Chronic lymphedema of filarial origin: a very rare etiology of cutaneous lymphangiosarcoma.

Lymphedema-associated angiosarcoma also known as lymphangiosarcoma is the commonest type of cutaneous angiosarcoma. Post-mastectomy lymphedema is the most frequent cause, while chronic filarial lymphedema is one of the most uncommon etiology for development of lymphangiosarcoma. We report a case of a 50 year old male suffering from chronic filarial lymphedema of right lower extremity, presented with brownish nodules on the right leg, which were diagnosed histopathologically as lymphangiosarcoma.

What was known?

Chronic filarial lymphedema is an uncommon etiology for the development of cutaneous angiosarcoma. To the best of our knowledge only three cases have been reported previously.

Introduction

Cutaneous angiosarcoma is a rare type of angiosarcoma. Lymphedema-associated angiosarcoma also known as lymphangiosarcoma is the commonest type of cutaneous angiosarcoma. Post-mastectomy lymphedema is the most frequent cause, while chronic filarial lymphedema is one of the most uncommon etiology for development of lymphangiosarcoma.[1] We report the case of cutaneous lymphangiosarcoma developing in chronic filarial lymphedema, because of its rarity and review previously reported three cases.

The prognosis is very poor, with a 5-year survival rate of between 12 and 33%.[1]

Case Report

A 50 year old male patient was admitted with swelling of right leg since 25 years. Painful nodules and ulcerations were observed on the same leg since three months [Figure 1]. On examination, the right leg showed markedly thickened skin with three brownish nodules with raw surface and oozing of blood. The larger nodule measured 3 cm and smaller one measured 2 cm in diameter. The nodules were soft to firm. Right inguinal lymph nodes (2 in number) were palpable, each measuring 2 × 2 cm. Routine laboratory investigations did not reveal any abnormality. The patient was HBsAg, HCV; and HIV1 and 2 negative. Right leg venous Doppler study revealed subcutaneous edema with normal wall to wall colour flow. Patient was a known case of filariasis and had chronic lymphedema of 25 years duration. Aspiration cytology of right inguinal lymph nodes showed chronic lymphadenitis with no evidence of any live or dead microfilariae. Chest roentgenograms, abdominal ultrasound and CT abdomen did not reveal any abnormal findings. Biopsy was done from one of the nodules. Grossly two skin covered brownish tissues bits were received [Figure 2]. The histopathological examination revealed skin comprised of epidermis, dermis and subcutaneous fat. Epidermis showed irregular acanthosis and focal ulceration. Dermis showed a tumour comprised of ill-defined lobules of malignant spindle cells with intervening stroma showing proliferating slit-like vascular channels lined by plump cells with scant cytoplasm and hyperchromatic nucleus [Figure 3]. Tubular pattern of vascular architecture was confirmed by reticulin stain. Some of the cells showed prominent nucleoli. The mitotic activity was 25/10 HPF [Figure 4]. There were foci of hemorrhages. Dermis and subcutaneous fat also showed focal areas of fibrosis due to chronic lymphedema. The vascular nature of the tumour was confirmed immunohistochemically with endothelial markers like CD 34 and CD 31 displaying distinct membranous positivity [Figures 5 and 6].

Figure 1

Marked thickening of the skin of the right lower leg with two ulcerated nodular lesions

Figure 2

Gross photograph showing two brownish tissue bits

Figure 3

Photomicrograph showing a dermal tumour comprised of ill-defined lobules of malignant spindle cells with intervening stroma showing proliferating slit-like vascular channels lined by plump cells with scant cytoplasm and hyperchromatic nucleus (H and E, ×40)

Figure 4

Photomicrograph showing high mitotic activity (H and E, ×400)

Figure 5

Photomicrograph showing distinct membranous positivity by malignant endothelial cells (CD34, ×100)

Figure 6

Photomicrograph showing distinct membranous positivity by malignant endothelial cells (CD31, ×40)

Discussion

Angiosarcoma includes lymphangiosarcoma and malignant hemangioendothelioma, as there are no currently reliable means of distinguishing blood vascular from lymphatic endothelial differentiation (or origin). It is likely that individual cases of angiosarcoma may differentiate in either or both directions. Angiosarcoma may be cutaneous, soft tissue and visceral. Cutaneous angiosarcoma are further divided into (1) idiopathic angiosarcoma of head and face; (2) lymphedema-associated angiosarcoma also known as lymphangiosarcoma; and (3) post radiation angiosarcoma. Lymphangiosarcoma arises in arm of females 1-30 years after mastectomy with removal of axillary lymph nodes, with or without radiation therapy (Stewart-Treves syndrome). More rarely this type can also occur in other types of chronic lymphedema, including congenital, iatrogenic, lymphatic malformations and filarial lymphedema. The prognosis is very poor, with a 5-year survival rate of between 12 and 33%.[1]

The association of lymphangiosarcoma with chronic filarial lymphedema is very rare. To the best of our knowledge only three cases have been reported in the world literature till date and ours is the fourth case.[2-4] We report this case because of its rarity and to highlight this rare complication of chronic filarial lymphedema, so that the treating physician is aware of this impending fatal complication and early radical surgery may save the life of the patient. In our case, there was no history of leg or groin trauma, surgery, radiation, or lymphadenopathy before the development of lymphedema. Although we did not find viable parasites, the patient's history and tissue findings support a diagnosis of chronic filariasis. In two previously reported cases, areas of calcifications were noted consistent with prior filarial infection, which was not seen in our case.[23] Histologically, all the four cases including ours, showed above described characteristic histological features.[2-4] We have ruled out epithelioid hemangioendothelioma, which is usually seen in middle aged people in soft tissue and visceral organs with no report of any cutaneous location. Kaposi sarcoma can be ruled out, as it has never been described in association with chronic lymphedema. Our patient was HIV 1 and 2 negative and there was no history of receiving any immunosuppressive therapy.[1]

Patients suffering from chronic filarial lymphedema should be monitored for possible development of lymphangiosarcoma and any suspicious lesion should be biopsied. The prognosis of lymphangiosarcoma due to chronic lymphedema is similar to idiopathic angiosarcoma of head and face, however the behaviour of lymphangiosarcoma due to chronic filarial lymphedema is not known and therefore more cases need to be studied for proper understanding of its course.

Conclusion

Chronic filarial lymphedema is one of the most uncommon etiology for development of lymphangiosarcoma.

What is new?

We recommend biopsy of any suspicious lesion in a case of chronic filarial lymphedema. We have provided clinical, histopathological and immunohistochemical photographs. We have reviewed three previously reported cases and ours is the fourth case.