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PubMed This is a summary of 11 peer-reviewed journal articles Updated
Infectious Disease

Diagnosing DILS and Distinguishing It from Other Conditions

At a Glance

DILS is diagnosed by combining HIV-positive status with persistent CD8+ T-cell elevation, ongoing dry eyes or mouth or bilateral parotid swelling, and tissue showing CD8-predominant lymphocyte infiltration, while ruling out Sjögren syndrome, lymphoma, hepatitis C, and other causes.

Diagnosing Diffuse Infiltrative Lymphocytosis Syndrome (DILS) can be a complex process because its symptoms overlap with several other conditions [1][2]. Because it is rare—occurring in roughly 0.28% of people living with HIV—doctors must carefully rule out more common causes of dryness and swelling [3].

The Diagnostic Criteria

A diagnosis of DILS is not based on a single, universally accepted test. Instead, historical definitions generally require persistent symptoms and the exclusion of other causes [1][4]. A doctor will consider:

  1. HIV-Positive Status: The syndrome is specifically linked to the body’s reaction to HIV [1].
  2. Persistent CD8 Elevation: A blood test called flow cytometry often shows a persistently high absolute CD8+ T-cell count over time [1][5].
  3. Sicca Symptoms or Parotid Swelling: Persistent dryness of the eyes and mouth, or painless swelling of the glands in the cheeks (parotid glands) on both sides [1][2].
  4. Tissue Infiltration: Histologic evidence of CD8-predominant infiltration, often from a biopsy [1].

Understanding Your Biopsy Report

If your doctor suspects DILS, they may perform a labial salivary gland biopsy. This involves taking a tiny sample of tissue from the inside of your lower lip [1][2]. When you read your pathology report, look for these specific terms:

  • Focus Score: A “focus” is a cluster of at least 50 lymphocytes within a 4-mm² area. A focus score of ≥ 1 (which corresponds to a Chisholm-Mason grade of 3 or 4) is primarily a standardized measure used in evaluating Sjögren-pattern salivary-gland inflammation [1][6]. A positive score is not diagnostic of DILS on its own and must be interpreted with clinical findings.
  • CD8+ Predominance: In DILS, there is a tendency for the cells “clogging” the gland to be CD8+ T-cells. In contrast, in typical Sjögren syndrome, the cells are more often CD4+ T-cells [1][7].
  • Polyclonal vs. Monoclonal: Your report may mention that the cells are polyclonal. If the cells are monoclonal (all identical clones), it raises a red flag for a different condition, like lymphoma [1][8]. However, reactive HIV-associated lesions can sometimes show restricted or clonal populations, and a polyclonal result does not exclude lymphoma. An experienced pathologist must interpret the entire specimen.

Differentiating DILS from Other Conditions

DILS is often called a “Sjögren-like” syndrome, but it is evaluated distinctly. These are typical patterns, not absolute rules:

Feature Typical DILS Pattern Typical Primary Sjögren Pattern
Primary Cell Type Tends to be CD8+ T-cells [1] Tends to be CD4+ T-cells [7]
Antibodies Often negative for SSA/SSB [9] Often positive for anti-SSA [1]
Parotid Swelling Very common, often large and bilateral [1] Less common; glands may be less enlarged [2]
HIV Status HIV Positive [1] Often HIV Negative, though HIV infection does not exclude Sjögren’s [1]

Other conditions your doctor will consider include:

  • Hepatitis C (HCV): This virus can also cause dry eyes and mouth. Your doctor will likely run an HCV antibody or RNA test to rule this out [1][9].
  • Lymphoma: Because DILS involves an overgrowth of white blood cells, it can look like a cancer of the lymph nodes. Doctors evaluate clonality, tissue architecture, and clinical course [1][10].
  • Benign Lymphoepithelial Cysts: These are fluid-filled sacs in the parotid glands that are common in people with HIV but do not involve the same systemic CD8+ overreaction as DILS [11][2].

Extraglandular involvement is investigated when symptoms, examination, laboratory results, or imaging warrant it; tissue confirmation from internal organs is not routinely needed simply to diagnose DILS, and biopsies are reserved for specialist-directed cases where the result would change management [1][4].

Common questions in this guide

What tests are used to diagnose DILS?
There is no single test that confirms DILS. Clinicians combine HIV-positive status, a persistently elevated absolute CD8+ T-cell count, ongoing dry eyes or mouth or bilateral parotid swelling, and tissue showing CD8-predominant lymphocyte infiltration while excluding other causes.
Can a salivary-gland focus score confirm DILS?
No. A focus score of 1 or higher, corresponding to Chisholm-Mason grade 3 or 4, shows a pattern of salivary-gland inflammation but is mainly used in Sjögren-pattern evaluation. DILS requires the biopsy finding to be interpreted with symptoms, HIV status, blood counts, and other results.
What does CD8-positive mean on a DILS biopsy?
It means many of the lymphocytes in the sampled tissue are CD8+ T-cells, a pattern that can support DILS. It is not diagnostic on its own, and the full tissue appearance and clinical findings still matter.
How can doctors tell DILS from Sjögren syndrome?
DILS is associated with HIV, often has a persistently high CD8 count, prominent bilateral parotid swelling, and CD8-predominant tissue. Primary Sjögren syndrome more often has CD4-predominant inflammation and anti-SSA antibodies, but these are typical patterns rather than absolute rules.
Does a monoclonal biopsy result mean I have lymphoma?
A monoclonal population means the lymphocytes appear to come from one dominant clone and can raise concern for lymphoma, but it does not establish the diagnosis by itself. Reactive HIV-associated lesions can sometimes show restricted or clonal populations, and even a polyclonal result does not completely exclude lymphoma; pathologists consider tissue architecture and clinical course.
What other conditions should be ruled out before diagnosing DILS?
Doctors may test for hepatitis C with an antibody or RNA test and consider other infections such as HTLV-1, depending on the clinical situation. They also assess for lymphoma and benign lymphoepithelial cysts in the parotid glands, which can resemble parts of the presentation.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Does my pathology report show a focus score of 1 or higher, and was it a Chisholm-Mason grade 3 or 4?
  2. 2.Did the immunohistochemistry stains show that the majority of the cells were CD8+ T-cells rather than CD4+ cells?
  3. 3.Was the lymphocyte population described as polyclonal or monoclonal on my report?
  4. 4.Are my blood tests for Sjögren-specific antibodies (anti-SSA/Ro and anti-SSB/La) negative?
  5. 5.Is my absolute CD8 count consistently elevated, and how does that affect our confidence in the DILS diagnosis?
  6. 6.Do we need to test for Hepatitis C or HTLV-1 to make sure they aren't the cause of these symptoms?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (11)
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    The diffuse infiltrative lymphocytosis syndrome (DILS). A comprehensive review.

    Ghrenassia E, Martis N, Boyer J, et al.

    Journal of autoimmunity 2015; (59()):19-25.

    PMID: 25660200
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    Human immunodeficiency virus and salivary gland pathology: an update.

    Meer S

    Oral surgery, oral medicine, oral pathology and oral radiology 2019; (128(1)):52-59 doi:10.1016/j.oooo.2019.01.001.

    PMID: 30827854
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    Risk of Diffuse Infiltrative Lymphocytosis Syndrome in HIV-Infected Patients: A Nationwide Population-Based Cohort Study.

    Chen M, Yen YF, Lan YC, et al.

    Journal of acquired immune deficiency syndromes (1999) 2018; (79(2)):158-163 doi:10.1097/QAI.0000000000001802.

    PMID: 29995702
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    [Efficacy of highly active antiretroviral therapy alone in the treatment of diffuse lymphocytic infiltration syndrome in an ivorian patient living with HIV: a case report].

    Cherif I, Tsevi YM, Bawe LD, et al.

    Medecine tropicale et sante internationale 2021; (1(3)) doi:10.48327/mtsibulletin.2021.118.

    PMID: 35686173
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    Navigating Parotid Lymphoepithelial Cysts in HIV Patients: A Tale of Two Distinct Scenarios.

    Pedaprolu AS, Jajoo S, Mahakalkar C, et al.

    Cureus 2023; (15(12)):e50399 doi:10.7759/cureus.50399.

    PMID: 38213382
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    Employing immunohistochemical staining to labial minor salivary gland biopsies from patients with Sjogren's syndrome increases diagnostic certainty.

    Trivedi A, Cornejo KM, O'Donnell P, et al.

    Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 2021; (50(1)):98-102 doi:10.1111/jop.13119.

    PMID: 33150616
  7. 7

    Clinical, histopathological, and immunohistochemical characteristics of patients with sicca syndrome with a focus score ≥ 1 in the minor salivary gland biopsy

    Lamos-Duarte AF, Parra-Medina R, Rivadeneira-Chamorro CS, et al.

    Biomedica : revista del Instituto Nacional de Salud 2025; (45(1)):80-93 doi:10.7705/biomedica.7315.

    PMID: 40257948
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    Minor salivary gland biopsy in Sjogren's disease: a diagnostic and prognostic tool toward precision medicine.

    Chatzis L, Tzioufas AG

    Current opinion in immunology 2026; (99()):102737 doi:10.1016/j.coi.2026.102737.

    PMID: 41689940
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    Diffuse connective tissue disorders in HIV-infected patients.

    Christoforidou A, Galanopoulos N

    Mediterranean journal of rheumatology 2018; (29(3)):148-155 doi:10.31138/mjr.29.3.148.

    PMID: 32185316
  10. 10

    HIV-associated benign lymphoepithelial cysts of the parotid glands confirmed by HIV-1 p24 antigen immunostaining.

    Sekikawa Y, Hongo I

    BMJ case reports 2017; (2017()) doi:10.1136/bcr-2017-221869.

    PMID: 28963391
  11. 11

    Benign lymphoepithelial cysts of parotid and submandibular glands in a HIV-positive patient.

    Shivhare P, Shankarnarayan L, Jambunath U, Basavaraju SM

    Journal of oral and maxillofacial pathology : JOMFP 2015; (19(1)):107 doi:10.4103/0973-029X.157213.

    PMID: 26097320

This page is for informational purposes only and does not constitute medical advice. A qualified clinician should interpret your DILS symptoms, blood tests, and biopsy results in context.

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