Key words
lymph nodes - differential diagnosis - lower extremity
Schlüsselwörter
Lymphknoten - Differenzialdiagnose - untere Extremität
Introduction, functional anatomy
Introduction, functional anatomy
It is estimated that the tissues produce about two litres of lymph in 24 hours. This
fluid is transported together with immunocompetent cells via the open ends of the
lymphatic vessels to reach the nearest lymph node (LN). The lymph vessels have a delicate
valve system and run parallel to the blood vessels. The lymph flows through several
afferent lymphatics into the functional compartments of the LN, which are divided
by septa. As the lymph passes through the lymph node, antigens recognised as foreign
are filtered out ([Fig. 1a]). The lymph so ‘cleaned’ continues proximally via one or more efferent lymphatic
vessels ([Fig. 1b]). After passing through further LNs, it reaches the abdominal and thoracic lymphatics,
from where it is eventually returned to the central venous system [1].
Fig. 1 a Simplified diagram of a lymph node structure. The inflowing lymph is divided into
several compartments (the spaces between two trabeculae) After being filtered, the
fluid drains through one or more efferent lymphatics. Follicles (B cells) are found
in the outer cortical layer and the T lymphocytes in the inner layer. The blood supply
is situated in the hilum. At the end of the arterial and venous systems, are the high
endothelial venules (HEVs), through which immunocompetent cells from the blood vessels
enter the lymph node tissue. In the node, antigens are captured by dendritic cells
and presented to the activated lymphocytes for cellular and humoral elimination. b Lymphography image of the afferent and efferent lymphatics [2].
Of an estimated 300–700 lymph nodes in the body, about one-third are found in the
neck region (frequent portal of entry for many pathogens). Ultrasound scanning can
therefore always detect LNs in the neck. Lymph nodes can also be found in the groin
of almost every person, as long as an appropriate transducer is used.
An intact lymph node consists of cortex, medulla and hilar region and is enveloped
by a capsule. High frequency transducers may occasionally reveal small hypoechoic
follicles in inflamed or lymphomatous LNs ([Fig. 3]). Blood vessels supplying the node are found in the hilum, together with the draining
(efferent) lymphatic vessel.
Ultrasound tools and examination
Ultrasound tools and examination
As a rule, linear transducers of between 7.5 and 20 MHz are used in the periphery:
the shallower the LN lies, the higher the selected transducer frequency should be.
Besides B-mode scans, colour-coded Doppler ultrasound is used regularly and a few
companies have even patented flow-detection procedures such as B-Flow (demonstration
of flowing blood as shining white points by discriminating stationary echoes from
moving echoes) and Superb Microvascular Imaging (SMI) with artefact-reducing duplex
ultrasound [3]
[4]
[5]. Elastography and contrast-enhanced ultrasound (CEUS), as shown in [Fig. 4b], are only used in exceptional circumstances [6]. If necessary, a C-plane (panoramic image) can be generated from a frozen tissue
block, whereupon the sectional plane is then parallel to the cutis ([Fig. 2], [6b]). Ultrasonography is also used to guide fine needle aspiration (FNA) or core needle
biopsy, often obtaining a firm diagnosis. Open resection of a lymph node is particularly
recommended for the definitive typing of lymphomas. The AWMF guidelines do not recommend
the elective surgical removal of the sentinel lymph node [7]
[8] ([Table 1]).
Fig. 2 Horizontally lying lymph nodes transformed by non-Hodgkin lymphoma (yellow arrows).
The LN on the left shows a clearly thickened cortex, the one in the middle does not
have a recognisable echogenic centre, the LN on the right still has a thin cortex
while the medial part is clearly hypoechoic and thickened. The femoral vessels lie
posteriorly and can be seen in oblique section.
Table 1
Technical ultrasound scanning procedures.
|
Technique, assessment criteria
|
|
Choice of transducer
|
Linear transducer, the more superficial the LN, the higher the frequency; the frequency
for colour coding is lower than in the underlying B-mode image
Display modes: C-plane, extended field of view
|
|
B-mode: Fundamental, tissue harmonic imaging (THI)
|
Number, difference between sides, local tenderness to pressure, distance from the
primary tumour
|
LN structure: cortex/medulla/hilum
|
Capsule intact, local oedema?
|
|
Colour Doppler: Power Doppler, B-Flow, SMI
|
Intranodal vessels? Vascular structure
|
Demonstration of arteries & veins
|
Perinodal vessels
|
|
Elastography (strain and shear wave elastography)
|
Colour-coded representation of local tissue firmness
|
Strain elastography
Please note: only comparative values are shown
|
Shear wave elastography: absolute local values are given in m/s or kPa
|
|
CEUS
|
Direction of contrast enhancement: centripetal, centrifugal
|
Homogeneous/absent enhancement?
|
Perinodal contrast enhancement?
|
The examination is initially performed along the inguinal ligament and proximal large
vessels in transverse section, using an anatomically suitable high frequency linear
transducer (probe). If a LN is detected, it must be measured in two planes. The ratio
between the longitudinal and transverse diameters (Solbiati or Vassallo Index) may
be of limited use in the differential diagnosis of metastatic disease ([Table 2]): if the ratio is less than 2, metastasis must be confirmed or ruled out [9]
[10]. Elongated LNs with a Solbiati Index > 2 are less specific with respect to whether
they are benign or malignant. A sweep in both ultrasound axes is then performed. In
B-mode, attention must be paid to a clear demarcation from the surrounding tissues.
With a sensitive flow detection procedure, colour Doppler can be used to show the
vascularisation of the node, while CEUS shows the tissue perfusion [6]
[11]. These procedures also serve to demonstrate the vascular structure. The role of
the imaging is therefore to detect and localise LNs, to establish their characteristics
and to assist with the biopsy, if necessary. CEUS can deliver additional information,
but requires an experienced examiner and is reserved for specific situations [5]. The value of elastography in the differential diagnosis has not yet been conclusively
clarified.
Table 2
General assessment criteria for lymph nodes. Characteristics in inflammatory/reactive,
lymphomatous and metastatically transformed lymph nodes.
|
Ultrasound tumour characteristics
|
|
Mode
|
Inflammatory/Reactive Lymph Nodes
|
|
B-mode
|
Acute inflammation: usually evenly thickened cortex, hypoechoic medulla. Usually elongated
(LD/TD > 2). Number and size decrease with distance from cause.
|
Chronic inflammation: evenly narrow cortex, echogenic centre
|
Acute: rarely perinodal streaky fluid (oedema)
|
|
Colour Doppler
|
Regional/global hyper-vascularisation, regressing as becomes chronic
|
Evidence of arteries and veins
|
Tree-like branching vascular structure
|
|
CEUS
|
Clear centrifugal homogeneous hyperperfusion (acute inflammation)
|
Little perfusion with chronic inflammation
|
Usually no evidence of perinodal perfusion
|
|
Lymphoma
|
|
B-mode
|
As inflammatory, sometimes pattern of small nodules in the perinodal thickened cortex
(follicles), no echogenic hilum
|
Multiple, usually bilateral, more peripheral LN stations affected
|
Usually no perinodal oedema; abdominal involvement (LNs and/or organs)
|
|
Colour Doppler
|
Hypervascularisation
|
Usually evidence of arteries and veins
|
Tree-like branching vascular structure
|
|
CEUS
|
Clear centrifugal homogeneous hyperperfusion
|
Possibly peripheral hypoperfusion
|
Usually no perinodal oedema
|
|
Carcinoma/sarcoma metastases
|
|
B-mode
|
Nodular thickening or spherical shape (LD/TD < 2) (route of spread?)
|
Rounded hypoechoic cystic LN, no echogenic hilum
|
Perinodal oedema with capsular infiltration
|
|
Colour Doppler
|
Slight to strong vascularisation, central vessels sometimes absent, supply via capsular
arteries
|
Usually chaotic vascular structure
|
Usually no perinodal vascularisation
|
|
CEUS
|
Slight to strong centripetal perfusion
|
Inhomogeneous perfusion, central ischaemia/necrosis
|
Perinodal contrast enhancement (with infiltration through the capsule)
|
LD: Longitudinal diameter, TD: Transverse diameter, CEUS: Contrast enhanced ultrasound.
Localisation, common differential diagnoses
Localisation, common differential diagnoses
A distinction is made between superficial horizontal (lying laterally and medially
immediately below the inguinal ligament), supero-lateral, and supero-medial LNs ([Fig. 2]). In contrast to the deeper-lying nodes, these superficial LNs can often be palpated.
The superficial inferior LNs lie somewhat inferior to the saphenous opening (saphenous
hiatus). The deeper-lying LNs are in the subfascial tissues medial to the femoral
vessels (see Brenner in this issue). Important clinical parameters are the LN size
and tenderness. Unlike chronically inflamed or reactive LNs, acutely inflamed nodes
are usually palpable or tender to touch and cause patients to visit their doctors.
Lymph nodes in the popliteal fossa are very rare and, as a rule, of inflammatory or
cancerous origin [12]. They are usually a result of distal inflammation or infection (e. g. erysipelas,
venous leg ulcers) or cutaneous malignancies [13].
Lymph drains from the legs, external genitalia and the buttocks drains via the inguinal
LNs as does lymph from the skin and subcutaneous tissues below the umbilicus.
Local differential diagnoses frequently include lipmas, hernias, joint effusions,
postoperative seromas and haematomas ([Fig. 3a–d], [4a, b]).
Fig. 3 a Postoperative seroma with surrounding oedema in the groin. b Baker’s cyst (knee joint). c Inguinal hernia (arrow) after Valsalva manoeuvre. d Palpable subcutaneous lipoma, without any vascularisation to be seen on colour Doppler
(arrows).
Fig. 4 a Palpable mass on the inner aspect of the thigh on the adductor longus muscle corresponds
to a clearly demarcated echogenic spindle-shaped lipoma measuring 53 mm × 9 mm. b Surgical resection was performed because of the clearly visible vascularisation seen
on colour Doppler and the hyperperfusion in the contrast enhanced ultrasound (CEUS).
Focal echogenic lesions, usually lying in the subcutaneous tissue, are most likely
to be consistent with palpable lipomas ([Fig. 3 d], [4a, b]). Colour Doppler scans reveal no vascularisation. Histological examination must
be performed, if there is growth or evidence of intralesional vessels [14].
Inflammatory/Reactive lymph nodes
Inflammatory/Reactive lymph nodes
Inguinal lymph nodes, which are usually of chronic inflammatory or reactive origin,
are found in nearly everyone. The cortex may be extremely narrow (< 1 mm) and there
is usually no vascularisation to be seen on colour Doppler. The centre of the LN usually
shows echogenicity (adipose tissue, see [Fig. 5b], [6a–d]), but in some instances may be less echogenic than the fatty tissue surrounding
the node ([Fig. 5b]).
Fig. 5 a Central echogenic (adipose), elongated LN with a cortex measuring approx. 0.7 mm
(red arrow). b Central less echogenic medulla (yellow arrows: fatty infiltrate); narrow cortex measuring
approx. 0.6 mm (red arrow). c, d LN measuring 7 mm with thickened cortex that is hypoechoic relative to the echogenic
hilum. b Regular vascular arrangement in the colour Doppler.
Fig. 6 a Regional adipose area (red arrow), narrow cortex (yellow arrow). b Reflection from the needle (white arrow) used for cytological confirmation. c, d Regional hypoechoic thickened segment of cortex, seen on colour Doppler to be hypervascularised
with a regular vascular arrangement. e Cause: hair follicle inflammation.
The thickness of the cortex (follicles, paracortex) and the degree of vascularisation
increase with the inflammatory activity ([Fig. 5a–d], [6c–e], [7a–c], [8]). Regional cortical expansion can be seen, if the afferent lymphatic vessels drain
antigens into the responsible LN compartments ([Fig. 1], [6a–e]) and thus trigger a regional immune response. Acutely inflamed LNs are usually unilateral.
Fig. 7 a Chronic lower leg ulcer, almost circumferential. b C-plane* demonstrating one of several LNs with follicles (yellow arrow); paracortex
(white arrow). c Colour Doppler shows considerable hypervascularisation with normal vascular arrangement
(tree-like branching arteries and veins). *C-plane: B-mode reconstruction parallel
to the skin from one sweep.
Fig. 8 Female patient with melanoma on interferon therapy. a Elongated inguinal LN with thickened cortex, Solbiati Index > 2 and b increased arterial and venous vascularisation with normal vascular structure. Reactive
LN confirmed on histology. c Inguinal LN with hypertrophied follicles (arrow), Solbiati Index > 2. d Hypervascularised LN with regular arterial vascular structure. e Patient with psoriasis, showing thickened cortex, Solbiati Index approx. 2, and f regular vascular arrangement at the hilum.
Benign lymphadenopathy is often self-limiting.
With respect to the aetiology, autoimmune diseases (e. g. rheumatoid arthritis, dermatomyositis,
lupus erythematosus), pharmacotherapy (e. g. interferon therapy), and iatrogenic causes
(e. g. local interventions) come into question besides acute and chronic inflammation
and infections of the skin such as psoriasis and atopic eczema ([Fig. 8a–f]) [14]
[15].
[Table 2] gives the most important ultrasound criteria for distinguishing between inflammatory/reactive
nodes, metastatic disease and nodal lymphoma. The size of the nodes alone is not a
differentiating characteristic.
Abscess formation in inflamed LNs is rare and usually found in the neck (e. g. tuberculosis)
or in the groin in the case of venereal diseases or immune incompetence.
Lymph nodes transformed by metastasis
Lymph nodes transformed by metastasis
Ultrasound scanning is clearly superior to palpation in the detection of lymph node
metastases [16]. Malignant infiltration of lymph nodes in the lower limb is most often due to malignant
melanoma, malignant lymphomas, squamous cell carcinoma of the anal canal, vulva and
penis, sarcomas and cutaneous squamous cell carcinomas, also of the trunk. As the
tumour cells usually grow concentrically from the edge or centre of the node, lymphatic
metastases usually appear as asymmetrical hypoechoic cortical nodules or rounded hypoechoic
lymph node lesions. With haematogenous spread, tumours may initially be confined to
the centre of the node, sparing the cortical region. In contrast to inflammatory and
sometimes lymphomatous changes in the LNs, the nodes are often spherical: the ratio
between the maximum longitudinal measurement and the maximum transverse measurement
is usually between 1 and < 2 [9]
[10]. A further important criterion concerns tumour vascularisation and perfusion. Tumour
blood vessels do not have a muscular layer and show pores of varying size in their
walls. Fluid can therefore be squeezed out of the vascular lumen into the LN tumour
tissue. This leads to an increase in the interstitial pressure and thus to a reduction
in tissue perfusion. The middle of the tumour becomes ischaemic and eventually necrotic
[17]
[18]. If the capsule is damaged by tumour invasion, fluid can leak out of the lymph tissue
and lead to a perinodal oedema ([Fig. 9]).
Fig. 9 Fine spicules of hypoechoic extension beyond the LN capsule (yellow arrows) indicate
tumour invasion, usually with accompanying regional oedema (red arrows).
The nutritional and O2 requirements are ensured not only by the hilar arterial branches but – especially
when there is central ischaemia or necrosis – also by capsular arteries radiating
into the LN ([Fig. 10a–f], [11a, b], [12a, b]).
Fig. 10 a Inguinal metastases from a sarcoma (yellow arrow: normal LN cortex; red arrow: round
metastasis, about 1 cm in size). b Tumour vessels entering from the periphery, ischemic tumour centre. c 5 mm spherical hypoechoic inhomogeneous metastasis from a melanoma, completely infiltrating
the LN with d vessels entering from the periphery. e Spherical melanoma metastasis appearing almost cystic and completely infiltrating
the LN with f central ischaemia and peripheral vascular supply via capsular arteries, central ischaemia.
Fig. 11 Hypervascularised inguinal melanoma metastasis. Solbiati Index < 2. a B-mode image of the hypoechoic cortex and hypoechoic medulla with central tumour
infiltration. b Colour Doppler shows an additional vascular supply via the capsular arteries.
Fig. 12 Situation after minimally invasive surgery for cervical cancer. Four months later,
there was an inguinal LN metastasis. a Enlargement of the proximal end of the LN (left in the picture), showing b only minimal peripheral vascularisation, while the still intact inferior cortex is
clearly hypervascular.
Lymphomas
When possibly malignant inguinal lymph nodes are an incidental finding, it must be
decided whether they are a manifestation of systemic disease or a regional LN metastasis.
Clinical data are decisive. In children and adolescents, an inflammatory/reactive
aetiology is most likely. Fine needle aspiration (FNA) to confirm the diagnosis is
recommended by some authors [19].
Isolated inguinal Hodgkin lymphoma (stage 1) tends to be rare and appears as a hypoechoic
or cystic cortical enlargement in the B-mode scan. In the case of non-Hodgkin lymphoma,
suspicious LNs are usually found at several LN stations; abdominal manifestations
(lymph nodes, involvement of the spleen or liver) are also not uncommon [20]. From the oncological point of view, an expert examination of the LN histology is
usually required to determine the subtype on which the treatment and prognosis depend.
Without any knowledge of the clinical background, it can be very difficult or even
impossible to differentiate with certainty between lymphoma and inflammatory/reactive
LNs on the basis of the ultrasound findings alone ([Fig. 15]). Non-Hodgkin lymphomas are usually hypoechoic and strongly vascularised with a
tree-like branching vascular structure. The cortex is typically thickened and hypoechoic,
occasionally small typical hypoechoic nodules can be found in the cortex and medulla
([Fig. 13a], [14a], [15a]). A complete cystic transformation may also be a typical ultrasound feature of NHL.
Depending on the subtype, several affected LNs may show great ultrasonographic variation
in a single patient.
Fig. 13 B cell non-Hodgkin lymphoma (B-NHL). a In the B-mode scan, multiple fine nodules can be seen in the medulla in addition
to a thin hypoechoic cortex (arrow). b Colour Doppler shows increased vascularisation with a preserved vascular structure.
Fig. 14 Typical peripheral lymph nodes in B-NHL, all with a Solbiati Index < 2. a In the B-mode scan, hypoechoic cortical thickening with small hypoechoic nodules
and still intact echogenic centre. b Hypervascularised LN with regular vascular structure. c Round hypoechoic B-NHL LN with echoes from the core biopsy needle (arrow); the hilum
can no longer be recognised in the B-mode scan. d Central vascular supply with regular tree-like branching and slight peripheral vascularization.
Fig. 15 56-year-old patient with mycosis fungoides (T-cell lymphoma). a B-mode scan of a superficial elongated LN (Solbiati Index > 2) with its structure
maintained (cortex, medulla, hilum). b Colour Doppler clearly shows a hypervascularised LN with a regular vascular structure.
As non-Hodgkin lymphoma in particular can compress the blood vessels, lymphoma must
also be considered when there is unilateral dilatation of the leg veins with signs
of venous stasis ([Fig. 16a–c]).
Fig. 16 a Pelvic veins with unilateral venous dilatation of the leg veins, showing spontaneous
echoes from the valves in the proximal femoral vein. b Loss of the spontaneous echoes after venous compression. c Venous compression leading to stenosis of the external iliac vein by pathological
LNs. d Accelerated flow seen in the area of stenosis (colour Doppler). e Morphological presentation of the stenosis in B-Flow procedure.