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.

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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.

SummaryThe expression of laminin and fibronectin isoforms varies with cellular maturation and differentiation and these differences may well influence cellular processes such as adhesion and motility. The basement membrane (BM) of fetal oral squamous epithelium contains the laminin chains, α2, α3, α5, β1, β2, β3, γ1 and γ2. The BM of adult normal oral squamous epithelium comprises the laminin chains, α3, α5, β1, β3, γ1 and γ2. A re-expression of the laminin α2 and β2 chains could be shown in adult hyperproliferative, dysplastic and carcinomatous lesions.In dysplasia and oral squamous cell carcinoma (OSCC), multifocal breaks of the BM are present as indicated by laminin chain antibodies. These breaks correlate to malignancy grade in their extent. Moreover, in the invasion front the α3 and γ2 chain of laminin-5 can immunohistochemically be found outside the BM within the cytoplasm of budding carcinoma cells and in the adjacent stroma. The correlation between the morphological pattern of invasive tumour clusters and a laminin-5 immunostaining in the adjacent stroma may suggest, first, that a laminin-5 deposition outside the BM is an immunohistochemical marker for invasion and second, that OSCC invasion is guided by the laminin-5 matrix. Expression of oncofetal fibronectins (IIICS de novo glycosylated fibronectin and ED-B fibronectin) could be demonstrated throughout the stromal compartment. However, the ED-B fibronectin synthesizing cells (RNA/RNA in situ hybridization) are confined to small stroma areas and to single stroma and inflammatory cells in the invasion front. A correlation of the number of ED-B fibronectin synthesizing cells to malignancy grade could not be seen. ED-B fibronectin mRNA-positive cells seem to be concentrated in areas of fibrous stroma recruitment with a linear alignment of stromal fibro-/myofibroblasts (desmoplasia). Double staining experiments (ED-B fibronectin in situ hybridization and α-smooth muscle actin immunohistochemistry) indicated that the stroma myofibroblasts are a preferential source of ED-B fibronectin. In conclusion, in OSCC, a fetal extracellular matrix conversion is demonstrable. Tumour cells (laminin α2 and β2 chain) and recruited stromal myofibroblasts (oncofetal ED-B fibronectin) contribute to the fetal extracellular matrix milieu.

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.

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 ...

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.

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