Several authors have already emphasized the histopathologic similarity of ASCC and angiosarcoma. [10
]. Although the WHO defines ASCC as an original entity for a long time [4
], there are less than thirty cases of ASCCs documented in the international literature so far [7
]. Both entities may have an association to previous exposal to ionizing radiation [9
]. To determine differential diagnosis and to differentiate ASCC from angiosarcoma an immunohistochemical typing is required regularly, because the epidermoid differentiation may be extremely masked by pseudovascular proliferation. Dyskeratoses may represent a rare pattern in ASCC. The immunohistochemical analysis has to consider on the one side that in soft tissue tumour angiosarcoma cytokeratin-positive cells may appear and on the other side that the plentiful vessels in the tumour stroma of ASCC are signed by endoepithelial differential markers, so that the classic discriminating differential markers cytokeratin, factor VIII-associated antigen and others are often difficult to be interpreted. [15
]. The Fli-1-protein, a member of the ETS family of DNA-binding transcription factors was recently highlighted as a new vascular differentiation marker [18
]. Although Fli-1 can be also rarely identified in carcinomas [20
], ASCC is immunonegative for this marker, so that Fli-1 can be recommended to discriminate between Angiosarcoma and ASCC.
The incomplete border of pericytes represents an accepted feature for identifying differentiation disturbed neoplastic vessels of angiosarcoma. The pericytes are emphasized by α-smooth-muscle-actin [6
]. However the incomplete border of pericytes in structures of angiosarcoma is not suitable for discriminating angiosarcoma versus ASCC, because in ASCC α-smooth-muscle-stromamyofibroblasts may mimic the pattern of pericytes lining discontinuously the slit-like tumour-spaces.
Interestingly in angiosarcoma ln-5 positive basal membranes were recognised. Ln-5 is a characteristic protein of epithelial basal membranes that is regularly identified in oral mucosa and in oral squamous cell carinoma [21
]. It connects the basal membrane with the hemidesmosomes of epithelial cells and has not been described in mesenchymal basal membranes so far. Because in angiosarcoma in contrast to ASCC no cytoplasmatic marking as a sign of synthesis of ln-5-γ2-chain could be made out and because ln-5 was only identified in parts of angiosarcoma localized next to preexisting oral epithelia, it is suggested, that ln-5 of the new formed basal membranes of angiosarcoma comes from the neighbouring preexisting epithelial structures and has only been integrated into the new formed basal membranes of angiosarcoma.
The cytoplasmatic ln-5 detection of ASCC cells presents on the one hand a distinguishing feature between ASCC and angiosarcoma and on the other hand a tumour biological indicator of the unfavourable prognosis of ASCC.
An abundant detection of γ2-chain of ln-5 in carcinoma cells is correspondingly accepted in literature as an unfavourable prognostic pattern. The extracellular matrix protein stimulates invasion of carcinoma cells [22
]. Hlubek and co-workers identified 2001 β-catenin as a transcription-factor of laminin-γ2-chain [25
]. The membrane-localized β-catenin-E-cadherin-complex mediates the cell-cell-adhesion, that is obviously disturbed in ASCC and that is responsible for forming of the typical intercellular spaces [13
]. In case of a disturbed forming of β-catenin-E-cadherin-complex at the carcinoma cell membrane β-catenin liberated from cell membrane is able to migrate into the cell nucleus, to act as a transcription-factor and to induce an overexpression of invasion-factor laminin-γ2-chain in ASCC.
The reduced cell-cell-adhesion and the extremely increased expression of laminin-γ2-chain are suggested as cell biological reasons for the extreme early distant metastasising of ASCC during therapy.
In summary angiosarcoma and ASCC do not only share identical clinical features and a similar histopathological pattern in common histological staining but also show overlaps of cytokeratin-expression and of expression of vascular differential markers. Expression of Fli-1 in angiosarcoma and cytoplasmatic immunoreaction for γ2-chain of ln-5 in ASCC are worked out as distinguishing features of both entities.