In accordance with previous findings,7
leiomyosarcomas in our series were more common in women than in men. Retroperitoneal and abdominal tumours outnumbered those in external soft tissue. Leiomyosarcomas were morphologically classified into conventional and pleomorphic types. Conventional leiomyosarcoma was characterised by interlacing, tightly organised fascicles composed of elongated cells with easily seen eosinophilic cytoplasm and elongated nuclei with rounded ends. Pleomorphic type tumours displayed predominantly pleomorphic areas containing anaplastic spindle or oval cells, often admixed with bizarre giant cells mimicking pleomorphic MFH, in addition to at least an ordinary fascicular pattern of elongated smooth muscle-like cells. Leiomyosarcomas showed a distinctive smooth muscle phenotype, as shown by a high frequency and degree of immunoreactivity for desmin, SMA, MSA, and HCD.
In contrast, so called MFH occurred predominantly in the extremities and trunk of elderly men. “MFH” was characterised by pleomorphic or spindle cells arranged in a storiform or small fascicular pattern, with a varying amount of inflammatory infiltrate, and myxoid and collagenous stroma. The neoplastic cells had pointed tapering nuclei, abundant pale eosinophilic or amphophilic cytoplasm, and indistinct cell borders. In our study, 30% of tumours were classified as “MFH” with myofibroblastic features, which had a morphological appearance identical to that of “MFH” and immunoreactivity for SMA.
In our immunohistochemical survey of leiomyosarcoma, the frequency and degree of positivity for smooth muscle markers, particularly HCD, in tumours of the retroperitoneum exceeded that in tumours of the external soft tissue. Recently, heavy caldesmon (HCD), an actin binding cytoskeleton associated protein, has been shown to be a specific immunohistochemical marker for smooth muscle cells and their tumours.8,9
Such variable expression of HCD according to location has been reported,10
but the histological subtype (conventional or pleomorphic) or different grade of leiomyosarcoma did not affect the results. We also found that EMA immunoreactivity was present in approximately half of all leiomyosarcomas, as described in a previous study.11
“As reflected in the latest World Health Organisation classification of soft tissue tumours, so called malignant fibrous histiocytoma can no longer be regarded as a definable entity, and is now viewed as a synonym for undifferentiated pleomorphic sarcoma”
In our present study, S-100 was always negative in so called MFH, and a small proportion of cases showed sporadic to focal immunoreactivity for cytokeratin and EMA, in keeping with previous results.12
CD34 corresponds to the cluster designation of a transmembrane glycoprotein that is expressed in human haemopoietic progenitor cells and vascular endothelial cells. In addition to its expression in primitive leukaemias and vascular tumours, CD34 has been found to be positive in Kaposi’s sarcoma, dermatofibrosarcoma protuberans, giant cell fibroblastoma, solitary fibrous tumour, gastrointestinal stromal tumour, epithelioid sarcoma, and inflammatory fibroid polyps of the stomach.13
The presence of CD34 has been reported in sporadic cases of “MFH”,14,15
but we found that CD34 positivity was a feature of myxoid MFH, being seen in 38% of cases. On the basis of the observation of CD34 expression in dendritic fibroblastic cells and a family of tumours derived from such cells,16
a subset of myxoid MFH, recently termed as myxofibrosarcoma, might share a common histogenesis, distinct from the pleomorphic type.
In our study, so called MFH displayed less frequent, and a lower degree of, immunoreactivity for the smooth muscle markers than did leiomyosarcoma. Among the histological subtypes of “MFH”, frequent positivity for SMA (22 of 47) and desmin (15 of 47) was seen in the pleomorphic type. A previous study also found frequent expression of smooth muscle markers in “MFH” of bone.17
Our present electron microscopic examination of “MFH” tumours with SMA positivity identified a myofibroblastic ultrastructure in approximately half of these tumours. The others contained only fibroblastic or undifferentiated tumour cells. Although various stages of ultrastructurally detectable myofibroblastic differentiation seem to be present in “MFH”,18
it is not meaningful to base the distinction on the ultrastructural examination of just 18 cases, particularly when electron microscopy is inevitably associated with sampling error, and the non-specificity of myofilaments means that electron microscopy should be used as an adjunctive study combined with other modalities.
From a morphological viewpoint, pleomorphic leiomyosarcoma may have areas that closely simulate so called pleomorphic MFH.19
As reflected in the latest World Health Organisation classification of soft tissue tumours,20
“MFH” can no longer be regarded as a definable entity, and is now viewed as a synonym for undifferentiated pleomorphic sarcoma. It has become a diagnosis of exclusion to be reserved for tumours showing no other line of differentiation—yet at least 30% of our cases showed another line of differentiation— that is, features consistent with limited smooth muscle or myofibroblastic differentiation. It has been reported that most “MFH” tumours and leiomyosarcomas have very similar comparative genomic hybridisation imbalances,21
and therefore an important subset of “MFH” could be leiomyosarcomas.
In conclusion, a large subset of so called MFH in fact shows poorly differentiated smooth muscle or myofibroblastic features and perhaps such tumours should be regarded as pleomorphic leiomyosarcomas and/or pleomorphic myofibroblastic sarcomas.