Ultrastructural distinctions between adult pleomorphic rhabdomyosarcomas, pleomorphic liposarcomas, and pleomorphic malignant fibrous histiocytomas

The ultrastructural features of five pleomorphic rhabdomyosarcomas, five high-grade malignant fibrous histiocytomas, and five pleomorphic liposarcomas were studied. Electron microscopy was found to be consistently useful in distinguishing between these tumors. The rhabdomyosarcomas showed thick and thin filaments in complexes and consistently contained glycogen. The malignant fibrous histiocytomas had numerous lysosomes, often in cells with ruffled borders, and contained cells showing "myofibroblastic" differentiation. The liposarcomas showed abundant and coalescing lipid droplets, sparse stroma with condensation of amorphous granular materials surrounding plasma membranes, and prominent vascularity. Fourteen of the 15 tumors could be identified on the basis of ultrastructure; thus, electron microscopic examination is an important diagnostic tool for pleomorphic tumors.     

The role of electron microscopy in the diagnosis of pleomorphic sarcomas of soft tissue

Classification of pleomorphic malignancies is frequently problematic and important with regard to treatment. Their histologic differential diagnosis is extremely wide, including sarcomatoid carcinoma, melanoma, anaplastic lymphoma, and a large number of sarcomas with overlapping light microscopic appearances. Not infrequently, immunohistochemical investigations of such tumors yield conflicting or confusing results. In such cases, electron microscopy remains an invaluable investigative and diagnostic adjunct, revealing certain subcellular features that indicate a specific line of differentiation. Combining ultrastructural and immunohistochemical studies is particularly useful in these tumors. This article focuses on the ultrastructural aspects of certain sarcomas that are predominantly pleomorphic, including high-grade fibrosarcoma, myxofibrosarcoma-malignant fibrous histiocytoma, acral myxoinflammatory fibroblastic sarcoma, pleomorphic liposarcoma, pleomorphic leiomyosarcoma, and pleomorphic rhabdomyosarcoma, as well as certain sarcomas that are occasionally quite pleomorphic, including angiosarcoma, malignant granular cell tumor, alveolar soft part sarcoma, and extraskeletal osteosarcoma. We also briefly comment on the common simulators of pleomorphic sarcomas, including melanoma, carcinoma, and lymphoma.     

The comparative role of immunohistochemistry and electron microscopy in the identification of myogenic differentiation in soft tissue pleomorphic sarcomas

There is increasing evidence that histological classification of pleomorphic soft tissue sarcomas is prognostically useful, since a number of studies have provided evidence that myogenic differentiation is associated with a more aggressive clinical behavior. The aim of the current study was to analyze the role of electron microscopy in comparison with immunohistochemistry in the classification of soft tissue pleomorphic sarcomas. Thirty-nine pleomorphic sarcomas of the somatic soft tissues for which material for immunohistochemical and ultrastructural analysis was available were selected for this study. Cases were classified according to the criteria of the WHO classification of soft tissue tumors on the basis of the histologic appearance and of the results of immunohistochemical analysis, and then diagnoses were reconsidered at the light of the results of the ultrastructural analysis. The group of myogenic sarcomas included 13 leiomyosarcomas, 8 myofibrosarcomas, and 1 rhabdomyosarcoma, while the group of nonmyogenic sarcomas included 11 undifferentiated pleomorphic sarcomas/malignant fibrous histiocytomas (MFH), 4 myxofibrosarcomas, and 2 liposarcomas. Overall, there was a good concordance between immunohistochemistry and electron microscopy in recognizing myogenic differentiation in soft tissue pleomorphic sarcomas. Discrepancies included 1 case showing no immunoreactivity for muscle markers, which displayed ultrastructural features allowing reclassification as leiomyosarcoma, and 2 cases initially classified as undifferentiated pleomorphic sarcoma/MFH, which were reclassified as myofibrosarcomas after ultrastructural analysis. Ultrastructural analysis allowed the identification of pleomorphic sarcomas with myofibroblastic phenotype, a category that is not identifiable based on histologic and immunohistochemical profile. Notably, fibronexus junction was identified in tumor cells of 4 pleomorphic myofibrosarcomas, while 2 other lesions showed putative fibronexus junction structures, consisting of electron-dense straight fibrils adjacent to the cell surface, not clearly in continuity with cytoplasmic actin filaments. In conclusion, the results indicate that immunohistochemistry and electron microscopy can usefully complement each other in the classification of soft tissue pleomorphic sarcomas.     

Liposarcoma of pleural cavity with recurrence as malignant fibrous histiocytoma

The case of a 54-year-old male, with a massive right pleural liposarcoma weighing over 3200 g, is presented. The tumor was found by light and electron microscopy to be of well-differentiated and pleomorphic subtypes, and it apparently represents the sixth reported case of liposarcoma primary to the pleura. Two years after excision of the primary tumor, it recurred as a neoplasm with histologic and ultrastructural features characteristic of malignant fibrous histiocytoma. The histogenetic and pathologic implications of the above findings are discussed, and the literature regarding intrathoracic liposarcoma and malignant fibrous histiocytoma is reviewed.     

Malignant fibrous histiocytoma within a recurrent chordoma. A light microscopic, electron microscopic, and immunohistochemical study

A histologically typical chordoma and its four recurrences (3.5, 4, 7, and 7.5 years later) were operated from the spinal canal and I-III lumbar vertebrae of a 49-year-old woman. In addition to the typical areas of chordoma, pleomorphic areas resembling malignant fibrous histiocytoma also were seen in the fourth recurrence. The chordoma-like areas of the fourth recurrence displayed typical epithelial features: clusters of epithelial-like cells, electron microscopically demonstrable vacuoles lined by microvilli and desmosomes, and cytokeratin positivity in immunostaining. The areas in the fourth recurrence that resembled malignant fibrous histiocytoma lacked epithelial features as judged by electron microscopy. They also were negative for cytokeratin but contained, instead, vimentin type of intermediate filaments. The results show that the sarcomatous areas as seen in the recurrent chordoma lack epithelial cell features of chordoma and suggest the possibility of altered differentiation pathway of the tumor stem cell or emergence of a new malignant cell population within the recurrent tumor.     

Cellular differentiation in storiform-pleomorphic malignant fibrous histiocytomas. An electron microscopic study of histogenesis

The most common form of malignant fibrous histiocytoma is the storiform-pleomorphic subtype composed of spindle-shaped fibroblast-like cells, mononucleated histiocytic elements and a changing amount of pleomorphic giant cells. In relation to the changing cellular structures 14 pleomorphic-storiform malignant fibrous histiocytomas were investigated electronmicroscopically. In all tumors several types of cells varying in shape, and size as well as in organelle composition could be demonstrated: 1. Undifferentiated cells, which are relatively small and have a scanty cytoplasm with few organelles. 2. Fibroblast-like cells with well developed rough endoplasmic reticulum, mostly arranged in a storiform pattern. 3. Myofibroblasts corresponding to fibroblasts and showing bundles of thin filaments (4 to 6 nm) with focal dense bodies in the peripheral area of the cytoplasm. 4. Histiocyte-like cells characterized by filopodia-like projections and abundant cytoplasm containing lysosomes and phagolysosomes and also lipid droplets. 5. Chimeric cells, which are intermediate forms with features of fibroblast-like and histiocyte-like tumor cells. 6. Multinucleated tumor giant cells which can be subdivided into fibroblast-like and histiocyte-like types and intermediate forms. On the basis of our ultrastructural studies the storiform pleomorphic malignant fibrous histiocytoma is interpreted as a tumor of an undifferentiated mesenchymal cell with the potency of fibroblastic or histiocytic differentiation. The origin of this cell is uncertain. Dedifferentiation of a differentiated connective tissue cell (fibroblast, pericyte) into a proliferating undifferentiated precursor cell is discussed.     

The myofibroblast: a study of normal, reactive and neoplastic tissues, with an emphasis on ultrastructure. part 2 - tumours and tumour-like lesions

This paper describes the ultrastructure of the commoner myofibroblastic tumours and tumour-like lesions. The objective is to complement mainstream pathology texts, which have concentrated on the clinical and light microscopy features of these lesions and which have arguably but understandably somewhat neglected electron microscopy as an ancillary diagnostic tool and a technique for investigating tumour cell biology. Ultrastructural features are described of nodular fasciitis, the myofibromatoses (including Dupuytren's disease), inflammatory myofibroblastic tumour, post-operative spindle cell nodule, fibroma of tendon sheath, fibrous pseudotumour, benign fibrous histiocytoma, atypical fibroxanthoma, dermatofibrosarcoma protuberans, myofibrosarcoma (myofibroblastic sarcoma), malignant fibrous histiocytoma (pleomorphic myofibrosarcoma), epithelioid sarcoma and spindle-cell carcinoma. Fibrosarcoma and leiomyosarcoma are illustrated for comparison. The fibronexus is emphasised as an important marker for the most confident diagnosis of myofibrosarcoma. Some pathologists accept a light microscope definition, which includes alpha-smooth-muscle actin positivity, h-caldesmon negativity and, in some cases, desmin positivity. Caution in the interpretation of desmin staining in a possible myofibroblastic lesion is urged, since, in combination with an ultrastructurally identified lamina, it more probably suggests true smooth-muscle differentiation. Myofibroblastoma and angiomyofibroblastoma are examples of tumours argued on the basis of ultrastructural findings (sometimes in combination with desmin staining) to be primitively differentiated smooth-muscle cell rather than myofibroblastic proliferations.     

Malignant peripheral nerve sheath tumour with annulate lamellae mimicking pleomorphic malignant fibrous histiocytoma.

The nature and nosologic status of malignant fibrous histiocytoma (MFH), or at least its most common pleomorphic variant, are a matter of controversy and it is possible that this entity represents the shared morphologic phenotype of a range of other dedifferentiated neoplasms. An unusual case of malignant peripheral nerve sheath tumour which very closely mimicked pleomorphic MFH is presented. Its true nature was only disclosed by ultrastructural examination. A further interesting and previously unreported feature in tumours of this type was the presence of annulate lamellae in many of the tumour cells. This case adds weight to the assertion that the light microscopic features of pleomorphic MFH may not be specific.     

Fibronexus in "malignant fibrous histiocytoma" of the bone: a case report of pleomorphic myofibrosarcoma

The fibronexus (fibronexus junction) has been thought to be a characteristic ultrastructural feature of myofibroblasts, but it is controversial whether the fibronexus is also a characteristic of various myofibroblastic tumors. We report here a case of pleomorphic bone sarcoma (pleomorphic/storiform malignant fibrous histiocytoma) with fibronexus junctions arising in the head of the left humerus of a 70-year-old woman. By light microscopy the tumor was composed of large spindle or polygonal cells occasionally arranged in fascicles. Foamy giant cells with bizarre nuclei were not uncommon. Immunohistochemically, the tumor cells were positive diffusely for vimentin and focally for muscle actin ( HHF35 ) and alpha-smooth muscle actin but were negative for desmin, high-molecular weight caldesmon, and S-100 protein. Ultrastructurally, the tumor cells had indented nuclei and spindle or polygonal cytoplasm, with little rough endoplasmic reticulum and small vesicles, and rather numerous mitochondria. The tumor cells had myofilaments with focal densities in the periphery, fibronectin fibrils adjacent to intracellular myofilaments, and by definition, therefore, fibronexus junctions. These findings suggest myofibroblastic differentiation, and a diagnosis of pleomorphic myofibrosarcoma is thought to be appropriate. We believe that the fibronexus is a characteristic and useful ultrastructural feature for differentiating myofibroblastic tumors from other pleomorphic myogenic sarcomas.     

Comparative Ultrastructure of Soft-Tissue Myxoid Tumors

This comparative analysis of the characteristic ultrastructural features specific for intramuscular myxoma, myxoid liposarcoma, extraskeletal myxoid chondrosarcoma, myxoid malignant fibrous histiocytoma, myxoid variant of dermatofibrosarcoma protuberans, and myxoid neurilemoma is based on our own studies of 52 cases. In spite of the histologic resemblance frequently observed, these tumors can be easily distinguished on the basis of cytoplasmic and extracellular features by electron microscopy. The value of electron microscopy in the diagnosis of myxoid tumors of soft tissues lies mainly in its potential to provide additional information concerning the cell types involved in the neoplastic process and their line of differentiation.     

Primary pleomorphic malignant fibrous histiocytoma of the heart

Primary pleomorphic malignant fibrous histiocytoma of the heart is rare. The present study was performed to study the clinical and pathological features of the disease. We describe two rare cases of primary cardiac malignant fibrous histiocytoma and review the published individual data of the patients. Both patients complained of dyspnea, and underwent palliative tumor resection. However, they died several months after surgery. A thorough literature review with clinical presentations, diagnostic features, treatment, and outcomes was done. We have for the first time analyzed the factors related to the survival of malignant fibrous histiocytoma. It is usually difficult to make an appropriate preoperative diagnosis. Despite complete surgical resection and aggressive chemotherapy and radiotherapy, the prognosis is still poor.     

Testicular Nodule Incidentally Found in Elderly Male

This comparative analysis of the characteristic ultrastructural features specific for intramuscular myxoma, myxoid liposarcoma, extraskeletal myxoid chondrosarcoma, myxoid malignant fibrous histiocytoma, myxoid variant of dermatofibrosarcoma protuberans, and myxoid neurilemoma is based on our own studies of 52 cases. In spite of the histologic resemblance frequently observed, these tumors can be easily distinguished on the basis of cytoplasmic and extracellular features by electron microscopy. The value of electron microscopy in the diagnosis of myxoid tumors of soft tissues lies mainly in its potential to provide additional information concerning the cell types involved in the neoplastic process and their line of differentiation.     

Malignant fibrous histiocytoma: an ultrastructural perspective

Malignant fibrous histiocytoma is a frequent diagnosis, but the relationship of the tumors to histologically similar soft tissue neoplasms is controversial. In this study, 157 examples representing the 4 main subtypes were reviewed by light microscopy and each tumor was studied with the electron microscope. Immunohistochemical stains were performed on 77 tumors. Electron micrographs on 100 fibrosarcomas were reviewed for comparison. Malignant fibrous histiocytomas often closely resemble fibrosarcomas at the ultrastructural level and differences between the two are generally of degree only. Evidence for true histiocytic differentiation was not found. The immunohistochemical results did not contradict the authors' impression from electron microscopy that malignant fibrous histiocytoma forms part of the histologic spectrum of tumors of fibroblasts.     

Malignant Fibrous Histiocytoma: An Ultrastructural Perspective

Malignant fibrous histiocytoma is a frequent diagnosis, but the relationship of the tumors to histologically similar soft tissue neoplasms is controversial. In this study, 157 examples representing the 4 main subtypes were reviewed by light microscopy and each tumor was studied with the electron microscope. Immunohistochemical stains were performed on 77 tumors. Electron micrographs on 100 fibrosarcomas were reviewed for comparison. Malignant fibrous histiocytomas often closely resemble fibrosarcomas at the ultrastructural level and differences between the two are generally of degree only. Evidence for true histiocytic differentiation was not found. The immunohistochemical results did not contradict the authors' impression from electron microscopy that malignant fibrous histiocytoma forms part of the histologic spectrum of tumors of fibroblasts.     

The Rise and Fall of Malignant Fibrous Histiocytoma

The term malignant fibrous histiocytoma was coined by Stout and associates in the 1960s to encompass pleomorphic soft tissue sarcomas presumably derived from histiocytes that are capable of fibroblastic transformation. The concept was reaffirmed in the following 2 decades and malignant fibrous histiocytoma thus was regarded as the most common soft tissue tumor in older adults. However, recent more critical clinicopathologic, ultrastructural, and immunohistochemical studies have shown that malignant fibrous histiocytomas are not derived from histiocytic “facultative fibroblasts” and many neoplasms so diagnosed actually are pleomorphic subtypes of other sarcomas. Meticulous electron microscopic and immunohistochemical investigations also found that the more common storiform–pleomorphic, myxoid, and perhaps the giant cell subtypes are composed of variable mixtures of fibroblasts and phenotypically modulated fibroblastic cells, notably myofibroblasts and histiofibroblasts. On the basis of these findings, we propose a new classification for the above subtypes of so-called malignant fibrous histiocytoma, the majority of which are variants of pleomorphic fibrosarcoma.     

Myofibroblasts and related cells in malignant fibrous and fibrohistiocytic tumors.

Myofibroblasts were detected by electron microscopy in five of five cases of fibrosarcoma and in five of six cases of malignant fibrous histiocytoma. In some areas myofibroblasts constituted up to 75 per cent of the tumor cells. Most myofibroblasts contained only sheaves of myofilaments along the margins of the cells, but some cells contained larger bundles of myofilaments and very closely resembled smooth muscle cells. An additional related type of cell was seen in several cases; it was large and possessed abundant eosinophilic cytoplasm, resembling a rhabdomyoblast at the light microscopic level. By electron microscopy this type of cell was seen to contain plentiful rough endoplasmic reticulum and large aggregates of fine filaments with rare dense bodies. These findings suggest that fibrosarcomas and malignant fibrous histiocytomas contain cells showing a spectrum of differentiation from fibrocytic to myogenic and that at the ultrastructural level the distinction between fibroblast and smooth muscle tumors may be blurred.     

The rise and fall of malignant fibrous histiocytoma

The term malignant fibrous histiocytoma was coined by Stout and associates in the 1960s to encompass pleomorphic soft tissue sarcomas presumably derived from histiocytes that are capable of fibroblastic transformation. The concept was reaffirmed in the following 2 decades and malignant fibrous histiocytoma thus was regarded as the most common soft tissue tumor in older adults. However, recent more critical clinicopathologic, ultrastructural, and immunohistochemical studies have shown that malignant fibrous histiocytomas are not derived from histiocytic "facultative fibroblasts" and many neoplasms so diagnosed actually are pleomorphic subtypes of other sarcomas. Meticulous electron microscopic and immunohistochemical investigations also found that the more common storiform-pleomorphic, myxoid, and perhaps the giant cell subtypes are composed of variable mixtures of fibroblasts and phenotypically modulated fibroblastic cells, notably myofibroblasts and histiofibroblasts. On the basis of these findings, we propose a new classification for the above subtypes of so-called malignant fibrous histiocytoma, the majority of which are variants of pleomorphic fibrosarcoma.     

The Comparative Role of Immunohistochemistry and Electron Microscopy in the Identification of Myogenic Differentiation in Soft Tissue Pleomorphic Sarcomas

There is increasing evidence that histological classification of pleomorphic soft tissue sarcomas is prognostically useful, since a number of studies have provided evidence that myogenic differentiation is associated with a more aggressive clinical behavior. The aim of the current study was to analyze the role of electron microscopy in comparison with immunohistochemistry in the classification of soft tissue pleomorphic sarcomas. Thirty-nine pleomorphic sarcomas of the somatic soft tissues for which material for immunohistochemical and ultrastructural analysis was available were selected for this study. Cases were classified according to the criteria of the WHO classification of soft tissue tumors on the basis of the histologic appearance and of the results of immunohistochemical analysis, and then diagnoses were reconsidered at the light of the results of the ultrastructural analysis. The group of myogenic sarcomas included 13 leiomyosarcomas, 8 myofibrosarcomas, and 1 rhabdomyosarcoma, while the group of nonmyogenic sarcomas included 11 undifferentiated pleomorphic sarcomas/malignant fibrous histiocytomas (MFH), 4 myxofibrosarcomas, and 2 liposarcomas. Overall, there was a good concordance between immunohistochemistry and electron microscopy in recognizing myogenic differentiation in soft tissue pleomorphic sarcomas. Discrepancies included 1 case showing no immunoreactivity for muscle markers, which displayed ultrastructural features allowing reclassification as leiomyosarcoma, and 2 cases initially classified as undifferentiated pleomorphic sarcoma/MFH, which were reclassified as myofibrosarcomas after ultrastructural analysis. Ultrastructural analysis allowed the identification of pleomorphic sarcomas with myofibroblastic phenotype, a category that is not identifiable based on histologic and immunohistochemical profile. Notably, fibronexus junction was identified in tumor cells of 4 pleomorphic myofibrosarcomas, while 2 other lesions showed putative fibronexus junction structures, consisting of electron-dense straight fibrils adjacent to the cell surface, not clearly in continuity with cytoplasmic actin filaments. In conclusion, the results indicate that immunohistochemistry and electron microscopy can usefully complement each other in the classification of soft tissue pleomorphic sarcomas.     

The Comparative Role of Immunohistochemistry and Electron Microscopy in the Identification of Myogenic Differentiation in Soft Tissue Pleomorphic Sarcomas

There is increasing evidence that histological classification of pleomorphic soft tissue sarcomas is prognostically useful, since a number of studies have provided evidence that myogenic differentiation is associated with a more aggressive clinical behavior. The aim of the current study was to analyze the role of electron microscopy in comparison with immunohistochemistry in the classification of soft tissue pleomorphic sarcomas. Thirty-nine pleomorphic sarcomas of the somatic soft tissues for which material for immunohistochemical and ultrastructural analysis was available were selected for this study. Cases were classified according to the criteria of the WHO classification of soft tissue tumors on the basis of the histologic appearance and of the results of immunohistochemical analysis, and then diagnoses were reconsidered at the light of the results of the ultrastructural analysis. The group of myogenic sarcomas included 13 leiomyosarcomas, 8 myofibrosarcomas, and 1 rhabdomyosarcoma, while the group of nonmyogenic sarcomas included 11 undifferentiated pleomorphic sarcomas/malignant fibrous histiocytomas (MFH), 4 myxofibrosarcomas, and 2 liposarcomas. Overall, there was a good concordance between immunohistochemistry and electron microscopy in recognizing myogenic differentiation in soft tissue pleomorphic sarcomas. Discrepancies included 1 case showing no immunoreactivity for muscle markers, which displayed ultrastructural features allowing reclassification as leiomyosarcoma, and 2 cases initially classified as undifferentiated pleomorphic sarcoma/MFH, which were reclassified as myofibrosarcomas after ultrastructural analysis. Ultrastructural analysis allowed the identification of pleomorphic sarcomas with myofibroblastic phenotype, a category that is not identifiable based on histologic and immunohistochemical profile. Notably, fibronexus junction was identified in tumor cells of 4 pleomorphic myofibrosarcomas, while 2 other lesions showed putative fibronexus junction structures, consisting of electron-dense straight fibrils adjacent to the cell surface, not clearly in continuity with cytoplasmic actin filaments. In conclusion, the results indicate that immunohistochemistry and electron microscopy can usefully complement each other in the classification of soft tissue pleomorphic sarcomas.     

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.