Mammary Gland Neoplasia in the Cow - Veterinary Pathology

Pathologia Veterinaria 

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Mammary Gland Neoplasia in the Cow. A Review of the Literature and Report of a 

Fibrosarcoma 

R. C. Povey and A. D. Osborne 

Pathol Vet 1969 6: 502 

DOI: 10.1177/030098586900600603 

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Path. vet. 6: 502-512 (1969) 

From the Department of Veterinary Medicine, University of Bristol, Bristol 

Mammary Gland Neoplasia in the Cow 

A Review of the Literature and Report of a Fibrosarcoma 

R.C. POVEY and A.D. OSBORNE 

Mammary gland neoplasms, so common in the bitch, are very rare in the cow. 

SWETT, et al.40 examined in considerable detail the udders of 313 cows of lactating 

age and of 105 heifers and freemartins. Of the lactating cows, 31% were 8 years of 

age, or more, and this they considered to be beyond the ‘cancer age’, but in no instance 

was a neoplastic change noted. 

In 1945 the UNITED STATES DEPARTMENT OF 

reported that 

some 13 million bovine udders were subjected to routine inspection, but none was 

found to contain a tumour. The surveys of COT CHIN^^ in the United Kingdom, 

PLUMMER~~ in Canada, JACKSONZ4 in South Africa, MISDORP~~ in the Netherlands, 

and NAIR and SASTRY~~ in India cover 2,999 bovine neoplasms of which only 11 

involve the udder (PLUMMER 1 ; MISDOKP 1 ; NAIR and SASTRY 9,8 of which were 

intracanalicular fibromatous polyps). Tumours of the udder can be divided into 

a primary group of either glandular, ductular, or stromal elements; primary cutaneous 

tumours which directly invade the udder, e.g. melanomas2- or squamous 

cell carcinomasl4- 15; and secondary metastatic tumours, e. g. lymphosar~oma~~ 26. 

Previous reports of bovine primary mammary neoplasms are listed in Table I. 

Many of these reports are sketchy and inadequate. For the above reasons, our case 

of a suspected fibrosarcoma, with multinucleate giant cells as an unusual feature in 

some areas, is recorded. 

Case History 

A 4-year-old Ayrshire cow, which had calved 3 months previously, had 

steadily lost condition since calving. Hepatic fascioliasis was diagnosed and treated 

but weight loss continued and milk yield diminished. It was only 10 days before 

admission that induration of the udder was noted and a febrile reaction (105°F) 

detected. Treatment with oxytetracycline hydrochloride* intramuscularly for 4 

days was without effect. Staphylococcm pyogenes was cultured from the milk. 

When admitted to this department the animal was grossly emaciated. The 

temperature was 105°F and pulse and respiratory rate were raised. The udder, 

* Terramycin soluble. Pfizer Limited. 

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uble 1. Reports of primary mammary neoplasms in the cow 

Date Author Breed Age Diagnosis as made by author 

1902 

1903 

1906 

1908 

1908 

1909 

1910 

1912 

- 

1934 

1942 

1948 

1953 

1954 

1955 

1956 

1959 

1965 

1966 

1967 

STICKER 

KUHN* 

BOUCEK 

CLELAND 

MURRAY 

TROTTER 

JOEST* 

SCHLEGEL* 

KITT* 

HYNES 

KENNY 

JULIAN 

NAIR and SASTRY 

ELDER, KINTNER 

and JOHNSON 

RENK 

PLUMXER 

HOFMEYR 

ROTHENBACITER 

MONTRONI 

~IISDORP 

- 

- 

- 

- 

Highland 

- 

- 

- 

Shorthorn 

Shorthorn 

Holstein-Friesian 9 

- - 

Aberdeen Angus 3 

Hohenfleck 5 

Jersey - 

Holstein-Friesian 16 

1969 POVEY and OSBORNE Avrshire 4 

* Cited by FREI’~. 

** m = macroscopic illustration 

h = microscopic illustration 

Angioma 

Adenocarcinoma : metastases in int. iliac lymph 

nodes, lungs, and bronchial L.N. 

Papilloma 

Fibro-adeno-carcinoma 

Unclassified carcinoma 

‘hlammary tumour’ 

‘Intracanalicular papilliferous fibroma’ 

Fibroma 

Adenofibroma 

Osteoma 

Unclassified ‘cancer’ 

Adenocarcinoma : metastases in sup ram am mar^^ 

L.N., liver, lungs; possibly in bronchial and 

mediastinal L.N. and diaphragm 

hlultiple fibrous polyps of cistern wall 

Squamous cell carcinoma of milk ducts 

Undifferentiated carcinoma; metastases in both 

supramammaries and left prefemoral L.N. 

Papillarv cvst-adenonia involving whole L.H. 

quarter 

Fibroma 

‘Spindle-cell’ sarcoma 

Adenocarcinoma with metastases in supramammary, 

iliac, and renal L.N. 

‘Glandular cystic carcinoma’ 

Adenocarcinoma with metastases in superficial 

and deep inguinal L.N., lungs, pleura, pericardium, 

and kidney 

Fibrosarcoma with multinucleate giant cells 

histopathology Illus.** 

Studied Described 

- 

? 

? 

+ 

+ 

+ 

- 

? 

? 

? 

+ 

+ 

+ 

+ 

+ 

+ 

- 

wl 

0 w 

~ - 


504 POVEY/OSBORNE 

swollen to the size of that of a newly-calved heavy milker, contrasted markedly 

with the general emaciation. Palpation indicated a firmer than usual consistency of 

all quarters, but there was a softer area in the region of the supramammary lymph 

nodes. The subcutaneous abdominal (‘milk’) veins were engorged. No abnormality 

was detected on rectal examination. 

Among clinical pathological findings were a few fluke eggs in the faeces, 

a mild anaemia, and serum glutamic oxalacetic transaminase (SGOT) activity of 

124 pg pyruvate/ml (normal 56 5 148). S. progenes was isolated from the milk of all 

quarters but in low numbers except for the left hind from which a moderate 

growth was obtained. Cultures for yeasts were negative, as were smears for acidfast 

organisms. Treatment with 1 g of oxytetracycline ijv was instituted for 4 days 

with a lowering of temperature to 101.5’F and of pulse, and improvement of 

appetite. On the morning of the 5th day, however, the cow was found ‘down’ and 

in view of its state euthanasia was performed. 

Postmortal Findings 

The peritoneal cavity contained some clear transudate. The liver had typical 

lesions of chronic fascioliasis and numerous young and adult Fasciola hepatica. The 

mammary gland weighed approximately 20 kg. It was firm to hard but somewhat 

softer dorso-posteriorly. A large tumour (approx. 45 x 40 x 25 cm dorso-ventrally) 

occupied the major part of the udder. Peripherally there were large lobules of 

yellow-white, firm, relatively homogeneous tissue with necrosis which grew progressively 

more severe towards the centre, and with massive haemorrhage in the 

actual centre, yielding not less than 2 litres of blood and clots. There was a sharp 

demarcation between the tumour and normal mammary tissue. The forequarters 

were compressed rather more than the hind-quarters, the left of which had some 

haemorrhage and oedema. The supramammary lymph nodes were oedematous. 

No metastasis of the tumour was found. 

Histopathology 

Specimens for histology were taken from the apparently more normal tissue 

of each of the mammary quarters and from the tumour, at its periphery adjacent to 

the sub-pelvic fascia, in 1 area where it abutted onto the more normal mammary 

tissue, and from its more central friable part. Blocks of tissue were fixed for 24 h 

in 5% formol-saline solution and paraffin-embedded sections werc cut and stained 

by haematoxylin and eosin, Masson’s green trichrome, Gomori’s reticulin, Ziehl- 

Neelsen’s, Gram’s, periodic acid-Schiff, and Grocott’s methods. Some material 

was fixed in cold acetone and stained for alkaline phosphatase by GOMORI’S 

method20. 

Fig. I. Typical area of tumour showing pleomorphism of cells with mitotic figure, 

and several bi- and tri-nucleate forms. Masson’s green trichrome. 

Fig. 2. Sub-peripheral area of tumour where there are numerous multinucleate 

giant cells, many of which are vacuolated with some containing apparently 

phagocytosed material. Masson’s green trichrome. 


hlammary Gland Neoplasia in the Cow 505 


506 POVEY/~SBORNE 

The periphery of the tumour was well demarcated dorsally by dense collagenous 

tissue of the deep abdominal fascia in which was incorporated a thin strip 

of striated muscle and ventro-laterally by thin but fairly dense collagenous septa 

from normal glandular tissue. The neoplastic tissue was densely cellular, with the 

typical cell rather ellipsoid, averaging 20 by 15 ,LA, with a central round or oval 

nucleus with sharp nuclear membrane, stippling of chromatin, and a variable 

number of small nucleoli (Fig. 1). The cytoplasm was eosinophilic and tended to 

be drawn out into stellate strands, linking up with the cytoplasmic processes of 

neighbouring cells. Mitotic figures were few in number (averaging 1 per 10 fields 

at 320 x magnification). A striking feature was the large number of multinucleate 

giant cells with up to 30 nuclei, sometimes very hyperchromatic, which tended to 

be conglomerated towards the centre of the cell rather than around its periphery. 

Approximately 20% of these multinucleate cells were vacuolated (Fig. 2, 3). Unfortunately 

no fat stain was carried out and these vacuoles could not be identified 

further. However, some vacuoles contained well-stained material suggesting a 

possible phagocytic property of at least some of the giant cells. The tumour was 

moderately vascular, with some of the venules invaded by tumour cells. Its stroma 

was of fine collagen in a pericellular arrangement. Reticulin-staining revealed a 

meshwork of argyrophilic fibres surrounding each cell (Fig. 3). 

Fig. 3. Peripheral area of tumour. Giant cells, some vacuolated, have many densely 

staining nuclei, and are surrounded by a meshwork of argyrophil fibres. 

Gomori’s reticulin stain. 


Fig. 4. Pericentral area of tumour indicating degree of cellularity, pleomorphism, 

and whorling pattern. Masson’s green trichrome. 

F%. 5. Similar area to Fig. 4, showing pericellular network of argyrophil fibres. 

Gomori’s reticulin stain. 



More centrally there were noticeably fewer giant cells, and those present had 

fewer nuclei. The cell type was more typically spindle shaped and there was a 

definite tendency for streaming and whorling patterns to be formed (Fig. 4, 5). 

Mitotic figures were more frequent. 

At the edge of the central cavity with blood clots and tissue debris there 

was disruption of vessel walls with haemorrhage. In other vessels there were 

thrombi with numerous white cells many of which were eosinophils. 

The more nearly normal udder was a recently active gland beginning to involute. 

Adjacent to the tumour, although well separated by collagenous tissue, 

there was pressure collapse of the acini. There were some foci of plasma cells, 

neutrophils, and eosinophils in the interstitium. 

The tumour was negative for alkaline phosphatase when stained by GOMORI’S 

modified method, whereas apparently normal udders gave a positive reaction. 

Myoepithelial cells are particularly rich in this enzyme13. 

The tumour’s cell type and its pattern of growth, particularly as seen in the 

deeper parts with the collagenous and reticulin networks, were considered typical 

of a fibroblastic neoplasm. In view of its cellularity, and peripherally more disorganised 

structure, with the numerous giant cells, it was classified as a fibrosarcoma 

rather than a fibroma, although there was no evidence of any metastasis in the 

supramammary lymph nodes, or elsewhere. 

The possibility of the lesion being basically an infective granuloma was considered, 

but neither bacterium, yeast, nor fungus, was found in the histological 

sections. 

Discussion 

KENNY27, in a complete account of a primary adenocarcinoma of a bovine 

udder, considered the rarity of neoplasia of the mammary gland in the cow difficult 

to explain, ‘especially when one considers the demands which are made on this 

organ by present-day intensive methods of milk production, its proneness to 

chronic mastitis, and the fact that the dairy cow, unlike the majority of bovines is 

as a rule allowed to live well beyond what is described as the ‘cancer age”. ANDER- 

SON and JARRETT~ suggested, however, that as in women lactation is known to 

protect against mammary neoplasia, the almost constant lactation in cows may 

afford similar protection. FIDLER, ABT, and BRODEY’S postulated that excessive progesterone 

stimulation with recurrent milk retention be the key to the high incidence 

of mammary neoplasia in the bitch. RENK~~ described how cysts of various 

sizes could be found in the glandular tissue in cases of chronic bovine mastitis, 

which he likened to ‘mastopathia cystica’ in man. In 1 case he described such change 

proceeding to neoplasia in the form of a papillary cyst-adenoma. ROTHENBACHERS6 

suspected that some cases which were diagnosed as chronic bovine mastitis may 

have been neoplastic in nature. 

Pure fibrosarcoma of the mammary gland, in the dog at least, is much less 

common than mixed or glandular tumours. Thus SMITH and JONES.~~ in their compilation 

of tumours from various surveys included 934 canine mammary tumours 

of which only 19 were fibromata or fibrosarcomata. In the cow, as far as we are 

aware, apart from intercanalicular fibromatad1 and cisternal fibrous polyps25, there 


Mammary Gland Neoplasia in the Cow 509 

is only HOFMEYR’S report?’ of a ‘spindle-cell sarcoma’ in a Jersey cow which involved 

much of the left side of the udder, was some 22 cm in diameter, and had a 

necrotic centre. This tumour HOFMEYR successfully removed by complete mastectomy. 

A noteworthy feature of this present fibrosarcoma was the extremely high 

incidence of multinucleate giant cells. € 3 0 classifies ~ ~ ~ giant cells into 3 types: 

tumour giant cells ; foreign-body giant cells, characterised by being phagocytic; and 

a miscellaneous group including the Reed-Sternberg cell of Hodgkin’s disease in 

man. In foreign-body multinucleate cells, the nuclei tend to form a peripheral 

palisade, whereas in the tumour giant cell, as in the above case, the nuclei are 

either diffuse within the cytoplasm or tend to aggregate centrally. Giant cells can 

occur in virtually any type of tumour, but EvA~sl~, in the case of human fibrosarcomata 

at least, states that although multinucleated cells may be found they 

are not a spectacular feature, and indeed Srou~38 considers them exceedingly uncommon. 

WILL IS^^ on the other hand writes that the more undifferentiated fibrosarcomata 

often include many giant and multinucleated tumour cells. 

We have reviewed 50 tumours diagnosed as fibrosarcoma at this school over 

the past 10 years, and in only 2-1 dog (a metastatic fibrosarcoma in the liver), and 

1 horse (a sub-cutaneous neoplasm) were giant cells easily found. Giant cells were 

not mentioned in the mammary sarcoma reported by HOFMEYR~~. 

A neoplasm where multinucleated giant cells are a spectacular feature is the 

osteoclastoma or giant-cell tumour of bone. In gross and macroscopic appearance 

JAFFE’SZ3 account of this tumour indicates a fairly close similarity to the tumour 

presently described. NIELSEN~~ described a giant-cell tumour of the fore-leg 

in a cat. This tumour was extraskeletal and was presumed to have originated in the 

tendons or tendon sheaths. The type of giant cell and their distribution in a stroma 

which appeared to be of atypical fibroblasts arranged in a sarcomatous pattern, 

with evidence that these fibroblasts were in fact the precursors of the giant cells, 

is a picture bearing striking resemblance to the case here described. NIELSEN~I 

also observed that some giant cells had a darker cytoplasm and smaller hyperchromatic 

nuclei. This we also saw (Fig. 3). It is debatable whether these were 

merely older, pyknotic, forms of tumour giant cells or phagocytic foreign body 

giant cells of reticuloendothelial origin. The possible phagocytic property of many 

of the giant cells in our case as indicated by vacuolation with, in some cases, vacuoles 

containing stainable material is paralleled by the condition of man described 

by JAFFE~~ as nodular tenosynovitis. In this lesion, which JAFFE considers to represent 

an inflammatory reaction rather than a true neoplastic change, multinucleate 

giant cells able to phagocytose haemosiderin and lipid are a feature. These 

lesions apparently commonly arise from tendon sheaths and/or the fascia1 and 

ligamentous tissues adjacent to them. A similar condition has been described in the 

horse129 34. PLUMMER~~ in his review of tumours classified 2 bovine specimens as 

‘giant-cell sarcomas’. One involved rib, pleura, lung, and bronchial lymph nodes. 

No information was available on the location of the other. 

Multinucleate giant cells have been seen in those sarcomas of the mammary 

gland in the bitch which appear to be related to osteosarcomas, and may be of 

myoepithelial originlo. No bone or cartilage element was found in this reported 

case and there was no histochemical evidence for the presence of myoepithelial 

cells in the tumourous tissue. 



Very rarely granulomatous lesions occur in bovine mammary glands as a 

result of bacterial infection but such a cause has been ruled out in the case reported 

here. 

Central necrosis and liquefaction is not unusual in rapidly growing tumours 

and may be associated with tumour-cell invasion and thrombosis of blood vessels. 

In the case described there was evidence that this had occurred, and the massive haemrhage 

suggests that the necrotic process had extended to a major blood vessel 

which was still patent. HOFMEYR~~ reported similar central necrosis and haemorrhage 

in his case of mammary sarcoma. 

We feel that the lesion described in our case is definitely neoplastic. The 

classification of the sarcoma is open to dispute, but the balance of the evidence is 

in favour of a mesenchymal tumour showing fibrosarcomatous differentiation. 

An interesting feature of the clinical pathological findings was the approximate 

150% increase in SGOT activity. This enzyme is often used as an indicator 

of hepatic function, a raised level indicating damage to parenchymal cells with 

release of transaminase into the circulation. Such circumstances may have been 

expected to occur in hepatic fascioliasis, but VALCARENGHI and MOLINAR143 

showed there was no significant elevation of SGOT in this condition since necrosis 

was not a common finding. However, all major tissues contain a high concentration 

of GOTJ; therefore it would seem likely that the raised serum level of 

this case was a result of the massive necrosis at the centre of the neoplasm. 

A brief review is made of previous reports of neoplasms of the bovine mammary 

gland. A fibrosarcoma of the udder of a 4-year-old Ayrshire cow is described. 

The tumour was well circumscribed, had a number of multinucleate giant cells and 

mitoses, and invaded venules but had no metastasis. The serum glutamic oxalacetic 

transaminase activity was elevated. 

Eine kurze Ubersicht friiherer Berichte uber Tumoren der bovinen Brustdruse 

wird gegeben. Ein Fibrosarkom des Euters bei einer 4jahrigen Ayrshire 

Kuh wird beschrieben. Der Tumor war deutlich umschrieben, wies eine Anzahl 

mehrkerniger Riesenzellen und Mitosen auf und war in kleine venose Gefasse eingedrungen, 

zcigte aber keine Metastasen. Die Serum Glutamin-Oxalessigsaure- 

Transaniinase Aktivitat war erhoht. 

Acknowledgements 

We thank 1%. P. J.N. PINSENT for the clinical history of this case. We are 

extremely indebted to Professor E. COTCHIN of the Royal Veterinary College, 

London for the time and trouble he has taken in advising us. We have also been 

grateful for the help of Dr. W. MISDORP, Antoni van Leeuwenhock-Huis, Amsterdam, 

and Dr. LINDSAY ANDERSON of the University of Glasgow. 


Mammary Gland Neoplasia in the Cow 511 

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Author’s address: Dr. R. C. Poveu, Department of Vcterinary Medicinc, University of Bristol, Langford Housc, Langford, 

Urirloi (England).

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