• E-mail
• Print
• Comment
• Font Size
• Digg
• del.icio.us
• Discuss article

Severe Lower Limbs Lymphedema Following Breast Carcinoma Treatment Revealing Radiation-Induced Constrictive Pericarditis: A Case Report

Posted on: Thursday, 10 February 2005, 03:00 CST

In patients treated for breast carcinoma, unilateral lymphedema of the upper limb is usual. However, to the authors' knowledge, lower limb lymphedema has never been reported as a complication of breast carcinoma therapy. They report here the first case of a radiation-induced constrictive pericarditis revealed by severe lower limbs lymphedema. A 60-year-old woman was treated for left breast carcinoma with quadrantectomy, axillary lymphadenectomy, and combined radio chemotherapy (60 grays). Three and a half years later she suffered from a diffuse and increasing lower limbs lymphedema, which became huge and disabling. Radiation-induced constrictive pericarditis was evidenced by right cardiac cavities catheterization. A dramatic improvement was rapidly obtained after pericardectomy. Histopathologic analysis of the pericardium did not reveal neoplastic cells. Radiation-induced constrictive pericarditis is usually responsible for lower limbs edema, but lymphedema is exceptional. This case highlights the need to search for a constrictive pericarditis also in the case of lower limbs lymphedema, particularly in a patient treated with mediastinal radiotherapy or combined radio chemotherapy.

Introduction

Unilateral lymphedema of the upper limb is a usual complication of breast carcinoma therapy. We report here a severe lower limb lymphedema revealing a radiation-induced constrictive pericarditis (CP), an exceptional presentation of a CP.

Case Report

A 60-year-old woman was admitted to our medical department for a lower limbs lymphedema. In December 1995, she suffered from a left breast carcinoma (infiltrating duct carcinoma) with 7/22 neoplastic lymph nodes and without metastatic involvement. She was treated by quadrantectomy with axillary lymphadenectomy, and radiochemotherapy with the following protocol: at day 1: epirubicine (75 mg/m2), cyclophosphamide (500 mg/m^sup 2^), vindesine (2 mg/m^sup 2^), and from day 15 to day 20: combined radiochemotherapy regimen with cisplatin 20 mg/m^sup 2^/day associated with 5-fluorouracil (5-FU) 500 mg/m^sup 2^/day and radiotherapy (15 grays administered on 5 days). Irradiation was performed on the left breast and subclavicular area. The patient was then treated by adjuvant radiotherapy (15 grays on the left breast) and chemotherapy with methotrexate (1.5 g/m^sup 2^, at day 1, day 15, and day 30). She then received 6 courses of FEC (5-FU, epirubicine, and cyclophosphamide). Finally, 1 year later (December 1996), tamoxifen was started owing to positivity of estrogen receptors in the carcinoma tissue. The total dose of radiotherapy was 60 grays.

In August 1999, she presented a generalized pruritus treated with antihistaminic drugs without clinical improvement. Subsequently, erythematous lesions appeared on both lower limbs associated with diffuse and increasing lower limbs lymphedema. Cutaneous biopsy showed lymphangitis without neoplastic cells.

In February 2000, she was admitted to our department for progressive worsening of her lymphedema, which became painful. Physical examination revealed a body weight of 86 kg (22 kg over her normal weight), a blood pressure of 120/80 mm Hg and a lower limbs lymphedema, with indurated and fibrotic skin, reaching the pelvis and associated with an increase of her preexisting left upper limb lymphedema. A turgescence of external jugular veins was noted with hepatomegaly and dyspnea on exertion.

Biological evaluation was as follows: White blood cells count 9,130/mm^sup 3^, hemoglobin 114 g/L, and platelet count 202,000/ mm^sup 3^. Erythrocyte sedimentation rate was 30 mm per hour, protein C reactive was 26 mg/L, and fibrinogen was 2.98 g/L. There were elevated gammaglutamyl-transferase of 75 UI/L (N: 8-38) and alkaline phosphates of 107 UI/L (21-79). Electrolytes, proteinemia, urea nitrogen, lacticodeshydrogenase and proteins electrophoresis were all normal. Albuminemia was slightly decreased (36 g/L, N: 36- 45). The CA-125 antigen level was 74 μ/mL (N: < 35). No proteinuria was observed. An electrocardiogram revealed a low voltage of the QRS complex. Thoracic and abdominal computed tomography (CT) scan showed steatosis of liver associated with subcutaneous lymphedema without enlarged deep lymph nodes. Cervical and thoracic magnetic resonance imaging did not evidence thoracic duct compression. Mammography and 2 echocardiographies produced normal findings. Hepatic veins were not dilatated on echography and appeared normal on Doppler sonography.

The patient's general situation rapidly worsened, and she became bed ridden. In spite of the negative results of the 2 echocardiographies, a constrictive pericarditis (CP) was suspected owing to the turgescence of the jugular veins and past medical history of left breast radiotherapy. Cardiac catheterization was performed and showed a typical CP, with diastolic dip and plateau in right ventricular filling pressures (adiastole). Total pericardectomy was performed. The senior surgeon who operated on the patient observed that the right cavities expanded as soon as he had excised the thickened and fibrous pericardium. Pericardium was responsible for an important constriction of right-heart cavities and particularly the anterior portion of the right ventricle. Histopathologic analysis revealed a fibrous pericardium without inflammatory and malignant cells and without calcification.

Dramatic improvement of lower limbs lymphedema was rapidly obtained with 19 kg body weight loss during the month following surgery. Three years later, she had an ovarian carcinoma requiring surgery and chemotherapy, with a good outcome without cardiac event.

Discussion

We report here a severe and painful lower limbs lymphedema revealing a radiation induced-CP. To our knowledge, such a manifestation has never been described in the literature, and only some rare cases of chylous ascites related to alteration of digestive lymphatic flow have been observed in CP.1

Lymphedema arises following an intrinsic fault within the lymph- conducting pathways (primary lymphedema) or when damage occurs outside the lymphatic system (secondary lymphedema). Many causes of secondary lymphedema have been evoked including filariasis and tuberculosis infections, recurrent lymphangitis, lymphoma, pregnancy, lymphogranuloma venereum, rheumatoid arthritis, surgery, and radiation therapy.2 In the case of breast carcinoma, lymphedema usually concerns the upper limb. It is qualified as postmastectomy edema, and was evaluated as having a cumulative incidence of 28% in a large cohort of breast carcinoma patients.3 This lymphedema can be complicated by lymphangiosarcoma (Stewart Treves syndrome).

Causes of CP include infections (mainly tuberculosis), neoplastic diseases, trauma, cardiac surgery, rheumatoid arthritis, systemic lupus erythematosus or scleroderma, and chronic renal failure.4 Mediastinal irradiation for Hodgkin's lymphoma, breast carcinoma,5 or other thoracic neoplasms is also a common cause of CP and represents about 7% of cases of CP. Radiation-induced constrictive pericarditis most of the time requires surgery owing to cardiac dysfunction or, more rarely, to distinguish between pure autonomous pericardial fibrosis and recurrent neoplasia.6 Outcome is often poor.6 Moreover, combined radiochemotherapy exhibits well-known myocardial toxicity and can induce myocardial infarction7 and left ventricular dysfunction.8 In our patient, the combined radiochemotherapy has probably increased the pericardial toxicity.

Usual presentation of CP includes weakness, fatigue, weight loss, anorexia, and dyspnea on exertion. Congestive hepatomegaly and ascites are common and there may also be a palpable splenomegaly. Lower limbs edema is frequent, but lymphedema has never been reported in the literature. However, protein-losing gastroenteropathy due to impaired lymphatic drainage from the small intestine can be observed, as well as chylous ascites.1,9 Three mechanisms are possibly involved in the pathophysiology of lymphedema: elevated central venous pressure leading to alteration of the lymphatic drainage, thoracic duct lesion induced by radiotherapy, and increase of lymph production. In our case, we feel that constriction of right-heart cavities by fibrous pericardium led to increased central venous pressure. Owing to the anatomy of the thoracic duct (which joins the venous system at the junction of the subclavian and jugular veins), when pressure in the central venous system becomes higher than that in the thoracic duct, intralymphatic congestion arises and leads to development of functional lymph flow insufficiency.

Our case is characterized by unusual presentation (lower limbs lymphedema) and by an astonishing clinical recovery following pericardectomy. It recalls that search for a CP is justified when one is faced with lymphedema before concluding a neoplastic relapse.

REFERENCES

1. Savage MP, Munoz SJ, Herman WM, et al: Chylous ascites caused by constrictive pericarditis. Am J Gastroenterol 82:1088-1090, 1987.

2. Szuba A, Rockson SG: Lymphedema: Classification, diagnosis and therapy. Vasc Med 3:145-156, 1998.

3. Mortimer PS: The pathophysiology of lymphedema. Cancer 83:2798- 2802, 1998.

4. Braunwald E: Pericardial disease. In: Harrison's Principles of Internal Medicine, ed. by Isselbacher KJ, Braunwald E, Wilson JD, \et al. New York: McGraw-Hill, 1994, pp 1094-1101.

5. Green B, Zornoza J, Ricks JP: Eccentric pericardial effusion after radiation therapy of left breast carcinoma. Am J Roentgenol 128:27-30, 1977.

6. Loire R, Saint-Pierre A: Radiation-induced pericarditis. Long- term outcome: 45 cases with thoracotomy and biopsy. Presse Med 19:1931-1936, 1990.

7. Maurer U, Harle M, Jungius KP: 5-Fluorouracil: Cause of a fatal myocardial infarction in combined radiochemotherapy? Strahlenther Onkol 172:257259, 1996.

8. Unverdorben M, Birkenhake S, Kunkel B, et al: Extended reversible global left ventricular contraction dysfunction with symptomless coronary system as effect of cytostatic therapy with 5- fluorouracil. Strahlenther Onkol 170:461-466, 1994.

9. Williams AT, Schleider RP: Chylous ascites should suggest constrictive pericarditis even in a patient with cirrhosis. J Clin Gastroenterol 12:581-584, 1990.

B. Granel, MD,* C. Gaudy, MD,* J. Serratrice, MD,* Nicoleta Ene, MD,* T. Mesana, MD,[dagger] J. L. Bonnet, MD,[double dagger] H. Lepidi, MD, P. Disdier, MD,* L. Piana, MD,[open diamond] and P. J. Weiller, MD,* Marseille, France

Angiology 56:119-121, 2005

From the * Service de Mdecine Interne, [dagger]Service de Chirurgie Cardiaque, [double dagger] Service de Cardiologie Interventionnelle, Service d'Anatomie Pathologique, CHU Timone, Marseille; and [open diamond] Service de Gynco-Obsttrique, Hpital de la Conception, Marseille, France

Correspondence: Pr. P. Disdier, MD, Service de Mdecine Interne, Hopital de la Timone, 264 rue Saint Pierre, 13385 Marseille Cedex 5, France

E-mail: patrick.disdier@ap-hm.fr

2005 Westminster Publications, Inc., 708 Glen Cove Avenue, GlenHead, NY 11545, USA

Copyright Westminster Publications, Inc. Jan/Feb 2005

Source: Angiology

More News in this Category