ANGIOSARCOMA –STILL A DIAGNOSTIC AND THERAPEUTIC CHALLENGE

Pia Kleimann, Johannes Kleemann, Katharina Assmus, Eva Valesky, Markus Meissner, Roland Kaufmann

Department of Dermatology, Venerology and Allergy, University Hospital Frankfurt, Germany

Case presentation:

A 78-year old female Caucasian presented in our outpatient clinic with a fast growing nodule on the head. She reported occasional bleeding within the last month, therefore she had been treated several times with punctures and local wound management. There was no history of initial trauma.

On physical examination we found a soft, skin colored, ulcerated nodule, measuring 2 x 3 cm, with a blue-livid macule on the dorsal edge. No other pathological findings could be observed.

Diagnostic work up, treatment and outcome

Clinically the rapidly progressive and repetitively bleeding lesion was suspicious of a vascular proliferation. A punch biopsy confirmed on histological examination multiple vessel-like formations consisting of endothelium-like pleomorphic cells with prominent nucleoli. The cells were highly atypical and showed multiple mitoses. This histomorphological pattern is consistent with the diagnosis of angiosarcoma. Additional immunohistochemical stainings were positive for CD31 and CD34 which confirmed the diagnosis (Figure 1). 

         

Figure 1: Dermatohistological findings. Left: H/E staining shows multiple vessel-like formations with pleomorphic cells, consistent with the diagnosis of angiosarcoma. Right: Immunohistochemistry shows CD31 positive cells.

Initial staging including sonography of the regional lymph nodes, cerebral MRI and abdominal and thoracic CT scans showed no sign of metastasis so that a surgical treatment was recommended. Micrographically controlled excision was performed. After several re-excisions, R0 status could be reached. The result was a large tissue defect (Figure 2). Wound granulation was induced by trepanation of the outer table of the skull, followed by Vacuum-assisted closure (VAC) therapy. After sufficient granulation the wound was finally closed by mesh graft transplantation. Adjuvant radiotherapy was not performed due to the patient’s preferences. Six weeks later the patient developed severe dyspnea. Emergency CT scans showed multiple metastases in the liver, spleen and lung with marked pleural effusion.

The patient did not wish for any further therapies. Best supportive care was provided. The patient died within two months after initial diagnosis.

 

Figure 2: A Clinical presentation before surgery. B Surgical defect after complete resection.

Key message:

Angiosarcoma is a rare, highly malignant tumor with very poor prognosis. The disease is often diagnosed late due to the lack of symptoms in initial stages. 20-40% of patients are already metastasized by the time of initial diagnosis (1). For treatment micrographically controlled R0 resection should be pursued if possible. Discrepancies between the clinical and the histological extension are often observed. This can be explained by multifocal growth and the occurrence of skip lesions. Adjuvant radiotherapy can be recommended to reduce the risk of local recurrence (2). Among potential alternatives we reported about a successful combined use of interferon alfa-2a and 13-cis-retinoic acid following a recurrence after radiotherapy (3) In metastatic stages several palliative chemotherapies (including anthracycline-, ifosfamid- and taxane based regimes) are used with disappointing results (4). Based on this situation there is a strong need for new therapies. Multiple clinical trials for targeted therapies including VEGF and mTOR signaling pathways are ongoing. In this rare tumor entity participation in clinical trials should be encouraged.

References:

  1. Dossett LA, Harrington M, Cruse CW et al.: Cutaneous angiosarcoma. Curr ProblCancer 2015;39: 258–263
  2. Scott MT, Portnow LH, Morris CG et al.: Radiation Therapy for Angiosarcoma The 35 year University of Florida Experience. Am J Clin Oncol 2013;36:174–180
  3. Spieth K, Gille J, Kaufmann R. Therapeutic efficacy of interferon alfa-2a and 13-cis-retinoic acid in recurrent angiosarcoma of the head. Arch Dermatol. 1999;135:1035-7.
  4. Penel N, Bui BN, Bay JO, et al.: Phase II trial of weekly paclitaxel for unresectable angiosarcoma: the ANGIOTAX Study J Clin Oncol, 2008;26: 5269–5274