Diagnostic aspect of spindle-cell sarcomas by electron microscopy

Spindle-cell sarcomas in the somatic soft tissue and soft parts, including fibrosarcoma, leiomyosarcoma, malignant fibrous histiocytoma (MFH), and malignant schwannoma were examined by electron microscopy in order to delineate the most reliable cellular features for their diagnosis. Fibrosarcoma consisted largely of fibroblastic cells and leiomyosarcoma cells were packed in forming small cell groups with constant junctional complexes of nexus and zonula adherens types. MFH showed variable cellular features containing the cells with myofibroblastic and histiocytic differentiation. Malignant schwannoma was characterized by tumor cells having slender cytoplasmic processes with overlapping or interdigitation and thick basement membrane. These ultrastructural features were contributory to the differential diagnosis of the sarcomas examined.     

Gene expression analysis of soft tissue sarcomas: characterization and reclassification of malignant fibrous histiocytoma.

In soft tissue sarcomas, the diagnosis of malignant fibrous histiocytoma (MFH) has been a very controversial issue, and MFH is now considered to be reclassified into pleomorphic subtypes of other sarcomas. To characterize MFH genetically, we used an oligonucleotide microarray to analyze gene expression in 105 samples from 10 types of soft tissue tumors. Spindle cell and pleomorphic sarcomas, such as dedifferentiated liposarcoma, myxofibrosarcoma, leiomyosarcoma, malignant peripheral nerve sheath tumor (MPNST), fibrosarcoma and MFH, showed similar gene expression patterns compared to other tumors. Samples from those five sarcoma types could be classified into respective clusters based on gene expression by excluding MFH samples. We calculated distances between MFH samples and other five sarcoma types (dedifferentiated liposarcoma, myxofibrosarcoma, leiomyosarcoma, MPNST and fibrosarcoma) based on differentially expressed genes and evaluated similarities. Three of the 21 MFH samples showed marked similarities to one of the five sarcoma types, which were supported by histological findings. Although most of the remaining 18 MFH samples showed little or no histological resemblance to one of the five sarcoma types, 12 of them showed moderate similarities in terms of gene expression. These results explain the heterogeneity of MFH and show that the majority of MFHs could be reclassified into pleomorphic subtypes of other sarcomas. Taken together, gene expression profiling could be a useful tool to unveil the difference in the underlying molecular backgrounds, which leads to a rational taxonomy and diagnosis of a diverse group of soft tissue sarcomas.     

Reassessment and clinicopathological prognostic factors of malignant fibrous histiocytoma of soft parts

Recently, the category of malignant fibrous histiocytoma (MFH) has been under discussion and new entities resembling MFH have appeared. To clarify the recent situation regarding MFH, we reassessed previously diagnosed MFH cases in accordance with the most up-to-date diagnostic criteria, which included allied tumors. We carefully reassessed 428 cases that had been diagnosed in our institute during the past 28 years. Moreover, we searched for clinicopathological prognostic factors among the cases that were finally diagnosed as MFH. Among the 428 cases, 138 cases had their diagnoses changed. The revised cases included 78 leiomyosarcomas (57%; ordinary leiomyosarcoma, 45 cases; pleomorphic leiomyosarcoma, 23 cases; myxoid leiomyosarcoma, 10 cases), 12 liposarcomas (9%; pleomorphic liposarcoma, 11 cases; dedifferentiated liposarcoma, one case), seven dermatofibrosarcoma protuberans (5%), six unclassified sarcomas (4%), five primary or metastatic carcinomas (4%), four low-grade fibromyxoid sarcomas (3%), four inflammatory myofibroblastic tumors (3%), three rhabdomyosarcomas (2%), three malignant peripheral nerve sheath tumors (2%), three acral myxoinflammatory fibroblastic sarcomas (2%) and two atypical fibroxanthomas (1.5%). Among the 1974 soft tissue sarcomas registered in our institute, MFH (428 cases) had been the most common sarcoma, followed by liposarcoma, leiomyosarcoma and rhabdomyosarcoma. However, after reassessment, leiomyosarcoma proved to be the most common soft tissue sarcoma (322 cases), followed by 290 MFH, 273 liposarcomas and 202 rhabdomyosarcomas. Among these 290 cases finally diagnosed as MFH, survival data were available in 189 cases. Tumor location in the abdominal cavity, the retroperitoneum or the head and neck (P = 0.0024), tumor size of 5 cm or more (P < 0.0001), deep tumor location (P < 0.0001), high histological grade (grade 3) based on the French Federation of Cancer Centers' grading system (P = 0.0007), and high stage (stage III or IV) based on the American Joint Committee on Cancer (AJCC) staging system (P < 0.0001) were significantly worse prognostic factors by univariate analysis. In multivariate analysis, deep tumor location and high AJCC stage were independent adverse prognostic factors. We conclude that leiomyosarcoma is the most important differential diagnosis for MFH, especially pleomorphic leiomyosarcoma from storiform-pleomorphic type and myxoid leiomyosarcoma from myxoid type. Tumor depth and AJCC stage are the most important predictive prognostic factors in MFH.     

HLA-DR (Ia-like) reactivity in tumors of bone and soft tissue: an immunohistochemical comparison of monoclonal antibodies LN3 and LK8D3 in routinely processed specimens.

Recent studies of Class II histocompatibility antigen expression in bone and soft tissue sarcomas have suggested that malignant fibrous histiocytoma (MFH) may express HLA-DR, whereas histologically similar pleomorphic, epithelioid, and spindle cell malignant neoplasms generally do not. To test whether these observations are reproducible in the differential diagnosis of soft tissue sarcomas, anti-HLA-DR antibodies LK8D3 and LN3 were applied to formalin-fixed, paraffin-embedded sections of MFH, neurofibrosarcoma (NFS), leiomyosarcoma (LMS), synovial sarcoma (SS), fibrosarcoma (FS), angiosarcoma (AS), Kaposi's sarcoma (KS), chondrosarcoma (ChS), "dedifferentiated" chondrosarcoma (DChS), osteosarcoma (OS), epithelioid sarcoma (ES), and clear cell sarcoma (CCS; malignant melanoma of soft parts). The only consistent difference in Class II antigen expression was seen in the group of neoplasms composed of large polygonal cells. Among the latter lesions, four of six clear cell sarcomas were labeled by LK8D3 or LN3, but none of 12 epithelioid sarcomas were reactive. Otherwise, a diversity of tumors in other morphologic categories expressed Class II antigens, with no clear diagnostic patterns. These results may be of use in the diagnostic separation of large cell epithelioid tumors of soft tissue, but neither LN3 nor LK8D3 appears to be helpful in the identification of other sarcomas.     

Imprint cytological features of soft tissue sarcomas]

The imprint cytologic features in typical sarcomas, such as malignant fibrous histiocytoma (MFH), fibrosarcoma, malignant peripheral nerve sheath tumor (MPST), liposarcoma, synovial sarcoma, clear cell sarcoma and epithelioid sarcoma, were presented in comparison with each histologic feature. Cytological diagnosis of soft tissue sarcomas is usually difficult because of their rarity, various kinds, wide range of features in the tumor and similar features to those of other tumors. Based on the cellular morphology, sarcoma cells were divided into five cell types as follows: small cell type, spindle cell type, epithelioid cell type, epithelioid-spindle type, and pleomorphic type. The results obtained from "retrospective" immunostainings for decolorized Papanicolau's stained sections with a panel of markers, together with differentiation of the cell type, were useful for the cytological diagnosis of the tumors examined. Since the value of aspiration cytology is much higher than that of imprint cytology in the cytopathologic diagnosis, methods, such as immunostaining and differentiation of the cell type, are recommended in aspiration cytology to make a definitive cytological diagnosis in sarcoma cases.     

Characterization of human soft tissue sarcomas in nude mice. Evidence for histogenic properties of malignant fibrous histiocytomas.

Twenty-two human sarcomas were grafted subcutaneously into nude mice. Twelve tumors grew successfully. Nine of these 12 tumors had an aneuploid DNA content, whereas only 1 of 10 nonsuccessful tumors was aneuploid. The 12 sarcomas included two leiomyosarcomas, two malignant schwannomas, one synovial sarcoma, and seven malignant fibrous histiocytomas (MFHs). With light and electron microscopic and immunolabeling studies the original and xenografted tumors (the latter for at least two generations) were histopathologically compared. The xenografted leiomyosarcomas showed ultrastructurally a more pronounced leiomyodifferentiation, and one of the malignant schwannomas a more pronounced schwannian differentiation. The second malignant schwannoma and the synovial sarcoma, however, remained unchanged. Five storiform pleomorphic MFHs expressed features that were not observed in the original tumors. Tumor cells of three of these xenografted sarcomas showed leiomyogenic differentiation (filamentous densities, pinocytotic vescicles, and desmin immunoreactivity), whereas cells of the two others demonstrated schwannian differentiation (long cytoplasmic processes, basal lamina). A xenografted myxoid MFH and a pleomorphic MFH gave rise to pleomorphic sarcomas composed of undifferentiated cells. It appeared that under transplantation conditions tumor cells of storiform pleomorphic MFH can differentiate into various directions.     

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.     

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.     

Pleomorphic rhabdomyosarcoma in adults: immunohistochemistry as a tool for its diagnosis

Pleomorphic rhabdomyosarcoma in adults over 30 years of age was a diagnosis frequently made in the 1960s and 1970s. Since the general acceptance of malignant fibrous histiocytoma (MFH) as a tumor entity at the end of the 1970s, however, it has become a very rare tumor in adults. Therefore, 21 cases originally diagnosed on the basis of histology and clinical data as pleomorphic rhabdomyosarcoma in the 1960s and 1970s were reexamined immunohistochemically. Other types of pleomorphic sarcomas involved in the differential diagnosis were also studied. Specific antibodies against vimentin, desmin, creatine kinase subunit M, skeletal muscle actin and myosin, and myoglobin, and the avidin-biotin-peroxidase complex technique were used. The immunohistochemical findings indicate that rhabdomyosarcoma occurs only rarely in adults over 30 years of age and that the majority of the tumors have to be reclassified as MFH or leiomyosarcoma. On the other hand, several pleomorphic sarcomas were found to be diagnosed incorrectly as MFH or liposarcoma by routine histologic stains and electron microscopy. The revised diagnosis was pleomorphic rhabdomyosarcoma for one case and pleomorphic leiomyosarcoma for the other cases. Thus, this study clearly shows the usefulness of immunohistochemistry as a technique in the diagnosis of pleomorphic sarcomas in adults.     

Diagnostic application of immunohistochemistry in pleomorphic sarcomas

Eighteen cases of pleomorphic sarcoma diagnosed or supposed as rhabdomyosarcomas (RMS) and fourteen cases of other soft tissue lesions were stained with five specific antisera (myoglobin, desmin, alpha-1-antitrypsin, Lysozyme, and S-100) by peroxidase antiperoxidase method. The immunohistochemical findings indicated that the majority of the pleomorphic sarcomas (11/18) had to be reclassified as malignant fibrous histiocytoma (MFH), and pleomorphic RMS was indeed rare in adults over the age of 30 years. In this MFH group, desmin was present in all but 3 cases (8/11), supporting that MFH is a tumor originated from mesenchymal cells other than histiocytes. The success of using immunohistochemistry for making pathologic diagnosis depends upon rational application of panels of antibodies. The diagnostic features of pleomorphic sarcomas in routine or special stains are discussed.     

MALIGNANT FIBROUS HISTIOCYTOMA SHOWING CYTOPLASMIC HYALINE GLOBULES AND STROMAL OSTEOIDS: A Case Report with Light and Electron Microscopic, Histochemical, and Immunohistochemical Study

A 56-year-old man died of widespread metastases of malignant fibrous histiocytoma (MFH) primarily developed in the left lower gingiva after a rapid clinical course is reported. Primary and metastatic tumors showed light and electron microscopic, histochemical and immunohistochemical characteristics of MFH together with cytoplasmic hyaline globules and stromal osteoids. Hyaline globules revealed periodic acid-Schiff positive and diastase resistant reactions but not positive with any histochemical and immunohistochemical reactions. Osteoids were partially calcified and rimmed by osteoblastic tumor cells. The present case of MFH may provide difficulties in the differential diagnosis from some osteoid-forming sarcomas in soft tissues with relation to the histogenesis.     

A correlative cytologic and histologic study of malignant fibrous histiocytoma: an analysis of 40 cases examined by fine-needle aspiration cytology

A correlative cytologic and histologic study of 40 cases of histologically highly pleomorphic malignant fibrous histiocytoma (MFH) is presented. The fine-needle aspiration biopsy was performed preoperatively, and a diagnosis of malignant soft-tissue tumor could be established in all cases. The cytologic and histologic features corresponded well with each other. The two main cell types were mono- and multinucleated, large polymorphic, often bizarre, histiocyte-like cells and atypical fibroblast-like cells. For a correct diagnosis of pleomorphic MFH, it is important to recognize atypical large polymorphic tumor cells showing signs of phagocytosis: prominent cytoplasmic vacuolization, cell debris or even well-preserved cells within the tumor cell cytoplasm. Phagocytic activity was easily demonstrated in air-dried and May-Grünwald Giemsa-stained material. The differential diagnosis of MFH as opposed to other soft-tissue sarcomas and pleomorphic carcinomas is discussed.     

Malignant fibrous histiocytoma showing cytoplasmic hyaline globules and stromal osteoids. A case report with light and electron microscopic, histochemical, and immunohistochemical study

A 56-year-old man died of widespread metastases of malignant fibrous histiocytoma (MFH) primarily developed in the left lower gingiva after a rapid clinical course is reported. Primary and metastatic tumors showed light and electron microscopic, histochemical and immunohistochemical characteristics of MFH together with cytoplasmic hyaline globules and stromal osteoids. Hyaline globules revealed periodic acid-Schiff positive and diastase resistant reactions but not positive with any histochemical and immunohistochemical reactions. Osteoids were partially calcified and rimmed by osteoblastic tumor cells. The present case of MFH may provide difficulties in the differential diagnosis from some osteoid-forming sarcomas in soft tissues with relation to the histogenesis.     

Immunohistochemical staining for KIT (CD117) in soft tissue sarcomas is very limited in distribution

We performed immunohistochemical analysis for KIT in 365 soft tissue sarcomas. Most tumors evaluated were completely negative for KIT, including all cases of leiomyosarcoma, rhabdomyosarcoma, myxofibrosarcoma, liposarcoma, solitary fibrous tumor, synovial sarcoma, dermatofibrosarcoma protuberans, schwannoma, malignant peripheral nerve sheath tumor, clear cell sarcoma, low-grade endometrial stromal sarcoma, and follicular dendritic cell sarcoma. Tumors showing occasional immunoreactivity for KIT included extraskeletal myxoid chondrosarcoma (2/20), Ewing sarcoma/malignant primitive peripheral neuroectodermal tumor (4/20), melanotic schwannoma (3/5), metastatic melanoma (4/20), and angiosarcoma (5/20). In most cases, staining for KIT was focal. Rare tumor cells showing KIT positivity were identified in a small number of other tumors. This study demonstrates very limited expression of KIT in soft tissue tumors other than gastrointestinal stromal tumors and underscores the discriminatory value of KIT immunohistochemical analysis for differential diagnosis. As some of these findings differ markedly from previous reports, it is evident again that variations in immunohistochemical technique can lead to major discrepancies in positive staining. Since treatment eligibility for selective tyrosine kinase inhibitors such as STI571 hinges on positive immunostaining, standardization and reproducibility of meaningful results are critically important.     

Das maligne fibröse Histiozytom

The entity and nosology of pleomorphic malignant fibrous histiocytoma (MFH) is still ambiguous. The actual WHO-Classification uses pleomorphic malignant fibrous histiocytoma (MFH) and pleomorphic sarcoma NOS (not otherwise specified) synonymously. On the other hand text and illustrations convey the impression, that these tumors also could be pleomorphic lipo-, leio- or rhabdomyosarcomas etc. It would have been more informative to emphasize, that with the above mentioned specific sarcoma types MFH-like appearance may occur. Furthermore it would have been more up to date to consider pleomorphic sarcomas NOS as pleomorphic fibrosarcomas and include them in the chapter of fibroblastic and myofibroblastic tumors. This concept already has been carried out for the former myxoid variant of MFH, nowadays preferentially called myxofibrosarcoma.There is controversial discussion about the clinical significance of exact typing of pleomorphic sarcomas. Problems may also occur due to the lack of standards, which degree of desmin expression signifies leiomyosarcoma or just indicates myofibroblasts in MFH. The requirement of exclusion of other tumor-types before diagnosing pleomorphic fibrosarcoma still remains obligatory. After verification of the diagnosis pleomorphic sarcoma NOS or pleomorphic fibrosarcoma, grading e.g. according to criteria of the FFCCS can be carried out. Most cases of pleomorphic fibrosarcoma will qualify as high grade malignant.     

Malignant fibrous histiocytoma of visceral organs: clinicopathologic features and diagnostic value of ezrin and HMG-CoA reductase

Malignant fibrous histiocytoma (MFH) of the breast and visceral organs is extremely rare. There is an incomplete understanding of the clinical pathology of the primary MFH originating from the breast and visceral organs, especially in comparison with other soft tissue sarcomas. As a consequence we searched and analyzed the clinical and pathological records of all the nine patients with diagnosed breast and visceral MFH in our hospital. Immunohistochemical staining was performed for ezrin and HMG-CoA reductase in these MFH cases and relevant mesenchymal sarcomas. The 9 MFH cases presented with nonspecific symptoms and imaging manifestations. 6 cases were classified as storiform-pleomorphic MFH, 2 cases as inflammatory MFH, and the remaining 1 case as giant cell MFH. The results showed that ezrin expression, as well as HMG-CoA reductase expression, was significantly stronger in MFH cases than other non-MFH sarcomas. Poor prognosis seemed to be associated with younger age. Certain characteristics and clinicopathologic features can help us making the diagnosis of MFH. In conclusion, our study provided the potential value of ezrin and HMG-CoA reductase for diagnosis and differential diagnosis of MFH located in the breast and visceral organs. More accurate prognostic information of this rare disease needed to be further investigated.     

Leiomyosarcoma and malignant fibrous histiocytoma share similar allelic imbalance pattern at 9p

Formalin-fixed, paraffin-embedded tissue from 45 soft tissue sarcomas was analysed for allelic imbalance/loss of heterozygosity (AI/LOH) of chromosome 9. The specimens consisted of 17 cases of soft tissue leiomyosarcoma (LMS), 4 cases of cutaneous LMS, 22 cases of conventional malignant fibrous histiocytoma (MFH) and 2 cases of angiomatoid fibrous histiocytoma. All cases were categorised morphologically and immunohistochemically. DNA was microdissected from normal and neoplastic tissues. AI/LOH was performed using six microsatellite markers on the 9p region. The frequency of allelic imbalance at different loci on chromosome 9p was analysed in LMS and MFH and then compared with values previously examined in synovial sarcoma and malignant peripheral nerve sheath tumour. Although AI/LOH and microsatellite instability (MSI) were more frequent in MFH, LMS and MFH groups showed similar patterns of allelic imbalance at the 9p region. Alterations of chromosome 9p have been reported in many cell lines and tumours including LMS and MFH. 9p21 region encodes p16^INK4A and p15^INK4B. Allelic imbalance observed at 9p 21 in this study suggests that alterations of the negative cell cycle regulators may be an important step in the pathogenesis of MFH and LMS. However, the most frequent allelic imbalance was observed at 9p24 at D9S230. Alterations of this locus were very rare in synovial sarcoma and malignant peripheral nerve sheath tumours and were absent in cutaneous LMS and angiomatoid fibrous histiocytoma. This locus may point to the existence of a genetically altered tumour suppressor gene involved in the pathogenesis of LMS and MFH. Our results support the hypothesis that MFHs may represent a morphological pathway in tumour progression of LMSs.     

Comparative fine-needle aspiration and pathologic study of malignant fibrous histiocytoma: cytodiagnostic features of 95 tumors in 71 patients

To determine diagnostic cytomorphologic features of malignant fibrous histiocytoma (MFH) on fine-needle aspiration (FNA) materials, we reviewed the cytologic material and corresponding histologic slides of 95 tumors in 71 patients. Forty-four (46%) tumors were primary, 38 (40%) were recurrent, and 13 (14%) were metastatic. Histological variants of MFH were as follows: 52 (54.7%, 43 patients) were of the storiform/pleomorphic, seven (7.4%, five patients) were giant cells, four (4.2%, four patients) were inflammatory, and 31 (33.7%, 19 patients) were myxoid type. Review of original cytology reports showed that only 23 (24.2%) tumors were diagnosed as MFH and 68 (71.6%) as other types of malignancies. Four (4.2%) cases were reported as unsatisfactory/suspicious. Our findings showed that spindle-shaped, round, giant cells, osteoclastic-like giant, and inflammatory cells were the most consistent features that allow identification of the storiform/pleomorphic, giant cell, and inflammatory variants of MFH. The myxoid tumors had marked myxoid background matrix with spindle-shaped cells and, less frequently, round and giant cells. Pleomorphic leiomyosarcoma and dedifferentiated liposarcoma should be considered in the differential diagnosis of stroriphorm/pleomorphic, giant cells, and inflammatory variants of MFH. However, myxoid MFH may resemble their leiomyosarcoma and liposarcoma counterparts.