Abstract
Lymphedema of lower extremities is classified according to the International Society of Lymphology staging system; alternatively, the clinical, etiologic, anatomic, and pathophysiologic classification for venous edema can be used, adapted to lymphedema (CEAP-L). Objective measurement of limb edema can be problematic and different methods can be employed (circumferential measurements, immersion techniques). Bioimpedance spectroscopy and high-resolution cutaneous ultrasonography can be used to evaluate fluid accumulation, as well as the increased dermal thickness and skin echogenicity changes associated with edema. Differential diagnosis starts with the exclusion of other causes of lower extremity swelling. Venous Doppler ultrasound should be performed to exclude deep venous thrombosis or venous disease, which can be associated with lymphedema. Lymphatic impairment is demonstrated by lymphoscintigraphy, which is considered the method of choice to evaluate lymphatic pathways and their drainage pattern. In fact, contrast lymphangiography is no longer routinely performed because it can lead to severe complications, and magnetic resonance lymphangiography with the interstitial injection of an extracellular paramagnetic contrast agent is still an experimental procedure. The main clinical applications of lymphoscintigraphy and clinical results are described in this chapter.
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Keywords
- Lymphedema
- Differential diagnosis
- Lymphoscintigraphy
- Clinical classification of lymphedema
- Edema measurement
- Contrast lymphography
- Magnetic resonance lymphography
- Lymphoscintigraphic patterns
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Learn how lymphedema is defined in clinical practice, and classified and staged according to the International Society of Lymphology (ISL) guidelines and the Clinical, Etiologic, Anatomic, and Pathophysiologic approach in Lymphology (CEAP-L).
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Learn the conditions to be ruled out in the differential diagnosis of lymphedema.
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Learn the main therapeutic options for patients with lymphedema.
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Learn how to use properly different imaging modalities (such as bioimpedance spectroscopy, dual-energy X-ray absorptiometry, ultrasonography, venous Doppler ultrasound, conventional lymphoscintigraphy, PET/CT lymphoscintigraphy, magnetic resonance lymphography) for the diagnosis and management of patients with lymphedema.
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Learn how to integrate the information deriving from each imaging procedure for prognostic assessment and for treatment planning and evaluation.
5.1 Introduction
Patients with lower extremity lymphedema present initially unilateral painless swelling that starts on the dorsal aspect of the foot, but eventually progresses to involve also the proximal portion of the limb. The edema is initially a pitting edema, but over time the subcutaneous tissue becomes fibrotic, resulting in non-pitting brawny edema. The edema can then spread circumferentially if treatment is not initiated, involving the skin which becomes hyperkeratotic, hyperpigmented, and papillomatous or verrucous, with increased skin turgor. The Kaposi-Stemmer sign, in which the examiner is unable to pinch a fold of skin at the base of the second toe on the dorsal aspect of the foot, indicates clinical lymphedema [1,2,3]. Ultimately, the skin is at risk for ulcerating and is the site of subsequent infection. Swelling associated with lymphedema results in a sensation of heaviness, discomfort, and impaired mobility of the limb. Angiosarcoma may develop in chronic lymphedematous limbs (Stewart-Treves syndrome), but is most commonly seen in the upper extremity following mastectomy with axillary lymph node dissection [4]. This condition is often referred to as lymphangiosarcoma, which is actually a misnomer, since the tumor is not derived from lymphatic vessels, but is rather derived from vascular endothelial cells within a condition of chronic lymphedema.
The International Society of Lymphology (ISL) has established a staging system for defining the severity of this disease. It is thus possible to identify the progression of the condition and the potential for successful treatment and improvement. This staging system, which applies only to the limbs (arms and legs), is based on the degree of swelling and on the condition of the skin and tissues. In the latest revision of the document for the evaluation and management of peripheral lymphedema [5] a four-stage scale for classification of a lymphedematous limb has been defined for conditions with increasing severities, as follows:
5.1.1 Stage O Lymphedema: Latent or Preclinical Stage
At this stage the patient is at risk of developing lymphedema; however, no swelling or other visible evidence of impaired lymph drainage is present. Stage 0 can be present for months, or years, before more severe signs appear. If specialized treatment is started at this stage, it may be possible to prevent the development of further stages of lymphedema.
5.1.2 Stage I Lymphedema
This condition indicates an early accumulation of interstitial fluid that is relatively high in protein content. There is visible swelling with protein-rich lymph. The swelling can be temporarily reduced by elevation of the limb; however, it soon reappears when the limb is returned to a normal position. The swollen tissues are soft, and pitting edema is present. Treatment should initiate as early as these clinical signs are detected, since waiting for the swelling to increase, or for an infection to develop, only makes the condition more difficult to treat. Prompt treatment of this stage can often control the condition and may prevent it from becoming more severe.
5.1.3 Stage II Lymphedema
This stage denotes a further increase in swelling accompanied by concomitant tissue changes. Elevation of the limb will not reduce the swelling, and tissues become increasingly firm, due to fibrosis. Pressure against the limb produces only a slight pitting, or no pitting at all. The tissue changes at this stage increase the risks of even greater swelling, fibrosis, infections, and skin problems. Stage II lymphedema can usually be improved with intense treatment.
5.1.4 Stage III Lymphedema
Also known as lymphostatic elephantiasis , in this condition the tissue becomes extremely swollen and thickened, due to blockage of lymph flow and buildup of fluid in tissues. The tissues become increasingly fibrotic. Pressure does not produce any pitting. Normal elasticity is lost, and the skin hangs in folds and may change color. Papillomas and hyperkeratosis can develop. Changes in skin texture are disfiguring and can limit mobility. Infections become more common because of increased risks of ulcerations of the skin. These infections include fungal infections and open wounds that form within the skin folds. With intense therapy, stage III lymphedema can be improved and potentially be prevented from becoming even worse; however, it is rarely reversed to an earlier stage.
Within each stage, a functional severity assessment utilizes simple volume differences commonly determined using circumferential measurement (preferentially by flexible non-stretch tape) assessed as follows:
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Minimal (>5–<20% increase in limb volume), alternatively subdivided into
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>5–10% as minimal
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>10–<20% as mild
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Moderate (20–40% increase)
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Severe (>40% increase)
The above ISL stages only refer to the physical condition of the extremities. A more detailed and inclusive classification must be formulated according to improved understanding of the pathogenic mechanisms of lymphedema (e.g., nature and degree of lymphangiodysplasia, lymph flow perturbations, and nodal dysfunction as defined by anatomic features and physiologic imaging and testing), and underlying genetic disturbances, which are increasingly being elucidated. Recent publications combining both physical (phenotypic) findings with functional lymphatic imaging as well as those classifications which propose inclusion of disability grading, assessment of inflammation, and even immunohistochemical changes determined by biopsy of nodes/vessels may be forecasting the future evolution of staging. In addition, incorporation of genotypic information, expanded from what is available even in current screening, would further advance staging and classification of patients with peripheral (and other) lymphedema.
Factors such as extension, occurrence of erysipelas attacks, inflammation, and other descriptors or complications within their own individual severity determinations might also be included.
A new classification of limb lymphedema was proposed in 2009, inspired by the Clinical, Etiologic, Anatomic, and Pathophysiologic (CEAP) classification for chronic venous insufficiency of the lower limbs. It adopts the acronym CEAP by adding the letter L (Lymphatic) to underline the aspect “lymphedema.” This clinical classification is subdivided into five classes depending on the presence of clinical signs such as:
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The presence of lymphedema: 5-point scale:
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No edema
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Edema that disappears with night rest
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Edema that persists after night rest
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Fibrotic edema
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Elephantiasis with skin lesions
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Extension of lymphedema:
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Lower limbs:
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Foot, leg, thigh, genital, trunk
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Upper limbs:
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Hand, forearm, arm, shoulder
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Presence of lymphangitis and/or leg ulcers
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Loss of functionality of the limb (grade of disability)
The etiological aspect considers two types of alterations of the lymphatic system: congenital and acquired. Pathophysiological conditions are subdivided into five groups: agenesia or hypoplasia, hyperplasia, reflux, overload, and obstruction. The CEAP-L classification was created to categorize patients with definite and objective marks (Table 5.1), to generate clinical reports with a common and clear vocabulary, to stage the disease, to evaluate treatment, and to obtain epidemiological and statistical data [6]. Indeed, these authors found the application of the classification easy and highly reproducible in their experience.
Key Learning Points
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In patients with lower extremity lymphedema, clinical presentation progressively evolves from unilateral painless swelling on the dorsal aspect of the foot with pitting edema to circumferential involvement of the proximal portion of the limb; then to fibrosis of the subcutaneous tissue, non-pitting brawny edema, and skin changes that include hyperkeratosis and hyperpigmentation; and finally to papillomatous or verrucous skin, with increased skin turgor and increased risk for ulcers and subsequent infection.
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The Kaposi-Stemmer sign, in which the examiner is unable to pinch a fold of skin at the base of the second toe on the dorsal aspect of the foot, indicates clinical lymphedema.
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Angiosarcoma (Stewart-Treves syndrome) may develop in chronic lymphedematous limbs, as commonly seen in the upper extremity following mastectomy with axillary lymph node dissection.
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The ISL staging system applies only to the limbs and is based on the degree of swelling and on the condition of the skin and tissues. The current version is based on a three-stage scale for classification (from stage 0 to stage III); within each stage, a functional severity assessment (from minimal to severe) is used to assess the volume of the affected limb.
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The CEAP-L classification is subdivided into classes depending on the presence of clinical signs, such as presence and extension of lymphedema, presence of lymphangitis and/or leg ulcers, and loss of functionality of the limbs.
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The CEAP-L classification enables to categorize patients, generate clinical reports, stage the disease, evaluate treatment, and obtain epidemiological and statistical data.
5.2 Differential Diagnosis
Lymphedema should be considered whenever an edematous extremity without pain or inflammation is observed. Chronic venous insufficiency can be difficult to differentiate from early lymphedema because both exhibit pitting edema, and the skin changes typical of late-stage lymphedema are not present yet. Nevertheless, chronic venous insufficiency is often bilateral, rather than unilateral as is generally the case for lymphedema. Lymphoscintigraphy is often necessary to distinguish the two conditions, although such discrimination cannot always be made, since chronic venous insufficiency can actually lead to secondary lymphedema. Similarly, deep vein thrombosis can cause a postphlebitic syndrome, which can result in lipodermatosclerosis and chronic swelling of the limb [2, 3]. In nonfilarial regions of tropical Africa, Central America, and the Indian subcontinent, there is a condition that clinically presents in a similar fashion as filariasis, called podoconiosis, or nonfilarial elephantiasis. Moreover, in case of unilateral extremity lymphedema, especially in adults, solid tumors (primary and/or metastatic), lymphomas, and soft-tissue sarcomas, which may obstruct or invade more proximal lymphatics, must be considered.
Exclusion of general medical causes of lower extremity swelling should be a priority. These causes include, but are not limited to, renal failure, protein-losing nephropathy, hypoalbuminemia, congestive heart failure, pulmonary hypertension, drug-induced edema, obesity, and pregnancy [7]. Other conditions to consider in the differential diagnosis include lipedema (also known as lipomatosis of the leg), “armchair legs” (descriptive term that results from sitting in a chair all day and night with one’s legs in a dependent position), and postoperative swelling.
Key Learning Points
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Chronic venous insufficiency is similar in presentation to early-stage lymphedema, but it is often bilateral rather than unilateral.
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Deep vein thrombosis can cause a postphlebitic syndrome, which can result in lipodermatosclerosis and chronic swelling of the limb.
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In nonfilarial regions of tropical Africa, Central America, and the Indian subcontinent, there is a condition that clinically presents in a similar fashion as filariasis, called podoconiosis.
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In case of unilateral limb lymphedema, especially in adults, solid tumors (primary and/or metastatic), lymphomas, and soft-tissue sarcomas must be considered.
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Lower extremity swelling could originate from general medical causes such as renal failure, protein-losing nephropathy, hypoalbuminemia, protein-losing enteropathy, congestive heart failure, pulmonary hypertension, drug-induced edema, obesity, and pregnancy.
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The diagnostic differential includes also lipedema and “armchair leg” edema.
5.3 Diagnostic Characterization
In 1976, Stemmer described the inability to pinch the skin of the proximal phalanx of the second or third toe in patients with lymphedema [8]. If the examiner is unable to grab the dorsal skin between his/her thumb and index finger, then the “Stemmer sign” is positive suggesting lymphedema [9]. However, the thickened skin and excess subcutaneous fibroadipose tissue with edema (as a consequence of inflammation, adipose deposition, and fibrosis) [10,11,12] might prevent the pinching of the dorsal skin of the extremity in patients with lymphedema. In contrast, other causes of swelling or limb overgrowth such as venous stasis, heart disease, liver failure, renal insufficiency, rheumatologic disease, lipedema, hemihypertrophy, posttraumatic swelling, and vascular anomalies do not result in enough inflammatory fibroadipose formation to prevent the pinching of the dorsal skin of the hand or foot. Furthermore, abnormalities in the body mass index (BMI) have been found to be associated with both false-negative and false-positive Stemmer signs. In particular, patients with lymphedema and a normal or reduced BMI could exhibit minimal swelling and a falsely negative sign, whereas obese patients without lymphedema could have a false-positive sign. On the other hand, obesity per se negatively affects lymphatic function by causing inflammation, fibrosis, and destruction of lymphatics [13,14,15]. The Stemmer sign has a sensitivity of 92% to predict lymphedema in patients who have the disease and a specificity of 57% to exclude lymphedema in patients who do not have the condition. A negative Stemmer sign does not rule out lymphedema, typically in patients with a normal BMI and stage I disease [16].
Objective measurement of limb swelling can be problematic. On the other hand, assessing size differences of the extremities and quantitative discrepancies between the unaffected and the affected limbs is critical, particularly in the early phases of lymphedema. Estimating differences in limb volume has been used as an indirect measure of changes in lymph fluid volume over time or with treatment, and is typically done through circumferential measurements, or through immersion techniques based on the measurement of volume displacement [17]. However, these methods are time consuming and somewhat operator dependent. Moreover, since these techniques measure only the overall volume of the limbs, possible differences in volume caused by left-right dominance, asymmetrical muscle atrophy, fibrous tissue deposition, or weight gain may incorrectly be attributed to fluid accumulation [18].
Bioimpedance spectroscopy (BIS) is a noninvasive procedure wherein an electrical current is passed through a body segment, and impedance to flow of the current is measured. This technique, which attempts to directly measure lymph fluid volume [19], is based on the principle that tissues such as fat and bone act as insulators, while electrolytic fluids conduct electricity; these features would make it possible to assess properties unique to lymphatic fluid, through measurement of the flow of current. BIS measures lymphedema based on the fact that low-frequency currents selectively pass through extracellular fluid compartments, whereas high-frequency currents pass through both the intra- and the extracellular fluids (the latter being selectively expanded in lymphedema) [20]. BIS analyzes both lymph fluid impedance and total fluid impedance [21], and impedance to current flow has been found to inversely correlate with fluid accumulation; therefore, reduced impedance values in an extremity indicate the presence of lymphedema.
Dual-energy X-ray absorptiometry (DEXA, or bi-photonic absorptiometry) may help classify and define a lymphedematous limb but its greatest potential use may be to assess the chemical composition of limb swelling (especially increased fat deposition, which by its added weight can lead to muscle hypertrophy) [5].
A variety of other techniques have been described to measure limb edema, but most of them have not been validated or are either too complex or expensive for routine use [22, 23]. A practical difficulty in the clinical setting, even with validated techniques, is that extravascular fluid volume undergoes cyclic changes over days or weeks, and limb volume also has a pronounced circadian variation.
High-resolution cutaneous ultrasonography can be used to identify lymphedema, based on the presence of increased dermal thickness and decreased echogenicity as compared with lipedema and venous insufficiency [24]. In fact, in lymphedema loss of echogenicity of the skin and global and homogeneous dermal hypoechogenicity are observed, in contrast to the elective superficial dermis localization of edema described in patients with venous insufficiency [25, 26]. These findings are caused by the accumulation of protein-rich exudative interstitial fluid in the skin and subcutaneous tissue; this fluid remains trapped at the production site because of its high protein content, whereas transudate edema caused by venous insufficiency is more mobile and accumulates in the superficial dermis only. However, in order to analyze dermal changes for identifying and quantifying dermal edema, the ultrasound device should operate at 20 MHz [27]. Figure 5.1 shows the clinical and ultrasound appearance for patients with lymphedema and with lipedema, respectively.
Whenever the clinical diagnosis of lymphedema is controversial, it can be either confirmed or ruled out with lymphoscintigraphy, which is considered the method of choice to evaluate the lymphatic pathways and their drainage pattern [28]. Direct lymphangiography using an iodine oil contrast agent capable of visualizing the lymphatics [29] (Fig. 5.2) is no longer routinely performed, because it can lead to life-threatening complications and is difficult to perform [31].
A venous Doppler ultrasound examination is often required to assess for deep venous thrombosis or venous disease, which can be associated with lymphedema. In fact, 20–30% of the patients with advanced chronic venous disease have associated lymphatic dysfunction, presumably due to secondary damage from overload, or from recurrent cellulitis [32].
If filariasis is suspected, one can perform a blood smear (collected at night) looking for the presence of microfilariae. Antigen testing by immunochromatographic card test (Binax) or enzyme-linked immunosorbent assay (TropBio) is more sensitive than microfilaria detection, irrespective of the time of the day blood is drawn [33].
In addition to a thorough clinical history and physical examination, other diagnostic tests to rule out alternative causes of lower extremity edema include a complete metabolic profile, serum albumin, and urinalysis to screen for renal failure, hypoalbuminemia, and/or protein-losing enteropathy.
Key Learning Points
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The Stemmer sign has 92% sensitivity to predict lymphedema in patients who have the disease and 57% specificity to exclude lymphedema in patients without lymphedema.
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The body mass index (BMI) is associated with both false-negative and false-positive Stemmer signs, as a high BMI can lead to a false-positive while a low BMI can lead to a false-negative Stemmer sign.
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Circumferential measurements, or immersion techniques based on displacement, can be used to measure the limb volume.
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Reduced impedance values in an extremity are correlated with lymphedema.
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DEXA may be used to assess the chemical composition of limb swelling, especially increased fat deposition and muscle hypertrophy.
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Ultrasonography can rule out lipedema and venous insufficiency. In lymphedema a loss of echogenicity of the skin and a global and homogeneous dermal hypoechogenicity are observed, in contrast to the elective superficial dermis localization of edema described in venous insufficiency.
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A venous Doppler ultrasound examination is often needed to assess for deep venous thrombosis or venous disease, which can be associated with lymphedema.
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A blood smear or an antigen test can be performed to rule out filariasis.
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A complete metabolic profile, serum albumin, and urinalysis to screen for renal failure, hypoalbuminemia, and/or protein-losing enteropathy may be necessary for a complete differential diagnosis of lymphedema.
5.4 Management of Lymphedema
As a chronic and potentially disabling condition, lymphedema is associated with significant morbidity in terms of functional, cosmetic, and emotional consequences. Treatment efforts aim at minimizing the associated swelling, at restoring cosmesis and functionality of the limb, and at preventing potential complications associated with lymphedema, in particular infections such as cellulitis and lymphangitis. Treatments are lengthy and expensive, and involve a multidisciplinary approach that can include rehabilitative therapy (elevation, exercise, compression devices, manual lymph drainage), skin care, and surgery [34, 35]. Therapy of peripheral lymphedema can be classified into conservative or nonoperative procedures and operative procedures.
Nonoperative treatment consists of physical therapy and adjuvants such as combined physical therapy and intermittent pneumatic pressure (or “pneumomassage”). Pneumomassage, thermal therapy, simple elevation (particularly by bed rest) of a lymphedematous limb, low-level laser therapy, and aquatic therapy/water-based exercise programs are the most common nonoperative procedures.
Drug therapies have so far been disappointing in the management of lymphedema. Although diuretic drugs are often prescribed, this therapy is actually not beneficial in lymphedema and should be employed only in patients with specific comorbidities or complications. Coumarin, a benzopyrone, has been reported to have some favorable effect on lymphedema, probably due to its mechanism of action that reduces vascular permeability, and thus capillary filtration. In addition, coumarin is thought to activate macrophage activity, which increases protein degradation, thus resulting in a reduction in fibrotic tissue. However, the clinical trials reported so far are generally of poor quality and long-term results of treatment of lymphedema with these agents are not available. Furthermore, some reports of hepatotoxicity have raised serious concern on their use [36]. Antibiotics should be administered for superimposed acute lymph stasis-related inflammations (cellulitis/lymphangitis or erysipelas) [5]. In case of lymphatic filariasis to eliminate microfilariae from the bloodstream, diethylcarbamazine, albendazole, or ivermectin is recommended [5]. Efficacy of boosting immunity by intra-arterial injection of autologous lymphocytes is unclear and requires independent, reproducible validation. Recent proposals for the use of anti-inflammatory drugs have not yet demonstrated efficacy and may face drawbacks if administered in the long term [5].
No special diet or restricted fluid intake has proved to be of therapeutic value for most uncomplicated peripheral lymphedemas. In breast cancer-related lymphedema and in obese patients, weight reduction has been shown to help. In chylous reflux syndromes a diet as low as possible or even free of long-chain triglycerides (absorbed via intestinal lacteals) and high in short- and medium-chain triglycerides is of benefit especially in children. Specific vitamin supplements may be needed in very low or no-fat diets. Some groups suggest diets with substances that may lower inflammation, but current clinical evidence is not sufficiently validated [5].
In complicated patients with lymphatic system overgrowth such as lymphangiodysplasia, specialized centers utilize pharmacotherapeutic options such as octreotide, OK-432, rapamycin, or other antiproliferative agents, in particular in newborns and children [5].
Surgical procedures aim to alleviate peripheral lymphedema by enhancing lymph return. When performed in advanced stages, surgery usually requires long-term combined physical therapy and/or other “pneumomassage” after the procedure to maintain edema reduction and ensure vascular/shunt patency.
Worldwide, surgical resection (in several forms) is the most widely used operative technique to reduce the bulk of lymphedema, in particularly in cases affecting the genitalia. Microsurgical procedures include (1) derivative methods such as lympho-venous anastomoses and (2) multiple lymphatic-venous anastomoses in a single surgical site with both the superficial and deep lymphatics. By these procedures a positive pressure gradient (lymphatic-venous) is created, thus evading the phenomenon of gravitational reflux without interrupting the distal peripheral superficial lymphatic pathways. Reconstructive methods are sophisticated techniques involving the use of a lymphatic collector (LLA) or an interposition vein segment (LVLA) to restore lymphatic continuity in lymphedema conditions due to a locally interrupted lymphatic system. Autologous lymph vessel transplantation mimics the normal physiology and has shown long-term patencies of more than 10 years. This procedure has generally been reserved to patients with unilateral peripheral lymphedema of the leg (due to the need for one healthy leg to harvest the graft), but it has also been utilized for bilateral upper extremity lymphedema where two healthy legs are available for harvesting lymphatic vessels [5].
Transplantation of superficial lymph nodes from an uninvolved area together with its vascular supply (vascularized lymph node transplantation) to the site of lymphadenectomy for cancer has been proposed both as a preventive and therapeutic approach to limb lymphedema. Liposuction (or suction-assisted lipectomy) using a variety of methods has been shown to completely reduce non-pitting, primarily non-fibrotic, extremity lymphedema due to excess fat deposition that has not responded to nonoperative therapy in both primary and secondary lymphedemas [5]. Surgical resection by “debulking” of excess skin and subcutaneous tissue of the lymphedematous limb can be associated with complications such as superficial lymphatic removal, significant scarring, risk of infection, and difficult wound healing. Debulking has been used mainly in the treatment of the most severe forms of fibrosclerotic lymphedema (elephantiasis) and in cases of advanced genital lymphedema. Caution should be exercised in removing enlarged lymph nodes or soft-tissue masses (e.g., lymphangiomas) in the affected extremity, as lymphedema may worsen thereafter [5].
The implantation of engineering/lymphatic tubes to transport lymph or engineered tubes/devices to promote new substitute lymphatic growth have not yet documented long-term value in large-scale studies, and these techniques are currently under controlled clinical investigation [5].
Omental transposition, enteromesenteric bridge operations, and implantation of threads to promote perilymphatic spaces (substitute lymphatics) have not shown long-term value and at the moment should not be considered as valid surgical options [5].
Key Learning Points
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Lymphedema is associated with significant morbidity including functional, cosmetic, and emotional consequences.
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Therapy is based on a multidisciplinary approach including rehabilitative therapy, skin care, and surgery.
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Nonoperative treatments consist of physical therapy and adjuvants.
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Medical treatments (diuretics, coumarin), diet, or restricted fluid intake is of limited value in patients with peripheral lymphedema.
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Surgical procedures aim to alleviate peripheral lymphedema by enhancing lymph return.
-
Surgery usually requires long-term combined physical therapy and/or other “pneumomassage” treatments after the procedure.
-
Surgical resection (in several forms) is the most widely used operative technique to reduce the bulk of lymphedema.
-
Microsurgical procedures include (1) derivative methods such as lymphatic-venous anastomoses and (2) multiple lymphatic-venous anastomoses in a single surgical site with both the superficial and deep lymphatics.
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Sophisticated reconstructive techniques involve the use of a lymphatic collector or an interposition vein segment to restore lymphatic continuity.
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Liposuction has been shown to completely reduce non-pitting, primarily non-fibrotic, in patients with extremity lymphedema.
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Debulking has been used mainly in the treatment of the most severe forms of fibrosclerotic lymphedema (elephantiasis) and in cases of advanced genital lymphedema.
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The implantation of engineering/lymphatic tubes to transport lymph or engineered tubes/devices is currently under clinical investigation.
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Omental transposition, enteromesenteric bridge operations, and implantation of threads to promote perilymphatic spaces have not shown long-term value and at the moment should not be considered as valid surgical options.
5.5 Lymphoscintigraphy in the Management of Lymphedema
Qualitative and quantitative lymphoscintigraphy has been widely used for the differential diagnosis of lymphedema, for predicting the risk to develop lymphedema as well as for assessing the efficacy of physical and/or surgical treatments.
5.5.1 Lymphoscintigraphy for the Differential Diagnosis of Lymphedema
Lymphoscintigraphy has proved extremely useful for depicting the specific lymphatic abnormality and it has largely replaced conventional oil contrast lymphography for visualizing the lymphatic network. Although different protocols can be used (different radiotracers and administered activities, different injection volumes, intracutaneous versus subcutaneous or subfascial injections, one or more injections, different protocols of passive and active physical activity, varying imaging times, static and/or dynamic techniques—as discussed in detail in Chap. 4), the images, which can be easily repeated, offer remarkable insight into lymphatic structural abnormalities and (dys)function. Lymphoscintigraphy provides a functional assessment of lymphatic pumping, stasis, and obstruction that guides treatment and determines prognosis for expected outcome of treatment [37,38,39,40]. Lymphoscintigraphy is also employed to define the clinical characteristics, investigations, management, and outcomes of lymphedema in pediatric patients [41]. Purely qualitative analysis has been reported to be very accurate for confirming or excluding the diagnosis of lymphedema, with sensitivity as high as 92–96% and specificity as high as 100% [42]. Nevertheless, etiology of lymphedema is not invariably identified solely on the basis of lymphoscintigraphic images. In fact, despite the fact that patients with primary lymphedema tend to show a lack of lymphatic vessels and absent or delayed transport whereas those with secondary lymphedema tend to show obstruction with visualization of discrete lymphatic trunks and slow transport [43], primary lymphedema cannot be reliably differentiated from secondary lymphedema on the basis of lymphoscintigraphic findings alone [44].
For the lower limbs, a high positive association of popliteal lymph node uptake with the severity of lymphatic obstruction defined as appearance of dermal back flow was found in patients with both primary and secondary lymphedema [45, 46]. The duration of lymphedema was also longer in patients with dermal backflow and popliteal lymph nodes visualized during lymphoscintigraphy; both popliteal lymph node uptake and dermal backflow were important signs indicating longer disease duration and higher severity of lymphatic dysfunction [46]. In addition, a strong association between skin rerouting and popliteal lymph node visualization has been found; in particular, skin changes were detected in 38% of the patients with positive popliteal node uptake [45].
A recent study showed that transit time and dermal backflow at lymphoscintigraphy (found in about 97% of extremities by 45 min postinjection) did not predict clinical severity when adjusted for other clinical variables [47]. A subgroup analysis of a large study showed that false-negative lymphoscintigraphy occurs most likely in primary lymphedema with long duration of disease and infection history similar to patients with true-positive lymphoscintigraphy. However, repeated lymphoscintigraphies over time during follow-up showed appearance of lymphatic dysfunction consistent with lymphedema. Therefore, the results of this study suggest that patients with a high clinical suspicion of lymphedema and a normal lymphoscintigram are better treated conservatively, and that lymphoscintigraphy should be repeated in these cases [48].
Key Learning Points
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Qualitative and quantitative lymphoscintigraphy has been widely used for the differential diagnosis of lymphedema, for predicting the risk to develop lymphedema as well as for assessing the efficacy treatments, as it provides a functional assessment of lymphatic pumping, stasis, and obstruction in adults as well as in pediatric patients.
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Qualitative analysis of lymphoscintigraphy has 92–96% sensitivity and specificity close to 100% for the diagnosis of lymphedema.
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Primary lymphedema cannot be reliably differentiated from secondary lymphedema on the basis of lymphoscintigraphic examination alone.
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For the lower limbs, a high positive association of popliteal lymph node uptake with the dermal back flow was found in patients with both primary and secondary lymphedema.
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The duration of lymphedema is longer in patients with dermal back flow and popliteal lymph nodes visualized during lymphoscintigraphy.
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Patient with a high clinical suspicion of lymphedema and a normal lymphoscintigram are better treated conservatively; lymphoscintigraphy should be repeated in these cases to show the underlying lymphatic dysfunction.
5.5.1.1 Lymphoscintigraphy in Lipedema
In a recent study [49] in a prospective cohort study of women meeting the clinical criteria of lipedema, lymphoscintigraphy showed abnormal patterns in 47% of the patients, with no significant differences between the severity of lymphoscintigraphic abnormalities and clinical stage of lipedema. In addition, lymphoscintigraphic findings showed that patients with lipedema also presented impaired lymphatic transport assessed as transport index (TI) abnormalities. In addition, more severe lipedema may be associated with greater lymphatic transport abnormalities, with the mean TI being significantly greater for extremities with severe (stage 3/4) lipedema than those with mild or moderate (stage 1/2) lipedema (15.1 versus 9.7, P = 0.049). Mean difference in TI scores between each lower extremity for individual patients was 6.43 (±7.96 standard deviation) [50].
Key Learning Points
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Approximately 47% of patients with clinical lipedema have lymphoscintigraphic abnormalities indicating impaired lymphatic drainage.
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More severe lipedema may be associated with greater abnormalities in lymphatic transport.
5.5.1.2 Lymphoscintigraphy for Predicting the Risk to Develop Lymphedema
Lymphoscintigraphy can be used to predict the risk to develop lymphedema. In fact, in patients undergoing surgery for breast cancer, abnormalities of lymphatic drainage in postsurgical lymphoscintigraphy increases the risk of developing arm lymphedema [51,52,53]. It has also been shown that upper extremity lymphatic drainage after axillary lymph node dissection is not impaired in terms of lymphatic transport and/or venous function impairment after the axillary lymph node dissection procedure in comparison to the preoperative status. Qualitative analysis of lymphoscintigrams revealed most commonly disappearance of previously functioning lymph nodes and appearance of dermal backflow in subjects who developed lymphedema thereafter. Conversely, appearance of functioning lymph nodes in different locations after axillary lymph node dissection may indicate protection from development of upper extremity lymphedema [54]. In the postoperative period after breast surgery, a significant worsening of the degree of lymph node uptake and the velocity of lymph node visualization in the absence of dermal backflow and collateral circulation was observed, independently of postoperative complications or clinical characteristics [55]. On the contrary, the maximum lymphatic-pump pressure in the women who later developed breast cancer-related lymphedema was 1.7-fold higher than in those who did not develop lymphedema. Moreover, the rate of lymph tracer transport into the forearm was 2.2-fold greater in the women who later developed lymphedema [56]. Quantitative lymphoscintigraphy performed between 4 and 8 weeks after surgery to evaluate the lymphatic system in the early postoperative period, to be correlated with clinical results at the 1-year follow-up, revealed that the ratio of radiocolloid uptake rate of the affected to normal axilla and the ratio of radioactivity of the affected to normal axilla were significantly lower in the lymphedema group than in the non-lymphedema group. After adjusting the model for all significant variables (body mass index, N-stage, T-stage, type of surgery, and type of lymph node surgery), the ratio of radioactivity of the affected to normal axilla was associated with lymphedema (odds ratio = 0.14; 95% confidence interval, 0.04–0.46; P = 0.001) [57]. Similarly, functional lymphatic changes detected by lymphoscintigraphy after external beam radiation therapy can predict the development of arm lymphedema. Recently, lymphoscintigraphy including SPECT/CT of the axillary region has been employed to evaluate the impact of including, as target volumes in the radiation treatment plan, lymph nodes involved in arm drainage that could affect lymphedema [53]. This study demonstrated that radiation doses to these lymph nodes vary between zero and the full prescribed dose, therefore possibly affecting the development of lymphedema.
In patients with gynecological cancer-related lymphedema the prognostic assessment of qualitative lymphoscintigraphy before complex decompressive therapy showed that severity of dermal back flow, clinical stage, and therapy compliance are independent predictors of therapeutic response [58].
In patients undergoing surgery for melanoma of the trunk, primary prevention with microsurgical lympho-venous anastomosis prevented lymphedema after inguinal lymphadenectomy. In addition, lymphatic-venous multiple anastomoses proved to be successful for treating clinical lymphedema, particularly at the early stages [59]. Similar results have also been reported for patients with breast cancer [60, 61]. In addition, when lymphoscintigraphies performed in patients who underwent lymph node dissection (limited to the intra-abdominal lymph nodes) with or without radiotherapy for histologically confirmed ovarian, uterine, or prostate cancer were compared to lymphoscintigraphies obtained in patients with primary lower limb lymphedema, the appearance of lower limb lymphedema does not appear to be related to cancer treatment(s), but rather lower limb lymphedema may represent the development of a primary lymphatic disease that was latent prior to surgery [62].
The lack of visualization of inguinal lymph nodes predicted late postoperative leg edema also in patients with tibial fractures treated surgically [63].
Key Learning Points
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In patients undergoing surgery for breast cancer, lymphoscintigraphy shows disappearance of previously functional lymph nodes and appearance of dermal backflow in subjects who developed lymphedema, while appearance of functional lymph nodes in different locations after surgery indicates protection from the development of upper extremity lymphedema.
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Quantitative lymphoscintigraphy shows that the ratio of radioactivity of the affected to normal axilla is significantly lower in the lymphedema patients.
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Severity of dermal back flow, clinical stage, and therapy compliance are independent predictors of therapeutic response in patients with gynecological cancer-related lymphedema before complex decongestive therapy.
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In patients submitted to intra-abdominal lymph node dissection for histologically confirmed cancer, the appearance of lower limb lymphedema seems to be correlated with the development of a primary lymphatic disease that was latent prior to the therapeutic interventions.
5.5.1.3 Lymphoscintigraphy for Assessing the Efficacy of Physical and/or Surgical Treatments
Lymphoscintigraphy has been used in the assessment of interventional approaches in patients with lymphedema, including manual lymphatic massage [64,65,66,67,68,69], pneumatic compression [70,71,72], hyperthermia [73], pharmacologic therapies [74, 75], and surgery (both microsurgery [76,77,78,79] and vascularized lymph node transplantation [80]).
In women undergoing therapy for postmastectomy lymphedema, the degree of lymphatic function impairment prior to the treatment as assessed by lymphoscintigraphy correlates inversely with the outcome of manual lymphatic therapy [37]. Similarly, in patients with clinical stage I unilateral extremity lymphedema, lymphoscintigraphy can predict long-term response to multi-approach physical therapy. In this regard, the visualization of a main lymphatic vessel without collateral lymphatic vessels was the best predictor for a favorable response [81], as also was persisting lymph node visualization 4 h after radiocolloid administration [82].
In a recent study, the extent of dermal backflow (small extent/large extent), the level of lymphatic flow (trunk flow pattern/upper arm-restricted pattern/forearm-restricted pattern groups), and the visualization of lymph nodes (visualized/non-visualized) at lymphoscintigraphy were correlated with the change in the circumferential difference between the two sides of the body, the upper arm and forearm, with the clinical outcome being variable in patients undergoing nonsurgical treatment. Upper arm edema was more significantly reduced after sympathetic ganglion block rather than after complex decongestive therapy in the small extent group, the forearm-restricted pattern group, and the non-visualized group. In the other groups, sympathetic ganglion block and complex decongestive therapy showed comparable therapeutic effects without statistical differences [83]. Lymphatic regeneration following both free-tissue [84] and lymphatic vessel transplantation [85] has also been assessed with lymphoscintigraphy. Additionally, lymphoscintigraphic classification of patients with secondary lymphedema correlates closely with the clinical stage scale and with findings at intraoperative examination during lymphatico-venous anastomosis [86]. In unilateral lymphedema, lymphoscintigraphic abnormalities of the contralateral limb may also be demonstrated in about 32% of patients [87]. The changes in clinical symptoms and the postoperative lymphoscintigraphic changes did not always correspond. However, there was a trend for the percentage of lymphoscintigraphic deterioration to be greater in the group with clinical deterioration [88].
An improvement of the transport index, well correlated with arm’s volume reduction, was observed during long-term follow-up of patients with lymphedema treated with autologous lymph vessel transplantation, confirming that this procedure indeed improves lymph drainage [89, 90]. Similarly, postoperative lymphoscintigraphy showed improved lymphatic drainage in all cases of lymphedema submitted to a combined double-gastroepiploic vascularized lymph node transfer and a modified radical reduction with preservation of perforator vessels [80, 91].
The indications for lymphoscintigraphy can schematically be summarized as follows:
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Differential diagnosis of edema to distinguish venous from lymphatic etiology
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Assessment of pathways of lymphatic drainage
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Quantitation of lymph flow
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Identification of patients at high risk of developing lymphedema following axillary lymph node dissection
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Evaluation of the efficacy therapeutic interventions for lymphedema
Lymphoscintigraphy with 99mTc-sulfur colloid has recently been compared to the diagnostic performance of a new technique, PET/CT after interstitial injection of 68Ga-labeled NOTA Blue Evans (68Ga-NEB) [92]. This study showed that 68Ga-NEB activity could be clearly observed in the lymphatic route on the PET/CT images from all the patients, showing consistent results in 8/13 cases; diagnostic images of 68Ga-NEB PET/CT were obtained much faster than the conventional lymphoscintigraphic images. In the remaining five cases, 68Ga-NEB PET/CT provided additional information in five patients (38.5% of the whole group under study). In particular, one patient had chyloperitoneum, two had chylothorax, and one had postsurgical limp swelling; 99mTc-sulfur colloid lymphoscintigraphy was unable to localize the site of chyle leak, whereas 68Ga-NEB PET/CT successfully identified the leak (Figs. 5.3, 5.4, and 5.5). In addition, in a young woman who had cystic lesions and pleural effusion, the site of chest abnormality was visualized on 68Ga-NEB PET/CT but not on 99mTc-sulfur colloid lymphoscintigraphy (Fig. 5.6). Therefore, this study suggests the feasibility of using of 68Ga-NEB PET/CT as an alternative to conventional lymphoscintigraphy in the evaluation of lymphatic disorders.
Key Learning Points
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Lymphoscintigraphy has been used to assess interventional approaches in patients with lymphedema, including manual lymphatic massage, pneumatic compression, hyperthermia, pharmacologic therapies, and surgery, both microsurgery and vascularized lymph node transplantation.
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In women undergoing therapy for postmastectomy lymphedema, the degree of lymphatic function impairment prior to the treatment as assessed by lymphoscintigraphy correlates inversely with the outcome of manual lymphatic therapy.
-
In patients with clinical stage I unilateral extremity lymphedema the visualization of a main lymphatic vessel without collateral lymphatic vessels at lymphoscintigraphy is the best predictor of long-term response to multi-approach physical therapy.
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68Ga-NEB PET/CT provides more information than lymphoscintigraphy with 99mTc-sulfur colloid, is faster than conventional lymphoscintigraphy, and is able to localize the site of the leak especially inside the thorax and abdomen.
5.6 X-Ray Computed Tomography and Magnetic Resonance Imaging
X-ray computed tomography (CT) scanning or magnetic resonance imaging (MRI) of the lower extremities can detect in patients with lymphedema a “honeycomb” pattern of the subcutaneous tissue that is not characteristic of other types of edema. CT and MRI have been used to describe the morphologic changes due to the subcutaneous lipomatous hypertrophy [93,94,95,96].
CT-lymphography (CT-LG) was performed in patients with upper limb lymphedema [97]. Three-dimensional observation of deeper tissues at CT-LG has been used to help elucidating the mechanism of dermal backflow. According to the data obtained by Yamada et al. [98], lymphatic vessels that branch from collecting lymphatic vessels toward the dermis have an inner diameter wide enough to be confirmed with CT (Fig. 5.7). This was likely the observation of lymph flowing back to new or existing abnormal lymphatic vessels as it moves toward the dermis. From there, lymph flows back through capillary lymphatic vessels, leading to its storage in interstitial spaces (Fig. 5.8). It is unclear why such a phenomenon occurs there, but due to upstream blockage or increased internal pressure of lymphatic vessels, lymph appears to flow back from deeper areas to shallower areas, as if to escape [98].
High-resolution magnetic resonance lymphangiography (MRL) following interstitial, intracutaneous injection of an extracellular, paramagnetic contrast agent has recently been proposed for identifying abnormal lymphatic pathways [99,100,101]. This technique, that has proved to be technically feasible in patients with primary or secondary lymphedema [63, 102, 103], visualizes the lymphatic vessels in a limb with lymph flow disturbances, but not the lymphatic vessels of a healthy limb. This is most probably due to the faster lymph flow speed in the healthy limb. Therefore, lymph circulation disorders should be suspected when contrast-enhanced lymphatic vessels are visualized with this test. Migration of the contrast agent by the draining lymphatic system to regional lymph nodes also allows real-time observation of the transport function of the lymphatic system and of the lymph nodes within a reasonable length of time. Furthermore, the specificity of absorption and transport of the contrast agent by the lymphatic system permits to visualize detailed morphologic changes of the lymphatic vessels and of the regional lymph nodes. Finally, quantitative assessment of abnormal lymph flow kinetics may be achieved by tracing the flow within the lymphatic vessels and comparing dynamic nodal enhancement and time-signal intensity curves between edematous and contralateral limbs. Figures 5.9 and 5.10, and 5.11 depict different MRL patterns in patients with lymphedema. However, it should be noted that MRL is still in an experimental validation phase, since the extravascular intracutaneous injection of contrast agents is an off-label use of such compounds. Side effects such as moderate necrosis, hemorrhage, and edema have been described. Furthermore, incorrect interstitial injection of the contrast agent may lead to severe venous contamination.
The first correlations between lymphoscintigraphic pattern as evaluated with 99mTc-nanocolloid (injected subcutaneously at the interdigital web) and MRL findings (3 Tesla system, gadopentetate dimeglumine, and mepivacaine injected intracutaneously in the first three interdigital spaces of the forefoot) demonstrated clear concordance between the results of the two techniques, lymphoscintigraphy visualizing better the inguinal lymph nodes, and MR depicting the lymph vessels and morphology of lymph vessel abnormalities [30]. Figures 5.12 and 5.13 represent two examples of comparison between the two techniques in the same patient.
Further studies in upper extremity lymphedema [104] where MRL was performed before and after injection of a contrast agent by using a coronal T1-weighted 3D gradient-echo sequence with spectral fat saturation demonstrated higher spatial resolution and better depiction of lymph vessels with MRL than with lymphoscintigraphy. When MRL and lymphoscintigraphy are reported using a semiquantitative classification according to five patterns of lymphatic abnormalities (delay of drainage, drainage pattern, enhancement of lymph nodes, depiction of lymph vessels, anatomic levels), MRL lymphangiography showed sensitivities of 100% for all four categories, while lymphoscintigraphy yielded a sensitivity of 83.3% for delineation of lymph vessels and 100% for the other three categories. Specificity of MR lymphangiography was 85.7% for delay of drainage and 100% for other three categories, while lymphoscintigraphy showed specificity of 66.7% for pattern of lymphatic drainage and 100% for other three categories. Delay and pattern of drainage were the same in 83.3% and non-visualization of axillary LNs was indistinguishably noted in all patients on both techniques. Anatomic level of enhanced lymph vessel was identical in 66.7% of the patients (Figs. 5.14 and 5.15). MR lymphangiography showed better performance for depiction of abnormal lymph vessels. MR lymphangiography and lymphoscintigraphy yielded similar results in all or most patients for evaluation of axillary lymph node enhancement and lymphatic drainage in upper extremity.
In another study [105], contrast-enhanced MRL was applied to the evaluation of the lower limb, providing superior anatomical and functional information, with high spatial resolution, in comparison to various techniques used in the diagnosis of lower limb lymphedema (i.e., lymphoscintigraphy, direct lymphography, unenhanced MR), and allowing more accurate diagnosis and classification of patients suffering from lymphoedema.
Another application of contrast-enhanced MRL is in the diagnosis of occult chylous leak after thoracic duct embolization. In a case report [106] the direct contrast-enhanced MRL allowed the diagnosis of an occult chylous fluid leak from the right retroperitoneum into the right pleural space, after failure of both conventional lymphangiography and prophylactic TDE.
MRL has also been performed in combination with 68Ga-NEB PET or as part of a PET/MR examination for visualizing morphologic and functional characteristics of lymphatic vessels, evaluating lymphedema, and guiding surgical intervention. Preoperative 68Ga-NEB PET combined with MRL has been shown providing advantageous 3D images, higher temporal resolution, shorter time lapse before image acquisition after tracer injection, and more accurate pathological lymphatic vessel distribution with respect to traditional techniques (i.e., lymphoscintigraphy). This strategy has demonstrated significant advantages in the evaluation of lymphedema severity, staging, and pathological location of lymph vessels to make individualized treatment plans [107]. Combined 68Ga-NEB TOF-corrected PET/MR was used in patients with different clinical severity of unilateral lower limb lymphedema [108], with semiquantitative imaging assessment (ratio of the standardized uptake value (SUV) of superficial lymphatic vessel (SLV) versus SUV of deep lymphatic vessel (DVL) (SUVslv/dlv)). In this study, a significant difference in the SUVslv between the affected limbs and normal limbs in all subjects was found (not found in the SUVdlv) and the SUVslv/dlv of the affected limbs showed statistical differences within the groups with minimal, moderate, and severe lymphedema with a negative correlation, thus promising in evaluating bilateral lower limb lymphedema.
Key Learning Points
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Three-dimensional observation of deeper tissues at CT-LG has been used to help elucidating the mechanism of dermal backflow.
-
MRL following interstitial, intracutaneous injection of an extracellular, paramagnetic contrast agent has proved to be technically feasible in patients with primary or secondary lymphedema, although it is still an experimental procedure.
-
MRL allows real-time observation of the transport function of the lymphatic system and of the lymph nodes, depiction of detailed morphologic changes of the lymphatic vessels and of the regional lymph nodes, and quantitative assessment of abnormal lymph flow kinetics.
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MRL and lymphoscintigraphy have been compared in some studies.
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MRL has also been performed as part of 68Ga-NEB PET/MR.
5.7 Virtual Reality for Preoperative Planning
Conventional images of lymphoscintigraphy and SPECT/CT processed by dedicated software to visualize this 3D patient-specific model, creating detailed 3D image of the anatomical structures, were used to plan lympho-venous anastomosis through virtual reality in a patient with a lymphatic malformation. The strategy of this intervention was to identify the lymphatics leaking into the malformation and to interrupt the inflow towards the lesion by redirecting the lymph toward the venous system. Localization of the lymphatic malformation was achieved without iatrogenic damage to the adjacent structures, an important goal, as previous resection was only temporarily successful, and scarring is a well-known complication of multistage surgery [109].
Key Learning Point
A personalized planning for lympho-venous anastomosis was performed in virtual reality elaborating the SPECT/CT images, resulting in a better localization of the leak and avoiding iatrogenic damage to the adjacent structures.
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Clinical Cases
Clinical Cases
Case 5.1: Upper Limb Monocompartmental Lymphoscintigraphy in Stage III Primary Lymphedema of the Upper Left Arm Without Lymphadenomegaly
Luciano Feggi Chiara Peterle Corrado Cittanti Valentina de Cristofaro Stefano Panareo Ilaria Rambaldi Virginia Rossetti Ivan SantiBackground Clinical Case
A 45-year-old woman presented with spontaneous onset of mild non-pitting swelling in the upper left arm, in the absence of vascular lesions (stage III primary lymphedema with no lymphadenomegaly).
Anatomic location of edema: Left upper limb.
Lymphoscintigraphy
Lymphoscintigraphy was performed following administration of two aliquots of 2 mL containing 111 MBq 99mTc-albumin nanocolloid. Radiopharmaceutical injections were performed superficially in both hands (injection in first, second, third, and fourth interdigital spaces in each hand). A dual-detector SPECT gamma camera (E-cam Siemens Medical Solutions, Hoffman Estates, IL) equipped with low-energy high-resolution (LEHR) collimators was used to obtain planar images.
Planar images were acquired 5 min (early images) and 4 h (late images) after injection in anterior view (256 × 256 matrix, zoom factor 1.00, acquisition time 200 s for each view).
Case 5.2: Upper Limb Monocompartmental Lymphoscintigraphy in Non-pitting Edema of the Upper Left Limb in Patient with Rheumatoid Arthritis
Luciano Feggi Chiara Peterle Corrado Cittanti Valentina de Cristofaro Stefano Panareo Ilaria Rambaldi Virginia Rossetti Ivan SantiBackground Clinical Case
A 40-year-old woman with a history of rheumatoid arthritis and mild non-pitting edema in left upper limb (left hand and forearm) for 6 months.
Anatomic location of edema: Left upper limb.
Lymphoscintigraphy
Lymphoscintigraphy was performed following administration of two aliquots of 2 mL containing 74 MBq 99mTc-albumin nanocolloid. Radiopharmaceutical injections were performed superficially and bilaterally (injection in first, second, third, and fourth interdigital spaces in each hand). A dual-detector SPECT gamma camera (E-cam Siemens Medical Solutions, Hoffman Estates, IL) was used to obtain planar images. Time of acquisition after injection: 5 min after injections (early images): (a) hands and forearms (laid upon collimator); (b) arms and thorax; 4 h after injection (late images): (a) hands and forearms (laid upon collimator); (b) arms and thorax (256 × 256 matrix, zoom factor 1.00, acquisition time 200 s for each view).
Case 5.3: Axillary Reverse-Mapping Lymphoscintigraphy in Breast Cancer Patient with Positive Sentinel Lymph Node (SLN) Before Lymphadenectomy
Luciano Feggi Chiara Peterle Corrado Cittanti Valentina de Cristofaro Stefano Panareo Ilaria Rambaldi Virginia Rossetti Ivan Santi Paolo CarcoforoBackground Clinical Case
A 66-year-old woman underwent surgery for a left breast cancer finding positive SLN. Axillary dissection is necessary in patients with positive SLNs in breast cancer; in axillary basin lymph nodes may drain from either breast or arm; still, a lymph node which drains from both breast and arm is very rarely found, so the surgeon can spare a few nodes to preserve lymphatic arm drainage.
The ARM technique (axillary reverse mapping) allows to mark lymph nodes which drain from both hand and arm, so the surgeon can distinguish radioactive nodes (arm drainage) from “cold” ones (breast drainage) and remove only the breast-related ones.
Anatomic location of edema: No edema.
Lymphoscintigraphy
Lymphoscintigraphy was performed following administration of two aliquots of 0.4 mL containing 74 MBq 99mTc-albumin nanocolloid. Radiopharmaceutical injections were performed superficially and bilaterally (injection in first, second, third, and fourth interdigital spaces in each hand). A dual-detector SPECT gamma camera (E-cam Siemens Medical Solutions, Hoffman Estates, IL) equipped with low-energy high-resolution (LEHR) collimators was used to obtain planar images.
Time of acquisition after injection: (a) hands and forearms, 5 min after injection (laid upon collimator); (b) arms, 10 min after injection (anterior planar view); (c) axillary regions and thorax, 15 min after injection (anterior planar scan using cobalt wire as a landmark); (d) second acquisition only on axillary regions and thorax (anterior planar scan using cobalt wire as a landmark). Before late image of axillary regions and thorax, a radioguided occult lesion localization (ROLL) (after second nanocolloid intratumoral injection with ultrasound guidance) was performed to allow the surgeon to remove the breast primary tumor and left axillary nodes in one single time.
Case 5.4: Axillary Reverse-Mapping Lymphoscintigraphy in Breast Cancer Patient with Infiltrative Lobular Carcinoma and Positive SLN Before Lymphadenectomy
Luciano Feggi Chiara Peterle Corrado Cittanti Valentina de Cristofaro Stefano Panareo Ilaria Rambaldi Virginia Rossetti Ivan Santi Paolo CarcoforoBackground Clinical Case
A 49-year-old woman with left breast cancer (infiltrative lobular carcinoma with positive SLN); we performed an ARM lymphoscintigraphy (axillary reverse-mapping lymphoscintigraphy), before the surgeon performed axillary dissection to spare lymph nodes that drain from hand and arm.
Anatomic location of edema: No edema.
Lymphoscintigraphy
Lymphoscintigraphy was performed following administration of two aliquots of 0.4 mL containing 74 MBq 99mTc-albumin nanocolloid. Radiopharmaceutical injections were performed superficially and bilaterally (injection in first, second, third, and fourth interdigital spaces in each hand). A dual-detector SPECT gamma camera (E-cam Siemens Medical Solutions, Hoffman Estates, IL) equipped with low-energy high-resolution (LEHR) collimators was used to obtain planar images.
Planar images were acquired in anterior view (256 × 256 matrix, zoom factor 1.00, acquisition time 200 s for each view).
Time of acquisition after injection: (a) hands and forearms, 5 min after injection (laid upon collimator); (b) arms, 10 min after injection (anterior planar scan); (c) axillary regions and thorax, 15 min after injection (anterior planar scan using cobalt wire as a landmark); (d) second acquisition only (late image) on axillary regions and thorax (anterior planar scan using cobalt wire as a landmark).
Case 5.5: Lower Limb Monocompartmental Lymphoscintigraphy in Patient with Bilateral Swelling and Non-pitting Edema of the Lower Limbs
Luciano Feggi Chiara Peterle Corrado Cittanti Valentina de Cristofaro Stefano Panareo Ilaria Rambaldi Virginia Rossetti Ivan SantiBackground Clinical Case
A 62-year-old man with spontaneous onset of bilateral swelling and non-pitting edema in the lower limbs since 1 year.
Anatomic location of edema: Lower limbs.
Lymphoscintigraphy
Lymphoscintigraphy was performed following administration of two aliquots of 2 mL containing 111 MBq 99mTc-albumin nanocolloid. Radiopharmaceutical injections were performed superficially and bilaterally (injection in first, second, and fourth interdigital spaces and in the outer retromalleolar space in each foot). A dual-detector SPECT gamma camera (E-cam Siemens Medical Solutions, Hoffman Estates, IL) equipped with low-energy high-resolution (LEHR) collimators was used to obtain planar images. Planar images were acquired 10 min after radiopharmaceutical administration and walking exercise and 4 h, respectively, after injection (256 × 256 matrix, zoom factor 1.00, acquisition time 200 s for each view) in anterior planar scan from feet to abdominal region.
Case 5.6: Lower Limb Bicompartmental Lymphoscintigraphy in Patient with Edema of the Left Lower Limb
Paola Anna Erba Luisa LocantoreBackground Clinical Case
A 47-year-old woman with edema of the left lower limb. Normal Doppler ultrasound. No family history of lymphedema.
Anatomic location of edema: Lower left limb.
Lymphoscintigraphy
For the deep lymphatic circulation (DLC): two aliquots of 99mTc-nanocolloid, 7 MBq each of injection in 0.1 mL in the first and second intermetatarsal space, identified by palpating the soles of both feet immediately proximal to the distal heads of the metatarsal bones on each side, inserting the needle by about 12–13 mm to reach the intermetatarsal muscles below the deep fascia plantaris. For the superficial lymphatic circulation (SLC): three aliquots of about 10 MBq in 0.1 mL on the dorsum of each foot, inserting the needle subdermally in sites corresponding approximately to the prior palmar injections, about 1–2 cm proximally to the interdigital web. Spot and whole-body images were obtained from the distal feet up to the abdomen.
Spot images: 180 s/view, matrix 128 × 128, zoom 1.33
Whole-body images: matrix 128 × 1024, zoom 1, speed: 12 cm/min
Case 5.7: Lower Limb Monocompartmental Lymphoscintigraphy in Patient with Bilateral Lower Limb Lymphedema
Giuseppe Rubini Filippo AntonicaBackground Clinical Case
A 32-year-old man with bilateral lower limb lymphedema. Clinicians suspected congenital dysplasia of the lower limb lymphatic vessels. Legs appeared edematous, size increased and the patient complained about fatigue and continuous pain even during sleep time. His daily actions were very limited.
Anatomic location of edema: Lower limbs.
Lymphoscintigraphy
Lymphoscintigraphy was performed following injections of two aliquots containing 99mTc-albumin nanocolloid, 37 MBq each of injection in 0.1 mL in the first and second intermetatarsal spaces. A dual-detector SPECT gamma camera (Millennium GE Healthcare, Milwaukee, WI) equipped with low-energy high-resolution (LEHR) collimators was used to obtain whole-body images after radiopharmaceutical injection. Whole-body planar images were acquired in anteroposterior projection, with a 256 × 1024 matrix and zoom factor 1.00 (speed: 12 cm/min) from the distal feet up to the abdomen.
Case 5.8: Lower Limb Monocompartmental Lymphoscintigraphy in Patient Previously Submitted to Left Saphenectomy
Giuseppe Rubini Filippo AntonicaBackground Clinical Case
A 68-year-old woman previously submitted to saphenectomy of the left limb. Left limb appeared cold, size increased, and patient reported size increasing especially in the last year. Echo-color Doppler revealed decreased blood flow and tissue edema.
Anatomic location of edema: Lower limbs.
Lymphoscintigraphy
Lymphoscintigraphy was performed following injections of two 0.1 mL aliquots containing 36 MBq 99mTc-albumin nanocolloid, in the first and second intermetatarsal spaces. A dual-detector SPECT gamma camera (Millennium GE Healthcare, Milwaukee, WI) equipped with low-energy high-resolution (LEHR) collimators was used to obtain whole-body images after radiopharmaceutical injection. Whole-body planar images were acquired in anteroposterior projection, with a 256 × 1024 matrix and zoom factor 1.00 (speed: 12 cm/min) from the distal feet up to the abdomen.
Case 5.9: Lower Limb Monocompartmental Lymphoscintigraphy in Patient with History of Lymphadenectomy of the Groin Basin for Melanoma
Giuseppe Rubini Filippo AntonicaBackground Clinical Case
Patient with a history of cutaneous melanoma of the right foot already surgically removed and submitted to lymphadenectomy of the groin basin due to groin SLN positivity for metastasis. The surgeon also removed pelvic lymph nodes to guarantee surgical radicality. Physical examination did not reveal any lymphadenopathy or lymphedema.
Anatomic location of edema: Lower limbs.
Lymphoscintigraphy
Lymphoscintigraphy was performed following injections of two 0.1 mL aliquots containing 36 MBq 99mTc-albumin nanocolloid, in the first and second intermetatarsal spaces. A dual-detector SPECT gamma camera (Millennium GE Healthcare, Milwaukee, WI) equipped with low-energy high-resolution (LEHR) collimators was used to obtain whole-body images after radiopharmaceutical injection. Whole-body planar images were acquired in anteroposterior projection, with a 256 × 1024 matrix and zoom factor 1.00 (speed: 12 cm/min) from the distal feet up to the abdomen.
Case 5.10: Postexercise Lower Limb Monocompartmental Lymphoscintigraphy in Patient with Bilateral Leg Edema
Luciano Feggi Chiara Peterle Corrado Cittanti Valentina de Cristofaro Stefano Panareo Ilaria Rambaldi Virginia Rossetti Ivan SantiBackground Clinical Case
A 50-year-old woman with previous hysterectomy due to uterine fibromatosis and multiple removals of lipomas of the legs underwent investigation, because of mild edema of the legs, more noticeable in the right one; ultrasound, performed before lymphoscintigraphy, showed saphenous–femoral vein junction incontinence with ectasia. Lymphadenomegaly was found in the right inguinal region.
Anatomic location of edema: Lower limbs (more evident in right one).
Lymphoscintigraphy
Lymphoscintigraphy was performed following administration of two doses of 2 mL containing 111 MBq 99mTc-albumin nanocolloid. Radiopharmaceutical injections were performed superficially and bilaterally (injection in first, second, and fourth interdigital spaces and in the outer retromalleolar space in each foot). A dual-detector SPECT gamma camera (E-cam Siemens Medical Solutions, Hoffman Estates, IL) equipped with low-energy high-resolution (LEHR) collimators was used to obtain planar images. Planar images were acquired 10 min (after radiopharmaceutical administration and walking exercise) and 4 h, respectively, after injection (256 × 256 matrix, zoom factor 1.00, acquisition time 200 s for each view) in anterior planar scans from feet to abdominal region.
Case 5.11: Lower Limb Monocompartmental Lymphoscintigraphy at Rest and Postexercise with Semiquantitative Evaluation of the Tracer Appearance Time in Patient with Lymphedema of the Left Lower Limb Post-left Groin Lymphadenectomy
Girolamo Tartaglione Roberto Bartoletti Marco PaganBackground Clinical Case
A 45-year-old woman, with lymphedema of the left lower limb and history of cutaneous melanoma of the gluteus (pN1M0) and left groin lymph nodal dissection.
Anatomic location of edema: Lower limb.
Lymphoscintigraphy
All tight clothes and elastics were removed before tracer injection. Two aliquots of 0.3 mL containing 50 MBq 99mTc-albumin-nanocolloid were injected intradermally at the first interdigital area, on the top of the feet. Gentle massage was performed after injection in the area. Two scans were acquired starting immediately after injection (the first on the legs and the second on the thighs) following these parameters: planar static scan, preset time 5 min, matrix 128 × 128, 140 Kev ± 10%, and anterior and posterior views. A dual-head gamma camera (GE-Infinia) equipped with low-energy general-purpose (LEGP) collimators was used to provide increased sensitivity. If delayed or absent lymphatic drainage was perceived, then the patient was invited to perform 2 min of continuous isotonic exercise (walking). A postexercise static scan was acquired (128 × 128, 5 min) until the regional lymph nodes were visualized. The tracer appearance time (TAT, normal value less than 10 min) and lymph drainage patterns after exercise (see timeline) were evaluated.
Case 5.12: Lower Limb Monocompartmental Lymphoscintigraphy at Rest and Postexercise with Semiquantitative Evaluation of the Tracer Appearance Time in Patient with Right Lower Limb Primary Lymphedema, Clinical Stage 3 According to Foeldi
Girolamo Tartaglione Roberto Bartoletti Marco PaganBackground Clinical Case
A 54-year-old woman, affected by a right lower limb primary lymphedema of clinical stage 3 according to Foeldi. The tissue at this stage is hard (fibrotic) and edema is non-pitting. The swelling is almost irreversible and the limb is very large and swollen.
Anatomic location of edema: Right lower limb.
Lymphoscintigraphy
All tight clothes and elastics were removed before tracer injection. Two aliquots of 0.3 mL containing 50 MBq 99mTc-albumin-nanocolloid were injected intradermally at the first interdigital area, on the top of the feet. Gentle massage was performed after injection in the area. Two scans were acquired starting immediately after injection (the first on the legs and the second on the thighs) following these parameters: planar static scan, preset time 5 min, matrix 128 × 128, 140 Kev ± 10%, and anterior and posterior views. A dual-head gamma camera (GE-Infinia) equipped with low-energy general-purpose (LEGP) collimators was used to provide increased sensitivity. If delayed or absent lymphatic drainage was perceived, then the patient was invited to perform 2 min of continuous isotonic exercise (walking). A postexercise static scan was acquired (128 × 128, 5 min) until the regional lymph nodes were visualized. The tracer appearance time (TAT, normal value less than 10 min) and lymph drainage patterns after exercise (see timeline) were evaluated.
Case 5.13: Lower Limb Monocompartmental Lymphoscintigraphy at Rest and Postexercise with Semiquantitative Evaluation of the Tracer Appearance Time in Patient with Post-lymph Nodal Dissection Lymphedema of the Lower Limbs
Girolamo Tartaglione Roberto Bartoletti Marco PaganBackground Clinical Case
A 46-year-old man, affected by lymphedema of the lower limbs (clinical stage 2 according to Foeldi) secondary to bilateral groin lymph nodal dissection for cutaneous melanoma (7 years previously). The patient was treated in several centers with combined physical therapy programs, including a personalized program of exercise.
Anatomic location of edema: Lower limbs.
Lymphoscintigraphy
All tight clothes and elastics were removed before tracer injection. Two aliquots of 0.3 mL containing 50 MBq 99mTc-albumin-nanocolloid were injected intradermally at the first interdigital area, on the top of the feet. Gentle massage was performed after injection in the area. Two scans were acquired starting immediately after injection (the first on the legs and the second on the thighs) following these parameters: planar static scan, preset time 5 min, matrix 128 × 128, 140 Kev ± 10%, and anterior and posterior views. A dual-head gamma camera (GE-Infinia) equipped with low-energy general-purpose (LEGP) collimators was used to provide increased sensitivity. If delayed or absent lymphatic drainage was perceived, then the patient was invited to perform 2 min of continuous isotonic exercise (walking). A postexercise static scan was acquired (128 × 128, 5 min) until the regional lymph nodes were visualized. The tracer appearance time (TAT, normal value less than 10 min) and lymph drainage patterns after exercise were evaluated.
Case 5.14: Postexercise Lower Limb Monocompartmental Lymphoscintigraphy in Patient with Acute Edema of the Left Lower Limb and Painful Left Inguinal Lymphadenomegaly
Luciano Feggi Chiara Peterle Corrado Cittanti Valentina de Cristofaro Stefano Panareo Ilaria Rambaldi Virginia Rossetti Ivan Santi Paolo CarcoforoBackground Clinical Case
A 77-year-old woman with pain and swelling of the left lower limb; ultrasound detected left inguinal lymphadenomegaly; after surgical removal, histological diagnosis was metastasis of neuroendocrine carcinoma (poorly differentiated), consistent with Merkel cell carcinoma metastasis (T2N1Mx). Her clinical presentation included edema of the left lower limb and pain; there was a left inguinal scar after surgical removal.
Anatomic location of edema: Left lower limb.
Lymphoscintigraphy
Lymphoscintigraphy was performed following administration of two aliquots of 2 mL containing 111 MBq 99mTc-albumin nanocolloid. Radiopharmaceutical injections were performed superficially and bilaterally (injection in first, second, and fourth interdigital spaces and in the outer retromalleolar space in each foot). A dual-detector SPECT gamma camera (E-cam Siemens Medical Solutions, Hoffman Estates, IL) equipped with low-energy high-resolution (LEHR) collimators was used to obtain planar images. Planar images were acquired 5 min and 4 h, respectively, after injection (256 × 256 matrix, zoom factor 1.00, acquisition time 200 s for each view) in anterior planar views of the feet and legs, thighs, and inguinal regions.
Case 5.15: Lower Limb Monocompartmental Lymphoscintigraphy at Rest and Postexercise with Semiquantitative Evaluation of the Tracer Appearance Time in Patient with Secondary Lymphedema of the Right Lower Limb
Girolamo Tartaglione Roberto Bartoletti Marco PaganBackground Clinical Case
A 71-year-old woman was submitted to surgical removal of primary melanoma of the right leg and sentinel lymph node biopsy (SLNB) of the popliteal lymph node (pN0). About 3 months after surgery she developed a lymphedema of right lower limb.
Anatomic location of edema: Right lower limb.
Lymphoscintigraphy
All tight clothes and elastics were removed before tracer injection. Aliquots of 0.3 mL containing 50 MBq 99mTc-albumin-nanocolloid were injected intradermally at the first interdigital area, on the top of the feet. Gentle massage was performed after injection in the area. Two scans were acquired starting immediately after injection (the first on the legs and the second on the thighs) following these parameters: planar static scan, preset time 5 min, matrix 128 × 128, 140 Kev ± 10%, and anterior and posterior views. A dual-head gamma camera (GE-Infinia) equipped with low-energy general-purpose (LEGP) collimators was used to provide increased sensitivity. If delayed or absent lymphatic drainage was perceived, then the patient was invited to perform 2 min of continuous isotonic exercise (walking). A postexercise static scan was acquired (128 × 128, 5 min) until the regional lymph nodes were visualized. The tracer appearance time (TAT, normal value less than 10 min) and lymph drainage patterns after exercise were evaluated.
Case 5.16: Lower Limb Monocompartmental Lymphoscintigraphy in Patient with Secondary Bilateral Non-pitting Edema of the Lower Extremities, More Evident on the Left, and Left Ureteral Obstruction Due to Lymphocele
Luciano Feggi Chiara Peterle Corrado Cittanti Valentina de Cristofaro Stefano Panareo Ilaria Rambaldi Virginia Rossetti Ivan Santi Paolo CarcoforoBackground Clinical Case
A 47-year-old woman with melanoma of the left leg and metastasis of the inguinal homolateral lymph nodes underwent surgery (removal of melanoma and left inguinal and iliac lymphadenectomy). After 7 years, during follow-up, CT detected a large pelvic mass, which remained undiagnosed (lymphocele? ovarian cyst?). Two years later, the patient suffered from left ureteral obstruction by compression of a pelvic mass on the third tract of the ureter. Patient reported bilateral swelling in the lower limbs, more evident on the left. Therefore her clinical presentation includes bilateral non-pitting edema of the lower extremities, more evident on the left, and left ureteral obstruction, which needs nephrostomy.
Anatomic location of edema: Lower limbs (more evident in left one).
Lymphoscintigraphy
Lymphoscintigraphy was performed following administration of two aliquots of 2 mL containing 111 MBq 99mTc-albumin nanocolloid. Radiopharmaceutical injections were performed superficially and bilaterally (injection in first, second, and fourth interdigital spaces and in the outer retromalleolar space in each foot). A dual-detector SPECT gamma camera (E-cam Siemens Medical Solutions, Hoffman Estates, IL) equipped with low-energy high-resolution (LEHR) collimators was used to obtain planar images. Planar images were acquired 5 min, 1 h, 4 h, and 24 h, respectively, after injection in an anterior view (256 × 256 matrix, zoom factor 1.00, acquisition time 200 s for each view). SPECT/CT was acquired 24 h after radiopharmaceutical administration (60 s for each frame, CT slice thickness: 1 mm, tube current of 30 mA, tube voltage of 13 kV).
Case 5.17: Lower Limb Bicompartmental Lymphoscintigraphy in Patient with Posttraumatic Edema of the Left Leg Associated with Disability Grade 3 According to Ricci Scale, at Baseline and After 5 Years of Multiple Surgeries and Cycles of Therapy
Paola Anna Erba Luisa LocantoreBackground Clinical Case
A 36-year-old man with posttraumatic edema of the left leg. After crush injury, the patient had multiple surgical procedures for the presence of tissue necrosis and cheloids, with cutaneous graft. Before the accident, the patient had had a left leg saphenectomy performed. There is stage V lymphedema of the lower left limb with cutaneous retraction of the proximal and medial portion of the leg, hyperkeratosis, lymphatic vesicles, eczema, and ulcerations. A disability grade 3 according to Ricci scale was present.
Anatomic location of edema: Lower left limb.
Lymphoscintigraphy
Lower Limbs
For the deep lymphatic circulation (DLC): two aliquots of 99mTc-nanocolloid, 7 MBq each of injection in 0.1 mL in the first and second intermetatarsal spaces, identified by palpating the soles of both feet immediately proximal to the distal heads of the metatarsal bones on each side, inserting the needle by about 12–13 mm to reach the intermetatarsal muscles below the deep fascia plantaris.
For the superficial lymphatic circulation (SLC): three aliquots of about 10 MBq in 0.1 mL on the dorsum of each foot, inserting the needle subdermally in sites corresponding approximately to the prior palmar injections, about 1–2 cm proximally to the interdigital web. Spot and whole-body images were obtained from the distal feet up to the abdomen.
Spot images: 180 s/view, matrix 128 × 128, zoom 1.33.
Whole-body images: matrix 256 × 1024, zoom 1, speed: 12 cm/min
Case 5.18: Upper and Lower Limb Bicompartmental Lymphoscintigraphy in Patient with Bilateral Feet and Ankle Edema, More Prevalent on Left Side
Paola Anna Erba Luisa LocantoreBackground Clinical Case
A 62-year-old woman with bilateral edema mainly at the distal part of the leg and the feet, worsening in the last 10 months. Doppler ultrasound negative. Ultrasound of the soft tissue showing an increased thickening of the derma, which is hypoechogenic, representing an interstitial edema.
Anatomic location of edema: Bilateral feet and ankles, major at the left side.
Lymphoscintigraphy
Upper Limbs
For the deep lymphatic circulation (DLC): two aliquots of 99mTc-nanocolloid, 7 MBq each of injection in 0.1 mL in the first and second intermetacarpal spaces, identified by palpating the palms of both hands immediately proximal to the distal heads of the metacarpal bones on each side, inserting the needle by about 12–13 mm to reach the intermetacarpal muscles below the deep fascia. For the superficial lymphatic circulation (SLC): three aliquots of about 10 MBq in 0.1 mL on the dorsum of each hand, inserting the needle subdermally in sites corresponding approximately to the prior palmar injections, about 1–2 cm proximally to the interdigital web. Spot and whole-body images of both arms, thorax, and upper abdomen.
Lower Limbs
For the DLC: two aliquots of 99mTc-nanocolloid, 7 MBq each of injection in 0.1 mL in the first and second intermetatarsal spaces, identified by palpating the soles of both feet immediately proximal to the distal heads of the metatarsal bones on each side, inserting the needle by about 12–13 mm to reach the intermetatarsal muscles below the deep fascia plantaris.
For the SLC: three aliquots of about 10 MBq in 0.1 mL on the dorsum of each foot, inserting the needle subdermally in sites corresponding approximately to the prior palmar injections, about 1–2 cm proximally to the interdigital web. Spot and whole-body images were obtained from the distal feet up to the abdomen.
Spot images: 180 s/view, matrix 128 × 128, zoom 1.33
Whole-body images: matrix 256 × 1024, zoom 1, speed: 12 cm/min
This is a typical example of lower limb lymphedema due to an impairment of the DLC with conserved function of the SLC; however, signs of overload of the SLC are also present at the left lower limb. Arm circulation is normal.
Case 5.19: Upper and Lower Limb Bicompartmental Lymphoscintigraphy in Patient with Right Pelvic Paravesical and Inguinal Swelling
Paola Anna Erba Luisa LocantoreBackground Clinical Case
A 33-year-old man with right pelvic (alongside the bladder) and right inguinal swelling. CT finding of multiple cystic lesions suspected for cystic lymphangiomatosis, localized in the retroperitoneal space, at the splenic lodge, in the bone (ribs, vertebral bodies, and pelvic bones of maximum 23 mm) and in the pelvis (about 10 cm). Negative [18F]FDGPET/CT findings.
Anatomic location of edema: Right inguinal.
Lymphoscintigraphy
Upper Limbs
For the deep lymphatic circulation (DLC): two aliquots of 99mTc-nanocolloid, 7 MBq each of injection in 0.1 mL in the first and second intermetacarpal spaces, identified by palpating the palms of both hands immediately proximal to the distal heads of the metacarpal bones on each side, inserting the needle by about 12–13 mm to reach the intermetacarpal muscles below the deep fascia.
For the superficial lymphatic circulation (SLC): three aliquots of about 10 MBq in 0.1 mL on the dorsum of each hand, inserting the needle subdermally in sites corresponding approximately to the prior palmar injections, about 1–2 cm proximally to the interdigital web. Spot and whole-body images of both arms, thorax, and upper abdomen.
Lower Limbs
For the DLC: two aliquots of 99mTc-nanocolloid, 7 MBq each of injection in 0.1 mL in the first and second intermetatarsal spaces, identified by palpating the soles of both feet immediately proximal to the distal heads of the metatarsal bones on each side, inserting the needle by about 12–13 mm to reach the intermetatarsal muscles below the deep fascia plantaris.
For the SLC: three aliquots of about 10 MBq in 0.1 mL on the dorsum of each foot, inserting the needle subdermally in sites corresponding approximately to the prior palmar injections, about 1–2 cm proximally to the interdigital web. Spot and whole-body images were obtained from the distal feet up to the abdomen.
Spot images: 180 s/view, matrix 128 × 128, zoom 1.33
Whole-body images: matrix 256 × 1024, zoom 1, speed: 12 cm/min
Normal bilateral lymph flow was depicted, with only mild delay for the right SLC in the medial and distal part of the leg. Interestingly, two sites of radiopharmaceutical accumulation are evident. The first is at the pelvis localized near the bladder, at the right side, and which is receiving the lymph from the deep lymphatic system. The second is in the upper abdominal area, at the level of the upper right kidney portion which is supplied by the SLC. Normal lymph node images were seen for the popliteal lymph nodes bilaterally and for the left inguinal node. Progression through the lumbo-aortic lymph nodes is present, as well as faint liver uptake of the radiocolloids.
The exam demonstrated the lymphatic nature of both the pelvic and the abdominal collections, therefore confirming the clinical diagnosis of cystic lymphangiomatosis.
Case 5.20: Lower Limb Bicompartmental Lymphoscintigraphy in Patient with Edema of the Scrotum
Paola Anna Erba Luisa LocantoreBackground Clinical Case
A 72-year-old man with edema of the scrotum but no edema of upper or lower extremities. Previous surgery for left inguinal hernia.
Anatomic location of edema: Scrotum.
Lymphoscintigraphy
For the deep lymphatic circulation (DLC): two aliquots of 99mTc-nanocolloid, 7 MBq each of injection in 0.1 mL into the first and second intermetatarsal spaces, identified by palpating the soles of both feet immediately proximal to the distal heads of the metatarsal bones on each side, inserting the needle by about 12–13 mm to reach the intermetatarsal muscles below the deep fascia plantaris.
For the superficial lymphatic circulation (SLC): three aliquots of about 10 MBq in 0.1 mL on the dorsum of each foot, inserting the needle subdermally in sites corresponding approximately to the prior palmar injections, about 1–2 cm proximally to the interdigital web. Spot and whole-body images were obtained from the distal feet up to the abdomen.
Spot images: 180 s/view, matrix 128 × 128, zoom 1.33
Whole-body images: matrix 256 × 1024, zoom 1, speed: 12 cm/min
After injections for assessment of the SLC, a normal right lymph flow was depicted, with only mild delay in the medial and distal part of the leg. Conversely, at the left limb, multiple collateral vessels are evident with lymph collection at the proximal left leg; preservation of the main lymphatic vessel is present. New images of the lymph nodes appear at the inguinal region. The lymph collection at the left scrotum persists, without increasing significantly the uptake of the radiocolloid. Progression through the lumbo-aortic lymph nodes is present, as well as faint liver uptake of the radiocolloids.
The exam demonstrated the lymphatic origin of the edema of the scrotum, which is alimented by both the deep and the superficial lymphatic circulation and is evident after injection at the intermetatarsal space. Therefore, the same technique of injection was used for the subsequent injection of the blue dye during surgery performed to detect the site of lymphatic leakage. After the injection, which was performed after the preparation of the main operative field, a passive movement of the patient’s leg was performed to allow the blue dye to reach the site of leak. As soon as the operative field became blue, indicating blue dye extravasation, the surgeon searched for the site of leakage, and then performed the suture.
Case 5.21: Lower Limb Monocompartmental Lymphoscintigraphy in Patient with Postsurgical Chylopericardium (Ductus Arteriosus), Treated with Thoracentesis
Paola Anna Erba Luisa LocantoreBackground Clinical Case
Girl, aged 1 year, with postsurgical chylopericardium (ductus arteriosus), treated with thoracentesis.
Anatomic location of edema: Pericardium.
Lymphoscintigraphy
Lower Limbs
For the superficial lymphatic circulation (SLC): three aliquots of about 10 MBq in 0.1 mL on the dorsum of each foot, inserting the needle subdermally, about 1–2 cm proximally to the interdigital web. Spot and whole-body images were obtained from the distal feet up to the abdomen.
Spot images: 180 s/view, matrix 128 × 128, zoom 1.33
Whole-body images: matrix 256 × 1024, zoom 1, speed: 12 cm/min
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Sollini, M., Boni, R., Marciano, A., Zanca, R., Bartoli, F., Erba, P.A. (2020). Lymphoscintigraphy for the Differential Diagnosis of Peripheral Edema and Intracavitary Lymph Effusion. In: Mariani, G., Vidal-Sicart, S., Valdés Olmos, R. (eds) Atlas of Lymphoscintigraphy and Sentinel Node Mapping. Springer, Cham. https://doi.org/10.1007/978-3-030-45296-4_5
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