FATTY TISSUE TUMORS O F THJI: BREAST

JOHN (3. MENVILLE, M.D. (From the Surgical Pathological Laboratory, Departmrnt of Surgery, Johns Hopkins Hospital

and University)

Tumors of fatty tissue in the breast, including lipoma, fa t necrosis, and xanthoma, although unusual, arc ncvcrtheless important and should be recognized. Thc scarcity of discusRions in the literature on this sub- ject can be attributed to the relatively infrequent occurrence of these lesions. Of approximately 3,000 breast tumors collected in this labora- tory, only 58 cases could be classified as fatty tissue tumors (Table I).

TABLE I: Fat ty Tissue Tumors of the Breast: 58 Gases

Secondary Xau- thomatous De-

Lipoma Fat Necrosis geueration

Age ............... 44.6 ycurs 4G.3 years 44.6 years Duration of hyinp-

2.95 years 2.7 years

(24 cases) (25 cases) (9 cases)

toms ............ 3.1 yenrs

8% males Sex distribution .... 92% females 100% females 100% females

Raeo distribution ... 100% white 88.2% white 50% colored 11 .8% eolored 50% white

50% left 71.4% left 62.5% left Location ........... 50% right 28.G% right 37.5% right

Trauma ............ 26 % 4.4% 11% Pain .............. G5% 21.7% 33.370 BUn retractiou ..... 4.4% 12% 0 Orow appearance ... Golden yellow, firm Homogeueous, dull, gray- Brownish-y e 11 o w,

lobuluted mass with ish-white, Arm, stellate firm, i r r e g u 1 a r white fibrous septa mass. mass.

Microscopic appear- ance ............. Fat cells separated Foam cells (micro- and Foam celle, (miero-

by delicate fibrous macrophagee) , flbroblaets, and macrophagee), stroma lymphoid and giant cells. fibroblasts, hemo-

sideriu, lymphoid Incorrectly diaguosed and giant cells. aa malignant ..... 0 28% 11%

LIPOMA There were 24 cases of lipoma of the breast in this series. These

tumors arise from lipoblasts, which are themselves derived from mesen- chymal cells. They begin as small single lobules of fa t about a blood vessel and grow with varying degrees of rapidity. They occur wher- ever adipose tissue is found and for this reason are occasionally seen in the breast. The exact etiology is still a matter of discussion.

Lipomas of the breast are classified by Zesas (1) as intraglandular and extraglandular. Cases included in the former group have been

797

798 JOHN G. MENVILLE

reported by Cooper (2) and IIocnigsberger (3), while a large .retro- mammary lipoma was described by Billroth (4) and considered by him to be an exteiisioii of axillary fat. This latter case is included in the second group. Since the data on this series of cases reveal so little in- formation about the exact location of the tumor, a statistical study was not feasible. In general, however, it ctiii he stated that lipomas occur

PIO. 1. LIPOMA OF THE BREAST: G~ROSS BPECIMEN

in the supporting fatty tissue of the breast, gcncrally peripheral to the mammary ducts.

C1i)iicaZ Featzirrs: Lipomas of the hrcast may be unilateral, bilateral, or generalized. They are usually seen in white women, and occur with equal frequency on the right aiicl left sides. The age incidence varies from nine months to sixty-four years, the average being forty-five yyars. A history of trauma is givcii in 26 per cent of the cases. The size of the tumor varies from that of a pea to a child’s head. The lesioiis lire usually single, slightly firm, roundecl, nodular, aid circumscribed. They are attached to the skin in 4 per cent of the cases, and are painful in 65 per cent. Transillumination of lipomas reveals them as translucent tumors and thus aids in distinguishing them from the solid tumors such as car- cinoma and fibro-acleiioma. Because of their location, deep-seated blue-domed cysts may be difficult to distinguish from lipomas.

Gross Pathology: The gross appearance of lipomn is characteristic. The growth is usually a golden-yellow lobulated mass (Fig. 1) with delicate, white, fibrous iiitcrlobular septa. The tumors are usually less vascular than the normal fat tissue. Seventeen per cent of our caees were associated with other breast pathology.

Microscopic Pathology .- Lipomas present a typical microscopic pic- ture (Fig. 2). The so-called fat cell is a derivative of the meseiichymal cell and is formed by the deposition of f a t droplets in its cytoplasm. A fulsion of the droplets produces liquid fat, which distends the cell into a spheroidal cavity containing a single eccentric nucleus. In tumor formation there is sometimes tin incomplete deposition of fat

The average duration of symptoms is three years.

FATTY TISSUE TUMORS OF THE BREAST 799

and at times a tendency towards alveolar formation. The intercellular stroma is composed of thin strands of connective tissue containing oc- casional blood vessels and nerves. The stroma may at times be so prohinent that i t resembles spider-like processes encroaching on the fat tissue. An increase in the cellular elements described above seen in lipomas cannot be mistaken for any other type of tissue.

F l O . 2. LIPOMA OF THE &t.EAST: LOW-POWER VIEW

FAT NECROSIS The importance of distinguishing fat necrosis rests upon the fact

that clinically it is often confused with carcinoma. There were 25 cases of fa t necrosis in this series of 3000 breast tumors. Twenty-eight per cent of the cases were diagnosed preoperatively as malignant tumors.

Because of the location of the breast and its relative glandular in- sensitiveness, trauma here is frequently unnoticed. Large, heavy, pendulous breasts (Fig. 3), the type usually harboring fat necrosis, are subject, because of their size, to pressure from their own weight as well as to injury from external causes. 111 all probability the uncler- lying cause of fat iiccrosis is an ischemia of the part, produced either by trauma or by pressure.

The breaking up of fat tissue iiito fatty acid and glycerol was shown by Farr ( 5 ) to occur very readily in test tubes. This splitting of fa t tissue, although it occurs in fa t necrosis, is in itself a different process. E’arr, on the basis of experimental work, believes, contrary to many authors, that the fat splitting is not due to enzyme action. The rela-

800 JOHN G . MENVILLE

tionship between fat necrosis procluced by trauma and that produced by pancreatic ferments has not been sufficiently studied. Although we know that fat necrosis occurs in the absence of enzyme action (Farr), i t does not necessarily follow that it is not sometimes produced by enzymes obtained from the blood or from adjacent tissue. Hadfield (6) is one of those who hold firmly that f a t necrosis is produced by sterile autolysis. Infection, particularly of the chronic tubcrculous t,ype, may produce a tissue reaction quite similar to typical fa t necrosis.

The necrosis of f a t tissue accompanied by a splitting into fatty acids niid glycerine is consitlered as a tlegenerative phase which is closely fol- lowed by repair. This repair is characterized by the production of spintlle, round, and g imt cells. The influx of these cells represeiits t i

FIQ. 3. P E N l ) I I L O I ~ S BREASTS OF THE TYPE IN WHICII F A T NECROSIS USUALLY OU!URH

reaction on the part of the injured tissue and is typical of the recupera- tive powers possessed by all healthy tissue cells.

Cliwical Picture: The average age incidence in the present series was forty-six years, while the average duration of symptoms was three years. The lesion usually occurred in white women, and was more frequent in the left breast. Trauma, even though it is frequently an exciting cause in the production of fat necrosis, is not an essential factor, and was notcd in only 4 per cent of the present series of cases. The size of the tumor, which in some cases is only of microscopic pro- portions, varies according to the extent of necrosis. The lesion, al- though sometimes circumscribed, is more frequently stellate ; it is lobuluted, firm, and sometimes painful. The tumor was attached to the skin in 28 per cent of the cases in our series. Lee and Adair ('7) found skin adherence in 70 per cent of their series of cases. The skin retraction is easily explained when one understands the fibrous repair found in conjunction with fat necrosis. Since the majority of fa t

FATTY TISSUE TUMORS OF THE BREAST 801

necroses are subcutaneous, the fibrous repair tissue acts like strong fibrous cords which have no elasticity but which, like all fibrous repair tissue, have a tendency to retract.

Gross Pathology: The tumor differs from lipomas mainly in its pale, dull, grayish-white, stellate, homogcncous appciiruncc and firm con- sistency. The degree of change from virgin fatty tissue depends upon the amount of necrosis and repair present.

Microscopic Pathology: The prescncc of small, round-cell micro- phages (lymphoid cells) containing f rec fat, large multinucleated macrophages (giant cells) also containing frce fat, and frequently fatty acid crystals, surrounded and infiltrated by a spindle-cell stroma, com- pletes a picture which is characteristic of fat iiccrosis (Fig. 4). The

FIQ. 4. FAT NECROSIS IN T H E BREAST: IAOW-POWER VIEW

microphage is characterized by the presence of a lymphoid or round- oval clear nucleus situated in the midst of a reticulated pink cytoplasm representative of lipoid degeneration. The macrophages contain cells presenting scveral eccentric nuclei and reticulated cytoplasm having more of a tendency to vacuolation than that in the microphages (Fig. 5 ) . The stroma of fibrous tissuc is composed of elongated and spindle- shaped, clear staining, purple nuclei containing a small amount of pink- staining cytoplasm. This stroma is sometimes filled with giant cells. The presence of giant cells is probably the result of some chemotactic reaction resulting from the presence of lipoitl degeneration or of fatty acid crystals. B’atty acid crystals may be seen as regular, spindle- shaped, clear areas lying in the midst of a fibrous stroma. Although their appearance is characteristic, their presence is not essential to the

802 J O H N 0. MENVILLE

diagnosis of fat necrosis, for they may be found in other conditions as well.

From the microscopic study of these tumors one may say that fa t necrosis is represented by two tlistiiict phases : degeneration and re- generation. Dcgeneratioii is characterized by the presence of the microphages and macrophages, containing lipoid tlegeneratioii, and is in coiitradistiiictioii to the regenerative phase, which coiisists of tho invasion of coniiective-tissue clcments. The presence of both phases is seen in all cases of fa t necrosis, for one process is quickly followed by, and soon includes, tho other. The predominance of one type of tissue or the other is the cleciding factor in determining the stage of tumor growth. The clinical appearance of the tumor is also dependent upon

FIO. 5. FAT NECROSIS IN THE BREAST: HIOH-POWEB VIEW

the predomiiiaiicc of regeneration or degeneration ; when degeneration is prcdominant the characteristic, firm, utlhercnt appearaiice seen in the later regenerative phases is absent.

When the clcgcnerativc process is not followed completely by the reparative (fibrosis) stage, cystic change may result. The cystic struc- tures, which may be of any size, shape, or form, usually have an ir- regular, indefinite border and are often identified as connective-tissue cysts. The liniiig is sometimes very thin and is often indi~tiiiguishable from the surrounding stroma. Occasionally the cyst wall shows a slight increase in connective tissue, arid in some instances is infiltrated by giant cells. Such products as mucin, fa t crystals, and calcium de- posits may be fouiid within the cyst cavity.

The attempted organization which takes place in f a t necrosis is

FATTY TISSUE TUMORS OF THE BREAST 803

detected either accidentally when it is associated with more serious and prominent breast pathology or when it is extensive enough in itself to produce tumefaction. As a rule, whenever fat necrosis is found it has reached the reparative stage. In some instances the repair process continues to a dense fibrosis and ultimately to calcification. On mi- croscopic examination, calcium salts are found in the midst of repara- tive fibrous connective tissue, being represented by dense, irregular, amorphous clumps which take a deep purple stain.

Fat necrosis presents another interesting angle in its occasional association with muciiious degeneration of fa t tissue. Mucinous de- generation in association with myxomatous change occurs occasionally in conjunction with lipomas. Ewing (8) believes that this mucinous degeneration is one of the most frequent of secondary changes seen in lipomas, but the present study does not confirm this. Mallory (9) believes that when the fat disappears, mucin often appears between the collagen fibers and is taken up by the fibroblasts. Mucinous degenera- tion should not be mistaken for a poorly mounted section of fa t tissue which, when folded, produces a picture sometimes diagnosed as myxoma. The presence of myxomatous tissue is undoubtedly the result of a modified connective-tissue response to the presence of mucinous degen- eration, There was only one such case in the present series (Path. No. 18130).

XANTHOMATOUS DEGENERATION The term xanthoma has been applied to brownish-yellow tumors

usually occurring subcutaneously in the regions of the eyelid and in the joints. They have been so called bccausc grossly they present a yellow color. Microscopic study has revealed, however, that the tu- mors called xanthoma on the basis of their gross appearance, are of two general types. The first type of tumor consists wholly of the charasteristic xanthoma or foam cells. Into this class fall xanthoma palpebrarum, xanthoma multiplex, and xanthoma diabeticorum. Asch- off (10) reserves the designation xarithoma for this class. The second type of tumor shows scattered foci of foam cells lying in a lesion which is primarily inflammatory or neoplastic. This finding is common in all sorts of chronic inflammatory processes, particularly in the walls of old abscesses. It is occasionally seen in carcinoma and sarcoma, Because it is apparently a degenerative process, quite secondary to the primary lesion a t hand, Aschoff designates this type of xanthomatous change as pwudoxawthorna. While adopting Aschoff 's classification, we prefer the term xavtthomatous degeneratioit for this latter process.

I n the present scrics of breast tumors we found no example of true santhoma. Such isolated tumors composed wholly of xanthoma cells are apparently exceptionally rare in the breast. The only reports are those of Chcatle (11) and Hangensen (13). There were 9 cases of xanthomatous degeneration or pseudoxanthoma in our series, however.

The etiology of xanthoma in general has been a subject of much dispute. Ehrmann (13) thought that there might be an association

804 JOHN 0. MENVILLE

between xaiithoma and multiple lipomas. Virchow (14) said that xanthoma arose from fibroblasts and that it wau an intermediate state between connective and fat tissue. Ewing (8) believes that it is due to a peculiar formation of lipoids in the cells of a fibroma which are undcr the influence of a loctil and general metabolic disorder. The frequency of xanthoma in the Iibsencc of lipemia, together with tlic high frequency of lipcmia in the abseiice of xaiithomu, has promptccl Wilc and Eckstein (15, 16) to the conclusion that the knowledge con- cerning the ultimate cause of the xanthomatous state is still incomplete, although in a later article they suggest that the nature of lipids in xanthoma is more dependent on the activity of the neighboring tissue than on the nature of blood lipids. Bloch (17) associates hormone activity with santhomas aiid believes that tlie underlying factor is pro- duced by a disturbance of the mcclianism regulating lipid metabolism.

Study of our series of nine cases of xanthomatous degeneration sug- gested that tlic primary lcsioii in these cases had been fat necrosis. The secondary xanthornatous dcgeiicratioii which supervened w w probably due to some local disturbance in lipoid metabolism caused by the trauma or ischemia which had initiated the fat necrosis.

It seems probable that tlic foam cells, which are the Characteristic feature of xanthomatous degeneration, result from the engulfment of fatty acid products by the microphages and macrophages. The giant cells, which are sometimes numerous, are probably attracted by a cliemo- tactic action of lipoid degeiicriit ion or by tlic mechanical presence of the lipoid degeneration acting as a foreign body. The latter explana- tion is especially plausible when fatty acid crystals are present. The presence of fibroblasts, as in fat necrosis, may be attributed to a reac- tion of repair by fibroblasts following a degenerative process. The liemosiderin element results from the accumulation of pigment formed by some previous hemorrhage. Cholesterol crystals arc also found in xuntliomas aiid are representative of one of the products of fat com- bust ion. The crystals may be int racellular or estracellular, Hadfield (6) gives a clear illustration of the intracellular variety by his clcmoii- stration of the engulfment of cholesterol crystals by a macrophage.

Clinica2 Feat u w s : In our series of cases xanthomatous degeneration was usually seen in white female individuals about the age of forty-five. The tumors occurred more frcquently on the left than 011 the right side and produced symptoms averaging 2.7 pears in duration. A history of trauma aiid pain was given in 11 aiid 33 per cent of tlie cases, respec- tively. Of the nine cases in tlic present series, none was diagnosed pre- operatively. One was clinically diagnosed malignant and the patient subjected to an unnecessary radical breast amputation.

Gross Pathology: The brownish-yellow color is tlie characteristic gross feature. These tumors do not conform to any definite size, shape, or form.

Microsc.opic Pathology: Rlicroscopically the combined presence of foam cells, fibroblasts, hemosiderin, lymphoid and giant cells (Fig. 6) constitutes xanthomatous degeneration. The blood pigment is usually

FATTY TISSUE TUMOR8 OF THE BREAST 805

scattered through the tumor and is composed of large, coarse, granular clumps which give an iron-staining reaction. Some of the hemosiderin is phagocytizcd by macrophages, but the remainder lies loose in the surrounding tissue. Cholesterin crystals may be similarly located, but they a re not a diagnostic finding.

DISCUSSION The belief that lipomas, fa t necrosis, and xanthomatous degenera-

tion all arise from fat tissue, that 36 per cent of the cases of fa t necrosis arise in small lipomas, and that the relationship between xanthomatous degeneration and fat necrosis is very intimate, is based on a statistical study of 58 cases of fatty tissue tumors of the breast. Fat necrosis and xanthomatons degeneration are rarely reported in breast pathol- ogy. This oversight, in the majority of cases, results from a missed

FIO. 6. SECONDARY XANTIIOMATOIIS DEOENERAT~ON I N T H E BREAST: LOW-POWER AND HIGH-POWER VIEWS

diagnosis or from an incomplete pathological examination. However, the lesions occur incidental to other pathological conditions in a con- siderable percentage of cases and consequently may or may not be overshadowed. It must be remembered, nevertheless, that enlarge- ments of fatty tissue tumors occur as a single entity and that certain forms cannot be clinically distinguished from carcinoma.

The knowledge and recognition of these tumors should be empha- sized, for, regardless of the fact that they practically never show malig- nant change, they are sometimes found associated with malignant growths aiid tire themselves sometimes mistaken for malignant tumors. The association of fatty tissue tumors with malignant growths brings out the importaiice of a complete examination whenever a tumor is biopsied or removed, for the presence of fatty tissue tumors may be merely incidental to maligntincy. The frequency of unnecessary muti- lating radical amputations of the breast performed because of a mis- taken diagnosis (fat necrosis 20 per cent, xanthomatous degeneration

806 J O H N G. MENVILLE

11 per cent) indicates the necessity of the proper handling of such cases. The clinical diagnosis should always be supported by a properly per- formed biopsy and a frozen section of the tumor. This principle has been popularized by Bloodgood (18) and with its practice breast tumors present a less puzzling problem; a more efficient prognosis is assured; breasts are spared in benign lesions; and patients saved when early malignancy is found.

At the present time the most popular and efficient method of treat- ment of fatty tissue tumors of the breast is surgery. The majority arc safely treated by local excision. Enucleation is sometimes tried, but the nature of the growth aiid the percenttigc of reciirrcnces dis- courage this procedure. With repeated recurrences, amputation may be necessitated. In the presence of malignancy a radical amputation of the breast should be performed.

CONCLUSIONS 1. It is believed that fat necrosis and xanthomatous degeneration in

the breast urine from fat tissue and should, with lipomas, be classed as fatty tissue tumors.

2. Fatty tissue tumors of the breast are rare, 58 cases occurring among approximat ely 3,000 breast tumors.

3. The underlying cause of fa t necrosis and xanthomatous degenera- tion is believed to be a local disturbance in the lipid metabolism pro- duced by secondary factors such as trauma, ischemia, ctc.

4. At times fatty tissue tumors cannot be clinically differentiated from malignant growths.

5. Biopsy and frozen section examination are essential in the diag- nosis aiid treatment of these tumors.

BIBLIOGRAPHY 1. ZERAS: Arch. gen. de chir. 8: 924, 1912. 2. COOPER, SIR ASTLEY : Illustrations of Diseases of the Breast, 1845, pp. 48-49. 3. HOENIQRIIERGER: Miinchen. metl. Wrhnschr. 52 : 222, 1905. 4. BILLWTII: Quoted by Deaver and McFarlancl: The Breast, Its Anomalies, I t s Dis-

5. FARR, C. E.: Ann. Surg. 77: 513, 1923. 6. HADFIELD, Q.: Brit. J. Surg. 17: 673, 1930. 7. LEE, B. J., A N D ADAIR, F. B.: Ann. Surg. 80: 670, 1924. 8. EWINQ, JAMES: Neoplastic Diseases, W. B. Saunclers Co., 3rd ecl. 1928, pp. 192, 174. 9. ~IALLORY, F. B.: The Principles of Pathologic Histology, W. B. Saunderv Co., Phila-

eases and Their Treatment, P. Blakiston’s Son & co., Philntlelphia, 1917.

delphia, 1929, p. 80. 10. ASCHOFF, L.: Pathologische Anntomie, Qustav Fisrher, Jcna, 1923, vol. 2, p. 991. 11. CHFATLE, G. Id., A N D CIJTLER, M.: Tumors of the Breast, J. P. Lippincott Co., Phila-

12. HAAGENSBN, C. I).: Am. J. Cancer 16: 1077, 1932. 13. EHRMANN : Dissertntion, Heidelberg, 1889. 14. VIRCHOW, R.: Virchows Arch. f. path. Anat. 52: 504, 1871. 15. WILE, U. J., ECKSTEIN, H. c., AND CURTIR, A. c.: Arch. Deim. & Syph. 20: 489, 1929. 16. ECKSTEIN, H. C., A N D WILE, U. J . : J. Bid . Chem. 87: 311, 1930. 17. BIBCII, B. : Brit. J. Derm. 43: 61-87, 1931. 18. BLOODGOOD, J. C. : J. L J ~ . & Clin. Med. 16: 692, 1931.

dclpliia, 1932, p. 307.