Year : 2008 | Volume
: 51 | Issue : 4 | Page : 504--506
Cutaneous angiosarcoma in a patient with xeroderma pigmentosum
Raman Arora, Alok Sharma, Ruchika Gupta, M Vijayaraghavan
Department of Pathology, All India Institute of Medical Sciences, New Delhi 110 029, India
Department of Pathology, All India Institute of Medical Sciences, New Delhi 110 029
Xeroderma pigmentosum (XP) is a rare, autosomal recessive disorder characterized by photosensitivity, cutaneous pigmentary changes, premature skin ageing and development of various cutaneous and internal malignancies at an early age as a result of a defect in nucleotide excision repair following ultraviolet light exposure. Cutaneous angiosarcomas are aggressive neoplasms that are rarely associated with XP. In this communication, we report the case of a 40-year-old male patient with XP who developed an angiosarcoma of the face and discuss the implications of this association in view of recent developments in this field.
|How to cite this article:|
Arora R, Sharma A, Gupta R, Vijayaraghavan M. Cutaneous angiosarcoma in a patient with xeroderma pigmentosum.Indian J Pathol Microbiol 2008;51:504-506
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Arora R, Sharma A, Gupta R, Vijayaraghavan M. Cutaneous angiosarcoma in a patient with xeroderma pigmentosum. Indian J Pathol Microbiol [serial online] 2008 [cited 2020 May 28 ];51:504-506
Available from: http://www.ijpmonline.org/text.asp?2008/51/4/504/43741
Xeroderma pigmentosum (XP) is a rare, genetically heterogeneous, autosomal recessive disorder characterized by photosensitivity, cutaneous pigmentary changes, premature skin ageing, and the development of various cutaneous and internal malignancies at an early age. The basic defect underlying the clinical manifestations is a nucleotide excision repair (NER) defect leading to the defective repair of DNA damaged by ultraviolet (UV) radiation.  In addition, these patients also exhibit enhanced sensitivity to ionizing radiation. ,
Cutaneous angiosarcomas are aggressive neoplasms that arise in three distinct clinical settings: 1) sporadic (involving face, scalp, and neck regions of elderly patients), 2) following long-standing lymphedema, and 3) post-irradiation. Although patients with XP develop several cutaneous malignancies during the course of their disease, cutaneous angiosarcomas are extremely rare and only four previous cases have been described in literature. ,,,
A 40-year-old male presented with a papulonodular lesion on the lateral aspect of the right eyebrow of 7 months duration and a sudden increase in size and redness of the lesion over the last 1 week. He had already been diagnosed with Xeroderma pigmentosum with a proven defect in the NER on cultured skin fibroblasts, diagnosed at 16 years of age and had been on follow-up since then. There was no history of consanguinity in the family. There was no evidence of exposure to radiation. His viral serology markers including HIV were negative. He suffered from a biopsy-proven malignant melanoma of the forearm (AJCC stage 1B: T2a N0M0), which was diagnosed 5 years earlier and was treated with wide local excision. On examination, a reddish papulonodular lesion measuring about 2x1.5 cm was seen near the lateral aspect of the right eyebrow. There was no regional lymphadenopathy. Routine laboratory investigations were within normal limits. A work-up for metastatic deposits was negative. With the clinical diagnosis of a malignant melanoma, a wide local excision of the lesion was performed.
A histopathological examination of the excised lesion revealed a skin-covered vasoformative tumor in the dermis composed of intercommunicating vascular channels [Figure 1]. These were lined by large hyperchromatic, markedly pleomorphic tumor cells with a high mitotic rate [Figure 2]. Immunohistochemically, the tumor cells were positive for CD 34, CD 31 [Figure 3], vimentin and negative for cytokeratin, HMB 45, S100, and Factor VIII-related antigen. Margins of the excised lesion were free from tumor. A final diagnosis of cutaneous angiosarcoma of the face was thus rendered. The patient is currently well 1 year after the diagnosis of angiosarcoma.
XP is a rare disease with an estimated annual incidence of about 1 case per 250,000 in the U.S. The disease is transmitted in an autosomal recessive manner. A history of consanguinity may be elicited in about 30% of the cases. 
The pathophysiology and genetic basis of XP is complex. UV radiation elicits the formation of pyrimidine-dimers of adjoining thymidine residues in the same DNA strand. Normally, excision of these dimers occurs either by a process of NER or photoactivation. The majority of patients with XP have defects in one of the seven genetically distinct NER genes referred to as complementation groups A-G. This leads to increased cellular susceptibility to UV induced killing, and genetic instability leading to mutations. In addition, about 20% of the patients have normal NER but have a faulty post replication repair mechanism due to a defect in the DNA polymerase (XP variant). Although several cutaneous and internal malignancies occur frequently in patients with XP, cutaneous angiosarcomas have rarely been reported. ,,, This association was first reported by Leake, et al.  and since then only three more cases have been described in literature [Table 1]. ,, Cutaneous angiosarcomas are rare and account for only about 1% of all malignant mesenchymal tumors. The three clinical settings where angiosarcomas arise include 1) sporadic mostly in the head and neck regions of elderly patients, 2) following long-standing lymphedema, and 3) post radiation. When the tumors from all of the three settings are combined the head and neck are still the most common locations. Histologically, angiosarcomas are composed of vascular spaces lined by pleomorphic and atypical endothelial cells and exhibit varying levels of differentiation from well to poorly differentiated forms within the same lesion. This reflects in the inaccurate predictability of prognosis based on histological features alone.
Histogenesis of angiosarcomas is uncertain. Initially, these tumors were thought to arise from the lymphatic endothelium. However, further immunohistochemical and ultrastructural studies have established the view that angiosarcomas are derived from the endothelium of blood vessels. Immunohistochemical staining for CD31, as seen in the present case, has been found to be a relatively specific and sensitive marker for vascular endothelium derived tumors. Other immunohistochemical markers including Factor VIII-related antigen, CD 34, and Ulex Europeus antigen are not sensitive or specific for neoplastic vascular endothelium.
The development of angiosarcoma with xeroderma pigmentosum has been envisaged as a result of UV-induced damage as is true for other malignancies developing in these patients; , however, angiosarcoma of the face and neck is also known to develop in areas not normally exposed to sunlight. It was also suggested that cutaneous angiosarcomas could arise from the abnormal ectatic vessels present in telangiectatic lesions commonly seen in patients with XP.  However, no telangiectatic lesions were seen in our patient either in the vicinity of the lesion or elsewhere. Angiosarcoma is a known complication in patients exposed to ionizing radiation as in with patients undergoing radiation therapy for other cancers, like breast cancer. This is of particular interest in patients with XP, since one of the reported cases has been shown to exhibit enhanced cellular sensitivity to ionizing radiation.  This finding raises the important issue of determination of radiosensitivity in patients with XP, particularly because such patients are more likely to undergo radiation therapy than the general population due to a high incidence of malignant lesions. Hence, the risk of the development of cutaneous angiosarcoma in these patients is increased remarkably. Although our patient did not give a history of exposure to excess ionizing radiation, the possibility of unrecognized low dose exposure in the setting of enhanced cellular sensitivity eventually giving rise to angiosarcoma cannot be completely excluded.
Angiosarcomas of the head and neck carry a poor prognosis. Histological grade and mitotic activity are poor markers of clinical aggressiveness. Tumor size, depth of tumor invasion, and completeness of surgical resection are more reliable prognostic indicators. 
The development of cutaneous angiosarcoma in a patient with XP is rare and may result from increased sensitivity of these patients to non UV (ionizing radiation) induced skin damage. Due to the defect in DNA repair, radiation treatment for cutaneous malignancy in patients with XP should be administered with caution and these patients need more careful follow-up and early biopsy of suspicious lesions as a routine protocol.
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