Spectrum of Fibrosarcomas: Including Low-grade Fibromyxoid Sarcoma,
Sclerosing Epithelioid Fibrosarcoma, Myxofibrosarcoma, and Adult Fibrosarcoma
Cristina E. Antonescu
Memorial Sloan Kettering Cancer Center
New York, NY
Pathologists have come to appreciate that tumors composed of malignant fibroblastic
cells and their variants once thought to be rare, represent a large group of soft tissue sarcomas.
Factors contributing to this conclusion include the following: ultrastructural demonstration of
neoplastic fibroblastic cells in so-called malignant fibrous histiocytoma (MFH), recognition that a
significant number of myxoid soft tissue sarcomas of the extremities and trunk are fibrous tumors (e.g.
myxofibrosarcomas); and the recent identification of some fibrosarcomas that can be classified as
low-grade fibrosing subset of fibrosarcomas.
I. Fibrosing fibrosarcomas is a group of predominantly fibrosed or sclerosed
tumors primarily affecting the extremities of adults of either sex. Recognition of this group started
with the description by Evans of low-grade fibromyxoid sarcoma
, a deceptively bland fibrous
tumor simulating desmoid tumor, but which had focal myxoid changes and surprisingly a definite metastatic
potential. Identification of this tumor has been also hampered by its histologic resemblance to
myxofibrosarcoma . More recently, Folpe et al , in a large study encompassing 73 cases, showed
that up to 30% of low-grade fibromyxoid sarcomas show overlapping histologic features with hyalinizing
fibrosarcoma with giant rosettes
. Furthermore, a very recent cytogenetic report demonstrated
an identical recurrent t(7;16)(q34;p11) translocation in both of these subtypes of fibrosarcoma, thereby
providing genetic proof that these two tumors are variants of the same entity .
The third member of this group is sclerosing epithelioid fibrosarcoma (SEF}
, which is
characterized by a diffuse, dense sclerosis, separating closely packed strands and nests of uniform
hyperchromatic epithelioid cells. Overlapping histologic features of SEF with the other two members have
been marginally suggested in different reports, but further genetic analysis is needed to unequivocally
confirm this hypothesis. The earliest observation of increased cellularity and anaplastic round cell
change in low grade fibromyxoid sarcoma, as seen routinely in SEF, was provided by Evans in 1993 ,
which was interpreted as evidence of "dedifferentiation". Furthermore, Folpe et al  described
epithelioid cell foci in up to 45% of their tumors having low grade fibromyxoid sarcoma/hyalinizing
fibrosarcoma with giant rosettes features.
Ultrastructurally, the unifying concept of fibrosing fibrosarcomas is based on well-developed
fibroblastic features of the neoplastic cells embedded in a dense collagenous extracellular stroma and
admixed with a peculiar amorphous granular material. Nielsen et al  reported the ultrastructural
findings of three cases of hyalinizing fibrosarcomas with giant rosettes. The neoplastic cells showed
fibroblastic features with long branching RER complexes. In all tumors in addition to a abundant
extracellular collagen fibers, large aggregated of granular amorphous material resembling "basement
membrane-like" substance was noted admixed with the collagen fibers but also seen within the dilated
cisternae. Similar findings were also identified in sclerosing epithelioid fibrosarcoma . In a study
from our group , five of the eight SEF cases studied ultrastructurally showed intermixed with the
collagenous matrix, confluent areas of basement membrane-like amorphous substance. Furthermore, the
prominent extracellular matrix was arranged in evenly spaced columns of collagen fibrils squeezing the
fibroblastic cells of varying size. Eyden et al  described in addition to prominent RER, large Golgi
apparati, which in one case was producing collagen secretion granules. Similar with our findings, Eyden
and colleagues did not identify myofibroblastic ultrastructural differentiation in their 5 SEF cases
studied. Just as significant is the absence of smooth-muscle actin immunostaining in the overwhelming
majority of these tumors classified under fibrosing fibrosarcoma family.
II. Myxoid fibrosarcomas (myxofibrosarcomas)
Myxofibrosarcoma (MFS} is the most common sarcoma affecting limbs of old patients
, and its
high-grade end of the spectrum is considered as a myxoid variant of malignant fibrous histiocytomas (MFH)
by some authors . MFS comprises a very wide morphological spectrum. For high grade lesions, they
tend to form solid parts with a continuous transition to a storiform-pleomorphic type MFH. A continuity
between high grade and low grade areas of MFS was indicated by the presence of solid high grade
components within the low grade tumors as well as the progression of a subset of low grade MFS into high
grade tumors in local recurrences . Owing to its ultrastructural features closely resembling
ordinary fibroblasts, other investigators favored the nomenclature, MFS, instead of myxoid MFH and
regarded it as a distinct fibroblastic neoplasm characterized by the myxoid nodular appearance and
curvilinear vasculatures with a considerably broad spectrum of nuclear pleomorphism, cellularity, and
- Evans HL. Low-grade fibromyxoid sarcoma. A report of two metastasizing neoplasms having a deceptively bland appearance. Am J Clin Pathol 1987; 88:615-619.
- Evans HL. Low-grade fibromyxoid sarcoma. A report of 12 cases. Am J Surg Pathol 1993; 17:595-600.
- Mentzel T, Calonje E, Wadden C, Beham A, Smith MA, Fletcher CDM. Myxofibrosarcoma: clinical analysis of 75 cases with emphasis on the low grade variant. Am J Surg Pathol 1996; 20:391-405.
- Folpe AL, Lane KL, Paull G, Weiss SW. Low grade fibromyxoid sarcoma and hyalinizing spindle cell tumor with giant rosettes. A clinicopathologic study of 73 cases supporting their identity and assessing the impact of high-grade areas. Am J Surg Pathol 2000; 24:1353-1360.
- Lane KL, Shannon RJ, Weiss SW. Hyalinizing spindle cell tumor with giant rosettes: a distinctive tumor closely resembling low grade fibromyxoid sarcoma. Am J Surg Pathol 1997; 21:1481-8.
- Woodruff JW, Antonescu CR, Erlandson RA, Boland PJ. Low-grade fibrosarcoma with palisaded granuloma-like bodies (giant rosettes). Am J Surg Pathol 1999; 23:1423-8.
- Reid R, de Silva CMV, Paterson L, et al. Low grade fibromyxoid sarcoma and hyalinizing spindle cell tumor with giant rosettes share a common t(7;16)(q34;p11) translocation. Am J Surg Pathol 2003; 27:1229-1236.
- Meis-Kindblom JM, Kindblom L-G, Enzinger FM. Sclerosing epithelioid fibrosarcoma: a variant of fibrosarcoma simulating carcinoma. Am J Surg Pathol 1995; 19:979-93.
- Antonescu CR, Rosenblum MK, Pereira P et al. Sclerosing epithelioid fibrosarcoma. A study of 16 cases and confirmation of a clinicopathologically distinct tumor. Am J Surg Pathol 2001; 25:699-709.
- Nielsen GP, Selig MK, O'Connel JX, et al. Hyalinizing spindle cell tumor with giant rosettes. Am J Surg Pathol 1999; 23:1227-1232.
- Eyden BP, Manson C, Banerjee SS, Roberts ISD, Harris M. Sclerosing epithelioid fibrosarcoma: a study of five cases emphasizing diagnostic criteria. Histopathology 1998; 33:354-360.
- Angervall, L., Kindblom, L.G., Merck, C. Myxofibrosarcoma. A study of 30 cases. Acta Pathol Microbiol Scand [A] 1977; 85A, 127-40.
- Weiss, S.W., Enzinger, F.M. Myxoid variant of malignant fibrous histiocytoma. Cancer 1977; 39, 1672-85.
- Merck, C., Angervall, L., Kindblom, L.G., et al. Myxofibrosarcoma. A malignant soft tissue tumor of fibroblastic- histiocytic origin. A clinicopathologic and prognostic study of 110 cases using multivariate analysis. Acta Pathol Microbiol Immunol Scand Suppl1983; 282, 1-40.
- Kindblom, L.G., Merck, C. & Angervall, L. The ultrastructure of myxofibrosarcoma. A study of 11 cases. Virchows Arch A Pathol Anat Histol 1979; 381, 121-39.