An immunohistochemical study of differentiation in malignant fibrous histiocytoma

Immunohistochemistry was used to examine 10 cases of malignant fibrous histiocytoma. Malignant cells in all cases expressed vimentin and in eight there was co-expression of either desmin or neurofilament, both of these being present in four cases. In addition, cytokeratin was found in one case. In each tumour, a population of small cells was identified which had the staining characteristics of benign macrophages, and this was distinct from the tumour cells. This study supports the concept that malignant fibrous histiocytoma is a tumour of mesenchymal cells rather than of histiocytes and emphasizes the diversity of its cytostructure.     

Immunohistochemical study of malignant fibrous histiocytoma

Malignant fibrous histiocytomas (MFH) and other soft-tissue tumors were examined immunochemically (by the peroxidase-antiperoxidase technique) for the presence and location of alpha 1-antitrypsin (alpha 1-AT) and alpha 1-antichymotrypsin (alpha 1-ACT). alpha 1-AT and alpha 1-ACT were found in substantial amounts in 19 and 20 of the 20 MFH tumors examined, respectively. In the other soft-tissue tumors, they occurred inconsistently and in less than 50% of cells, mostly those with signs of damage. It is concluded that assays for alpha 1-AT and alpha 1-ACT may aid in the diagnosis and characterization of malignant fibrous histiocytoma.     

Immunohistological study on malignant fibrous histiocytoma

Malignant fibrous histiocytoma (MFH) shows a mixed proliferation of both fibroblastic and histiocytic cells. Because of their complex morphologic appearances, the nature of truly neoplastic cells in MFH has been controversial. In the present study, immunoperoxidase method (PAP method) was used to examine the intracytoplasmic lysozyme (LY), alpha-1-antitrypsin (A1AT), fibronectin (FN), and polyvalent immunoglobulin (PI) in the fibroblastic and histiocytic cells. Twenty-three cases with MFH were histologically divided into three groups; predominantly fibroblastic type (Group I; 5 cases), mixed fibroblastic and histiocytic type (Group II; 15 cases), and almost pure histiocytic type (Group III; 3 cases). Fibroblastic cells showed a strong positive reaction for LY and A1AT, suggesting the histiocytic nature, while the proliferating cells in Group II were more intensely stained by each of the antibodies than in Groups I and III. Enzyme histochemical examinations on fresh materials were available in 3 cases. These findings suggest that proliferating cells in MFH possess a histiocyte nature.     

Angiomatoid "malignant fibrous histiocytoma": an immunohistochemical study indicative of myoid differentiation.

Six cases of angiomatoid malignant fibrous histiocytoma (MFH), the rarest subtype of MFH, have been studied immunohistochemically using a broad panel of commercially available antisera in formalin-fixed, paraffin-embedded tissue in an attempt to define the pattern of differentiation shown by this unusual tumor. As has been reported in the more common types of MFH, no evidence of histiocytic differentiation was found. However, five cases strongly expressed desmin (DER-11) and two also expressed muscle actin (HHF 35). All tissues examined were negative for myoglobin and alpha-smooth muscle actin. These results provide good evidence for some sort of myogenic or possibly myofibroblastic differentiation in angiomatoid MFH. Given its clinicopathologically and immunohistochemically distinctive features, which are very different from the other variants of MFH, redesignation of angiomatoid MFH as a low-grade myogenic sarcoma of uncertain histogenesis is tentatively proposed. The new term angiomatoid myosarcoma is suggested.     

Recurrent dedifferentiated liposarcoma of the spermatic cord simulating malignant fibrous histiocytoma: an immunohistochemical and ultrastructural study

A case of recurrent dedifferentiated liposarcoma simulating malignant fibrous histiocytoma, with complete absence of lipoblastic differentiation, is described. The tumour cells showed strongly positive immunostaining for alpha-1-antichymotrypsin. Electron microscopy revealed a mixture of fibroblasts and histiocytes. Our findings suggest that the dedifferentiated component reflects an altered differentiation pathway of the primitive mesenchymal cells in the original liposarcoma.     

Immunohistological study on malignant fibrous histiocytoma3

Malignant fibrous histiocytoma (MFH) shows a mixed proliferation of both fibroblastic and histiocytic cells. Because of their complex morphologic appearances, the nature of truly neoplastic cells in MFH has been controversial. In the present study, immunoperoxidase method (PAP method) was used to examine the intracytoplasmic lysozyme (LY), alpha-1-antitrypsin (A***1AT), fibronectin (FN), and polyvalent immunoglobulin (PI) in the fibroblastic and histiocytic cells. Twenty-three cases with MFH were histologically divided into three groups; predominantly fibroblastic type (Group I; 5 cases), mixed fibroblastic and histiocytic type (Group II; 15 cases), and almost pure histiocytic type (Group III; 3 cases). Fibroblastic cells showed a strong positive reaction for LY and A1AT, suggesting the histiocytic nature, while the proliferating cells in Group II were more intensely stained by each of the antibodies than in Groups I and III. Enzyme histochemical examinations on fresh materials were available in 3 cases. These findings suggest that proliferating cells in MFH possess a histiocytic nature. Acta pathol. jpn. 34: 759～765, 1984.     

Histiocyte-like cells expressing factor XIIIa do not belong to the neoplastic cell population in malignant fibrous histiocytoma

The term malignant fibrous histiocytoma (MFH) is widely used for pleomorphic soft tissue sarcomas without a specific line of differentiation. MFH is included in the category of fibrohistiocytic soft tissue tumors. MFH has a broad range of histological appearances, and it has several subtypes. All of these subtypes are composed of spindled fibroblast-like cells, undifferentiated cells, and histiocytic or histiocyte-like cells. A large number of fibroblast-like and pleomorphic cells express factor XIIIa in MFH. The cytological pleomorphism of factor XIIIa cells suggests that these cells may belong to the neoplastic population. It is equally possible that the factor XIIIa-positive cells are only activated stromal cells. The relation of factor XIIIa-positive cells to the neoplastic cell population in MFH is addressed in the present study. A morphometric approach compares the measure of nuclear pleomorphism of the factor XIIIa-positive cells with that of the factor XIIIa-negative tumor cells in high-grade MFH. The immunohistochemical approach compares the factor XIIIa-positive and -negative cell populations with regard to mutations of p53 tumor suppressor gene in p53-positive MFH cases. We selected 58 cases of soft tissue pleomorphic or storiform-pleomorphic MFH on the basis of histopathological examinations. A combination of incident light immunofluorescence for factor XIIIa and transmitted light examination for nuclear staining was used for morphometrical analysis. We found cytoplasmic factor XIIIa positivity in at least 2% of cells in 39 cases; the number of factor XIIIa-positive cells was under 0.5% in two cases, and the number of factor-positive cells ranged between 0.5% and 2% in 13 cases. Eighteen cases were analyzed with nuclear morphometry. We found that mean nuclear area and mean nuclear Ferret diameter in factor XIIIa-positive cells differed significantly from those of the tumor cells in all cases. The mean nuclear roundness factor differed significantly only in four cases. The latter finding showed that the microscopic polymorphism of factor XIIIa cells is measurable and is not merely a suspicion. The immunohistochemical positivity for p53 positivity can be accepted as the manifestation of a missense mutation of TP53 gene and as a marker of neoplastic cells. The simultaneous immunohistochemical detection of factor XIIIa and p53 in the same section revealed that factor XIIIa-positive cells were invariably p53 negative in MFH. This finding implies that the factor XIIIa cell population is non-neoplastic and belongs to the stromal component of MFH.     

Near-haploid clones in a malignant fibrous histiocytoma

Near-haploid solid tumors are very rare. In a storiform-pleomorphic malignant fibrous histiocytoma (MFH) of bone, we found three cell populations: one with a near-haploid, a second with a near-diploid, and a third with a near-tetraploid chromosome number. The near-haploid cells had few structural rearrangements: i(12p) and t(13q21q) in one clone, and these two and an additional t(19;?)(p11;?) in another clone. One structurally normal copy of all chromosomes was also present, except that the only chromosome 13 was involved in the t(13q21q). There were also two near-diploid clones, one without the t(19;?) and one with a single copy of this derivative chromosome. This is the first MFH reported to have a near-haploid modal chromosome number, and also the first tumor with i(12p) among bone and soft tissue tumors.     

Angiomatoid malignant fibrous histiocytoma: cytologic, immunohistochemical, ultrastructural, and flow cytometric study of 20 cases

Twenty examples of angiomatoid malignant fibrous histiocytoma (AMFH) were studied. Patients ranged in age from 3 mo to 42 yr, with a mean of 13.4 yr (median 10.5 yr). There were 12 males and eight females. Tumors occurred in the upper extremities in eight cases, lower extremities in 10 cases, and one case each in the buttock and neck. Five patients had local recurrence from 5 to 18 mo after initial surgery, and one patient developed regional lymph node metastases and eventually died of disease. Eight of nine patients with follow-up information were alive from 11 to 31 mo after the diagnosis. Preoperative fine needle aspiration cytology performed in two patients showed features that suggested the correct diagnosis. Ultrastructural and immunohistochemical studies demonstrated findings consistent with a fibroblastic-histiocytic nature of the neoplasm and failed to detect endothelial differentiation of the tumor cells. Flow cytometric analysis performed in six cases, including three recurrent tumors, revealed a DNA diploid pattern in all instances. AMFH appears to be a distinctive low grade sarcoma in the spectrum of malignant fibrous histiocytoma.     

Primary malignant fibrous histiocytoma of the spleen: an ultrastructural study

A primary malignant fibrous histiocytoma of the spleen was studied by light and electron microscopy and is believed to be the first reported. The neoplasm was predominantly fibroblastic, with a characteristic storiform pattern, and included histiocyte-like cells, giant and foam cells confirmed by ultrastructural studies. Additionally, undifferentiated cells, intermediate cells and myofibroblasts were seen. The differential diagnosis from other sarcomas and the histogenesis of this tumour are discussed.     

Primary fibrosarcoma and malignant fibrous histiocytoma of bone--a comparative ultrastructural study: evidence of a spectrum of fibroblastic differentiation

As primary bone fibrosarcoma (FS) and malignant fibrous histiocytoma (MFH) have similar clinical, radiographic, or survival manifestations, ultrastructural and immunohistochemical studies were undertaken to determine the differentiation pathways of constituent malignant cells. Twelve cases of primary intraosseous FS and MFH were selected for this ultrastructural comparative study and were analyzed for fibroblastic or modified fibroblastic differentiation. There were 4 FS cases and 8 MFH cases, of which 5 were storiform-pleomorphic, 2 were giant cell, and 1 was myxoid type. All FS consisted of spindle fibroblasts with a prominent rough endoplasmic reticulum and Golgi apparatus, variable amounts of vimentin intermediate filaments, and extracellular collagen fibrils. The MFH were composed of a mixture of spindle and pleomorphic fibroblasts (8/8), histiofibroblasts (4/8), and myofibroblasts (3/8). Variable numbers of undifferentiated cells were found in both tumors. In conclusion, fibroblastic differentiation and collagen production was noted in all cases. The often pleomorphic histiofibroblasts present in some MFH cases most likely represent "modified fibroblasts," similar to myofibroblasts. These findings support the hypothesis that the fibroblast and its variants are the predominant cell types found in these tumors, suggesting that the diagnostic entity MFH should be classified as a pleomorphic fibrosarcoma.     

Cytogenetic findings in malignant fibrous histiocytoma

The cytogenetic findings of two malignant fibrous histiocytomas from two unrelated patients are discussed. Both tumors were characterized by trisomy 7.     

Undifferentiated (embryonal) sarcoma of the liver: ultrastructural and immunohistochemical similarities with malignant fibrous histiocytoma

Two undifferentiated (embryonal) sarcomas of liver were studied ultrastructurally and immunohistochemically. Electron microscopic examination of the pleomorphic tumor cells revealed fibroblastic and histiocytic characteristics. There were no specific findings to support rhabdomyoblastic, leiomyoblastic, or epithelial differentiation. Cytoplasmic peroxidase-antiperoxidase (PAP) immunohistochemical staining for vimentin, alpha1-antitrypsin, and alpha1-antichymotrypsin was found. No staining for epidermal or internal organ cytokeratins, desmin, myoglobin, or alpha-fetoprotein was observed. The ultrastructural correlates of the cytoplasmic periodic acid-Schiff-positive, diastase-resistant hyaline globules were large, membrane-bound, heterogenous electron-dense inclusions, probably lysosomal in origin. These inclusions did not react on either alpha1-antitrypsin or alpha1-antichymotrypsin PAP staining. Tumor specimens from two metastatic sites were also examined. Neither contained the ducts or cysts that characterized the primary tumor. These studies confirm the mesenchymal nature of this uncommon childhood neoplasm and support the suggestion that the cytoplasmic hyaline globules represent a degenerative phenomenon. There are ultrastructural and immunohistochemical similarities with malignant fibrous histiocytoma.     

An ultrastructural study of malignant fibrous histiocytoma of the larynx

Malignant fibrous histiocytoma (MFH) of the vocal cord occurring in a 46-year-old male was studied immunohistochemically and ultrastructurally. The tumor consisted of the two main areas, pleomorphic and storiform. Immunohistochemical staining was strongly positive for α1-antitrypsin and α1-antichymotrypsin, and negative for desmin, keratin, myoglobin, actin, carcinoembryonic antigen, and S100 protein. Ultrastructurally, this MFH consisted of four different types of cells which were either fibroblast-like, histiocyte-like, myofibroblast-like, or with features of both the fibroblast and histiocyte types. Transition forms between the four types of cells were also found. This suggests that cells of MFH are derived from the same undifferentiated stem cells.     

Myofibroblastic differentiation in malignant fibrous histiocytoma (pleomorphic myofibrosarcoma): a clinicopathological study

Myofibroblastic differentiation in malignant fibrous histiocytoma (pleomorphic myofibrosarcoma): a clinicopathological study
Aims : We compared the clinical and pathological features of pleomorphic malignant fibrous histiocytoma (MFH)-like soft tissue sarcomas with and without myofibroblastic differentiation on electron microscopy.
Methods and Results : Fifty-three soft tissue tumours designated as MFH by light and electron microscopy were reassessed. Eighteen were specifically diagnosed and excluded, and follow-up (FU) information obtained for 24 of the other 35 cases. Myofibroblastic ultrastructure was seen in 7/24 (29%). Seventeen of 24 (71%) lacked myofibroblasts on electron microscopy, which showed fibroblastic or undifferentiated cells. Histologically, all tumours but one had storiform-pleomorphic areas; one myofibroblastic neoplasm was fascicular and myxoid. No other morphological differences were seen. In seven myofibroblastic cases, smooth muscle in four cases and muscle-specific actin in two cases, desmin in three cases and S100 in one case were present. In 15 other tumours, smooth muscle in five cases and muscle-specific actin in one case, and desmin in one case were present; none of these cases expressed S100. CD34 was found in the myxoid areas of one myofibrosarcoma and 3/15 other tumours. Positivity for bcl-2 was seen only in non-myofibroblastic sarcomas (4/14). On follow-up (median 41 months), 2/7 (29%) myofibroblastic tumours recurred, 5/7 (71%) metastasized, and 3/7 (43%) patients died of disease. Among the non-myofibroblastic sarcomas, with a median follow-up of 47 months, 6/17 cases (35%) recurred, 10/17 (59%) metastasized, and 7/17 patients (41%) died of disease.
Conclusions : Pleomorphic sarcomas with and without myofibroblastic differentiation on electron microscopy are clinically and histologically similar. The former display myoid immunohistochemical markers more frequently.