Cystosarcoma phyllodes.SD Deodhar, SS Joshi, SS Khubchandani
Ten cases of cystosarcoma phyllodes are reported along with review of literature. The pathological features are outlined and principles of management are discussed.
Keywords: Adolescent, Adult, Breast Neoplasms, pathology,surgery,Female, Human, Middle Age, Phyllodes Tumor, pathology,surgery,Prognosis,
Cystosarcoma phyllodes is a rare breast tumour of uncertain aetiology. We recently had a case of cystosarcoma phyllodes at the K.E.M. Hospital, Bombay. The rarity of this case has prompted us to publish this report along with nine other cases at our hospital during the last five years (May 1983 to May 1988).
From May 1983 to May 1988, ten cases of histologically proven cystosarcoma phyllodes were seen at our hospital. A retrospective study of these cases forms the basis of the present report.
All our ten patients were females; the youngest patient was 13 year old, the oldest 55 year, the average age being 32.4 years. There were three cases below the age of 20 and one above the age of 50.
The duration of symptoms varied from one month to one year. Four patients had painful swellings whereas in six, pain was absent. One patient had prolonged low grade pyrexia and one patient, an elderly primipara, developed the breast lump during the early lactation phase. Two patients had undergone resection of breast lumps previously; however, the exact histological nature of these lumps could be ascertained.
In six cases, the breast lump measured more than 10 cm in diameter. The left breast was affected in six cases, the right in two and in two cases there were bilateral lumps. In five cases, the swelling was present in upper half of the breast, while in three cases all the quadrants of the breast were involved. The breast swelling had an irregular surface in seven cases and the skin was adherent to the lump in five cases; there was recent retraction of nipple in three cases. In four cases, the overlying veins were prominent and dilated.
Resection of lump along with healthy breast margin was carried out in six cases and a simple mastectomy in four cases.
Histologically our case showed presence of a tumour mass consisting of both epithelial and stromal elements. The stroma was cellular and consisted of spindle shaped cells having spindle nuclei. Occasional mitotic figures were seen, but there was no evidence of any atypia. At places, the stroma was thrown into finger-like projections lined by benign epithelial cells [Fig. I]. A similar picture was presented by eight other cases. In one case the histological diagnosis was malignant phyllodes tumour (liposarcoma).
Pathologists and surgeons should have a healthy respect for cystosarcoma phyllodes. These tumours should not be regarded merely as 'overgrown' fibro-adenomas. Although several excellent reviews of this neoplasm have appeared in recent years,,,,,,,,, there is still confusion in the minds of surgeons and pathologists with respect to usefulness and accuracy of histologic assessment of malignancy. Furthermore, there is uncertainty regarding prognostic importance of the histological report and proper treatment of the condition.
Definition: Cytosarcoma phyllodes is defined as 'a distinctive fibroepithelial neoplasm of breast tissue.' It differs from ordinary fibroadenoma in being usually larger and in its possession of distinctive connective tissue which is more cellular, more pleomorphic and mitotically more active. It is the cellularity of the connective tissue which is the most important distinguishing point. Thus, the term 'Giant fibroadenoma' is a misnomer. Though the name 'cystosarcoma phyllodes' was given by Johannes Muller in 1838, he clearly stated that this was a benign tumour. Since then it has been variously named as giant intracanalicular fibroadenoma, giant myxomatous fibroadenoma, Brodie's tumour, cellular intracanalicular fibroadenoma (term given by Scarff and Torloni of World Health Organisation in 1968 as quoted by Azzopardi) etc. The term 'cystosarcoma phyllodes' suffers from several defects. It is not self-explanatory and it implies a relationship to cystic disease. Its most important deficiency is that the word 'sarcoma' tends to overstate the malignant potential of the lesion and it is certainly difficult to justify the term 'benign cystosarcoma'. To avoid confusion, Azzopardi used the suitable terminology of naming this tumour as 'phyllodes tumour' and to classify it further as benign and malignant depending on microscopic features and likely behaviour of the neoplasm.
Cystosarcoma phyllodes (CP) accounts for about 0.5% of all breast tumours and occurs equally commonly in the Orients as well as in the West.
Though cystosarcoma phyllodes is commonly seen in female breast, as many as five cases have been reported in the male' breast, all of them occurring in a pre-existing gynaecomastia.
The first major study on CP was done by Lee and Pack, in 1931 (105 cases). They recorded an average age incidence of 44.6 years; while majority of cases reported by Norris and Taylor had average age incidence of 45 years, 5% being adolescents. However, Nambiar and Kutty from Malaysia found as many as 25 cases in adolescent girls and they named these tumours as giant fibroadenomas. In our series, the average age incidence was 32.4 years, though there were 3 cases in 1irls under 20 years of age.
The median duration of symptoms was reported as 4.5 years by Norris and Taylor. In our series, five patients had history of a lump of 6 months' duration and two of them had recurrent lumps. In many patients, there is history of sudden increase in size of the lump, though this does not correlate with the histological type. Two patients in our series complained of sudden increase in size of pre-existing longstanding growth, yet both had benign disease. Thus, rapid growth does not necessarily imply malignancy.
In our series, one patient was found to be lactating and was clinically suspected to be having a galactocoele; however, no other series have reported any relationship of the tumour with pregnancy or lactation. The relationship with menstruation was studied by Nambiar and Kutty and they found that the tumours which occur around the onset of puberty grow rapidly whereas those occurring in late adulthood grow slowly.
In literature, one-third of cases are reported as bilateral. Norris and Taylor reported one bilateral case out of 94. Nambiar and Kutty reported three bilateral cases out of 25. In our series, there were two cases with bilateral humps. In Nambiar and Kutty's series, more commonly the lumps in the opposite breast were ordinary fibroadenomas and not cystosarcoma phyllodes.
Tumours are more common in left breast (56%) than in the right (44%). In our series, eight lumps were on left side, one on right side and one patient had bilateral lumps.
Thus it will be seen that almost 50%,of the tumours occupy the upper half of the breast and majority are centrally located.
Size: The average diameter of a benign tumour is 4 cm and that of malignant one is 6 cm. Norris and Taylor have categorically stated that no tumour smaller than 4 cm is fatal. In the series by Oberman, one-third of cases had size smaller than 5 cm and these included both benign and malignant variants. Thus small tumours can belong to the malignant variety and there cannot be a definite correlation between the size of the tumour and its malignant potential. In our series, five tumours were larger than 10 cm; however, only one of them was malignant.
Axillary lymph node enlargement occurs mainly due to ulceration and infection of the lump, but almost never due to metastasis. None of our patients had axillary lymph node enlargement.
[Table - 1]shows clinical features as reported by Norris and Taylor, Nambiar and Kutty and present series.
Pathology and behaviour of the neoplasm
Grossly, the features of the tumour are well described and hardly any information has been added in the last three decades. It is a lobulated lump with finger-like processes projecting into the surrounding tissue. The line of demarcation is indistinct i.e. they are non-capsulated. Tumours of small size are often more compact, uniform and grayish white in colour. Larger tumours are less homogenous with a tendency to form cysts, haemorrhage and necrosis. Rarely, the entire tumour may undergo haemorrhagic infarction. Cut surface shows cavities containing a number of firm, irregular laminae in close apposition with each other [Figure - 4]. The term phyllodes refers to these leaf-like formations, while sarcoma refers to the fleshy nature of the tumour. On gross examination it is difficult to distinguish between a benign and malignant growth.
Microscopically, these neoplasms manifest a spectrum of histology malignancy. Adequate sampling of the neoplasm, especially of the peripheral area, is essential. The sine qua non for the diagnosis of cystosarcoma phyllodes is stromal overgrowth and hypercellularity associated with elongated and compressed ducts. The cellular aggregation occurs around epithelial canaliculi and sometimes around blood vessels.
It is the connective tissue element which indicates whether a CP should be classified as benign or malignant.
The signs suggestive of malignancy are: (1) poor circumscription, (2) three or more mitoses per ten HPF, (3) moderate or high degree of cellular atypia and (4) presence of broad areas of stromal overgrowth and outstripping of epithelial elements at periphery [Figure - 1] to [Figure - 3]. This is the most important indicator.
The malignant variant may show various types of further differentiation. In order of frequency it can be a fibrosarcoma, liposarcoma, chondrosarcoma, osteosarcoma, myosarcoma or haemangiopericytoma.
The incidence of malignancy varies in different series. Lee and Pack in 1931 described only one malignant case out of 111 cases, while Oberman gives incidence of about 25%. These differences are probably due to controversies among pathologists.
About 3-12% of malignant tumours metastasize., They metastasize by haematogeneous route to lungs (66%), bones (28%), brain (9%) and rarely to liver and heart. The chest wall is involved by direct spread. Axillary lymph node metastasis is virtually unknown. Rhodes et al reported two cases of CNS metastasis who presented several years after mastectomy for the primary tumour-one of them being diagnosed as 'benign' cystosarcoma on histology, at earlier operation.
The metastasic lesions interestingly show only stromal sarcoma and do not show any epithelial cells.
There is only report by Minkowitz et al (as quoted by Azzopardi) of multifocal CP in the same breast.
Bilateral cystosarcomas are rare, but malignant bilateral variants have been reported.,,
Norris and Taylor reported 30% recurrence rate, with most recurrences within 2 years of initial operation. Haagensen recorded 28% recurrence in patients treated by local excision. These include both benign and malignant variants. Hajdu et al have studied this aspect in detail and also reported a malignant transformation of a previously benign tumour which had recurred. This emphasises the need for wider excision when benign neoplasm recurs.
Cystosarcomas in young patients under 20 years of age have favourable prognosis; and, even though microscopic picture is strongly suggestive of malignancy, only simple excision of the tumour gives excellent results with almost 100% five year survival. On microscopic examination, a 'pushing' or well demarcated outline has a favourable prognosis. Thus mastectomy is not indicated even for the malignant variant in a young patient.
Various studies,, show mortality ranging from 0 to 20%. This depends upon recurrence rate and the malignant potential of the tumour irrespective of the type of operation performed.
The spectrum of surgical treatment has ranged from simple enucleation to radical mastectomy. However, of late, conservative operations are being performed more often.
Nambiar and Kutty, after their study in adolescent girls stressed that local excision of the tumour should be the treatment of choice, since even malignant tumours in adolescents have a favourable prognosis.
There is poor correlation between biologic behaviour of the tumour and histologic appearance. The tumours which are reported as benign initially can recur and they may show evidence of malignancy or spread (as in one of our cases in whom excision of lump in left breast was carried out for a benign phyllodes tumour. Eight months later, the patient came back with local recurrence which showed low grade malignancy.
On the other hand, majority of the malignant tumours, especially in adolescents, have excellent prognosis irrespective of the type of operation. Further, these tumours hardly ever spread to axillary lymph nodes. Hence radical mastectomy is absolutely unnecessary and mutilating.
However, total excision of the tumour is essential, since even 15-30% of benign tumours can recur. This recurrence has been attributed to inadequate primary excision. If demonstrated as malignant (on paraffin section), simple mastectomy should be carried out. Frozen section biopsy is not reliable since it cannot differentiate between anaplastic cystosarcoma and undifferentiated carcinoma and may lead to unnecessary radical mastectomy. Hence histological report should be given only on paraffin section and if necessary, a two staged operation be performed.
Although axillary clearance is not necessary, Norris and Taylor have suggested that if available, one low-lying axillary lymph node should be taken for histological sampling.
Blichert-Toft et al have clearly demonstrated that additional radiotherapy does not improve the prognosis and is unnecessary.
[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4][Table - 1]