[Histological classification of soft tissue tumors and staging according to the TNM system]. / Histologische Klassifikation von Weichgewebstumoren und Stadieneinteilung gemäß TNM-System.

The classification of soft tissue tumors is based on their resemblance to normal non-neoplastic tissues and provides an indication of how the tumor will behave in the further disease course. The current article presents the principles to be considered when classifying tumors into categories and discusses additional findings to be taken into account in the diagnosis. The importance of considering combinations of findings when classifying a tumor is underscored; individual (in particular immunohistochemical) findings can be misleading. A statement on the grade of malignancy of a soft tissue tumor requires its identification as a known entity, otherwise incorrect prediction of its biological behaviour is possible. The category of "intermediate malignancy" has been added to the categories of "benign" and "malignant", whereby locally aggressive and incidentally metastasizing tumors have been included in this new category. The staging of soft tissue tumors according to the TNM system is explained, emphasizing that one important feature compared with carcinomas is the inclusion of depth localisation and grade of malignancy.

[Update from the soft tissue tumour registry in Jena]. / Neues aus dem Jenaer Weichteiltumor-Register.

The Jena Institute of Pathology has been serving as a consultation and reference center for soft tissue tumors in Germany since 1978. The present study provides an overview of the clinicopathological data from a two-year period and an update on diagnostics and research. Retrospectively, 7043 cases sent to the institute in the years 2006 and 2007 were analyzed. The majority of cases (>77.7%) were soft tissue tumors, of which 49% were categorized as malignant, 11.4% as intermediate, 35% as benign and 4.6% as tumors of uncertain biological potential. Neoplasms with fibroblastic differentiation were the most frequent. The mean age of patients with a sarcoma was 63 years. The molecular pathological analysis of soft tissue tumors has attained a major role in diagnosis. This is further advanced at the Jena institute in the context of a German Federal Ministry of Education and Research (BMBF) project for molecular sarcoma diagnosis with the aim of developing and validating DNA probes for in situ hybridization detection of translocations and their associated chromosomal breaks on the one hand, and DNA chips for the detection of fusion transcripts on the other. Research projects relate to the analysis of specific biomarkers in large tumor collectives and the pathomechanisms in several sarcoma entities.

[Solitary fibrous tumor and haemangiopericytoma: what is new?]. / Solitärer fibröser Tumor und Hämangioperizytom : Was ist neu?

Soft-tissue tumors with haemangiopericytoma (HPC)-like growth patterns can now be divided into three categories: (1) The solitary fibrous tumour (SFT) group with its variants; (2) lesions showing clear evidence of myoid/pericytic differentiation and corresponding to "true" HPCs (myopericytoma/glomangiopericytoma and a subset of sinonasal HPCs); (3) neoplasms that occasionally display HPC-like features (e.g. synovial sarcoma). In this study 268 intrathoracic and extrathoracic SFTs from the German consultation and reference center of soft tissue tumors in Jena were evaluated and analyzed immunohistochemically with antibodies CD34, Bcl-2, CD99, SMA, S100, PanCK and Ki-67. Furthermore, SFTs were categorized into the newly proposed SFT designation: Fibrous variant, cellular variant (more than 90% hypercellularity), fat-forming variant, giant cell-rich variant and malignant SFTs. This article should provide insights into the diagnosis of this entity with emphasis on the new international standard.

Hibernoma-like brown fat in the bone marrow: report of a unique case.

We report on a bone-marrow biopsy of a 61-year-old female patient that was performed because of the clinical suspicion of a myeloproliferative disease. The trephine biopsy showed morphological features that were consistent with an essential thrombocythaemia (ET). The diagnosis of a myeloproliferative disease could be corroborated by demonstration of the V617F mutation of JAK2. Besides the histological features of ET, the marrow showed a peculiar infiltrate that consisted of multivacuolated cells that were immunohistochemically identified as brown adipose tissue with a hibernoma-like picture. To the best of our knowledge, this is the first report on brown adipose tissue in the bone marrow.

[Gastrointestinal stromal tumors. Diagnosis and estimating aggressiveness]. / Gastrointestinale Stromatumoren. Diagnose und Malignitätseinschätzung.

A diagnosis of gastrointestinal stromal tumor must be considered if a mesenchymal tumor is localized in the gastrointestinal tract, especially in the stomach. In daily practice diagnosis is based on the histology (cellular features and histologic architecture) and immunohistochemistry (cellular positivity with antibodies to CD117 and often to CD34). Expression of CD117 indicates the autoactivation of a type-III-receptor tyrosine kinase mediated by mutation of the KIT gene. This is lacking in the roughly 5% of cases which instead show a mutation of the PDGF receptor alpha gene. The estimation of dignity is difficult and can be uncertain in some cases. A malignancy grading according to the procedure in soft tissue tumors is not possible. Nowadays, however, the general consensus is that size of the tumor and number of mitoses are the most important criteria for appraising tumor aggressiveness and risk of metastasis. The tumor localization was later added to these criteria. Recent years have shown that mutation analysis can also provide information for judging tumor aggressiveness and predicting possible metastasis and response to therapy.

Primary breast cancer therapy in six regions of Germany.

Studies from six regions of Germany (Aachen (W1), Dresden (E1), Jena (E2), Marburg (W2), Munich (W3), and Stuttgart (C1)) have been compared to verify and assess the quality of healthcare using breast cancer as an example. All of the data collection was carried out in comprehensive cancer centres and is population-based, with the exception of C1. Classic prognostic factors and the initial treatment of 8661 women with breast cancer, diagnosed between 1996 and 1998, were examined. Primary therapy, breast conserving therapy (BCT), and the use of subsequent local radiation and/or systemic therapy (chemotherapy or hormonal therapy) were analysed. BCT was performed on 39.3-57.7% of patients. By pT-category, the proportion of BCT in the six regions were as follows: for pTis between 37.8 and 64.3%, for pT1 between 51.7 and 71.5%, for pT2 between 25.9 and 51.1%, for pT3 between 0 and 13.1% and for pT4 between 0 and 15.2%. Multivariate analyses, adjusted for age and biological factors, showed a significant influence of the treating hospital on the mastectomy rate. The use of radiotherapy after BCT (80%) was quite homogeneous in the six regions. The application of radiotherapy after mastectomy, however, varied between 10.4 and 32.2%. In all regions, for premenopausal patients, the use of adjuvant systemic therapy almost reflected the St. Gallen-Consensus recommendations. In contrast, post-menopausal women with positive lymph nodes were not always treated according to these standards. In all regions, age had an influence on the administration of treatment: elderly breast cancer patients received less BCT, less radiotherapy and less adjuvant therapy than recommended in the St. Gallen-Consensus. Feedback of the results was made available to each hospital, providing a comparative summary of patient care that could be used by the participating hospitals for self-assessment and quality-control.

Low-grade myofibroblastic sarcoma: analysis of 18 cases in the spectrum of myofibroblastic tumors.

The clinicopathologic, immunohistochemical, and ultrastructural features of a seemingly distinctive low-grade spindle cell sarcoma showing myofibroblastic differentiation have been analyzed in a series of 18 patients. The age range of the patients (7 women and 11 men) was 19-72 years (median: 42 years). A painless, enlarging mass was the most common clinical presentation. Five tumors arose in the oral cavity (including four lesions in the tongue), four in the lower extremities and three in the upper extremities, four cases in the abdominal/pelvic cavity, and two on the trunk. Eight soft-tissue cases involved skeletal muscle, three cases were located in perifascial tissues, and two arose in subcutaneous tissue. Tumor size ranged from 1.4 to 17 cm (median: 4 cm); in six cases (of which four were abdominal/pelvic) the lesion was larger than 5 cm. All patients were treated surgically, and four received additional adjunctive therapy. Histologically, most cases were cellular lesions showing a diffusely infiltrative pattern, and were composed of spindle-shaped tumor cells arranged mainly in fascicles. Tumor cells had poorly defined, palely eosinophilic cytoplasm and fusiform nuclei, which were either tapering and wavy or plumper and vesicular with indentations and small inconspicuous nucleoli. Tumor cells were set in a collagenous matrix often with prominent hyalinization. Mild nuclear atypia was noted in 16 cases; in the other 2 cases, and in the metastases of one other lesion, a greater degree of nuclear atypia was seen. In all but one case, the mitotic rate ranged from 1 to 6 mitoses in 10 HPFs (mean: 2/10 HPFs); in a single case, there were more than 20 mitoses in 10 HPFs. Immunohistochemically, all cases stained positively for at least one myogenic marker; 12 cases were positive for desmin, 11 for alpha-smooth muscle actin, and 6 for muscle actin (HHF35). Seven neoplasms were desmin positive/ alpha-smooth-muscle actin negative, and five cases were desmin negative/alpha-smooth-muscle actin positive emphasizing the variable immunophenotype of myofibroblastic lesions. In addition, 7 of 10 tumors stained at least focally positive for fibronectin. Ultrastructural examination in five cases showed characteristic features of myofibroblasts. Follow-up in 11 patients (median: 29 months) revealed local recurrence in 2 cases, and multiple distant soft-tissue, intraosseous, and pulmonary metastases in one other patient. Low-grade myofibroblastic sarcoma seems to represent a distinct entity in the spectrum of low-grade myofibroblastic neoplasms and is distinguishable from fibromatosis, myofibromatosis, solitary fibrous tumor, fibrosarcoma, and leiomyosarcoma.

Epithelioid hemangioendothelioma of skin and soft tissues: clinicopathologic and immunohistochemical study of 30 cases.

Epithelioid hemangioendothelioma of soft tissues (EHE) represents a distinct entity with an unpredictable clinical course. We analyzed the clinicopathologic and immunohistochemical features in a series of 30 patients. Patient age range was 16-74 years (median 50); 18 of 30 patients were female. Eight tumors arose in the lower and two in the upper extremities, seven on the trunk, five each in the head/ neck and anogenital regions, two in the mediastinum, and one in the abdomen. Seventeen neoplasms were located in deep soft tissues, nine were subcutaneous or perifascial, and four were dermal; size ranged from 0.4 to 10 cm; in 11 cases the tumor was > 5 cm. Tumors with an infiltrative growth pattern were more common than entirely circumscribed lesions. The tumors were composed histologically of short strands, cords, or small clusters of epithelioid, round, to slightly spindled endothelial cells that formed at least focally, intracellular lumina and were set in a frequently myxohyaline stroma. Thirteen of 30 lesions showed angiocentric growth, which was occlusive in many cases. Immunohistochemically, all cases tested were positive for at least one endothelial marker (CD31, CD34, factor VIII, Ulex europaeus), six of 23 (26%) were positive for cytokeratin, and five of 11 (45%) were positive for alpha-smooth muscle actin. Median follow-up of 36 months (range 2-96) in 24 cases showed local recurrence in three cases and systemic metastases in five cases (21%); four patients (17%) died of tumor. Although more aggressive histologic features (striking nuclear atypia in eight cases, numerous spindled cells in 10, more than two mitoses per 10 high-power fields in nine, and small, more solid angiosarcomalike foci in four cases) tended to be related to poor clinical outcome, there was no clear correlation. Two metastasizing cases showed no histologically atypical features whatever. We suggest that EHE of soft tissue is better regarded as a fully malignant, rather than borderline, vascular neoplasm, albeit the prognosis is better than in conventional angiosarcoma.

Fibrosarcomatous ("high-grade") dermatofibrosarcoma protuberans: clinicopathologic and immunohistochemical study of a series of 41 cases with emphasis on prognostic significance.

The fibrosarcomatous variant of dermatofibrosarcoma protuberans (FS-DFSP) represents an uncommon form of DFSP, in which the prognostic influence of the fibrosarcomatous component is still debated. We analyzed the clinicopathologic and immunohistochemical features in a series of 41 patients. Patient age ranged from 8 to 87 years (median, 48 years), and 19 patients were female. Twenty five lesions were seen on the trunk, 6 on the upper limbs, and 4 on the lower limbs, and five neoplasms were located in the head/neck region; in one case, exact anatomic site was unknown. Twenty seven tumors involved purely dermal and subcutaneous tissues, in 10 cases, deeper structures were also involved, 1 case arose in the breast, and, in 3 cases, it was impossible to define exact depth of the lesion. Preoperative duration ranged from 1 month to 60 years (median, 3 years). Twenty six tumors were excised locally with clear margins, 7 were treated by wide excision, 3 by incomplete excision, and, in 4 patients, the lesion was shelled out. In one case, exact treatment was unknown. In addition, radiotherapy was administered in three cases and chemotherapy in one case. Histologically, the lesions showed areas of typical, low-grade DFSP adjacent to fibrosarcomatous areas. In four cases, a previously ordinary DFSP recurred as pure fibrosarcoma, in two cases, local recurrence of FS-DFSP showed features of ordinary DFSP. Fibrosarcomatous change was more common in the primary (de novo) lesions than in recurrent lesions (3.6:1). Proportion of fibrosarcoma varied between < 30% in 6 cases to > 70% of tumor tissue in 21 cases. An abrupt transition between both components was seen in 19 cases. The fibrosarcomatous component showed focal necrosis in seven cases and showed a higher mitotic rate in comparison with ordinary DFSP areas (mean, 13.4 versus 2.3 mitoses in 10 high-power fields). Additional histologic features included progression to pleomorphic sarcoma in 2 recurrent cases, melanin-pigmented cells (Bednar FS-DFSP) in 1 case, focal myxoid change in 13 cases, plaque or keloidlike hyalinization in 3 cases, and myoid bundles and nodules in 9 cases. Immunohistochemically, tumor cells in DFSP areas stained positively for CD34, whereas, in FS-DFSP areas, only 15 out 33 cases were positive for CD34. Follow-up in 34 of 41 patients (mean, 90 months; median, 36 months) revealed local recurrence in 20 patients (58%) (recurrence occurred in 5 patients on two or more occasions). Metastases (5 lung, 1 bone, and 1 soft tissue) were seen in 5 patients (14.7%), and 2 patients have died of tumor to date (5.8%). Necrosis, high mitotic rate (> 10 mitoses per 10 high-power fields), and presence of pleomorphic areas in FS-DFSP tended to be related with poor clinical outcome, but no statistically significant association was detected. Fibrosarcomatous change in DFSP represents a form of tumor progression in DFSP and is associated with a significantly more aggressive clinical course than in ordinary DFSP, indicating a possible need for treatment intensification in such cases.

Solitary fibrous tumor of urinary bladder: report of two cases.

The clinical and pathologic features of two cases of solitary fibrous tumor arising from urinary bladder wall are described. To our knowledge, solitary fibrous tumors have not been previously reported at this site. Both tumors showed typical histologic features of solitary fibrous tumor, were CD34 immunostain positive and pursued a benign clinical course on short term follow-up.

The impact of comorbidity on the survival of postmenopausal women with breast cancer.

PURPOSE: The aim was to assess the impact of comorbidity on survival of postmenopausal women with breast cancer diagnosis in the period 1995-1997. METHODS: The level of comorbidity was described by the methods suggested by Satariano and Charlson. Cox's proportional hazard models were used to explore the impact of comorbidity on all-cause mortality. RESULTS: After a median follow-up time of 52 months, an increasing level of comorbidity was associated with a higher all-cause mortality. Compared to patients with-out comorbid conditions, the hazard ration of death (HR) was 1.2 (95% CI: 0.8-1.7) for Satariano index 1 and HR 2.3 (95% CI: 1.5-3.5) for Satariano index >or=2, and HR 1.6 and 2.1 for the Charlson comorbidity index, respectively. Independent of comorbidity, the treatment pattern had a strong impact on survival. The level of comorbidity has an influence on the 3-year survival of postmenopausal women with breast cancer. CONCLUSIONS: Long-term follow-up is required to appraise these findings in relation to treatment strategies.

A population-based study on variations in the use of adjuvant systemic therapy on postmenopausal patients with early stage breast cancer.

PURPOSE: To assess adherence to treatment recommendations regarding adjuvant systemic therapy of postmenopausal patients with early stage breast cancer. METHODS: A population-based cohort of women from Eastern Thuringia/Germany with first diagnosis of breast cancer in 1995-2000 was studied. The use of adjuvant therapy was assessed separately for patients with positive and negative nodal status fitting polytomous logistic regression models. RESULTS: Among 396 women with positive lymph nodes and 832 with negative lymph nodes, 92.9% and 87.3% received an adjuvant systemic treatment, respectively. Age, comorbidity, hormone receptor status, histological grading, and additionally, in nodal positives, the number of involved lymph nodes, were associated with treatment patterns. Age had the strongest impact on treatment decision. Older women more often received hormone- or no adjuvant therapy. However, 26.3% of the women with lymph node involvement and positive hormone receptor status received no hormone therapy, whereas 35.7% of women with negative hormone receptor status received hormone therapy. CONCLUSION: The number of patients with adjuvant systemic therapy is high in women with positive and those with negative lymph nodes, reflecting adherence to the recommendations. Better outcome could be expected if hormone therapy was used adequately in receptor positives. Further follow-up is required to monitor the outcome and changes in adherence to treatment recommendations.

Evaluation of microvessel density by computerised image analysis in human renal cell carcinoma. Correlation to pT category, nuclear grade, proliferative activity and occurrence of metastasis.

A high microvessel density is suspected to favour tumour progression and the occurrence of metastasis. To elucidate the significance of abundant vessels for the behaviour of human renal carcinomas, the microvessel density of 110 renal cell carcinomas was correlated to pT category, nuclear grade, proliferative activity, occurrence of metastasis and relapse-free survival interval. The microvessels were quantified using CD31 immunostaining of endothelial cells and computer-aided image analysis. The rules for reproducible microvessel counting, as defined by Weidner, were strictly observed. A statistically significant relationship between the microvessel density and nuclear grade, proliferative activity, occurrence of metastasis and relapse-free survival was found; only for tumour size could no such relation be seen. Perplexingly, there is a diminution of microvessel density in association with increasing nuclear grade, proliferative activity, relapse-free survival interval and frequency of metastasis. This finding is contradictory to the hypothesis that an increasing microvessel density indicates a worsening prognosis.

Programmed cell death in nodular palmar fibromatosis (Morbus Dupuytren).

The regular loss of cellularity during involutional phase of nodular palmar fibromatosis (Morbus Dupuytren) indicates a regulated process known as programmed cell death (apoptosis). Using the TUNEL method apoptosis-related DNA fragmentation is detected in numerous cells as a characteristic feature of fibromatosis noduli of involutional phase. By means of double labelling technique, alpha-smooth muscle actin immunohistochemistry and TUNEL method for apoptosis, it is demonstrated that the cells which underwent apoptotosis are myofibroblasts. As anticipated, the antidote to apoptosis bcl-2 is not detected in involutional phase, but neither it is evidenced in proliferative phase. Immunohistochemically, Fas/APO-1 is shown to be existent in a very small number of fibroblasts in involutional phase. However, in view of the high number of TUNEL-stained cells a significance in regulating apoptosis in nodular palmar fibromatosis seems improbable. Taking into account that the development of the fibromatosis noduli, the expression of myofibroblast phenotype, basement membrane formation and growth factor expression including TGF beta culminates in involutional phase the initiation of apoptotic cell death can be discussed in relation to these growth factors and matrix protein action and the programmed cell death may be considered as the final step of myofibroblast phenotype evolution.

Laminin matrix formation and S-100 protein and/or desmin-positive cells in malignant fibrous histiocytoma (MFH).

16/30 human storiform-pleomorphic malignant fibrous histiocytomas (MFH) showed a focal pericellular immunostaining for laminin. 14/16 of these laminin-positive tumours additionally revealed an atypical cellular differentiation (desmin- and/or S-100 protein-positive cells). The significance of focal laminin positivity along with atypical, non-entity specific differentiated cells is discussed before the background of laminin as being an indicator and promoter of differentiation in MFH. The limited value of a laminin detection in MFH for solving differential diagnostic questions (MFH versus other poorly differentiated sarcomas with basement membrane formation) has been pointed out.

Sclerosing, pseudovascular rhabdomyosarcoma in adults. Clinicopathological and immunohistochemical analysis of three cases.

Rhabdomyosarcoma in adults represents a rare soft tissue neoplasm which is seen most frequently in its pleomorphic subtype in this age group. Very rarely, clear cell and spindle-cell variants have been reported. In this study we describe three cases of rhabdomyosarcoma in adult patients, characterised by prominent hyaline sclerosis and a pseudovascular growth pattern. All cases were identified in the consultation files of one of the authors and routinely processed. Immunohistochemical studies were performed on paraffin sections with the alkaline phosphatase-antialkaline phosphatase method. The patients, two women and one man, were 40, 41, and 56 years old. One developed a deep-seated soft tissue mass in the left lower leg, and one, a tumour of the left upper jaw. In one patient a bone tumour in the proximal body of the sacrum without extension into soft tissues was seen. The patients were treated by wide excision, piecemeal excision and incomplete excision in one case each; additional radiotherapy was performed in all three cases, and chemotherapy in two patients. In one patient multiple pulmonary metastases were noted, which showed progression despite systemic chemotherapy. Histologically, the neoplasms were composed of round/polygonal and spindle-shaped tumour cells including typical rhabdomyoblasts. In all cases a pseudovascular pattern and prominent hyaline sclerosis of the intercellular matrix was seen. Immunohistochemically, tumour cells stained positively for desmin and muscle actin (HHF35) and also for markers of striated muscle differentiation (myogenin, MyoD1, fast myosin). In this paper an unusual morphological variant of rhabdomyosarcoma arising in adult patients is described, which should be added to the morphological spectrum of these neoplasms.

Molecular variants of fibronectin and laminin: structure, physiological occurrence and histopathological aspects.

This review deals with biological and pathological aspects of various isoforms of the matrix molecules fibronectin and laminin. They are generated by different molecular mechanisms: ED-A+ and ED-B+ fibronectin by alternative splicing of pre mRNA, de novo-glycosylated fibronectin by alternative post-translational O-linked glycosylation of the IIICS region, and the laminin isoforms by exchange of single chains of the heterotrimeric molecule. In contrast to the "common" fibronectin, the distribution of ED-B+ and de novo-glycosylated fibronectin is restricted to embryonic tissues; they subsequently reappear in granulation tissue, in fibrosing processes and in tumour stroma. The expression of these so-called oncofetal fibronectins is stimulated by growth factors (TGF beta). The association of the ED-B+ fibronectin with proliferative activity and newly formed vessels identifies this fibronectin variant as a marker of cellular activity in the process of fibrosis and as a suitable agent for the evaluation of tumour angioneogenesis. Initial results suggest a correlation between the amount of ED-B+ and de novo-glycosylated fibronectin in tumour stroma and the behaviour of carcinomas with regard to their invasiveness and propensity for metastatic dissemination. The current nomenclature of the laminin molecule family is presented. The laminin chain constitution of basement membranes switches from embryonic or proliferatively active to adult terminally differentiated tissues [disappearance of the laminin beta 2 (s) chain] and depends on the tissue type. The discrepancy between the loss of basement membranes (multiple basement membrane defects) in carcinomas and the recently reported increased laminin chain synthesis in these tumours may be explained by abundant laminin chain deposition outside the basement membrane in the carcinoma invasion front, possibly associated with enhanced adhesion of budding tumour cells.

Solitary fibrous tumour: clinicopathological, immunohistochemical, and ultrastructural analysis of 12 cases arising in soft tissues, nasal cavity and nasopharynx, urinary bladder and prostate.

The clinicopathological features of 12 extraserosal solitary fibrous tumours (SFT) are described. The age of the patients ranged from 18 to 72 years (mean: 48.2 years; median: 54 years); 5 were female patients. Seven lesions arose in soft tissue (5 in perifascial, and 1 each in subcutaneous and intramuscular tissues). They were situated in the groin (2 cases) and the neck, right buttock, left scapula, upper arm, and anterior abdominal wall (1 case each). One polypoid lesion was seen in in the nasal cavity and 1 in the nasopharynx; 2 neoplasms arose in the urinary bladder and 1 was located in the prostate and periprostatic tissue. Nine lesions were excised; in 1 patient wide excision was performed and in 2 patients, transurethral resection. Limited follow-up of 3 cases revealed a benign clinical course. The size of the neoplasms ranged from 1.7 cm to 20.0 cm (mean: 5.4 cm; median: 3.5 cm). Histologically, the neoplasms were well circumscribed and composed of cytologically bland spindle cells arranged without an obvious pattern; focally storiform or fascicular growth patterns were seen. Tumour cells were separated by thick bands of collagen demonstrating foci of keloid-like hyalinization. Prominent vascularity showing a haemangiopericytoma-like vascular pattern and vessels with thick, hyalinized vessel walls were seen in all cases. Increased mitotic activity was noted in 2 soft tissue cases (4-6 mitoses in 10 high-power fields); the other cases showed fewer than 2 mitotic figures in 10 highpower fields. Immunohistochemically, all cases tested stained positively for vimentin, CD34 and CD99, and 2 cases showed focal myofibroblastic differentiation. Two cases examined ultrastructurally showed a fibroblastic phenotype; focally pinocytic vesicles and microfilaments were identified. SFT represents a distinct neoplasm that should be included in the differential diagnosis of spindle-cell neoplasms in soft tissue, nasal cavity and nasopharynx, urinary bladder, and prostate. Strict diagnostic criteria are necessary to avoid overdiagnosis or confusion with more aggressive neoplasms in these locations.

Intravascular ("intimal") epithelioid angiosarcoma: clinicopathological and immunohistochemical analysis of three cases.

Angiosarcomas are rare malignant mesenchymal tumours, characterized morphologically by anastomosing vascular channels lined by atypical and proliferative active endothelial cells. An epithelioid cytomorphology of tumour cells is often seen focally in angiosarcoma, whereas purely epithelioid angiosarcomas are rare. Although angiosarcomas show a vascular differentiation they are almost never confined to pre-existing blood vessels. We describe three cases of intravascular epithelioid angiosarcoma arising in the carotid artery of a 60-year-old man, in the infrarenal part of the abdominal aorta and both renal arteries of a 69-year-old woman, and in the abdominal aorta of a 68-year-old man. In all cases malignant tumour tissue was found incidentally after disobliteration of thrombosed vessels. Histologically, purely epithelioid angiosarcoma composed of solid sheets of epithelioid tumour cells was seen; immunohistochemistry confirmed the endothelial differentiation of neoplastic cells. The reported cases show that angiosarcoma can occasionally arise within a pre-existing vessel.

New developments in the pathology of skull base tumors.

As an anatomical interface between various tissues, the skull base harbors an exceptionally broad variety of neoplasms, some of which pose a major challenge for surgical pathology. The characterization of distinct immunohistochemical expression profiles and the identification of molecular genetic alterations associated with different tumor entities have significantly advanced this field. The new World Health Organization (WHO) classification of tumors of the nervous system lists 15 histopathological variants of meningioma. Of clinical importance are those entities that carry an increased risk of recurrence and a poor prognosis, i.e., the atypical meningioma (WHO grade II), clear-cell meningioma (WHO grade II), chordoid meningioma (WHO grade II), rhabdoid meningioma (WHO grade III), papillary meningioma (WHO grade III), and anaplastic meningioma (WHO grade III). Diagnostic criteria for atypical and anaplastic meningioma variants have now been stringently defined. The differential diagnosis of meningiomas includes hemangiopericytoma, hemangioblastoma, solitary fibrous tumor, sarcomas, and chordoid neoplasms. Recent data highlight the importance of distinguishing chordoma and chondrosarcoma of the skull base since chondrosarcomas show a significantly better clinical outcome. Among the less common, aggressive tumor entities in this anatomical region, infiltrating pituitary adenoma/pituitary carcinoma, superficial malignant gliomas, rhabdomyosarcoma, olfactory neuroblastoma, various sarcomas, and malignant lymphoma must be considered. Profiles of molecular genetic alterations have been established for several of these neoplasms and may facilitate the differential diagnosis. This review summarizes recent developments in the histopathological characterization, classification, and molecular pathology of neoplasms arising at the skull base.