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Primary/Congenital Immunodeficiency: 2015 SH/EAHP Workshop Report-Part 5
Dita Gratzinger1, Elaine S Jaffe2, Amy Chadburn3
1From the Stanford University School of Medicine, Stanford, CA.
Insights
Primary immunodeficiencies can lead to various lymphoproliferations, including autoimmune lymphoproliferative syndrome (ALPS) and common variable immunodeficiency (CVID). Recognizing specific T-cell expansions is crucial to avoid misdiagnosing these conditions as lymphoma.
Area of Science:
- Hematopathology
- Immunology
- Genetics
Background:
- Primary immunodeficiencies (PIDs) encompass a range of conditions affecting the immune system.
- Lymphoproliferative disorders can arise in the context of PIDs, necessitating careful evaluation.
- The 2015 Society for Hematopathology/European Association for Haematopathology workshop focused on PIDs and related lymphoproliferations.
Purpose of the Study:
- To review and categorize primary immunodeficiencies and their associated lymphoproliferative disorders.
- To highlight the spectrum of lymphoproliferations seen in PIDs.
- To provide guidance on differentiating PID-related lymphoproliferations from other conditions.
Main Methods:
- Classification of PIDs into categories: immune dysregulation, DNA repair defects, low immunoglobulins, and combined immunodeficiencies.
- Review of clinical and pathological features of lymphoproliferations in PIDs.
- Analysis of T-cell subset expansions and their diagnostic implications.
Main Results:
- Autoimmune lymphoproliferative syndrome (ALPS) exemplifies immune dysregulation, characterized by T-cell signaling/apoptosis defects and predisposition to hemophagocytic lymphohistiocytosis.
- DNA repair defects are directly linked to an increased risk of malignancy.
- Low immunoglobulin immunodeficiencies, such as common variable immunodeficiency (CVID), involve T-cell repertoire abnormalities contributing to autoimmunity and B-cell lymphoproliferations.
- The full spectrum of B-cell lymphoproliferative disorders is observed in patients with PIDs.
Conclusions:
- Lymphoproliferations in PIDs share similarities with those in other immunodeficiency settings.
- Monomorphic B- and T-cell lymphoproliferative disorders are frequently observed in PIDs with DNA repair defects.
- Distinctive T-cell subset expansions in ALPS, CVID, and related conditions can mimic lymphoma.
- Accurate identification of double-negative T-cell or cytotoxic T-cell expansions is essential to prevent overdiagnosis of lymphoma.
Objectives:
The 2015 Workshop of the Society for Hematopathology/European Association for Haematopathology aimed to review primary immunodeficiency and related lymphoproliferations.
Methods:
Primary immunodeficiencies were divided into immune dysregulation, DNA repair defects, low immunoglobulins, and combined immunodeficiencies.
Results:
Autoimmune lymphoproliferative syndrome (ALPS) is a prototypical immune dysregulation-type immunodeficiency, with defects in T-cell signaling or apoptosis, expansion of T-cell subsets, and predisposition to hemophagocytic lymphohistiocytosis. DNA repair defects directly predispose to malignancy. Low immunoglobulin immunodeficiencies such as common variable immunodeficiency (CVID) have underlying T-cell repertoire abnormalities predisposing to autoimmunity and B-cell lymphoproliferations. The full spectrum of B-cell lymphoproliferative disorders occurs in primary immunodeficiency.
Conclusions:
Lymphoproliferations in primary immunodeficiency mirror those in other immunodeficiency settings, with monomorphic B- and sometimes T lymphoproliferative disorders enriched in DNA repair defects. Distinctive T-cell subset expansions in ALPS, CVID, and related entities can mimic lymphoma, and recognition of double-negative T-cell or cytotoxic T-cell expansions is key to avoid overdiagnosis.
