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This is a soft tissue sarcoma which may be confused with other spindle cell soft tissue tumors. It most commonly occurs on the extremities of elderly patients. Tumors can arise in the lower and upper extremities, trunk, retroperitoneum, and the head and neck region. More than half of the cases were located in dermal or subcutaneous tissues.The size has ranged from 1.5 to 12 cm with a median size of 3.4 cm.

A history of repeated local recurrences with progressive poorer histologic differentiation may occur. A small set of patients may die of metastatic disease.

The cell of origin is the myofibroblast. They are classified as indolent low-grade or occasionally aggressive intermediate-grade sarcomas. The pathologist needs to correctly diagnose these rare tumors because of its resemblance to reactive or pseudosarcomatous conditions. Some investigators believe this tumor is represents the myxoid variant of malignant fibrous histiocytoma.


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AGE RANGE-MEDIAN Range, 22-91 years
Median, 66 years


Minichromosome maintenance protein in myxofibrosarcoma.

Sington JD, Freeman A, Morris LS, Vowler SL, Arch BN, Fisher C, Coleman N.

Department of Molecular Histopathology, University of Cambridge, Cambridge, UK.
Mod Pathol. 2004 Feb;17(2):235-40 Abstract quote.  

Histopathological assessment of myxofibrosarcoma may be difficult, especially on the basis of a small core biopsy, which enables only a crude evaluation of grade and prognosis.

We have tested the hypothesis that determination of cell cycle state may assist in the diagnostic assessment of myxofibrosarcoma. We have studied 51 cases of high-grade (n=20), intermediate-grade (n=21), and low-grade (n=10) myxofibrosarcomas, as well as nine cases of benign myxoma. Cell cycle state within tumors was determined by immunostaining for the recently described marker minichromosome maintenance protein 2 (MCM2), together with Ki67. Labelling indices for both markers were correlated with tumor grade, mitotic index, and time to first recurrence. The MCM2 labelling indices were significantly higher than the Ki-67 labelling indices. Both indices showed a significant correlation with the mitotic index and both showed significant increases with increasing grade of myxofibrosarcoma. The MCM2 labelling index (but not the Ki67 labelling index) showed a significant inverse exponential correlation with the time to first recurrence. Myxoid and cellular areas showed no difference in the MCM2 and Ki-67 labeling index, suggesting that clinically useful information could be obtained from any component of a myxofibrosarcoma sampled in a needle biopsy and/or cytological specimen.

We therefore suggest that assessment of cell cycle state may be a useful diagnostic adjunct in the histopathological assessment of myxofibrosarcoma, by enabling more accurate determination of grade and prediction of outcome.


Myxofibrosarcoma. Clinicopathologic analysis of 75 cases with emphasis on the low-grade variant.

Mentzel T, Calonje E, Wadden C, Camplejohn RS, Beham A, Smith MA, Fletcher CD.

Soft Tissue Tumour Unit, St. Thomas's Hospital, London, England.

Am J Surg Pathol 1996 Apr;20(4):391-405 Abstract quote

Myxofibrosarcoma is one of the most common sarcomas in the extremities of elderly patients.

We analysed the clinicopathologic features in a series of 75 patients. All patients were adults (range, 22-91 years; median, 66 years) with an approximately equal incidence in men and women. Thirty-five tumors arose in the lower and 25 in the upper extremities, nine on the trunk, two each in the retroperitoneum and the head and neck region, and one each in the pelvis and penis. Forty-eight cases (69.5%) were located in dermal or subcutaneous tissues. Distinctive histologic features included the following: a commonly nodular growth pattern; a myxoid matrix containing elongated, curvilinear capillaries; and fusiform, round or stellate tumor cells with indistinct cell margins, slightly eosinophilic cytoplasm, and hyperchromatic atypical nuclei. These lesions varied from a hypocellular, mainly myxoid, and purely spindle-cell appearance (low-grade neoplasms) to high-grade, pleomorphic (malignant fibrous histiocytoma-like) lesions with multinucleated giant cells, high mitotic activity, and areas of necrosis. Immunohistochemistry in 44 cases revealed only vimentin and occasional actin positivity.

Ultrastructurally, tumor cells had a fibroblastic phenotype. DNA flow cytometry and proliferation analysis showed an association between aneuploidy and histologic grade.

An average follow-up of 45 months (range, 5-300 months) in 60 cases has revealed local recurrence in 33 cases (54%). Thirteen patients developed metastases, and 13 tumor-related deaths occurred. A short interval to first local recurrence was associated with poor clinical outcome. The rate of local recurrence was independent of histologic grade, but only intermediate and high-grade neoplasms metastasized. The depth of the primary lesion did not influence the incidence of local recurrence. However, in deep-seated neoplasms, the incidence of metastases was higher and the percentage of tumor-related deaths was twice as high as in superficially located lesions, reflecting the fact that deep-seated lesions tended to be higher-grade, larger tumors.

Myxofibrosarcoma tends to become progressively higher grade in recurrences, as demonstrated in five cases in our series. The poorly recognized low-grade myxofibrosarcoma is emphasized, as proper diagnosis and treatment and scrupulous follow-up are mandatory to avoid local recurrence and gradual tumor progression to a higher-grade neoplasm that may then metastasize.


Myxofibrosarcoma of the sphenoid sinus.

Lam PK, Trendell-Smith N, Li JH, Fan YW, Yuen AP.

Department of Surgery and Pathology, The University of Hong Kong Medical Centre, Queen Mary Hospital, HongKong.

J Laryngol Otol. 2002 Jun;116(6):464-6. Abstract quote

Myxofibrosarcoma was originally described as the myxoid variant of malignant fibrous histiocytoma (MFH). It is uncommon in the head and neck region.

We hereby report a case of myxofibrosarcoma in the sphenoid sinuses. The diagnostic and management difficulties are discussed.

Close collaboration between surgeon, radiologist, histopathologist and clinical oncologist in makng accurate diagnosis and appropriate management of this rare tumour are emphasized.

Myxofibrosarcoma (myxoid malignant fibrous histiocytoma) showing cutaneous presentation: report of two cases.

Fujimura T, Okuyama R, Terui T, Okuno K, Masu A, Masu T, Chiba S, Kunii T, Tagami H, Aiba S.

Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan.
J Cutan Pathol. 2005 Aug;32(7):512-5. Abstract quote  

Myxofibrosarcoma or myxoid malignant fibrous histiocytoma is one of the most common fibroblastic sarcomas in older patients. It is characterized by a tendency for predominantly subcutaneous, multinodular, diffusely infiltrative growth, which may extend to the overlying dermis and present as a cutaneous lesion.

Histologically, it comprises a spectrum ranging from hypocellular low-grade myxoid to high-grade pleomorphic sarcoma. Because the dermal presentation usually appears relatively banal, accurate diagnosis is sometimes challenging.

In this report, we present two cases of myxofibrosarcoma with dermal involvement.

Myxofibrosarcoma presenting in the skin: clinicopathological features and differential diagnosis with cutaneous myxoid neoplasms.

Mansoor A, White Jr CR.


Am J Dermatopathol. 2003 Aug;25(4):281-6 Abstract quote

Myxofibrosarcoma (myxoid malignant fibrous histiocytoma) is one of the most common fibroblastic sarcomas in the older patient, where it can sometimes present with anatomically deceptive boundaries.

Myxofibrosarcoma is now fully characterized as a distinctive and definable pathologic entity. Clinically there is a tendency for predominantly subcutaneous, multinodular, diffusely infiltrative growth, which may extend to the overlying dermis and present as a cutaneous lesion.

Histologically myxofibrosarcoma comprises a spectrum ranging from hypocellular low-grade myxoid to high-grade pleomorphic sarcoma.

We report herein 6 cases of myxofibrosarcoma each with dermatological presentation as a cutaneous nodule. The dermal component in each of the lesions was low- to intermediate-grade and predominantly myxoid resulting in confusion with benign myxoid neoplasms in small biopsy specimens.

The purpose of this series is to focus the attention of workers in dermatology on a subject rarely discussed in dermatopathology literature: the cutaneous presentation of myxofibrosarcoma and the potential for clinical and histologic misinterpretation, as benign dermal lesions.


Commonly nodular growth pattern; a myxoid matrix containing elongated, curvilinear capillaries; and fusiform, round or stellate tumor cells with indistinct cell margins, slightly eosinophilic cytoplasm, and hyperchromatic atypical nuclei.

Varied from a hypocellular, mainly myxoid, and purely spindle-cell appearance (low-grade neoplasms) to high-grade, pleomorphic (malignant fibrous histiocytoma-like) lesions with multinucleated giant cells, high mitotic activity, and areas of necrosis

Myxofibrosarcoma with an infiltrative growth pattern: a case report.

Wada T, Hasegawa T, Nagoya S, Kawaguchi S, Kaya M, Ishii S.

Department of Orthopaedic Surgery, Sapporo Medical University, School of Medicine, Japan.

Jpn J Clin Oncol 2000 Oct;30(10):458-62 Abstract quote

Myxofibrosarcoma, also known as a myxoid variant of malignant fibrous histiocytoma, is one of the most common sarcomas in the extremities of elderly people and is characterized by a high frequency of local recurrence.

We report a case of myxofibrosarcoma, intermediate grade, involving the thigh along the fascial plane and between the muscles without the formation of an apparent nodular lesion. On microscopic examination, the tumor lacked areas of necrosis and pronounced cellular pleomorphism, but it was highly cellular with proliferation of spindle cells which contained large elongated, hyperchromatic and irregularly shaped nuclei, slightly eosinophilic cytoplasm and indistinct cell margins, arranged in both interlacing fascicles and a storiform pattern. Immunohistochemically, many of the tumor cells showed intense reactivity to vimentin and CD34.

More than 20% of the cells were positive for p53 protein and the MIB-1 labeling index was approximately 30%. Desmin, alpha-smooth muscle actin, muscle-specific actin, S-100 protein, cytokeratin, epithelial membrane antigen, bcl-2 protein and neurofilament were negative. The absence of a discrete mass lesion and diffuse infiltrative nature precluded early recognition of tumor. Seven years after hindquarter amputation, the patient has been alive without evidence of local recurrence or distant metastasis.

This case indicates that myxofibrosarcoma can demonstrate a highly infiltrative growth pattern. It is possible that this infiltrative nature is associated with a high rate of local recurrence of the tumor. A careful radiological examination of the extension of the tumor prior to surgery is mandatory considering the infiltrative nature of myxofibrosarcoma.


Myxofibrosarcomas contain large numbers of infiltrating immature dendritic cells.

Soilleux EJ, Rous B, Love K, Vowler S, Morris LS, Fisher C, Coleman N.

Medical Research Council Cancer Cell Unit, Hutchison/Medical Research Council Research Centre, Department of Histopathology, Addenbrooke's Hospital, Cambridge, England.

Am J Clin Pathol. 2003 Apr;119(4):540-5. Abstract quote

Myxofibrosarcoma is a malignant tumor with distinctive histologic features and is believed to be derived from fibroblasts. The function of infiltrating myeloid cells in myxofibrosarcoma is poorly understood. It previously has been shown that a combination of dendritic morphologic features and expression of the C-type lectin, dendritic cell-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN), is useful for identifying DC populations in tissue sections.

In the present study, we found that 3% to 61% (median, 22%) of cells in myxofibrosarcomas express DC-SIGN and have dendritic morphologic features. These DC-SIGN--positive cells are not in cell cycle and are consistent with infiltrating DCs. The percentage of DCs in myxofibrosarcomas is independent of tumor grade. It previously has been shown that DC-SIGN--positive cells are either immature DCs or DCs that predominantly activate TH2 cells, both subsets likely to give rise to ineffective antitumor responses.

The DC-SIGN--positive DCs that we have identified in myxofibrosarcoma may, therefore, be involved in the induction of ineffective immune responses or even tolerance to tumor antigens.

Epithelioid Variant of Myxofibrosarcoma: Expanding the Clinicomorphologic Spectrum of Myxofibrosarcoma in a Series of 17 Cases.

*Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA daggerServizio di Anatomia Patologica, Istituti Ortopedici Rizzoli, Bologna, Italy.


Am J Surg Pathol. 2007 Jan;31(1):99-105. Abstract quote

Myxofibrosarcoma (MFS) is one of the most common soft tissue sarcomas of elderly patients and has a predilection for the limbs.

Herein, we report a previously undescribed variant of MFS showing epithelioid morphology. Seventeen cases diagnosed as epithelioid MFS were retrieved from the authors' files from among 570 cases of MFS. Hematoxylin and eosin-stained sections were reexamined and immunostains for pan-keratin (15 cases), S-100 protein (15), desmin (15), and alpha-smooth muscle actin (13) were performed. Nine patients were men and 8 were women (age range 43 to 89 y; median 63.5). Fifteen patients presented with a mass, and in 2 of these there was also pain. Duration of symptoms varied from 1 to 24 months (median 3). Tumor size ranged from 2 to 15 cm (median 6.75). In 10 cases, the tumor was located in subcutaneous tissue and in 6 cases it was subfascial. The majority of the tumors were located on the limbs (8 lower extremities and 6 upper extremities) followed by neck (1), scalp (1), and trunk (1). Follow-up was available for 14 patients (range 2 to 240 mo; median 16).

Twelve patients were treated by surgery followed by chemotherapy and/or radiation (8 cases). One patient received chemotherapy after an incisional biopsy and 1 patient was treated by surgery alone. Ten patients (71.4%) developed local recurrences. Seven patients (50%) developed metastases to lungs or retroperitoneum. Five patients (35.7%) have died of disease so far. Two patients were lost to follow-up.

Morphologically, 14 cases were high grade, 2 were intermediate, and 1 was low grade. Tumors were characterized by a multinodular, infiltrating growth pattern with alternation of hypercellular and hypocellular myxoid areas; the latter showed prominent curvilinear vessels. Neoplastic cells were arranged singly and in small clusters in the myxoid areas or formed sheets in the hypercellular areas, where they showed epithelioid morphology with round nuclei, vesicular chromatin, prominent nucleoli, and moderate amounts of eosinophilic cytoplasm. The epithelioid areas were generally multifocal with admixed areas of conventional MFS.

Immunostains were negative for all markers studied. Differential diagnosis included carcinoma, melanoma, myoepithelial carcinoma, pleomorphic liposarcoma, and pleomorphic rhabdomyosarcoma.

In conclusion, epithelioid MFS is a rare variant of MFS, accounting for <3% of MFS in consultation material. Its natural history seems more aggressive than usual high-grade MFS, with approximately 70% local recurrence and 50% metastases, even within a relatively short follow-up period.


IMMUNOPEROXIDASE Vimentin and occasional actin positivity
ELECTRON MICROSCOPY Fibroblastic phenotype


Primary Cutaneous Myxofibrosarcoma Mimicking Pleomorphic Hyalinizing Angiectatic Tumor (PHAT): A Potential Diagnostic Pitfall.

Mitsuhashi T, Barr RJ, Machtinger LA, Cassarino DS.

From the *Dermatopathology Laboratory, Department of Pathology, University of California, Irvine, California; daggerDepartment of Dermatology, University of California, Irvine, California; and double daggerDepartment of Pathology, Stanford University, Stanford, California.
Am J Dermatopathol. 2005 Aug;27(4):322-326. Abstract quote  

Myxofibrosarcoma (MFS) is one of the most common sarcomas of adults, and includes lesions ranging from low to high grade based on increasing cellularity, nuclear pleomorphism, and mitotic activity.

We present an unusual case of MFS, which initially showed features of a pleomorphic hyalinizing angiectatic tumor (PHAT), a rare soft-tissue tumor considered benign in the WHO classification. The initial lesion showed a subcutaneous proliferation of spindled to polygonal eosinophilic cells with striking cellular pleomorphism, set in a myxoid to sclerotic stroma with prominent hyalinized and angiectatic vasculature, classic characteristics of PHAT. Rare mitotic figures were identified. The preliminary diagnosis of PHAT was confirmed by a consultant expert soft-tissue pathologist. Four months after the initial surgery, local recurrence was noted. The recurrent tumor demonstrated findings of a high-grade MFS, with a diffuse and cellular proliferation of atypical spindle cells set in a prominent myxoid stroma. Multiple mitoses, including atypical ones, were present. In light of these findings, the original specimen was reexamined and the initial diagnosis was amended to MFS. MFS may mimic or be confused with several benign soft-tissue lesions. Cases mimicking PHAT have not been previously reported.

We describe a unique case of a high-grade MFS that initially showed characteristic features of a PHAT, to illuminate the fact that MFS may rarely arise in, or have areas that masquerade as, PHAT. It is also conceivable, although speculative, that at least some cases of PHAT, currently considered a benign tumor by the WHO, may actually represent or evolve into a unique form of MFS of low malignant potential.


METASTASES 13/60 patients developed metastases
RECURRENCE Local recurrence in 33 cases (54%)
Local recurrence of myxofibrosarcoma is associated with increase in tumour grade and cytogenetic aberrations, suggesting a multistep tumour progression model.

Willems SM, Debiec-Rychter M, Szuhai K, Hogendoorn PC, Sciot R.

1Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.

Mod Pathol. 2006 Mar;19(3):407-16. Abstract quote  

Myxofibrosarcoma is one of the most frequent soft tissue tumours in elderly patients, mostly arising in the extremities. Grade I lesions are only locally aggressive whereas grade II and grade III lesions have metastatic potential. The differential diagnosis contains several other (benign) myxoid soft tissue tumours. A number of sarcomas are characterised by specific cytogenetic aberrations, giving not only insight in their biological pathways; they also serve as molecular markers in difficult diagnoses. Cytogenetic data on myxofibrosarcoma are scarce with only few isolated cases described in the literature. No specific chromosomal aberrations have been detected so far. Moreover, molecular pathways in tumorigenesis and progression of myxofibrosarcoma are barely understood.

We studied the clinicopathologic data and karyotypes of 32 myxofibrosarcomas using conventional banding and multicolour COmbined Binary RAtio labelling fluorescence in situ hybridisation technique. We included eight grade I, eight grade II and 16 grade III lesions. In all, 22 were primary tumours, nine were local recurrences and one a lymph node metastasis. The myxofibrosarcomas showed equal sex distribution, were mostly located at the extremities with two thirds deep-seated and had an average age of occurrence of 66 years.

We found normal karyotypes in eight cases and clonal beside nonclonal aberrations in 22 cases. Complex cytogenetic anomalies were found in all grades. However, no tumour-specific chromosomal abnormalities could be withdrawn. Local recurrences showed increase in grade compared to their primary lesions. Interestingly, these recurrences showed more complex cytogenetic aberrations. Increase in grade seems to parallel increase in cytogenetic aberrations and malignant potential. Since the chromosomal aberrations found were not tumour type specific, they seem to be rather the result of secondary events in tumour progression and tumour genetic instability.

Based on these findings, we suggest that tumorigenesis of myxofibrosarcoma is mainly a multistep genetic process, probably ruled by genetic instability caused by targeted checkpoint genes.

Low-grade myxofibrosarcoma: progression in recurrence.

Fukunaga M, Fukunaga N.

Department of Pathology, Jikei University School of Medicine, Tokyo, Japan.


Pathol Int 1997 Feb-Mar;47(2-3):161-5 Abstract quote

A case of low-grade myxofibrosarcoma with histologic progression in recurrence occurring in a 51-year-old male is described. The patient had a well-circumscribed encapsulated myxoid mass, which measured 2.5 cm at its greatest diameter, in the subcutis of the left forearm.

Microscopically, the tumor was characterized by a proliferation of sparsely distributed spindle or stellate cells, curvilinear small vessels and myxoid stroma. It demonstrated mild pleomorphism without mitotic figures. The patient had the first recurrence at 3 years, which was histologically identical to the primary tumor. The patient had a second recurrence at 11 years, which was predominantly composed of sheets of anaplastic, rounded or oval cells with focal osteoid formation. Immunohistochemically, the tumor cells in the primary and the first recurrent lesions were focally positive for vimentin. In the second recurrence, the tumor cells contained vimentin, alpha-smooth muscle actin and muscle specific actin (HHF35).

The primary lesion had a diploid DNA content with low S-phase fractions. The second recurrence showed a polyploidy. The patient was well with no evidence of disease 18 months after the second recurrence.

These findings suggest that this neoplasm showed histological progression with an increasing risk of metastasis. Low-grade myxofibrosarcoma, which commonly is misinterpreted as benign, has a tendency for histological and biological progression in local recurrences, underlining the importance of accurate diagnosis and wide surgical excision of the primary lesion.


13/60 tumor-related deaths occurred

Short interval to first local recurrence was associated with poor clinical outcome

Low-grade myxofibrosarcoma: A clinicopathologic analysis of 49 cases treated at a single institution with simultaneous assessment of the efficacy of 3-tier and 4-tier grading systems.

Huang HY, Lal P, Qin J, Brennan MF, Antonescu CR.
Hum Pathol. 2004 May;35(5):612-21. Abstract quote  

Grading of myxofibrosarcoma (MFS) is contentious and based on a variety of factors, such as the percentage of myxoid or solid areas, tumor necrosis, mitotic counts, and so on. These factors are often used in combination for different grading schemes, which have not been uniformly evaluated by consistent criteria for patients treated and prospectively followed up at a single institution.

Because only a subset of low-grade (LG) MFS will progress to high grade and metastasize after relentless local recurrences, we analyze various histologic parameters and grading methods to identify prognostic predictors of the LGMFS. Forty-nine cases were classified as LGMFS after review, by using >/=30% of myxoid component, but </=20% of solid areas and only focal, </=10%, of tumor necrosis as cutoffs, as modified from a 2-tier system that is used in our hospital.

These cases were also graded in parallel by French Federation of Cancer Centers Sarcoma Group (FNCLCC) 3-tier and 4-tier grading schemes. The study cohort consisted of 26 men and 23 women, with a median age of 60.5 years. Nineteen cases were superficial, and 30 were deep seated, with the most common site being the lower limb (57%), followed by the upper limb (31%), trunk (8%), and head and neck (4%). The primary tumors ranged from 1.5 to 24 cm in size. Solid areas (5% to 20%) were seen in 23 cases, tumor necrosis (5% to 10%) was observed in 4 cases, and a predominant myxoid area (>/=75%) was noted in 22 cases. Mitotic activity ranged from 0 to 16 (median, 2) per 10 HPF. Comparing FNCLCC 3-tier versus 4-tier grading, respectively, 26 versus 10 tumors were classified as grade I, and 23 versus 39, as grade II, with 16 cases (33%) graded discordantly by 2 schemes. A median follow-up of 55 months in 49 patients (range, 9 to 171 months) revealed local recurrence occurring in 28 patients (57%), 15 and 7 of which developed multiple local recurrences and distant metastases, respectively. There was only 1 case with pulmonary metastasis without a prior local recurrence.

Currently, 33 patients are alive with no evidence of disease, 4 are alive with disease, 9 are dead of disease, and 3 are dead of unknown causes. The 5-year recurrence-free survival, metastasis-free survival (MeFS), and disease-specific mortality (DSM) rates were 41%, 90%, and 4.4%, respectively. Size of larger than 5 cm (P = 0.032), tumor necrosis (P = 0.033), and <75% of myxoid area (P = 0.042) were significant risk factors for DSM; the former two (P = 0.011 for size larger than 5 cm, P = 0.038 for necrosis) were also significantly related to MeFS. Both FNCLCC 3-tier and 4-tier schemes failed to show a significantly better outcome in grade I LGMFS than grade II lesions with respect to all 3 endpoints.

In conclusion, our data statistically validated the previous impression that even the blandest LGMFS still carries a recurrent potential that cannot be foreseen by either different grading schemes or other clinicopathologic parameters. However, DSM rate is significantly related to tumor necrosis, large size, and decreased myxoid area. Tumors having necrosis or exceeding 5 cm are at significant risk of metastatic relapse.


GENERAL Wide local excision

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Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
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Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.

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