Case 3C -

"Fibromatosis-like" carcinoma (FibLCa)

History: 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 lesion? Case 3C - Figure 1 Case 3C - Figure 2 Diagnosis: 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). Discussion: 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 FibLCa Fibromatosis Phyllodes tumor Myoepithelioma Myofibroblastoma Periductal sarcoma Hamartoma Inflammatory psuedotumor 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. 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. References: 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.