Bone & Soft Tissue Pathology
Case 3 -
Low Grade, Fibromatosis-like Metaplastic Carcinoma Arising in Association with a Complex Sclerosing Lesion
Stuart J. Schnitt
Beth Israel Deaconess Medical Center and Harvard Medical School
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A 54 year old female presented with a 1.6 cm palpable breast mass. An excisional biopsy
Case 3 - Figure 1
Low power view of the lesion showing central sclerotic zone with entrapped glands and slightly more cellular areas at the periphery.
Case 3 - Figure 2
High power view of glands in the central sclerotic zone, some of which show usual ductal hyperplasia.
Case 3 - Figure 3
Medium power view of the periphery of the lesion showing spindle cells in a collagenous stroma extending irregularly into surrounding adipose tissue.
Case 3 - Figure 4
High power view to demonstrate the bland cytologic features of the spindle cells and low cellularity that characterized most of the lesion.
Case 3 - Figure 5
High power view of the most cellular area of the lesion. A rare mitotic figure is present.
The specimen contained an irregular, firm, grey white area measuring approximately
1.5 cm. Histologic sections of this area revealed a central focus of hyalinized collagen with scattered
entrapped benign ducts, a few of which showed papillary hyperplasia. The histologic features in this
area were consistent with those of a complex sclerosing lesion. Circumferentially around this central
sclerotic area, there was a proliferation of spindle cells that extended irregularly into the surrounding
adipose tissue. The stroma associated with the spindle cells was variably collagenized. In most areas
the cellularity of the lesion was relatively low imparting a scar-like appearance. In a few areas, the
density of spindle cells was somewhat higher. The spindle cells were cytological bland and only rare
mitotic figures were observed.
The differential diagnosis included a scar or other reactive spindle cell proliferation, fibromatosis
and low grade, fibromatosis-like metaplastic carcinoma. Immunostains showed that the spindle cells were
negative for cytokeratin using antibodies AE1/AE3 and CAM5.2. However, these cells were variably
cytokeratin-positive with pan-keratin antibody MNF-116 and cytokeratin antibody 34βE12. The spindle
cells also showed variable nuclear staining for p63. These cells were negative for estrogen receptor and
progesterone receptor and lacked HER2 protein overexpression.
Low grade, fibromatosis-like metaplastic carcinoma arising in association with a complex sclerosing
A variety of reactive and neoplastic lesions of the breast are characterized by a proliferation of
spindle cells. Among these are spindle cell carcinomas, a subtype of metaplastic carcinomas. These
tumors may occur in pure spindle cell form or may consist primarily of spindle cells with associated
glandular, squamous, or heterologous elements (most often chondroid or osseous). Tumors of this type
have been variously designated metaplastic carcinoma, sarcomatoid carcinoma, and spindle cell carcinoma
Spindle cell carcinomas are uncommon, accounting for <1% of invasive breast cancers.
On gross examination, the tumors are most often gray or white, firm masses that are
frequently circumscribed. Microscopically, the appearance of the spindle cells can vary from bland to
highly pleomorphic and may show fascicular, fasciitis-like, storiform, or haphazard growth patterns.
Areas suggestive of vascular spaces may sometimes be seen. The mitotic rate is highly variable. The
borders of the lesion are usually infiltrative with entrapment of mammary ducts and lobules, but some
cases exhibit pushing margins. Higher grade lesions tend to obliterate the normal breast architecture.
In some cases, the spindle cells aggregate into small clusters that exhibit a more epithelioid appearance
or merge with an overt epithelial component. Areas of squamous differentiation are not infrequent and
foci of heterologous chondroid or osseous differentiation may be seen.
Foci of conventional types of invasive breast carcinoma and/or ductal carcinoma in situ may be seen in
association with the spindle cell component, and when present provide useful clues to the epithelial
nature of the tumor. However, in pure spindle cell carcinomas without associated DCIS,
immunohistochemical stains for cytokeratin may be required to arrive at the correct diagnosis. It should
be noted however, that cytokeratin immunoreactivity may be focal and a panel of anti-cytokeratin
antibodies may be required to demonstrate cytokeratin positivity. In our experience broad spectrum
cytokeratin antibodies (such as antibody MNF116) and antibodies to high molecular weight/basal
cytokeratins (such as antibody 34βE12 or antibodies to cytokeratin 5/6) are the most sensitive for
the detection of cytokeratin expression in this setting . The neoplastic cells also commonly express
vimentin, smooth muscle actin, muscle specific actin and p63. Expression by these tumors of actins, p63,
basal cytokeratins and other markers commonly associated with myoepithelial cells has been used as
evidence supporting a myoepithelial or basal phenotype for many of these tumors
distinction between spindle cell carcinomas and lesions previously described as myoepithelial
carcinomas/malignant myoepitheliomas is probably just one of semantics. Spindle cell carcinomas are
typically negative for estrogen receptor and progesterone receptor expression and for HER2 protein
One type of spindle cell carcinoma that may create particular diagnostic problems is low grade
fibromatosis-like metaplastic carcinoma, as illustrated by this case
These lesions may arise
de novo but may also be seen arising in association with papillomas and benign sclerosing lesions .
They are composed of bland spindle cells resembling those seen in scars or fibromatosis. In contrast to
the cells of scars or fibromatosis, however, the spindle cells comprising these lesions show expression
of cytokeratin, and some cases show epithelioid cell clusters or small foci of squamous differentiation.
These tumors have been reported to be associated with a high rate of local recurrence. While no
instances of metastasis were observed in the intial report of these cases  regional and distant
metastases have subsequently been reported in a small proportion of patients with these lesions .
Spindle cell carcinomas are rarely associated with axillary lymph node metastases. Recent studies
suggest a poorer prognosis than for conventional mammary carcinomas  and some have suggested that the
clinical behavior of these tumors, particularly those that lack or have a minimal recognizable epithelial
component is more akin to that of sarcomas than carcinomas .
Given the wide range of appearances of spindle cell carcinomas, the differential diagnosis is broad.
Spindle cell carcinomas composed of cytologically bland spindle cells must be distinguished from scars,
fibromatosis, myofibroblastoma, the fascicular form of pseudoangiomatous stromal hyperplasia,
adenomyoepithelioma, and the stromal component of benign phyllodes tumors. Spindlec cell carcinomas
composed of cytologically atypical spindle cells must be distinguished from the stromal component of
malignant phyllodes tumors, nodular fasciitis, primary mammary sarcoma, metatstatic sarcoma and
metastatic malignant melanoma. It is important to note that a malignant spindle cell tumor of the breast
is much more likely to represent a spindle cell carcinoma or a malignant phyllodes tumor than a sarcoma.
As noted above, the presence of areas of overt epithelial differentiation and/or associated DCIS are
valuable clues to the diagnosis of spindle cell carcinoma. However, in cases without such features, the
demonstration of cytokeratin expression by the neoplastic cells may be required to arrive at the correct
diagnosis. A panel of cytokeratin antibodies may be required. In our experience and that of others,
broad spectrum cytokeratin antibodies (such as MNF-116) and antibodies to high molecular weight
cytokeratins (e.g., CK5/6, CK14, 34βE12) are the most sensitive for detecting epithelial
differentiation in spindle cell carcinomas.
The most important take-home message from this case is that when any spindle cell lesion is
encountered in the breast, no matter how bland and benign-appearing at first glance, the diagnosis of
spindle cell/metaplastic carcinoma should always be considered, and that diagnosis should not be
dismissed unless there is histologic and/or immunophenotypic evidence to exclude it. It is also
important to note that the definitive categorization of any spindle cell lesion of the breast may be
difficult or impossible in the limited sampling afforded by core needle biopsy and a cautious approach to
the diagnosis of spindle cell lesions on needle biopsy specimens is prudent.
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