Atypical post-radiation vascular lesion Dr. Eduoardo Calonje

Clinical history Female, 81. Pleomorphic lobular carcinoma of the left breast in November 1992. Treated with radiotherapy. Ductal carcinoma of the right breast in October 2004. treated with wide excision. Now, an irregular patch has developed on left breast. Two weeks after the biopsy, the lesion appears to have regressed and no recurrence has been noticed after follow-up of three months. Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Histological features A punch biopsy showing part of a dermal vascular proliferation mainly occupying the superficial part of the dermis The epidermis is normal In the papillary and superficial reticular dermis and extending focally into the mid and deep reticular dermis there are irregular, thin-walled, lymphatic-like, congested vascular spaces lined by a single layer of endothelial cells In the surrounding dermis there is a mild to focally moderate, mononuclear inflammatory cell infiltrate composed of lymphocytes Tiny papillary projections are focally present in the lumina of vascular channels Endothelial cells lining the vascular channels are slightly prominent with focal hyperchromatism but cytological atypia is mild A few endothelial cells have a hobnail-like appearance Multilayering is not seen and mitotic figures are not seen in endothelial cells Diagnosis: Atypical post-radiation vascular lesion Atypical post-radiation vascular lesion (AVL) In the past AVL has been designed in the literature under many different names including lymphangioma circumscriptum, benign lymphangiomatous papule and benign lymphangioendothelioma (acquired progressive lymphangioma). AVL usually present a few years or months after radiotherapy for breast cancer. Although post-irradiation angiosarcomas tend to present many years after radiotherapy this is not always the case and the time span between radiotherapy and the appearance of a vascular lesion cannot be used as a reliable guide to distinguish between a benign and a malignant lesion. Although AVL characteristically arises in irradiated skin for the treatment of breast carcinoma, cases have been described after radiotherapy for multiple myeloma and ovarian and endometrial carcinoma. Clinical lesions are not distinctive and vary from macules to papules. There is a 10% local recurrence rate and additional new lesions arise in 15% of patients. In the series published so far with limited follow-up most cases have a benign behavior. Rare examples of AVL have progressed to angiosarcoma and this suggests that AVL may form a morphologic continuum with low-grade cutaneous post-radiation angiosarcoma. This emphasises the need for complete surgical excision and close clinical surveillance. Histologically, irregular lymphatic-like vascular channels lined by a single layer of endothelial are seen in the dermis. They do not usually extend into the subcutaneous tissue. Often vascular channels mainly occupy the upper dermis as illustrated in this case. Endothelial cells may be plump or have a hobnail appearance and papillary projections may also be found. Cytological atypia, multilayering and mitotic activity is usually absent. As mentioned before, in a minority of cases, distinction from a well-differentiated angiosarcoma may be extremely difficult and it has been suggested that AVL and the latter form part of a spectrum. Differential diagnosis None of the entities described below except post-irradiation angiosarcoma, tend to occur in the field of previous radiotherapy. Hobnail (targetoid hemosiderotic) hemangioma Hobnail hemangioma (HH) is an acquired vascular lesion that presents on the trunk or extremities of young or middle-aged adults with male predilection. Occasional lesions present in the oral cavity. This tumor was previously known as targetoid haemosiderotic haemangioma to highlight what was considered to be its typical clinical presentation consisting of a small round lesion with concentric ecchymotic halos. Many lesions however, do not show this typical clinical appearance and the alternative name of hobnail hemangioma has been suggested. Lesions identical to hobnail hemangioma may occur after trauma. Histologically, in the superficial dermis, there are irregular dilated thin-walled vascular channels lined by bland endothelial cells with occasional papillary projections. The endothelial cells in the superficial blood vessels typically show a hobnail appearance. The lesion has a wedge-shaped architecture as a result of the vascular channels disappearing as they descend further into the deeper dermis. Deeper vascular channels display flattened endothelial cells. The surrounding dermis shows extravasation of red blood cells and often, quite prominent hemosiderin deposition. Inflammatory cells are not usually seen. Benign lymphangioendothelioma (acquired progressive lymphangioma) This is a fairly rare tumor that presents predominantly in middle-aged or old adults. There is an equal sex incidence and predilection for the extremities, particularly the lower limbs. The clinical presentation is that of a solitary macular or plaque-like erythematous or purplish lesion that evolves over a long period of time. Spontaneous regression is occasionally seen. Local recurrence after excision is very rare. Histologically, lesions show dilated irregular thin-walled vascular spaces, which tend to be parallel to the epidermis. Most vascular channels are in the superficial and mid reticular dermis but extension into the deep dermis and superficial subcutis can be seen. The endothelial cells in the vascular channels are flat and there is little or no cytological atypia. Proteinaceous material or red blood cells can be seen in the lumina. Inflammatory cells are not usually seen. Post-irradiation angiosarcoma. This tumour is relatively rare and most cases arise in the breast. The time from radiotherapy to presentation varies from 5 to 20 years. There is usually no associated lymphedema and the latency period is shorter than that in Stewart-Treves syndrome. Some cases of post-irradiation angiosarcoma of the breast may be associated with chronic lymphedema and this may contribute to the development of the disease. Prognosis is poor. Local recurrences and rapid dissemination (lymph nodes and lungs) are frequent. A mortality rate of up to 80% of cases has been reported. Features associated with adverse prognosis include size of the tumor, depth of invasion and mitotic rate. The histological appearances are very similar regardless of the clinical setting. Tumors vary from well to poorly differentiated. Irregular channels lined by atypical endothelial cells with hyperchromatism and frequent mitotic figures infiltrate the dermis and subcutaneous tissue. Multilayering is frequent and this may be associated with papillary projections. Tumor cells line and dissect collagen bundles and this produces a characteristic appearance described as "dissection of collagen bundles". Hemorrhage and hemosiderin deposition is often seen. Focal epithelioid change is present in some cases. Less differentiated tumors become more solid and vascular differentiation is focal or absent. Pleomorphism becomes more prominent. 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