Multifocal histogenesis of a cystosarcoma phyllodes · Multifocal histogenesis ofa...

Journal of Clinical Pathology, 1978, 31, 897-903

Multifocal histogenesis of a cystosarcoma phyllodesR. SALM

From the Department ofHistopathology, Royal Postgraduate Medical School, Hammersmith Hospital,London W12 OHS, UK

SUMMARY An unusual multifocal cystosarcoma phyllodes is reported. It presented as a small,circumscribed tumour mass, which was associated with two diffuse neoplastic lesions which arosesequentially in two geographically separate parts of the mammary disc. Microscopically the tumourappeared to have been enlarging by the formation of isolated satellite tumour nodules within theadjacent normal breast tissue, which represents a third, though rarer way in which a cystosarcomaphyllodes may enlarge.

Cystosarcoma phyllodes (CSP) usually presents as awell-circumscribed mass, and some examples of thistumour are invested by a pseudocapsule due tocompression of the adjacent breast tissues. Theirmicroscopical appearances are similar to those offibroadenomas, except for a greater cellularity oftheir fibrous component (Willis, 1967; McDivittet al., 1968), and they are held to enlarge mainly bya process of expansion.

In contrast, the following case of CSP consistedonly partly of a tumour with well-defined margins;microscopically it proved to extend much further. Itwas characterised by the presence of many scatteredsatellite foci, and by an unusual micronodularstructure throughout, a tumour pattern which isvirtually unknown.

Case report

A woman aged 50 years first presented with a smalllump medial to the left nipple, and this was excisedin April 1976. A few months later another lump hadbecome palpable at some distance from the site ofthe previous excision, above and lateral to the nipple,and this was excised in November 1976. Because oftumour extension up to the excisional margin, thiswas followed a few days later by a simple mastectomywith removal of axillary lymph nodes. Because theopposite breast showed a general nodularity, andalso in view of the multifocal nature of the tumourin the left breast, the surgeon considered that asimple mastectomy of the right breast was indicated,and this was carried out in January 1977.

Received for publication 8 February 1978

MACROSCOPICAL FEATURESThe two biopsy specimens of the left breast, andboth mastectomy specimens, showed much naked-eye evidence of fibrocystic disease. The largest cyst ofthe first biopsy contained a polypoid ingrowth, about1-4 x 0 7 cm, and the tissues adjacent to this cystwere of increased consistency. A similar firm, ill-defined area was noted in the second biopsy specimen.In the area immediately adjoining the second biopsysite the left mastectomy specimen incorporated afairly well-circumscribed, roughly spherical mass,2 5 cm in diameter. The right breast contained manytense cysts, up to 2 cm across.

MICROSCOPICAL EXAMINATION

Left breast, first biopsyThe intracystic polypus consisted of a bulky fibroustissue core, covered by intact and patchily hyper-plastic epithelium. The subepithelial zones tended tobe more cellular than the central parts, but mitoticactivity was low.The adjacent breast tissue showed the features of

fibrocystic disease. In addition, there were a fewscattered breast lobules with moderately dilated andelongated acini, separated from each other byproliferating fibroblasts with many mitotic figures(Fig. 1). A few of these acini, which were devoid ofany surrounding elastic fibres, had become soelongated that they formed long tubular structures.Apart from these tubules, clearly arising from thebreast lobules, the mammary tissues incorporatedmany isolated tubules of larger diameters whichwere not obviously related to any of the adjacentbreast lobules. These also lacked elastic coats andwere surrounded by thick collars of oedematous

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Fig. 1 Breast lobule with dilated, elongated, and tubular acini separated by proliferatingfibroblasts.Haematoxylin and eosin (H and E) x 30.

fibrous tissue showing many mitotic figures; some ofthem were dilated, their lumina accommodatingpolypoidal protuberances.

Left breast, second biopsyThe features were essentially identical with those ofthe first biopsy. However, in an area about 2-5 x 2cm the tumour nodules were more closely spaced,lying in a collagenous grid (Fig. 2), though withoccasional interspersed groups of uninvolved breastlobules. In the more central parts these nodules werequite tightly packed without, however, having losttheir individuality, silver impregnations showingeach nodule to be clearly demarcated by a ring ofreticulin fibres (Fig. 3).Each single nodule consisted of a central duct-like

structure, lacking any elastic investment, and theseepithelial tubules were surrounded by a thickfibroblastic cuff with up to four mitoses per high-power field. The fibroblasts of many nodules wereseparated by much slightly alcianophilic oedema.Another distinct feature, present throughout, was

the occasionally very marked peritheliomatousarrangement of the immediately pericanalicularfibroblasts. These were placed parallel to each otherand perpendicularly to the tubular epithelium, fromwhich they were separated by a distinct, hyaline,

eosinophilic zone (Fig. 4). Silver stains confirmedthat this zone represented a thickened basementmembrane to which the palisading fibroblastsappeared to be firmly attached. Thin reticulin fibresradiated outward from the thick basement membrane,between the fibroblasts, in parallel fashion (Fig. 5).In contrast, the more peripheral fibroblasts werelying haphazardly, or they were arranged in con-centric fashion.

It was evident that extension of the neoplasm inthe diffuse neoplastic areas had occurred in one oftwo ways. In the first place occasional breastductules had become involved. Less often a largerbreast duct had merged with a neoplastic nodule,resulting in the destruction of its wall and elasticcoat; or an isolated duct had been affected by theneoplastic process, which was nevertheless identifi-able as such, as its thick fibroblastic wall was stillencased by an elastic coat.However, more often newly formed, isolated

neoplastic nodules were lying among somewhatatrophic but otherwise unremarkable breast tissue(Fig. 6), sometimes as far as 1 cm from the nearest,more compact tumour area (Fig. 7).The tubular epithelium within the neoplastic

nodules showed much patchy hyperplasia, especiallywhen covering polypoidal ingrowths, but the

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Multifocal histogenesis ofa cystosarcomaphyIIodes 89

Fig. 2 Tumour nodules lying in a collagenous grid. van Gieson-elastic. x 30.

Fig. 3 Closely spaced tumour nodules sharply demarcated by surrounding reticulin fibres. Silverimpregnation. x 30.

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Fig. 4 Glandular tubule surrounded by rings offibroblasts, three in mitosis. Perpendicularlyarranged fibroblasts separated from epithelium by hyaline zone. H and F x 30.

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Fig. 5 Silver impregnation ofadjacent section. Thickened basement membrane below epitheliumfrom which parallel reticulin fibres irradiate outward between perpendicular fibroblasts. x 30.

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Multifocal histogenesis ofa cystosarcomaphyilodes 901

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epithelial cells lacked mitotic activity and atypicalfeatures.

Left mastectomy specimenThe fibrocystic breast tissue contained a single smallneoplastic nodule, as noted on naked-eye examina-tion, with features similar to the central area of thesecond biopsy but with fairly well-defined margins(Fig. 8). Thus this mass met the conventionaldiagnostic criteria of a CSP. The six small lymphnodes found were unremarkable.

Right mastectomy specimenThe multiple blocks cut all showed the features offibrocystic disease.

Discussion

The present case of CSP is unusual in severalaspects-firstly, because of the presence, in additionto a small CSP, of two macroscopically separateareas of diffuse involvement, the nature of whichbecame apparent only on microscopical examination.Multiple CSPs in the same breast are exceedinglyrare. Minkowitz et al. (1968) reported the syn-chronous occurrence of one circumscribed malignantCSP, one circumscribed benign CSP, and twoseparate well-delimited fibroadenomas in a singlebreast of a woman aged 29 years.

Secondly, the tumours of the biopsy sites in theleft breast were separated from each other in spaceand time. They were situated on either side of thenipple, separated by lactiferous ducts and normalbreast tissue. It is, of course, possible that thesecond neoplastic focus was already present at thetime of the first biopsy, though enlarging only sub-sequently and thereby becoming obvious clinically.Alternatively, it may have arisen during the ensuingfive months. This is a comparatively short intervalbut would be in keeping with known data. ThusMcDivitt et al. (1968) reported that in 28 of their 73patients the tumours had been noticed only onemonth or less before treatment, suggesting a rapidgrowth potential, and they observed a recurrenceafter 11 months. And in case 15 of Oberman's(1965) series of CSP the tumour recurred after onlythree months.

Thirdly, all tumour foci, especially in the twobiopsy excisions, showed a marked micronodularstructure throughout, the nodules being separatedfrom each other by a grid of collagenous fibroustissue and reticulin fibres. This nodular structurehad been preserved even in the more central, pre-sumably older, and at any rate more compact areas.In the less crowded parts the tumour nodules wereoften separated by much uninvolved breast tissue.Towards the periphery of the diffuse lesions there

were breast lobules showing only a minor degree of

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Fig. 8 Sharply defined periphery ofsmall CSP in left mastectomy specimen. H and E x 45.

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neoplastic involvement. These were composed ofenlarged and elongated acini separated by proliferat-ing fibroblasts. Occasionally, however, extreme acinarelongation had produced tubular structures. Else-where the breast tissues incorporated many isolatedduct-like tubules, sometimes lying in small groups,which were not obviously connected to any of theneighbouring breast lobules, and these were sur-rounded by thick fibroblastic cuffs. Both short andlong tubules lacked elastic coats, a finding whichsuggests that most, if not all of them were of lobularorigin. The pre-existing breast ducts had on thewhole remained intact, except for an occasionalduct which was merging with a tumour nodule, itswall and elastic coat being destroyed by proliferatingfibroblasts; and there were a few isolated, thickenedneoplastic ducts still contained within their elasticcoats.Many of the tumour nodules showed a perithelio-

matous arrangement of the pericanalicular fibro-blasts. These were separated from the epithelium bya distinct eosinophilic zone representing a thickenedbasement membrane, to which the palisading flbro-blasts appeared to be firmly attached. These weresupported by parallel reticulin fibres, which radiatedoutward from the basement membrane.

Finally, single, isolated tumour nodules werefound up to 1 cm from the more compact tumourareas, indicating that tumour expansion had occurredby the induction of satellite tumours within theadjacent breast tissues. This must be regarded as athird mechanism by which CSP may enlarge, theother and more common modes being expansionfrom within, or by the extension of tumour pro-jections from the periphery. It appears thatMcDonald and Harrington (1950) had previouslyobserved this growth pattern, for they suggested,though they did not illustrate the process, that someof their cases of CSP had started from multiple foci

throughout the breast, a mode of growth which,however, was subsequently denied by Treves andSunderland (1951).

I acknowledge my gratitude to Professor H. K.Weinbren for affording me the hospitality of hisdepartment. Material and information were gener-ously put at my disposal by Dr A. R. Kittermaster,Tunbridge Wells. I am indebted to Professor J. G.Azzopardi for much encouragement and advice.The photomicrography was the work of Mr W.Hinkes.

References

McDivitt, R. W., Stewart, F. W., and Berg, J. W. (1968).Tumors of the Breast (Atlas of Tumor Pathology, 2ndseries, p. 119, Fascicle 2), Armed Forces Institute ofPathology, Washington, D.C.

McDonald, J. R., and Harrington, S. W. (1950). Giantfibro-adenoma ofthe breast-'Cystosarcoma phyllodes.Annals ofSurgery, 131, 243-251.

Minkowitz, S., Zeichner, M., DiMaio, V., and Nicastri,A. (1968). Cystosarcoma phyllodes: A unique case withmultiple unilateral lesions and ipsilateral axillarymetastasis. Journal ofPathology and Bacteriology, 96,514-517.

Oberman, H. A. (1965). Cystosarcoma phyllodes. Aclinicopathologic study of hypercellular periductalstromal neoplasms of the breast. Cancer, 18, 697-710.

Treves, N., and Sunderland, D. A. (1951). Cystosarcomaphyllodes of the breast: a malignant and a benigntumor. A clinicopathological study of seventy-sevencases. Cancer, 4, 1286-1332.

Willis, R. A. (1967). Pathology of Tumours, 4th edition,p. 217. Butterworths, London.

Requests for reprints to: Dr R. Salm, HistopathologyDepartment, Royal Postgraduate Medical School,Hammersmith Hospital, Ducane Road, London W12OHS.



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