Acquired lymphangiectasis following surgery and radiotherapy of breast cancer.

Acquired lymphangiectasia (AL) is a significant and rare complication of surgery and radiotherapy. We report lymphangiectasia in a 40-year-old woman who had undergone radical mastectomy and radiotherapy. After 4 years of combined therapy, she developed multiple vesicles and bullae. Skin biopsy confirmed the diagnosis of lymphangiectasia. The case is unique as it is not associated with lymphedema, which is a usual accompaniment of lymphangiectasia following surgery and radiotherapy. AL is usually asymptomatic, but trauma may cause recurrent cellulitis. Treatment modalities include electrodessication, surgical excision, sclerotherapy and carbon dioxide laser ablation.

What was known?

Acquired lymphangiectasia is known to occur following surgery and/or radiotherapy for carcinoma breast. It is usually associated with lymphedema.

Introduction

Acquired lymphangiectasia (AL) is a dilation of lymphatic vessels, which results after damage caused to the previously normal lymphatics. The damage can primarily be due to surgical intervention alone, irradiation alone, or by surgery and irradiation combined or secondary to scarring. In 1956, Plotnick and Richfield first described it as a complication of radical mastectomy.[1] AL most commonly occurs in adults as a late sequel of surgery and radiation therapy (RT). It has also been associated with metastatic lymph node invasion and obstruction. AL clinically manifests as translucent vesicles in a chronic lymphedematous area several years after surgery with or without RT.[2]

Case Report

A 40-year-old woman was reported with multiple vesicles and bullae on the front and right side of the chest for 2 years. She was diagnosed as a case of infiltrating duct cell carcinoma of the right breast in the year 2006 for which she underwent radical mastectomy followed by the radiotherapy. She noticed the vesicular eruption 4 years after surgery and radiotherapy. Cutaneous examination revealed the absence of the right breast (post mastectomy). Multiple grouped vesicles and bullae were spread over the right anterior, lateral wall of the chest, and the hypochondrium. A Y-shaped scar was noticed in the middle of the right mammary region (mastectomy scar) with no evidence of lymphedema underneath [Figure 1]. Few of the vesicles and bullae were purple in color; pedunculated, and hypertrophic [Figure 2]. The clinical findings prompted us to diagnose AL. However, lymphangioma circumscriptum (LC), lymphangiomatous cutaneous metastases, and angiosarcoma were considered in the differential diagnosis. Histopathological examination of skin biopsy revealed, numerous dilated lymphatics in the superficial and papillary dermis lined by flattened endothelial cells, with mild hyperkeratosis consistent with diagnosis of lymphangiectasia [Figures 3 and 4]. Immunohistochemistry with podoplanin (specific marker for lymphatic endothelium) could not be carried out due to paucity of funds. She was managed with electrodessication.

Figure 1

Multiple grouped vesicles and bullae on the right mammary region and lateral wall of chest and right hypochondrium

Figure 2

Purple and translucent vesicles and hypertrophic pedunculated bullae

Figure 3

Histopathology skin showing numerous dilated lymphatics in the superficial and papillary dermis (H and E, ×10)

Figure 4

Histopathology skin showing dilated lymphatics in the superficial and papillary dermis lined by flattened endothelial cells with mild hyperkeratosis (H and E, ×40)

Discussion

AL represents acquired vesicular dilation of lymphatic channels secondary to an external cause. It has been reported in the literature with an increased frequency in the past 20 years due to increase in surgical excision, surgery and RT for certain malignancies of breast and cervix.[345] AL was also reported as a sequel to the treatment of myxoid chondrosarcoma and bronchial carcinoid.[67] It characteristically presents with the vesicles and bullae. Some of these may turn purple due to the presence of red cells, which arise from hemangiolymphatic connections. Occasionally, they may become pedunculated with the hyperkeratotic and verrucous surface resembling wart. The index case is presented with similar features. Coexisting lymphedema is a usual association in most patients of AL. However, there was no associated lymphedema in the reported case. It is usually asymptomatic, but trauma may provide portal of entry for infection giving rise to recurrent cellulitis.[3] Scarring from scrofuloderma, scleroderma, and cirrhosis are also known to cause AL without lymphedema.[8910] Chiyomaru and Nishigor in a retrospective study of 73 cases of AL following treatment for malignant neoplasm notified external genitalia as the most frequent site. Furthermore, they reported that the combination of surgery and irradiation (77%) was the most frequent preceding therapy, followed by surgery alone (18%) and irradiation alone (5%). In addition, it was found that the mean interval from completion of therapy to the development of AL was shorter after combination therapy (5.8 years) than after surgery (12.2 years) or irradiation (11.8 years) alone.[11] Stewart et al., have also reported AL in their study of 8 patients of carcinoma cervix following surgery and/or radiotherapy.[12] Gnanraj et al., have also notified two cases of AL following surgery and radiotherapy for carcinoma cervix.[13] AL has been reported to occur 3-26 years after the surgery,[1213141516] [Table 1]. The index case developed AL 4 years after surgery and radiotherapy, which is relatively short, compared to the other studies in the literature.

Table 1

Interval between therapy and development of lymphangiectasia in various case studies

The pathogenesis of AL is unclear; however, surgical damage most likely causes fibrosis and lymphatic obstruction at the base of the reticular dermis and accumulation of lymph fluid in the dermal lymphatics with resultant increased pressure. This can then lead to dilation of the superficial lymphatic channels with subsequent vesicle formation. RT also contributes in its pathogenesis because the main site of injury of RT is at the junction of the fat and reticular dermis.,[517] RT itself is known to cause lymphangiectasia by causing lymphangiogenesis in the exposed area during the 1st year of therapy. Recently, it was found that there was an increased number of podoplanin-positive lymphatic vessels and CD68-positive histiocytes in cancer patients treated with the radiotherapy.[18] AL patients with the chronic lymphedema following mastectomy and/or radiotherapy may develop angiosarcoma.[19] These angiosarcomas are characterized immunohistochemically by expression and amplification of myelocytomatosis (MYC) gene, which differentiates post radiation angiosarcomas from benign vascular proliferations following radiotherapy.[20] In addition, immunohistochemical staining for MYC not only helps in the diagnosis but also helps in mapping the neoplasm.

AL is indistinguishable both clinically and histopathologically from LC. Histologically, both reveal ectatic lymphatic spaces in the papillary dermis, which are lined by normal or flattened endothelial cells. The overlying epidermis may show hyperkeratosis and acanthosis. Although, there are no histological criteria to differentiate LC from AL some believe that the subcutaneous muscle-coated cisternae characteristic of LC are absent in AL.

Various therapeutic modalities have been advocated for the treatment of lymphangiectasis. These include surgical excision, cryotherapy, electrodesiccation, sclerotherapy, and laser therapy.[345] Various types of lasers have been used for the treatment including the carbondioxide,[21] argon and tunable dye.[22] The combination of radiofrequency ablation with sclerotherapy was found to be simple, efficacious and cost-effective with a long-term satisfactory results.[23] Gianelli and Rockley found electrodessication superior to the other treatment modalities.[4] Each therapeutic option is effective, but recurrences are common and may be complicated by scarring.

What is new?

AL without lymphedema is known to occur following scarring in scrofuloderma, scleroderma, and cirrhosis. The absence of lymphedema in the reported case of AL without an underlying disease is novel and interesting. The short time interval between the treatment (surgery and radiotherapy) and the development of AL is noteworthy in the reported case.