Recent Developments in Diagnostic and Therapeutic Approaches to Breast Diseases
Daniel W. Visscher, M.D.
Carol Reynolds, M.D.
Case 3C -
"Fibromatosis-like" carcinoma (FibLCa)
This is a 56 year old woman with mammographic density. What is
your differential diagnosis? What additional studies would be appropriate to further classify this
This is a "fibromatosis-like" carcinoma (FibLCa), which may be
largely confirmed using special stains for cytokeratins. The differential diagnosis includes a variety
of low grade spindle cell lesions (see below).
Two recent articles, by Gobbi et al. and Sneige et al., have
highlighted the features of a cytologically bland variant of metaplastic breast carcinoma comprised of
fibroblast-like spindle cells. At low magnification, they are variably cellular and have relatively
abundant, dense collagen, comprising >75% of most lesions, accounting for the term
"fibromatosis-like". Gobbi et al., owing to the indolent clinical behavior of cases in their series (see
later), employed the term "metaplastic breast tumor" rather than carcinoma. These tumors are probably
not truly new entities; initial series of metaplastic breast carcinomas described low grade variants.
FibLCa are infiltrative and have an irregular border. It is not uncommon to identify entrapped
benign ducts within the lesion. The neoplastic spindle cells, in addition to a deceptively monotonous
appearance, have pale vesicular chromatin with variable amounts of cytoplasm. Most cases (at least
two-thirds) will contain vaguely defined "cords" of cytologically bland epithelioid cells, sometimes
having a squamous character. However, these neoplasms lack malignant epithelial proliferation that forms
nodules or masses. By definition, at least 95% of the tumor must be comprised of spindle cells. Mitotic
activity is extremely rare, in keeping with the bland cytologic features. Gobbi and Sneige both describe
less than 2 mitoses per 10 high power fields. Approximately 10% are accompanied by low grade ductal
carcinoma in situ. Apparent origin of these lesions from radial sclerosing lesions or papillomas has
also been described.
The most important diagnostic feature of these cases is establishing epithelial differentiation with
the presence of staining for cytokeratins. This may, however, be difficult to demonstrate. We have
observed that AE1/AE3 immunoreactivity is often weak/equivocal in these tumors, possibly since most
FibLCa express high molecular weight CK, in keeping with squamous differentiation. Utilization of
"wide-spectrum" keratin reagents are thus useful in these cases. FibLCa also contain a reactive
fibroblastic proliferation, and therefore the cytokeratin positive cells may be admixed with stromal
cells exhibiting smooth muscle actin immunoreactivity.
Fibromatosis-like carcinomas/tumors typically arise in older age group patients (mean age 63-67 years)
and form palpable infiltrative masses. In both recent studies, the mean size of the lesions was 2.5 to
3.0 cm. The clinical behavior of these lesions remains unsettled. Neither Gobbi nor Sneige identified
nodal metastases, however, Sneige et al. described recurrence in four out of sixteen cases and death due
to lung metastases in two out of sixteen. In contrast, Gobbi et al. identified no evidence of distant
metastases during a median follow-up interval of 27 months. Although 27% of their patients experienced
local recurrence, most of the patients had been treated with biopsy only.
The histologic differential diagnosis of FibLCa is considerable, and quite subtle as reviewed
previously in our discussion of fibroadenoma vs phyllodes tumor.
"Low Grade" Spindle cell Lesions of the Breast
In the setting of a core biopsy a definitive classification may not be possible; such cases will
require open excision for unequivocal diagnosis. It is important to have a high index of suspicion in
this diagnostic category in order to avoid confusing FibLCa with benign lesions.
- Phyllodes tumor
- Periductal sarcoma
- Inflammatory psuedotumor
In addition to lacking cytokeratin immunoreactivity, squamoid cells or evidence of any precursor
epithelial lesions fibromatosis usually occurs in a young age group. It also has a proclivity to develop
in superficial breast tissue, close to the skin surface. In our experience, phyllodes tumor and
periductal sarcoma tend to be more cellular that FibLCa, however in a small sample that would be a
difficult criterion on which to rely. Lack of CK immunoreactivity is obviously important in this
setting. Spindle cell myoepitheliomas resemble leiomyomas and, unlike fibromatosis-like carcinomas, they
are positive for actin and S-100. Similarly, myofibroblastomas also have a low grade cytologic
appearance, but there should be immunoreactivity with desmin (and lack of cytokeratin staining). Actin
staining is also identified in true fibromatosis. Thus, utilization of cytokeratin stains is useful when
confronted with spindle cell lesions, particularly in the setting of core biopsies.
- Nafussi A. Spindle cell tumours of the breast: Practical approach to diagnosis. Histopathology 1999; 35:1-13.
- Gobbi H, Simpson J, Borowsky A, Jensen R, Page D. Metaplastic breast tumors with a dominant fibromatosis-like phenotype have a high risk of local recurrence. Cancer 1999; 85:2170-2182.
- Sneige N, Yaziji H, Mandavilli S, Perez E, Ordonez N, Gown A, Ayala A. Low-grade (fibromatosis-like) spindle cell carcinoma of the breast. American Journal of Surgical Pathology 2001; 25(8):1009-1016.
- McMenamin M, DeSchryver K, Fletcher C. Fibrous lesions of the breast. International Journal of Surgical Pathology 2000; 8(2):99-108.