Case 4 -
Metaplastic Carcinoma Arising from a Phyllodes Tumor of the Breast
Fouad Boulos, American Univ/Beirut, Beirut, Lebanon
Click on slide thumbnail images for an enlarged view.
If you have any difficulties viewing these slides, email the webmaster.
67-year-old patient with a 6 cm right breast mass.
Case 4 - Figure 7
Metaplastic carcinoma with epithelioid tumor cells.
Case 4 - Figure 8
High power of metaplastic carcinoma with atypical mitosis, mild atypia, tearing artifact, and few inflammatory cells.
Case 4 - Figure 9
CK5/6 positivity in the metaplastic carcinoma
This case illustrates the rare but noteworthy potential of phyllodes tumors to harbor neoplasms of
epithelial origin, and the clear potential to misdiagnose an epithelial spindle cell proliferation
(metaplastic carcinoma) arising in a phyllodes tumor as originating from the phyllodal stroma.
Pathological/Microscopic Findings and any Immunohistochemical or Other Studies:
Sections show two morphologically distinct components. One component consists of a leaf-like biphasic
proliferation typical of phyllodes tumor. The phyllodal stroma shows intermediate cellularity without
significant atypia or pleomorphism, and the epithelium is bland and mildly hyperplastic, as is customary
in phyllodes tumors. The second component consists of an overgrowth of spindle cells with mild typia,
intersecting banana-shaped fascicles, and scattered mononuclear chronic inflammatory cells. Foci of
necrosis were present but not extensive. The interface between the two components shows few squamoid
islands. A histologically malignant adenocarcinomatous component was not present, but focally within the
spindle cell proliferation, tumor cells acquired a slightly more epithelioid appearance with more rounded
nuclei and clear to amphophilic cytoplasm. The spindle cell proliferation accounted for the majority of
the mass and obscured the majority of phyllodal and non- phyllodal epithelial structures.
Immunohistochemical analysis with antibodies against AE1/AE3 cytokeratin cocktail, CK5/6 and p63 were
performed and showed diffuse and strong staining for CK5/6 and p63 while AE1/AE3 was patchy and weak.
CD34 was negative in tumor cells.
The main differential diagnosis in this case is a borderline or malignant phyllodes tumor. In the
absence of an obvious phyllodes tumor component, the differential diagnosis would also include a variety
of spindle cell lesions in the breast, such as fibromatosis, inflammatory pseudotumor, and nodular
fasciitis, the characteristics of which are beyond the scope of this discussion.
Metaplastic carcinoma arising from a phyllodes tumor of the breast.
The association between metaplastic carcinoma and phyllodes tumors of the breast has only been
reported in the literature on exceedingly rare occasions, essentially either as an isolated occurrence in
a series describing metaplastic carcinomas , or as orphan case reports depicting squamous cell
carcinomas (if one were to consider squamous cell carcinomas metaplastic) arising in phyllodes tumors
This paucity of cases is probably quite representative of the rarity of this event, but may also
well be due to predictable under-recognition, given that one is much more likely to diagnose a malignant
phyllodes tumor (mPT) with stromal overgrowth than a metaplastic spindle cell carcinoma arising in a
phyllodes tumor (MCPT). Familiarity with certain morphologic clues and a high level of suspicion are
therefore necessary to differentiate these similar yet biologically distinct neoplasms. The primary
pathophysiologic difference between mPT and MCPT is that malignant phyllodes tumors derive from the
phyllodal stroma, while metaplastic tumors arise from phyllodal epithelium. Morphologically, this
results in subtle but recognizable differences.
Metaplastic carcinomas (especially of low and intermediate grades) arising in phyllodes tumors, have
similar architectural features as usual metaplastic tumors of the breast. They include the
hemi-storiform pattern with curvilinear intersecting fascicles, the diffuse "tearing" artifact around
individual tumor cells and fascicles, and the occasional presence of epithelioid groups of tumor
These features become much less conspicuous when metaplastic carcinomas acquire a high grade
sarcomatous phenotype, essentially rendering it indistinguishable from any undifferentiated sarcoma of
mammary or extra-mammary tissues.  Additional clues that might help the pathologist suspect this
process include the presence of fibrosclerotic foci with squamoid islands (FSIs)
, and/or a neoplastic
epithelial component i.e. ductal carcinoma in-situ (DCIS) within the epithelial compartment of the
phyllodes tumor. FSIs are small groups of mildly atypical cells with eosinophilic cytoplasm and squamoid
character, embedded in an active fibroblastic milieu. FSIs were initially linked to metaplastic
carcinomas by Denley et al. who reported their presence in four low-grade and one high-grade metaplastic
carcinoma arising within complex sclerosing lesions.  This finding was later corroborated by Gobbi et
al who reported a series of 33 metaplastic tumors arising in association with papillomas, complex
sclerosing lesions, and nipple adenomas, with additional emphasis on the consistent finding of squamoid
islands within fibrosclerotic foci.  These squamoid islands, even when isolated in the re- excision
specimen, were associated with recurrences in several cases as low-grade metaplastic tumors.  In
phyllodes tumors, the presence of FSIs has so far not been documented, but has been noted in the
experience of the breast consultation service at Vanderbilt University. Their presence has specifically
been identified in all the MCPT, similar to what was reported for metaplastic tumors arising in complex
sclerosing lesions. FSIs should of course be distinguished from biopsy site changes and reactive
metaplastic alterations secondary to tissue displacement, ischemia and infarction.
distinction is usually possible due to the additional overall changes that accompany squamoid metaplasia
in these settings, such as the cell culture-like reactive fibroblastic proliferation, as well as the
usual histiocytic reaction and hemosiderin pigment deposition.  Inevitably, some cases will have
enough overlap to make a definitive call arduous, if not unrealistic.
The second clue is also related to the rare transformations of the phyllodal epithelium, from
inconsequential squamous metaplasia , to neoplastic lesions such as in-situ carcinoma.
is a frequent companion of metaplastic carcinomas, though not as persistently as with invasive no special
type carcinoma. Davis et al documented DCIS in 10 of 22 metaplastic carcinomas in their series.  It
is also generally implied that metaplastic carcinomas that lack any morphologic or immunohistochemical
evidence of epithelial differentiation should be associated with an intraductal component, in order to
comfortably make the diagnosis of metaplastic tumor.
It therefore follows that a malignant
phyllodes tumor harboring DCIS should certainly raise the suspicion for MCPT. Interestingly however,
even in the MCPT that contains unequivocal DCIS (unpublished observation), squamoid foci are apparent
upon close inspection of the neoplastic proliferation.
Once the diagnosis is suspected based on the aforementioned clues, confirmatory immunohistochemical
studies are essential. As mentioned earlier, metaplastic carcinomas within phyllodes tumors will have
the same histologic and immunohistochemical profiles as when they occur independently in the breast
parenchyma. This would include positivity for high molecular weight and other cytokeratins, and for p63;
hormonal receptors and Her2-neu are almost always negative.
Other markers that may prove
useful from a therapeutic standpoint include ones from the EGFR family, which have been noted in a
significant portion of metaplastic tumors. 
Clinically, distinguishing these two entities is expected to be important, for prognostic and
therapeutic considerations. Although the metastatic behavior of metaplastic tumors is comparable to that
of malignant mesenchymal neoplasms and mPT in terms of their hematogenous pattern of distant spread, 
metaplastic carcinomas are more aggressive tumors with high short-term mortality. This is occasionally
true even for morphologically low-grade tumors.
Also, while complete surgical excision is the mainstay of therapy for phyllodes tumors, a combination
of surgery, chemotherapy, and radiation remains the treatment of choice for metaplastic tumors.  The
final designation should therefore be specific as to the nature and grade of both processes in order to
appropriately direct clinical management. It is not clear, at this point, whether the localization of
the metaplastic tumor to the phyllodal environment would have an effect on its overall biologic behavior.
Reports by Parfitt and Korula did show lymph node metastases from an invasive mammary carcinoma confined
to a phyllodes tumor, questioning the theoretically protective nature of a preexistent confined
We therefore assume that in the presence of expansile and infiltrative growth, the metaplastic tumor
is to be regarded as if it were occurring outside the confines of a phyllodes tumor, and its prognosis
and management should be assessed accordingly.
Metaplastic spindle cell carcinoma arising in a phyllodes tumor is undeniably a very rare occurrence,
but one that has potentially important prognostic and therapeutic implications. It is therefore prudent
to keep this differential diagnostic possibility in mind, especially when faced with certain clues such
as squamoid islands and DCIS within the phyllodal epithelial component.
- Leibl S, Gogg-Kammerer M, Sommersacher A, Denk H, Moinfar F. Metaplastic breast carcinomas: are they of myoepithelial differentiation?: immunohistochemical profile of the sarcomatoid subtype using novel myoepithelial markers. Am J Surg Pathol. 2005;29:347-53.
- de Rosa G, Ferrara G, Goglia P, Ghicas C, Zeppa P. In situ and microinvasive carcinoma with squamoid differentiation arising in a phyllodes tumor: report of a case. Tumori. 1989;75:514-7.
- Sharma R, Usmani S, Siegel R. Primary squamous cell carcinoma of breast in background of phyllodes tumor--a case report. Conn Med. 2009;73:341-3.
- Hunger E, Türk R, Wurster K. [Malignant cystosarcoma phylloides and squamous cell carcinoma of the breast. A rare tumor combination]. Geburtshilfe Frauenheilkd. 1984;44:640-2.
- Ramdass MJ, Dindyal S. Phyllodes breast tumour showing invasive squamous-cell carcinoma with invasive ductal, clear-cell, secretory, and squamous components. Lancet Oncol. 2006;7:880.
- Gobbi H, Simpson JF, Borowsky A, Jensen RA, Page DL. Metaplastic breast tumors with a dominant fibromatosis- like phenotype have a high risk of local recurrence. Cancer. 1999;85:2170-82.
- Gobbi H, Simpson JF, Jensen RA, Olson SJ, Page DL. Metaplastic spindle cell breast tumors arising within papillomas, complex sclerosing lesions, and nipple adenomas. Mod Pathol. 2003;16:893-901.
- Carter MR, Hornick JL, Lester S, Fletcher CD. Spindle cell (sarcomatoid) carcinoma of the breast: a clinicopathologic and immunohistochemical analysis of 29 cases. Am J Surg Pathol. 2006;30:300-9.
- Denley H, Pinder SE, Tan PH et al. Metaplastic carcinoma of the breast arising within complex sclerosing lesion: a report of five cases. Histopathology. 2000;36:203-9.
- Lee KC, Chan JK, Ho LC. Histologic changes in the breast after fine-needle aspiration. Am J Surg Pathol. 1994;18:1039-47.
- Davies JD, Nonni A, D'Costa HF. Mammary epidermoid inclusion cysts after wide-core needle biopsies. Histopathology. 1997;31:549-51.
- Flint A, Oberman HA. Infarction and squamous metaplasia of intraductal papilloma: a benign breast lesion that may simulate carcinoma. Hum Pathol. 1984;15:764-7.
- Wang JS, Liu HC, Su CH. [Breast cystosarcoma phyllodes. A clinicopathologic study of twenty-seven cases]. Zhonghua Yi Xue Za Zhi (Taipei). 1990;46:96-103.
- Abdul Aziz M, Sullivan F, Kerin MJ, Callagy G. Malignant phyllodes tumour with liposarcomatous differentiation, invasive tubular carcinoma, and ductal and lobular carcinoma in situ: case report and review of the literature. Patholog Res Int. 2010;2010:501274.
- Korula A, Varghese J, Thomas M, Vyas F. Malignant phyllodes tumour with intraductal and invasive carcinoma and lymph node metastasis. Singapore Med J. 2008;49:e318- 21.
- Macher-Goeppinger S, Marme F, Goeppert B et al. Invasive ductal breast cancer within a malignant phyllodes tumor: case report and assessment of clonality. Hum Pathol. 2010;41:293-6.
- Nishimura R, Hasebe T, Imoto S, Mukai K. Malignant phyllodes tumour with a noninvasive ductal carcinoma component. Virchows Arch. 1998;432:89-93.
- Nomura M, Inoue Y, Fujita S et al. A case of noninvasive ductal carcinoma arising in malignant phyllodes tumor. Breast Cancer. 2006;13:89-94.
- Davis WG, Hennessy B, Babiera G et al. Metaplastic sarcomatoid carcinoma of the breast with absent or minimal overt invasive carcinomatous component: a misnomer. Am J Surg Pathol. 2005;29:1456-63.
- Koker MM, Kleer CG. p63 expression in breast cancer: a highly sensitive and specific marker of metaplastic carcinoma. Am J Surg Pathol. 2004;28:1506-12.
- Dunne B, Lee AH, Pinder SE, Bell JA, Ellis IO. An immunohistochemical study of metaplastic spindle cell carcinoma, phyllodes tumor and fibromatosis of the breast. Hum Pathol. 2003;34:1009-15.
- Reis-Filho JS, Milanezi F, Steele D et al. Metaplastic breast carcinomas are basal-like tumours. Histopathology. 2006;49:10-21.
- Fou A, Schnabel FR, Hamele-Bena D et al. Long-term outcomes of malignant phyllodes tumors patients: an institutional experience. Am J Surg. 2006;192:492-5.
- Macdonald OK, Lee CM, Tward JD, Chappel CD, Gaffney DK. Malignant phyllodes tumor of the female breast: association of primary therapy with cause-specific survival from the Surveillance, Epidemiology, and End Results (SEER) program. Cancer. 2006;107:2127-33.
- Lester TR, Hunt KK, Nayeemuddin KM et al. Metaplastic sarcomatoid carcinoma of the breast appears more aggressive than other triple receptor-negative breast cancers. Breast Cancer Res Treat. 2012;131:41-8.
- Rayson D, Adjei AA, Suman VJ, Wold LE, Ingle JN. Metaplastic breast cancer: prognosis and response to systemic therapy. Ann Oncol. 1999;10:413-9.
- Parfitt JR, Armstrong C, O'malley F, Ross J, Tuck AB. In-situ and invasive carcinoma within a phyllodes tumor associated with lymph node metastases. World J Surg Oncol. 2004;2:46.