PULMONARY PATHOLOGIES AND MANAGEMENT STRATEGIES IN PRIMARY IMMUNODEFICIENCIES

pulmonary_pathologies_kapak

MALIGNANCY AND RARE PULMONARY COMPLICATIONS IN PRIMARY IMMUNODEFICIENCIES

Şükran Aslan Savaş 1
Eray Yıldız2

1Konya Necmettin Erbakan University, Faculty of Medicine, Department of Immunology and Allergic Diseases, Konya, Türkiye
2Necip Fazıl City Hospital, Department of Immunology and Allergic Diseases, Kahramanmaraş, Türkiye

Aslan Savaş Ş, Yıldız E. Malignancy and Rare Pulmonary Complications in Primary Immunodeficiencies. In: Arslan Ş editor. Pulmonary Pathologies and Management Strategies in Primary Immunodeficiencies. 1st ed. Ankara: Türkiye Klinikleri; 2025. p.89-101.

ABSTRACT

Primary immunodeficiencies (PIDs) are a heterogeneous group of disorders resulting from genetically determined defects in the immune system. In addition to recurrent infections, these conditions predispose affected individuals to autoimmunity, autoinflammation, immune dysregulation, lymphoproliferation, allergic diseases, malignancies, and gastrointestinal and pulmonary complications. The pulmonary system is among the most frequently affected organ systems in patients with PIDs. Recurrent infections, chronic inflammation, and dysregulated immune responses contribute to structural and functional alterations in lung tissue.

Notably, persistent inflammatory processes and lymphoproliferative disorders may increase the risk of malignant transformation within the lung parenchyma, potentially leading to the development of hematologic malignancies such as pulmonary lymphomas. Underlying mechanisms include intrinsic factors such as impaired genomic stability and defective immune surveillance, as well as extrinsic factors such as chronic inflammation and oncogenic viral infections, particularly Epstein-Barr virüs. Specific PID subtypes, including common variable immunodeficiency,ataxia-telangiectasia, DOCK8 deficiency, and Nijmegen breakage syndrome, have been associated with an increased risk of cancer development.

In addition, rare pulmonary complications associated with primary immunodeficiencies include interstitial lung disease, granulomatous inflammation, as well as vasculitis, amyloidosis, pulmonary alveolar proteinosis and pulmonary hypertension, Pulmonary alveolar proteinosis results from surfactant accumulation due to impaired macrophage function and may develop in certain (PIDs) as a consequence of genetic or autoimmune mechanisms. Although rare, pulmonary hypertension can occur in patients with PIDs due to factors such as recurrent infections, chronic hypoxia, vascular inflammation, and extrinsic arterial compression; it is particularly notable in severe combined immunodeficiency. Pulmonary amyloidosis is characterized by the deposition of insoluble amyloid fibrils within the lung tissue and may mimic other pulmonary diseases in its clinical and radiological presentation. Pulmonary vasculitis is predominantly associated with autoimmune mechanisms and has been linked to several monogenic (PIDs), including Adenosine deaminase 2 deficiency, COPA syndrome, RAG mutations, X-linked lymphoproliferative syndrome, STING-associated vasculopathy, and activated PI3K delta syndrome.

Early diagnosis, multidisciplinary evaluation, and the implementation of individualized treatment strategies are of critical importance in the management of these complex clinical conditions and in improving patient prognosis.

Keywords: Malignancy; Pulmonary complications; Primary immunodeficiency; Lymphoma; Pulmonary alveolar proteinosis

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