Mammary angiomatosis is a rare, benign vascular lesion that morphologically mimics inflammatory carcinoma. The purpose of this case report study was to further characterize mammary angiomatosis by clinical, histological, and immunohistochemical means while emphasizing distinguishing features from different pathological lesions.

A 31-year-old woman with a known history of systemic lupus erythematosus presented with a slow onset of symptoms that have developed within one year. Bilateral painful mammary erythema and edema, with no palpable mass, typically involve two-thirds or more of both breasts. Clinically there is peau d’orange, a French term meaning “skin of an orange” that describes the pitted, dimpling skin. Both breasts are enlarged, warm, and tender, which are symptoms that mimic inflammatory breast carcinoma (Figure 1).

The risk of inflammatory breast carcinoma was raised, which was aided by magnetic resonance imaging (MRI) and ultrasonographic evaluation demonstrating patchy areas of skin thickening with hyperenhancement post-gadolinium administration, no primary breast lesion was detected (Figure 2).

Histopathological examination reveals a proliferation of bland spindle endothelial cells involving the reticular dermis and extending to superficial panniculus in a patchy distribution. The lesion displays compactly arranged cells without atypia or significant mitosis. No extravasated erythrocytes identified. These endothelial cells are forming a thin wall, variable-sized lumina dissecting between dermal collagen bundles. There was no evidence of vasculitis, thrombotic vasculopathy, or papillary endothelial hyperplasia (Figure 3A and Figure 3B).

Immunohistochemically, CD31 was diffusely positive in both hemangiomatous and lymphangiomatous appearing vessels, while the latter vessels were also reactive for D2-40.

Cytokeratin was negative ruling out inflammatory breast carcinoma. Staining for (HHV-8) was negative. Special stains of Grocott’s methenamine-silver (GMS) and periodic acid–Schiff (PAS) show no reactivity for infectious organisms. Angiosarcoma was ruled out by the absence of atypia and mitosis and a lack of history of prior radiation. Based on histopathologic findings and the patient’s history, mixed diffuse angiomatosis/lymphangiomatosis was justified (Figure 3C, Figure 3D, Figure 3E, Figure 3F).

The case was discussed extensively in the multidisciplinary meeting in our institution and the outlined treatment plan included: trial of local steroid ointments and antibiotics for the occasional skin infection. These trials ended by minimal response.

Then laser therapy to the affected area was also attempted with no satisfactory relief of the patient’s symptoms. The consensus was to perform a limited mammoplasty and total excision of the affected area with the patient’s full understanding that this procedure may need to be revised in case the condition recurs.

Diffuse dermal angiomatosis (DDA) is a rare cutaneous vascular disorder described initially as an entity of reactive angioendotheliomatosis in 1994 [1]. Breast involvement by DDA has been reported for a total of 45 published cases in literature with the largest series consisting of 22 patients [2]. In contrast, lymphangiomatosis is a diffuse lymphangiomatous lesion. It is miscommunication between lymphatic and venous channels that more commonly occurs in utero rather than late presentation [3].

Diffuse dermal angiomatosis clinically presented as slow growing, reticulated erythematous to violaceous or purpuric patches and indurated plaques with vessels prominence, complicated by tender shallow ulceration. The pathogenesis of DDA is incompletely explained, but the attribute consequences is most likely produced by ischemia and tissue hypoxia due to partially occlusive or inflammatory vascular process. New vessels are increasing to restore diminished blood circulation and tissue oxygenation. A wide scope of predisposing comorbidities has been associated with DDA, such as atherosclerosis [4], iatrogenic arteriovenous malformation [5], monoclonal gammopathy [6], a hypercoagulopathy state in anti-phospholipid syndrome [7]. The most predisposing conditions for DDA were large pendulous breast, obesity, and smoking.

While lymphangiomatosis usually develops as acute incidence following blockage of thoracic lymph duct leading to the development of ascites, chylothorax, and redundant hyperpigmented skin.

Pathologically, it is the presence of both hemangiomatous—appearing [contains extravasated red blood cell (RBC) and hemosiderin] and lymphangiomatous—appearing (empty or containing lymph) channels with an absence of smooth muscle around the vessels. These channels are lined by flat, endothelial cells that infiltrate mammary stroma and adipose tissue and display diffuse, perilobular, and extralobular growth. Ancillary studies are used to confirm the normal endothelial phenotypic of cells lining the blood channels. Positivity is found for vascular markers (CD31 and CD34) and SMA-alpha. D2-40, a marker of lymphatic endothelium, is typically positive in lymphatic spaces. This gives us a clue that this case is mixed diffuse angiomatosis/lymphangiomatosis.

The vascular tumors of mammary origin are extremely rare, and the majority of them are malignant. The vascular lesions of the breast include hemangioma, perilobular hemangioma, pseudoangiomatous stromal hyperplasia, Kaposi sarcoma (KS), and angiosarcoma [8].

Hemangioma is a benign vascular lesion. It is composed of well-circumscribed, cavernous spaces. It does not invade or destroy the lobule but may change the surrounding tissue. Papillae or tufting can be seen while atypia, hemorrhage, and necrosis are absent [9].

Perilobular hemangioma is composed of vascular channels that range from capillary to cavernous vessels. This is an incidental finding that occurs within the lobular stroma or in the extralobular stroma. There are no atypia, papillae, or mitosis [9].

Pseudoangiomatous stromal hyperplasia (PASH) shows anastomosing pseudovascular slit-like spaces in collagen bundles without true vascular lining or extravasated RBC. These show variable cellularity with dense hyalinized collagen bundles [10].

Kaposi sarcoma has variants of histological features, including spindle cell with atypia, diffuse slit-like lumen, and formation with promontory sign and inflammatory compartments. These findings supported by the positivity of CD31, CD34, and HHV8.

The discrimination between angiomatosis and low-grade angiosarcoma (LGAS) is of great importance due to the high impact of differences in prognosis and treatment. Both angiomatosis and LGAS demonstrate anastomosing blood vessels that show diffuse, perilobular growth. However, LGAS diagnostic features include the destruction of the lobules and histomorphological finding of endothelial atypia, nuclear hyperchromasia, and infrequent mitosis. Neither of the vascular markers would be helpful in distinguishing angiomatosis from LGAS. Also, D2-40 can be expressed in a few cases of angiosarcoma [10]. Low-grade angiosarcoma shows an increased Ki-67 proliferation index (typically >20%) in comparison to angiomatosis with low Ki-67 proliferation index (<5%) [11],[12],[13].

Ulceration is a common complication of DDA due to newly developed superficial blood vessels through the skin. The recommendation for treatment is focused on smoking cessation and control of cardiovascular risk factors. Medical treatment includes isotretinoin, acetylsalicylic acid, and oral steroid [8].

Surgical management of DDA of the breast includes excisional biopsy as adequate therapy for mammary angiomatosis. However, simple mastectomy sometimes is needed due to the diffuse nature of this disease. Re-excision is indicated for incompletely excised tumors due to the risk of local recurrence, but it has not known to metastasize [3].

Angiomatosis/lymphangiomatosis is a rare, reactive angioproliferative lesion in the skin and is considered to be a subtype in the group of cutaneous reactive angiomatoses. However, few cases of DDAB have been reported in the literature. Currently, there is no agreement on the best therapeutic approach. Isotretinoin and other medical therapies have been used with limited success. Laser therapy and breast reduction appears to be a reliable treatment option for DDAB and might provide definitive treatment.