COMEDO CARCINOMA (OR COMEDO-ADENOMA) O F THE F E M A L E BREAST

JOSEPH COLT BLOODGOOD

I n 1893, forty-one years ago, I assisted Dr. Halstecl in exploring a clinically benign tumor of the breast. The patient was sixty-seven years of age and had observed a small tumor for about eleven months. It was our custom then to cut into the tumor and decide on its patho- logical nature from the naked-eye appearance of the tissues. This tumor was not encapsulated and not oystic, but distinctly circumscribed and buried in a senile breast. The moment we cut into and pressed on it, there exuded from its surface many grayish-white, granular cyl- inders, which I called at that time comedos. From the gross appear- ance the tumor was diagnosed as malignant, and the radical operation was performed. The nodes were not involved, the breast was senile, and there was no gross or microscopic evidence of chronic cystic mas- titis. This patient lived nineteen years after operation, dying at the age of eighty-six.

Since then I have been recording such cases and have divided them into two groups-pure comedo-adenocarcinoma and comedo-adeno- carcinoma with areas of fully developed cancer of the breast. Ex- amples of the latter group, in which areas of pure comedo tumor are present in an otherwise fully developed cancer of the breast, are the more frequent, and for this reason the operator must always bear in mind the possibility of cancer when comedos are present in a tumor. Hence, if the tumor is too large to exclude the presence of malignant areas by frozen sections, a radical mastectomy should be done.

Until three years ago it was my practice to perform the complete operation for cancer of the breast in all operable cases, whether of pure comedo or of comedo with cancer. In reviewing the records of these cases the striking feature is that none of the cases of pure comedo-adenocarcinoma was associated with metastasis to the axillary nodes, and not a single patient died of cancer. The majority have lived over five years, a few over ten years, and two almost twenty years. In one case, in which the disease involved both breasts, the patient is liv- ing today, more than twenty-one years after the removal of the second breast, and twenty-three years after removal of the first breast. In two instances the tumors had broken down, ulcerated, and produced a fungous growth. In a third case the fungous tumor was recurrent in the scar of a previous operation at which only the tumor had been re- moved. This is the first example of a permanent cure following rad- ical mastectomy for recurrent cancer of the breast.

In contrast to the pure comedo group, is the larger number of case8 in which pure comedo areas were found, both grossly and with the

1 Read before the American Association for Cancer Research, Toronto, March 28, 1934. 842

COMEDO CARCINOMA OF THE FEMALE BREAST 843

microscope, to be associated with fully developed cancer of the breast. Of these patients in whom nodes in the axilla were not involved, 30 per cent died of metastasis. Among the large number with axillary in- volvement the percentage of five-year cures was identical with that in fully developed cancer of the breast without comedo areas.

Pure comedo-adenocarcinoma is a rare but distinct tumor of the breast, and I am confident it can be recognized on frozen section when

FIG, 1. FUNQOUS TUMOR IN SCAR AFpER REMOVAL OF THE BREAST, ONE YEAR EARLIER, FOR A

Halsted’s complete operation was done. The nodes were not involved and the patient lived more than fifteen years without recurrence. This was the first so-called recurrent breast ancer treated in the Halstod Clinic without further recurrence five years or more after the second operation. For gross and microscopic pictures, see Figs. 2 and 3.

Incidentally this picture, taken in 1897, is of historic interest, as it shows the sterile gown in which patients were dressed at that time before leaving the ward for the operating room,

PRIMARY TUMOR OF EIGHTEEN MONTHS’ DURATION. PATE. No. 1705

Original photograph by Dr. Harvey Gushing.

explored as a small tumor, removed by cutting through normal breast tissue, and then bisected. In the past two years three such tumors have come under my observation. All three were clinically benign; all were completely excised, with immediate postoperative irradiation, and none has recurred. MicroscopicalIy they were pure comedo. A fourth case was seen by my associate, Dr. L. C. Cohn, who was so con- vinced that he was dealing with a pure comedo tumor that he did not

844 JOSEPH COLT BLOODGOOD

completely remove the mass occupying the upper hemisphere of the breast, nor did he give postoperative irradiation. Today, after more than three years, there is no induration left in the patient's breast, there are no palpable nodes in the axilla, the other breast is not in- volved, and there is no evidence of internal metastasis. These addi- tional cases, together with the late results in the earlier ones, lead to the conclusion that when the tumor is small and the frozen section shows a pure comedo neoplasm, it is sufficient to excise only the tumor.

It is my object in this paper to give a pic$we-Of the clinical pos- sibilities and the gross microscopic characteristics of comedo car-

$'I& 2. CBOSS sECfrON THBOUGH FUNGOUS TUlirOE AND PECTORAL MUBCLE, PROM CASE SHOWN IN FIQ 1

Note the superficial nature of the fungous tumor.

cinoma. As the comedos may'not be present in the earliest and small- est tumors, the final diagnosis must rest upon the microscopic picture. After the removal of the breast tumor, in the interval before the patho- logical report is received, the axillary nodes may be irradiated and, if healing is completed, the breast may also be irradiated after ten days have elapsed.

Larger ulcerating fungous tumors of the breast should be irradi- ated before being subjected to operation. A patient of sixty-five whom I saw six months ago had a large, oozing, fungous ulcer in the periph- ery of the upper outer quadrant of the left breast (Fig. 4). She was weak and anemic. The axillary nodes were palpable, but the tumor was operable. Irradiation with deep x-rays checked the hemor- rhage and the tumor has gradually receded to an ulcer less than 2 cm. in diameter. Clinically, the patient is well in spite of the fact that the supraclavicular nodes are now palpable. She is still receiving irradia- tion over the axillary and supraclavicular nodes. Frozen sections of the fungus showed the tissue so infiltrated with blood and so much in-

COMEDO CARCINOMA OF THE FEMALE BREAST 845

flammatory reaction that it was impossible to tell whether o r not areas of comedo were present. I am confident that if this patient had had the complete operation for cancer there would have been a serious risk of death from an infection such as occurred in another case after an operation for a similar tumor. I mention t,hese two cases to empha- size that when on exploration a tumor too large for complete excision is found, which is microscopically a comedo, it may be wiser to give the patient the benefit of radiotherapy before, rather than after, radical operation, since if the growth is a pure comedo it may disappear after irradiation.

FIo. 3. TYPICAL, FULLY DEVELOPED PURE COMEDO TUMOR, SHOWING SOME SOLID BASAL-CELL DUCT ADENOXATOUS ALvEoLr WITHOUT CENTRAL AREAS OF NECROSIS

From case shown in Figs. 1 and 2.

I will not discuss here the relationship, if any, of chronic cystic mas- titis to pure comedo-adenocarcinoma. In an earlier article (Arch. Surg. 3: 445, 1921) I recorded (page 540) under the group solid ade- noma, four types. The first three of these, (1) small alveolar ade- noma, (2) large alveolar adenoma apparently in the ducts, and (3) small, irregular stellate adenoma are present in chronic cystic mastitis, while the fourth, comedo-adenoma, is not observed in chronic cystic mastitis. It is quite possible that the large solid adenoma may be the beginning of an area of pure comedo; but the typical pure comedo with a central area of necrosis is not a frequent occurrence in the breast the seat of chronic cystic mastitis. This subject, however, needs fur- ther investigation. Undoubtedly, the pure comedo tumors will be ob-

846 JOSEPH COLT ULOODQOOD

served much more frequently in clinically benign tumors of the breast exposed at operation. Nevertheless, late cases will still be seen, and when more clinically malignant tumors are given preoperative irradia- tion with and without biopsy, more comedo-adenomas will be found and their radiosensitivity more fully determined. I believe that the majority of pathologists class comedo-adenoma with duct cancer. Comedo-adenoma is a basal-cell tumor and apparently arises in ducts, but it is rarely, if ever, present in the zone of the nipple and areola.

The accompanying illustrations show the clinical, gross, and micro- scopic appearances of the typical comedo-adenoma tumor. To avoid confusion I propose to call this pure comedo-adenoma tumor, since in spite of clinical signs of cancer and gross and microscopic pictures of malignancy, and in spite of recurrence after excision of the tumor,

FIO. 4. ULCERATED FUNQOUS TUXOR OF BBEAST AFTER X-RAY IlLRAnIATSON HAD CHECKED HEMORRHAOE. PATH. No. 62418

See also Figs. 5 and 8,

there has never been, in this group, metastasis to nodes nor death from cancer. As has been said, however, when this tumor occurs with fully developed cancer of the breast, it behaves like cancer of the breast.

Fig. 1 shows a recurrent tumor developing into a fungus after simple excision of the breast. There are three such cases among our 25 comedo tumors, two of them primary, one recurrent. The recurrent tumor in the case illustrated was of one year’s duration; the primary tumor was of eighteen months’ duration. The very superficial growth of this fungous tumor in the scar is shown in Fig. 2, its histology in Fig. 3. This case is the best evidence we have of the relative benig- nancy of the pure comedo tumor. The tumor was clinically malignant, it recurred after excision of the breast, and is the first permanently cured recurrent tumor of the breast observed in Halsted’s clinic at Johns Hopkins. Yet the presence of the comedos in the gross speci- men and the characteristic histological picture placed it in 1897 with the first case of comedo tumor observed in 1893. Up to that time there

COMEDO CARUINOMA OF THE FEMALE B&PIAST 847

had been three other cases. Subsequently we have observed 22 addi- tional cases.

Figs. 4, 5, and 6 introduce the subject of irradiation for ulcerating and fungous tumors of the breast. When Fig. 4 was photographed, Nov. 23, 1933, bleeding from the fungous tumor of the left breast had ceased as the result of x-ray irradiation, and the tumor was beginning to shrink. By the following June only an ulcer some 2 cm. in diameter remained. When irradiation was first given, in November, the axillary nodes were palpable. Under continued irradiation they became smaller, but have not yet completely disappeared, while the supra- clavicular nodes have enlarged. This patient is clinically well. We cannot tell the exact nature of this fungous growth, since the tumor tissue was ohscured hy blood and inflammatory reaction. I am in-

F I G & 3 AND 6. PATIEKT SHOWN IN FIff. 4 TWO MONTHS AND SEVEN MONTHS LATER The tumor has been reduced to au ulcer about 2 em. in diameter.

clined to feel that it is largely a cbmedo tumor, but in view of the in- volvement of the nodes, it probably contains cancer areas. This pa- tient refused operation, but had she consented to it, irradiation would still have been continued.

The specimen shown in Fig. 7 was a clinically benign tumor. The surgeon, Dr. Ben Johnson of Richmond, Virginia, wrote me: “I am sending you two specimens f o r microscopic examination. One is a small lump taken from the b&st of a young woman twenty-six years old. She noticed this little button about two and a half months ago. I removed it under cocaine yesterday and am of the opinion that it is benign.” I am inclined to think today that ,Johnson was right, but not until about one year ago did I encounter a similar lump and then I did what Johnson had done in 1907-1 removed only the tumor, recog- nized it as benign comedo-adenoma in the frozen section, closed the

FIG. 1. SPECIMEN TYPICAL GROSSLY AND MICROSCOPICALLY OF PURE COMEDO TUMOR. CASE OF DR. JOHNSON. PATH. No. 8349

This is the type we may expect to see more frequently today. The complete operation for cantor was advised.

FIG. 8. SECTION THROUGH TISSUE REMOVED IN COMPLETE BREAST OPE~ATION FOR CANCER, SHOWIKG PURE COMEDO TUMOR. CASE OF DR. JAB. F. M I T C H ~ L . PATH. No. 4819

This specimen shows more comedos than that in Fig. 7.

FIG. 9. COMPLETE INVOLVEMENT OF BREAST BY PURE COMEDO ADENOMA. PATH. NO. 15427 The patient is well more than twenty-one years after removal of the breast.

848

COMEDO CARCINOMA OF THE FEMALE BREAST 849

wound, and gave immediate irradiation. My patient is well today. Dr. Johnson’s patient was lost track of after having been followed for more than ten years.

Fig. 8 is another example of comedo-adenoma, recognized in the gross by Dr. J a s F. Mitchell.

Fig. 9 is the photograph of a gross section through the left breast. I n this instance the entire breast was involved by pure comedo tumor. This patient had been operated on by me some three years previously for a pure comedo tumor of the right breast. It was a small tumor, and the complete operation was performed; but the nodes were not in- volved. The patient returned once a year for examination and at the

PIQ. 10.

the older pictures of pure comedo tumor.

SECTION OF THE FIRST PURE COMEDO ADENOMA OPERATED ON IN 1893. PATH. NO. 123 This photomicrograph was made from a section thirty-seveu years old. It is typical of

last examination a nodule was present in the remaining breast. At that time I was persuading many of my breast cancer patients to allow me to remove the remaining breast because of the greater danger of cancer in that breast-at least 6 to 8 per cent more than that of pri- mary cancer. For this reason the breast was completely removed.

Figs. 10 and 11 are microscopic pictures which should be compared with Fig. 3. There is nothing particularly difficult in the recognition of the pure comedo tumor in its fresh appearance, or in frozen and permanelit sections. But as this tumor often occurs with fully devel- oped and metastasizing cancer of the breast, the latter must always be looked for. When the palpable tumor is small and can be com- pletely excised by cutting through normal breast tissue and closing

850 JOSEPH COLT BLOODQOOD

the wound without injury to the symmetry of the breast, there is no reason why the breast should not be saved without danger to the pa- tient. Older women may be spared the complete operation for cancer by an aspiration biopsy, when pure comedo tumor involving a large part of, or the entire breast, is recognized.

An interesting case was observed by Dr. (3. A. MacCallum, of Dunn- ville, Ontario, and the specimen was sent to me in August 1899. The letter from which I am about to quote was sent to me by his son, Dr. TI7. G. MacCallum. The case is remarkable clinically as both breasts were involved. Dr. MacCallum wrote that he operated simply to make

FIG. 11. PURE COMEDO TUMOR WITHOUT ALVFXILI OF PSEUDO-LACTATION TYPE, PATH. No. 20198

the woman more comfortable for the time she had to live. The tumors in each breast proved to be pure comedo tumors. The nodes in the axilla were not involved. The patient died about fifteen years later (1914), at the age of sixty-seven, without any evidence of external or internal malignant disease.

Dr. MacCallum’s letter of Nov. 28, 1901, reads as follows: “Mrs. B., aged fifty-two, presented herself at my office on August 1, 1899, in a very weakened condition. On examination, I found her right breast much enlarged, very hard and with an open, red, fungating mass about an inch and a half in diameter, below the nipple. She said she suf- fered intense pain and could get no rest. I found a mass of enlarged nodes in the right axilla. The left breast also contained a tumor as large as a goose egg and there were enlarged nodes in the left axilla.”

The swelling of the right breast had been present two years and the patient had not observed any growth in the left breast. ‘(1, however,

COMEDO CARCINOMA OF THE FEMALE BREAST 851

told her,” wrote Dr. MacCallum, “that if we could remove the tumor of the right breast she would probably have less pain and would prob- ably be relieved for a time. Accordingly next day I did Halsted’s op- eration, having to graft a large piece of skin . . . everything went well, and in two weeks the wound was nearly healed.” Dr. MaeCallum later performed the complete operation on the left breast, and the pa- tient fully recovered.

As I read this letter, thirty-three years after it was written, I am more and more impressed that it is the best of evidence for the relative benignancy of the pure comedo tumor. It may involve the entire breast,

FIQ. 12. MOST 8tISPICIOUS AREA FROM A PURE COMEDO TUMOR EXPLORED AND PARTIALLY REMOVED, THREE YEARS AQO. CASE OF DR. COHN. PATH. NO. 44244

This patient received no preoperative or postoperative irradiation. The breast is now nermal both to palpation aiid transillumination.

occur at the same time in both breasts, produce a fungous tumor and palpable nodes in the axilla, and yet the patient remain well and free from recurrence sixteen years after operation. In this case only the tumor from the right breast was sent to the laboratory, and I described this in my original note as “pure comedo-adenocarcinoma, ” comparing its gross and microscopic appearances with the tumors in Figs. 3 and 10. It was the fifth pure comedo tumor observed in the laboratory.

Fig. 12 shows the most suspicious microscopic area in the pure comedo tumor explored more than three years ago and incompletely removed by my colleague Dr. L. C. Cohn (see above). The tumor in- volved too much of the breast to remove it completely. In the gross it was a typical comedo tumor and comedo cylinders could be expressed.

852 JOSEPH COLT BLOOMOOD

Under the microscope, in frozen and permanent sections, the majority of areas are pure comedo. Undoubtedly this is the most interesting among the recent border-line tumors in which the breast has not been removed, because not all the tumor tissue was excised, and there was no preoperative or postoperative irradiation.

Fig. 13 is a section from a very small tumor of the breast which T completely removed more than one year ago. After making a frozen section of the entire tumor, and diagnosing it a pure comedo tumor, I dosed the defect in the breast and gave a course of irradiation.

FIQ. 13. SECTION OF A TUMOR 1.5 CM. IN DIAMETE~L PRESENT FOR THE- WEEKS IN THE

This tumor was completely excised under local anesthesia and was diagnosed as pure There were no gross comedos

PERIPHERY OF THE BBEAET OF A THIN WOMAN. PATH. NO. 61020

comedo tumor. in the fresh tumor, which was circumscribed but not encapsulated.

The patient L well more than a year later.

There is no sign of trouble today. This tumor, in the gross, had no comedos. Since that date I have explored another pure comedo tumor after a thorough course of irradiation, which had changed the morph- ology of the cells more than the gross appearance of the tumor. The tumor had been aspirated before it was explored and from examination of the stained aspirated cells we could only decide that they suggested a malignant tumor. We did not recognize the comedo tumor.

SUMMARY AND CONCLUSIONS In 1908, in Chapter 31 of Kelly and Noble’s Gyfiecology amd Ab-

do+nnifiaZ Surgery (Vol. 11), I described the comedo tumor of the breast

COMEDO CARCINOMA O F THE F E M A L E BREAST 853

and classified it among the adenocarcirwmas as adenocarcinoma comedo I wrote: “Among 12 cases of the pure type I have yet to observe me- tastasis to the axilla. All so far have been permanently cured. In one the tumor was bilateral (specimen sent to me by MacCallum of Can- ada), The only positive cure of a recurrent carcinoma belongs to this group.” I used at that time many of the illustrations which are again shown here.

In 1917, in Chapter XXIII on Lesions of the Female Breast, in Binney’s Regional Surgery (page 611) I again described comedo- adenocarcinoma with illustrations. At that time I wrote: “At the ex- ploratory incision this (tumor) has such a distinct gross appearance that one should never fail to recognize it.” Now I know that in the earlier tumor the typical comedos may be absent. In this article, also, I used the term duct cancer f o r comedo-adenocarcinoma.

In the past two years I have restudied all the cases of pure comedo and also those cases in which the comedo tumor was mixed with fully developed cancer. There is but one conclusion, and that is that pathol- ogists can learn to recognize the pure comedo tumor in all its histo- logical pictures by repeatedly studying the actual sections in the cases in which the tumors have been removed, the breasts saved, and the patients followed. Less difficulty is found in recognizing the later picture of pure comedo, as shown in Figs. 3,lO and 11, than the earlier cases, shown in Figs. 12 and 13.

The pure comedo tumor takes its place among the border-line tumors of the breast, which are growing in importance. It must be recognized in frozen and permanent sections if progress is to be made in diagnosis and treatment.

NOTE (Nov. 23, 1934) : I t is now over four months since this paper was completed. All the patients mentioned as living are still alive. The patient shown in Fig. 4, in whom the fungous tumor disappeared under x-ray irradiation, is clinically well. The glands in the axilla and neck are still palpable. No new cases are added and all the evidence is that the pure comedo-adenoma does not give metastases, and can be cured by excision of the local tumor only. When the tumor is of fungous nature or is too large f o r local excision, irradiation should be tried first.