What are Lymph nodes & Swollen lymph nodes?  

Lymph nodes are small bean shaped structures (of which there are hundreds through the body) which are connected to one another to form what is called the lymphatic system, This system serves as a biological filter by trapping and destroying harmful things/cells including bacteria, viruses or damaged cells which can become cancer.  Through this lymphatic system the predominant cell type is the white blood cells (Lymphocytes) which is an immune response cell that uses these channels to travel to areas of where they are needed to fight infection and disease.  

 

How do lymph nodes spread cancer?

On occasion lymph nodes can trap bacteria, viruses or cancerous cells that the lympocytes cannot destroy in order to keep disease at bay. Although these lymph nodes help destroy cancer cells they can also provide a conduit or a highway for these cancer cells to spread sometimes to distant sites which are not other lymph nodes.  For example breast cancer is notorious for traveling to the arm pit lymph nodes which can then spread to other parts of the body including the bones.  Cancer can sometimes originate in the lymph nodes themselves.  This is called lymphoma which is a cancer of the lymph nodes but unlike infections is usually a cause of painless lymph node swelling which can be diffuse throughout the body when progressed.

 

What do lymph nodes do?

The lymphatic system has several different functions:

  • It functions to move fluid that is within the tissue into the bodies blood circulatory system mainly through lymphocapullaries that penetrate organs and superficial tissues. 
  • it contains white blood cells or lymphocytes, which are cells specific for fighting infections and disease
  • it gets rid of any waste that cells make.

 

Lymph node groups/Where are lymph nodes located?

The groups of lymph nodes throughout the body are arranged in such a way as to become an obstacle to infection and cancer.  These individual lymph nodes can enlarge as more lymphocytes travel to the lymph node to help fight infections and disease.  So, these normal lymph nodes can be located in the elbow, armpit, behind the knee, and also in the groin area as well as multitude of other locations. 

For example the lymph nodes in the neck provide protection against infections and tumors that can arise in the head and organs in the neck. A very large number of lymph nodes are found in the abdomen and chest cavity. Additionally Lymphocapillaries penetrate organs as well as superficial tissues to allow more local access of these lymphocytes even beyond lymph nodes themselves. The lymph nodes along the blood vessels perform the same functions.

Commonly described location for lymph nodes include the following groups

  • intrathoracic, mediastinal ,
  • bronchopulmonary (hilar),
  • ulnar (epitrochlear and brachial),
  • splenic (spleen),
  • paraaortic ( paraaortic ),
  • mesenteric ( mesenteric ) ( mesentery )
  • iliac (Iliac: common , internal and external )
  • inguinal (Inguinal: deep and superficial ),
  • femoral (femoral),
  • popliteal ( popliteal ).

The following lipid- related lymph node enlargement syndromes should be noted :

  • Gaucher syndrome
  • Niemann-Pick syndrome.

Most common sites of swollen lymph nodes

  • Swollen lymph nodes in the neck – These lymph nodes drain the head, face and neck area and can be related to anything from cancers of the mouth and lymphoma to simple infections of the teeth or tonsils.  Read below to find out how to evaluate them.
  • Swollen lymph nodes in the armpits – this is a common complaint and new lymphadenopathy should be evaluated by your physician.  The differential diagnosis differs based on bilateral axillary/armpit swollen lymph nodes/lymphadenopathy or one sided lymphadenopathy.
  • Swollen lymph nodes in the groin are also a common complaint that need to be evaluated for an can be caused by infectious etiologies or various cancers.

 

Swollen lymph nodes in neck

Swollen neck lymph nodes are classified by their location.  Diffusely swollen lymph nodes on both sides of the neck can suggest lymphoma.  Swollen lymph nodes/lymphadenopathy in the head and neck has several classifications including submental, submandibular, anterior or posterior cervical, preauricular, and supraclavicular.  The most common cause of swollen lymph nodes in their area includes infections.  children have a particular higher likelihood of showing swollen lymph nodes/lymphadenopathy in this area that is related to self limited viral infections.  More concerning can be lymph nodes that quickly become fluctuant (feel like wave like motion when pushing on the swollen lymph node) which are generally associated with bacterial infections caused by  staphylococcus and streptococcus which requires early diagnosis and antibiotic treatment.  at times these bacterially infected lymph nodes require incision and drainage.  if swollen lymph nodes in this area lasts several months one cause can be atypical mycobacterial infections, cat-scratch disease, Kikuchi lymphadenitis, sarcoidosis, and Kawasaki disease, and these can be commonly mistaken for cancer/neoplasm.  The most concerning location for swollen lymph nodes in the neck is supraclavicular (Swollen lymph nodes above the clavicle) because they can in both children and adults be associated with a risk of cancers within the abdomen and should be evaluated quickly.  Some studies have shown that nearly half of the patients who have swollen lymph nodes above the clavicle especially those patients over 40 years of age have cancer.

 

Submandibular swollen lymph nodes are found in the neck below the jaw. These lymph nodes drain the tongue, submaxillary gland, lips and mouth, conjunctivae of the eye. Causes of these swollen neck lymph nodes include infections of head, neck, sinuses, ears, eyes, scalp, pharynx

Submental refers to swollen lymph nodes under the chin.  These lymph nodes drain the lower lip, floor of mouth, tip of tongue, skin of cheek. Causes of these swollen neck lymph nodes include mononucleosis syndromes, Epstein-Barr virus, cytomegalovirus, toxoplasmosis

Jugular lymph nodes refers to the area in the anterior neck along the large jugular vein.  These lymph nodes drain the tongue, tonsil, pinna, parotid.  Causes of swollen lymph nodes in this are include pharyngitis organisms, rubella infection or cancers in the area.  

Posterior cervical refers to lymph nodes in the back of the neck.  These lymph nodes drain the scalp and neck, skin of arms and pectorals/chest, thorax, cervical/neck and axillary/armpit nodes.  Causes of swollen lymph nodes in this area includes tuberculosis, lymphoma, head and neck malignancy

Suboccipital refers to the area on the back of the scalp/head.  A group of lymph nodes can occur here.  These lymph nodes drain the scalp and head. These lymph nodes usually swell because of local infection

Postauricular refers to the area behind the ear lobe. The lymph nodes behind the ear drain the external auditory meatus, pinna, scalp. swollen lymph nodes in this area are commonly cause by local infection

Preauricular refers to the area in front of the the ear lobe.  These lymph nodes in front of the ear lobe drain the eyelids and conjunctivae, temporal region, pinna.  Swollen lymph nodes in this area are generally caused by problems in the external auditory canal

Right supraclavicular node refers to the area right above the right clavicle or collarbone.  The lymph nodes above the collarbone on the right generally drain the mediastinum, lungs, esophagus.  Swollen lymph nodes in this area can be related to issues in the lung, retroperitoneal or gastrointestinal cancer

Left supraclavicular node refers to the area above the left clavicle or collarbone.  The lymph nodes above the collarbone on the left generally drain the Thorax, abdomen via thoracic duct.  Swollen lymph nodes above the left collar bone can commonly be related to Lymphoma, thoracic or retroperitoneal cancer, bacterial or fungal infection

 

Swollen lymph node in armpit

A common cause of armpit swollen lymph nodes/axillary lymphadenopathy are infections or injuries of the upper extremities. with regard to infections a common infection effecting these lymph nodes include cat-scratch disease, tularemia, and sporotrichosis because these infections are directly introduced into the lymphatic system of the arm where they begin to spread to the armpit.  With lack of infection or injury/trauma to this area things such as lymphoma both hodgkins and non-hodgkins are a consideration.  other cancers including breast cancer, lung cancer, thyroid cancer, stomach, colorectal, pancreatic, ovarian, kidney, and skin cancers/melanoma can cause lymphadenopathy or swollen armpits in this area.  Another consideration in female patients is breast implants particularly silicone implants are known to cause inflammatory reactions with silicone particles leaking and traveling to the armpit where it causes swollen lymph nodes in this area.

 

Axillary also referred to as armpit lymph nodes can become swollen These lymph nodes drain the arm, thoracic wall, breast Causes for swollen armpit lymph nodes include Infections, cat-scratch disease, lymphoma, breast cancer, silicone implants, brucellosis, melanoma

Swollen Lymph node in groins

Inguinal lymphadenopathy/swollen groin lymph nodes can be present in normal healthy adults.   Multiple studies have noted that people who walk outside barefoot especially those in tropical regions tend to have chronically swollen lymph nodes in the groin which are otherwise considered normal.  Sexually transmitted diseases (STDs) are a common cause of swollen lymph nodes in this region.  infections such as herpes. chancroid, syphillis, lymphogranuloma venereum or localized or lower leg skin infections can cause this lymph nodes to swell.   Cancers can also commonly cause lymphadenopathy in this region with lymphoma or penile/penis cancers, ureteral cancers or vulvar/vaginal cancers (Squamous cell carcinoma or melanoma).

 

Inguinal or groin lymph nodes can become swollen Groin lymph nodes drain the penis, scrotum, vulva, vagina, perineum, gluteal region, lower abdominal wall, lower anal canal The most common causes of swollen groin lymph nodes include infections of the leg or foot, secually transmitted diseases (STDs) (e.g., herpes simplex virus, gonococcal infection, syphilis, chancroid, granuloma inguinale, lymphogranuloma venereum), lymphoma, pelvic malignancy, bubonic plague

 

How can you tell if a swollen lymph node is cancer?

 

Lymph nodes can feel swollen for lots of  reasons.  A physical exam is important not only in being able to see if a lymph node is truly enlarged but to also identify if there are multiple locations of enlarged lymph nodes so that you can direct imaging to that location and possibly consider biopsy.  The causes of lymph node swelling in 1 spot differs from the causes of lymph node swelling in multiple spots.  Classically painless lymph node swelling is thought of as an indication of neoplasm/cancer because most infections are thought to cause painful lymph node enlargement but this is not always the case.  

There are size criteria which we will discuss here regarding what lymph nodes are considered benign or reactive (reactive to an infection) and which are considered pathologically enlarged (generally concerning for cancer).  These criteria are however not perfect and for example in patients with history of breast cancer lymph nodes that have changed in size/enlarged in the axilla/armpit always warrant further evaluation even if they do not fit classic descriptors of pathological lymph nodes.  There are some general considerations and evaluation that can be performed by imaging to help guide if lymph nodes are cancerous.  

As a base consideration cancer does not generally (this is not definitive) decrease in size on its own.  So for those lymph nodes which may have been enlarged but have decreased in size spontaneously (Without treatment) in patients without other history we defer to following these lymph nodes rather than intervening or biopsying them.

The decision to biopsy a swollen lymph node depends on many factors.  In patients who have a history of cancer we are somewhat quicker to biopsy because these patients have a higher risk.  for swollen lymph nodes that are confirmed by imaging (Ultrasound/CT/MRI or PET scan) and are new without infection or injury we  will likely biopsy early.  For lymph nodes that may have been present for a long time and have benign features on imaging, generally thought of as associated with infections in the area and measuring less than 1cm in short axis (measurements do differ for different sites of the body) we usually follow them by imaging.

 

How to evaluate a swollen lymph node by CT/PET scan and ultrasound

Ultrasonographic Criteria of Benign and Neoplastic Lymphadenopathy

  
Shape
Border
L/s Ratio*
Internal Echogenicity
Hilum
RI**
PI***
Blood Flow Distribution
Benign Disorders
ovoid
various
High>2
Isoechoic
Present-Normal
Low<0.8
<1.5
Hilar
Neoplastic Disorders
Round
sharp†
Low<2
Hypoechoic
Absent
High> 0.8
>1.5
Peripheral or miscellaneous

 

*Long axis to short axis (L/S); **Resistive index (RI); ***Pulsatility index (PI); †In matted lymph nodes, the border is not sharp. The data of the table are derived from references cited in the text.

Signs of low risk for malignancy

is suggested when lymphadenopathy is present for less than 2 weeks or persists for more than one year with no increase in size. With no cause identified, 4 weeks of observation and evaluation for infectious causes is recommended before invasive biopsy. CT, Ultrasound, PET, and biopsy should be considered early for large, concerning masses. 

 

Signs of high risk for malignancy

is suggested in patients who are ≥50 years, present with constitutional symptoms, have lymphadenopathy >1 cm in short axis (more specific measurements will be discussed later) >2 regions of the body, history of cancer, or have nodes that are rapidly enlarging, firm, fixed, or painless.  Supraclavicular lymphadenopathy has the highest risk for malignancy, especially in patients ≥40 years.  Enlarged iliac, popliteal, epitrochlear, and umbilical lymph nodes are never considered normal and should be evaluated.  Biopsy should be considered early in these patients. 

https://link.springer.com/article/10.1007/s40134-013-0036-6

 

Patients with history of malignancy

Are often biopsied earlier when a change in lymph node size or appearance of a new lymph node is noted.  Rectal cancer patients have pathologic lymph node size cutoff of 5mm in short axis.  

 

 

How are lymph nodes measured?

 

Lymph nodes are measured on CT, Ultrasound or MRI in their short axis diameter not long axis per nearly all standard measurement techniques.  

 

The majority of lymph nodes are considered normal if they measure less than 1 cm in short axis.

 

There are a few exceptions including inguinal region where lymph nodes less than 1.5cm in short axis are considered normal.  Additionally palpable supraclavicular, iliac and popliteal nodes, epitrochlear nodes which should measure less than 0.5cm. In general, normal lymph nodes are larger in children (ages 2-10), in whom a size of more than 2 cm is suggestive of a malignancy (i.e., lymphoma) or a granulomatous disease

 

Lymph nodes are evaluated based on size, shape (length to width ratio), appearance (cortical thickening or loss of fatty hilum) and vascularity (peripheral versus central vascularity)

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2821588/

 

A normal lymph node is ovoid is kidney bean in shape, hypoechoic (dark appearing on ultrasound) relative to the adjacent muscle and frequently contains an echogenic fatty hilum.

normal lymph node on ultrasound

Normal appearance of a lymph node on ultrasound. The darker rip of the elongated lymph node is thin which is a normal appearance and the central portion within the dark rim is bright/echogenic and represents fat within the lymph node hilum which is normal. additionally the lymph node is longer than it is tall and measures less than 1cm in its shortest axis (from top to bottom)

 

 

 

 

 

 

 

 

 

The hilum is a linear, echogenic(Bright on ultrasound), non-shadowing(ultrasound feature that denotes fat as opposed to calcification) structure seen on ultrasound that contains the vessels going into the lymph node and it appears continuous with the fat around the node. 

 

The following criteria is usually applied to differentiate between normal and malignant nodes on ultrasound (US) evaluation.

 

Nodal size

 

Lymph nodes are measured in the shortest diameter as opposed to the longest diameter as this has been found to be more indicative of nodal pathology.  If the short axis measures more than 1 cm in diameter the lymph node is generally considered malignant. However, the size threshold does vary with the site of the lymph node (Armpit and groin lymph ndoes are considered malignant when the short axis measures greater than 1.5cm) and underlying tumor type; e.g. in rectal cancer, lymph nodes larger than 5 mm are considered pathological.

A normal sized lymph node is usually less than 1cm in diameter. As mentioned many times, there are exceptions in lymph nodes in different regions and at different ages have different sizes. For example, groin lymph node size up to 1.5 cm should be considered normal, while the normal range for the epitrochlear nodes is up to 0.5cm. In general, normal lymph nodes are larger in children (ages 2-10), in whom a size of more than 2 cm is suggestive of a malignancy (i.e., lymphoma) or a granulomatous disease (such as tuberculosis or cat scratch disease).(Ref)

It is suggested that palpable supraclavicular, iliac and popliteal nodes, epitrochlear greater than 0.5cm, and inguinal nodes larger than 1.5 cm are abnormal.(Ref) The nodes in other areas are considered as abnormal if their diameter exceeds one cm.(Ref) However, there is no uniform nodal size at which the greater diameter can raise suspicion of a neoplastic etiology.

Studies on swollen lymph node sizes.

in one series(Ref) of 213 adults with unexplained lymphadenopathy, no patient with a lymph node smaller than 1 cm2 (1 cm × 1 cm) had cancer, while cancer was present in 8 percent of those with nodes from 1 cm2 to 2.25 cm2 (1 cm × 1 cm to 1.5 cm × 1.5 cm) in size, and in 38 percent of those with nodes larger than 2.25 cm2 (1.5 cm × 1.5 cm). In children, lymph nodes larger than 2 cm in diameter (along with an abnormal chest radiograph and the absence of ear, nose and throat symptoms) were predictive of granulomatous diseases (i.e., tuberculosis, cat-scratch disease or sarcoidosis) or cancer (predominantly lymphomas).(Ref) These studies were performed in referral centers, and conclusions may not apply in primary care settings.

 

Nodal shapes

 

Benign lymph nodes are more likely to be ovoid/kidney bean shaped but they become more rounded as a result of malignant infiltration (Where they begin to loose their fatty hilum). If the ratio of the long axis to short axis diameter is less than 2 the lymph node is more likely to be malignant.

 

Nodal appearance

 

The sonographic/ultrasound features that are encountered in malignancy include loss of the echogenic/bright central nodal hilum, irregular nodal contour of the outer dark/hypoechoic cortex and or internal nodal heterogeneity.

 

Vascularity on Doppler ultrasound

 

Normal and benign nodes tend to have central hilar vascularity and central symmetric vascularity. Malignant nodes have been noted to demonstrate eccentric or absent hilar vascularity, multifocal aberrant vascularity, peripheral perfusion, focal perfusion defects or peripheral subcapsular vascularity in essence much like other cancers as they become more malignant in appearance the more abnormal the vascular flow into the lymph node becomes.  Much as with other cancers blood flow begins to be recruited from nearby areas causing abnormal vascular flow into the lymph node. Malignant nodes have higher resistive index (>1.0) and pulsatility index (>1.5) which can be measured by ultrasound although this is not commonly done. 

 

currently, the only widely accepted method for differentiating between normal and pathologic nodes is by size although we take into account nearly all factors before deciding to intervene/biopsy a lymph node. Reproducibility of measurement is important to avoid interobserver differences/differences in measurements made by different doctors.  This is one reason that the short axis diameter of a lymph node is a widely used measure as it has been demonstrated that this is constant despite orientation because it is likely to become rounder before it elongates. The short axis diameter is measured perpendicular to the longest diameter of the lymph node.

 

In the abdomen, the upper limit of the short axis diameter of normal nodes varies from 6 to 10 mm. For example the upper limit of a normal retrocrural node is 6 mm, a retroperitoneal node is 10 mm and 8–10 mm for nodes in the pelvis.

 

Unfortunately in the setting of cancer approximately 10–20% of normal-sized lymph nodes in the area of the cancer/locoregional nodes will actually contain tumur deposits and 30% of enlarged nodes will demonstrate only inflammatory hyperplasia. In some tumors, the incidence of metastatic disease within normal-sized nodes is greater than others. For example, in patients with colorectal cancer, 90% of nodal metastases occur in nodes <1 cm.

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3993046/