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MINOR SALIVARY GLAND BIOPSY
(LIP BIOPSY)

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The minor salivary gland biopsy (MSGB) is commonly referred to as the “lip biopsy.” Another name for it is the labial salivary gland biopsy. This test plays a central role in the diagnosis and classification of Sjogren’s. SS-A positive patients can usually be diagnosed without undergoing a MSGB.

It is important to take into account the flaws and limitations of this test when interpreting test results.  About 20 % of Sjogren’s patients have a negative MSGB. 
 

The reasons for this are described below. A positive MSGB in the context of clinical symptoms strongly supports a Sjogren’s diagnosis. A negative MSGB does not rule out Sjogren’s.

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When is the MSGB performed?

MSGB is indicated in SS-A negative ("seronegative") patients who have signs and symptoms of Sjogren’s.  Seronegative patients often rely on MSGB to support a Sjogren’s diagnosis. Rheumatologists may decide to order the MSGB for other reasons, such as assessing risk for lymphoma or to look for other diseases such as amyloidosis or IgG4-related disease. 

How is the MSGB performed?

Small slivers of tissue are taken from the inside of the lower lip, using local anesthesia. Patients sometimes require a few stitches. This minor procedure removes a few small glands, but not enough to reduce overall salivary flow. If the biopsy is performed by a skilled practitioner, only about 2% of patients experience long-term pain (usually mild) or numbness at the biopsy site. It is important to find out if the person performing the biopsy does this procedure frequently, not just a few times a year. 

Special training/ experience is required to obtain a good lip biopsy sample. The procedure is generally well-tolerated when done by a skilled clinician, usually an oral surgeon or ENT. Equally important is the skill of the pathologist who reads the specimen. The sample should be read by a head and neck pathologist with special training to read these biopsies for Sjogren's. This is more likely to be available in large medical centers and teaching hospitals. 

As a veteran of three MSGB procedures, I can attest to the fact that the procedure was minimally painful. However, I did have highly experienced clinicians who performed the biopsies. My second two biopsies, performed by Dr. Ava Wu for the UCSF SICCA study, required no stitches. I was able to eat lunch immediately following biopsy #2 and #3.   ~ Sarah Schafer

What does it mean to have a positive MSGB? 

A pathologist looks at the sample under a microscope and finds collections (foci) of inflammatory cells that cluster around ductal cells in the salivary gland.  A “focus score” is then assigned based on the number of foci (clusters) seen per 4 square mm  in a particular sample.
A focus score of 1 or higher is positive (4). A focus score of 1 is considered positive, just like a focus score of 4 is positive. A positive test usually correlates with dryness. The MSGB may be negative early on, especially when oral sicca lags behind other symptoms (20). A positive MSGB in a patient with clinical Sjogren's features is usually considered a firm diagnosis.

 

While a positive MSGB usually indicates Sjogren’s, false-positive test results are occasionally seen with Hepatitis C, HIV, graft-versus-host disease, smokers, and in some healthy controls (19).

Advantages of MSGB

  1. MSGB is currently the best way to confirm a diagnosis of SS-A negative Sjogren’s. Salivary gland ultrasound is sometimes performed in lieu of MSGB. This requires special training and is not widely available as of 2022.

  2. The biopsy specimen may provide valuable prognostic information for lymphoma and other direct complications of Sjogren’s (1116, 17)  Germinal Center (GC)- like structures are seen in about 25 % of positive biopsies. GCs are associated with an increased risk of developing lymphoma (20).  Many pathologists do not report GC structures at this time.

Disadvantages/limitations of MSGB

The MSGB reflects the salivary component of Sjogren’s, which is just one aspect of this multi-system disease. Salivary sicca is present in most Sjogren’s patients, but may not be present early on in the disease, or in patients with organ system (especially neurological) presentations. 

  1. The test is not always available. Seronegative patients may wish to travel to a provider who can perform this procedure, especially if their doctor insists they do not have Sjogren’s due to being SS-A negative.
     

  2. While the test should be minimally invasive, provider technique varies. Some patients refuse the procedure, especially when they hear about others who experienced a painful MSGB. It is important to ask about the clinician's experience.  Doing a handful of biopsies a year is not enough.
     

  3. Sampling procedure is not standardized. Many providers (dentists, ENTs, others) do not take adequate samples due to a lack of consistent training.
     

  4. Until recently, no clear standards have been available for reading and reporting biopsy specimens. Mistakes in reading the sample may lead to an incorrect diagnosis.
     

  5. A negative finding does not rule out Sjogren’s. False negative results may occur due to problems with the biopsy sample, the reading of the sample, or an inadequate number of representative glands. Early in the disease, inflammation may not have developed into clusters of cells that qualify as foci. Late in the disease, atrophy and scarring may predominate. The focus score may drop to less than 1 as the disease progresses (3, 17).

Major differences have been reported in samples that were given to several pathologists to read (20). A large group of expert researchers recently created the first set of standards for assessing and reporting biopsy specimens (17).

My MSGB Window of Opportunity

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My own experience with three biopsies performed over a nine year span illustrates the limitations of the MSGB.
In short: Each of my three MSGBs were abnormal, but #1 and #3 were officially negative. I clearly had Sjogren's at the time of each biopsy. Learn more about how the limitations of the MSGB (lip biopsy) delayed my diagnosis in the blog post, 12 Reasons People With Sjogren's Don't Get Diagnosed. 

Biopsy # 1: Inflammation present but not focal. This is considered to be a negative result. Despite severe Sjogren’s symptoms, including longstanding dry eye disease, my rheumatologist did not believe I had Sjogren’s because the typical antibodies, SS-A, SS-B, RF, and ANA, were all negative.

Biopsy #2:  Performed seven years after biopsy #1. Positive result, with a focus score of 1.5. I continued, and remain to this day, negative for all of the typical Sjogren's antibodies.  Based on this biopsy, and tests for eye and oral sicca, I met the classification criteria for Sjogren's. 

 

Biopsy #3: Performed two years following biopsy #2 as part of my participation in a research study.  Result: Scarring and atrophy, with a focus score described as N/A. This is officially a negative MSGB, although in the clinical context, it is considered evidence of advanced salivary gland damage caused by Sjogren's. 

I was fortunate that a second biopsy was performed. Clinicians often do not realize that widespread inflammation can be seen leading up to a positive focus score. It was also fortunate that I had the positive reading before I had too much scarring to give a focus score reading. 

 

How many patients are denied a Sjogren's diagnosis because of the limitations of the test?  Sjogren's is a clinical diagnosis. Diagnosis should never be reduced to a box-ticking exercise. 

For self-advocacy tools and more information about the uses and limitations of the lip biopsy, see Myth #5 in the Myths About Diagnosis section


  ~ Sarah Schafer, MD and Sjogren's patient

Updated 10-07-2023

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