafter operation, totalled from ten to 29years. The fact that carcinoma did notappear in any of these patients during thislong period of time is good evidence thattheir lesions were indeed benign.

DISCUSSION

Perhaps because intraductal papillarycystoadenoma is such a relatively infre-quent type of neoplasm of the breast, therehas been considerable confusion concerningits natural history and disagreement regard-ing its treatment. This is due, we believe,chiefly to the lack of knowledge of thepathology of intraductal papilloma on thepart of the surgeons. Many are not familiarenough with the gross appearance of a ductcontaining a papilloma to be able to find itat operation. The dissection, must more-

over, be a meticulous one in which bleedingis carefully controlled or it will not be pos-

sible to see the lesion. Handicapped by

these difficulties the average surgeon whoattempts local excision of an intraductalpapilloma has been content merely to exciseblindly the area of breast tissue which hepresumes contains the lesion, without dis-secting it out and identifying it. When localexcision is done in this manner it is not sur-

TABLE V.-Thirty-one Patients with IntraductalPapilloma Treated by Local Excision Observed

for More Than Ten YearsPresbyterian Hospital-1916-1941

Duration of Symptoms Follow-upYears Plus

Case Nipple Breast Follow-up Sym ptomsNo. Discharge Tumor Years Years

358944 4 2 13 1771209 4 ? 12 1645146 1/4 ? 21 21-1/467993 ? ? 13 13

367344 1/12 ? 15 15-1/12377443 3 ? 14 17267438 7 1/6 3 10-1/6347669 0 1/6 11 11-1/6665915 1/12 0 17 17-1/12356666 1/6 0 18 18-1/6276101 ? 1/4 17 17-1/4266658 3 ? 12 15481047 1/6 1/2 11 11-1/2471962 0 3 10 13386472 1/52 ? 11 11492976 0 3 10 13493048 17 2 12 29503008 11 ? 9 20504405 10 5 11 21809774 1/3 1 10 11508051 1 ? 10 11506120 5/6 13 9 22552775 1/3 1/12 10 10-1/3560461 0 1 10 11329775 1/6 0 10 10-1/6598150 1 0 10 11477715 1/3 ? 10 10-1/3538808 6 ? 9 15589488 10 ? 4 14616350 3 1/4 7 10401127 4 1/6 13 17

prising that recurrence occasionally devel-ops from papilloma left behind. In our ownexperience recurrence has not followedwhen the papilloma is accurately identifiedand excised with a wedge-shaped sector ofbreast tissue around it.

Another cause for confusion regardingthe treatment of intraductal papilloma isthe fact that pathologists have difficulty indistinguishing microscopically benign pap-illoma from papillary carcinoma, and tendto classify a good many entirely benign

32



lesions as malignant. We recognize thatthis distinction is not an easy one, but we

believe that with adequate experience it canbe made with certainty in almost every case.

When the pathologist is in doubt, he hadbetter delay and seek more experienceddiagnostic help before deciding that thelesion is malignant. He should rememberthat papillary carcinomas are very rare andthat even if the lesion in question proves

to be one a reasonable delay will not impairthe chance of cure by radical surgery be-cause the growth vigor of papillary carci-

nipple discharge may mean that the lesionis growing within the duct lumen, and thepressure of intraductal injection might forcecarcinoma cells into lymphatics. We makesmears of the nipple discharge, and exam-

ine them using the Papanicolaou stain. Wehave correctly diagnosed both benign pap-

illomas and carcinomas in this way, but themethod is not sufficiently reliable to baseour therapy upon it.

In our Presbyterian Hospital data only1.3 per cent of carcinomas have been ac-

companied by a serous or bloody nipple dis-

FIG. 12 FIG. 13

FIG. 12.-Coincidental occurrence of a benign papillary tumor in a duct close to the surfaceof the nipple present for 20 years and an unrelated carcinoma in the same breast.FIG. 13.-Low power photomicrograph of the lesions shown in Fig. 12. The intraductal

papillary tumor in the nipple is shown not far from the skin surface. Deep to this are dilatednipple ducts showing cholesterol clefts. In the upper right corner is a carcinoma.

nomas, like the other well differentiatedcarcinomas of the breast, is decidedly lessthan that of the ordinary breast carcinoma.

A patient who comes to us with a his-tory of bloody or serous discharge from thenipple, and in whom a tumor is palpable, isadmitted to the hospital and all prepara-

tions made for a radical mastectomy. Wedo not ordinarily bother to examine thebreast by transillumination, because the in-formation thus obtained is not of decisivedifferential value. We regard injection ofthe ducts for roentgenographic studies as a

potentially dangerous procedure. If thelesion is a carcinoma, a serous or bloody

charge. In the overwhelming proportion ofpatients with this symptom the lesion is be-nign intraductal papilloma. If there is an

accompanying tumor that has the clinicalcharacteristics of a carcinoma, our proce-

dure at the operating table is to biopsy it as

we would a carcinoma, making a small in-cision directly over it, exposing the surface,and excising a small wedge for frozensection.

In rare instances intraductal papillomaand carcinoma occur simultaneously in thesame breast, but appear to be of independ-ent origin. Two such cases were found inthe present study (Figs. 12 and 13).

33

Volume 133Number 1


If, on the other hand, the accompanyingtumor has the characteristics of an intraduc-tal papilloma, that is, if it is a small elon-gated pencil-like thickening radiating outfrom beneath or near the areola, or a moreor less rounded and circumscribed mass sit-

Fic. 14

AGE GROUP0- 1 9

20- 29 130- 3940- 4 950- 59 _60- 6970+ I

of the nipple and dissect out the ductsNwhich radiate from it. The dissectioni mustbe performed with delicacy, and meticuloushemostasis achieved with mosquito hemo-stats, otherwise the pathologic changeswill be obscured. The duct containing the

o - 9

200- 2 930 - 3 9 m40- 4 950- 59 160- 6970+

10 - 1 9

20- 29 -30- 39 _40- 49 _50- 5 9 _60- 69 _70+ m

NO OF CASES

27 PERIPHERAL INTRADUCTAL PAPILLOMAS

876 CARCINOMAS OF BREAST

80, 0I 0I4 0 8 0 120 160 200 240 280 32C

40

35

30

cn 25i

uo 20 * \EACH DOT REPRESENTS ONE CASE

uj 15 L:

,':\ 1 -

6 12 2 3 4 5 6 7 8 9 10 12 13 14 15 16 17MONTHS YEARS

Fic. 15

FIG. 14.-The age distribution of intraductal papillonlas and arcinomas

of the breast in tile Presbyterian Hospital.FIc. 1.5.-Duration of syrmptomlls of intraduetal papillomiia of the breast

in the Presbyterian Hospital.

uated near the center of the breast, it is our

practice to miake our inlcisioIn at the edge ofthe areola, centering at the radiuis in whichthe tumor lies and extencding arounid aboutone-half of the areolar circumference. WN'ethen dissect up the areolar flap to the base

34

papillomIa caIn usually be identified by itssize and color. It will be dilated to a diam-eter of something like 3 to 6 mm, and theserum or blood which it contains gives it a

bluish appearaince. Having identified andisolated it, Nwe clamp it and cut across it at

Annals of 'SurgeryJaiuairy, 1 9 5 1

81 CENTRAL INTRADUCTAL PAPILLOMAS


the base of the nipple. Unless the involvedduct is dissected out to the very base ofthe nipple there is danger of not removingthe papilloma in its entirety, for the branch-ing processes commonly grow along theduct very close to the nipple base. Not in-frequently several ducts are involved by thepapillary proliferation and then each onemust be dissected out and severed at thebase of the nipple. We do not hesitate tosacrifice as many ducts as is necessary toenable us to be certain that we have in-cluded all those diseased in our dissection.Frequently we appear to cut across all ofthe ducts in the course of our search. Noharm seems to follow.

When the diseased duct or ducts are cutacross their enlarged caliber, the escape ofcharacteristic yellowish or bloody fluidfrom them will confirm the fact that theducts containing the papilloma have beenfound, even if the papilloma itself is notidentified through the wall of the terminalportion of the ducts thus far dissected out.

Without further effort to trace the dis-eased duct out into the breast we then ex-

cise a wedge-shaped sector of mammarytissue surrounding the involved duct. Inorder to accomplish this it is first necessary

to elevate a flap of skin and subcutaneoustissue from the mesial edge of the wound,uncovering the area of breast tissue to beexcised. The size of the sector excised variessomewhat with the size of the breast, but itis our practice to carry the excision abouthalf-way out toward the periphery of thebreast. As the base of the wedge of breasttissue is being cut across, great care is takento keep the operative field dry so that if anyof the ducts are seen to contain extensionsof the papilloma as they are cut across, a

wider excision can be carried out. Aftercareful hemostasis the wound is closed with-out drainage. The circumareolar incision,if properly closed with subcuticular andskin sutures of silk, leaves a scar which isalmost invisible.

If a patient develops a bloody or serousdischarge from the nipple, and careful pal-pation fails to reveal any tumor in thebreast, it can safely be assumed that such apatient does not have a carcinoma. Blood-good drew this conclusion many years agofrom his Johns Hopkins' data, and the rulehas proved true in our experience in thePresbyterian Hospital. When such a patientwith a serous or bloody nipple dischargebut no tumor comes to us, we do not, how-ever, dismiss her. We must assume thatshe has an intraductal papilloma, and it isour duty to find it and remove it. We re-examine her at intervals of two weeks ormore. In almost every case, after severalexaminations we find a tumor, or discoverthe point in the circumference of the sub-areolar area where pressure produces a

drop of discharge from the nipple. It maybe helpful in finding this pressure point tocaution the patient not to press upon it or

squeeze her breast in the intervals betweenre-examination. This gives the dilated ductcontaining the papilloma a chance to fill up.The pressure point gives the necessary clueas to the proper sector in which to makethe circumareolar incision, and the opera-tion is then carried out as above described.

Low grade infectious processes in thedeeply situated sebaceous glands of theareola, or in the mammary gland of thesubareolar region, sometimes break into a

terminal duct and discharge pus from thenipple. The discharge may be chronic butthe accompanying signs of inflammationbetray its nature. A white or milk discharge,on the other hand, is indicative of a minordegree of functional activity of the breast.Such a milky discharge persists in somewomen for months or even years after lac-tation. It is ordinarily bilateral and is usu-

ally obtained only by squeezing the nipple.The serous or bloody discharge caused byepithelial proliferation in the duct systemescapes spontaneously in droplets whichstain the patient's nightgown or brassiere.

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Volume 133Number 1

HAAGENSEN, STOUT AND PHILLIPS Annals of Surgery

We can see no justification for the ten-dency of many surgeons to recommendsimple mastectomy for intraductal papil-loma. Our own follow-up data, and thatof such careful students as Hart, clearly es-tablish the benign nature of intraductalpapilloma. In our own experience we haveno evidence that intraductal papilloma,even when persisting in the breast overmany years, transforms into papillary carci-noma. The rare papillary carcinomas beginas such, de novo, and maintain their char-acteristic low grade of malignancy through-out their natural history. They can be dif-ferentiated microscopically from intraductalpapilloma.

Local excision, carried out meticulouslyaccording to a plan which makes it possibleto identify the duct or ducts containing thepapilloma, and to remove them with a rea-sonable margin of surrounding breast tis-sue, suffices for cure, and spares the patienta needless and mutilating mastectomy.

BIBLIOGRAPHYAdair, Frank E.: Sanguinous Discharge from

the Nipple and Its Significance in Relationto Cancer of the Breast. Ann. Surg., 91: 197,1930.

2 Bartlett, E. I.: Papilloma of the Breast. West.J. Surg., 56: 12, 1948.

3 Bloodgood, Joseph Colt: Benign Lesions of theFemale Breast for which Operation is notIndicated. J. A. M. A., 78: 859, 1922.

4 Bloodgood, Joseph Colt: Borderline Breast Tu-mors. Am. J. Cancer, 16: 103, 1932.

5 Cheatle, G. L. and Max Cutler: Tumors of theBreast. J. B. Lippincott Co., Philadelphia,1931.

6 Estes, A. C. and C. Phillips: Papilloma of Lac-

teal Duct. Surg., Gynec. & Obst., 89: 345,1949.

7 Gray, H. K. and G. A. Wood: Significance ofMammary Discharge in Cases of Papillomaof the Breast. Arch. Surg., 42: 203, 1941.

8 Greenough, Robert B. and Channing C. Sim-mons: Papillary Cystoadenoma of the Breast.Ann. Surg., 45: 188, 1907.

9 Greenough, Robert B. and Channing C. Sim-mons: The Results of Conservative Treat-ment of Cystic Disease of the Breast. Ann.Surg., 60: 42, 1914.

10 Hart, Deryl: Intracystic Papillomatous Tumorsof the Breast, Benign and Malignant. Arch.Surg., 14: 793, 1927.

11 Judd, E. S.: Intracanalicular Papillomas of theBreast. Journal-Lancet, 37: 141, 1917.

12 Lewis, Dean: Bleeding Nipples. Surg., Gynec.& Obst., 22: 666, 1916.

13 McDonald, Ian: The Bleeding Nipple as a Di-agnostic and Therapeutic Problem. Califor-

nia & West. MIed., 68: 1, 1948.14 Miller, Edwin W. and Dean Lewis: The Sig-

nificance of Sero-hemorrhagic or Hemor-rhagic Discharge from the Nipple. J. A.M. A., 81: 1651, 1923.

15 Miller, Edwin W.: Lesions of the Breast Asso-ciated with the Discharging Nipple. S. Clin.North America, 4: 757, 1924.

16 Pribam, Bruno Oskar: Die blutende mamma.Ergebnisse der Chirurgie und Orthopaedic,13: 311, 1921.

17 Saphir, Otto and Morris L. Parker: IntracysticPapilloma of the Breast. Am. J. Path., 16:189, 1940.

18 Sistrunk, Walter E.: The Surgical Aspects ofBenign Lesions of the Breast. New OrleansM. & S. J., 75: 47, 1922.

19 Stowers, James E.: The Significance of Bleedingor Discharge from the Nipple. Surg., Gynec.& Obst., 61: 537, 1935.

20 Warren, J. C.: The Surgeon and the Pathologist.J. A. M. A., 45: 149, 1905.

21 Warren, Shields: Prognosis of Benign Lesionsof the Female Breast. Surgery, 19: 32, 1946.

036

thie papillary neoplasms of the breast* similar way

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