Phyllodes tumor is an uncommon biphasic breast tumor and it constitutes 1% of all breast tumors and 2-3% of fibroepithelial neoplasm.2
Its histologic features include stromal hypercellularity and long clefts lined with several layers of epithelium. Despite a lack of the standard grading system, phyllodes tumors are traditionally graded into benign, borderline, and malignant.1
According to three tiered grading subgroups of the WHO classification, a benign phyllodes tumor has modest degree of the stromal hypercellularity, little cellular pleomorphism, few mitotic figures, well circumscribed margin and uniform stromal distribution. On the other hand, a malignant phyllodes tumor shows marked stromal hypercellularity, marked cellular pleomorphism, numerous mitotic figures (>10 /10 high power fields), an infiltrative margin and stromal overgrowth. A phyllodes tumor which displays indeterminate features is categorized as a borderline malignancy.9
All phyllodes tumors may recur, but only the borderline and malignant phyllodes tumors metastasize.10
Although the mitotic activity was modest (6/10 high power fields) in our case, the tumor had stromal overgrowth, marked stromal hypercellularity and marked cellular pleomorphism. These findings are suggestive of the malignant phyllodes tumor.
The epithelial component of phyllodes tumor may show some proliferative changes. However, its malignant changes within phyllodes tumor are very rare. To date, only several cases of lobular carcinoma in situ
invasive lobular carcinoma,11
ductal carcinoma in situ
invasive ductal carcinoma,4
ductal and lobular carcinoma in situ16
and squamous carcinoma13
in phyllodes tumors have been reported.
First described by Page et al.18
in 1983, invasive cribriform carcinoma is very rare and it is a unique type of the breast carcinoma. The invasive cribriform carcinoma is defined as the invasive carcinoma of breast showing more than 50% of cribriform pattern in the invasive component. Page et al.18 divided it into the classical and mixed invasive cribriform carcinoma. The classical invasive cribriform carcinoma exclusively shows cribriform pattern or mainly cribriform pattern with a limited extent of tubular structure, while mixed one contains the areas of less well-differentiated invasive carcinoma. In our case, the invasive carcinoma component showed the characteristic features of invasive cribriform carcinoma, i.e., a cribriform pattern of the growth of tumor cell nests and a few well-formed tubules with mild nuclear atypia. According to criteria of Page et al.,18
our case can be diagnosed as a classical invasive cribriform carcinoma arising in a malignant phyllodes tumor. In our case, however, the cribriform nests were not aggregated. This is in contrast to the classic invasive cribriform carcinoma arising in normal breast. They were widely dispersed by the expanded stroma in some areas, thus making the differential diagnosis difficult. The cribriform pattern of tumor cells may also be present in ductal carcinoma in situ
, adenoid cystic carcinoma and secretory carcinoma, all of which should also be considered in the differential diagnosis. Ductal carcinoma in situ
typically has myoepithelial component. In our case, however, immunohistochemical staining of p63 and calponin revealed no myoepithelial cell layers. Adenoid cystic carcinoma also may exhibit cribriform patterns. And it has biphasic cellular components of the basaloid cells and ductal epithelial cells. Besides, it is negative for estrogen receptor, progesterone receptor and HER-2/neu.19
In the current case, there were no basaloid cells and basement membrane-like material in the lumen, both of which are the histopathologic findings of the adenoid cystic carcinoma, and there was a positive response to estrogen receptor and progesterone receptor by immunohistochemistry. Secretory carcinoma has similar characteristics to lactating mammary glands and it is characterized by extensive secretions.20
However, these findings were not seen in our case.
A majority of previous reports have shown that patients with carcinoma in phyllodes tumor achieve a good prognosis. To date, however, there are no methodical studies about or consensus on the prognosis of the above cases. Of a total of 13 cases that have been reported up to present, 11 were followed up to monitor a clinical course. Nine patients survived with no evidence of disease progression during the follow-up period ranging from three months to nine years,3
and one patient died of the unrelated disease after a 9-year follow-up observation with no recurrence or metastasis.7
However, one patient experienced tumor recurrence. Sugie et al.5
reported a case of 54-year-old woman who had invasive ductal carcinoma with squamous differentiation arising in malignant phyllodes tumor. Two years and eight months postoperatively, this patient experienced lung and facial bone metastases of the sarcomatous component. Approximately 22% of patients with malignant phyllodes tumors develop distant metastases where the lung and bone are affected most frequently and these patients eventually die of disease.9
In our case, it is difficult to predict the prognosis. The patient was followed up for short-term period and there were no recurrence or metastasis.
In conclusion, our case is the first report of invasive cribriform carcinoma arising within malignant phyllodes tumor. Although carcinoma arising in phyllodes tumor is rare, it should be considered in the diagnosis of phyllodes tumors with abnormal epithelial proliferation.