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Angiosarcoma is a very rare vascular neoplasm, comprising less than 1% of all sarcomas. Involvement of the bone marrow is distinctly uncommon and almost invariably seen in patients with disseminated disease. Primary angiosarcoma of the bone/bone marrow, however, is extremely rare and, to the best of the authors knowledge, has not been reported to be diagnosed in a trephine biopsy.1
A 77-year-old woman presented with acute back pain. A mastectomy had been performed for carcinoma of the left breast 16 years previously. Her past medical history was otherwise unremarkable. On physical examination, the patient showed hemisensory loss of the left leg. MRI and radionuclide bone scan revealed a large tumour mass and a pathological fracture of the left iliac bone. A trephine biopsy was removed from the left iliac crest for histological confirmation of a suspected bone marrow carcinosis. The biopsy disclosed sheets of large pleomorphic tumour cells almost completely replacing the normal bone marrow architecture (fig 1). The tumour cells were found to be round to ovoid with pleomorphic nuclei and prominent nucleoli. The main growth pattern of the tumour was solid and only partly tubular. Focally, the tumour was composed of irregular channel-like spaces lined by epithelioid tumour cells (fig 1).
Immunohistochemical investigations revealed that neoplastic cells strongly expressed vimentin and CD31 (fig 2), while expression of other endothelial-related markers like CD34 and FVIII-related antigen was much less intensive. Moreover, the tumour cells were found to react strongly with antibodies against vascular endothelial growth factor (VEGF) and mast cell chymase (fig 2). The tumour cells did not express detectable amounts of CD25, KIT protein (CD117), and mast cell tryptase. Epithelial (EMA, TTF1, KL-1) and lymphocytic (CD5, CD10, CD20, CD23, CD30, and CD79), antigens were absent. Based on this unusual immunophenotype, the diagnosis of an angiosarcoma of bone marrow was established.
Primary angiosarcoma of the bone represents a challenging diagnosis in bone marrow biopsies, especially in poorly vasoformative tumours, as in the present case.2 The differential diagnosis includes a variety of neoplasms ranging from undifferentiated large-cell carcinoma and other subtypes of sarcoma to malignant melanoma and blastic haematopoietic neoplasms.
Expression of VEGF in angiosarcomas has been reported previously.3 The strong expression of chymase—as in our case—has yet not been demonstrated in this tumour. Therefore, we examined tissue samples from five archival cases of angiosarcoma and found expression of chymase in three of them.
Functional properties of the serine protease chymase, which is expressed in normal/reactive mast cells, are not fully elucidated. In endothelial cells, chymase may play an important role in the development of vascular proliferation via induction of angiotensin II formation.4 Moreover, it has been suggested that chymase could mediate apoptosis in smooth muscle cells through a mechanism involving degradation of pericellular fibronectin and disruption of focal adhesions.5
In conclusion, it may be speculated that chymase might play a role in the tumourigenesis of angiosarcoma and could be added as a marker in the immunohistochemical investigation of these rare malignancies.
Competing interests: None declared.