Phyllodes Tumor

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Diagnosis and reasoning

It would not be unjustified to assert that most medical professionals are at least passingly familiar with the diagnostic approach to a newly discovered breast mass. However, the patient in this clinical scenario has presented with recent rapid enlargement of a longstanding, seemingly benign breast lump - a problem which initially appears to be entirely different. Nevertheless, the diagnostic principles involved are the same - a through history and clinical breast examination, followed by appropriate imaging, and tissue sampling; this is commonly termed the 'triple assessment'. Note that the clinical findings in this patient suggest at a benign lesion; given that the mass was diagnosed as a fibroadenoma, one possibility is that it has started to enlarge again (although it is uncommon for these lesions to do so once they have stabilized in size). Another possibility is that the lump is a phyllodes tumor, a rare fibroepithelial neoplasm; these are often misdiagnosed as fibroadenomas, as they share many clinical, imaging, and histological characteristics; they can also arise de novo from an existing fibroadenoma. The last possibility is that the fibroadenoma has undergone malignant transformation; however, that this is exceedingly rare, affecting only 0.002% to 0.0125% of all fibroadenomas. The next step in her assessment should be imaging of the breasts; as she is less than 30 years of age, this is best performed via ultrasound (which has a higher diagnostic yield than mammography in this age group). The resultant sonographic findings are essentially that of a benign lesion; unfortunately, they are not specific enough to differentiate between the conditions listed above. Note that there is no clear justification to immediately proceed to magnetic resonance imaging (MRI) of the breasts; not only is this is costly, but it too is also often incapable of reliably distinguishing between the above differentials. Thus, tissue sampling should follow, with the question being whether one should attempt fine-needle aspiration cytology (FNAC) first, or perform core-needle biopsy (CNB) immediately, particularly given the possibility of a phyllodes tumor (for which FNAC has poor sensitivity). In such a situation, the Paddington Clinicopathological Suspicion Score is of value; application of this instrument shows that this patient has sufficient clinical and imaging findings to justify an immediate CNB. This in turn reveals the lump to be a fibroepithelial proliferative lesion, a category which includes both fibroadenomas and phyllodes tumors. However, the hypercellular stroma favors a phyllodes tumor, as does the presence of stromal overgrowth, the leaf-like architecture, and elevated stromal mitotic rate. Note that in fibroadenomas, the stroma is hypocellular, with no overgrowth, and few or no mitotic figures. Thus, the diagnosis is indeed a phyllodes tumor; based on the 2003 World Health Organization (WHO) classification of tumors, the histological characteristics indicate this to be borderline in nature. Note that there is no rationale to request a tumor marker assay here. Even in cases where frank breast carcinoma is suspected, tumor markers are not of diagnostic value. They are mainly of use in screening for malignancies, and for monitoring recurrence. Wide local excision is the treatment of choice for phyllodes tumors, regardless of whether they are benign, borderline, or malignant. Note that even with malignant lesions, axillary clearance is not routinely recommended. While estrogen receptors (ER) and progesterone receptors (PR) are found in 43% and 84% of phyllodes tumors respectively, it is unclear if hormonal therapy is of benefit in these patients. Similarly, the benefit of radiotherapy is still under debate.


Phyllodes tumors are rare fibroepithelial lesions which account for less than 1% of all tumors of the breast. They are most common in women between 40 to 50 years, although all age groups are affected; sporadic cases have also been reported in men. Despite the name, phyllodes tumors are not a single homogeneous entity, but rather a spectrum of neoplasms ranging from completely benign lesions, to high grade malignancies demonstrating rapid growth and metastatic spread. Histologically, these are "biphasic tumors" (i.e. two different cellular elements), with a benign epithelium arranged in clefts surrounded by a hypercellular stroma organized into leaf-like structures (hence the name phyllodes tumor, as the Greek word for 'leaf' is phyllos). It should be appreciated that is the stroma which is the neoplastic component, thus determining the pathological behavior of the tumor. In benign lesions, the stromal element can be bland, resembling that of a fibroadenoma; in malignant tumors, it is usually atypical, resembling that of a soft-tissue sarcoma. Between these two extremes, the stroma may resemble that of a low-grade sarcoma. Note that the 2003 World Health Organization (WHO) classification of tumors categorizes phyllodes tumors as benign, borderline, or malignant, based on stromal cellularity and atypia, stromal overgrowth, the number of mitoses, and tumor margin. Macroscopically, smaller tumors have a uniform white consistency with a lobulated surface, while larger lesions may have a red or grey "meaty" consistency with fibro-gelatinous, haemorrhagic, and necrotic areas. Phyllodes tumors are believed to arise from the intralobular or periductal stroma; there is evidence that they can also arise from Fibroadenomas, although the pathogenesis is still unclear. Affected women typically present with a rapidly growing breast lump which is clinically benign; while malignant tumors tend to grow faster and reach larger sizes, the rate of growth is not a good differentiator in this regard. In certain instances, a lesion may have been apparent for months or years, with recent rapid growth causing the patient to seek medical attention. Overall, phyllodes tumors are most common in the upper outer quadrant of the breast, with both sides equally affected. Rarely, bilateral synchronous lesions may be seen. In the case of large tumors, the overlying skin may demonstrate dilated veins and a blue discoloration; fixation to the skin and/or pectoralis muscles may also occur. Note that skin ulceration and nipple retraction are uncommon, even with malignant lesions. In up to 20% of patients palpable axillary lymphadenopathy may also be present, although nodal metastases are seen in less than <1%. Upon mammography, phyllodes tumors are hyperdense or isodense, round or oval shaped masses, with circumscribed or obscured margins. A lucent halo representing a fat component may sometimes be seen. While coarse calcifications similar to those of a fibroadenoma have been reported, microcalcifications (as classically associated with malignancies) are rare. Ultrasonography typically shows an oval shaped, well-circumscribed, homogeneous hypoechoic solid mass; note that this is almost identical to the appearance of a fibroadenoma. Sonographic features which favor a phyllodes tumor include the presence of internal cystic spaces, lobulations, and marked posterior acoustic enhancement. Note that there are no imaging indicators which allow reliable differentiation between benign and malignant lesions. Where magnetic resonance imaging (MRI) is performed, the morphologic features are similar to those seen in the other imaging modalities, e.g. an oval shape with circumscribed margins. The lesion is usually isointense on T1-weighted images and heterogeneously hyperintense on T2-weighted images. Diagnosis via fine needle aspiration (FNAC) is often difficult, with an overall accuracy of only 63%; note that a C3 (possibly benign) or C4 (possibly malignant) cytology report favors a phyllodes tumor over a fibroadenoma. Core biopsy is much more sensitive, possibly because of the extra architectural information available; however, given the heterogeneity of these lesions, sampling errors may occur. Surgery is the treatment of choice, with wide local excision (with at least 1 cm margins) the preferred technique in most instances. Mastectomy is not mandatory if the lesion is borderline or malignant; wide local excision is adequate if sufficient margins can be achieved. However, in the case of very large tumors, mastectomy may prove necessary. As malignant tumors metastasize via the hematogenous route, axillary clearance is not routinely indicated. The role of adjuvant radiotherapy, chemotherapy, or endocrine therapy is still unclear. Unfortunately, many phyllodes tumors are only detected after enucleation or local excision of what initially appeared to be a fibroadenoma. In the case of benign lesions thus diagnosed, a "watch and wait" policy appears to be safe; however, in the case of borderline and malignant lesions, re-excision should be considered. Note also that phyllodes tumors have a tendency to recur, with local recurrence rates ranging from 10% to 40%. This typically occurs within the first few years after surgery. Local recurrence can usually be controlled by further wide excision; however, mastectomy may need to be considered in the case of borderline or malignant tumors. Approximately 20% of patients with histologically malignant tumors develop distant metastases, most often to the lung, bone, and abdominal viscera. This appears to be predetermined by tumor biology, and is not influenced by the extent of the initial surgery. Overall, essentially all benign and borderline phyllodes tumors have an excellent prognosis, as do most (but not all) malignant lesions. However, metastatic disease has a very poor prognosis, with no long-term survival reported.

Take home messages

  1. Clinically, sonographically, and even cytologically, it is difficult to differentiate between a phyllodes tumor and fibroadenoma; thus, many phyllodes tumors are misdiagnosed preoperatively.
  2. Surgery is the treatment of choice for phyllodes tumors, with wide local excision the preferred technique.
  3. Recurrences are very common, typically occurring within the first few years post-surgery.
  4. The vast majority of phyllodes tumors have an excellent long-term prognosis.

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