Minor Salivary Gland Biopsy

"Lip Biopsy"

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.  10-20 % of Sjogren’s patients have a negative MSGB.  The reasons for this are described below.   A positive MSGB strongly supports a Sjogren’s diagnosis, but a negative MSGB does not rule out Sjogren’s.

When is 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 lymphoma risk.

How is MSGB performed?

Small slivers of tissue are taken from the inside of the lower lip under local anesthesia.   Patients sometimes require a few stitches.   This minor procedure removes a few small glands, but not enough to reduce overall salivary flow.  Approximately 2 % of patients experience long term pain (usually mild) or numbness at the biopsy site. The procedure is generally well tolerated.

As a veteran of three MSGB procedures, I can attest to the fact that the procedure is minimally painful.  My first biopsy required multiple stitches, but was only mildly uncomfortable and swollen for a few days.  The second two biopsies (performed by Dr Ava Wu for the UCSF SICCA study) were a breeze.  They required no stitches, and I was able to eat lunch immediately following these procedures.

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 positive MSGB has a focus score of 1 or higher. A positive test usually correlates with dryness.  It may be negative early on, especially when oral sicca lags behind other symptoms. (18, 20)

While a positive MSGB usually indicates Sjogren’s, false-positive test results are occasionally seen with Hepatitis C, HIV, graft-versus-host disease, and in some healthy controls. (18, 19)

Advantages of MSGB

  1. MSGB is currently the best way to confirm a diagnosis of SS-A negative Sjogren’s. Salivary gland ultrasound might eventually take the place of MSGB in some patients.

  2. The biopsy specimen may provide valuable prognostic information for lymphoma and other direct complications of Sjogren’s. (11, 16, 17) Germinal Center (GC)- like structures are seen in about 25 % of positive biopsies. GCs are associated with an increased risk for 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 or neurologic 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.

  3. Sampling procedure is not standardized. Many providers (dentists, ENTs, others) do not take adequate samples due to 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 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. (18)  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 < 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

My own experience with three biopsies is a good illustration of the benefits and limitations of the MSGB for SS-A negative patients.

Biopsy # 1: Inflammation present but not focal, 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.

Biopsy #2:  Seven years following #1.  Positive result, with focus score of 1.5.  This was my first –and only- laboratory confirmation of Sjogren’s.

 

Biopsy #3: Two years following the second biopsy, a third biopsy was performed for research purposes.   Result: Scarring and atrophy, with a focus score described as N/A. This is officially a negative MSGB, although in the clinical context, it was considered evidence of advanced salivary gland damage caused by Sjogren's. 

 I was lucky to hit the window when I read positive, but before I progressed to a reading that threw me back into an officially "negative” reading.   

Updated 4-23-19