18 F-FDG PET/CT in a Rare Case of Stewart–Treves Syndrome: Future Implications and Diagnostic Considerations

Introduction

Lymphedema of the lower extremities is a progressive debilitating disease characterized by chronic swelling due to interstitial edema caused by insufficient lymphatic drainage capacity.^1,2,3 Lower extremity lymphedema is often undiagnosed or misdiagnosed, and treatment therefore absent, delayed, or inadequate.^4–7 Progression is common and is mainly caused by abundant remodeling of the skin and subcutaneous tissue with dermal thickening, subcutaneous fibrosis, and increased adipose tissue deposition.^8–11 The underlying pathophysiologic process is still incompletely understood, but evidence from animal lymphedema models show that inflammation probably plays a key role.^12,13

A rare but often fatal complication of lymphedema is Stewart–Treves syndrome (STS), which is defined as the development of a highly malignant angiosarcoma secondary to chronic lymphedema. ¹⁴

The uptake of ¹⁸F-FDG is a measure of tissue carbohydrate metabolism and is visualized by PET/CT scanning. ¹⁸F-FDG PET/CT has been demonstrated to be a very sensitive tool in detecting inflammation and many neoplasms.^15,16 The role of ¹⁸F-FDG PET/CT in the management of lymphedema and its complications has to our knowledge yet to be elucidated. Future possible applications are illustrated by the following case report.

Case Report

A 44-year-old woman with known lymphoscintigraphy-verified lymphedema (Fig. 1) presented with newly developed macular skin changes in the affected lower left extremity (Fig. 2). The patient had acquired secondary lymphedema 6 years earlier following repeated surgery for an intrapelvic carcinoma of unknown origin involving resection of the sigmoid colon and multiple retroperitoneal lymph nodes. An initial histological skin biopsy showed no signs of malignancy. The symptoms were interpreted as cellulitis, but repeated treatments with antibiotics had no effect. In the months prior to admission, the lymphedema progressed rapidly, resulting in a total weight gain of approximately 35 kilograms. The skin changes progressed and ulceration and clinical signs of cellulitis developed. The patient was admitted for optimized compression treatment and intravenous antibiotics.

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FIG. 1.

^99mTc-nanocolloid lymphoscintigraphy showing no visualization of subcutaneous lymphatic collectors or lymph nodes in the affected lower left extremity on either the early (15 min post injection, left) or the late scan (120 min post injection, right). In the lower right extremity, there are signs of tracer leakage from subcutaneous lymphatic collectors at knee level.

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FIG. 2.

Clinical photograph at admission showing macular skin lesions in the affected lower left extremity.

Among a host of different diagnostic examinations to determine the cause of the sudden edema progression, a ¹⁸F-FDG PET/CT scan was performed to rule out recurrence of the intrapelvic neoplasm (Fig. 3). The scan showed massive edema of the subcutaneous tissue of the lower left extremity and surprisingly a pronounced ¹⁸F-FDG accumulation primarily in the skin and subcutaneous tissue, with sharp demarcation at the ankle and groin level. There was no evidence of intrapelvic tumor recurrence. In spite of large treatment efforts to treat the cellulitis and reduce the edema (compression, elevation, loop-diuretics, broad spectrum antibiotics), the patient's condition continued to deteriorate over the following weeks with treatment refractory edema and progressive ulceration (Fig. 4). A second ¹⁸F-FDG PET/CT scan was performed 6 weeks later to make sure a neoplasm was not overlooked due to the massive FDG accumulation in the affected leg on the first scan (Fig. 5). It showed a marked decrease in overall ¹⁸F-FDG-uptake, however, multiple focal lesions in the skin and subcutaneous tissue remained. A histologic skin biopsy was repeated due to the lack of treatment effect and the diagnosis of angiosarcoma was made. The general condition of the patient was too poor to offer surgery or chemotherapy and she died shortly thereafter due to the massive tumor burden, infection, and kidney failure.

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FIG. 3.

¹⁸F-FDG PET/CT showing massive subcutaneous edema (left) and increased ¹⁸F-FDG uptake in the skin and subcutaneous tissue with unusual sharp demarcations (right) in the affected lower left extremity.

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FIG. 4.

Clinical photograph approximately 8 weeks after admission showing extensive progression of skin lesions.

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FIG. 5.

The second ¹⁸F-FDG PET/CT 6 weeks later showing a decrease in edema volume and soft tissue ¹⁸F-FDG accumulation compared to the first scan, but multifocal lesions with increased ¹⁸F-FDG uptake in the skin and subcutaneous tissue in the lower left extremity remain.

Discussion

The case report described above represents an example of the possible applications of ¹⁸F-FDG PET/CT in chronic extremity lymphedema and its complications. Lymphedema is a chronic progressive disease but the speed of progression is very individual. It is, however, generally accepted that conservative treatment with manual lymphatic drainage massage, compression therapy, and meticulous skin care results in a better outcome. ¹⁷ The pathophysiologic mechanisms governing skin and subcutaneous tissue remodeling in extremity lymphedema have yet to be fully elucidated. If chronic inflammation plays a central role, then the degree of inflammation may be associated with the progression speed. ¹⁸F-FDG PET/CT scanning has been shown to be a very sensitive modality in the diagnosis of focal inflammatory processes. ¹⁵ We suggest that ¹⁸F-FDG PET/CT can become an important tool in identifying the patients at risk of tissue remodelling progression.

STS is a rare and often fatal complication to chronic lymphedema with an estimated incidence in breast cancer-related lymphedema (BCRL) of 0.07% –0.45%. ¹⁸ The average debut of STS in BCRL is 10 years after mastectomy and the prognosis is poor with a median survival of 19 months. In lower extremity lymphedema, STS is even rarer but seems to have a later debut (average 19 years) and perhaps a slightly better prognosis (median survival 34 months). ¹⁹

Local extensive spread via satellite lesions and metastasis to the lungs are common. ¹⁸ Early diagnosis and radical surgical treatment is associated with a better prognosis. ¹⁹ Thus pretreatment staging is paramount in choosing the correct treatment modality. ¹⁸F-FDG PET/CT has the potential to become a first line choice in initial staging and treatment follow-up because STS has been demonstrated to have a high ¹⁸F-FDG uptake.^20–22

This case furthermore represents one of the possible pitfalls in applying ¹⁸F-FDG PET/CT on lymphedema patients. In the first scan, the STS changes were masked by the inflammation caused by the present cellulitis. The STS changes first became evident after the cellulitis had been sufficiently treated. Since ¹⁸F-FDG accumulate in all cells with a high glucose metabolism such as some forms of cancer cells and activated immune cells, the modality has a low specificity under circumstances where infection and malignancies are present concomitantly. ¹⁵