Atypical Vascular Lesions After Radiotherapy: A Case Series : The American Journal of Dermatopathology

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Atypical Vascular Lesions After Radiotherapy: A Case Series

Soto-García, Diego MD*,†; Batalla, Ana PhD*,†; Gonzalez-Sixto, Beatriz PhD*,†; Rodríguez-Jato, Queila MD*,†; Alvarez, Carlos MD; Flórez, Ángeles PhD*,†

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The American Journal of Dermatopathology 44(5):p 390-393, May 2022. | DOI: 10.1097/DAD.0000000000002069
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To the Editor:

Atypical vascular lesions (AVLs) are heterogeneous-looking vascular proliferations that frequently appear as erythematous or flesh-colored papules or plaques in areas where the patient has previously received radiotherapy.1–3 Traditionally, most cases have occurred in the chest of women with a history of breast cancer, but they may appear associated with other cancers.

AVLs can be difficult to distinguish clinically from other postradiotherapy lesions, such as erysipeloid breast carcinoma and cutaneous angiosarcoma (AS), being AS their main differential diagnosis.4,5 The distinction between AVLs and AS is of relevance because AS is associated with poor survival (angiosarcomas have an overall 5 years survival around 35%), whereas theoretically AVLs do not affect it.4,6 Because the clinical appearance of a large AVL and an incipient AS may be identical, its diagnosis is fundamentally histologic.7

Usually, AVLs are identified as benign lesions, but there is some controversy in relation to this topic. Some authors propose that AVLs could be precursors of AS, although they would represent a small percentage of cases.5,8,9 Most AVLs are treated with complete excision, but so far, there are no clinical guidelines in this regard and close follow-up of patients also seems to be a reasonable option.7

We present a 4-case series of AVLs in the radiotherapy field of different types of cancer.


We report 4 female patients with previous history of ductal or papillary breast carcinoma or vulvar squamous cell carcinoma who received combined treatment (surgery and radiotherapy) and developed AVLs within the irradiated area (Table 1, Fig. 1). Cutaneous lesions appeared between 2 and 14 years after radiotherapy, with a mean latency period of 7 years.

TABLE 1. - Summary of the Main Characteristics and Oncological Record of the Four Patients Who Developed AVLs, Clinical Presentation, Histopathologic Examination, and Management
Case 1 Case 2 Case 3 Case 4
Age 41 80 66 49
Location Left breast Left breast Vulva Vulva
Previous neoplasm Ductal carcinoma in situ (low-grade) Left breast: invasive papillary carcinoma
Right breast: invasive ductal carcinoma
Well-differentiated invasive squamous cell carcinoma Invasive squamous cell carcinoma moderately differentiated
Treatment for the neoplasm Mastectomy, lymphadenectomy, radiotherapy (50 Gy), hormonal treatment. Left breast: mastectomy, lymphadenectomy, chemotherapy, radiotherapy (61.2 Gy), hormonal treatment
Right breast: tumorectomy, lymphadenectomy, radiotherapy (60 Gy), hormonal treatment
Tumorectomy and radiotherapy (66 Gy) Tumorectomy and radiotherapy (60 Gy)
Latency from radiotherapy 7 yrs 14 yrs 2 yrs 4 yrs
Clinical presentation Indurated and sclerotic irregular plaque surrounded by telangiectasias Skin-coloured elastic papule surrounded by telangiectasias Discoloration and erythematous maculo-papules Erythematous-purpuric, sharply demarcated and indurated lesion
Histopathologic examination Dilated irregular vessels within the dermis, lined by a single layer of endothelial cells with slight atypia and hyperchromatism, with stromal fibrosis and focal chronic inflammation Irregular and dilated vascular spaces, lined by minimally atypical endothelial cells were evidenced within the dermis. Relatively circumscribed, wedge-shaped collections of dilated, small vessels were present in the superficial to mid dermis Irregular and dilated vascular spaces with thin projections of endothelium-covered stroma.
Intervention Free-margin excision and periodic follow-up. Biopsy. Multiple punch biopsies (mapping).
Close follow-up.
Punch biopsy.
Close follow-up
Evolution No recurrence No adherence to programmed visits No changes No changes

A, Case 1. Ill-defined sclerotic and slightly erythematous areas, surrounded by numerous telangiectasias and dyschromatosis. B, Case 2: Erythema with telangiectasias and dyschromatosis close to the mastectomy scar. C, Case 4. Vulvar discoloration intermingled with erythematous and purpuric areas. D, Case 4. Dermoscopic appearance of the previous lesion, showing dilated, irregular, and polymorphous vessels.

In case 1, dilated irregular vessels within the dermis, lined by a single layer of endothelial cells with slight atypia and hyperchromatism, with stromal fibrosis and focal chronic inflammation were observed.

Case 2 presented irregular and dilated vascular spaces, lined by minimally atypical endothelial cells within the dermis. There were erythrocytes in the lumen of the vascular spaces, indicating the diagnosis of AVL of the vascular type.

In case 3, relatively circumscribed, wedge-shaped collections of dilated, small vessels were present in the superficial to mid dermis. The blood vessels were lined by a single layer of endothelial cells that were monomorphous, flat, and plump without significant atypia.

In case 4, irregular and dilated vascular spaces with thin projections of endothelium-covered stroma were seen. This was concordant with the diagnosis of AVL.

All but one of the AVLs were of the lymphatic type. Histopathologic findings are shown in (Fig. 2). One patient did not attend to programmed visits after the diagnosis. Close clinical follow-up was decided in 2 patients, while free-margin excision was performed in one of them. No clinical changes or recurrences were observed in the follow-up of those patients.

A, Case 3. Hematoxilin and eosin, 20x. Irregular vascular spaces within the dermis, lined by a single layer of endothelial cells, lymphatic type. B, Hematoxilin and eosin, 20x. Irregular dilated vascular spaces, thin walls, and lymphatic appearance, were seen in the superficial dermis. A discontinuous single layer of endothelial cells with flattened nuclei lined these vascular channels and their lumina appeared empty. C, Case 2. Hematoxilin and eosin, 100x. Irregular vascular channels with associated chronic inflammation. D, Case 2 Hematoxilin and eosin, 400x. Endothelium cells with hyperchromatic nuclei and erythrocytes in the lumen.


Cutaneous vascular lesions are well-established complications of radiotherapy.10 The dynamic process of postradiotherapy skin changes usually stops 3 years after finishing radiotherapy, so subsequent changes in the radiotherapy field should alert the clinician to the possibility of other different entities such as AVLs or AS.11 According to some recent reviews, the median latency period from radiotherapy to the appearance of AVLs is 3–6 years and their mean size at the time of diagnosis is 0.5 cm, while ASs appears with an average latency of 5–7 years and their average diameter is 7.5 cm.8,12

In reference to histologic characteristics, both AVLs and AS show anastomotic vessels and hyperchromatic endothelial cells. Dissection of dermal collagen can be present in both entities.

AVLs are wedge-shaped, with well-circumscribed proliferation of dilated vessels with a single-layer thin wall, anastomotic channels without hemorrhage and limited to the superficial or medial dermis.7,12 Some authors have observed that AVLs histologically display dilated vascular spaces within the papillary dermis with plump endothelial cells, differentiated from AS by lack of destruction of adnexa.2,7 Endothelial cell nuclei can be prominent and hyperchromatic, but there is no significant cytologic atypia or multilayering. Mitoses, necrosis, and blood lakes are also absent in AVLs. AVLs immunohistochemical phenotype can be lymphatic (CD31+, D2-40+, CD34±) or vascular (CD31+, CD 34+ and D2-40−).9 Patton et al suggested that the vascular type had a higher risk for malignant progression; however, other studies have not been able to confirm this.9,13,14 In our series, all but one of the cases were of the lymphatic type and there was no AS progression up until now.

AS shows anastomotic channels that infiltrate the subcutaneous tissue presenting nuclear atypia, various layers of endothelial cells, abundant mitosis, and perilesional hemorrhage. Its immunophenotype is CD34+, CD31+ and Factor VIII±.7,12 AS usually lacks chronic inflammation, circumscription, and stromal projections into the lumen, features that are commonly seen in AVLs. Although these features help distinguish AVLs from AS, there are no characteristics that allow an absolute distinction because both entities present a variable degree of overlap in their appearance.2,15–18 Some studies have claimed that the amplification of MYC by Fluorescence in situ hybridization or its detection by Immunohistochemistry is seen in secondary AS (radiotherapy and lymphedema-related) but not in AVLs.15,19–22 Such ancillary studies may be of aid in some cases for arriving at the correct diagnosis, particularly on limited biopsies or if the biopsy is taken from the periphery of the lesion.20

Regarding their behavior, AVLs were considered a benign entity.1 However, confirmed histologically cases of evolution from AVL to AS have been reported.5,9 In a recent series of 193 patients, 3% of the patients initially diagnosed with AVLs subsequently presented AS.8 There was no agreement whether these events are due to errors in the initial histologic characterization, concurrent diseases, or progression from one entity to another.8

With improved outcomes associated with radiotherapy, postirradiation tumors are increasingly seen in long-term cancer survivors.15 It is important that both clinicians and pathologists take into consideration these conditions and the difficulties that their management presents.


AVLs may occur on the field of previous radiotherapy. Distinguishing postradiation benign from malignant vascular lesions can be challenging because they share overlapping clinical and histopathologic features. There is a slight chance that a minority of the cases that have been diagnosed as AVLs are indeed AS precursors and therefore, multiple biopsies during the follow-up are needed to rule out this possibility. We highlight AVLs different clinical presentations and remark that, although these vascular proliferations are more frequent after radiation treatment for breast carcinomas, they may appear after radiotherapy for other neoplasms.


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