Lymphoscintigraphic patterns in lymphedema with normal body mass index, obesity-induced lymphedema, phlebolymphedema, and lipedema

INTRODUCTION

Lymphedema is a chronic, progressive condition resulting from impaired lymphatic transport, leading to interstitial fluid accumulation, inflammation, tissue remodeling, and swelling.^[1] In the lower extremities, chronic swelling has a broad differential diagnosis and is categorized into four classes: Primary or secondary lymphedema, obesity-induced lymphedema, chronic venous insufficiency with phlebolymphedema, and lipedema. Dean et al., reported that among 440 patients with lower-extremity lymphedema, the most common cause was phlebolymphedema related to chronic venous insufficiency (41.8%), followed by cancer-related lymphedema (33.9%), primary lymphedema (12.5%), and lipedema with secondary lymphedema (11.8%).^[2] Severe obesity is also increasingly recognized as an independent cause of lower-extremity lymphatic dysfunction, with obesity-induced lymphedema reported to occur at very high body mass index (BMI) levels.^[3] Differentiating these four classes is important, as management and prognosis can differ significantly across the classes.^[4,5]

Lymphoscintigraphy (LSG) is a standard functional imaging modality for evaluating suspected lymphedema through two-dimensional (2D) planar imaging using gamma cameras.^[6] However, interpretation is often qualitative and can be challenging in patients with overlapping conditions or atypical presentations.^[7] Furthermore, as mentioned above, obesity, venous disease, and lipedema may alter tracer transport patterns and complicate image interpretation.^[8-10] Thus, we selected four representative cases to illustrate key clinical and pathophysiologic categories relevant to lower-extremity enlargement: Lymphedema patient with normal BMI (case 1), obesity-induced lymphedema (case 2), phlebolymphedema (case 3), and lipedema (case 4).

At our institution, LSG is performed using 99mTc-filtered sulfur colloid, with 2D planar imaging acquired at 4 time points: Immediately after injection, and at 30, 60, and 120 min, without exercise during the study. Imaging findings were assessed qualitatively, including tracer migration, visualization of inguinal lymph nodes, symmetry of nodal uptake, delayed transport, and abnormal features such as dermal backflow.

CASE REPORTS

Case 1. Lymphedema in a patient with normal BMI

A 50-year-old female (BMI: 27.1 kg/m²) presented with a 9-year history of left lower extremity swelling. Her medical history was significant for uterine cancer, for which she underwent total laparoscopic hysterectomy with bilateral salpingo-oophorectomy and left pelvic lymph node dissection in 2017. On physical examination, asymmetric swelling of the left lower extremity was noted, with increased limb circumference compared to the right.

In this patient with normal BMI, LSG demonstrated markedly decreased lymphatic transport in the left lower extremity, with prominent dermal backflow most evident at 120 min and delayed tracer migration [Figure 1]. Inguinal lymph node visualization on the left side was reduced compared to the contralateral side. The right lower extremity and central lymphatic system showed no significant abnormalities. These findings are consistent with unilateral secondary lymphedema, related to prior pelvic lymph node dissection, in a patient without severe obesity.

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Figure 1: A 50-year-old woman with chronic left lower extremity swelling and unilateral secondary lymphedema. Anterior lymphoscintigraphy images were obtained at (a) 0, (b) 30, (c) 60, and (d) 120 min. Rectangular regions of interest are placed over the bilateral inguinal nodal regions and injection sites. The red and green boxes indicate the right and left ilioinguinal lymph nodes, respectively; the blue and purple boxes indicate the right and left injection sites, respectively. The images show delayed lymphatic transport in the left lower extremity with reduced left inguinal nodal visualization and dermal backflow, most prominent at 120 min. The right lower extremity and central lymphatic system are unremarkable. (e) Clinical photograph shows asymmetric left lower extremity swelling.

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Case 2. Obesity-induced lymphedema

A 49-year-old male (BMI 43 kg/m²) presented with longstanding left lower extremity swelling for more than 10 years, with worsening over the past 4 years. His medical history was notable for hypertension, hyperlipidemia, type 2 diabetes mellitus, and prior incision and drainage of the left thigh.

This patient with high BMI showed delayed lymphatic transport in the left lower extremity, with dermal backflow in the mid-thigh region, most evident at 60 and 120 min, and delayed visualization of the inguinal lymph nodes [Figure 2]. The right lower extremity showed preserved lymphatic flow. Although the imaging findings support lymphedema, the nodal uptake on the affected side was relatively higher than expected for the degree of clinical severity. In the setting of severe obesity, this may reflect increased lymphatic load affecting tracer dynamics. Overall, these findings are consistent with left lower extremity lymphedema in the setting of severe obesity and suggest that quantitative metrics should be interpreted with caution in obese patients.

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Figure 2: A 49-year-old man with left lower extremity swelling and severe obesity (body mass index 43 kg/m²), consistent with obesity-induced lymphedema. Anterior lymphoscintigraphy images were obtained at (a) 0, (b) 30, (c) 60, and (d) 120 min. Rectangular regions of interest are placed over the bilateral inguinal nodal regions and injection sites. The red and green boxes indicate the right and left ilioinguinal lymph nodes, respectively; the blue and purple boxes indicate the right and left injection sites, respectively. Serial anterior lymphoscintigraphy images show delayed lymphatic transport in the left lower extremity with mid-thigh dermal backflow, most evident at 60 and 120 min, and delayed left inguinal nodal visualization. Multiple prominent lymphatic vessels are identified in both legs. The right lower extremity otherwise shows preserved lymphatic flow.

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Case 3. Phlebolymphedema

A 77-year-old female (BMI 28.4 kg/m²) presented with a 3-year history of bilateral lower extremity swelling, more prominent on the left side. Physical examination revealed both pitting and non-pitting edema. Her medical history included hypertension, hyperlipidemia, and atrial fibrillation. Venous duplex studies demonstrated bilateral superficial venous reflux in the small saphenous veins, with reflux times of 1.6 s on the right and 1.5 s on the left, as well as additional deep venous reflux in the right popliteal vein (1.9 s) and left common femoral vein (2.2 s), consistent with venous insufficiency.^[11]

In this patient with phlebolymphedema, LSG showed rapid tracer uptake in the inguinal and pelvic lymph nodes, with symmetric nodal visualization from 30 min onward [Figure 3]. Lymphatic channels were relatively well visualized bilaterally with early tracer migration. Unlike Cases 1 and 2, which demonstrated impaired lymphatic transport, this case shows relatively preserved and symmetric lymphatic flow despite clinical swelling. In the setting of bilateral edema and documented venous insufficiency, these findings are suggestive of phlebolymphedema. Overall, the imaging findings, in combination with clinical and venous data, support a diagnosis of phlebolymphedema rather than lymphatic obstruction.

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Figure 3: A 77-year-old woman with bilateral lower extremity swelling, greater on the left, and documented venous insufficiency, consistent with phlebolymphedema. Anterior lymphoscintigraphy images were obtained at (a) 0, (b) 30, (c) 60, and (d) 120 min. Rectangular regions of interest are placed over the bilateral inguinal nodal regions and injection sites. The red and green boxes indicate the right and left ilioinguinal lymph nodes, respectively; the blue and purple boxes indicate the right and left injection sites, respectively. Serial anterior lymphoscintigraphy images show rapid tracer uptake in the inguinal and pelvic lymph nodes, with symmetric nodal visualization from 30 min onward. Lymphatic channels are relatively well visualized bilaterally with early tracer migration. (e) Clinical photograph shows bilateral lower extremity swelling, greater on the left.

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Case 4. Lipedema

A 76-year-old female (BMI 35.7 kg/m²) presented with a long history (>10 years) of bilateral lower extremity enlargement. On examination, both legs showed symmetric enlargement with prominent subcutaneous fat accumulation and relative sparing of the feet, consistent with lipedema. Her medical history included hypertension, type 2 diabetes mellitus, and obesity.

In this patient with lipedema, LSG showed early tracer drainage in both lower extremities, without delayed transport and dermal backflow [Figure 4]. No evidence of lymphatic obstruction was seen on either side. Unlike Cases 1 and 2, which showed impaired lymphatic transport, and Case 3, which reflected venous-related changes, this case shows preserved lymphatic flow despite long-standing swelling. Taken together, the findings are most consistent with lipedema.

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Figure 4: A 76-year-old woman with bilateral lower extremity enlargement, consistent with lipedema. Anterior lymphoscintigraphy images were obtained at (a) 0, (b) 30, (c) 60, and (d) 120 min. Rectangular regions of interest are placed over the bilateral inguinal nodal regions and injection sites. The red and green boxes indicate the right and left ilioinguinal lymph nodes, respectively; the blue and purple boxes indicate the right and left injection sites, respectively. Serial anterior lymphoscintigraphy images show normal tracer drainage in both lower extremities without delayed transport or dermal backflow. No evidence of lymphatic obstruction is seen on either side. (e) Clinical photograph shows symmetric bilateral lower extremity enlargement with relative sparing of the feet.

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DISCUSSION

Lower extremity swelling has a broad differential diagnosis, and in clinical practice, it can be difficult to distinguish among lymphedema, obesity-induced lymphedema, phlebolymphedema, and lipedema. Although these conditions may present with similar clinical features, their underlying pathophysiology differs, which can affect both image interpretation and treatment decisions.

The selected four cases show that LSG should not be interpreted separately from the clinical context. In particular, obesity may complicate the interpretation of quantitative imaging metrics, as increased lymphatic load may coexist with lymphatic dysfunction and influence nodal uptake patterns.^[3] Likewise, venous insufficiency may cause chronic swelling despite relatively preserved lymphatic flow, resulting in an imaging pattern different from that of classic obstructive lymphedema.^[8,12]

Distinguishing among these conditions is clinically important because management strategies differ. Lymphedema is generally managed with lymphatic-directed therapies, including compression, manual lymphatic drainage, pneumatic compression, exercise, and skin care.^[13] In contrast, phlebolymphedema requires not only treatment of the lymphatic component but also evaluation and management of the underlying venous insufficiency, including assessment for venous reflux or obstruction and, when indicated, venous intervention. If venous insufficiency is the primary cause of swelling in the setting of relatively preserved lymphatic function, interventions such as endovenous ablation may help reduce edema by decreasing the lymphatic burden to a manageable level.^[14] Lipedema differs from both entities in that its abnormal fibrotic and nodular adipose tissue is typically resistant to reduction by diet, exercise, or bariatric surgery. Accordingly, management of lipedema is focused on symptom control and supportive care, including compression, exercise, pain management, and psychosocial support, with lipedema reduction surgery considered in selected patients. Therefore, accurate differentiation of lower extremity swelling is important not only for image interpretation but also for appropriate treatment planning.^[15]

The limitation of this case report is that the above cases were selected to illustrate representative imaging patterns rather than to assess diagnostic performance or statistical associations. Accurate interpretation depends on integration with clinical and pathophysiologic context. In this case report, we aimed to demonstrate that LSG can help distinguish the causes of lower extremity swelling.

CONCLUSION

We demonstrated that LSG provides critical information for evaluating lower extremity swelling. Although some imaging findings may overlap, interpreting them together with the clinical history, BMI, physical examination, and venous findings can help distinguish among lymphedema, obesity-induced lymphedema, phlebolymphedema, and lipedema. This is important not only for making the diagnosis but also for choosing the most appropriate treatment.