#202 LIVE! Lymphadenopathy: Taking Your Lumps

March 30, 2020 | By Matthew Watto, MD

A practical approach to lymphadenopathy with Carrie Thompson MD, Hematology-Oncology 

LIVE! from Mayo Clinic, a practical approach to lymphadenopathy with Carrie Thompson MD @cathompsonmd (Hematology Oncology, Mayo Clinic). Dr. Thompson provides her simplified approach to the history, differential diagnosis, high yield lab testing, imaging, how to counsel patients with adenopathy and tips on when, where and how to biopsy!

Special Thanks!

The Curbsiders are insanely grateful to the Mayo Clinic  Internal Medicine Residency Chief Residents @mayomn_imres (@JasonEckmannMD @SamiRyanMD @BHuffmanMD @CourtHarrisMD) and their amazing program director @AmyOxentenkoMD for an amazing trip to Rochester! 

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Credits

• Written and Produced by: Carrie Thompson MD and Matthew Watto MD, FACP
• Infographic: Matthew Watto MD, FACP
• Cover Art: Kate Grant MBChB DipGUMed

• Hosts: Stuart Brigham MD; Matthew Watto MD, FACP; Paul Williams MD, FACP   
• Editor: Matthew Watto MD (written materials); Clair Morgan of nodderly.com
• Guest: Carrie Thompson MD

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Time Stamps

• 00:00 Announcement: We’re looking for Medical Student members. Send applications to thecurbsiders@gmail.com by April 10, 2020.
• 01:20 Intro, guest bio, one-liner, career advice; Pick of the week*: In Shock by Rana Awdish
• 07: 00 Lymphatic system
• 09:19 Differential diagnosis for lymphadenopathy
• 11:38 Taking a history (ALL AGES mnemonic), Red Flags
• 19:15 Physical exam for lymphadenopathy
• 22:30 Which labs to order; Flow cytometry
• 26:05 Imaging
• 28:30 Counseling patients with LAD
• 31:10 Biopsy: How to choose type and location
• 37:35 Take Home Points
• 39:00 Audience Questions
• 42:25 Outro

*The Curbsiders participates in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising commissions by linking to Amazon. Simply put, if you click on our Amazon.com links and buy something we earn a (very) small commission, yet you don’t pay any extra.

Lymphadenopathy Pearls

1. Most lymphadenopathy (LAD) seen in primary care is not caused by malignancy.
2. No physical exam signs can differentiate benign from malignant.
3. Initial labs: CBC with differential, Peripheral smear, HIV. 
4. Additional tests to consider: ANA, EBV, CMV, Monospot, RPR, Hep B sAg, TB testing, Serology for tick borne illness if risk factors.
5. Flow cytometry on peripheral blood is usually unhelpful in the workup for LAD since lymphomas are a disease of the lymph nodes and do not have abnormal circulating lymphocytes.
6. Imaging: CT scan is usually the first choice for adults because it delineates the extent of LAD including deeper lymph node involvement. Ultrasound is preferred in pediatrics. 
7. Biopsy: Excisional lymph node biopsy preferred if lymphoma suspected. Biopsy the largest palpable lymph node. Core needle biopsy preferred for deeper, non-palpable nodes.

Lymphadenopathy Notes 

Lymphatic system

• Returns fluid from the organs to the cardiovascular system.
• Integral part of the immune system where lymphocytes are developed.
• It includes: the thymus, bone marrow, lymph nodes, spleen, tonsils and Peyer’s patches in the GI tract.

Differential Diagnosis (DDx) for Lymphadenopathy

Most lymphadenopathy (LAD) seen in primary care is not caused by malignancy, which makes up about 4% in those over 40 and 0.4% of those under 40 years old [Fitjen, 1988*]. NOTE*: This was a small retrospective study from the Netherlands. We wouldn’t put too much stock in percentages, but the general consensus is that the rate of malignant LAD in primary care is low. 

MIAMI Mnemonic

Mnemonic suggested by Gaddey, 2016

• Malignancy
• Infection -probably the most common cause for LAD.
• Autoimmune e.g. SLE, RA
• Miscellaneous e.g. Castleman’s, sarcoidosis
• Iatrogenic e.g. allopurinol, anti-epileptic drugs, beta blockers

Keep a broad DDx. Don’t anchor!

Mini Case #1

65F with a history of sarcoma who’s been doing well, but now with new inguinal LAD and low grade fevers. Excisional lymph node biopsy showed reactive disease. Eventually, ID figured out that she had a new kitten and cat scratch disease.

Mini Case #2

A woman presents with B symptoms and abdominal pain. A CT in the ED showed generalized LAD and splenomegaly. After a more thorough history and exam she was noted to have a mechanical heart valve and new murmur. Eventually, blood cultures were positive and she was treated for endocarditis.

Taking a history for lymphadenopathy

Use the ALL AGES Mnemonic

Mnemonic suggested by Dr. Thompson

• Age
• Location
• Length of time present -most reactive nodes are gone in 2 weeks or so.
• Associated symptoms e.g. fever, wt loss
• Generalized or localized?
• Extranodal associations e.g. joint pain, rash
• Splenomegaly

Red Flags

As suggested by Gaddey, 2016

• Older age, usually >40 yo because about 4% of these patients will have malignancy [Fitjen, 1988]
• Present more than 4-6 weeks (or not to baseline by 8-12 weeks)
• Male sex
• White race
• Supraclavicular location, which drains the lungs, GI tract and GU system
• Systemic symptoms (e.g. wt loss, fevers)
• Generalized LAD (more than 2 regions) is more likely to be malignant than localized LAD, which is often infection.

Physical exam

Dr. Thompson recommends checking for lymphadenopathy as part of the routine exam (expert opinion). Check for cervical, supraclavicular, axillary and inguinal lymphadenopathy. 

• Any palpable nodes are abnormal.
• No physical exam signs can differentiate benign from malignant.
• Shotty LAD refers to pea sized or smaller. Usually benign.

Kashlak Pearl: Tender LAD is caused by stretching of the capsule during rapid growth. This can occur with malignancy, inflammation or infection. No physical exam signs can differentiate benign from malignant.

Lab studies in lymphadenopathy

Dr. Thompson recommends obtaining the following lab studies to evaluate lymphadenopathy:

• CBC with differential
• Peripheral smear
• HIV

The following additional tests can be considered if clinical suspicion is high (list based on both Gaddey, 2016 algorithm and our conversation with Dr. Thompson):

• +/-EBV, CMV, Monospot if viral symptoms
• +/- ANA, ONLY IF history is suggestive of an autoimmune condition
• +/- PPD or IGRA if TB risk factors
• +/- RPR
• +/- Hep B sAg
• +/- Serology for tick borne illness if risk factors

Kashlak Pearl: Flow cytometry can be performed on various types of tissue. Flow cytometry on peripheral blood is usually unhelpful in the workup for LAD since lymphomas are a disease of the lymph nodes and do not have abnormal circulating lymphocytes.

Imaging

Dr. Thompson notes that a CT scan is usually the first choice for adults because it delineates the extent of LAD including deeper lymph node involvement. Ultrasound can be helpful to avoid radiation in pediatric patients or to help plan for a needle biopsy in adults. 

Kashlak Pearl: DO NOT jump right to a PET scan. BUT, this may be necessary after making a tissue diagnosis as part of staging.

Counseling patients with LAD

Dr. Thompson might say something like this to a patient with red flags present:

“I am concerned about malignancy as a possibility, but there are so many other things that can cause your lymph nodes to be enlarged including infections, autoimmune conditions, etc. …and so we wanna be thorough and workup these other things…but finding a diagnosis of cancer…we don’t wanna miss that.”

“I would like to proceed with a biopsy to rule out malignancy.”

Kashlak Pearl: Patients with localized LAD and no red flags can be reassured and brought back in 4-6 weeks for repeat examination.

Biopsy for Lymphadenopathy

Fine needle aspiration (FNA) acquires a small piece of tissue to examine the cell type present i.e. malignant vs benign. Dr. Thompson might choose an FNA if a patient has cervical or supraclavicular adenopathy and lung cancer or head & neck cancer is suspected because an excisional biopsy in these cases might make future neck dissection more difficult (expert opinion).

A core needle biopsy is larger and gives some idea of the histopathology i.e. “what the cells look like in place next to each other”. This is most useful for non-palpable lymph nodes (expert opinion).

Excisional biopsy gives the lymph node’s entire architecture and is particularly important in diagnosing lymphoma. For example, in Hodgkin’s lymphoma the pathognomonic Reed Sternberg cells are the minority of cells and, thus might be missed by an FNA or core needle biopsy  (expert opinion).

Which lymph node should you biopsy?

Generally, Dr. Thompson recommends a biopsy of the largest palpable lymph node (LN). If equal size LNs in the inguinal and axillary region, then go with the axillary LN since they’re less likely reactive. If no palpable LN and significant internal LAD (e.g. mesenteric or mediastinal) then a core needle biopsy of these sites is appropriate (expert opinion).

Take Home Points

Dr. Thompon’s reminds the audience:

1. Most patients with lymphadenopathy in the PCP office do not have cancer.
2. Use the mnemonic MIAMI for your differential diagnosis (DDx) and ALL AGES when taking a history.
3. Perform an excisional LN biopsy if lymphoma is in the DDx.

Audience Questions

Should a PET scan be done before biopsy? 

Dr. Thompson notes that the cost and radiation exposure are often unnecessary, but a PET scan may be done for staging if the patient is ultimately found to have a PET avid malignancy.

When should a patient with LAD be referred to Heme Onc?

Usually the referral is made after a biopsy has been obtained, but one might consider referral for fever of unknown origin or to help interpret the initial biopsy results.

Links*

1. In Shock (book) by Rana Awdish
2. Fijten GH, Blijham GH. Unexplained lymphadenopathy in family practice. An evaluation of the probability of malignant causes and the effectiveness of physicians’ workup. J Fam Pract. 1988;27(4):373-376. https://www.ncbi.nlm.nih.gov/pubmed/3049914 
3. Freeman AM and Matto P. Adenopathy – StatPearls – NCBI Bookshelf https://www.ncbi.nlm.nih.gov/books/NBK513250/. Last updated November 27, 2019.
4. Gaddey HL and Riegel AM. Unexplained Lymphadenopathy/Evaluation and Differential Diagnosis. Am Fam Physician December 2016 https://www.ncbi.nlm.nih.gov/pubmed/27929264. 

*The Curbsiders participates in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising commissions by linking to Amazon. Simply put, if you click on our Amazon.com links and buy something we earn a (very) small commission, yet you don’t pay any extra.

Goals

Listeners will develop a framework and systematic approach to evaluating the patient with lymphadenopathy. 

Learning objectives

After listening to this episode listeners will…

1. Describe differential diagnosis of enlarged lymph nodes.
2. Summarize the evaluation of lymphadenopathy.
3. Identify the most appropriate type and timing of lymph node biopsy.

Disclosures

Dr Thompson reports no relevant financial disclosures. The Curbsiders report no relevant financial disclosures. 

Citation

Thompson C, Williams PN, Brigham SK, Watto MF. “#202 LIVE! Lymphadenopathy: Taking Your Lumps”. The Curbsiders Internal Medicine Podcast. http://thecurbsiders.com/episode-list. March 30, 2020.